Divergent Total Syntheses of Yaequinolone-Related Natural Products by Late-Stage C–H Olefination

Abstract

Divergent total syntheses of 10 yaequinolone-related natural products have been achieved for the first time by late-stage C–H olefination of 3,4-dioxygenated 4-aryl-5-hydroxyquinolin-2(1H)-ones, core structures of this family of natural products. A robust synthetic methodology to construct the core structures has been established, and the C–H olefination reaction has been carried out with synthetically useful yields and high levels of site-selectivity under mild reaction conditions in the presence of a Pd/S,O-ligand catalyst.

Introduction

Yaequinolones and related compounds that comprise 3,4-dioxygenated 4-aryl-quinolin-2(1H)-one cores represent a growing family of biologically active alkaloids isolated from marine and plant fungi (Figure 1a).¹ The first two members, NTC-47A and B, were isolated from the second metabolites of Penicillium sp. by Nakaya in 1995 and they showed promising insecticidal activities.² Since then, many more related compounds have been discovered and their structures, bioactivities, and biosynthetic mechanisms have been intensively studied.³⁻⁶ Structurally, the two oxygenated functional groups at 3- and 4-positions have a cis-configuration for most of the members.⁷ Moreover, the majority of these natural products possess a hydroxyl group at the 5-position and only differ from each other in the olefin moiety present at the 6-position (Figure 1b).

Figure 1.

Structures of yaequinolone-related natural products.

This family of natural products has attracted great attention in the last few years due to their unique structures and biological activities, and the total syntheses of few members of this family of natural products have been reported. The first total synthesis of this family of natural products was the synthesis of (±)-yaequinolone A2, the structurally simplest molecule among the family (Scheme 1a).⁸ The key step of this approach is the intramolecular aldol reaction of N-glycolated 2-aminobenzophenone to construct the quinolone core, generating the two oxygenated functional groups in a cis-fashion. The first enantioselective total syntheses of (−)-yaequinolones J1 and J2 were reported in 2018 by the group of Hanessian (Scheme 1b).⁹ The authors used an Evans-type chiral auxiliary to provide the syn-aldol diol as a 1:1 mixture of diastereoisomers that differ in the configuration of the pyranyl tertiary methyl group. The group of Christmann successfully synthesized (±)-peniprequinolone, (±)-aflaquinolones E and F, (±)-6-deoxyaflaquinolone E, (±)-quinolinones A and B, and (±)-aniduquinolone C by developing a general method for the construction of N-glycolated 2-aminobenzophenone via aryne insertions into unsymmetrical imides in flow (Scheme 1c).¹⁰

Scheme 1. Total Syntheses of Yaequinolone-Related Natural Products.

In spite of this progress, a general strategy to access these natural products in a direct and divergent manner is still elusive.¹¹ As many members of this family of natural products (>20) only differ from each other in the structure of the olefin at the 6-position, we envisioned that their syntheses can be achieved from a key common intermediate in a divergent manner using late-stage site-selective C–H olefination.¹² Herein, we report a new methodology for the late-stage C(6)–H olefination of 3,4-dioxygenated 4-aryl-5-hydroxy-quinolin-2(1H)-ones and its successful application in the divergent total syntheses of 10 yaequinolone-related natural products, which are synthesized for the first time (Scheme 1d).

Results and Discussion

In 2019, we reported a highly selective C(6)–H olefination reaction of tetrahydroquinolines (THQs) in the presence of a Pd/S,O-ligand catalyst (Scheme 2a).¹³ We hypothesized that late-stage selective C(6)–H olefination of 3,4-dioxygenated 4-aryl-5-hydroxy-quinolin-2(1H)-one cores could be developed in the presence of a Pd/S,O-ligand catalyst to directly access yaequinolone-related natural products in a divergent manner.

Scheme 2. Reactivity Comparison of THQs and 1a.

First, we evaluated the C–H olefination reaction of N-methyl-3,4-dihydroquinolin-2(1H)-one (1a), the simplified backbone of yeaquinolone-related natural products, with ethyl acrylate under reported reaction conditions for the olefination of THQs. As expected, because the aromatic ring is less activated,^13,14 the reaction only provided the olefinated product in less than 10% ¹H NMR yield (Scheme 2b). When the reaction was performed at 80 °C, a slightly higher yield of 23% was achieved (Scheme 2b).

Because all our target natural products have a hydroxyl group at the 5-position, we decided to investigate the effect of this functional group on the reactivity of the C–H olefination of quinolin-2(1H)-ones. We tested N-methyl-3,4-dihydro-2(1H)-quinolinones bearing an OMe, OEt, or/and OMOM group at the 5-position (2a–4a, Scheme 3). As expected, because these substrates are more activated, synthetically useful yields (45–57%) were observed and the C(6)-olefinated products were exclusively formed. The reaction of the OMe derivative 2a without the S,O-ligand only gave a trace amount of olefinated product, highlighting the key role of the S,O-ligand in this transformation. We also evaluated the olefination reaction of substrate 5a bearing a free OH group at the 5-position, but the olefinated product 5b was obtained only in 27% yield due to its instability under the reaction conditions.¹⁵ Having established the beneficial effect of the oxygenated moiety at the 5-position in the C–H olefination reaction, we decided to evaluate other protecting groups at the nitrogen atom. The reaction with the MOM-protected substrate 6a provided the desired olefinated product 6b in 46% yield with slightly lower C(6)-selectivity. When the benzyl-protected substrate 7a was subjected to the standard reaction conditions, the olefinated product was obtained in 48% yield with good C(6)-selectivity.

Scheme 3. C–H Olefination of 5-Oxgenated N-Methyl-3,4-dihydro-2(1H)-quinolinones^,b,c.

Reaction conditions: a (0.1 mmol), ethyl acrylate (0.15 mmol), Pd(OAc)₂ (0.01 mmol), S,O-ligand (0.01 mmol), and PhCO₃^tBu (0.1 mmol) in DCE (0.5 mL) at 80 °C for 16 h. ^bIsolated yield. ^cRegioselectivity was determined based on the analysis of crude mixture.

After having proved the suitability of the C–H olefination reaction on model substrates, we proposed the retrosynthetic route for 3,4-dioxygenated 4-aryl-5-hydroxy-quinolin-2(1H)-ones as outlined in Figure 2. 3,4-dioxygenated 4-aryl-5-hydroxy-quinolin-2(1H)-one can be obtained by cyclization as reported by the group of She.⁸ The starting diarylketone can be synthesized from the nucleophilic addition of the lithiated 3-oxygenated 2-bromonitrobenzene, which can be prepared from commercially available 2-bromo-3-nitrophenol, to para-anisaldehyde, followed by oxidation.

Figure 2.

Retrosynthetic analysis of 3,4-dioxygenated 5-hydroxy-4-aryl-quinolin-2(1H)-ones.

The synthesis of the core structure is shown in Scheme 4. 2-Bromo-3-nitrophenol (8) was first protected with a benzyl group in 91% yield, followed by lithiation at low temperature and reaction with para-anisaldehyde, providing the corresponding alcohol 10 in 86% yield. We then reduced the nitro group using sodium sulfide to form the aniline intermediate 11, followed by amide formation with methoxyacetyl chloride. The formed amide intermediate 12 was oxidized with PCC, providing the ketone 13 in 94% yield. The cyclization of 13 under reported reaction conditions produced (±)-14 in 80% yield as a single diastereoisomer.⁸ Then, we decided to protect the nitrogen atom with 2-(trimethylsilyl)ethoxymethyl (SEM), as it can be deprotected using mild reagents, such as tetrabutylammonium fluoride (TBAF).¹⁶ Then, we introduced the SEM-protecting group to (±)-14 using LiHMDS as the base. SEM-protected 3,4-dihydro-2(1H)-quinolinone derivative (±)-16 was obtained in 95% yield after benzyl deprotection of (±)-15 using Pd/C and H₂ (Scheme 4).

Scheme 4. Synthesis of the Core Structure (±)-16.

For the C–H olefination of (±)-16, we slightly optimized the reaction conditions and found that the best conditions were 2.0 equiv of PhCO₃^tBu in dichloroethane (DCE) at 80 °C for 16 h, providing the olefinated product (±)-17 in 59% isolated yield with a regioselectivity of 6:1 (A/B) together with 5% of the diolefinated product (Table 1). However, the regioisomers were not separable by flash column chromatography. We, therefore, continued the total synthesis with the mixture of regioisomers.

Table 1. Reaction Conditions for the C–H Olefination of (±)-16.

entry	temp. (°C)	x	time (h)	1H NMR yielda
1	80	1.5	16	49%
2	60	1.5	16	31%
3	80	1.5	6	45%
4	80	1.0	16	42%
5	80	2.0	16	54% (59%b,c+ 5%b,d)
6e	80	1.5	16	55%

^a1H NMR yield of the desired regioisomer was determined by using CH₂Br₂ as the internal standard.

^bIsolated yield.

^cRegioselectivity was determined from the crude mixture: A/B = 6:1.

^dDiolefinated product.

^e15 mol % of Pd(OAc)₂ and S,O-ligand were used.

We performed the deprotection of the SEM group with TBAF, and it was found out that a high concentration of TBAF is required to obtain the desired product in good yield. For instance, when the concentration of TBAF was 0.1 M, no product was observed even after refluxing the reaction for 20 h. When we increased the concentration to 1.0 M, to our delight, the reaction reached full conversion after refluxing for 15 h and (±)-yaequinolone B was obtained in 60% isolated yield as a single regioisomer (Scheme 5). Its ¹H and ¹³C NMR data matched with those reported in the literature.^4c Hence, the total synthesis of (±)-yaequinolone B was achieved in 10.6% overall yield in 10 synthetic steps starting from commercially available 2-bromo-3-nitrophenol.

Scheme 5. Synthesis of (±)-Yaequinolone B.

Encouraged by these results, we moved our attention to the total syntheses of (±)-penigequinolones A and B, which can be accomplished by only changing the olefin coupling partner while keeping the same core structure (±)-16. Olefin (±)-18 was prepared in six synthetic steps starting from ethyl isobutyrate (see the Experimental Section). The C–H olefination of (±)-16 using (±)-18 as the olefin under standard reaction conditions furnished the olefinated product (±)-19 in 50% yield with a regioselectivity of 8.8:1 (A/B) and a diastereoselectivity of 1:1. The SEM deprotection of (±)-19 with TBAF (4.0 M) almost quantitatively yielded a mixture of (±)-penigequinolones A and B (dr = 1:1) with improved regioselectivity (13.5:1) (Scheme 6). Their ¹H and ¹³C NMR data matched with those reported in the literature.^4c

Scheme 6. Syntheses of (±)-Penigequinolones A and B.

For the synthesis of (±)-yaequinolone C, as the relative stereochemistry of the olefin moiety was not determined in the initial report from the group of O̅mura, we decided to first try the olefin (±)-trans-20 (see the Experimental Section).^4c To our delight, the olefinated product (±)-21 was isolated in 52% yield with a regioselectivity of 7:1 (A/B) (Scheme 7a). However, we observed the formation of four diastereoisomers, indicating that racemization of one of the stereocenters of the olefin moiety has occurred. To prove this, we performed the olefination of (±)-16 with a mixture of (±)-trans- and (±)-cis-20 (1:1), and we observed the formation of the same four diastereoisomers (Scheme 7b). Moreover, we further tried the olefination of the model substrate 5a with (±)-trans-20 and with a 1:1 mixture of (±)-trans- and (±)-cis-20 and in both cases, the olefinated product was obtained as a mixture of diastereoisomers in almost 1:1 ratio, confirming that racemization has occurred in one of the stereocenters of the olefin moiety during the C–H olefination (Scheme 7c).¹⁷

Scheme 7. C–H Olefination of (±)-16 and 5a with (±)-19.

The deprotection of the olefinated product (±)-21 (A/B = 7:1) using 4.0 M of TBAF reached full conversion after refluxing overnight, providing (±)-yaequinolone C together with three other diastereoisomers in 79% isolated yield with an improved regioselectivity of 10.4:1 (Scheme 8). Based on the results obtained from the reaction of (±)-16 with (±)-trans-20 and with a 1:1 mixture of (±)-trans- and (±)-cis-20, we proposed that the olefin moiety has a trans-configuration (see Supporting Information). Therefore, the structure of (±)-yaequinolone C is either 22-A or 22-B.

Scheme 8. Synthesis of (±)-Yaequinolone C.

In an effort to synthesize (±)-aspoquinolones C and D, we performed the olefination reaction of (±)-16 with (±)-cis-23, but no desired product was observed and (±)-16 was fully recovered (Scheme 9a). Considering that the free hydroxyl group from the olefin might be the problem, we protected the OH of (±)-cis-23 with the TMS group. The reaction of (±)-16 with TMS-protected olefin (±)-cis-24 gave a mixture of TMS-protected and unprotected olefinated products with 50% conversion (Scheme 9b). To simplify the purification, we directly treated the crude mixture with TBAF to deprotect the TMS group.¹⁸ After purification, the olefinated product (±)-25 was isolated in 43% yield as a single regioisomer [the other regioisomer was detected by ¹H NMR analysis of the crude and separated by preparative thin layer chromatography (TLC)]. Unfortunately, like in the previous case, epimerization also occurred and four diastereoisomers were detected with a ratio of 2.2:2.2:1:1. The SEM deprotection of (±)-25 with TBAF led to full decomposition of the starting material. Then, we performed the deprotection reaction using Me₂AlCl.¹⁹ This two-step deprotection procedure provided (±)-aspoquinolones C and D together with two other diastereoisomers with diastereoselectivity (2.2:2.2:1:1) remaining in 73% combined yield (Scheme 9c). As the relative stereochemistry of the olefin moieties of aspoquinolones C and D was not determined in the initial report,^4b we propose, based on our results, that one has the cis-configuration on the olefin moiety and the other one has the trans-configuration.

Scheme 9. Syntheses of (±)-Aspoquinolones C and D.

After proving the synthetic power of late-stage C–H olefination by the Pd/S,O-ligand catalyst in the divergent synthesis of (±)-yaequinolones B and C, (±)-penigequinolones A and B, and (±)-aspoquinolones C and D, we decided to move our attention to the total syntheses of another class of closely related quinolone natural products, which all share a slightly different backbone (a phenyl group located at the 4-position instead of a 4-methoxyphenyl group). We prepared the corresponding 3,4-dihydro-2(1H)-quinolinone derivative (±)-27 in seven synthetic steps starting from 9 using the same procedure for the preparation of (±)-16 (see Experimental Section) (Scheme 10).

Scheme 10. Syntheses of (±)-Aflaquinolones A, C, and D and (±)-Scopuquinolone B.

To synthesize (±)-aflaquinolones A, C, and D, we prepared olefin (±)-28 as a mixture of diastereoisomers (trans/cis = 5:4) in seven synthetic steps starting from ethyl 4-oxocyclohexanecarboxylate (see the Experimental Section).²⁰ The coupling of this unactivated olefin 28 with (±)-27 gave the olefinated product (±)-29 in 34% yield with perfect regioselectivity (>20:1) and with a diastereoselectivity of 1:1:1.6:1.6. The SEM deprotection of (±)-29 with TBAF failed to give any desired product, while the reaction with Me₂AlCl provided (±)-aflaquinolones A, C, and D together with another diastereoisomer in near-quantitative yield with a diastereoselectivity of 1:1:1:1. Thus, epimerization occurred during the deprotection reaction probably at the α-position of the ketone.

Our last target was the synthesis of (±)-scopuquinolone B that can be synthesized by coupling the core structure (±)-27 with the trans-olefin (±)-31. The olefination reaction of (±)-27 with olefin (±)-31 furnished the olefinated product (±)-32 in 39% yield with a diastereoselectivity of 1:1:1:1. The SEM deprotection of (±)-32 with Me₂AlCl provided (±)-scopuquinolone B together with three other diastereoisomers in 89% yield with retained diastereoselectivity of 1:1:1:1.

Conclusions

In summary, we have developed novel divergent syntheses of 10 yaequinolone-related natural products, which are synthesized for the first time, by late-stage C–H olefination of 3,4-dioxygenated 4-aryl-5-hydroxyquinolin-2(1H)-ones, core structures of this family of natural products. A robust synthetic methodology is established to construct the core structures and the C–H olefination reaction is efficient and site-selective under mild reaction conditions in the presence of a Pd/S,O-ligand catalyst. The power of the olefination reaction was showcased by successfully using unactivated olefins as coupling partners. Through this synthetic approach, the relative configuration of the olefin moiety of some of these natural products has been elucidated. Our future efforts will be devoted toward the divergent enantioselective total syntheses of this family of natural products.

Experimental Section

General Information

Chromatography: Silicycle Silica Flash P60 size 40–63 μm (230–400 mesh), TLC: Merck silica gel 60 (0.25 mm), and preparative TLC: Analtech silica gel G 1500 μm 20 × 20 cm. Visualization of the TLC plate was performed with phosphomolybdic acid or KMnO4 staining reagent and UV light. Mass spectra were recorded on AccuTOF GC v 4g, JMS-T100GCV mass spectrometers. ¹H and ¹³C were recorded on Bruker 500 AMX, 400 and Bruker DRX 300 using CDCl₃ as the solvent otherwise it will be noted. Chemical shift values are reported in ppm with the solvent resonance as the internal standard (CDCl₃: δ 7.26 for ¹H and δ 77.16 for ¹³C; dimethyl sulfoxide: δ 2.50 for ¹H and δ 39.52 for ¹³C; and acetone: δ 2.05 for ¹H and δ 206.26 for ¹³C). Data are reported as follows: chemical shifts, multiplicity (s = singlet, d = doublet, dd = doublet of doublets, t = triplet, q = quartet, and m = multiplet), coupling constants (Hz), and integration. IR spectra were recorded on a Bruker Alpha Fourier transform infrared machine and wavelengths are reported in cm^–1. The melting point was measured in melting point apparatus Büchi M-565. Tetrahydrofuran (THF) and diethyl ether were dried over Na using benzophenone as the indicator. Dichloromethane was dried over CaH₂ and was used freshly after distillation. Anhydrous dimethylformamide (DMF) was purchased from Acros and used as received. Absolute ethanol was purchased from VWR Amsterdam and was used as received. TBAF solution (1.0 M in THF) was purchased from Fluorochem And Pd(OAc)₂ was purchased from Strem. The S,O-ligand was prepared using the procedure reported in the literature.^13b

Synthesis of Olefins

2,5,5-Trimethyl-2-vinyltetrahydro-2H-pyran (18) was prepared using the following procedures: Step A: In a flame-dried Schlenk flask were added ethyl isobutyrate (5.563 mL, 4.84 g, 41.7 mmol, 1.0 equiv) and anhydrous THF (40 mL) under N₂. In another flask, lithium diisopropylamide (LDA) (50 mmol, 1.2 equiv) was prepared and transferred to the substrate flask at −78 °C via a cannula over a period of 0.5 h. The reaction was stirred for 2 h before 1-bromo-2-chloroethane (8.613 mL, 14.34 g, 100 mmol, 2.4 equiv) was added. The reaction was then warmed up to room temperature and stirred overnight. The reaction was quenched by adding saturated aqueous NH₄Cl solution and was extracted with EtOAc three times. The combined extracts were washed with brine, dried over Na₂SO₄, and evaporated in vacuo. The product was purified by flash column chromatography (PE/Et₂O, 100:1 to 50:1) giving ethyl 4-chloro-2,2-dimethylbutanoate (Int-A) as a colorless oil (6.10 g, 82%). Its ¹H NMR data matched with those reported in the literature.²¹¹H NMR (400 MHz): δ 4.16 (q, J = 7.1 Hz, 2H), 3.57–3.48 (m, 2H), 2.12–2.03 (m, 2H), 1.28 (t, J = 7.1 Hz, 3H), 1.24 (s, 6H).

Step B: In a flame-dried Schlenk flask were added LiBH₄ (0.92 g, 42 mmol, 1.5 equiv) and anhydrous DCM (20 mL). To this suspension was then slowly added MeOH (1.7 mL). After the evolution of H₂ has ceased, Int-A (5.00 g, 28 mmol, 1.0 equiv) was added. The reaction was then heated under reflux at 45 °C overnight. The reaction was quenched by carefully adding water and the mixture was extracted with EtOAc three times. The combined extracts were washed with brine, dried over Na₂SO₄, and evaporated in vacuo. The product was purified by flash column chromatography (PE/Et₂O, 100:1 to 1:1) giving 4-chloro-2,2-dimethylbutan-1-ol (Int-B) as a colorless oil (2.50 g, 65%). Its ¹H NMR data matched with those reported in the literature.²²¹H NMR (300 MHz): δ 3.64–3.51 (m, 2H), 3.35 (d, J = 0.7 Hz, 2H), 1.88–1.75 (m, 2H), 0.93 (s, 6H).

Step C: In a round-bottom flask were successively added Int-B (1.37 g, 10 mmol, 1.0 equiv), DCM (15 mL), and TBSCl (3.01 g, 20 mmol, 2.0 equiv). After stirring the mixture for 5 min, 1-imidazole (1.36 g, 20 mmol, 2.0 equiv) was then added and the stirring was continued for another 2 h. Saturated aqueous NH₄Cl solution was added to quench the reaction and the mixture was extracted with EtOAc three times. The combined extracts were washed with brine, dried over Na₂SO₄, and evaporated in vacuo. The product was purified by flash column chromatography (PE/Et₂O, 20:1) giving tert-butyl(4-chloro-2,2-dimethylbutoxy)dimethylsilane (Int-C) as a colorless oil (2.50 g, quantitative yield). ¹H NMR (300 MHz): δ 3.62–3.50 (m, 2H), 3.25 (s, 2H), 1.84–1.72 (m, 2H), 0.89 (s, 9H), 0.81 (s, 6H), 0.03 (s, 6H). ¹³C{H} NMR (75 MHz): δ 71.7, 42.7, 41.8, 36.0, 26.0, 24.3, 18.4, −5.4. HRMS (FD) m/z: [M – ^tBu]⁺ calcd for C₈H₁₈ClOSi⁺, 193.0815; found, 193.0854.

Step D: In a flame-dried Schlenk flask were added Int-C (1.50 g, 5.98 mmol, 1.0 equiv), Mg (0.18 g, 7.41 mmol, 1.24 equiv), and anhydrous THF (2 mL) under N₂. The mixture was then heated to reflux and a few drops of 1,2-dibromoethane were slowly added to the reaction. The reaction was continued to stir for another 6 h while refluxing at 80 °C. In another flame-dried Schlenk flask were added anhydrous CeCl₃ (1.47 g, 5.98 mmol, 1.0 equiv) and anhydrous THF (12 mL), and the suspension was stirred at room temperature for 1 h. The freshly prepared Grignard reagent was transferred to the suspension via a cannula at 0 °C. The reaction was further stirred at 0 °C for 1 h before but-3-en-2-one (1.0 mL, 11.96 mmol, 2.0 equiv) was added. After stirring it at 0 °C for 1 h, the reaction was quenched by adding saturated aqueous NH₄Cl solution and the mixture was extracted with EtOAc three times. The combined extracts were washed with brine, dried over Na₂SO₄, and evaporated in vacuo. The product was purified by flash column chromatography (PE/EtOAc, 15:1) giving 7-[(tert-butyldimethylsilyl)oxy]-3,6,6-trimethylhept-1-en-3-ol (Int-D) as a colorless oil (1.01 g, 59%). ¹H NMR (400 MHz): δ 5.89 (dd, J = 17.4, 10.7 Hz, 1H), 5.20 (dd, J = 17.3, 1.4 Hz, 1H), 5.04 (dd, J = 10.8, 1.4 Hz, 1H), 3.22 (s, 2H), 1.51–1.46 (m, 2H), 1.27 (s, 3H), 1.25–1.20 (m, 2H), 0.89 (s, 9H), 0.02 (s, 6H). ¹³C{H} NMR (75 MHz): δ 145.4, 111.8, 77.4, 73.5, 71.4, 36.5, 35.0, 32.5, 27.8, 26.1, 24.3, 24.3, 18.4, −5.4. HRMS (EI) m/z: [M]⁺ calcd for C₁₆H₃₄O₂Si⁺, 286.2328; found, 286.2295.

Step E: In a round-bottom flask were added Int-D (1.00 g, 3.49 mmol, 1.0 equiv) and THF (15 mL). TBAF solution (1.0 M in THF, 8.7 mL, 8.7 mmol, 2.5 equiv) was added dropwise. The reaction was left to stir at room temperature for 4 h before it was quenched by adding saturated aqueous NH₄Cl solution. The mixture was extracted with EtOAc three times. The combined extracts were washed with brine, dried over Na₂SO₄, and evaporated in vacuo. The product was purified by flash column chromatography (n-hexane/EtOAc, 11:1) giving 2,2,5-trimethylhept-6-ene-1,5-diol (Int-E) as a white solid (0.50 g, 83%). ¹H NMR (300 MHz): δ 5.85 (dd, J = 17.3, 10.7 Hz, 1H), 5.16 (dd, J = 17.4, 1.3 Hz, 1H), 5.01 (dd, J = 10.8, 1.3 Hz, 1H), 3.33–3.18 (m, 2H), 2.76 (br s, 2H), 1.48–1.42 (m, 2H), 1.28–1.20 (m, 2H), 1.25 (s, 3H), 0.82 (s, 3H), 0.81 (s, 3H). ¹³C{H} NMR (75 MHz): δ 145.2, 111.8, 73.4, 70.7, 35.9, 34.75, 31.6, 27.9, 24.5, 24.2. HRMS (FD) m/z: [M]⁺ calcd for C₁₀H₂₀O₂⁺, 172.1463; found, 172.1470.

Step F: In a flame-dried Schlenk flask were successively added Int-E (200 mg, 1.16 mmol, 1.0 equiv), DCE (25 mL), and anhydrous ZnCl₂ (158 mg, 1.16 mmol, 1.0 equiv) under N₂. The reaction was then stirred at 70 °C for 2 h before it was quenched by adding saturated aqueous NH₄Cl solution. The mixture was extracted with Et₂O three times. The combined extracts were passed through a short plug of silica gel and rinsed with Et₂O. The filtrate was evaporated in vacuo giving 2,5,5-trimethyl-2-vinyltetrahydro-2H-pyran (18) as a colorless oil (130 mg, 73%). ¹H NMR (400 MHz): δ 5.78 (dd, J = 17.4, 11.4 Hz, 1H), 5.17 (s, 1H), 5.13 (dd, J = 7.9, 1.3 Hz, 1H), 3.33 (d, J = 11.3 Hz, 1H), 3.21 (dd, J = 11.3, 2.0 Hz, 1H), 1.73–1.61 (m, 2H), 1.45–1.37 (m, 1H), 1.35–1.28 (m, 1H), 1.23 (s, 3H), 0.99 (s, 2H), 0.81 (s, 2H). ¹³C{H} NMR (101 MHz): δ 143.3, 114.3, 74.2, 72.7, 33.5, 30.7, 29.8, 28.7, 26.7, 24.2. HRMS (FD) m/z: [M + Na]⁺ calcd for C₁₀H₁₈NaO⁺, 177.1255; found, 177.1268.

trans-Linalool oxide (trans-20) was prepared using the following procedures: Linalool oxide was purchased from TCI as a mixture of diastereoisomers (1:1) not separable by flash column chromatography. To separate the diastereoisomers, the hydroxyl group was first protected with TMS using the following procedure:

In a round bottom flask were successively added linalool oxide (20, dr = 1:1) (1.01 g, 5.92 mmol, 1.0 equiv), DCM (12 mL), 1-imidazole (1.21 g, 17.8 mmol, 3.0 equiv), and TMSCl (1.13 mL, 8.88 mmol, 1.5 equiv). The reaction was then stirred at room temperature for 0.5 h before water was added. The mixture was extracted with Et₂O three times. The combined organic extracts were washed with brine, dried over Na₂SO₄, and evaporated in vacuo. The product TMS-trans-linalool oxide (TMS-trans-20) was obtained as a colorless oil after purification by flash column chromatography using PE as the eluent. Its ¹H NMR data matched with those reported in the literature.²⁴¹H NMR (400 MHz): δ 5.86 (dd, J = 17.2, 10.5 Hz, 1H), 5.16 (d, J = 17.3 Hz, 1H), 4.97 (d, J = 10.6 Hz, 1H), 3.74 (t, J = 6.1 Hz, 1H), 1.94–1.76 (m, 3H), 1.71–1.63 (m, 1H), 1.30 (s, 3H), 1.21 (s, 3H), 1.20 (s, 3H), 0.11 (s, 9H).

TMS-trans-20

The TMS-protecting group was then removed by using the following step: In a round bottom flask were added (2.70 g, 11.13 mmol, 1.0 equiv) and THF (50 mL). TBAF solution (33 mL, 1.0 M in THF, 3.0 equiv) was then added slowly. The reaction was stirred for 1 h before water was added. The mixture was extracted with Et₂O three times. The combined organic extracts were washed with brine, dried over Na₂SO₄, and evaporated in vacuo. The sample was purified by flash column chromatography (n-hexane/EtOAc, 5:1) giving trans-linalool oxide (trans-20) as a colorless oil (1.70 g, 89%). Its ¹H NMR data matched with those reported in the literature.²³¹H NMR (400 MHz): δ 5.88 (dd, J = 17.3, 10.6 Hz, 1H), 5.19 (d, J = 17.3 Hz, 1H), 5.00 (d, J = 10.7 Hz, 1H), 3.80 (t, J = 7.1 Hz, 1H), 2.10–1.79 (m, 5H), 1.78–1.67 (m, 1H), 1.32 (s, 3H), 1.23 (s, 3H), 1.14 (s, 3H).

TMS-cis-2,2,6-trimethyl-6-vinyltetrahydropyran-3-ol (cis-24)

2,2,6-Trimethyl-6-vinyltetrahydropyran-3-ol (23) was purchased from TCI as a mixture of diastereoisomers (1:1) not separable by flash column chromatography. The TMS protection and deprotection strategy was used to separate them as presented for the separation of linalool oxide (20). TMS protection was performed using the same procedure as the TMS protection of linalool oxide, and cis-24 was isolated as a colorless oil after purification by flash column chromatography with PE as the eluent. ¹H NMR (400 MHz): δ 5.96 (ddd, J = 18.2, 10.9, 1.2 Hz, 1H), 4.99–4.91 (m, 2H), 3.40 (dd, J = 11.3, 4.1 Hz, 1H), 2.10 (dt, J = 12.7, 3.3 Hz, 1H), 1.80–1.65 (m, 1H), 1.62–1.48 (m, 2H), 1.15 (s, 3H), 1.14 (s, 3H), 1.13 (s, 3H), 0.10 (d, J = 1.1 Hz, 9H). ¹³C{H} NMR (101 MHz): δ 146.6, 110.6, 76.6, 75.7, 73.5, 32.9, 32.2, 30.1, 26.4, 20.9, 0.05. HRMS (FD) m/z: [M – Me]⁺ calcd for C₁₂H₂₃O₂Si⁺, 227.1467; found, 227.1485.

cis-2,2,6-Trimethyl-6-vinyltetrahydropyran-3-ol (cis-23)

Deprotection of cis-24 (0.60 g, 2.475 mmol) was performed using the same procedure as the deprotection of TMS-trans-linalool oxide (TMS-trans-20). cis-23 was isolated as a wax (0.42 g, quantitative yield) and its ¹H NMR data matched with those reported in the literature.²⁴¹H NMR (400 MHz): δ 5.99 (dd, J = 18.1, 11.0 Hz, 1H), 5.03 (d, J = 5.5 Hz, 1H), 4.99 (d, J = 1.1 Hz, 1H), 3.51–3.43 (m, 1H), 2.15 (dt, J = 13.6, 3.7 Hz, 1H), 1.77–1.71 (m, 2H), 1.64–1.58 (m, 1H), 1.28 (s, 3H), 1.20 (s, 3H), 1.19 (s, 3H).

2,4-Dimethyl-4-vinylcyclohexanone (28) and 2,4-dimethyl-4-vinylcyclohexanol (31) were prepared using the following procedures: Step A: In a round-bottom flask were successively added ethyl 4-oxocyclohexane-1-carboxylate (9.29 mL, 10.00 g, 58.8 mmol, 1.0 equiv), ethylene glycol (11.5 mL, 12.77 g, 205.8 mmol, 3.5 equiv), p-toluenesulfonic acid monohydrate (137 mg, 0.012 equiv), and anhydrous toluene (30 mL). The reaction was then stirred overnight at room temperature. Saturated aqueous Na₂CO₃ solution was added and the reaction was extracted with EtOAc three times. The combined organic extracts were washed with brine, dried over Na₂SO₄, and evaporated in vacuo. The product was purified by flash column chromatography (PE/EtOAc, 15:1) giving ethyl 1,4-dioxaspiro[4.5]decane-8-carboxylate as a colorless oil (10.94 g, 87%). Its ¹H NMR data matched with those reported in the literature.²⁵¹H NMR (400 MHz): δ 4.05 (q, J = 7.1 Hz, 2H), 3.86 (s, 4H), 2.29–2.22 (m, 1H), 1.91–1.80 (m, 2H), 1.79–1.64 (m, 4H), 1.54–1.42 (m, 2H), 1.17 (t, J = 7.1 Hz, 3H).

Step B: In a flame-dried Schlenk flask were successively added 1,4-dioxaspiro[4.5]decane-8-carboxylate (10.94 g, 51.1 mmol, 1.0 equiv) and anhydrous THF (70 mL). The solution was slowly transferred to another Schlenk flask containing freshly prepared LDA (66.4 mmol, 1.3 equiv) at −78 °C over a period of 0.5 h. THF (10 mL) was used to rinse the flask and was also transferred. The reaction was then slowly warmed up to room temperature and stirred for 0.5 h before it was cooled to −78 °C again. MeI (6.36 mL, 14.50 g, 102.2 mmol, 2.0 equiv) was added dropwise and the reaction was slowly warmed up to room temperature. After stirring it overnight, the reaction was quenched by adding saturated aqueous NH₄Cl solution and was extracted with EtOAc three times. The combined organic extracts were washed with brine, dried over Na₂SO₄, and evaporated in vacuo. The product was purified by flash column chromatography (PE/EtOAc, 20:1) giving ethyl 8-methyl-1,4-dioxaspiro[4.5]decane-8-carboxylate as a colorless oil (9.68 g, 83%). Its ¹H NMR data matched with those reported in the literature.²⁵¹H NMR (400 MHz): δ 4.02 (q, J = 7.1 Hz, 2H), 3.81 (s, 4H), 2.00 (dt, J = 13.0, 3.6 Hz, 2H), 1.58–1.32 (m, 6H), δ 1.13 (t, J = 7.1 Hz, 3H), 1.06 (s, 3H).

Step C: In a flame-dried Schlenk flask were added ethyl 8-methyl-1,4-dioxaspiro[4.5]decane-8-carboxylate (7.20 g, 31.5 mmol, 1.0 equiv) and anhydrous DCM (70 mL). LAH (2.63 g, 69.4 mmol, 2.2 equiv) was added in small portions at 0 °C. The reaction was stirred at 0 °C for 0.5 h before it was warmed up to room temperature slowly. After the reaction was stirred for 1.5 h, the reaction was diluted with DCM and saturated aqueous potassium sodium tartrate solution was carefully added. The reaction was then stirred vigorously for 1 h. The mixture was extracted with DCM three times. The combined organic extracts were washed with brine, dried over Na₂SO₄, and evaporated in vacuo to give (8-methyl-1,4-dioxaspiro[4.5]decan-8-yl)methanol as a white solid (5.81 g, 99%), which was pure enough to continue for the next step without further purification. Its ¹H NMR data matched with those reported in the literature.²⁵¹H NMR (400 MHz): δ 3.94 (d, J = 1.7 Hz, 4H), 3.39 (s, 2H), 1.73–1.49 (m, 6H), 1.45–1.34 (m, 3H), 0.96 (s, 3H).

Step D: In a round-bottom flask were successively added (8-methyl-1,4-dioxaspiro[4.5]decan-8-yl)methanol (4.90 g, 26.3 mmol, 1.0 equiv), DCM (60 mL), and PCC (12.48 g, 57.9 mmol, 2.2 equiv). After the reaction was stirred at room temperature for 1 h, it was filtrated through a plug of silica gel and rinsed with EtOAc. The filtrate was evaporated and purified by flash column chromatography (PE/EtOAc, 5:1) giving 8-methyl-1,4-dioxaspiro[4.5]decane-8-carbaldehyde a colorless oil (4.20 g, 87%). Its ¹H NMR data matched with those reported in the literature.²⁶¹H NMR (400 MHz): δ 9.46 (s, 1H), 3.93 (s, 4H), 2.07–1.92 (m, 2H), 1.70–1.49 (m, 6H), 1.04 (s, 3H).

Step E: In a flame-dried Schlenk flask were added methyl triphenylphosphonium bromide (13.44 g, 37.6 mmol, 1.65 equiv) and anhydrous THF (75 mL) at 0 °C under N₂. n-BuLi (13.7 mL, 2.5 M in hexanes, 34.25 mmol, 1.5 equiv) was then added dropwise. The reaction was warmed up to room temperature and stirred for 0.5 h before it was cooled to 0 °C again. In another flask, a solution of 8-methyl-1,4-dioxaspiro[4.5]decane-8-carbaldehyde (4.20 g, 22.8 mmol, 1.0 equiv) in anhydrous THF (20 mL) was prepared and the solution was slowly transferred to the Wittig reagent flask via a cannula over a period of 0.5 h. 10 mL of anhydrous THF was used to rinse the flask and was also transferred. The reaction was then stirred at room temperature for 3 h. Acetone (5 mL) was added to quench the Wittig reagent. The mixture was filtrated and washed with Et₂O. The filtrate was evaporated and purified by flash column chromatography (n-pentane/Et₂O, 15:1) giving 8-methyl-8-vinyl-1,4-dioxaspiro[4.5]decane as a pale yellow oil (3.46 g, 83%). Its ¹H NMR data matched with those reported in the literature.²⁶¹H NMR (400 MHz): δ 5.79 (dd, J = 17.8, 10.7 Hz, 1H), 5.01 (d, J = 4.6 Hz, 1H), 4.98 (s, 1H), 3.93 (s, 4H), 1.69–1.61 (m, 6H), 1.53–1.44 (m, 2H), 1.01 (s, 3H).

Step F: 8-Methyl-8-vinyl-1,4-dioxaspiro[4.5]decane (3.40 g, 18.7 mmol) was dissolved in acetone (60 mL). 10% HCl (24 mL) was then added dropwise. The reaction was stirred for 2.5 h before brine was added. The mixture was extracted with DCM/Et₂O (1:2) three times. The volatiles were carefully evaporated in vacuo giving 4-methyl-4-vinylcyclohexan-1-one as a colorless oil (2.57 g, quantitative yield). Its ¹H NMR data matched with those reported in the literature.²⁶¹H NMR (400 MHz): δ 5.89 (dd, J = 17.5, 11.0 Hz, 1H), 5.18–5.08 (m, 2H), 2.45–2.25 (m, 4H), 1.97–1.90 (m, 2H), 1.74–1.67 (m, 2H), 1.12 (d, J = 0.9 Hz, 3H).

Step G: In a flame-dried Schlenk flask was added LiHMDS (7.6 mL, 1.0 M in THF, 7.6 mmol, 1.05 equiv) under N₂ and 4-methyl-4-vinylcyclohexan-1-one (1.00 g, 7.2 mmol, 1.0 equiv) in DMF (4 mL) was added dropwise at −78 °C. The reaction was then left to stir for 1.5 h before MeI (446 μL, 7.2 mmol, 1.0 equiv) was added dropwise. The reaction was slowly warmed up to room temperature and stirred overnight. The reaction was quenched by adding saturated aqueous NH₄Cl solution and was extracted with Et₂O three times. The combined extracts were washed with water three times and brine, dried over Na₂SO₄, and evaporated in vacuo. The product was purified by flash column chromatography (n-pentane/Et₂O, 20:1) giving 2,4-dimethyl-4-vinylcyclohexan-1-one (28) as a pale yellow oil (0.82 g, 74%, dr: trans/cis = 5:4). ¹H NMR (400 MHz): δ 5.98 (dd, J = 17.6, 10.9 Hz, 1H_trans), 5.84 (dd, J = 17.5, 10.7 Hz, 1H_cis), 5.26–5.19 (m, 1H_trans and 1H_cis), 5.04–4.95 (m, 1H_trans and 1H_cis), 2.66–2.41 (m, 2H_trans and 2H_cis), 2.34 (dt, J = 14.4, 3.8 Hz, 1H_cis), 2.25 (ddd, J = 14.0, 4.5, 2.5 Hz, 1H_trans), 2.10–2.01 (m, 1H_trans and 1H_cis), 1.81–1.77 (m, 1H_trans), 1.73–1.65 (m, 1H_cis), 1.51 (t, J = 13.4 Hz, 1H_cis), 1.44 (m, t, J = 13.4 Hz, 1H_trans), 1.33 (s, 3H_cis), 1.06 (s, 3H_trans), 1.04 (d, J = 6.5 Hz, 2H_cis), 1.01 (d, J = 6.5 Hz, 3H_trans). ¹³C{H} NMR (75 MHz): δ 213.9, 213.5, 148.3, 144.8, 113.5, 110.6, 47.0, 46.4, 41.3, 40.7, 38.5 (trans and cis), 37.9 (trans and cis), 37.7, 37.5, 30.3, 22.1, 14.7, 14.5. HRMS (FD) m/z: [M]⁺ calcd for C₁₀H₁₆O⁺, 152.1201; found, 152.1211.

Step H: In a flame-dried Schlenk flask were added 37 (dr = 5:4, 0.36 g, 2.36 mmol, 1.0 equiv) and anhydrous Et₂O (70 mL). LAH (0.18 g, 4.74 mmol, 2.0 equiv) was added in small portions at 0 °C. The reaction was stirred for 0.5 h before it was warmed up to room temperature slowly. After the reaction was stirred for 1.5 h, the reaction was diluted with Et₂O and saturated aqueous potassium sodium tartrate solution was carefully added. The reaction was then stirred vigorously for 1 h. The mixture was extracted with Et₂O three times. The combined organic extracts were washed with brine, dried over Na₂SO₄, and evaporated in vacuo. The product was purified by flash column chromatography (n-pentane/Et₂O, 5:1) giving 2,4-dimethyl-4-vinylcyclohexanol (31) as a pale yellow oil (0.35 g, 96%, dr: A/B = 5:4). ¹H NMR (300 MHz): δ 5.78 (dd, J = 17.6, 10.8 Hz, 1H_A and 1H_B), 5.07–4.84 (m, 2H_A and 2H_B), 3.14–3.05 (m, 1H_A and 1H_B), 1.87–1.22 (m, 7H_A and 7H_B), 1.05 (s, 3H_B), 0.99 (d, J = 6.5 Hz, 3H_B), 0.97 (d, J = 6.7 Hz, 3H_A), 0.95 (s, 3H_A). ¹³C{H} NMR (75 MHz): δ 150.4, 146.2, 112.5, 109.4, 45.4, 44.4, 37.2, 36.5, 36.4, 36.1, 35.5, 35.5, 31.9 (A and B), 31.2, 31.1, 22.4 (A and B), 18.8, 18.7. HRMS (FD) m/z: [M]⁺ calcd for C₁₀H₁₈O⁺, 154.1358; found, 154.1360.

Synthesis of Model Substrates

5-Methoxy-N-methyl-3,4-dihydroquinolin-2(1H)-one (2a)

In a flame-dried Schlenk flask were added 5-hydroxy-3,4-dihydroquinolin-2(1H)-one (326 mg, 2.0 mmol, 1.0 equiv) and anhydrous DMF (10 mL) under N₂. NaH (240 mg, 60% in mineral oil, 6.0 mmol, 3.0 equiv) was then added at 0 °C and stirred for 0.5 h. MeI (500 μL, 8.0 mmol, 4.0 equiv) was then added dropwise at 0 °C. The reaction was then warmed up to room temperature and stirred overnight. The reaction was quenched by adding water and extracted with EtOAc three times. The combined organic extracts were washed with water three times and brine two times, dried with Na₂SO₄, filtrated, and concentrated in vacuo to give 2a as a pale yellow solid (380 mg, 99%). Its ¹H NMR data matched with those reported in the literature.²⁷¹H NMR (400 MHz): δ 7.21 (t, J = 8.2 Hz, 1H), 6.64 (d, J = 8.3 Hz, 2H), 3.85 (s, 3H), 3.35 (s, 3H), 2.89 (dd, J = 8.6, 6.4 Hz, 2H), 2.60 (dd, J = 8.6, 6.4 Hz, 2H).

5-Hydroxy-N-methyl-3,4-dihydroquinolin-2(1H)-one (5a)

In a flame-dried Schlenk flask were added 2a (1.15 g, 6.0 mmol, 1.0 equiv) and anhydrous DCM (10 mL) under N₂. A solution of BBr₃ in DCM (18 mL, 1.0 M, 18.0 mmol, 3.0 equiv) was added dropwise at −78 °C. After stirring the reaction for another 1 h at −78 °C, the reaction was slowly warmed up to room temperature and stirred for additional 3 h. Water was slowly added to quench the reaction and the reaction was extracted with DCM three times. The combined organic extracts were washed with water and brine, dried with MgSO₄, filtrated, and concentrated in vacuo to give 5a as a pale yellow solid (1.02 g, 96%). Its ¹H NMR data matched with those reported in the literature.²⁸¹H NMR (400 MHz): δ 7.11 (t, J = 8.2 Hz, 1H), 6.61 (d, J = 8.2 Hz, 1H), 6.54 (d, J = 7.9 Hz, 1H), 3.35 (s, 3H), 2.90 (dd, J = 8.7, 6.3 Hz, 2H), 2.64 (dd, J = 8.5, 6.4 Hz, 2H).

5-(Methoxymethoxy)-N-methyl-3,4-dihydroquinolin-2(1H)-one (4a)

In a flame-dried Schlenk flask were added 5a (532 mg, 3.0 mmol, 1.0 equiv) and freshly distilled THF (10 mL) under N₂. NaH (156 mg, 60% in mineral oil, 3.9 mmol, 1.3 equiv) was then added portionwise at 0 °C. After stirring it at room temperature for 0.5 h, MOMCl (1.127 g, 15.1 mmol, 1.2 equiv) was added to the reaction dropwise at 0 °C. After stirring it for 3 h at room temperature, the reaction was quenched by slowly adding water and extracted with EtOAc three times. The combined organic extracts were washed with brine, dried over Na₂SO₄, and evaporated in vacuo. The product was purified by flash column chromatography (n-hexane/EtOAc, 3:1) giving 4a as a pale yellow solid (500 mg, 75%). ¹H NMR (400 MHz): δ 7.18 (t, J = 8.3 Hz, 1H), 6.85 (dd, J = 8.4, 0.9 Hz, 1H), 6.68 (d, J = 8.2 Hz, 1H), 5.21 (s, 2H), 3.49 (s, 3H), 3.35 (s, 3H), 2.93 (dd, J = 8.6, 6.4 Hz, 2H), 2.61 (dd, J = 8.6, 6.4 Hz, 2H). ¹³C{H} NMR (75 MHz): δ 170.6, 154.1, 141.9, 127.8, 115.5, 109.3, 108.8, 94.8, 56.3, 31.2, 29.9, 18.3. HRMS (FD) m/z: [M]⁺ calcd for C₁₂H₁₅NO₃⁺, 221.1052; found, 221.1061.

5-Ethoxy-3,4-dihydroquinolin-2(1H)-one

In a flame-dried Schlenk flask were added 5-hydroxy-3,4-dihydroquinolin-2(1H)-one (0.70 g, 4.29 mmol, 1.0 equiv), K₂CO₃ (1.23 mg, 8.93 mmol, 2.1 equiv), EtBr (0.7 mg, 6.42 mmol, 1.5 equiv), and anhydrous DMF (5 mL) under N₂. The reaction was then stirred at 70 °C for 5 h. Water was then added and the mixture was extracted with EtOAc three times. The combined organic extracts were washed with water three times and brine two times, dried with MgSO₄, filtrated, and concentrated in vacuo to yield 5-ethoxy-3,4-dihydroquinolin-2(1H)-one as a white solid (800 mg, 98%), which was pure enough to be directly used for the next step. Its ¹H NMR data matched with those reported in the literature.²⁹¹H NMR (400 MHz): δ 7.58 (br s, 1H), 7.10 (t, J = 8.1 Hz, 1H), 6.56 (d, J = 8.2 Hz, 1H), 6.35 (d, J = 7.9 Hz, 1H), 4.05 (q, J = 7.0 Hz, 2H), 2.97 (t, J = 7.7 Hz, 2H), 2.60 (dd, J = 8.4, 6.9 Hz, 2H), 1.42 (t, J = 7.0 Hz, 3H).

5-Ethoxy-N-methyl-3,4-dihydroquinolin-2(1H)-one (3a)

In a flame-dried Schlenk flask were added 5-ethoxy-3,4-dihydroquinolin-2(1H)-one (191 mg, 1.0 mmol, 1.0 equiv) and anhydrous DMF (2 mL) under N₂. NaH (60 mg, 60% in mineral oil, 1.5 mmol, 1.5 equiv) was then added at 0 °C and stirred for 0.5 h. MeI (170 mg, 1.2 mmol, 1.2 equiv) was then added dropwise at 0 °C. The reaction was then warmed up to room temperature and stirred overnight. The reaction was quenched by adding water and extracted with EtOAc three times. The combined organic extracts were washed with water three times and brine two times, dried with MgSO₄, filtrated, and concentrated in vacuo to give 3a as a white solid (200 mg, 98%). Its ¹H NMR data matched with those reported in the literature.²⁹¹H NMR (400 MHz): δ 7.20–7.15 (m, 1H), 6.63–6.61 (m, 2H), 4.05 (q, J = 7.0 Hz, 2H), 3.34 (s, 3H), 2.93–2.88 (m, 2H), 2.60 (t, J = 7.3 Hz, 2H), 1.42 (t, J = 7.0 Hz, 3H).

5-Ethoxy-N-(methoxymethyl)-3,4-dihydroquinolin-2(1H)-one (6a)

In a flame-dried Schlenk flask were added 5-ethoxy-3,4-dihydroquinolin-2(1H)-one (150 mg, 0.78 mmol, 1.0 equiv) and freshly distilled THF (3 mL) under N₂. NaH (47 mg, 60% in mineral oil, 1.17 mmol, 1.5 equiv) was then added at 0 °C. After stirring it for 0.5 h at 0 °C, MOMCl (70 μL, 0.94 mmol, 1.2 equiv) was added to the reaction at 0 °C dropwise. After stirring it for 2 h at room temperature, the reaction was quenched by slowly adding water and extracted with EtOAc three times. The combined organic extracts were washed with brine, dried over Na₂SO₄, and evaporated in vacuo. The product was purified by flash column chromatography (PE/EtOAc, 4:1) giving 6a as a pale yellow solid (99 mg, 54%). ¹H NMR (300 MHz): δ 7.21–7.12 (m, 1H), 6.93 (d, J = 7.9 Hz, 1H), 6.63 (d, J = 8.2 Hz, 1H), 5.30 (s, 2H), 4.05 (q, J = 6.5 Hz, 2H), 3.40 (s, 3H), 2.93 (t, J = 7.5 Hz, 2H), 2.68–2.62 (m, 2H), 1.42 (t, J = 7.0 Hz, 3H). ¹³C{H} NMR (101 MHz): δ 171.7, 155.7, 140.9, 127.9, 114.7, 108.8, 107.1, 74.2, 64.1, 56.4, 31.5, 18.3, 15.0. HRMS (FD) m/z: [M]⁺ calcd for C₁₃H₁₇NO₃⁺, 235.1208; found, 235.1219.

4-{[5-Ethoxy-2-oxo-3,4-dihydroquinolin-1(2H)-yl]methyl}phenyl Acetate (7a)

In a flame-dried Schlenk flask were added 5-ethoxy-3,4-dihydroquinolin-2(1H)-one (215 mg, 1.12 mmol, 1.0 equiv) and anhydrous DMF (3 mL) under N₂. NaH (54 mg, 60% in mineral oil, 1.35 mmol, 1.2 equiv) was then added at 0 °C and stirred for 0.5 h at 0 °C. 4-(Bromomethyl)phenyl acetate (332 mg, 1.46 mmol, 1.3 equiv) was then added at 0 °C. The reaction was then warmed up to room temperature and stirred overnight. The reaction was quenched by adding water and extracted with EtOAc three times. The combined organic extracts were washed with water three times and brine two times, dried over MgSO4, filtrated, and concentrated in vacuo. The product was purified by flash column chromatography (n-hexane/EtOAc, 3:1) giving 7a as a pale yellow solid (250 mg, 66%). mp 102.0–103.3 °C. ¹H NMR (400 MHz): δ 7.22 (d, J = 8.2 Hz, 2H), 7.07–7.01 (m, 3H), 6.58 (d, J = 8.3 Hz, 1H), 6.51 (d, J = 8.2 Hz, 1H), 5.15 (s, 2H), 4.04 (q, J = 6.9 Hz, 2H), 2.98 (dd, J = 8.6, 6.3 Hz, 2H), 2.73 (dd, J = 8.7, 6.3 Hz, 2H), 2.27 (s, 3H), 1.42 (t, J = 6.9, 3H). ¹³C{H} NMR (101 MHz): δ 170.8, 169.6, 155.9, 149.7, 141.0, 135.0, 127.8, 127.6, 121.9, 114.8, 108.5, 106.8, 64.1, 46.0, 31.5, 21.3, 18.3, 15.0. IR ν: 2977, 1758, 1671, 1594, 1467, 1188, 728 cm^–1. HRMS (FD) m/z: [M]⁺ calcd for C₂₀H₂₁NO₄⁺, 339.1471; found, 339.1471.

Synthesis of Core Structures (±)-16 and (±)-27 of Yaequinolone-Related Natural Products

Synthesis of (±)-16

1-(Benzyloxy)-2-bromo-3-nitrobenzene (9)

In a round-bottom flask were added 2-bromo-3-nitrophenol (8) (2.18 g, 10.0 mmol, 1.0 equiv), K₂CO₃ (4.15 g, 30.0 mmol, 3.0 equiv), benzyl chloride (2.3 mL, 20 mmol, 2.0 equiv), and EtOH (15 mL) successively. The mixture was then refluxed at 85 °C overnight. The volatiles were removed in vacuo. The product was purified by flash column chromatography (PE/EtOAc, 3:1) giving 9 as a yellow solid (2.80 g, 91%). mp 73.0–74.0 °C. ¹H NMR (400 MHz): δ 7.49 (d, J = 7.6 Hz, 2H), 7.48–7.26 (m, 5H), 7.17–7.09 (m, 1H), 5.25 (s, 2H). ¹³C{H} NMR (101 MHz): δ 156.6, 135.6, 128.9, 128.7, 128.5, 127.2, 117.0, 116.4, 105.5, 71.8. HRMS (FD) m/z: [M]⁺ calcd for C₁₃H₁₀BrNO₃⁺, 306.9844; found, 306.9816.

[2-(Benzyloxy)-6-nitrophenyl](4-methoxyphenyl)methanol (10)

In a flame-dried Schlenk flask were added 9 (4.00 g, 13.0 mmol, 1.0 equiv) and freshly distilled THF (50 mL) under N₂. At −95 °C, n-BuLi (6.24 mL, 2.5 M in hexanes, 15.6 mmol, 1.2 equiv) was then added dropwise. The reaction was continued to stir at −95 °C for 1.5 h before a solution of p-anisaldehyde (3.54 g, 26.0 mmol, 2.0 equiv) in THF (10 mL) was added dropwise. After stirring the reaction for another 2 h, the reaction was quenched by slow addition of saturated solution of NH₄Cl and extracted with EtOAc three times. The combined organic extracts were washed with brine, dried over Na₂SO₄, and concentrated in vacuo. The sample was purified by flash column chromatography (n-hexane/EtOAc, 5:1 to 3:1) giving 10 as a pale yellow oil (2.20 g, 46%). Another reaction using 4.00 g of 9 (13.0 mmol) with 0.95 equiv of n-BuLi and 0.5 equiv of para-anisaldehyde was also performed, and 2.06 g of 10 was obtained (86% based on para-anisaldehyde). ¹H NMR (400 MHz): δ 7.44–7.36 (m, 2H), 7.31–7.27 (m, 3H), 7.24–7.18 (m, 3H), 7.02 (dd, J = 7.5, 2.1 Hz, 2H), 6.86–6.82 (m, 2H), 6.23 (d, J = 10.5 Hz, 1H), 5.07 (d, J = 11.5 Hz, 1H), 4.99 (d, J = 11.5 Hz, 1H), 3.81 (s, 3H). ¹³C{H} NMR (101 MHz): δ 158.8, 157.1, 150.7, 135.1, 134.6, 129.2, 128.6, 128.4, 127.5, 127.1, 126.4, 116.6, 116.5, 113.5, 71.2, 69.4, 55.3. IR ν: 3545, 2934, 1604, 1509, 1356, 1246, 1025, 737 cm^–1. HRMS (FD) m/z: [M]⁺ calcd for C₂₁H₁₉NO₅⁺, 365.1263; found, 365.1248.

[2-Amino-6-(benzyloxy)phenyl](4-methoxyphenyl)methanol (11)

In a round bottom flask were added 10 (2.00 g, 5.5 mmol, 1.0 equiv), EtOH (30 mL), and Na₂S (1.28 g, 16.4 mmol, 3.0 equiv) successively. The reaction was then refluxed at 85 °C for 15 min before water was added to quench the reaction. The mixture was then extracted with EtOAc three times. The combined organic extracts were washed with brine, dried over Na₂SO₄, and evaporated in vacuo. The obtained 11 was directly used for the next step. ¹H NMR (400 MHz): δ 7.38–7.30 (m, 8H), 7.04 (t, J = 8.1 Hz, 1H), 6.87–6.82 (m, 2H), 6.49 (s, 1H), 6.45 (dd, J = 8.3, 1.0 Hz, 1H), 6.32 (dd, J = 8.0, 0.9 Hz, 1H), 5.08 (d, J = 11.7 Hz, 1H), 5.02 (d, J = 11.7 Hz, 1H), 3.78 (s, 3H). ¹³C NMR (101 MHz): δ 158.7, 156.9, 146.4, 137.1, 135.0, 129.1, 128.6, 128.0, 127.5, 127.2, 116.6, 113.7, 111.1, 102.7, 70.6, 68.4, 55.4.

N-{3-(Benzyloxy)-2-[hydroxy(4-methoxyphenyl)methyl]phenyl}-2-methoxyacetamide (12)

In a flame-dried Schlenk flask were added crude 11 obtained from the previous step, ⁱPr₂NEt (853 mg, 6.6 mmol, 1.2 equiv), and freshly distilled DCM (25 mL). 2-Methoxyacetyl chloride (657 mg, 6.05 mmol, 1.1 equiv) was then added dropwise at 0 °C. The reaction was stirred for another 40 min at room temperature before it was quenched by adding water. The reaction was extracted with DCM three times and the combined extracts were washed with brine, dried over Na₂SO₄, and concentrated in vacuo. The product was purified by flash column chromatography (n-hexane/EtOAc, 2:1) giving 12 as a pale yellow oil (1.40 g, 61% over two steps). ¹H NMR (400 MHz): δ 10.09 (br s, 1H), 7.95 (d, J = 8.3 Hz, 1H), 7.38–7.22 (m, 8H), 6.82–6.78 (m, 3H), 6.65 (s, 1H), 5.11 (d, J = 11.7 Hz, 1H), 5.04 (d, J = 11.7 Hz, 1H), 3.87 (d, J = 15.4 Hz, 1H), 3.77 (s, 3H), 3.69 (d, J = 15.5 Hz, 1H), 3.28 (s, 3H). ¹³C{H} NMR (101 MHz): δ 168.2, 158.3, 155.4, 137.6, 136.6, 134.4, 128.5, 128.3, 127.7, 127.1, 127.0, 121.1, 115.2, 113.2, 108.0, 72.0, 70.3, 67.4, 59.1, 54.9. IR ν: 3282, 2934, 2834, 1665, 1593, 1472, 1249, 1116 cm^–1. HRMS (FD) m/z: [M]⁺ calcd for C₂₄H₂₅NO₅⁺, 407.1733; found, 407.1746.

N-[3-(Benzyloxy)-2-(4-methoxybenzoyl)phenyl]-2-methoxyacetamide (13)

In a round bottom flask were added 12 (1.40 g, 3.44 mmo, 1.0 equiv) and DCM (30 mL). PCC (1.48 g, 6.88 mmol, 2.0 equiv) was then added portionwise. After stirring it at room temperature for 1 h, TLC showed full conversion of the reaction. The reaction was then quenched by a saturated solution of Na₂SO₃ and extracted with DCM three times. The combined organic extracts were washed with brine, dried over Na₂SO₄, and evaporated in vacuo. The product was purified by flash column chromatography (n-hexane/EtOAc, 1.5:1) giving 13 as a pale yellow oil (1.30 g, 94%). ¹H NMR (400 MHz): δ 9.32 (br s, 1H), 7.99 (d, J = 8.3 Hz, 1H), 7.82–7.75 (m, 2H), 7.37 (t, J = 8.4 Hz, 1H), 7.19–7.06 (m, 3H), 6.91–6.82 (m, 4H), 6.78 (d, J = 8.3 Hz, 1H), 4.89 (s, 2H), 3.87 (s, 2H), 3.78 (s, 3H), 3.32 (s, 3H). ¹³C{H} NMR (101 MHz): δ 194.9, 168.1, 163.7, 156.6, 136.3, 136.0, 131.7, 131.5, 128.0, 127.4, 126.5, 119.1, 114.8, 113.5, 108.3, 71.9, 70.0, 59.2, 55.3. IR ν: 3359, 2935, 2837, 1692, 1592, 1461, 1253, 927 cm^–1. HRMS (FD) m/z: [M]⁺ calcd for C₂₄H₂₃NO₅⁺, 405.1576; found, 405.1591.

(3R*,4R*)-5-(Benzyloxy)-4-hydroxy-3-methoxy-4-(4-methoxyphenyl)-3,4-dihydroquinolin-2(1H)-one [(±)-14]

In a flame-dried Schlenk flask were added 13 (0.94 g, 2.32 mmol, 1.0 equiv) and freshly distilled THF (50 mL) at 0 °C under N₂. A solution of KO^tBu (16.2 mL, 1.0 M in THF, 16.2 mmol, 7.0 equiv) was then added dropwise. After stirring it at 0 °C for 2 h, TLC showed full conversion of the reaction. The reaction was quenched by adding water and extracted with EtOAc (three times). The combined organic extracts were washed with brine, dried over Na₂SO₄, and evaporated in vacuo. The product was purified by flash column chromatography (n-hexane/EtOAc, 1:1.5) giving (±)-14 as a single diastereoisomer: white solid (0.75 g, 80%). ¹H NMR (400 MHz): δ 8.80 (br s, 1H), 7.32–7.25 (m, 3H), 7.25–7.16 (m, 3H), 7.12 (dd, J = 6.3, 2.7 Hz, 2H), 6.86–6.77 (m, 2H), 6.73 (d, J = 8.4 Hz, 1H), 6.55 (dd, J = 8.1, 0.9 Hz, 1H), 5.33 (s, 1H), 5.07 (d, J = 11.5 Hz, 1H), 4.99 (d, J = 11.5 Hz, 1H), 3.83 (s, 1H), 3.77 (d, J = 1.0 Hz, 3H), 3.61 (s, 3H). ¹³C{H} NMR (101 MHz): δ 168.3, 159.7, 158.0, 137.1, 135.7, 133.6, 129.9, 128.7, 128.4, 127.6, 127.5, 115.3, 114.0, 109.6, 108.7, 85.1, 78.1, 71.1, 59.7, 55.3. IR ν: 3509, 2932, 1692, 1607, 1509, 1259, 1103 cm^–1. HRMS (FD) m/z: [M]⁺ calcd for C₂₄H₂₃NO₅⁺, 405.1576; found, 405.1591.

(3R*,4R*)-5-(Benzyloxy)-4-hydroxy-3-methoxy-4-(4-methoxyphenyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-3,4-dihydroquinolin-2(1H)-one [(±)-15]

In a flame-dried Schlenk flask were added (±)-14 (1.20 g, 2.96 mmol, 1.0 equiv) and anhydrous THF (50 mL) under N₂. LiHMDS solution in THF (3.26 mL, 1.0 M, 3.26 mmol, 1.1 equiv) was then added dropwise at 0 °C. After stirring it for 0.5 h, SEMCl (0.59 g, 3.55 mmol, 1.2 equiv) was added dropwise. The reaction was continued to stir at 0 °C for 2 h before water was added to quench the reaction. The mixture was extracted with EtOAc three times. The combined organic extracts were washed with brine, dried over Na₂SO₄, and evaporated in vacuo. The product was purified by flash column chromatography (PE/EtOAc, 3:1) giving (±)-15 as a white solid (1.40 g, 88%). ¹H NMR (400 MHz): δ 7.33 (t, J = 8.3 Hz, 1H), 7.30–7.26 (m, 3H), 7.19–7.11 (m, 5H), 6.84–6.80 (m, 3H), 5.67 (d, J = 11.0 Hz, 1H), 5.49 (s, 1H), 5.10 (d, J = 11.5 Hz, 1H), 5.01 (d, J = 11.5 Hz, 1H), 4.96 (d, J = 11.0 Hz, 1H), 3.92 (s, 1H), 3.78 (s, 3H), 3.67–3.54 (m, 2H), 3.58 (s, 3H), 0.98–0.94 (m, 2H), 0.00 (s, 9H). ¹³C{H} NMR (101 MHz): δ 167.6, 159.8, 157.4, 139.8, 135.7, 133.5, 129.7, 128.8, 128.4, 127.7, 127.5, 116.9, 114.0, 110.0, 109.3, 85.3, 77.4, 72.2, 71.2, 66.0, 59.4, 55.3, 18.1, −1.3. IR ν: 3508, 2952, 1693, 1594, 1465, 1385, 1247, 1064, 832 cm^–1. HRMS (FD) m/z: [M]⁺ calcd for C₃₀H₃₇NO₆Si⁺, 535.2390; found, 535.2383.

(3R*,4R*)-4,5-Dihydroxy-3-methoxy-4-(4-methoxyphenyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-3,4-dihydroquinolin-2(1H)-one [(±)-16]

In a Schlenk flask were added (±)-15 (430 mg), EtOH (5 mL), EtOAc (5 mL), and Pd/C (100 mg, 10 wt %) under N₂. The flask atmosphere was then changed to H₂ by using a balloon filled with H₂. The reaction was then stirred for 2 h under H₂ (1 atm. pressure). The reaction was filtrated and evaporated in vacuo. The product was purified by flash column chromatography (n-hexane/EtOAc, 3:1) giving (±)-17 as a white solid (446 mg, 95%). 430 mg of (±)-15 (0.80 mmol) and 100 mg Pd/C (10% wt) were used. Purification was performed using PE/EtOAc (3:1) as an eluent. Product (±)-16 was isolated as a white solid in 95% yield (340 mg). ¹H NMR (400 MHz): δ 8.86 (s, 1H), 7.28 (t, J = 8.2 Hz, 1H), 7.17–7.15 (m, 2H), 6.98 (d, J = 8.3 Hz, 1H), 6.85–6.82 (m, 2H), 6.74 (d, J = 8.3 Hz, 1H), 5.65 (d, J = 11.0 Hz, 1H), 5.00 (d, J = 10.9 Hz, 1H), 4.53 (s, 1H), 3.85 (s, 1H), 3.77 (s, 3H), 3.63–3.53 (m, 2H), 3.59 (s, 3H), 0.96 (t, J = 8.3 Hz, 2H), 0.00 (s, 9H). ¹³C{H} NMR (101 MHz): δ 166.1, 160.4, 157.6, 138.1, 130.4, 129.0, 128.2, 114.3, 113.8, 112.3, 107.7, 84.6, 78.1, 72.2, 66.1, 58.8, 55.3, 18.1, −1.3. IR ν: 3353, 2953, 1677, 1613, 1470, 1243, 1073, 834 cm^–1. HRMS (FD) m/z: [M]⁺ calcd for C₂₃H₃₁NO₆Si⁺, 445.1921; found, 445.1939.

Synthesis of (±)-27

[2-(Benzyloxy)-6-nitrophenyl](phenyl)methanol (Int-F)

The procedure for the preparation of 10 was followed. 4.00 g of 9 (13.0 mmol) was used and purification was performed using PE/EtOAc (7:1 to 3:1) as an eluent. Product Int-F was isolated as a yellow oil in 48% yield (2.10 g). Another reaction using 4.00 g of 9 (13.0 mmol) with 0.95 equiv of n-BuLi and 0.5 equiv of anisaldehyde was also performed, and 1.93 g of Int-F was obtained (88% based on anisaldehyde). ¹H NMR (400 MHz): δ 7.41–7.36 (m, 2H), 7.34–7.20 (m, 8H), 7.15 (d, J = 7.9 Hz, 1H), 6.94–6.87 (m, 2H), 6.26 (s, 1H), 5.02 (dd, J = 11.6, 2.8 Hz, 1H), 4.92 (d, J = 11.5 Hz, 1H). ¹³C{H} NMR (101 MHz): δ 157.3, 151.0, 142.6, 135.0, 129.4, 128.8, 128.6, 128.3, 127.6, 127.3, 126.6, 125.8, 116.8, 77.4, 71.5, 69.6. IR ν: 3031, 1528, 1452, 1356, 1023, 737, 697 cm^–1. HRMS (EI) m/z: [M – OH]⁺ calcd for C₂₀H₁₆NO₃⁺, 318.1130; found, 318.1110.

[2-Amino-6-(benzyloxy)phenyl](phenyl)methanol (Int-G)

The procedure for the preparation of 11 was followed. 1.80 g of Int-F (5.4 mmol) was used and the reaction was refluxed for 0.5 h. Product Int-G was used for the next step without purification. ¹H NMR (400 MHz): δ 7.46 (d, J = 7.5 Hz, 2H), 7.42–7.16 (m, 8H), 7.08 (t, J = 8.2 Hz, 1H), 6.57 (s, 1H), 6.49 (d, J = 8.3 Hz, 1H), 6.35 (d, J = 7.9 Hz, 1H), 5.17–5.02 (m, 2H). ¹³C{H} NMR (101 MHz): δ 156.9, 146.1, 143.0, 137.1, 129.2, 128.6, 128.3, 128.0, 127.5, 127.0, 125.9, 116.7, 111.2, 102.9, 70.6, 68.5.

N-{3-(Benzyloxy)-2-[hydroxy(phenyl)methyl]phenyl}-2-methoxyacetamide (Int-H)

The procedure for the preparation of 12 was followed. The crude sample Int-G from the previous step was used and purification was performed using PE/EtOAc (2.5:1) as an eluent. Product Int-H was isolated as a yellow oil in 67% yield (2.10 g) over two steps. ¹H NMR (400 MHz): δ 9.76 (s, 1H), 7.89 (d, J = 8.3 Hz, 1H), 7.41–7.16 (m, 11H), 6.82 (d, J = 8.4 Hz, 1H), 6.67 (s, 1H), 5.13 (d, J = 11.6 Hz, 1H), 5.05 (d, J = 11.6 Hz, 1H), 3.89 (d, J = 15.4 Hz, 1H), 3.67 (d, J = 15.3 Hz, 1H), 3.29 (s, 3H). ¹³C{H} NMR (101 MHz): δ 168.3, 156.0, 142.0, 137.7, 136.7, 129.3, 128.7, 128.2, 128.2, 127.6, 127.2, 125.8, 121.4, 116.1, 108.7, 72.4, 71.0, 68.2, 59.5. IR ν: 3293, 2934, 1665, 1592, 1443, 1261, 1117, 736 cm^–1. HRMS (EI) m/z: [M – H₂O]⁺ calcd for C₂₃H₂₁NO₃⁺, 359.1521; found, 359.1513.

N-[2-Benzoyl-3-(benzyloxy)phenyl]-2-methoxyacetamide (Int-I)

The procedure for the preparation of 13 was followed. 1.46 g of Int-H (3.87 mmol) was used and purification was performed using PE/EtOAc (2:1) as eluent. Product Int-I was isolated as a pale yellow solid in 89% yield (1.29 g). ¹H NMR (400 MHz): δ 9.53 (s, 1H), 8.04 (d, J = 8.4 Hz, 1H), 7.79 (d, J = 8.5 Hz, 1H), 7.59–7.50 (m, 3H), 7.46–7.40 (m, 3H), 7.20–7.11 (m, 3H), 6.81 (d, J = 8.4 Hz, 1H), 6.76 (d, J = 7.6 Hz, 2H), 4.88 (d, J = 2.0 Hz, 2H), 3.92 (d, J = 1.9 Hz, 2H), 3.39 (d, J = 2.3 Hz, 3H). ¹³C{H} NMR (101 MHz): δ 197.0, 168.4, 157.3, 139.3, 137.0, 135.9, 133.0, 132.4, 129.2, 128.4, 128.2, 127.7, 126.7, 118.6, 115.0, 108.4, 72.2, 70.3, 59.5. IR ν: 3354, 2936, 1692, 1581, 1466, 1274, 1070, 923, 697 cm^–1. HRMS (EI) m/z: [M]⁺ calcd for C₂₃H₂₁NO₄⁺, 375.1471; found, 375.1464.

(3R*,4R*)-5-(Benzyloxy)-4-hydroxy-3-methoxy-4-phenyl-3,4-dihydroquinolin-2(1H)-one [(±)-Int-J]

The procedure for the preparation of (±)-14 was followed. 1.15 g of Int-I (3.06 mmol) was used and purification was performed using PE/EtOAc (1:1) as an eluent. Product (±)-Int-J was isolated as a white solid in 95% yield (1.10 g). ¹H NMR (400 MHz): δ 8.76 (br s, 1H), 7.27–7.18 (m, 9H), 7.06–7.03 (m, 2H), 6.70 (d, J = 8.3 Hz, 1H), 6.55 (d, J = 8.3 Hz, 1H), 5.28 (br s, 1H), 5.03 (d, J = 11.6 Hz, 1H), 4.93 (d, J = 11.6 Hz, 1H), 3.83 (s, 1H), 3.59 (s, 3H). ¹³C{H} NMR (101 MHz): δ 168.1, 158.0, 141.9, 137.2, 135.7, 130.0, 128.7, 128.7, 128.4, 128.3, 127.4, 126.2, 115.2, 109.6, 108.7, 85.0, 78.3, 71.0, 59.8. Its NMR data matched with those reported in the literature.^10a

(3R*,4R*)-5-(Benzyloxy)-4-hydroxy-3-methoxy-4-phenyl-1-{[2-(trimethylsilyl)ethoxy]methyl}-3,4-dihydroquinolin-2(1H)-one [(±)-Int-K]

In a flame-dried Schlenk flask were added (±)-Int-J (0.90 g, 2.40 mmol, 1.0 equiv) and anhydrous THF (35 mL). LiHMDS solution in THF (3.12 mL, 1.0 M, 3.12 mmol, 1.3 equiv) was then added dropwise at 0 °C. After stirring it for 0.5 h, SEMCl (0.60 g, 3.60 mmol, 1.5 equiv) was added dropwise. The reaction was first stirred at 0 °C for 0.5 h and then 2 h at room temperature. Water was added to quench the reaction. The mixture was extracted with EtOAc three times. The combined organic extracts were washed with brine, dried over Na₂SO₄, and evaporated in vacuo. The sample was purified by flash column chromatography (PE/EtOAc, 4:1) giving (±)-Int-K as a white solid (1.15 g, 94%). ¹H NMR (400 MHz): δ 7.31 (t, J = 8.3 Hz, 1H), 7.29–7.20 (m, 8H), 7.16 (d, J = 8.4 Hz, 1H), 7.08–6.99 (m, 2H), 6.80 (d, J = 8.4 Hz, 1H), 5.64 (d, J = 11.0 Hz, 1H), 5.47 (br s, 1H), 5.05 (d, J = 11.5 Hz, 1H), 4.97–4.94 (m, 2H), 3.91 (s, 1H), 3.66–3.53 (m, 2H), 3.56 (s, 3H), 0.98–0.93 (m, 2H), −0.02 (s, 9H). ¹³C{H} NMR (101 MHz): δ 167.5, 157.4, 141.7, 139.9, 135.7, 129.8, 128.7, 128.6, 128.5, 128.3, 127.4, 126.3, 116.7, 109.9, 109.2, 85.2, 77.6, 72.2, 71.2, 66.0, 59.5, 18.1, −1.3. IR ν: 3507, 2951, 1693, 1593, 1469, 1376, 1247, 1062, 833, 730, 696 cm^–1. HRMS (FD) m/z: [M]⁺ calcd for C₂₉H₃₅NO₅Si⁺, 505.2284; found, 505.2302.

(3R*,4R*)-4,5-Dihydroxy-3-methoxy-4-phenyl-1-{[2-(trimethylsilyl)ethoxy]methyl}-3,4-dihydroquinolin-2(1H)-one [(±)-27]

The procedure for the preparation of (±)-16 was followed. 0.90 g of (±)-Int-K (2.17 mmol) was used and purification was performed using PE/EtOAc (4:1) as an eluent. Product (±)-27 was isolated as a white solid in 94% yield (0.70 g). ¹H NMR (400 MHz): δ 8.80 (br s, 1H), 7.32–7.29 (m, 3H), 7.28–7.20 (m, 3H), 6.98 (d, J = 8.2 Hz, 1H), 6.72 (d, J = 8.3 Hz, 1H), 5.65 (d, J = 10.9 Hz, 1H), 5.00 (d, J = 10.9 Hz, 1H), 4.54 (s, 1H), 3.82 (s, 1H), 3.60–3.54 (m, 2H), 3.58 (s, 3H), 0.97–0.92 (m, 2H), −0.02 (s, 9H). ¹³C{H} NMR (101 MHz): δ 165.9, 157.6, 138.3, 137.3, 130.6, 129.5, 129.0, 126.7, 113.9, 112.2, 107.8, 84.6, 78.3, 72.3, 66.2, 58.9, 18.1, −1.3. IR ν: 3325, 2952, 1680, 1470, 1241, 1070, 834 cm^–1. HRMS (FD) m/z: [M]⁺ calcd for C₂₂H₂₉NO₅Si⁺, 415.1815; found, 415.1836.

C(6)–H Olefination of 3,4-Dihydro-2(1H)-quinolinone Derivatives

General Procedure

In a pressure tube containing a suitable stirring bar were added the corresponding 3,4-dihydro-2(1H)-quinolinone derivative (1.0 equiv), Pd(OAc)₂ (10 mol %), PhCO₃^tBu (1.0–2.0 equiv), olefin (1.5 equiv), S,O-ligand stock solution in DCE (0.1 M, 10 mol %), and DCE. The tube was introduced into an oil bath preheated at 80 °C and was stirred for 16 h. The tube was then removed from the oil bath and cooled to room temperature. The reaction was filtrated through Celite and rinsed with DCM. The filtrate was then washed with a saturated solution of Na₂CO₃, dried with MgSO₄, filtrated, and concentrated in vacuo. The product was purified by flash column chromatography.

(E)-Ethyl 3-(1-Methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)acrylate (1b)

Substrate 1a (16.1 mg, 0.1 mmol) was olefinated using ethyl acrylate (16.3 μL, 0.15 mmol, 1.5 equiv) and PhCO₃^tBu (18.6 μL, 0.1 mmol, 1.0 equiv) for 16 h following the general procedure, and the sample was purified by preparative TLC (PE/EtOAc, 5:1) to give 1b as a yellow oil (9.0 mg, 35%) as a mixture of regioisomers (para/others 4.3:1). ¹H NMR (400 MHz): δ 7.63 (d, J = 16.1 Hz, 1H), 7.42 (dd, J = 8.4, 2.1 Hz, 1H), 7.35 (d, J = 1.9 Hz, 1H), 6.98 (d, J = 8.4 Hz, 1H), 6.37 (d, J = 16.0 Hz, 1H), 4.26 (q, J = 7.1 Hz, 2H), 3.37 (s, 3H), 2.93 (dd, J = 8.6, 6.1 Hz, 2H), 2.68 (dd, J = 8.7, 6.0 Hz, 3H), 1.34 (t, J = 7.1 Hz, 4H). HRMS (FD) m/z: [M]⁺ calcd for C₁₅H₁₇NO₃⁺, 259.1208; found, 259.1184.

(E)-Ethyl 3-(5-Methoxy-1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)acrylate (2b)

Substrate 2a (19.1 mg, 0.1 mmol) was olefinated using ethyl acrylate (16.3 μL, 0.15 mmol, 1.5 equiv) and PhCO₃^tBu (18.6 μL, 0.1 mmol, 1.0 equiv) following the general procedure, and the sample was purified by flash column chromatography (PE/EtOAc, 3:1) to give 2b as a yellow oil (13.0 mg, 45%, C6/others > 20:1). ¹H NMR (400 MHz): δ 7.88 (d, J = 16.1 Hz, 1H), 7.47 (d, J = 8.6 Hz, 1H), 6.80 (d, J = 8.6 Hz, 1H), 6.45 (d, J = 16.1 Hz, 1H), 4.27 (q, J = 7.1 Hz, 2H), 3.74 (s, 3H), 3.36 (s, 3H), 2.97 (dd, J = 8.6, 6.3 Hz, 2H), 2.63 (dd, J = 8.6, 6.2 Hz, 2H), 1.34 (t, J = 7.1 Hz, 3H). ¹³C{H} NMR (101 MHz): δ 170.3, 167.4, 156.7, 143.7, 139.0, 127.2, 123.1, 120.1, 118.3, 111.4, 62.0, 60.6, 31.1, 29.9, 18.8, 14.5. IR ν: 2923, 2852, 1675, 1628, 1596, 1265, 1167 cm^–1. HRMS (FD) m/z: [M]⁺ calcd for C₁₆H₁₉NO₄⁺, 289.1314; found, 289.1319. A parallel reaction was performed without using the S,O-ligand and only a trace amount of desired product was detected.

(E)-Ethyl 3-(5-Ethoxy-1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)acrylate (3b)

Substrate 3a (20.5 mg, 0.1 mmol) was olefinated using ethyl acrylate (16.3 μL, 0.15 mmol, 1.5 equiv) and PhCO₃^tBu (18.6 μL, 0.1 mmol, 1.0 equiv) following the general procedure, and the sample was purified by flash column chromatography (PE/EtOAc, 3:1) to give 3b as a yellow oil (17.3 mg, 57%, C6/others > 20:1). ¹H NMR (400 MHz): δ 7.90 (d, J = 16.1 Hz, 1H), 7.47 (d, J = 8.6 Hz, 1H), 6.79 (d, J = 8.6 Hz, 1H), 6.42 (d, J = 16.1 Hz, 1H), 4.25 (q, J = 7.1 Hz, 2H), 3.86 (q, J = 7.0 Hz, 2H), 3.35 (s, 3H), 2.95 (dd, J = 8.6, 6.2 Hz, 2H), 2.61 (dd, J = 8.5, 6.2 Hz, 2H), 1.42 (t, J = 7.0 Hz, 3H), 1.33 (t, J = 7.1 Hz, 3H). ¹³C{H} NMR (101 MHz): δ 170.3, 167.3, 155.7, 143.7, 139.3, 126.8, 123.3, 120.3, 118.0, 111.3, 70.7, 60.5, 31.2, 29.9, 19.0, 15.6, 14.5. IR ν: 2977, 1679, 1598, 1441, 1352, 1177, 1125, 1044 cm^–1. HRMS (FD) m/z: [M]⁺ calcd for C₁₇H₂₁NO₄⁺, 303.1471; found, 303.1488.

(E)-Ethyl 3-[5-(Methoxymethoxy)-1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl]acrylate (4b)

Substrate 4a (22.1 mg, 0.1 mmol) was olefinated using ethyl acrylate (16.3 μL, 0.15 mmol, 1.5 equiv) and PhCO₃^tBu (18.6 μL, 0.1 mmol, 1.0 equiv) following the general procedure, and the sample was purified by flash column chromatography (PE/EtOAc, 3:1) to give 4b as a yellow oil (15.0 mg, 47%, C6/others > 20:1). ¹H NMR (400 MHz): δ 7.93 (d, J = 16.1 Hz, 1H), 7.50 (d, J = 8.5 Hz, 1H), 6.82 (d, J = 8.6 Hz, 1H), 6.38 (d, J = 16.2 Hz, 1H), 4.97 (s, 2H), 4.25 (q, J = 7.2 Hz, 2H), 3.62 (s, 3H), 3.35 (s, 3H), 2.97 (dd, J = 8.6, 6.2 Hz, 2H), 2.61 (dd, J = 8.6, 6.3 Hz, 2H), 1.33 (t, J = 7.1 Hz, 3H). ¹³C{H} NMR (101 MHz): δ 170.3, 167.2, 154.2, 143.7, 139.4, 126.5, 123.5, 120.5, 118.0, 111.8, 100.7, 60.6, 58.1, 31.2, 30.0, 19.6, 14.5. IR ν: 2852, 1677, 1598, 1354, 1251, 1124, 812 cm^–1. HRMS (FD) m/z: [M]⁺ calcd for C₁₇H₂₁NO₅⁺, 319.1420; found, 319.1415.

(E)-Ethyl 3-(5-Hydroxy-1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)acrylate (5b)

Substrate 5a (17.7 mg, 0.1 mmol) was olefinated using ethyl acrylate (16.3 μL, 0.15 mmol, 1.5 equiv) and PhCO₃^tBu (18.6 μL, 0.1 mmol, 1.0 equiv) following the general procedure, and the sample was purified by preparative TLC (PE/EtOAc, 2:1) to give 5b as a yellow oil (7.4 mg, 27%). (The product is not stable, as after the sample solution in CDCl₃ was stored overnight at room temperature and was measured again, many new peaks appeared.) ¹H NMR (300 MHz): δ 7.97 (d, J = 16.0 Hz, 1H), 7.40 (d, J = 8.6 Hz, 1H), 6.64 (d, J = 8.6 Hz, 1H), 6.45 (d, J = 15.9 Hz, 1H), 5.88 (s, 1H), 4.27 (q, J = 7.2 Hz, 2H), 3.36 (s, 3H), 2.96–2.83 (m, 2H), 2.67 (dd, J = 8.8, 6.2 Hz, 2H), 1.34 (t, J = 7.1 Hz, 3H).

(E)-Ethyl 3-[5-Ethoxy-1-(methoxymethyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl]acrylate (6b)

Substrate 6a (81.6 mg, 0.35 mmol) was olefinated using ethyl acrylate (57.0 μL, 0.525 mmol, 1.5 equiv), PhCO₃^tBu (67.0 μL, 0.35 mmol, 1.0 equiv) following the general procedure, and the sample was purified by flash column chromatography (PE/EtOAc, 3:1) to give a mixture of 6b-a and 6b-b as a yellow oil (50.8 mg, 44%, 6b–a/6b–b = 9.1:1) and 6b–c as a yellow oil (1.7 mg, 1.5%). ¹H NMR (400 MHz) (6b–a): δ 7.91 (d, J = 16.2 Hz, 1H), 7.46 (d, J = 8.5 Hz, 1H), 7.11 (d, J = 8.5 Hz, 1H), 6.43 (d, J = 16.1 Hz, 1H), 5.31 (s, 2H), 4.26 (q, J = 7.1 Hz, 2H), 3.86 (q, J = 6.4 Hz, 2H), 3.41 (s, 3H), 2.97 (t, J = 7.2 Hz, 2H), 2.76–2.63 (m, 2H), 1.43 (t, J = 6.3 Hz, 3H), 1.34 (t, J = 7.2 Hz, 3H). ¹³C{H} NMR (101 MHz) (6b–a): δ 171.1, 167.3, 155.6, 142.6, 139.2, 126.9, 123.9, 120.3, 118.2, 112.5, 74.0, 70.8, 60.5, 56.5, 31.3, 19.1, 15.6, 14.4. IR (6b–a) ν: 2976, 1711, 1680, 1626, 1598, 1393, 1166, 1041 cm^–1. HRMS (6b–a) (FD) m/z: [M]⁺ calcd for C₁₈H₂₃NO₅, 333.1576; found, 333.1575. ¹H NMR (400 MHz) (6b–c): δ 7.64 (d, J = 16.0 Hz, 1H), 7.12 (d, J = 1.3 Hz, 1H), 6.79 (d, J = 1.4 Hz, 1H), 6.41 (d, J = 15.9 Hz, 1H), 5.31 (s, 2H), 4.27 (q, J = 7.1 Hz, 2H), 4.08 (q, J = 7.0 Hz, 2H), 3.41 (s, 3H), 2.95–2.92 (m, 2H), 2.66 (dd, J = 8.4, 6.3 Hz, 2H), 1.44 (t, J = 7.0 Hz, 3H), 1.34 (t, J = 7.1 Hz, 3H). ¹³C{H} NMR (101 MHz) (6b-c): δ 171.4, 167.0, 156.0, 144.7, 141.3, 134.5, 118.5, 117.2, 109.0, 106.1, 74.2, 64.2, 60.7, 56.5, 31.2, 18.5, 15.0, 14.5. IR (6b–c) ν: 2979, 2931, 1690, 1601, 1270, 1177 cm^–1. HRMS (6b–c) (FD) m/z: [M]⁺ calcd for C₁₈H₂₃NO₅⁺, 333.1576; found, 333.1575.

(E)-Ethyl 3-[1-(4-Acetoxybenzyl)-5-ethoxy-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl]acrylate (7b)

Substrate 7a (33.9 mg, 0.1 mmol) was olefinated using ethyl acrylate (16.3 μL, 0.15 mmol, 1.5 equiv) and PhCO₃^tBu (18.6 μL, 0.1 mmol, 1.0 equiv) following the general procedure, and the sample was purified by flash column chromatography (PE/EtOAc, 3:1 to 2:1) to give 7b as a yellow oil (21.0 mg, 48%, C6/others > 20:1). ¹H NMR (400 MHz): δ 7.87 (d, J = 16.1 Hz, 1H), 7.34 (d, J = 8.7 Hz, 1H), 7.23–7.21 (m, 2H), 7.05–7.03 (m, 2H), 6.69 (d, J = 8.7 Hz, 1H), 6.37 (d, J = 16.1 Hz, 1H), 5.15 (s, 2H), 4.25 (q, J = 7.1 Hz, 2H), 3.87 (q, J = 7.0 Hz, 2H), 3.02 (dd, J = 8.6, 6.1 Hz, 2H), 2.78–2.72 (m, 2H), 2.28 (s, 3H), 1.44 (t, J = 7.0 Hz, 3H), 1.33 (t, J = 7.1 Hz, 3H). ¹³C{H} NMR (101 MHz): δ 170.4, 169.6, 167.3, 155.8, 149.9, 142.8, 139.1, 134.4, 127.7, 126.8, 123.6, 122.0, 120.5, 118.1, 112.0, 70.8, 60.6, 45.9, 31.4, 21.3, 19.2, 15.7, 14.5. IR ν: 2927, 1761, 1681, 1371, 1166 cm^–1. HRMS (FD) m/z: [M]⁺ calcd for C₂₅H₂₇NO₆⁺, 437.1838; found, 437.1837.

(E)-5-Hydroxy-6-{2-[5-(2-hydroxypropan-2-yl)-2-methyltetrahydrofuran-2-yl]vinyl}-1-methyl-3,4-dihydroquinolin-2(1H)-one (5c) and 2-[5-(2-Hydroxypropan-2-yl)-2-methyltetrahydrofuran-2-yl]-6-methyl-8,9-dihydrofuro[2,3-f]quinolin-7(6H)-one (5d)

Substrate 5a (44.3 mg, 0.25 mmol) was olefinated using trans-29 (63.8 mg, 0.375 mmol, 1.5 equiv) and PhCO₃^tBu (86.0 μL, 0.45 mmol, 1.8 equiv) for 16 h following the general procedure, and the sample was purified by preparative TLC (PE/EtOAc, 3:1) to give 5c as a yellow oil (41.4 mg, 48%, dr = 1.3:1) and 5d as a yellow oil (15.4 mg, 18%, dr not determined). Another reaction was also performed using a mixture of trans-29 and cis-29 as the olefin, and the same results were obtained regarding both the yield and diastereoselectivity. ¹H NMR (5c) (300 MHz) (two diastereoisomers: A/B = 1:1.3): δ 7.17 (d, J = 8.5 Hz, 1H_B), 7.15 (d, J = 8.5 Hz, 1H_A), 6.83 (d, J = 16.0 Hz, 1H_A), 6.71 (d, J = 15.9 Hz, 1H_B), 6.55 (d, J = 8.5 Hz, 1H_B), 6.54 (d, J = 8.5 Hz, 1H_A), 6.12 (d, J = 15.9 Hz, 1H_A), 6.10 (d, J = 15.9 Hz, 1H_B), 3.96–3.90 (m, 1H_A and 1H_B), 3.33 (s, 3H_B), 3.33 (s, 3H_A), 2.93–2.86 (m, 2H_A and 2H_B), 2.63–2.57 (m, 2H_A and 2H_B), 2.04–1.81 (m, 4H_A and 4H_B), 1.42 (s, 3H_B), 1.32 (s, 3H_A), 1.18 (s, 3H_A), 1.16 (s, 3H_B). ¹³C{H} NMR (5c) (75 MHz): δ 170.6 (A and B), 150.3 (A and B), 141.0 (A and B), 137.7 (A or B), 137.1 (A or B), 125.7 (A or B), 125.6 (A or B), 122.0 (A or B), 121.1 (A or B), 120.3 (A or B), 120.0 (A or B), 113.2 (A and B), 107.5 (A and B), 86.1 (A or B), 86.0 (A or B), 83.6 (A or B), 83.1 (A or B), 72.1 (A or B), 72.0 (A or B), 38.7 (A or B), 38.3 (A or B), 31.2 (A and B), 29.9 (A and B), 27.5 (A and B), 27.0 (A or B), 26.9 (A or B), 26.7 (A or B), 26.5 (A or B), 25.3 (A or B), 23.9 (A or B), 18.4 (A and B). IR (5c) ν: 3306, 2972, 2929, 1652, 1624, 1472, 1372, 1126, 1041, 729 cm^–1. HRMS (5c) (FD) m/z: [M]⁺ calcd for C₂₀H₂₅NO₄, 343.1784; found, 343.1771. ¹H NMR (5d) (400 MHz) (two diastereoisomers: A and B. Ratio was not determined): δ 7.38 (d, J = 8.5 Hz, 1H_A and 1H_B), 6.94 (d, J = 8.5 Hz, 1H_A and 1H_B), 6.57 (s, 1H_A and 1H_B), 4.05–4.01 (m, 1HA and 1HB), 3.44 (s, 3H_A and 3H_B), 3.19–3.14 (m, 2H_A and 2H_B), 2.77–2.72 (m, 2H_A and 2H_B), 2.52–2.43 (m, 1H_A and 1H_B), 2.10–1.97 (m, 3H_A and 3H_B), 1.70 (s, 3H_A), 1.69 (s, 3H_B), 1.31 (s, 3H_A), 1.30 (s, 3H_B), 1.21 (s, 3H_B), 1.20 (s, 3H_A). ¹³C{H} NMR (5d) (75 MHz): δ 170.2 (A and B), 162.4 (A and B), 152.4 (A or B), 152.2 (A or B), 137.8 (A or B), 137.6 (A or B), 124.0 (A or B), 123.8 (A or B), 119.0 (A or B), 118.9 (A or B), 110.9 (A or B), 110.8 (A or B), 109.7 (A and B), 101.5 (A or B), 101.3 (A or B), 86.7 (A and B), 81.0 (A or B), 80.7 (A or B), 71.5 (A or B), 71.3 (A or B), 38.6 (A or B), 37.5 (A or B), 31.3 (A and B), 30.3 (A and B), 27.9 (A and B), 27.4 (A or B), 27.1 (A or B), 26.7 (A or B), 26.6 (A or B), 24.7 (A or B), 24.4 (A or B), 18.7 (A or B), 18.6 (A or B). IR (5d) ν: 3444, 2975, 2928, 1671, 1632, 1470, 1375, 1127, 1026, 819 cm^–1. HRMS (5d) (FD) m/z: [M]⁺ calcd for C₂₀H₂₇NO₄⁺, 345.1940; found, 345.1944.

(3R*,4R*)-4,5-Dihydroxy-3-methoxy-4-(4-methoxyphenyl)-6-[(E)-3-oxobut-1-en-1-yl]-1-{[2-(Trimethylsilyl)ethoxy]methyl}-3,4-dihydroquinolin-2(1H)-one [(±)-17]

The substrate (±)-16 (44.5 mg, 0.1 mmol) was olefinated using but-3-en-2-one (12.5 μL, 0.15 mmol, 1.5 equiv) and PhCO₃^tBu (38.0 μL, 0.2 mmol, 2.0 equiv) following the general procedure, and the sample was purified by flash column chromatography (n-hexane/EtOAc, 3:1) to give (±)-17 as a mixture of regioisomers [30.3 mg, 59%, yellow oil, (±)-17-A/(±)-17-B = 6:1], and (±)-17-di (2.9 mg, 5%, yellow oil). ¹H NMR (300 MHz) [(±)-17-A]: δ 9.52 (s, 1H), 7.82 (d, J = 16.5 Hz, 1H), 7.55 (d, J = 8.7 Hz, 1H), 7.15–7.10 (m, 2H), 6.99 (d, J = 8.6 Hz, 1H), 6.84–6.78 (m, 2H), 6.72 (d, J = 16.5 Hz, 1H), 5.61 (d, J = 10.9 Hz, 1H), 5.01 (d, J = 11.1 Hz, 1H), 4.62 (s, 1H), 3.84 (s, 1H), 3.75 (s, 3H), 3.58–3.52 (m, 5H), 2.34 (s, 3H), 0.96–0.93 (m, 2H), −0.03 (s, 9H). ¹³C{H} NMR (75 MHz) [(±)-17-A]: δ 199.3, 165.9, 160.6, 156.9, 139.9, 138.1, 129.5, 128.4, 128.1, 127.0, 119.5, 114.5, 112.6, 108.2, 84.4, 78.2, 72.0, 66.4, 58.9, 55.4, 27.0, 18.1, −1.3. IR [(±)-17-A] ν: 3259, 2953, 2926, 1692, 1605, 1369, 1252, 1081, 834 cm^–1. HRMS [(±)-17-A] (FD) m/z: [M]⁺ calcd for C₂₇H₃₅NO₇Si⁺, 513.2183; found, 513.2208. ¹H NMR (400 MHz) [(±)-17-di]: δ 9.41 (s, 1H), 7.82 (d, J = 16.5 Hz, 1H), 7.75 (d, J = 16.5 Hz, 1H), 7.58 (d, J = 8.7 Hz, 1H), 7.53 (d, J = 2.4 Hz, 1H), 7.05 (dd, J = 8.8, 2.4 Hz, 1H), 7.02 (d, J = 8.8 Hz, 1H), 6.81 (d, J = 8.8 Hz, 1H), 6.74 (d, J = 16.5 Hz, 1H), 6.67 (d, J = 16.5 Hz, 1H), 5.64 (d, J = 10.9 Hz, 1H), 5.01 (d, J = 10.8 Hz, 1H), 4.59 (s, 1H), 3.86 (s, 3H), 3.81 (s, 1H), 3.60 (s, 3H), 3.60–3.53 (m, 2H), 2.37 (s, 2H), 2.36 (s, 3H), 0.96–0.92 (m, 2H), −0.03 (s, 9H). ¹³C{H} NMR (101 MHz) [(±)-17-di]: δ 199.2, 199.1, 165.7, 159.1, 156.8, 139.8, 138.2, 137.9, 129.9, 129.8, 128.9, 128.7, 127.2, 127.2, 124.2, 119.8, 112.1, 111.6, 108.4, 84.3, 78.0, 72.1, 66.4, 59.0, 55.8, 27.4, 27.2, 18.1, −1.3. IR [(±)-17-di] ν: 3251, 2954, 1692, 1604, 1368, 1253, 1082, 836 cm^–1. HRMS [(±)-17-di] (FD) m/z: [M]⁺ calcd for C₃₁H₃₉NO₈Si⁺, 581.2445; found, 581.2443.

(E)-4,5-Dihydroxy-3-methoxy-4-(4-methoxyphenyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-6-[2-(2,5,5-trimethyltetrahydro-2H-pyran-2-yl)vinyl]-3,4-dihydroquinolin-2(1H)-one (19)

Substrate (±)-16 (111.2 mg, 0.25 mmol) was olefinated using olefin 18 (57.8 mg, 0.375 mmol, 1.5 equiv) and PhCO₃^tBu (86.0 μL, 0.45 mmol, 1.8 equiv) following the general procedure, and the sample was purified by preparative TLC (n-hexane/acetone, 6:1) to give 19 as a mixture of regioisomers (75.0 mg, 50%, yellow oil, regioselectivity: 8.8:1, dr = 1:1). ¹H NMR (400 MHz) (two diastereoisomers: A and B): δ 9.18 (br s, 1H_A or 1H_B), 9.17 (br s, 1H_A or 1H_B), 7.48 (d, J = 8.6 Hz, 1H_A and 1H_B), 7.18–7.13 (m, 2H_A and 2H_B), 6.96 (d, J = 8.6 Hz, 1H_A and 1H_B), 6.83–6.80 (m, 2H_A and 2H_B), 6.77 (d, J = 16.7 Hz, 1H_A and 1H_B), 6.18 (d, J = 16.7 Hz, 1H_A or 1H_B), 6.17 (d, J = 16.7 Hz, 1H_A or 1H_B), 5.63 (d, J = 10.9 Hz, 1H_A and 1H_B), 4.99 (d, J = 10.9 Hz, 1H_A and 1H_B), 4.45 (s, 1H_A and 1H_B), 3.81 (s, 1H_A or 1H_B), 3.80 (s, 1H_A or 1H_B), 3.76 (s, 3H_A or 3H_B), 3.75 (s, 3H_A or 3H_B), 3.59–3.53 (m, 2H_A and 2H_B), 3.58 (s, 3H_A or 3H_B), 3.57 (s, 3H_A or 3H_B), 3.41–3.36 (m, 1H_A and 1H_B), 3.25–3.21 (m, 1H_A and 1H_B), 1.86–1.79 (1H_A and 1H_B), 1.75–1.67 (1H_A and 1H_B), 1.52–1.44 (1H_A and 1H_B), 1.36–1.32 (1H_A and 1H_B), 1.31 (s, 3H_A and 3H_B), 1.01 (s, 3H_A or 3H_B), 1.00 (s, 3H_A or 3H_B), 0.95–0.91 (2H_A and 2H_B), 0.79 (s, 3H_A and 3H_B), −0.03 (s, 9H_A and 9H_B). ¹³C{H} NMR (101 MHz): δ 165.9 (A and B), 160.5 (A and B), 154.7 (A and B), 137.1 (A and B), 134.8, 134.7, 128.8 (A and B), 128.2 (A and B), 127.4, 127.3, 123.3 (A and B), 122.4 (A and B), 114.4 (A and B), 112.3 (A and B), 107.7 (A and B), 84.7 (A and B), 78.3 (A and B), 74.5 (A and B), 73.0, 72.9, 72.1 (A and B), 66.2 (A and B), 58.9 (A and B), 55.4 (A and B), 33.7 (A and B), 31.3, 31.1, 29.9 (A and B), 29.4, 29.2, 26.8 (A and B), 24.2, 24.1, 18.2 (A and B), −1.3 (A and B). IR ν: 3314, 2950, 1690, 1611, 1511, 1441, 1390, 1250, 1083, 834 cm^–1. HRMS (FD) m/z: [M]⁺ calcd for C₃₃H₄₇NO₇Si⁺, 597.3122; found, 597.3134.

(E)-4,5-Dihydroxy-6-{2-[5-(2-hydroxypropan-2-yl)-2-methyltetrahydrofuran-2-yl]vinyl}-3-methoxy-4-(4-methoxyphenyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-3,4-dihydroquinolin-2(1H)-one (21)

Substrate (±)-16 (44.5 mg, 0.1 mmol) was olefinated using trans-20 (25.5 mg, 0.15 mmol, 1.5 equiv) and PhCO₃^tBu (34.2 μL, 0.18 mmol, 1.8 equiv) following the general procedure, and the sample was purified by flash column chromatography (n-hexane/EtOAc, 3:1) to give 21 as a mixture of regioisomers (32.0 mg, 52%, yellow oil, A/B = 7:1, dr: not determined). From the ¹H NMR spectra of 21, we mainly found two groups of peaks. That is because the ¹H NMR spectra of (±)-21-A and (±)-21-B were highly identical, while the ¹H NMR spectra of (±)-21-C and (±)-21-D were also highly identical. Therefore, we were not able to determine the ratios of (±)-21-A/(±)-21-B and (±)-21-C/(±)-21-D, but we assumed that they were both 1:1. Also, because of overlapping of these two groups of peaks, we were not able to determine their ratio. A reaction using a mixture of trans- and cis-20 (1:1) as the olefin was also performed [0.1 mmol scale for (±)-16], and the product 21 was isolated as a mixture of regioisomers (A/B = 5.3:1) (30.0 mg, 50%, mixture of four diastereoisomers). ¹H NMR (400 MHz): δ 9.19 (br s, 1H_A, 1H_B, 1H_C and 1H_D), 7.43 (d, J = 8.6 Hz, 1H_A and 1H_B), 7.41 (d, J = 8.6 Hz, 1H_C and 1H_D), 7.16–7.11 (m, 2H_A, 2H_B, 2H_C and 2H_D), 6.93 (d, J = 8.6 Hz, 1H_A, 1H_B, 1H_C and 1H_D), 6.82–6.77 (m, 3H_A, 3H_B, 3H_C and 3H_D), 6.33 (d, J = 16.4 Hz, 1H_C or 1H_D), 6.32 (d, J = 16.4 Hz, 1H_C or 1H_D), 6.28 (d, J = 16.3 Hz, 1H_A or 1H_B), 6.27 (d, J = 16.3 Hz, 1H_A or 1H_B), 5.62 (d, J = 10.9 Hz, 1H_A and 1H_B), 5.61 (d, J = 10.9 Hz, 1H_C and 1H_D), 4.98 (d, J = 11.0 Hz, 1H_A and 1H_B), 4.97 (d, J = 11.0 Hz, 1H_C and 1H_D), 4.47 (s, 1H_A, 1H_B, 1H_C and 1H_D), 3.91–3.82 (m, 1H_A, 1H_B, 1H_C and 1H_D), 3.80 (s, 1H_A, 1H_B, 1H_C and 1H_D), 3.75 (s, 3H_A, 3H_B, 3H_C and 3H_D), 3.59–3.52 (m, 2H_A, 2H_B, 2H_C and 2H_D), 3.57 (s, 3H_A and 3H_B), 3.56 (3H_C and 3H_D), 2.05–1.73 (m, 4H_A, 4H_B, 4H_C and 4H_D), 1.41 (s, 3H_C and 3H_D), 1.40 (s, 3H_A and 3H_B), 1.24 (s, 3H_A and 3H_B), 1.23 (s, 3H_C and 3H_D), 1.14 (s, 3H_C and 3H_D), 1.13 (s, 3H_A and 3H_B), 0.95–0.91 (m, 2H_A, 2H_B, 2H_C and 2H_D), −0.03 (s, 9H_A, 9H_B, 9H_C and 9H_D). ¹³C{H} NMR (101 MHz): δ 165.9 (A, B, C, and D), 160.4 (A, B, C, and D), 154.9 (A, B, C, and D), 137.2 (C or D), 137.1 (C or D), 137.0 (A and B), 136.0 (C or D), 135.9 (C or D), 135.6 (A or B), 135.5 (A or B), 128.9 (A and B), 128.8 (C and D), 128.2 (A, B, C, and D), 127.8 (A or B), 127.7 (A or B), 127.6 (C and D), 122.3 (A, B, C, and D), 121.3 (C and D), 120.9 (A and B), 114.4 (A, B, C, and D), 112.2 (A, B, C, and D), 107.7 (A, B, C, and D), 85.8 (C and D), 85.7 (A and B), 84.7 (A, B, C, and D), 83.4 (A and B), 83.2 (C and D), 78.3 (A, B, C, and D), 72.1 (A, B, C, and D), 71.3 (A and B), 71.2 (C and D), 66.2 (A, B, C, and D), 58.9 (A, B, C, and D), 55.4 (A, B, C, and D), 38.7 (C or D), 38.6 (C or D), 38.1 (A and B), 27.5 (A, B, C, and D), 26.6 (A, B, C, and D), 24.3 (A, B, C, and D), 18.1 (A, B, C, and D), −1.3 (A, B, C, and D). IR ν: 3295, 2967, 2929, 1688, 1611, 1511, 1441, 1374, 1082, 835 cm^–1. HRMS (FD) m/z: [M]⁺ calcd for C₃₃H₄₇NO₈Si⁺, 613.3071; found, 613.3064.

(E)-4,5-Dihydroxy-6-[2-(5-hydroxy-2,6,6-trimethyltetrahydro-2H-pyran-2-yl)vinyl]-3-methoxy-4-(4-methoxyphenyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-3,4-dihydroquinolin-2(1H)-one (25)

Substrate (±)-16 (44.5 mg, 0.1 mmol) was olefinated using olefin cis-24 (36.4 mg, 0.15 mmol, 1.5 equiv) and PhCO₃^tBu (34.2 μL, 0.18 mmol, 1.8 equiv) following the general procedure.

Before performing purification, the crude sample was deprotected by using the following procedure: The sample was dissolved in THF (2 mL) and TBAF solution (1.0 mL, 1.0 M in THF) was added dropwise. After stirring it for 4 h, the reaction was quenched by adding water. The mixture was extracted with EtOAc three times. The combined extracts were washed with brine, dried with MgSO₄, and evaporated in vacuo. the sample was purified by preparative TLC (n-hexane/EtOAc, 4:1) to give 25 as a single regioisomer (26.3 mg, 43%, yellow oil, dr = 2.2:2.2:1:1). ¹H NMR (300 MHz) [two groups of diastereoisomers: (A + B)/(C + D), 2.2:1] 9.21–9.19 (m, 1H_A, 1H_B, 1H_C, and 1H_D), 7.45 (d, J = 8.6 Hz, 1H_A), 7.45 (d, J = 8.6 Hz, 1H_A and 1H_B), 7.44 (d, J = 8.6 Hz, 1H_C and 1H_D), 7.19–7.14 (m, 2H_A, 2H_B, 2H_C, and 2H_D), 6.96 (d, J = 8.7 Hz, 1H_A, 1H_B, 1H_C, and 1H_D), 6.89–6.79 (m, 3H_A, 3H_B, 3H_C, and 3H_D), 6.38–6.26 (m, 1H_A, 1H_B, 1H_C, and 1H_D), 5.64 (d, J = 10.9 Hz, 1H_A, 1H_B, 1H_C, and 1H_D), 5.01 (d, J = 10.9 Hz, 1H_A, 1H_B, 1H_C, and 1H_D), 4.48 (s, 1H_A and 1H_B), 4.47 (s, 1H_C and 1H_D), 3.95–3.88 (m, 1H_A, 1H_B, 1H_C, and 1H_D), 3.78 (s, 3H_A, 3H_B, 3H_C, and 3H_D), 3.62–3.54 (m, 2H_A, 2H_B, 2H_C, and 2H_D), 3.59 (s, 3H_A, 3H_B, 3H_C, and 3H_D), 2.08–1.70 (m, 4H_A, 4H_B, 4H_C, and 4H_D), 1.44 (s, 3H_C and 3H_D), 1.42 (3H_A and 3H_C), 1.26 (s, 3H_A, 3H_B, 3H_C, and 3H_D), 1.16 (s, 3H_A, 3H_B, 3H_C, and 3H_D), 0.98–0.92 (m, 2H_A, 2H_B, 2H_C, and 2H_D), −0.01 (s, 9H_A, 9H_B, 9H_C, and 9H_D). ¹³C{H} NMR (75 MHz): δ 167.2 (A, B, C, and D), 161.7 (A, B, C, and D), 156.1 (A, B, C, and D), 138.4 (C and D), 136.8 (A and B), 137.3 (C or D), 137.1 (C or D), 136.8 (A and B), 130.1 (A, B, C, and D), 129.4 (A, B, C, and D), 129.1 (A or B), 129.0 (A or B), 128.9 (C or D), 128.8 (C or D), 123.6 (A or B), 123.5 (A or B), 123.51 (C and D), 122.6 (C or D), 122.5 (C or D), 122.2 (A or B), 122.1 (A or B), 115.6 (A, B, C, and D), 113.5 (A, B, C, and D), 109.0 (A, B, C, and D), 87.1 (C and D), 86.9 (A and B), 85.9 (A, B, C, and D), 84.7 (A and B), 84.4 (C and D), 79.5 (A, B, C, and D), 73.4 (A, B, C, and D), 72.6 (A, B, C, and D), 67.5 (A and B), 67.4 (C and D), 60.1 (A, B, C, and D), 56.6 (A, B, C, and D), 40.0 (C or D), 39.9 (C or D), 39.4 (A and B), 29.0 (C or D), 28.9 (C or D), 28.8 (A and B), 28.7 (A, B, C, and D), 28.0 (C and D), 27.8 (A and B), 25.8 (C and D), 25.6 (A and B), 19.4 (A, B, C, and D), 0.0 (A, B, C, and D). IR ν: 3296, 2956, 2927, 1688, 1611, 1511, 1441, 1250, 1082, 834 cm^–1. HRMS (FD) m/z: [M]⁺ calcd for C₃₃H₄₇NO₈Si⁺, 613.3071; found, 613.3084.

(E)-6-[2-(1,3-Dimethyl-4-oxocyclohexyl)vinyl]-4,5-dihydroxy-3-methoxy-4-(4-methoxyphenyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-3,4-dihydroquinolin-2(1H)-one (29)

Substrate (±)-27 (103.9 mg, 0.25 mmol) was olefinated using olefin 28 (dr = 5:4, 57.1 mg, 0.375 mmol, 1.5 equiv) and PhCO₃^tBu (86.0 μL, 0.45 mmol, 1.8 equiv) following the general procedure, and the sample was purified by flash column chromatography (n-hexane/EtOAc, 2.5:1) to give 29 as a yellow oil (48.0 mg, 34%, regioselectivity > 20:1, dr = 1:1:1.6:1.6). ¹H NMR (400 MHz) [two groups of diastereoisomers: (A + B)/(C + D), 1:1.6]: δ 9.18 (s, 1H_A and 1H_B), 9.17 (C and D), 7.49 (d, J = 8.7 Hz, 1H_A and 1H_B), 7.42 (d, J = 8.6 Hz, 1H_C and 1H_D), 7.31–7.21 (m, 5H_A, 5H_B, 5H_C and 5H_D), 6.98 (d, J = 8.7 Hz, 1H_A and 1H_B), 6.95 (d, J = 8.6 Hz, 1H_C and 1H_D), 6.82 (d, J = 16.6 Hz, 1H_A and 1H_B), 6.65 (d, J = 16.5 Hz, 1H_C and 1H_D), 6.31 (d, J = 16.6 Hz, 1H_A and 1H_B), 6.18 (d, J = 16.4 Hz, 1H_C and 1H_D), 5.65 (d, J = 10.9 Hz, 1H_A and 1H_B), 5.63 (d, J = 10.9 Hz, 1H_C and 1H_D), 5.02 (d, J = 10.8 Hz, 1H_A and 1H_B), 5.00 (d, J = 10.8 Hz, 1H_C and 1H_D), 4.59 (s, 1H_A and 1H_B), 4.58 (s, 1H_C and 1H_D), 3.80 (s, 1H_A, 1H_B, 1H_C, and 1H_D), 3.59–3.53 (m, 2H_A, 2H_B, 2H_C, and 2H_D), 3.58 (s, 3H_A and 3H_B), 3.57 (s, 3H_C and 3H_D), 2.66–2.46 (m, 2H_A, 2H_B, 2H_C, and 2H_D), 2.37–2.09 (m, 2H_A, 2H_B, 2H_C, and 2H_D), 1.91–1.84 (m, 1H_A, 1H_B, 1H_C, and 1H_D), 1.76–1.68 (m, 1H_C and 1H_D), 1.63–1.55 (m, 1H_A and 1H_B), 1.51–1.43 (m, 1H_A, 1H_B, 1H_C, and 1H_D), 1.40 (s, 3H_C and 3H_D), 1.11 (s, 3H_A and 3H_B), 1.02 (d, J = 6.4 Hz, 3H_C and 3H_D), 0.99 (d, J = 6.5 Hz, 3H_A and 3H_B), 0.95–0.91 (m, 2H_A, 2H_B, 2H_C, and 2H_D), −0.03 (s, 9H_A, 9H_B, 9H_C, and 9H_D). ¹³C{H} NMR (75 MHz): δ 213.9 (A and B), 213.5 (C and D), 165.8 (A, B, C, and D), 154.5 (A, B, C, and D), 139.9 (A, B, C, and D), 137.2 (A or B), 137.1 (C or D), 137.1 (A or B), 137.0 (C or D), 136.2 (A, B, C, and D), 129.5 (A and B), 129.0 (C and D), 129.0 (A, B, C, and D), 127.2 (A, B, C, and D), 126.6 (A, B, C, and D), 122.8 (C and D), 122.6 (A and B), 119.8 (A, B, C, and D), 112.3 (A and B), 112.2 (C and D), 107.8 (A, B, C, and D), 84.6 (A, B, C, and D), 78.5 (A, B, C, and D), 72.1 [(A and B) or (C and D)], 71.5 [(A and B) or (C and D)], 66.3 [(A and B) or (C and D)], 66.0 [(A and B) or (C and D)], 58.9 (A, B, C, and D), 47.7 (A and B), 46.9 (C or D), 46.8 (C or D), 41.4 (A and B), 40.8 (C and D), 38.7 (A, B, C, and D), 38.5 (A and B), 38.2 (C or D), 38.1 (C or D), 38.0 (C and D), 37.5 (A and B), 30.6 (A, B, C, and D), 18.2 (A, B, C, and D), 14.7 (C and D), 14.6 (A and B), −1.3 (A, B, C, and D). IR ν: 3294, 2955, 2926, 1689, 1612, 1439, 1376, 1246,1079, 836 cm^–1. HRMS (FD) m/z: [M]⁺ calcd for C₃₂H₄₃NO₆Si⁺, 565.2860; found, 565.2885.

(E)-4,5-Dihydroxy-6-[2-(4-hydroxy-1,3-dimethylcyclohexyl)vinyl]-3-methoxy-4-(4-methoxyphenyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-3,4-dihydroquinolin-2(1H)-one (32)

Substrate (±)-27 (41.6 mg, 0.1 mmol) was olefinated using olefin 31 (dr = 5:4, 23.1 mg, 0.15 mmol, 1.5 equiv) and PhCO₃tBu (34.2 μL, 0.18 mmol, 1.8 equiv) using the following the general procedure, and the sample was purified by flash column chromatography (n-hexane/EtOAc, 3:1 to 1:1) to give 32 as a yellow oil (22.0 mg, 39%, regioselectivity: >20:1, dr = 1:1:1:1). ¹H NMR (400 MHz) [two groups of diastereoisomers: (A + B)/(C+ D), 1:1]: δ 9.13 [s, (1H_A and 1H_B) or (1H_C and 1H_D)], 9.11 [s, (1H_A and 1H_B) or (1H_C and 1H_D)], 7.45 [d, J = 8.6 Hz, (1H_A and 1H_B) or (1H_C and 1H_D)], 7.43 [d, J = 8.6 Hz, (1H_A and 1H_B) or (1H_C and 1H_D)], 7.31–7.21 (m, 5H_A, 5H_B, 5H_C, and 5H_D), 6.95 [d, J = 8.6 Hz, (1H_A and 1H_B) or (1H_C and 1H_D)], 6.93 [d, J = 8.6 Hz, (1H_A and 1H_B) or (1H_C and 1H_D)], 6.63 [d, J = 16.7 Hz, (1H_A and 1H_B) or (1H_C and 1H_D)], 6.59 [d, J = 16.7 Hz, (1H_A and 1H_B) or (1H_C and 1H_D)], 6.17 [d, J = 16.4 Hz, (1H_A and 1H_B) or (1H_C and 1H_D)], 6.16 [d, J = 8.6 Hz, (1H_A and 1H_B) or (1H_C and 1H_D)], 5.63 (d, J = 10.9 Hz, 1H_A, 1H_B, 1H_C, and 1H_D), 5.00 (d, J = 10.9 Hz, 1H_A, 1H_B, 1H_C, and 1H_D), 4.55 (s, 1H_A, 1H_B, 1H_C, and 1H_D), 3.79 (s, 1H_A, 1H_B, 1H_C, and 1H_D), 3.57 (s, 3H_A, 3H_B, 3H_C, and 3H_D), 3.59–3.53 (m, 2H_A, 2H_B, 2H_C, and 2H_D), 3.15–3.06 (m, 1H_A, 1H_B, 1H_C, and 1H_D), 1.88–1.73 (m, 3H_A, 3H_B, 3H_C, and 3H_D), 1.66–1.20 (m, 4H_A, 4H_B, 3H_C, and 3H_D), 1.14 (s, 3H_C and 3H_D), 1.07 (t, J = 12.9 Hz, 1H_A and 1H_B), 1.06 (s, 3H_A and 3H_B), 1.01–0.98 (m, 3H_A, 3H_B, 3H_C, and 3H_D). ¹³C{H} NMR (101 MHz): δ 165.8 (A, B, C, and D), 154.4 [(A and B) or (C and D)], 154.3 [(A and B) or (C and D)], 142.3 (A, B, C, and D), 138.0 (A, B, C, and D), 137.2 (A, B, C, and D), 129.5 (A, B, C, and D), 129.0 (A, B, C, and D), 127.1 [(A and B) or (C and D)], 127.0 [(A and B) or (C and D)], 126.7 (A, B, C, and D), 123.3 (A, B, C, and D),121.6 (A, B, C, and D), 112.1 (A, B, C, and D), 107.8 [(A and B) or (C and D)], 107.7 [(A and B) or (C and D)], 84.6 (A, B, C, and D), 78.5 (A, B, C, and D), 76.3 (A, B, C, and D), 72.1 (A, B, C, and D), 66.2 (A, B, C, and D), 58.9 (A, B, C, and D), 46.0 [(A and B) or (C and D)], 44.8 [(A and B) or (C and D)], 37.4 (A, B, C, and D), 37.4 (A, B, C, and D), 37.2 (A, B, C, and D), 34.0 (C and D), 32.9 (A and B), 32.1 [(A and B) or (C and D)], 32.0 [(A and B) or (C and D)], 18.8 [(A and B) or (C and D)], 18.7 [(A and B) or (C and D)], 18.2 (A, B, C, and D), −1.3 (A, B, C, and D). IR ν: 3338, 2952, 2926, 2855, 1689, 1612, 1440, 1375, 1247, 1080, 1043, 804 cm^–1. HRMS (FD) m/z: [M]⁺ calcd for C₃₂H₄₅NO₆Si⁺, 567.3016; found, 567.3011.

Deprotection of SEM to Complete the Total Syntheses of Yaequinolone Natural Products

General Procedure for the Deprotection of SEM with TBAF

In a 10 mL round bottom flask containing the substrate (1.0 equiv) was added a solution of TBAF (1.0 M in THF, 10–15 equiv) (in cases where more concentrated TBAF was required, after mixing TBAF solution with the substrate in the flask, the THF was quickly evaporated using a rotary evaporator and the right amount of THF was then added). The reaction was then left to stir under reflux at 80 °C overnight. The reaction was then quenched by adding water. The mixture was extracted with EtOAc three times. The combined extracts were washed with brine, dried with Na₂SO₄, and concentrated in vacuo. The sample was purified by flash column chromatography.

General Procedure for the Deprotection of SEM with Me₂AlCl

In a flame-dried Schlenk flask were added substrate (1.0 equiv) and anhydrous DCM (0.4–0.5 M) under N₂. A solution of Me₂AlCl (1.0 in hexanes, 6.0 equiv) was then added dropwise at −78 °C and the reaction was stirred for 1 h before it was warmed up to 0 °C. After stirring it for another 1 h, the reaction was quenched by adding water. The mixture was extracted with EtOAc three times. The combined extracts were washed with brine, dried with Na₂SO₄, and concentrated in vacuo to give the hydroxymethyl protected intermediate, which was then mixed with MeOH (0.4–0.5 M) and ⁱPr₂NEt (7.0 equiv) and heated at 55 °C overnight. The reaction was quenched by adding saturated solution of NH₄Cl and extracted with EtOAc three times. The combined extracts were washed with brine, dried with Na₂SO₄, and concentrated in vacuo. The sample was purified by flash column chromatography.

(±)-Yaequinolone B

SEM Deprotection of (±)-17 with TBAF

20 mg of (±)-17 [regioisomers (6:1), 0.039 mmol, 1.0 equiv] and 600 μL TBAF (1.0 M in THF, 15 equiv) solution were used. Purification was performed using n-hexane/EtOAc (1:1) as an eluent to give (±)-yaequinolone B as a single regioisomer (pale yellow solid, 9.0 mg, 60%). ¹H NMR (400 MHz): δ 9.44 (s, 1H), 7.80 (d, J = 16.5 Hz, 1H), 7.70 (br s, 1H), 7.49 (d, J = 8.4 Hz, 1H), 7.20–7.13 (m, 2H), 6.86–6.78 (m, 2H), 6.70 (d, J = 16.5 Hz, 1H), 6.40 (d, J = 8.3 Hz, 1H), 4.62 (s, 1H), 3.77 (s, 3H), 3.73 (s, 1H), 3.62 (s, 3H), 2.35 (s, 3H). ¹³C{H} NMR (101 MHz): δ 199.3, 165.5, 160.6, 157.5, 138.1, 137.2, 129.8, 128.6, 127.9, 126.8, 119.3, 114.5, 111.2, 107.5, 84.0, 78.8, 59.1, 55.5, 27.1. IR ν: 3251, 2926, 1691, 1599, 1257, 1079, 805 cm^–1. Its data matched with those reported in the literature.^4c

(±)-Penigequinolones A and B

Deprotection of 19 with TBAF

23 mg of 19 [regioisomers (8.8:1), dr = 1:1, 0.0385 mmol, 1.0 equiv] and 385 μL TBAF (1.0 M in THF, 10 equiv) solution were first mixed in the reaction flask. After quickly removing the THF using a rotary evaporator, 90 μL THF was added. Purification was performed using n-hexane/EtOAc (2:1) as an eluent to give the product as a mixture of regioisomers (A/B = 13.5:1, dr = 1:1) (pale yellow solid, 16.9 mg, 94%). ¹H NMR (400 MHz) (Two diastereoisomers): δ 9.12 (br s, 1H_A and 1H_B), 7.84 (br s, 1H_A and 1H_B), 7.40 (d, J = 8.3 Hz, 1H_A or 1H_B), 7.39 (d, J = 8.3 Hz, 1H_A or 1H_B), 7.21–7.16 (m, 2H_A and 2H_B), 6.84–6.80 (m, 2H_A and 2H_B), 6.73 (d, J = 16.3 Hz, 1H_A and 1H_B), 6.35 (d, J = 8.3 Hz, 1H_A or 1H_B), 6.34 (d, J = 8.3 Hz, 1H_A or 1H_B), 6.14 (d, J = 16.7 Hz, 1H_A or 1H_B), 6.13 (d, J = 16.7 Hz, 1H_A or 1H_B), 4.56 (br s, 1H_A and 1H_B), 3.76 (s, 3H_A and 3H_B), 3.70 (d, J = 1.5 Hz, 1H_A or 1H_B), 3.69 (d, J = 1.5 Hz, 1H_A or 1H_B), 3.60 (s, 3H_A and 3H_B), 3.38 (d, J = 11.3 Hz, 1H_A or 1H_B), 3.37 (d, J = 11.3 Hz, 1H_A or 1H_B), 3.24–3.20 (m, 1H_A and 1H_B), 1.84–1.76 (m, 1H_A and 1H_B), 1.73–1.66 (m, 1H_A and 1H_B), 1.51–1.46 (m, 1H_A and 1H_B), 1.30 (s, 3H_A and 3H_B), 1.00 (s, 3H_A and 3H_B), 0.79 (s, 3H_A and 3H_B). ¹³C{H} NMR (101 MHz): δ 165.8 (A and B), 160.4 (A and B), 155.3 (A and B), 134.5, 134.43, 134.37 (A and B), 129.1 (A and B), 127.6, 127.5, 123.3 (A and B), 122.1 (A and B), 114.4 (A and B), 110.9 (A and B), 107.0 (A and B), 84.3 (A and B), 74.5 (A and B), 72.9 (A and B), 59.0 (A and B), 55.4 (A and B), 33.7 (A and B), 31.2, 31.1, 29.9 (A and B), 29.3 (A and B), 26.8, 26.7, 24.2 (A and B). IR ν: 3269, 2927, 1686, 1616, 1508, 1256, 1079, 806 cm^–1. HRMS (FD) m/z: [M]⁺ calcd for C₂₇H₃₃NO₆⁺, 467.2308; found, 467.2287. The data matched with those reported in the literature.^4c

(±)-Yaequinolone C

Deprotection of 21 with TBAF

24 mg of 21 [regioisomers (6.8:1), dr not determined, 0.039 mmol, 1.0 equiv] and 400 μL TBAF (1.0 M in THF, 10 equiv) solution were first mixed in the reaction flask. After quickly removing the THF using a rotary evaporator, 100 μL THF was added. Purification was performed using n-hexane/EtOAc (1.5:1) as an eluent to give the product 22 as a mixture of regioisomers (10:1, dr = 1:1:0.6:0.6) (pale yellow solid, 15.0 mg, 79%). ¹H NMR (400 MHz), two groups of diastereoisomers: (A + B)/(C + D) = 1:0.6. The NMR data of groups A and B matched with those of yaequinolone C reported in the literature.^4c Therefore, either (±)-22-A or (±)-22-B is (±)-yaequinolone C. The olefin moiety of (±)-yaequinolone C has a trans-configuration]: δ 9.16 (A and/or B and/or C and/or D), 9.15 (A and/or B and/or C and/or D), 7.84 (A, B, C, and D), 7.37 [d, J = 8.2 Hz, (1H_A and 1H_B) or (1H_C and 1H_D)], 7.36 [d, J = 8.2 Hz, (1H_A and 1H_B) or (1H_C and 1H_D), 7.22–7.17 (m, 2H_A, 2H_B, 2H_C, and 2H_D), 6.85–6.83 (m, 2H_A, 2H_B, 2H_C, and 2H_D), 6.79 [d, J = 16.4 Hz, (1H_A and 1H_B) or (1H_C and 1H_D)], 6.78 [d, J = 8.2 Hz, (1H_A and 1H_B) or (1H_C and 1H_D)], 6.34–6.21 (m, 2H_A, 2H_B, 2H_C, and 2H_D), 4.56 [s, (1H_A and 1H_B) or (1H_C and 1H_D)], 4.57 [s, (1H_A and 1H_B) or (1H_C and 1H_D)], 3.91–3.83 (m, 1H_A, 1H_B, 1H_C, and 1H_D), 3.76 [s, (3H_A and 3H_B) or (3H_C and 3H_D)], 3.75 [s, (3H_A and 3H_B) or (3H_C and 3H_D)], 3.69–3.68 (m, 1H_A, 1H_B, 1H_C, and 1H_D), 3.60 (s, 3H_A, 3H_B, 3H_C, and 3H_D), 2.04–1.75 (m, 4H_A, 4H_B, 4H_C, and 4H_D), 1.40 [s, (3H_A and 3H_B) or (3H_C and 3H_D)], 1.39 [s, (3H_A and 3H_B) or (3H_C and 3H_D)], 1.24 (s, 3H_A, 3H_B, 3H_C, and 3H_D), 1.14 (s, 3H_A, 3H_B, 3H_C, and 3H_D). ¹³C{H} NMR (101 MHz): δ 165.7 (A, B, C, and D), 160.4 (A, B, C, and D), 155.4 (A, B, C, and D), 135.7 (A or B or C or D), 135.6 (A or B or C or D), 135.3 (A and/or B and/or C and/or D), 134.5 (A or B or C or D), 134.4 (A or B or C or D), 134.3 (A and/or B and/or C and/or D), 129.2 [(A and B) or (C and D)], 129.1 [(A and B) or (C and D)], 128.0 (A, B, C, and D), 127.9 [(A and B) or (C and D)], 127.8 [(A and B) or (C and D)], 122.0 [(A and B) or (C and D)], 121.9 [(A and B) or (C and D)], 121.3 [(A and B) or (C and D)], 121.0 (A or B or C or D), 120.9 (A or B or C or D), 114.4 (A, B, C, and D), 110.9 (A, B, C, and D), 107.0 (A, B, C, and D), 85.8 [(A and B) or (C and D)], 85.7 [(A and B) or (C and D)], 84.3 (A, B, C, and D), 83.4 [(A and B) or (C and D)], 83.2 [(A and B) or (C and D)], 78.9 (A, B, C, and D), 71.4 [(A and B) or (C and D)], 71.3 [(A and B) or (C and D)], 59.0 (A, B, C, and D), 55.4 (A, B, C, and D), 38.7 (A or B or C or D), 38.6 (A or B or C or D), 38.1 [(A and B) or (C and D)], 27.5 (A, B, C, and D), 26.7 (A, B, C, and D), 26.6 (A, B, C, and D), 24.6 (A or B or C or D), 24.5 (A or B or C or D), 24.3 [(A and B) or (C and D)]. IR ν: 3249, 2966, 2927, 1686, 1602, 1419, 1373, 1254, 1030, 804 cm^–1. HRMS (FD) m/z: [M]⁺ calcd for C₂₇H₃₃NO₇⁺, 483.2257; found, 483.2262.

(±)-Aspoquinolones C and D

Deprotection of 25 with Me₂AlCl

38 mg of 25 (dr = 2.2:2.2:1:1, 0.062 mmol) was used and the product 26 was isolated as a mixture of diastereoisomers (A/B/C/D = 2.2:2.2:1:1) (pale yellow solid, 22.0 mg, 73%) after purification with n-hexane/EtOAc (1:1) as an eluent. ¹H NMR (400 MHz), two groups of diastereoisomers: (A + B)/(C + D) = 2.2:1. Aspoquinolones C and D were reported as a mixture and we found out that one of the mixtures matched with the NMR data of group A and the other one matched with those of Group B.^4b Therefore, we concluded that one of the natural products has a cis-configuration for the olefin moiety and the other has a trans-configuration for the olefin moiety. δ 9.13 (br s, 1H_A or 1H_B), 9.13 (br s, 1H_C or 1H_D), 9.12 (br s, 1H_A or 1H_B), 9.11 (br s, 1H_C or 1H_D), 8.12 (br s, 1H_C and 1H_D), 8.08 (br s, 1H_A and 1H_B), 7.35–7.31 (m, 1H_A, 1H_B, 1H_C, and 1H_D), 7.18–7.14 (m, 2H_A, 2H_B, 2H_C, and 2H_D), 6.82–6.73 (m, 3H_A, 3H_B, 3H_C, and 3H_D), 6.34–6.21 (m, 2H_A, 2H_B, 2H_C, and 2H_D), 4.59–4.57 (m, 1H_A, 1H_B, 1H_C, and 1H_D), 3.90–3.83 (m, 1H_A, 1H_B, 1H_C, and 1H_D), 3.75–3.74 (m, 3H_A, 3H_B, 3H_C, and 3H_D), 3.69–3.68 (m, 1H_A, 1H_B, 1H_C, and 1H_D), 3.60–3.59 (m, 3H_A, 3H_B, 3H_C, and 3H_D), 2.03–1.74 (m, 4H_A, 4H_B, 4H_C, and 4H_D), 1.40–1.38 (m, 3H_A, 3H_B, 3H_C, and 3H_D), 1.25–1.23 (m, 3H_A, 3H_B, 3H_C, and 3H_D), 1.13 (s, 3H_A, 3H_B, 3H_C, and 3H_D). ¹³C{H} NMR (75 MHz): δ 165.9 (A, B, C, and D), 160.4 (A, B, C, and D), 155.4 (A, B, C, and D), 135.7 (C or D), 135.6 (C or D), 135.3 (A or B), 135.2 (A or B), 134.4 (C and D), 134.4 (C and D), 129.2 (A and B), 129.1 (C and D), 128.0 (A and B), 127.9 (C or D), 127.8 (C or D), 122.0 (C and D), 121.9 (A and B), 121.4 (C or D), 121.3 (C or D), 121.0 (A or B), 120.9 (A or B), 114.4 (A, B, C, and D), 110.9 (A, B, C, and D), 107.0 (A, B, C, and D), 85.8 (C and D), 85.7 (A and B), 84.3 (A, B, C, and D), 83.4 (A and B), 83.2 (C and D), 78.9 (A and B), 78.8 (C and D), 71.4 (C and D), 71.3 (A and B), 59.0 (A, B, C, and D), 55.4 (A, B, C, and D), 38.7 (C and D), 38.6 (A and B), 27.7 (C and D), 27.5 (A, B, C, and D), 27.4 (A and B), 26.8 (C or D), 26.7 (C or D), 26.7 (A or B), 26.6 (A or B), 24.6 (C or D), 24.5 (C or D), 24.3 (A and B). IR ν: 3261, 2924, 1686, 1600, 1377, 1262, 1077, 1026, 734 cm^–1. HRMS (FD) m/z: [M]⁺ calcd for C₂₇H₃₃NO₇⁺, 483.2257; found, 483.2272.

(±)-Aflaquinolones A, C, and D

Deprotection of 29 with Me₂AlCl

40 mg of 29 (dr = 1:1:1.6:1.6, 0.071 mmol) was used and the product 30 was isolated as a mixture of diastereoisomers (dr = 1:1:1:1) (pale yellow solid, 30.0 mg, 97%) after purification with n-hexane/EtOAc (1.5:1) as an eluent. ¹H NMR (400 MHz) [two groups of diastereoisomers: (A + B)/(C + D) = 1:1, The ¹H NMR data of (±)-aflaquinolones A, C, and D matched with those reported in the literature.:^5b δ 9.11 [br s, (1H_A and 1H_B) or (1H_C and 1H_D)], 9.09 [br s, (1H_A and 1H_B) or (1H_C and 1H_D)], 8.35 [br s, (1H_A and 1H_B) or (1H_C and 1H_D)], 8.33 [br s, (1H_A and 1H_B) or (1H_C and 1H_D)], 7.39 (d, J = 8.3 Hz, 1H_A and 1H_B), 7.34–7.25 (m, 5H_A, 5H_B, 6H_C, and 6H_D), 6.78 (d, J = 16.6 Hz, 1H_C and 1H_D), 6.61 (d, J = 16.5 Hz, 1H_A and 1H_B), 6.39 (d, J = 8.1 Hz, 1H_C and 1H_D), 6.36 (d, J = 8.2 Hz, 1H_A and 1H_B), 6.27 (d, J = 16.6 Hz, 1H_A and 1H_B), 6.13 (d, J = 16.4 Hz, 1H_C and 1H_D), 4.69 [s, (1H_A and 1H_B) or (1H_C and 1H_D)], 4.67 [s, (1H_A and 1H_B) or (1H_C and 1H_D)], 3.69 (d, J = 1.6 Hz, 1H_A, 1H_B, 1H_C, and 1H_D), 3.61 (s, 3H_A, 3H_B, 3H_C, and 3H_D), 2.65–2.44 (m, 2H_A, 2H_B, 2H_C, and 2H_D), 2.36–2.31 (m, 1H_C and 1H_D), 2.28–2.21 (m, 1H_A and 1H_B), 2.21–2.08 (m, 2H_A, 2H_B, 2H_C, and 2H_D), 1.76–1.68 (m, 1H_A and 1H_B), 1.62–1.54 (m, 1H_C and 1H_D), 1.43–1.39 (m, 1H_A, 1H_B, 1H_C, and 1H_D) 1.39 (s, 3H_C and 3H_D), 1.10 (s, 3H_A and 3H_B), 1.02 (d, J = 6.5 Hz, 3H_C and 3H_D), 0.93 (d, J = 6.5 Hz, 3H_A or 3H_B), 0.92 (d, J = 6.5 Hz, 3H_A or 3H_B). ¹H NMR (400 MHz, acetone-d₆): δ 9.62 (br s, 1H_A or 1H_B or 1H_C or 1H_D), 9.61 (br s, 1H_A or 1H_B or 1H_C or 1H_D), 9.59 [br s, (1H_A and 1H_B) or (1H_C and 1H_D)], 9.37 [br s, (1H_A and 1H_B) or (1H_C and 1H_D)], 9.36 [br s, (1H_A and 1H_B) or (1H_C and 1H_D)], 7.53 (d, J = 8.3 Hz, 1H_A or 1H_B), 7.52 (d, J = 8.3 Hz, 1H_A or 1H_B), 7.43 (d, J = 8.4 Hz, 1H_C and 1H_D), 7.37–7.32 (m, 5H_A, 5H_B, 5H_C, and 5H_D), 6.84 (d, J = 16.7 Hz, 1H_A and 1H_B), 6.65 (d, J = 16.5 Hz, 1H_C and 1H_D), 6.60 [d, J = 8.6 Hz, (1H_A and 1H_B) or (1H_C and 1H_D)], 6.57 [d, J = 8.6 Hz, (1H_A and 1H_B) or (1H_C and 1H_D)], 6.44 (d, J = 16.6 Hz, 1H_A and 1H_B), 6.37 (s, 1H_A or 1H_B or 1H_C or 1H_D), 6.36 (s, 1H_A or 1H_B or 1H_C or 1H_D), 6.36 [s, (1H_A and 1H_B) or (1H_C and 1H_D)], 6.23 (d, J = 16.4 Hz, 1H_C and 1H_D), 3.68 (d, J = 1.4 Hz, 1H_A, 1H_B, 1H_C and 1H_D), 3.52 [s, (3H_A and 3H_B) or (3H_C and 3H_D)], 3.51 [s, (3H_A and 3H_B) or (3H_C and 3H_D)], 2.73–2.47 (m, 2H_A, 2H_B, 2H_C, and 2H_D), 2.22–2.09 (m, 1H_A, 1H_B, 1H_C, and 1H_D), 1.91–1.81 (m, 2H_A, 2H_B, 2H_C, and 2H_D), 1.75–1.67 (m, 1H_A and 1H_B), 1.58–1.49 (m, 1H_C and 1H_D), 1.42 (s, 3H_C and 3H_D), 1.11 (s, 3H_A and 3H_B), 0.95 (d, J = 6.5 Hz, 3H_C and 3H_D), 0.93 (d, J = 6.5 Hz, 3H_A or 3H_B), 0.92 (d, J = 6.5 Hz, 3H_A or 3H_B). ¹³C{H} NMR (101 MHz): δ 214.0 [(A and B) or (C and D)], 213.6 [(A and B) or (C and D)], 165.9 (A, B, C, and D), 155.0 (A, B, C, and D), 137.4 (A, B, C, and D), 136.0 (A, B, C, and D), 134.5 [(A and B) or (C and D)], 134.4 [(A and B) or (C and D)], 129.4 (A, B, C, and D), 129.1 [(A and B) or (C and D)], 129.0 [(A and B) or (C and D)], 127.4 [(A and B) or (C and D)], 127.3 [(A and B) or (C and D)], 126.4 (A, B, C, and D), 122.6 (A, B, C, and D), 122.5 [(A and B) or (C and D)], 122.4 [(A and B) or (C and D)], 110.9 [(A and B) or (C and D)], 110.8 [(A and B) or (C and D)], 107.2 (A, B, C, and D), 84.2 (A, B, C, and D), 79.0 (A, B, C, and D), 59.1 (A, B, C, and D), 47.7 (A or B), 47.6 (A or B), 46.9 (C or D), 46.8 (C or D), 41.5 (A and B), 40.8 (C and D), 38.7 (A, B, C, and D), 38.5 [(A and B) or (C and D)], 38.2 [(A and B) or (C and D)], 38.0 (C and D), 37.4 (A and B), 30.6 (A, B, C, and D), 14.7 (A or B or C or D), 14.6 (A or B or C or D), 14.3 [(A and B) or (C and D)]. IR ν: 3221, 2923, 1689, 1377, 1260, 1080, 1026, 800 cm^–1. HRMS (FD) m/z: [M]⁺ calcd for C₂₆H₂₉NO₅⁺, 435.2046; found, 435.2047.

(±)-Scopuquinolone B

Deprotection of 32 with Me₂AlCl

19 mg of 32 (dr = 1:1:1:1, 0.0335 mmol) was used and the product 33 was isolated as a mixture of daistereosiomers (dr = 1:1:1:1) (pale yellow solid, 13.0 mg, 89%) after purification with n-hexane/EtOAc (1:1) as an eluent. ¹H NMR (400 MHz, acetone-d₆) [two groups of diastereoisomers: (A + B)/(C + D) = 1:1. The NMR data of groups C and D matched with those of scopuquinolone B reported in the literature.:^6c δ 9.55 (br s, 1H_A, 1H_B, 1H_C, and 1H_D), 9.33 (br s, 1H_A, 1H_B, 1H_C, and 1H_D), 7.44 [d, J = 8.3 Hz, (1H_A and 1H_B) or (1H_C and 1H_D)], 7.42 [d, J = 8.3 Hz, (1H_A and 1H_B) or (1H_C and 1H_D)], 7.37–7.32 (m, 5H_A, 5H_B, 5H_C, and 5H_D), 6.65–6.55 (m, 2H_A, 2H_B, 2H_C, and 2H_D), 6.20 [d, J = 16.5 Hz, (1H_A and 1H_B) or (1H_C and 1H_D)], 6.17 [d, J = 16.5 Hz, (1H_A and 1H_B) or (1H_C and 1H_D)], 3.66 (d, J = 1.5 Hz, 1H_A, 1H_B, 1H_C, and 1H_D), 3.52 [s, (3H_A and 3H_B) or (3H_C and 3H_D)], 3.51 [s, (3H_A and 3H_B) or (3H_C and 3H_D)], 3.06–2.97 (m, 1H_A, 1H_B, 1H_C, and 1H_D), 1.81–1.68 (m, 3H_A, 3H_B, 3H_C, and 3H_D), 1.64–1.27 (m, 3H_A, 3H_B, 4H_C, and 4H_D), 1.13 (s, 3H_A and 3H_B), 1.07 (t, J = 12.9 Hz, 1H_c and 1H_d), 1.01 (s, 3H_C and 3H_D), 0.98 (d, J = 6.4 Hz, 3H_A and 3H_B), 0.96 (d, J = 6.4 Hz, 3H_A and 3H_B). ¹³C{H} NMR (101 MHz, acetone-d₆): δ 166.3 (A, B, C, and D), 156.1 (C and D), 155.9 (A and B), 141.8 (A and B), 140.3 (C and D), 137.6 (A, B, C, and D), 136.9 (A, B, C, and D), 129.7 (A, B, C, and D), 129.6 (A, B, C, and D), 127.5 [(A and B) or (C and D)], 127.5 [(A and B) or (C and D)], 127.4 [(A and B) or (C and D)], 127.3 [(A and B) or (C and D)], 122.6 (A, B, C, and D), 122.3 (A, B, C, and D), 112.1 (A, B, C, and D), 107.7 (A, B, C, and D), 85.8 (A, B, C, and D), 80.0 (A, B, C, and D), 76.8 (A, B, C, and D), 59.0 (A, B, C, and D), 46.9 (C and D), 45.9 (A and B), 37.7 (A, B, C, and D), 37.7 (A, B, C, and D), 37.0 [(A and B) or (C and D)], 36.9 [(A and B) or (C and D)], 34.0 (A and B), 33.1 (C and D), 31.9 [(A and B) or (C and D)], 31.8 [(A and B) or (C and D)], 19.5 [(A and B) or (C and D)], 19.4 [(A and B) or (C and D)]. IR ν: 3274, 2926, 1687, 1620, 1452, 1378, 1261, 1082, 1039, 803 cm^–1. HRMS (FD) m/z: [M]⁺ calcd for C₂₆H₃₁NO₅⁺, 437.2202; found, 437.2198.

Supporting Information Available

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.joc.1c00042.

• General schemes for the synthesis of 18, trans-20, 28, 31, and (±)-27; comparison of the ¹H NMR spectra of olefinated product 21 when using trans-20 or a mixture of trans- and cis-20; comparison of the NMR data of natural and synthetic products; and copies of the ¹H and ¹³C NMR spectra for all new compounds (PDF)

The authors declare no competing financial interest.