Catalyst-Controlled Divergent Annulation Reactions of Allenoates and Fully Substituted 1,3-Indandione Derived Electron-Deficient Alkenes

Abstract

Two catalyst-controlled, regiodivergent annulation protocols for allenoates with fully substituted 1,3-indandione derived electron-deficient alkenes have been developed, furnishing a series of spiroindane-1,3-diones and 3,4-dihydro-2H-pyran derivatives in high yields. Plausible mechanistic pathways for both annulation reactions are proposed: spiroindane-1,3-diones are obtained via a [3 + 2] annulation, while 3,4-dihydro-2H-pyran derivatives arise from a [4 + 2] annulation.

Introduction

The spiroindane-1,3-diones are widely found in natural products, pharmaceutical molecules, and bioactive compounds (Figure ). For example, fredericamycin A is an antitumor compound with antibiotic properties. The highly rigid spirocyclic structure allows it to interact with specific enzymatic targets. Biphenyl-based spirocyclic ketone 1 are recognized as new anticancer agents. In addition, pyrans are useful building blocks that have a wide range of remarkable biological activities. Like racemate warfarin and annulin B, they show good anticoagulant medication and indoleamine 2,3-dioxygenase (IDO) inhibition activity, respectively. In recent decades, an increasing number of chemists have devoted efforts to the synthesis of such molecules. Among various reported methodologies for synthesizing the spiroindane-1,3-dione skeletons, organocatalytic domino reactions using readily accessible 2-arylidene Indane-1,3-diones have been demonstrated as a powerful strategy. Moreover, organocatalytic [4 + 2] annulations of allenoates with activated olefins will be most efficient way for the synthesis of pyran structural motif. ,

1.

Examples of pharmaceuticals and bioactive molecules containing spiroindane-1,3-dione and pyran scaffolds.

Although significant progress has been made in the synthesis of these compounds, their practical applications are still limited by factors such as the difficulty in preparing starting materials, harsh reaction conditions, and the high cost of catalysts. Therefore, developing efficient synthetic methods for spirocyclic compounds and pyran derivatives using readily available catalysts and substrates under mild conditions remains a significant challenge.

Allenes and allenoates are easily accessible building blocks and exhibit high activity toward electrophiles, especially the Lewis base catalyzed annulation reaction with allenoates have emerged as powerful synthetic tools in the rapid construction of a variety of complex structures under mild conditions. Recently, phosphine- , and nitrogen- ,, containing Lewis base catalyzed annulation reactions of allenoates has been largely demonstrated by the preparation of biologically active natural products and pharmaceutically interesting substances. It was found that the nature of these Lewis base catalysts has a pronounced effect on these reactions, which often allows for orthogonal reactivities and connectivities when utilizing different catalyst principles, thus allowing for diversity-oriented approaches as well. For example, the annulation reaction of allenoates 2 with 2-arylidene-1,3-indanediones 3 generated different annulation products when different Lewis base catalysts were used (Scheme A). In the presence of DABCO, this reaction yields the formal (4 + 2) cycloaddition products (E)-4 and 5, whereby the location of the double bond depends on the reaction conditions. In contrast, the use of PPh₃ gives the regioisomeric (3 + 2) cycloaddition products 6. , However, the examples of Lewis base-dependent divergent annulation reaction of allenoates 2 with tetra-substituted Michael acceptors are rare. In 2011, Shi and co-workers reported a phosphine catalyzed [3 + 2] cycloaddition of isatin-derived α,β-unsaturated diesters with allenoates 2, while the amine catalyst gave [4 + 2] annulation adducts selectively (Scheme B).

1. Orthogonal Reactivities of Allenoates 2 with Enones 3 Using Different Lewis Bases (A); Orthogonal Reactivities of Allenoates 2 with Tetra-Substituted Michael Acceptors 7 Using Different Lewis Bases (B); and the Herein Reported Catalyst-Controlled Sequential Annulation of Allenoates and Fully Substituted 1,3-Indandione Derived Electron-Deficient Alkenes (C).

Hence, inspired by the above-mentioned work, we envisioned that fully substituted enones 10 will proceed different annulation reaction pathways with allenoates 2 when different Lewis base catalysts were used (Scheme C). In this regard, we recognized that enones 10 indeed reacted with allenoates 2 in the presence of DMAP and the formal (4 + 2) cycloaddition products with a quaternary center 11 and 12 were formed in good to high yields (Scheme C, path a). When enones 10 reacted with allenoates 2 with PPh₃ as the catalyst, the unusual [3 + 2] cycloaddition products 13 were generated in moderate to high yields (Scheme C, path b). In general, the [3 + 2] cycloaddition of enones with allenoates 2 gave the annulation products with bondings at α and γ positions. However, the [3 + 2] cycloaddition products 13 were obtained through β and γ linkages. Moreover, we observed that more complex spiroindane-1,3-diones containing a fused carbocycle were synthesized when γ-vinyl allenoates 14 were used and PPh₃ was the catalyst (Scheme C, path c). Continuing our efforts on developing efficient vinylogous reactions of 1,3-indanedione derivatives, we herein describe a catalyst-controlled protocol for these three annulation reactions, their substrate scope, and plausible reaction mechanism to rationalize of the site-selectivity reaction pathway.

Results and Discussion

We first focused our effort on the investigation of tertiary amines for their ability to catalyze the reaction of 1,3-indanedione 10a with allenoate 2a. On the basis of previous work, , the expected [4 + 2] annulation product 11a was obtained in 67% total reaction yield (Z-11a: 44%, E-11a: 23%) when 20 mol % of DMAP was used as the catalyst (Table , entry 1). Neither DABCO nor DBU provided any reactivity in this reaction (Table , entries 2 and 3). We then chose DMAP as the catalyst and examined the solvent effects (Table , entries 4–7). Among the tested solvents, THF was found to be the solvent of choice, improving the total reaction yield to 76% (Table , entry 7). Lowing the reaction temperature to 40 °C had almost the same results as in 60 °C (Table , entries 8 and 9). The survey on the reaction concentration indicated that a further improvement in reaction yield when 2 mL of THF was used (Table , entries 10 and 11). In order to maximize the total reaction yield of 11a, we attempted to elevate the reaction temperature to 80 °C; however, the solvent had to change to high boiling point solvent like toluene. Encouragingly, the total reaction yield of 11a was increased to 92% (Table , entry 12). The investigation showed that there was no positive effect observed when increasing the catalyst loading from 20 to 50 and 100 mol % (Table , entries 13 and 14). Hence, the final optimal conditions were chosen by conducting the reaction at 80 °C in 2 mL of toluene with 20 mol % DMAP (Table , entry 12).

1. Optimization of the Reaction Conditions for the [4 + 2] Annulation of 10a and 2a Catalyzed by Nitrogen-Containing Lewis Bases.

entry	Cat.(mol %)	temp. (°C)	solvent (mL)	time (h)	yield (%)Z/E-11a
1	DMAP (20)	60	toluene (3)	48	44/23
2	DABCO (20)	60	toluene (3)	72	trace
3	DBU (20)	60	toluene (3)	72	trace
4	DMAP (20)	60	CH3CN (3)	48	trace
5	DMAP (20)	60	EA (3)	48	35/23
6	DMAP (20)	60	1,2-DCE (3)	24	36/22
7	DMAP (20)	60	THF (3)	48	49/27
8	DMAP (20)	40	THF (3)	48	48/27
9	DMAP (20)	20	THF (3)	48	45/24
10	DMAP (20)	40	THF (2)	48	50/29
11	DMAP (20)	40	THF (1)	48	34/21
12	DMAP (20)	80	toluene (2)	48	60/32
13	DMAP (50)	80	toluene (2)	48	53/13
14	DMAP (100)	80	toluene (2)	48	57/2

^aThe reaction was carried out by using 0.10 mmol of 10a, 0.15 mmol of 2a, and catalyst (20–100 mol %) in solvent (1–3 mL) at 20–80 °C for 24–72h.

^bIsolated yields.

With the optimal conditions in hand, the evaluation of substrate scope applying 1,3-indanediones 10 and allenoates 2 under the standard reaction conditions was performed. As shown in Scheme , the reaction proceeded smoothly regardless of the steric and electronic properties of the substituents on the aromatic ring, providing the corresponding [4 + 2] annulation products 11ab–11ag in good to high yields. In addition, 1,3-indanedione 10h showed relatively high reactivity and provided the product 11ah in high yield (90% total yield). A larger scale reaction (1 mmol) of compounds 10e and 2a could smoothly take place to give product 11ae with the almost same reaction yield and diastereoselectivity. The change of ester groups at the allenoates 2 have some effects on the reaction activity. The 3-nitrophenyl allenoate 2c gave the corresponding [4 + 2] annulation product 11ca in moderate yield due to its poor solubility in toluene. The t-butyl allenoate 2k also delivered the annulation product 11ka in moderate yield because the steric effect on the reactivity.

2. Scope of [4 + 2] Annulation Products.,

^a Unless otherwise noted, the reaction was carried out by using 0.1 mmol of 10, 0.15 mmol of 2, and 20 mol % of DMAP in 2 mL of toluene at 80 °C for 48h.

^b Isolated yields.

However, other allenoates worked well with 10a and provided the corresponding products 11ba-11ja in good to high yields regardless of the electronic properties of the substituents on the aromatic ring. The structure of 11ad (CCDC 2479629), including the assignment of the olefin as the E isomer, was determined by single-crystal X-ray structural analysis. With the advantage of the crystallographic structure of 11ad, all other product structures were deduced by referring to that.

We next started to investigate the scope of applying various dialkyl-substituted 1,3-indanediones 10i–m. As shown in Scheme , intriguingly, the endocyclic [4 + 2] annulation products 12 were obtained when the reaction with allenoate 2a. Reaction of dimethyl-1,3-cyclohexanodiones 10i and 2a gave the product 12a in 71% reaction yield. Application of the cyclic ring-substituted 1,3-indanediones 10j–m with allenoate 2a only led to products 12c and 12d with 77% and 71% reaction yields, respectively. No annulation products were observed when cyclopentyl- and cycloheptyl-substituted 1,3-indanediones (10j and 10m) were used.

3. Scope of [4 + 2] Annulation Products Using Dialkyl-Substituted 1,3-Indanediones.,

^a Unless otherwise noted, the reaction was carried out by using 0.1 mmol of 10i–m, 0.15 mmol of 2, and 20 mol % of DMAP in 2 mL of toluene at 80 °C for 48h.

^b Isolated yields.

In comparison to amines, phosphines display a markedly different behavior in the reactions of allenoates with electrophilic partners. Hence, the investigation commenced with the reaction of 1,3-indanedione 10a with allenoate 2a catalyzed by PPh₃ at 110 °C for 24h (Table , entry 1). To our delight, the [3 + 2] cycloaddition product 13aa was obtained in 35% yield (Table , entry 1). The evaluation of reaction temperature showed that reaction yield could be increased to 47% when the reaction conducted at 60 °C for 48h (Table , entries 2–5). Increasing the amounts of 2a did not improve the reaction yield (Table , entries 6 and 7). Among the tested solvents, like CH₃CN, CH₂Cl₂, EA, MeOH, THF, PhCF₃, m-xylene or mesitylene resulted in low efficiency, while the original toluene still gave a better result (Table , entries 8–15). Increasing the reaction concentration from 0.05 to 0.1 M showed lower product yield outcome (Table , entry 16). In contrast, decreasing the reaction concentration from 0.05 to 0.033 M improved the reaction yield (Table , entry 17). The next investigation showed that there was no positive effect observed when increasing the catalyst loading from 20 to 30 mol % (Table , entry 18), whereas reducing the catalyst amount to 10 mol % resulted in a slight decrease of the product yield (Table , entry 19). Finally, the optimal conditions were selected by conducting the reaction at 60 °C in toluene with 20 mol % of PPh₃ at 0.033 M substrate concentration (Table , entry 17).

2. Optimization of the Reaction Conditions for the [3 + 2] Annulation of 10a and 2a Catalyzed by Monophosphine Lewis Bases.

entry	Cat.(mol %)	temp.	solvent (mL)	time (h)	yield (%)
		(°C)			13aa
1	PPh3 (20)	110	toluene (2)	24	35
2	PPh3 (20)	85	toluene (2)	24	41
3	PPh3 (20)	60	toluene (2)	48	47
4	PPh3 (20)	50	toluene (2)	48	28
5	PPh3 (20)	rt	toluene (2)	48	trace
6	PPh3 (20)	60	toluene (2)	48	36
7	PPh3 (20)	60	toluene (2)	48	35
8	PPh3 (20)	60	CH3CN (2)	48	trace
9	PPh3 (20)	60	CH2Cl2 (2)	48	trace
10	PPh3 (20)	60	EA (2)	48	34
11	PPh3 (20)	60	MeOH (2)	48	trace
12	PPh3 (20)	60	THF (2)	24	34
13	PPh3 (20)	60	PhCF3 (2)	48	35
14	PPh3 (20)	60	m-xylene (2)	48	42
15	PPh3 (20)	60	mesitylene (2)	48	35
16	PPh3 (20)	60	toluene (1)	48	32
17	PPh3 (20)	60	toluene (3)	48	50
18	PPh3 (30)	60	toluene (3)	48	47
19	PPh3 (10)	60	toluene (3)	48	42

^aThe reaction was carried out by using 0.10 mmol of 10a, 0.15 mmol of 2a, and catalyst (20–100 mol %) in solvent (1–3 mL) at 20–110 °C for 24–72h.

^bIsolated yields.

^c2.5 equiv of 2a.

^d3.5 equiv of 2a.

Having identified the optimal reaction conditions, we set out to examine the scope and the limitations of the Lewis base catalyzed [3 + 2] annulation. It was intriguing to find that this reaction demonstrated a wide scope of substrates, providing products 13 with good yields. A diverse array of 1,3-indanediones 10 with different substituents bearing halide, electron-donating, or electron-withdrawing groups of the phenyl ring, were amenable to this strategy, delivering the desired products 13aa–13ah in moderate to good yields. Notably, the substrates bearing 4-Cl, 4-Br or 4-OMe substituents on the phenyl ring (10c, 10d and 10f) could also afford the desired products (13ac, 13ad and 13af) albeit with decreased yields (36%, 28% and 33% respectively). The structure of 13ac (CCDC 2479639) was confirmed by single-crystal X-ray structural analysis. A larger scale reaction (1 mmol) of compounds 10e and 2a could smoothly take place to give product 13ae with a slightly decreased reaction yield. Moreover, the change of ester groups at the allenoates 2 also worked well with 10a and provided the corresponding products 13ba-11ka in moderate to good yields. The 4-methoxyphenyl allenoate 2h and t-butyl allenoate 2k gave the corresponding [3 + 2] annulation product 13ha and 13ka in moderate yields (28% and 22%).

Recently, the γ-vinyl allenoates had been shown to undergo [3 + 2]/ [3 + 2] sequential annulation with alkylidenemalononitriles enabled by phosphine catalysis. , Therefore, we then carried out the annulation reactions of 1,3-indanediones 10 with γ-vinyl allenoate 14 catalyzed by Lewis base PPh₃. As shown in Scheme , a broad range of spiroindane-1,3-diones 15 containing a bicyclic­[3,3,0]­octane scaffold can be synthesized in good to high yields (58–88%) under the same standard conditions in Scheme . The relative configuration of 15c (CCDC 2479640) was revealed by X-ray diffraction analysis, and the configurations of other products were assigned by analogy (Scheme ).

5. Scope of [3 + 2]/[3 + 2] Annulation Products,

^a Unless otherwise noted, the reaction was carried out by using 0.1 mmol of 10, 0.15 mmol of 2, and 20 mol % of PPh₃ in 2 mL of toluene at 60 °C for 48h.

^b Isolated yields. dr was determined from ¹H NMR of the crude reaction mixture, and in all cases >20:1 dr were observed.

4. Scope of [3 + 2] Annulation Products.,

^a Unless otherwise noted, the reaction was carried out by using 0.1 mmol of 10, 0.15 mmol of 2, and 20 mol % of PPh₃ in 2 mL of toluene at 60 °C for 48h.

^b Isolated yields.

To illustrate the usefulness of of annulation products 11 and 13, the postfunctionalization of products (Z)-11aa and 13aa were carried out, providing reduction products 16 and 17 in 67% and 60% yields, respectively (Scheme ). The diastereoselectivity was high (>20:1) beacuse the hydride attacked the sterically less-hindered face and provided the high stereoselective products. (See the Supporting Information for the relative configuration determination)

6. Further Transformation.

On the basis of earlier reports ,,, and our experimental results, possible mechanism processes under the catalysis of phosphine- and nitrogen-containing Lewis bases are proposed in Scheme . In the case of the DMAP-catalyzed reaction, , the catalyst reacts with the allenoate 2a to generate a zwitterionic intermediate A, which serves as a nucleophile for the subsequent Michael addition with 10a to give intermediate B. The following cyclization produces [4 + 2] annulation product 11aa and regenerates the DMAP catalyst. In the PPh₃-catalyzed phathway, , the methyl group of 10a is believed to be deprotonated by the zwitterion D first to form the carbanion because of its acidic property. The formed carbanion could react with intermediate D-1 via the γ-addition and generated zwitterion F. The subsequent intramolecular cyclization yielded [3 + 2] annulation compound 13aa. For the PPh₃-catalyzed (3 + 2)/(3 + 2) annulation reaction , of 1,3-indanediones 10a with γ-vinyl allenoate 14, the plausible mechanism is shown in Scheme . Initially, nucleophilic addition of phosphine to γ-vinyl allenoates would generate the zwitterionic intermediate G, which would abstract hydrogen from a pronucleophile 10a to yield nucleophile 10a-1 and acyclic diene intermediate G-1. The ε-C position of G-1 was electrophilic and induced the 1,7-addition to form the intermediate H. Then subsequent stepwise proton shifts of H gave rise to the key intermediate I, in which the following intramolecular 1,4-addition of I happened and produced intermediate J, which finished the first (3 + 2) annulation process. The subsequent another intramolecular umpolung addition (the second (3 + 2) annulation) to yield K. Finally, the desired product 15a was obtained through proton transfer and 1,2-elimination of phosphine catalyst via intermediate L.

7. Proposed Mechanisms for the Lewis Base Catalyzed Reactions of 1,3-Indanedione 10a with Allenoate 2a .

8. A Plausible Reaction Mechanism for the Lewis Base Catalyzed Reaction of 1,3-Indanedione 10a with γ-Vinyl Allenoate 14 .

To gain further mechanistic insights into the process, we conducted DFT calculations performed DFT calculations at the M06–2X-D3/def2-TZVPP/SMD (Toluene, SAS)//M06–2X/6–31G (d,p)/SDM (Toluene, SAS) theoretical level.

On the basis of catalytic cycles listed in Scheme , a comprehensive depiction of the energy profiles for this cascade reaction is provided in Figure . For the DMAP-catalyzed reaction, the Michael addition of intermediate A to 10a proceeds with a lower activation barrier (6.0 kcal/mol) than the deprotonation of 10a by intermediate A (11.9 kcal/mol). Therefore, the [4 + 2] annulation pathway is kinetically favored, leading to the formation of product 11aa (Figure a).

2.

Energy profiles for the DMAP- and PPh₃-catalyzed reactions of 10a and 2a. The relative free energies are given in kcal mol^–1.

In contrast, for the PPh3-catalyzed reaction, deprotonation of 10a by intermediate A occurs with a lower activation barrier (10.1 kcal/mol) than the Michael addition pathway (15.1 kcal/mol). Consequently, the [3 + 2] annulation pathway is preferred, affording product 13aa as the major product.

Conclusion

In summary, a detailed investigation on the different reactivity patterns shown by phosphine- and nitrogen-containing catalysts in the reactions of allenoates with fully substituted 1,3-indandione derived electron-deficient alkenes was accomplished. Under the catalysis of nitrogen-containing Lewis base (DMAP), the formal (4 + 2) annulations occurred and produced 3,4-dihydro-2H-pyran derivatives 11 and 12 with a quaternary center in good to high yields. With PPh₃ as the catalyst, an unusual [3 + 2] annulation proceeded smoothly to afford spiroindane-1,3-diones 13 in moderate to high yields. Moreover, we observed that more complex spiroindane-1,3-diones containing a fused carbocycle could be synthesized via a (3 + 2)/(3 + 2) annulation reaction when γ-vinyl allenoate 14 were used with PPh₃ as the catalyst. These studies provide an opportunity for diverse synthesis of a variety of 1,3-indandiones and indanones from the same starting materials. We believe that these new libraries of 1,3-indandione derivatives will facilitate their further biological investigation.

Experimental Section

All reaction solvents were purified before use. Proton nuclear magnetic resonance (¹H NMR) spectra were recorded on a commercial instrument at 400 MHz. Carbon-13 nuclear magnetic resonance (¹³C­{¹H } NMR) spectra were recorded at 100 MHz. The proton signal for residual nondeuterated solvent (δ 7.26 for CHCl₃) was used as an internal reference for ¹H NMR spectra. For ¹³C­{¹H} NMR spectra, chemical shifts are reported relative to the δ 77.0 resonance of CDCl₃. Coupling constants are reported in Hz. Melting points were determined on a BUCHI B-545 melting point apparatus and are uncorrected. High resolution mass spectra were recorded on a commercial high-resolution mass spectrometer with TOF analyzer. The single crystal was measured by Bruker D8 VENTURE X-ray Single Crystal Diffractometer. Analytical thin-layer chromatography (TLC) was performed on silica gel 60 F254 precoated plates with visualization under UV light. Column chromatography was generally performed using 40–63 μm (230–400 mesh) silica gel, typically using a 50–100:1 weight ratio of silica gel to crude product.

General Procedure for the Synthesis of 11 and 12

In a 7 mL glass vial, 1,3-indandiones 10 (0.1 mmol, 1.0 equiv), allenoates 2 (0.15 mmol, 1.5 equiv) and DMAP (2.44 mg, 0.02 mmol, 20 mol %) were dissolved in 2.0 mL toluene and stirred for 48 h at 80 °C (oil bath). The solvent was removed in vacuo, then the reaction mixture was purified by column chromatography (SiO₂, Hexanes: EtOAc, 30:1 to 20:1 to 10:1) to obtain the pure products 11 and 12.

Scale-Up Procedure for the Synthesis of Compound 11ae

In a 25 mL glass vial, 1,3-indandiones 10e (262 mg, 1.0 mmol, 1.0 equiv), 2a (261 mg, 1.5 mmol, 1.5 equiv) and DMAP (24.4 mg, 0.2 mmol, 20 mol %) were dissolved in 20 mL toluene and stirred for 48 h at 80 °C (oil bath). The solvent was removed in vacuo, then the reaction mixture was purified by column chromatography (SiO₂, Hexanes: EtOAc, 30:1 to 20:1 to 10:1) to obtain the pure products (Z)-11 (240 mg, 55% yield) and (E)-11(144 mg, 33% yield).

General Procedure for the Synthesis of 13

In a 7 mL glass vial, 1,3-indandiones 10 (0.1 mmol, 1.0 equiv), allenoates 2 (0.15 mmol, 1.5 equiv) and PPh₃ (5.24 mg, 0.02 mmol, 20 mol %) were dissolved in 3.0 mL toluene and stirred for 48 h at 60 °C (oil bath). The solvent was removed in vacuo, then the reaction mixture was purified by column chromatography (SiO₂, Hexanes: THF, 12:1 to 8:1) to obtain the pure products 13.

General Procedure for the Synthesis of 15

In a 7 mL glass vial, 1,3-indandiones 10 (0.1 mmol, 1.0 equiv), allenoate 14 (0.15 mmol, 1.5 equiv) and PPh₃ (5.24 mg, 0.02 mmol, 20 mol %) were dissolved in 2.0 mL toluene and stirred for 48 h at 60 °C (oil bath). The solvent was removed in vacuo, then the reaction mixture was purified by column chromatography (SiO₂, Hexanes: EtOAc, 20:1 to 10:1) to obtain the pure products 15.

Benzyl-(E)-2-(4-Methyl-5-Oxo-4-Phenyl-4,5-Dihydroindeno­[1,2-b]­Pyran-2­(3H)-Ylidene)­Acetate ((E)-11aa)

Purified by silica gel column chromatography eluting with Hexane/EA 30:1 to 20:1; 32% yield (13.5 mg); Yellow oil; ¹H NMR (400 MHz, CDCl₃): δ 7.47 (d, J = 6.7 Hz, 1H), 7.41–7.24 (m, 11H), 7.21–7.17 (m, 2H), 5.93 (d, J = 1.7 Hz, 1H), 5.20 (s, 2H), 4.49 (d, J = 15.2 Hz, 1H), 2.74 (dd, J = 15.2, 1.7 Hz, 1H), 1.82 (s, 3H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 191.8, 169.1, 165.7, 165.1, 144.9, 136.0, 135.8, 132.3, 132.0, 130.3, 128.5, 128.4, 128.1, 128.0, 126.5, 125.7, 121.7, 118.0, 115.6, 104.0, 66.0, 37.7, 37.4, 27.3; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₈H₂₃O₄: 423.1591, Found: 423.1594.

Benzyl-(Z)-2-(4-Methyl-5-Oxo-4-Phenyl-4,5-Dihydroindeno­[1,2-b]­Pyran-2­(3H)-Ylidene)­Acetate ((Z)-11aa)

Purified by silica gel column chromatography eluting with Hexane/EA 20:1 to 10:1; 60% yield (25.5 mg); Yellow soild; m.p.: 93–94 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.46–7.35 (m, 6H), 7.33–7.29 (m, 6H), 7.24–7.20 (m, 1H), 7.12–7.07 (m, 1H), 5.31 (d, J = 1.3 Hz, 1H), 5.20 (s, 2H), 2.90 (d, J = 14.8 Hz, 1H), 2.72 (dd, J = 14.7, 1.5 Hz, 1H), 1.80 (s, 3H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 191.4, 169.3, 163.3, 159.6, 144.4, 135.9, 135.7, 132.3, 132.0, 130.2, 128.45, 128.38, 128.3, 128.1, 126.6, 125.6, 121.5, 118.4, 114.7, 102.4, 66.0, 43.5, 37.3, 26.3; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₈H₂₃O₄: 423.1591, Found: 423.1597.

Benzyl-(E)-2-(4-(4-Fluorophenyl)-4-Methyl-5-Oxo-4,5-Dihydroindeno­[1,2-b]­Pyran-2­(3H)-Ylidene)­Acetate ((E)-11ab)

Purified by silica gel column chromatography eluting with Hexane/EA 30:1 to 20:1; 22% yield (9.6 mg); Yellow oil; ¹H NMR (400 MHz, CDCl₃): δ 7.47–7.45 (m, 1H), 7.41–7.28 (m, 9H), 7.21–7.19 (m, 1H), 6.93–6.87 (m, 2H), 5.91 (d, J = 1.5 Hz, 1H), 5.18 (s, 2H), 4.41 (d, J = 15.2 Hz, 1H), 2.72 (dd, J = 15.2, 1.7 Hz, 1H), 1.77 (s, 3H); ¹³C­{¹H }­NMR (101 MHz, CDCl₃): δ 191.9, 169.3, 165.8, 164.9, 162.7 (d, J = 245.0 Hz), 140.7, 136.0, 135.8, 132.5, 132.0, 130.5, 128.6, 128.3, 128.1, 127.6 (d, J = 7.9 Hz), 121.9, 118.2, 115.4, 115.3 (d, J = 21.0 Hz), 104.3, 66.2, 37.7, 37.4, 27.5; ¹⁹F NMR (376 MHz, CDCl₃): δ −116.3; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₈H₂₂O₄F: 441.1497, Found: 441.1495.

Benzyl-(Z)-2-(4-(4-Fluorophenyl)-4-Methyl-5-Oxo-4,5-Dihydroindeno­[1,2-b]­Pyran-2­(3H)-Ylidene)­Acetate ((Z)-11ab)

Purified by silica gel column chromatography eluting with Hexane/EA 20:1 to 10:1; 57% yield (25.8 mg); Yellow oil; ¹H NMR (400 MHz, CDCl₃): δ 7.42–7.34 (m, 6H), 7.32–7.22 (m, 5H), 7.06–7.03 (m, 1H), 6.99–6.93 (m, 2H), 5.26 (d, J = 1.3 Hz, 1H), 5.16 (s, 2H), 2.81 (d, J = 14.8 Hz, 1H), 2.70 (dd, J = 14.8, 1.5 Hz, 1H), 1.75 (s, 3H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 191.5, 169.6, 163.4, 162.7 (d, J = 245.8 Hz), 159.5, 140.2 (d, J = 2.9 Hz), 135.9, 135.7, 132.5, 132.0, 130.5, 128.5, 128.5, 128.2, 127.5 (d, J = 8.0 Hz), 121.8, 118.7, 115.5 (d, J = 20.9 Hz), 114.6, 102.8, 66.3, 44.0, 37.1, 26.5; ¹⁹F NMR (376 MHz, CDCl₃): δ −115.9; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₈H₂₂O₄F: 441.1497, Found: 441.1499.

Benzyl-(E)-2-(4-(4-Chlorophenyl)-4-Methyl-5-Oxo-4,5-Dihydroindeno­[1,2-b]­Pyran-2­(3H)-Ylidene)­Acetate ((E)-11ac)

Purified by silica gel column chromatography eluting with Hexane/EA 30:1 to 20:1; 30% yield (13.9 mg); Yellow oil; ¹H NMR (400 MHz, CDCl₃): δ 7.47–7.45 (m, 1H), 7.41–7.31 (m, 7H), 7.29–7.25 (m, 2H), 7.20–7.16 (m, 3H), 5.90 (d, J = 1.5 Hz, 1H), 5.17 (s, 2H), 4.40 (d, J = 15.2 Hz, 1H), 2.71 (dd, J = 15.2, 1.7 Hz, 1H), 1.75 (s, 3H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 191.9, 169.4, 165.8, 164.7, 143.6, 136.0, 135.8, 132.5, 132.4, 132.0, 130.6, 128.9, 128.6, 128.6, 128.3, 128.3, 128.2, 127.4, 121.9, 118.2, 115.2, 104.4, 66.2, 37.5, 37.4, 27.3; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₈H₂₂O₄Cl: 457.1201, Found: 457.1200.

Benzyl-(Z)-2-(4-(4-Chlorophenyl)-4-Methyl-5-Oxo-4,5-Dihydroindeno­[1,2-b]­Pyran-2­(3H)-Ylidene)­Acetate ((Z)-11ac)

Purified by silica gel column chromatography eluting with Hexane/EA 20:1 to 10:1; 57% yield (26.1 mg); Yellow oil; ¹H NMR (400 MHz, CDCl₃): δ 7.44–7.34 (m, 6H), 7.32–7.29 (m, 2H), 7.27–7.22 (m, 4H), 7.09–7.04 (m, 1H), 5.27 (d, J = 1.3 Hz, 1H), 5.18 (s, 2H), 2.82 (d, J = 14.8 Hz, 1H), 2.72 (dd, J = 14.7, 1.5 Hz, 1H), 1.76 (s, 3H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 191.4, 169.7, 163.4, 159.3, 143.1, 135.9, 135.8, 132.7, 132.6, 132.1, 130.5, 128.7, 128.6, 128.5, 128.3, 127.3, 121.8, 118.8, 114.3, 102.9, 66.3, 43.8, 37.2, 26.3; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₈H₂₂O₄Cl: 457.1201, Found: 457.1197.

Benzyl-(E)-2-(4-(4-Chlorophenyl)-4-Methyl-5-Oxo-4,5-Dihydroindeno­[1,2-b]­Pyran-2­(3H)-Ylidene)­Acetate ((E)-11ad)

Purified by silica gel column chromatography eluting with Hexane/EA 30:1 to 20:1; 21% yield (10.4 mg); Yellow oil; ¹H NMR (400 MHz, CDCl₃): δ 7.47–7.45 (m, 1H), 7.41–7.31 (m, 9H), 7.23–7.18 (m, 3H), 5.91 (d, J = 1.5 Hz, 1H), 5.18 (s, 2H), 4.41 (d, J = 15.2 Hz, 1H), 2.71 (dd, J = 15.2, 1.7 Hz, 1H), 1.76 (s, 3H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 191.9, 169.4, 165.8, 164.7, 144.1, 135.9, 135.7, 132.5, 132.0, 131.5, 130.6, 128.6, 128.3, 128.2, 127.8, 121.9, 120.6, 118.2, 115.1, 104.4, 66.2, 37.6, 37.3, 27.3; HRMS (ESI-TOF) m/z: [M + Na]⁺ calcd. for C₂₈H₂₁O₄BrNa: 523.0515, Found: 523.0523.

Benzyl-(Z)-2-(4-(4-Chlorophenyl)-4-Methyl-5-Oxo-4,5-Dihydroindeno­[1,2-b]­Pyran-2­(3H)-Ylidene)­Acetate ((Z)-11ad)

Purified by silica gel column chromatography eluting with Hexane/EA 20:1 to 10:1; 53% yield (26.8 mg); Yellow oil; ¹H NMR (400 MHz, CDCl₃): δ 7.43–7.36 (m, 8H), 7.34–7.29 (m, 2H), 7.17 (d, J = 8.6 Hz, 2H), 7.09–7.04 (m, 1H), 5.28 (d, J = 1.4 Hz, 1H), 5.18 (s, 2H), 2.82 (d, J = 14.8 Hz, 1H), 2.71 (dd, J = 14.8, 1.5 Hz, 1H), 1.75 (s, 3H); ¹³C­{¹H }­NMR (101 MHz, CDCl₃): δ 191.4, 169.7, 163.4, 159.3, 143.6, 135.9, 135.8, 132.6, 132.1, 131.7, 130.5, 128.6, 128.5, 128.3, 127.7, 121.8, 120.8, 118.8, 114.2, 103.0, 66.3, 43.8, 37.3, 26.3; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₈H₂₂O₄Br: 501.0696, Found: 501.0698.

Benzyl-(E)-2-(4-Methyl-5-Oxo-4-(p-Tolyl)-4,5-Dihydroindeno­[1,2-b]­Pyran-2­(3H)-Ylidene)­Acetate ((E)-11ae)

Purified by silica gel column chromatography eluting with Hexane/EA 30:1 to 20:1; 28% yield (12.1 mg); Yellow oil; ¹H NMR (400 MHz, CDCl₃): δ 7.45 (d, J = 7.1 Hz, 1H), 7.41–7.30 (m, 7H), 7.24 (d, J = 8.2 Hz, 2H), 7.18 (d, J = 6.2 Hz, 1H), 7.04 (d, J = 8.0 Hz, 2H), 5.90 (d, J = 1.6 Hz, 1H), 5.19 (s, 2H), 4.43 (d, J = 15.3 Hz, 1H), 2.72 (dd, J = 15.3, 1.7 Hz, 1H), 2.28 (s, 3H), 1.76 (s, 3H); ¹³C­{¹H }­NMR (101 MHz, CDCl₃): δ 192.0, 169.1, 165.9, 165.3, 142.1, 136.2, 136.1, 135.9, 132.4, 132.1, 130.4, 129.2, 128.6, 128.2, 128.1, 125.7, 121.8, 118.0, 115.9, 104.1, 66.1, 37.5, 37.5, 27.5, 20.9; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₉H₂₅O₄: 437.1747, Found: 437.1745.

Benzyl-(Z)-2-(4-Methyl-5-Oxo-4-(p-Tolyl)-4,5-Dihydroindeno­[1,2-b]­Pyran-2­(3H)-Ylidene)­Acetate ((Z)-11ae)

Purified by silica gel column chromatography eluting with Hexane/EA 20:1 to 10:1; 61% yield (26.7 mg); Yellow solid; m.p.: 110–111 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.43–7.36 (m, 5H), 7.32–7.28 (m, 2H), 7.19 (d, J = 8.3 Hz, 2H), 7.10 (d, J = 8.5 Hz, 2H), 7.06–7.02 (m, 1H), 5.28 (d, J = 1.3 Hz, 1H), 5.18 (s, 2H), 2.87 (d, J = 14.7 Hz, 1H), 2.71 (dd, J = 14.7, 1.5 Hz, 1H), 2.30 (s, 3H), 1.76 (s, 3H); ¹³C­{¹H }­NMR (101 MHz, CDCl₃): δ 191.6, 169.4, 163.6, 159.9, 141.5, 136.4, 136.1, 135.9, 132.4, 132.2, 130.3, 129.3, 128.6, 128.5, 128.2, 125.6, 121.7, 118.6, 115.1, 102.5, 66.2, 43.9, 37.2, 26.5, 20.9; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₉H₂₅O₄: 437.1747, Found: 437.1745.

Benzyl-(E)-2-(4-(4-Methoxyphenyl)-4-Methyl-5-Oxo-4,5-Dihydroindeno­[1,2-b]­Pyran-2­(3H)-Ylidene)­Acetate ((E)-11af)

Purified by silica gel column chromatography eluting with Hexane/EA 30:1 to 20:1; 11% yield (5.1 mg); Yellow oil; ¹H NMR (400 MHz, CDCl₃): δ 7.44 (d, J = 7.6 Hz, 1H), 7.39–7.28 (m, 7H), 7.24 (d, J = 2.8 Hz, 3H), 7.16 (d, J = 6.8 Hz, 1H), 6.74 (d, J = 8.8 Hz, 2H), 5.89 (d, J = 1.6 Hz, 1H), 5.17 (s, 2H), 4.40 (d, J = 15.2 Hz, 1H), 3.74 (s, 2H), 2.68 (dd, J = 15.2, 1.8 Hz, 1H), 1.75 (s, 3H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 192.0, 169.1, 165.9, 165.3, 158.1, 137.1, 136.2, 135.9, 132.4, 132.1, 130.4, 128.6, 128.4, 128.2, 128.1, 126.9, 121.8, 118.0, 116.0, 113.8, 104.1, 66.1, 55.1, 37.7, 37.2, 27.5; HRMS (ESI-TOF) m/z: [M + Na]⁺ calcd. for C₂₉H₂₄O₅Na: 475.1516, Found: 475.1505.

Benzyl-(Z)-2-(4-(4-Methoxyphenyl)-4-Methyl-5-Oxo-4,5-Dihydroindeno­[1,2-b]­Pyran-2­(3H)-Ylidene)­Acetate ((Z)-11af)

Purified by silica gel column chromatography eluting with Hexane/EA 20:1 to 10:1; 35% yield (15.7 mg); Yellow oil; ¹H NMR (400 MHz, CDCl₃): δ 7.43–7.35 (m, 5H), 7.32–7.28 (m, 3H), 7.22 (d, J = 8.8 Hz, 2H), 7.06–7.04 (m, 1H), 6.82 (d, J = 8.8 Hz, 2H), 5.27 (d, J = 1.3 Hz, 1H), 5.18 (s, 2H), 3.76 (s, 3H), 2.84 (d, J = 14.7 Hz, 1H), 2.70 (dd, J = 14.7, 1.5 Hz, 1H), 1.75 (s, 3H); ¹³C­{¹H }­NMR (101 MHz, CDCl₃): δ 191.6, 169.4, 163.6, 160.0, 158.2, 136.6, 136.1, 135.9, 132.4, 132.2, 130.3, 128.6, 128.5, 128.2, 126.9, 121.7, 118.6, 115.1, 113.9, 102.6, 66.2, 55.2, 44.1, 36.9, 26.6; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₉H₂₅O₅: 453.1697, Found: 453.1694.

Benzyl-(E)-2-(4-Methyl-4-(Naphthalen-2-yl)-5-Oxo-4,5-Dihydroindeno­[1,2-b]­Pyran-2­(3H)-Ylidene)­Acetate ((E)-11ag)

Purified by silica gel column chromatography eluting with Hexane/EA 30:1 to 20:1; 21% yield (9.8 mg); Yellow solid; m.p.: 134–135 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.66–7.63 (m, 3H), 7.54–7.52 (m, 1H), 7.47 (dd, J = 8.7, 2.0 Hz, 1H), 7.41–7.39 (m, 1H), 7.33–7.23 (m, 9H), 7.12–7.10 (m, 1H), 5.82 (d, J = 1.5 Hz, 1H), 5.13 (d, J = 12.4 Hz, 1H), 5.08 (d, J = 12.4 Hz, 1H), 4.54 (d, J = 15.3 Hz, 1H), 2.69 (dd, J = 15.3, 1.7 Hz, 1H), 1.78 (s, 3H); ¹³C­{¹H }­NMR (101 MHz, CDCl₃): δ 192.0, 169.4, 166.0, 165.2, 142.4, 136.1, 135.9, 133.2, 132.4, 132.1, 130.5, 128.6, 128.3, 128.24, 128.18, 127.3, 125.9, 125.7, 124.8, 124.0, 121.9, 118.1, 115.7, 104.2, 66.2, 38.1, 37.3, 27.4; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₃₂H₂₅O₄: 473.1747, Found: 473.1750.

Benzyl-(Z)-2-(4-Methyl-4-(Naphthalen-2-yl)-5-Oxo-4,5-Dihydroindeno­[1,2-b]­Pyran-2­(3H)-Ylidene)­Acetate ((Z)-11ag)

Purified by silica gel column chromatography eluting with Hexane/EA 20:1 to 10:1; 60% yield (28.5 mg); Yellow oil; ¹H NMR (400 MHz, CDCl₃): δ 7.81–7.77 (m, 3H), 7.70 (d, J = 2.0 Hz, 1H), 7.49–7.33 (m, 11H), 7.13–7.10 (m, 1H), 5.30 (d, J = 1.2 Hz, 1H), 5.17 (s, 2H), 3.01 (d, J = 14.8 Hz, 1H), 2.78 (dd, J = 14.8, 1.5 Hz, 1H), 1.88 (s, 3H); ¹³C­{¹H}­NMR (101 MHz, CDCl₃): δ 191.6, 169.7, 163.4, 159.7, 141.8, 136.0, 135.8, 133.2, 132.5, 132.2, 130.4, 128.5, 128.4, 128.2, 128.1, 127.4, 126.1, 125.9, 124.4, 124.1, 121.8, 118.7, 114.7, 102.7, 66.2, 43.8, 37.7, 26.4; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₃₂H₂₅O₄: 473.1747, Found: 473.1747.

Benzyl-(E)-2-(4-Methyl-5-Oxo-4-(Thiophen-2-yl)-4,5-Dihydroindeno­[1,2-b]­Pyran-2­(3H)-Ylidene)­Acetate ((E)-11ah)

Purified by silica gel column chromatography eluting with Hexane/EA 30:1 to 20:1; 16% yield (6.8 mg); Yellow solid; m.p.: 132–133 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.46–7.44 (m, 1H), 7.40–7.31 (m, 7H), 7.22–7.20 (m, 1H), 7.10 (dd, J = 5.0, 1.3 Hz, 1H), 6.87–6.83 (m, 2H), 5.97 (d, J = 1.7 Hz, 1H), 5.20 (d, J = 12.5 Hz, 1H), 5.16 (d, J = 12.4 Hz, 1H), 4.37 (d, J = 15.2 Hz, 1H), 2.79 (dd, J = 15.2, 1.8 Hz, 1H), 1.87 (s, 3H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 191.2, 169.0, 165.7, 164.4, 150.1, 135.9, 135.8, 132.4, 132.0, 130.6, 128.6, 128.3, 128.2, 126.7, 123.9, 123.3, 121.9, 118.3, 115.0, 105.0, 66.2, 39.0, 35.5, 28.0; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₆H₂₁O₄S: 429.1155, Found: 429.1153.

Benzyl-(Z)-2-(4-Methyl-5-Oxo-4-(Thiophen-2-yl)-4,5-Dihydroindeno­[1,2-b]­Pyran-2­(3H)-Ylidene)­Acetate ((Z)-11ah)

Purified by silica gel column chromatography eluting with Hexane/EA 20:1 to 10:1; 74% yield (31.6 mg); Yellow solid; m.p.: 127–128 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.43–7.36 (m, 6H), 7.32–7.29 (m, 2H), 7.14 (dd, J = 5.1, 1.2 Hz, 1H), 7.07–7.05 (m, 1H), 6.90–6.88 (m, 1H), 6.85–6.84 (m, 1H), 5.33 (s, 1H), 5.20 (s, 2H), 2.85 (d, J = 14.7 Hz, 1H), 2.79 (d, J = 14.7 Hz, 1H), 1.86 (s, 3H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 191.0, 169.1, 163.4, 159.2, 149.6, 135.8, 132.5, 132.1, 130.5, 128.6, 128.5, 128.2, 126.8, 124.0, 123.7, 121.8, 118.8, 114.2, 103.3, 66.3, 44.9, 35.6, 27.3; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₆H₂₁O₄S: 429.1155, Found: 429.1155.

3-Chlorobenzyl-(E)-2-(4-Methyl-5-Oxo-4-Phenyl-4,5-Dihydroindeno­[1,2-b]­Pyran-2­(3H)-Ylidene)­Acetate ((E)-11ba)

Purified by silica gel column chromatography eluting with Hexane/EA 30:1 to 20:1; 17% yield (7.8 mg); Yellow oil; ¹H NMR (400 MHz, CDCl₃): δ 7.48–7.45 (m, 1H), 7.41–7.29 (m, 7H), 7.28–7.13 (m, 5H), 5.90 (d, J = 1.6 Hz, 1H), 5.14 (s, 2H), 4.44 (d, J = 15.3 Hz, 1H), 2.73 (dd, J = 15.3, 1.7 Hz, 1H), 1.80 (s, 3H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 191.9, 169.2, 165.7, 165.5, 144.9, 137.9, 136.1, 134.4, 132.4, 132.1, 130.4, 129.8, 128.5, 128.4, 128.0, 126.7, 126.0, 125.8, 121.8, 118.1, 115.7, 103.8, 65.1, 37.8, 37.6, 27.4; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₈H₂₂O₄Cl: 457.1201, Found: 457.1201.

3-Chlorobenzyl-(Z)-2-(4-Methyl-5-Oxo-4-Phenyl-4,5-Dihydroindeno­[1,2-b]­Pyran-2­(3H)-Ylidene)­Acetate ((Z)-11ba)

Purified by silica gel column chromatography eluting with Hexane/EA 20:1 to 10:1; 63% yield (28.5 mg); Yellow oil; ¹H NMR (400 MHz, CDCl₃): δ 7.43 (ddd, J = 7.4, 4.3, 1.5 Hz, 2H), 7.35–7.23 (m, 9H), 7.22–7.21 (m, 1H), 7.14–7.12 (m, 1H), 5.28 (d, J = 1.4 Hz, 1H), 5.14 (s, 2H), 2.90 (d, J = 14.8 Hz, 1H), 2.74 (dd, J = 14.8, 1.2 Hz, 1H), 1.79 (s, 3H); ¹³C­{¹H}­NMR (101 MHz, CDCl₃): δ 191.6, 169.4, 163.3, 160.1, 144.4, 137.8, 136.0, 134.4, 132.5, 132.1, 130.4, 129.8, 128.6, 128.3, 128.2, 126.8, 126.3, 125.7, 121.8, 118.5, 114.9, 102.2, 65.2, 43.8, 37.5, 26.5; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₈H₂₂O₄Cl: 457.1201, Found: 457.1201.

3-Nitrobenzyl-(Z)-2-(4-Methyl-5-Oxo-4-Phenyl-4,5-Dihydroindeno­[1,2-b]­Pyran-2­(3H)-Ylidene)­Acetate ((Z)-11ca)

Purified by silica gel column chromatography eluting with Hexane/EA 20:1 to 10:1; 37% yield (17.2 mg); Yellow oil; ¹H NMR (400 MHz, CDCl₃): δ 8.25 (s, 1H), 8.19–8.17 (m, 1H), 7.69 (d, J = 7.7 Hz, 1H), 7.55–7.51 (m, 1H), 7.43–7.41 (m, 1H), 7.32–7.28 (m, 6H), 7.20–7.15 (m, 2H), 5.28 (s, 1H), 5.23 (d, J = 2.6 Hz, 2H), 2.89 (d, J = 14.6 Hz, 1H), 2.74 (d, J = 14.8 Hz, 1H), 1.78 (s, 3H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 191.5, 169.4, 163.0, 160.7, 148.3, 144.4, 138.1, 136.0, 134.0, 132.5, 132.1, 130.5, 129.6, 128.7, 126.9, 125.7, 123.1, 122.9, 121.9, 118.5, 115.0, 101.8, 64.6, 43.9, 37.6, 26.5; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₈H₂₂O₆N: 468.1442, Found: 468.1442.

4-(Trifluoromethyl)­Benzyl-(E)-2-(4-Methyl-5-Oxo-4-Phenyl-4,5-Dihydroindeno­[1,2-b]­Pyran-2­(3H)-Ylidene)­Acetate ((E)-11da)

Purified by silica gel column chromatography eluting with Hexane/EA 30:1 to 20:1; 16% yield (7.7 mg); Yellow solid; m.p.: 114–115 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.63 (d, J = 8.0 Hz, 2H), 7.47–7.43 (m, 3H), 7.38–7.33 (m, 4H), 7.25–7.17 (m, 4H), 5.91 (d, J = 1.5 Hz, 1H), 5.22 (s, 2H), 4.44 (d, J = 15.3 Hz, 1H), 2.73 (dd, J = 15.2, 1.7 Hz, 1H), 1.79 (s, 3H); ¹³C­{¹H }­NMR (101 MHz, CDCl₃): δ 191.9, 169.1, 165.7, 144.9, 139.9, 136.1, 132.5, 132.1, 130.5, 128.5, 128.2 (q, J = 21.7 Hz) 128.0, 126.8 (q, J = 286.6 Hz), 126.7, 125.8, 125.5 (q, J = 3.8 Hz), 121.9, 118.1, 115.7, 103.7, 65.1, 37.8, 37.6, 27.4; ¹⁹F NMR (376 MHz, CDCl₃): δ −62.5 (s, 3F); HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₉H₂₂O₄F₃: 491.1465, Found: 491.1466.

4-(Trifluoromethyl)­Benzyl-(Z)-2-(4-Methyl-5-Oxo-4-Phenyl-4,5-Dihydroindeno­[1,2-b]­Pyran-2­(3H)-Ylidene)­Acetate ((Z)-11da)

Purified by silica gel column chromatography eluting with Hexane/EA 20:1 to 10:1; 60% yield (29.1 mg); Yellow solid; m.p.: 105–106 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.64 (d, J = 8.0 Hz, 2H), 7.51 (d, J = 8.0 Hz, 2H), 7.45–7.43 (m, 1H), 7.32–7.29 (m, 6H), 7.25–7.19 (m, 1H), 7.08–7.06 (m, 1H), 5.29 (d, J = 1.4 Hz, 1H), 5.22 (s, 2H), 2.91 (d, J = 14.8 Hz, 1H), 2.75 (dd, J = 14.8, 1.5 Hz, 1H), 1.79 (s, 3H); ¹³C­{¹H}­NMR (101 MHz, CDCl₃): δ 191.5, 169.4, 163.3, 160.3, 144.4, 139.9, 136.0, 132.4, 132.1, 130.5, 130.0 (q, J = 33.3 Hz), 128.7, 128.4, 126.9, 126.8 (q, J = 292.1 Hz), 125.8, 125.5 (q, J = 3.3 Hz), 121.9, 118.5, 115.0, 102.2, 65.2, 43.9, 37.6, 26.5; ¹⁹F NMR (376 MHz, CDCl₃): δ −62.4 (s, 3F); HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₉H₂₂O₄F₃: 491.1465, Found: 491.1463.

4-Chlorobenzyl-(E)-2-(4-Methyl-5-Oxo-4-Phenyl-4,5-Dihydroindeno­[1,2-b]­Pyran-2­(3H)-Ylidene)­Acetate ((E)-11ea)

Purified by silica gel column chromatography eluting with Hexane/EA 30:1 to 20:1; 19% yield (8.5 mg); Yellow solid; m.p.: 133 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.40–7.38 (m, 1H), 7.30–7.25 (m, 6H), 7.21–7.11 (m, 6H), 5.81 (d, J = 1.5 Hz, 1H), 5.06 (s, 2H), 4.36 (d, J = 15.3 Hz, 1H), 2.65 (dd, J = 15.3, 1.7 Hz, 1H), 1.72 (s, 3H); ¹³C­{¹H}­NMR (101 MHz, CDCl₃): δ 191.9, 169.2, 165.8, 165.4, 144.9, 136.1, 134.4, 134.1, 132.4, 132.1, 130.4, 129.5, 128.7, 128.5, 126.7, 125.8, 121.8, 118.1, 115.7, 103.9, 65.2, 37.8, 37.6, 27.4; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₈H₂₂O₄Cl: 457.1201, Found: 457.1202.

4-Chlorobenzyl-(Z)-2-(4-Methyl-5-Oxo-4-Phenyl-4,5-Dihydroindeno­[1,2-b]­Pyran-2­(3H)-Ylidene)­Acetate ((Z)-11ea)

Purified by silica gel column chromatography eluting with Hexane/EA 20:1 to 10:1; 66% yield (29.9 mg); Yellow oil; ¹H NMR (400 MHz, CDCl₃): δ 7.44–7.42 (m, 1H), 7.37–7.29 (m, 10H), 7.23–7.21 (m, 1H), 7.04–7.02 (m, 1H), 5.27 (d, J = 1.3 Hz, 1H), 5.13 (s, 2H), 2.89 (d, J = 14.8 Hz, 1H), 2.73 (dd, J = 14.8, 1.5 Hz, 1H), 1.79 (s, 3H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 191.5, 169.4, 163.3, 160.0, 144.4, 135.9, 134.4, 134.1, 132.4, 132.1, 130.4, 129.8, 128.7, 128.6, 126.8, 125.7, 121.8, 118.5, 114.8, 102.3, 65.3, 43.8, 37.5, 26.5; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₈H₂₂O₄Cl: 457.1201, Found: 457.1200.

4-Bromobenzyl-(E)-2-(4-Methyl-5-Oxo-4-Phenyl-4,5-Dihydroindeno­[1,2-b]­Pyran-2­(3H)-Ylidene)­Acetate ((E)-11fa)

Purified by silica gel column chromatography eluting with Hexane/EA 30:1 to 20:1; 19% yield (9.7 mg); Yellow solid; m.p.: 139–140 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.51–7.45 (m, 3H), 7.37–7.33 (m, 4H), 7.26–7.18 (m, 6H), 5.88 (d, J = 1.5 Hz, 1H), 5.11 (s, 2H), 4.43 (d, J = 15.3 Hz, 1H), 2.72 (dd, J = 15.3, 1.7 Hz, 1H), 1.79 (s, 3H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 191.9, 169.2, 165.8, 165.4, 144.9, 136.1, 134.9, 132.4, 132.1, 131.7, 130.4, 129.8, 128.5, 126.7, 125.8, 122.2, 121.8, 118.1, 115.7, 103.9, 65.3, 37.8, 37.6, 27.3; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₈H₂₂O₄Br: 501.0696, Found: 501.0695.

4-Bromobenzyl-(Z)-2-(4-Methyl-5-Oxo-4-Phenyl-4,5-Dihydroindeno­[1,2-b]­Pyran-2­(3H)-Ylidene)­Acetate ((Z)-11fa)

Purified by silica gel column chromatography eluting with Hexane/EA 20:1 to 10:1; 60% yield (30.2 mg); Yellow solid; m.p.: 128–129 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.46 (d, J = 8.2 Hz, 2H), 7.40–7.38 (m, 1H), 7.32–7.22 (m, 8H), 7.18–7.14 (m, 1H), 6.98 (dd, J = 6.1, 1.8 Hz, 1H), 5.22 (d, J = 1.3 Hz, 1H), 5.07 (s, 2H), 2.85 (d, J = 14.7 Hz, 1H), 2.68 (dd, J = 14.8, 1.6 Hz, 1H), 1.74 (s, 3H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 191.5, 169.4, 163.3, 160.0, 144.4, 136.0, 134.9, 132.4, 132.1, 131.7, 130.4, 130.1, 128.6, 126.8, 125.7, 122.2, 121.8, 118.5, 114.9, 102.3, 65.4, 43.8, 37.5, 26.5; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₈H₂₂O₄Br: 501.0696, Found: 501.0695.

4-Methylbenzyl-(E)-2-(4-Methyl-5-Oxo-4-Phenyl-4,5-Dihydroindeno­[1,2-b]­Pyran-2­(3H)-Ylidene)­Acetate ((E)-11ga)

Purified by silica gel column chromatography eluting with Hexane/EA 30:1 to 20:1; 20% yield (8.6 mg); Yellow oil; ¹H NMR (400 MHz, CDCl₃): δ 7.47–7.45 (m, 1H), 7.37–7.32 (m, 4H), 7.24–7.17 (m, 8H), 5.88 (d, J = 1.5 Hz, 1H), 5.14 (s, 2H), 4.45 (d, J = 15.3 Hz, 1H), 2.73 (dd, J = 15.3, 1.7 Hz, 1H), 2.37 (s, 3H), 1.79 (s, 3H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 192.0, 169.2, 165.9, 165.0, 145.0, 138.1, 136.2, 132.8, 132.4, 132.1, 130.4, 129.2, 128.5, 128.3, 126.6, 125.9, 121.8, 118.1, 115.7, 104.3, 66.1, 37.8, 37.5, 27.4, 21.2; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₉H₂₅O₄: 437.1747, Found: 437.1749.

4-Methylbenzyl-(Z)-2-(4-Methyl-5-Oxo-4-Phenyl-4,5-Dihydroindeno­[1,2-b]­Pyran-2­(3H)-Ylidene)­Acetate ((Z)-11ga)

Purified by silica gel column chromatography eluting with Hexane/EA 20:1 to 10:1; 48% yield (20.8 mg); Yellow oil; ¹H NMR (400 MHz, CDCl₃): δ 7.44–7.41 (m, 1H), 7.33–7.28 (m, 8H), 7.23–7.19 (m, 3H), 7.11–7.05 (m, 1H), 5.27 (d, J = 1.4 Hz, 1H), 5.14 (s, 2H), 2.89 (d, J = 14.8 Hz, 1H), 2.72 (dd, J = 14.8, 1.5 Hz, 1H), 2.39 (s, 3H), 1.79 (s, 3H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 191.6, 169.5, 163.6, 159.6, 144.5, 138.1, 136.0, 132.8, 132.4, 132.2, 130.3, 129.2, 128.6, 126.8, 125.8, 121.7, 118.7, 114.8, 102.7, 66.2, 43.8, 37.5, 26.5, 21.2; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₉H₂₅O₄: 437.1747, Found: 437.1747.

4-Methoxybenzyl-(E)-2-(4-Methyl-5-Oxo-4-Phenyl-4,5-Dihydroindeno­[1,2-b]­Pyran-2­(3H)-Ylidene)­Acetate ((E)-11ha)

Purified by silica gel column chromatography eluting with Hexane/EA 30:1 to 20:1; 25% yield (11.4 mg); Yellow solid; m.p.: 123–124 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.46 (d, J = 6.9 Hz, 1H), 7.38–7.15 (m, 10H), 6.90 (d, J = 8.1 Hz, 2H), 5.87 (d, J = 1.7 Hz, 1H), 5.13 (d, J = 12.4 Hz, 1H), 5.09 (d, J = 12.2 Hz, 1H), 4.44 (d, J = 15.2 Hz, 1H), 3.82 (s, 3H), 2.73 (dd, J = 15.1, 1.8 Hz, 1H), 1.79 (s, 3H); ¹³C­{¹H} NMR (101 MHz, CDCl₃): δ 191.9, 169.2, 165.9, 164.9, 159.6, 145.0, 136.1, 132.4, 132.1, 130.4, 130.0, 129.5, 128.5, 127.9, 126.6, 125.9, 121.8, 118.1, 115.7, 113.9, 104.3, 66.0, 55.3, 37.8, 37.5, 27.4; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₉H₂₅O₅: 453.1697, Found: 453.1698.

4-Methoxybenzyl-(Z)-2-(4-Methyl-5-Oxo-4-Phenyl-4,5-Dihydroindeno­[1,2-b]­Pyran-2­(3H)-Ylidene)­Acetate ((Z)-11ha)

Purified by silica gel column chromatography eluting with Hexane/EA 20:1 to 10:1; 58% yield (26.3 mg); Yellow oil; ¹H NMR (400 MHz, CDCl₃): δ 7.39–7.37 (m, 1H), 7.32–7.22 (m, 8H), 7.18–7.14 (m, 1H), 7.02–6.97 (m, 1H), 6.89–6.85 (m, 2H), 5.21 (d, J = 1.3 Hz, 1H), 5.07 (s, 2H), 3.78 (s, 3H), 2.84 (d, J = 14.8 Hz, 1H), 2.67 (dd, J = 14.8, 1.5 Hz, 1H), 1.73 (s, 3H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 191.6, 169.5, 163.6, 159.6, 159.6, 144.5, 136.0, 132.4, 132.1, 130.34, 130.29, 128.6, 127.9, 126.8, 125.7, 121.7, 118.6, 114.8, 113.9, 102.7, 66.0, 55.2, 43.7, 37.5, 26.5; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₉H₂₅O₅: 453.1697, Found: 453.1697.

Naphthalen-2-Ylmethyl-(E)-2-(4-Methyl-5-Oxo-4-Phenyl-4,5-Dihydroindeno­[1,2-b]­Pyran-2­(3H)-Ylidene)­Acetate ((E)-11ia)

Purified by silica gel column chromatography eluting with Hexane/EA 30:1 to 20:1; 24% yield (11.1 mg); Yellow oil; ¹H NMR (400 MHz, CDCl₃): δ 7.87–7.83 (m, 4H), 7.52–7.44 (m, 4H), 7.39–7.30 (m, 4H), 7.23–7.14 (m, 4H), 5.94 (d, J = 1.5 Hz, 1H), 5.35 (s, 2H), 4.47 (d, J = 15.2 Hz, 1H), 2.74 (dd, J = 15.3, 1.7 Hz, 1H), 1.80 (s, 3H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 192.0, 169.2, 165.9, 165.2, 145.0, 136.1, 133.2, 133.1, 133.1, 132.4, 132.1, 130.4, 128.5, 128.4, 127.9, 127.7, 127.2, 126.6, 126.31, 126.28, 125.8, 125.7, 121.8, 118.1, 115.7, 104.1, 66.3, 37.8, 37.5, 27.4; HRMS (ESI-TOF)m/z: [M + H]⁺ calcd. for C₃₂H₂₅O₄: 473.1747, Found: 473.1751.

Naphthalen-2-Ylmethyl-(Z)-2-(4-Methyl-5-Oxo-4-Phenyl-4,5-Dihydroindeno­[1,2-b]­Pyran-2­(3H)-Ylidene)­Acetate ((Z)-11ia)

Purified by silica gel column chromatography eluting with Hexane/EA 20:1 to 10:1; 61% yield (28.9 mg); Yellow oil; ¹H NMR (400 MHz, CDCl₃): δ 7.89–7.83 (m, 4H), 7.55–7.50 (m, 3H), 7.40 (dt, J = 7.1, 0.9 Hz, 1H), 7.39–7.28 (m, 4H), 7.24–7.19 (m, 2H), 7.02 (ddd, J = 7.8, 7.1, 1.1 Hz, 1H), 6.87 (dt, J = 7.2, 0.9 Hz, 1H), 5.35 (s, 2H), 5.31 (d, J = 1.3 Hz, 1H), 2.89 (d, J = 14.8 Hz, 1H), 2.71 (dd, J = 14.8, 1.5 Hz, 1H), 1.78 (s, 3H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 191.6, 169.4, 163.6, 159.8, 144.5, 135.9, 133.2, 133.11, 133.06, 132.3, 132.0, 130.3, 128.6, 128.4, 127.9, 127.7, 127.6, 126.8, 126.3, 126.2, 125.7, 121.6, 118.5, 114.7, 102.6, 66.4, 43.7, 37.5, 26.5; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₃₂H₂₅O₄: 473.1747, Found: 473.1750.

Ethyl-(E)-2-(4-Methyl-5-Oxo-4-Phenyl-4,5-Dihydroindeno­[1,2-b]­Pyran-2­(3H)-Ylidene)­Acetate ((E)-11ja)

Purified by silica gel column chromatography eluting with Hexane/EA 30:1 to 20:1; 25% yield (9.0 mg); Yellow oil; ¹H NMR (400 MHz, CDCl₃): δ 7.47–7.45 (m, 1H), 7.40–7.24 (m, 6H), 7.21–7.15 (m, 2H), 5.84 (d, J = 1.6 Hz, 1H), 4.43 (d, J = 15.3 Hz, 1H), 4.18 (qd, J = 7.1, 1.7 Hz, 2H), 2.73 (dd, J = 15.2, 1.7 Hz, 1H), 1.79 (s, 3H), 1.28 (t, J = 7.1 Hz, 3H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 192.0, 169.3, 166.1, 164.6, 145.1, 136.2, 132.4, 132.1, 130.4, 128.5, 126.6, 125.9, 121.8, 118.1, 115.7, 104.5, 60.3, 37.8, 37.5, 27.4, 14.2.; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₃H₂₁O₄: 361.1434, Found: 361.1433.

Ethyl-(Z)-2-(4-Methyl-5-Oxo-4-Phenyl-4,5-Dihydroindeno­[1,2-b]­Pyran-2­(3H)-Ylidene)­Acetate ((Z)-11ja)

Purified by silica gel column chromatography eluting with Hexane/EA 20:1 to 10:1; 56% yield­(20.0 mg); Yellow solid; m.p.: 130–131 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.45–7.27 (m, 8H), 7.23–7.19 (m, 1H), 5.22 (s, 1H), 4.19 (q, J = 7.1 Hz, 2H), 2.88 (d, J = 14.7 Hz, 1H), 2.72 (dd, J = 14.7, 1.1 Hz, 1H), 1.79 (s, 3H), 1.31 (t, J = 7.1 Hz, 3H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 191.6, 169.6, 163.7, 159.3, 144.6, 136.2, 132.5, 132.2, 130.4, 128.6, 126.8, 125.8, 121.8, 118.6, 114.9, 102.9, 60.2, 43.9, 37.6, 26.5, 14.3; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₃H₂₁O₄: 361.1434, Found: 361.1434.

tert-Butyl-(Z)-2-(4-Methyl-5-Oxo-4-Phenyl-4,5-Dihydroindeno­[1,2-b]­Pyran-2­(3H)-Ylidene)­Acetate ((Z)-11ka)

Purified by silica gel column chromatography eluting with Hexane/EA 20:1 to 10:1; 54% yield (20.8 mg); Yellow solid; m.p.: 182–183 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.40–7.22 (m, 8H), 7.19–7.15 (m, 1H), 5.10 (d, J = 1.4 Hz, 1H), 2.81 (d, J = 14.7 Hz, 1H), 2.64 (dd, J = 14.7, 1.4 Hz, 1H), 1.73 (s, 3H), 1.47 (s, 9H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 191.7, 169.8, 163.0, 158.1, 144.7, 136.3, 132.4, 132.3, 130.4, 128.6, 126.7, 125.9, 121.7, 118.6, 114.9, 104.8, 80.6, 43.9, 37.5, 28.2, 26.6; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₅H₂₅O₄: 389.1747, Found: 389.1742.

Benzyl-2-(4,4-Dimethyl-5-Oxo-4,5-Dihydroindeno­[1,2-b]­Pyran-2-yl)­Acetate (12a)

Purified by silica gel column chromatography eluting with Hexane/EA 20:1 to 10:1; 71% yield (25.4 mg); Yellow solid; m.p.: 114–115 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.42–7.31 (m, 6H), 7.25–7.20 (m, 2H), 6.99–6.94 (m, 1H), 5.36 (s, 1H), 5.19 (s, 2H), 2.37 (s, 2H), 1.29 (s, 6H). ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 191.6, 168.5, 163.5, 160.4, 136.1, 135.8, 132.3, 132.2, 129.9, 128.5, 128.4, 128.2, 128.1, 121.3, 118.2, 116.1, 102.5, 66.1, 43.3, 29.9, 26.6; HRMS (ESI-TOF) m/z: [M + Na]⁺ calcd. for C₂₃H₂₀O₄Na: 383.1254, Found: 383.1258.

Benzyl-2-(5′-Oxo-5′H-Spiro­[Cyclohexane-1,4′-Indeno­[1,2-b]­Pyran]-2′-yl)­Acetate (12c)

Purified by silica gel column chromatography eluting with Hexane/EA 30:1 to 20:1; 77% yield (30.7 mg); Yellow oil; ¹H NMR (400 MHz, CDCl₃): δ 7.44–7.37 (m, 6H), 7.26–7.23 (m, 2H), 6.99–6.97 (m, 1H), 5.37 (s, 1H), 5.21 (s, 2H), 2.62 (s, 2H), 2.14 (td, J = 13.0, 3.9 Hz, 2H), 1.70–1.62 (m, 4H), 1.46–1.37 (m, 4H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 191.8, 168.3, 163.7, 160.8, 136.1, 135.9, 132.3, 132.2, 130.0, 128.6, 128.5, 128.2, 121.4, 118.2, 118.1, 102.3, 66.2, 41.0, 38.2, 36.8, 30.3, 23.2; HRMS (ESI-TOF) m/z: [M + Na]⁺ calcd. for C₂₆H₂₄O₄Na: 423.1567, Found: 423.1566.

Benzyl-2-(5′-Oxo-5′H-Spiro­[Cycloheptane-1,4′-Indeno­[1,2-b]­Pyran]-2′-yl)­Acetate (12d)

Purified by silica gel column chromatography eluting with Hexane/EA 20:1 to 10:1; 71% yield (29.2 mg); Yellow oil; ¹H NMR (400 MHz, CDCl₃): δ 7.44–7.35 (m, 6H), 7.26–7.24 (m, 2H), 6.98–6.96 (m, 1H), 5.36 (s, 1H), 5.21 (s, 2H), 2.47 (s, 2H), 2.12 (ddd, J = 14.8, 10.5, 1.5 Hz, 2H), 1.81–1.77 (m, 2H), 1.66–1.45 (m, 8H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 191.4, 169.2, 163.5, 159.8, 136.6, 136.0, 135.9, 133.4, 132.4, 132.3, 130.3, 129.0, 128.6, 128.6, 128.5, 128.2, 127.5, 126.4, 121.7, 118.6, 113.6, 103.0, 66.3, 42.0, 35.6, 24.9; HRMS (ESI-TOF) m/z: [M + Na]⁺ calcd. for C₂₇H₂₆O₄Na: 437.1723, Found: 437.1722.

Benzyl-2-(1′,3′-Dioxo-2-Phenyl-1′,3′-Dihydrospiro­[Cyclopentane-1,2′-Inden]-2-en-5-yl)­Acetate (13aa)

Purified by silica gel column chromatography eluting with Hexane/THF 12:1 to 8:1; 50% yield (21.5 mg); Yellow oil; ¹H NMR (400 MHz,CDCl₃): δ 7.97–7.93 (m, 2H), 7.85–7.80 (m, 2H), 7.34–7.29 (m, 3H), 7.20–7.17 (m, 2H), 7.11–7.03 (m, 3H), 6.93–6.90 (m, 2H), 6.42 (t, J = 2.5 Hz, 1H), 4.81 (s, 2H), 3.47 – 3.43 (m, 1H), 2.93 (ddd, J = 16.8, 8.3, 2.8 Hz, 1H), 2.60–2.46 (m, 3H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 202.3, 201.1, 171.3, 142.8, 142.1, 141.7, 135.8, 135.7, 135.3, 134.6, 134.1, 128.4, 128.23, 128.18, 128.1, 127.5, 126.3, 123.3, 71.0, 66.2, 44.6, 38.4, 35.4; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₈H₂₃O₄: 423.1591, Found: 423.1574.

Benzyl-2-(2-(4-Fluorophenyl)-1′,3′-Dioxo-1′,3′-Dihydrospiro­[Cyclopentane-1,2′-Inden]-2-en-5-yl)­Acetate (13ab)

Purified by silica gel column chromatography eluting with Hexane/THF 12:1 to 8:1; 40% yield (17.6 mg); Yellow oil; ¹H NMR (400 MHz, CDCl₃): δ 7.96–7.92 (m, 2H), 7.85–7.80 (m, 2H), 7.35–7.29 (m, 3H), 7.19–7.16 (m, 2H), 6.91–6.87 (m, 2H), 6.77–6.73 (m, 2H), 6.34 (t, J = 2.5 Hz, 1H), 4.80 (s, 2H), 3.49–3.41 (m, 1H), 2.92 (ddd, J = 16.9, 8.4, 2.8 Hz, 1H), 2.60–2.47 (m, 3H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 202.3, 201.2, 171.4, 162.1 (d, J = 247.1 Hz), 142.8, 141.8, 141.2, 136.0, 135.9, 135.3, 134.4, 130.9 (d, J = 3.3 Hz), 128.5, 128.3, 128.22, 128.15, 123.3, 115.2 (d, J = 21.6 Hz), 71.2, 66.3, 44.5, 38.4, 35.4; ¹⁹F NMR (376 MHz, CDCl₃): δ −114.1 (s, 1F); HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₈H₂₂O₄F: 441.1497, Found: 441.1485.

Benzyl-2-(2-(4-Chlorophenyl)-1′,3′-Dioxo-1′,3′-Dihydrospiro­[Cyclopentane-1,2′-Inden]-2-en-5-yl)­Acetate (13ac)

Purified by silica gel column chromatography eluting with Hexane/THF 12:1 to 8:1; 36% yield (16.6 mg); Yellow oil; ¹H NMR (400 MHz, CDCl₃): δ 7.97–7.93 (m, 2H), 7.86–7.80 (m, 2H), 7.35–7.29 (m, 3H), 7.17–7.16 (m, 2H), 7.03 (d, J = 8.3 Hz, 2H), 6.85 (d, J = 8.3 Hz, 2H), 6.40 (t, J = 2.5 Hz, 1H), 4.81 (s, 2H), 3.48–3.40 (m, 1H), 2.93 (ddd, J = 17.0, 8.4, 2.8 Hz, 1H), 2.60–2.46 (m, 3H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 202.1, 201.0, 171.3, 142.8, 141.8, 141.1, 136.0, 135.9, 135.3, 135.0, 133.4, 133.2, 128.5, 128.3, 128.2, 127.7, 123.4, 71.0, 66.3, 44.7, 38.5, 35.4; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₈H₂₂O₄Cl: 457.1201, Found: 457.1189.

Benzyl-2-(2-(4-Bromophenyl)-1′,3′-Dioxo-1′,3′-Dihydrospiro­[Cyclopentane-1,2′-Inden]-2-en-5-yl)­Acetate (13ad)

Purified by silica gel column chromatography eluting with Hexane/THF 12:1 to 8:1; 28% yield (14.1 mg); Yellow oil; ¹H NMR (400 MHz, CDCl₃): δ 7.97–7.93 (m, 2H), 7.86–7.80 (m, 2H), 7.33–7.28 (m, 3H), 7.21–7.16 (m, 4H), 6.8 (dt, J = 8.6, 2.5 Hz, 2H), 6.41 (t, J = 2.5 Hz, 1H), 4.81 (s, 2H), 3.48–3.40 (m, 1H), 2.92 (ddd, J = 16.9, 8.3, 2.9 Hz, 1H), 2.59–2.46 (m, 3H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 202.1, 201.0, 171.3, 142.8, 141.7, 141.1, 136.0, 135.9, 135.3, 135.1, 133.7, 131.4, 128.5, 128.2, 123.4, 121.6, 71.0, 66.3, 44.7, 38.5, 35.4; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₈H₂₂O₄Br: 501.0696, Found: 501.0684.

Benzyl-2-(1′,3′-Dioxo-2-(p-Tolyl)-1′,3′-Dihydrospiro­[Cyclopentane-1,2′-Inden]-2-en-5-yl)­Acetate (13ae)

Purified by silica gel column chromatography eluting with Hexane/THF 12:1 to 8:1; 55% yield (24.1 mg); Yellow oil; ¹H NMR (400 MHz, CDCl₃): δ 7.97–7.94 (m, 2H), 7.84–7.82 (m, 2H), 7.11–7.03 (m, 7H), 6.93–6.90 (m, 2H), 6.42 (t, J = 2.6 Hz, 1H), 4.77 (s, 2H), 3.48–3.40 (m, 1H), 2.92 (ddd, J = 16.9, 8.3, 2.9 Hz, 1H), 2.60–2.43 (m, 3H), 2.33 (s, 3H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 202.6, 201.5, 171.5, 143.0, 142.3, 142.0, 137.5, 136.0, 135.9, 135.5, 133.5, 131.9, 129.1, 128.6, 128.4, 128.3, 126.4, 123.5, 123.4, 71.1, 66.4, 44.9, 38.5, 35.6, 21.1; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₉H₂₅O₄: 437.1747, Found: 437.1736.

Benzyl-2-(2-(4-Methoxyphenyl)-1′,3′-Dioxo-1′,3′-Dihydrospiro­[Cyclopentane-1,2′-Inden]-2-en-5-yl)­Acetate (13af)

Purified by silica gel column chromatography eluting with Hexane/THF 12:1 to 8:1; 33% yield (14.9 mg); Yellow oil; ¹H NMR (400 MHz, CDCl₃): δ 7.97–7.93 (m, 2H), 7.83–7.81 (m, 2H), 7.33–7.28 (m, 3H), 7.19–7.17 (m, 2H), 6.88–6.83 (m, 2H), 6.61–6.57 (m, 2H), 6.32 (t, J = 2.5 Hz, 1H), 4.81 (d, J = 1.7 Hz, 2H), 3.66 (s, 3H), 3.48–3.40 (m, 1H), 2.91 (ddd, J = 16.7, 8.3, 2.8 Hz, 1H), 2.60–2.45 (m, 3H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 202.6, 201.4, 171.4, 159.0, 142.9, 141.8, 141.7, 135.8, 135.7, 135.4, 132.7, 128.5, 128.23, 128.15, 127.6, 127.3, 123.3, 113.7, 71.1, 66.2, 55.1, 44.7, 38.4, 35.5; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₉H₂₅O₅: 453.1697, Found: 453.1688.

Benzyl-2-(2-(Naphthalen-2-yl)-1′,3′-Dioxo-1′,3′-Dihydrospiro­[Cyclopentane-1,2′-Inden]-2-en-5-yl)­Acetate (13ag)

Purified by silica gel column chromatography eluting with Hexane/THF 12:1 to 8:1; 47% yield (22.0 mg); Yellow oil; ¹H NMR (400 MHz, CDCl₃): δ 7.99–7.97 (m, 2H), 7.84–7.82 (m, 2H), 7.66 (d, J = 6.8 Hz, 1H), 7.58 (d, J = 9.1 Hz, 1H), 7.42–7.30 (m, 6H), 7.22–7.19 (m, 4H), 6.56 (t, J = 2.5 Hz, 1H), 4.84 (s, 2H), 3.57–3.49 (m, 1H), 3.00 (ddd, J = 16.9, 8.4, 2.8 Hz, 1H), 2.67–2.52 (m, 3H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 202.5, 201.4, 171.4, 143.0, 142.2, 141.8, 136.0, 135.8, 135.4, 134.9, 132.9, 132.6, 132.2, 128.5, 128.3, 128.2, 128.0, 127.9, 127.4, 126.1, 126.0, 125.5, 125.3, 124.7, 123.4, 123.4, 71.1, 66.3, 44.7, 38.6, 35.5, 30.3; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₃₂H₂₅O₄: 473.1747, Found: 473.1755.

Benzyl-2-(1′,3′-Dioxo-2-(Thiophen-2-yl)-1′,3′-Dihydrospiro­[Cyclopentane-1,2′-Inden]-2-en-5-yl)­Acetate (13ah)

Purified by silica gel column chromatography eluting with Hexane/THF 12:1 to 8:1; 50% yield (21.3 mg); Yellow oil; ¹H NMR (400 MHz, CDCl₃): δ 8.03 (d, J = 6.8 Hz, 1H), 7.95 (d, J = 6.9 Hz, 1H), 7.89–7.82 (m, 2H), 7.33–7.29 (m, 3H), 7.19–7.17 (m, 2H), 6.99 (d, J = 5.1 Hz, 1H), 6.64 (t, J = 4.1 Hz, 1H), 6.45 (t, J = 2.7 Hz, 1H), 6.24 (d, J = 3.6 Hz, 1H), 4.81 (s, 2H), 3.50–3.42 (m, 1H), 2.94 (ddd, J = 17.2, 8.4, 2.9 Hz, 1H), 2.60–2.46 (m, 3H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 202.1, 200.9, 171.3, 143.0, 141.9, 137.5, 136.0, 135.9, 135.3, 135.2, 133.6, 128.5, 128.2, 128.1, 127.0, 124.6, 123.8, 123.4, 123.3, 70.6, 66.3, 44.5, 38.5, 35.4; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₆H₂₁O₄S: 429.1155, Found: 429.1147.

3-Chlorobenzyl-2-(1′,3′-Dioxo-2-Phenyl-1′,3′-Dihydrospiro­[Cyclopentane-1,2′-Inden]-2-en-5-yl)­Acetate (13ba)

Purified by silica gel column chromatography eluting with Hexane/THF 12:1 to 8:1; 31% yield (14.3 mg); Yellow oil;¹H NMR (400 MHz, CDCl₃): δ 7.95–7.93 (m, 2H), 7.84–7.80 (m, 2H), 7.29–7.22 (m, 3H), 7.15–7.03 (m, 5H), 6.92–6.90 (m, 2H), 6.41 (t, J = 2.5 Hz, 1H), 4.77 (s, 2H), 3.47 – 3.41 (m, 1H), 2.93 (ddd, J = 16.8, 8.4, 2.9 Hz, 1H), 2.62–2.50 (m, 3H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 202.3, 201.2, 171.3, 142.8, 142.3, 141.8, 137.4, 135.9, 135.8, 134.6, 134.3, 134.1, 129.8, 128.5, 128.4, 128.3, 128.1, 127.6, 126.4, 126.2, 126.1, 123.3, 71.0, 65.3, 44.5, 38.5, 35.4; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₈H₂₂O₄Cl: 457.1201, Found: 457.1183.

3-Nitrobenzyl-2-(1′,3′-Dioxo-2-Phenyl-1′,3′-Dihydrospiro­[Cyclopentane-1,2′-Inden]-2-en-5-yl)­Acetate (13ca)

Purified by silica gel column chromatography eluting with Hexane/THF 12:1 to 8:1; 30% yield (14.1 mg); Yellow oil; ¹H NMR (400 MHz, CDCl₃): δ 8.16 (dt, J = 7.6, 2.1 Hz, 1H), 8.02 (s, 1H), 7.95–7.91 (m, 2H), 7.84–7.79 (m, 2H), 7.54–7.48 (m, 2H), 7.08–7.03 (m, 3H), 6.91–6.89 (m, 2H), 6.40 (t, J = 2.5 Hz, 1H), 4.89 (s, 2H), 3.48–3.41 (m, 1H), 2.94 (ddd, J = 16.8, 8.4, 2.8 Hz, 1H), 2.61–2.54 (m, 3H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 202.3, 201.2, 171.3, 142.8, 142.3, 141.8, 137.4, 135.9, 135.8, 134.6, 134.1, 134.0, 129.6, 128.3, 127.6, 126.4, 123.3, 123.2, 122.9, 71.0, 64.8, 44.3, 38.4, 35.3; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₈H₂₂O₆N: 468.1442, Found: 468.1425.

4-(Trifluoromethyl)­Benzyl-2-(1′,3′-Dioxo-2-Phenyl-1′,3′-Dihydrospiro­[Cyclopentane-1,2′-Inden]-2-en-5-yl)­Acetate (13da)

Purified by silica gel column chromatography eluting with Hexane/THF 12:1 to 8:1; 43% yield (21.1 mg); Yellow oil; ¹H NMR (400 MHz, CDCl₃): δ 7.94–7.88 (m, 2H), 7.82–7.77 (m, 2H), 7.56 (d, J = 8.0 Hz, 2H), 7.29 (d, J = 8.0 Hz, 2H), 7.10–7.03 (m, 3H), 6.92–6.89 (m, 2H), 6.40 (t, J = 2.5 Hz, 1H), 4.86 (s, 2H), 3.50 – 3.42 (m, 1H), 2.94 (ddd, J = 16.8, 8.4, 2.8 Hz, 1H), 2.62–2.53 (m, 3H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 202.3, 201.3, 171.3, 142.8, 142.3, 141.8, 139.4, 135.9, 135.7, 134.6, 134.1, 130.3 (q, J = 32.9 Hz), 128.3, 128.1, 127.6, 126.6 (q, J = 274.6 Hz), 126.4, 125.5 (q, J = 3.6 Hz), 123.3, 71.0, 65.2, 44.4, 38.5, 35.3. ¹⁹F NMR (376 MHz, CDCl₃): δ −62.5 (s, 3F); HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₉H₂₂F₃O₄: 491.1465, Found: 491.1445.

4-Chlorobenzyl-2-(1′,3′-Dioxo-2-Phenyl-1′,3′-Dihydrospiro­[Cyclopentane-1,2′-Inden]-2-en-5-yl)­Acetate (13ea)

Purified by silica gel column chromatography eluting with Hexane/THF 12:1 to 8:1; 54% yield (24.9 mg); Yellow oil; ¹H NMR (400 MHz, CDCl₃): δ 7.95–7.90 (m, 2H), 7.84–7.79 (m, 2H), 7.27 (d, J = 8.5 Hz, 2H), 7.12–7.03 (m, 5H), 6.91 (dd, J = 7.8, 1.8 Hz, 2H), 6.40 (t, J = 2.6 Hz, 1H), 4.77 (s, 2H), 3.49–3.41 (m, 1H), 2.92 (ddd, J = 16.8, 8.3, 2.8 Hz, 1H), 2.61–2.49 (m, 3H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 202.3, 201.2, 171.3, 142.8, 142.2, 141.7, 135.9, 135.7, 134.6, 134.13, 134.05, 133.9, 129.5, 128.6, 128.3, 127.6, 126.3, 123.3, 70.9, 65.4, 44.5, 38.4, 35.3; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₈H₂₂O₄Cl: 457.1201, Found: 457.1208.

4-Bromobenzyl-2-(1′,3′-Dioxo-2-Phenyl-1′,3′-Dihydrospiro­[Cyclopentane-1,2′-Inden]-2-en-5-yl)­Acetate (13fa)

Purified by silica gel column chromatography eluting with Hexane/THF 12:1 to 8:1; 62% yield (31.4 mg); Yellow oil; ¹H NMR (400 MHz, CDCl₃): δ 7.94–7.90 (m, 2H), 7.83–7.80 (m, 2H), 7.44–7.41 (m, 2H), 7.08–7.03 (m, 5H), 6.92–6.89 (m, 2H), 6.40 (t, J = 2.3 Hz, 1H), 4.75 (s, 2H), 3.48–3.40 (m, 1H), 2.92 (ddd, J = 16.8, 8.4, 2.6 Hz, 1H), 2.61–2.48 (m, 3H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 202.3, 201.2, 171.3, 142.8, 142.3, 141.7, 135.8, 135.7, 134.6, 134.4, 134.1, 131.6, 129.8, 128.3, 127.6, 126.4, 123.3, 122.2, 71.0, 65.4, 44.4, 38.4, 35.4; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₈H₂₂O₄Br: 501.0696, Found: 501.0703.

4-Methylbenzyl-2-(1′,3′-Dioxo-2-Phenyl-1′,3′-Dihydrospiro­[Cyclopentane-1,2′-Inden]-2-en-5-yl)­Acetate (13ga)

Purified by silica gel column chromatography eluting with Hexane/THF 12:1 to 8:1; 43% yield (18.8 mg); Yellow oil;¹H NMR (400 MHz, CDCl₃): δ 7.97–7.94 (m, 2H), 7.85–7.80 (m, 2H), 7.13–7.03 (m, 7H), 6.93–6.90 (m, 2H), 6.42 (t, J = 2.6 Hz, 1H), 4.77 (s, 2H), 3.48 – 3.40 (m, 1H), 2.92 (ddd, J = 16.8, 8.3, 2.8 Hz, 1H), 2.60–2.43 (m, 3H), 2.33 (s, 3H); ¹³C­{¹H }­NMR (101 MHz, CDCl₃): δ 202.4, 201.2, 171.4, 142.9, 142.2, 141.8, 138.1, 135.9, 135.7, 134.7, 134.2, 132.4, 129.2, 128.34, 128.30, 127.6, 126.4, 123.4, 123.3, 71.0, 66.2, 44.8, 38.4, 35.4, 21.2; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₉H₂₅O₄: 437.1747, Found: 437.1732.

4-Methoxybenzyl-2-(1′,3′-Dioxo-2-Phenyl-1′,3′-Dihydrospiro­[Cyclopentane-1,2′-Inden]-2-en-5-yl)­Acetate (13ha)

Purified by silica gel column chromatography eluting with Hexane/THF 12:1 to 8:1; 28% yield (12.2 mg); Yellow oil; ¹H NMR (400 MHz, CDCl₃): δ 7.97–7.94 (m, 2H), 7.85–7.81 (m, 2H), 7.14–7.03 (m, 5H), 6.93–6.90 (m, 2H), 6.85–6.81 (m, 2H), 6.42 (t, J = 2.5 Hz, 1H), 4.75 (s, 2H), 3.79 (s, 3H), 3.48–3.40 (m, 1H), 2.91 (ddd, J = 16.8, 8.3, 2.8 Hz, 1H), 2.59–2.42 (m, 3H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 202.3, 201.2, 171.4, 159.5, 142.8, 142.1, 141.7, 135.8, 135.7, 134.6, 134.2, 130.0, 128.2, 127.52, 127.47, 126.3, 123.31, 123.27, 113.8, 71.0, 66.0, 55.2, 44.7, 38.4, 35.4; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₉H₂₅O₅: 453.1697, Found: 453.1681.

Naphthalen-2-Ylmethyl-2-(1′,3′-Dioxo-2-Phenyl-1′,3′-Dihydrospiro­[Cyclopentane-1,2′-Inden]-2-en-5-yl)­Acetate (13ia)

Purified by silica gel column chromatography eluting with Hexane/THF 12:1 to 8:1; 45% yield (21.2 mg); Yellow oil; ¹H NMR (400 MHz, CDCl₃): δ 7.92–7.78 (m, 5H), 7.75–7.64 (m, 3H), 7.52–7.47 (m, 2H), 7.29 (dt, J = 8.3, 1.5 Hz, 1H), 7.08–7.04 (m, 3H), 6.93–6.90 (m, 2H), 6.4 (t, J = 2.0 Hz, 1H), 4.98 (s, 2H), 3.51– 3.47 (m, 1H), 2.94 (ddd, J = 16.9, 8.3, 2.8 Hz, 1H), 2.65–2.55 (m, 3H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 202.4, 201.3, 171.4, 142.8, 142.2, 141.7, 135.8, 135.7, 134.6, 134.2, 133.0, 132.8, 128.3, 128.0, 127.9, 127.63, 127.55, 127.3, 126.34, 126.27, 125.7, 123.2, 71.0, 66.4, 44.6, 38.5, 35.4; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₃₂H₂₅O₄: 473.1747, Found: 473.1750.

Ethyl-2-(1′,3′-Dioxo-2-Phenyl-1′,3′-Dihydrospiro­[Cyclopentane-1,2′-Inden]-2-en-5-yl)­Acetate (13ja)

Purified by silica gel column chromatography eluting with Hexane/THF 12:1 to 8:1; 53% yield (18.9 mg); Yellow oil; ¹H NMR (400 MHz, CDCl₃): δ 8.00–7.95 (m, 2H), 7.86–7.82 (m, 2H), 7.09–7.03 (m, 3H), 6.93–6.90 (m, 2H), 6.42 (t, J = 2.5 Hz, 1H), 3.84–3.78 (m, 2H), 3.48–3.40 (m, 1H), 2.93 (ddd, J = 16.8, 8.3, 2.9 Hz, 1H), 2.60–2.41 (m, 3H), 1.04 (t, J = 7.1 Hz, 3H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 202.4, 201.3, 171.5, 142.2, 141.8, 135.9, 135.7, 134.7, 134.2, 128.3, 127.6, 126.4, 123.34, 123.30, 71.0, 60.4, 44.7, 38.4, 35.5, 13.9; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₃H₂₁O₄: 361.1434, Found: 361.1443.

tert-Butyl-2-(1′,3′-Dioxo-2-Phenyl-1′,3′-Dihydrospiro­[Cyclopentane-1,2′-Inden]-2-en-5-yl)­Acetate (13ka)

Purified by silica gel column chromatography eluting with Hexane/THF 12:1 to 8:1; 22% yield (8.6 mg); Yellow oil; ¹H NMR (400 MHz, CDCl₃): δ 8.00–7.96 (m, 2H), 7.86–7.82 (m, 2H), 7.09–7.03 (m, 3H), 6.94–6.91 (m, 2H), 6.44 (t, J = 2.5 Hz, 1H), 3.44–3.36 (m, 1H), 2.91 (ddd, J = 16.9, 8.3, 2.8 Hz, 1H), 2.55 (ddd, J = 16.9, 8.7, 2.3 Hz, 1H), 2.46–2.34 (m, 2H), 1.20 (s, 9H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 201.5, 170.9, 143.1, 142.2, 141.8, 135.8, 135.6, 134.8, 134.4, 128.3, 127.5, 126.3, 123.5, 123.3, 80.7, 71.0, 45.1, 38.3, 36.7, 27.7; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₅H₂₅O₄: 389.1747, Found: 389.1757.

Ethyl-1,3-Dioxo-6a′-Phenyl-1,3,3a′,5′,6′,6a′-Hexahydro-4′H-Spiro­[Indene-2,1′-Pentalene]-2′-Carboxylate (15a)

Purified by silica gel column chromatography eluting with Hexane/EA 20:1 to 10:1; 88% yield (34.0 mg); Yellow solid; m.p.: 125–126 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.03 (d, J = 9.7 Hz, 1H), 7.77 (t, J = 7.5 Hz, 1H), 7.62 (t, J = 7.4 Hz, 1H), 7.47 (d, J = 7.6 Hz, 1H), 7.18 (d, J = 2.2 Hz, 1H), 7.00–6.95 (m, 3H), 6.91–6.88 (m, 2H), 4.26 (d, J = 7.1 Hz, 1H), 4.03–3.90 (m, 2H), 2.79–2.77 (m, 1H), 2.01 – 1.71 (m, 4H), 1.30–1.24 (m, 1H), 0.99 (t, J = 7.1 Hz, 3H); ¹³C­{¹H }­NMR (101 MHz, CDCl₃): δ 199.81, 199.77, 163.2, 154.1, 143.3, 142.2, 140.3, 135.1, 135.0, 133.4, 127.8, 127.3, 126.6, 122.8, 122.7, 71.7, 68.4, 60.7, 51.9, 37.2, 27.9, 24.1, 13.6; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₅H₂₃O₄: 387.1591, Found: 387.1597.

Ethyl-6a′-(4-Fluorophenyl)-1,3-Dioxo-1,3,3a′,5′,6′,6a′-Hexahydro-4′H-Spiro­[indene-2,1′-Pentalene]-2′-Carboxylate (15b)

Purified by silica gel column chromatography eluting with Hexane/EA 20:1 to 10:1; 58% yield (23.5 mg); Yellow solid; m.p.: 132–133 °C; ¹H NMR (400 MHz, Acetone-D₆): δ 8.02 (dt, J = 7.7, 1.0 Hz, 1H), 7.94–7.90 (m, 1H), 7.78 (td, J = 7.4, 1.1 Hz, 1H), 7.47 (dt, J = 7.6, 1.0 Hz, 1H), 7.15 (d, J = 2.3 Hz, 1H), 6.99–6.96 (m, 2H), 6.77–6.72 (m, 2H), 4.22 (dt, J = 9.4, 3.1 Hz, 1H), 3.98–3.86 (m, 2H), 2.71 (ddd, J = 13.1, 11.6, 7.1 Hz, 1H), 2.00–1.95 (m, 1H), 1.88–1.80 (m, 2H), 1.75–1.67 (m, 1H), 1.26–1.14 (m, 1H), 0.97 (t, J = 7.1 Hz, 3H); ¹³C­{¹H } NMR (101 MHz, Acetone-D₆): δ 199.0, 162.8, 162.6 (d, J = 244.2 Hz), 153.7, 146.6, 143.5, 142.4, 136.8 (d, J = 3.3 Hz), 135.7, 135.6, 135.5, 133.6, 129.65, 129.57, 123.3, 122.7, 122.5, 114.5 (d, J = 21.5 Hz), 71.7, 67.5, 60.4, 52.5, 37.3, 30.3, 27.6, 23.9, 13.2; ¹⁹F NMR (376 MHz, Acetone-D₆): δ −117.5 (s, 1F); HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₅H₂₂O₄F: 405.1497, Found: 405.1490.

Ethyl-6a′-(4-Chlorophenyl)-1,3-Dioxo-1,3,3a′,5′,6′,6a’-Hexahydro-4′H-Spiro­[Indene-2,1′-Pentalene]-2′-Carboxylate (15c)

Purified by silica gel column chromatography eluting with Hexane/EA 20:1 to 10:1; 66% yield (27.9 mg); Yellow solid; m.p.: 137–138 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.03 (d, J = 7.6 Hz, 1H), 7.78 (t, 1H), 7.67 (t, J = 7.4 Hz, 1H), 7.53 (d, J = 7.6 Hz, 1H), 7.15 (d, J = 2.2 Hz, 1H), 6.96 (d, J = 8.2 Hz, 2H), 6.84 (d, J = 8.2 Hz, 2H), 4.20 (d, J = 9.3 Hz, 1H), 4.02–3.90 (m, 2H), 2.82–2.74 (m, 1H), 2.02–1.94 (m, 1H), 1.87–1.70 (m, 3H), 1.31–1.19 (m, 1H), 0.99 (t, J = 7.1 Hz, 3H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 199.7, 199.6, 163.0, 153.8, 143.2, 142.1, 139.1, 135.4, 135.2, 133.5, 132.5, 128.7, 128.0, 123.0, 122.8, 71.5, 67.8, 60.8, 52.2, 37.2, 27.9, 24.1, 13.6; HRMS (ESI-TOF) m/z: [M + Na]⁺ calcd. for C₂₅H₂₁O₄ClNa: 443.1021, Found: 443.1015.

Ethyl-6a’-(4-Bromophenyl)-1,3-Dioxo-1,3,3a’,5′,6′,6a′-Hexahydro-4′H-Spiro­[Indene-2,1′-Pentalene]-2′-Carboxylate (15d)

Purified by silica gel column chromatography eluting with Hexane/EA 20:1 to 10:1; 65% yield (30.3 mg); Yellow solid; m.p.: 133–134 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.04 (dt, J = 7.6, 0.9 Hz, 1H), 7.84–7.75 (m, 1H), 7.68 (td, J = 7.4, 1.0 Hz, 1H), 7.54 (dt, J = 7.6, 0.9 Hz, 1H), 7.15 (d, J = 2.3 Hz, 1H), 7.11 (d, J = 8.4 Hz, 2H), 6.78 (d, J = 8.7 Hz, 2H), 4.19 (dt, J = 9.9, 2.9 Hz, 1H), 4.00–3.90 (m, 2H), 2.82–2.74 (m, 1H), 1.99–1.94 (m, 1H), 1.87–1.73 (m, 3H), 1.28–1.19 (m, 2H), 0.99 (t, J = 7.1 Hz, 3H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 199.7, 199.5, 163.0, 153.7, 143.3, 142.1, 139.7, 135.4, 135.3, 133.5, 130.9, 129.1, 123.1, 122.8, 120.7, 71.4, 67.9, 60.8, 52.2, 37.2, 27.9, 24.1, 13.6; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₅H₂₂O₄Br: 465.0696, Found: 465.0700.

Ethyl-1,3-Dioxo-6a’-(p-Tolyl)-1,3,3a’,5′,6′,6a’-Hexahydro-4′H-Spiro­[Indene-2,1′-Pentalene]-2′-Carboxylate (15e)

Purified by silica gel column chromatography eluting with Hexane/EA 20:1 to 10:1; 68% yield (27.2 mg); Yellow solid; m.p.: 149–150 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.04 (d, J = 7.7 Hz, 1H), 7.77 (td, J = 7.5, 1.0 Hz, 1H), 7.63 (td, J = 7.4, 1.0 Hz, 1H), 7.50 (d, J = 7.6 Hz, 1H), 7.17 (d, J = 2.3 Hz, 1H), 6.80 (s, 2H), 6.76 (s, 2H), 4.23 (dt, J = 9.8, 2.9 Hz, 1H), 4.00–3.93 (m, 2H), 2.80–2.73 (m, 1H), 2.14 (s, 3H), 2.04–1.95 (m, 1H), 1.90–1.69 (m, 3H), 1.32–1.22 (m, 1H), 0.99 (t, J = 7.1 Hz, 3H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 199.9, 163.2, 154.2, 143.4, 142.3, 137.3, 136.2, 135.1, 134.9, 133.5, 128.5, 127.2, 122.9, 122.7, 60.7, 52.1, 37.3, 28.0, 24.1, 20.7, 13.6; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₆H₂₅O₄: 401.1747, Found: 401.1760.

Ethyl-6a’-(4-Methoxyphenyl)-1,3-Dioxo-1,3,3a’,5′,6′,6a′-Hexahydro-4′H-Spiro­[Indene-2,1′-Pentalene]-2′-Carboxylate (15f)

Purified by silica gel column chromatography eluting with Hexane/EA 20:1 to 10:1; 87% yield (36.2 mg); Yellow solid; m.p.: 141–142 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.02 (dt, J = 7.6, 0.9 Hz, 1H), 7.76 (td, J = 7.4, 1.1 Hz, 1H), 7.63 (td, J = 7.4, 1.1 Hz, 1H), 7.50 (dt, J = 7.6, 1.0 Hz, 1H), 7.16 (d, J = 2.2 Hz, 1H), 6.82 (d, J = 8.6 Hz, 2H), 6.51 (d, J = 8.6 Hz, 2H), 4.20 (dt, J = 9.6, 2.9 Hz, 1H), 4.01–3.92 (m, 2H), 3.65 (s, 3H), 2.73 (ddd, J = 12.7, 11.6, 6.9 Hz, 1H), 2.02–1.69 (m, 5H), 1.00 (t, J = 7.1 Hz, 3H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 199.9, 163.2, 158.0, 154.1, 143.3, 142.3, 135.1, 135.0, 133.4, 132.1, 128.5, 122.9, 122.7, 113.1, 71.9, 67.8, 60.7, 55.0, 52.3, 37.1, 27.9, 24.1, 13.7; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₆H₂₅O₅: 417.1697, Found: 417.1704.

Ethyl-6a’-(Naphthalen-2-yl)-1,3-Dioxo-1,3,3a’,5′,6′,6a’-Hexahydro-4′H-Spiro­[Indene-2,1′-Pentalene]-2′-Carboxylate (15g)

Purified by silica gel column chromatography eluting with Hexane/EA 20:1 to 10:1; 66% yield (26.1 mg); Yellow solid; m.p.: 152–153 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.10 (dt, J = 7.6, 0.9 Hz, 1H), 7.77 (td, J = 7.5, 1.1 Hz, 1H), 7.63–7.53 (m, 3H), 7.46 (d, J = 2.1 Hz, 1H), 7.38–7.34 (m, 3H), 7.23 (d, J = 2.2 Hz, 1H), 6.87 (d, J = 8.6 Hz, 1H), 4.42 (dt, J = 9.7, 2.9 Hz, 1H), 4.02–3.95 (m, 2H), 2.88 (ddd, J = 13.1, 11.7, 7.1 Hz, 1H), 2.10–1.74 (m, 5H), 1.00 (t, J = 7.1 Hz, 3H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 200.0, 199.6, 163.2, 154.1, 143.4, 142.2, 137.9, 135.2, 135.0, 133.5, 132.7, 131.8, 127.9, 127.3, 127.2, 126.4, 126.0, 125.8, 125.4, 123.0, 122.7, 71.6, 68.7, 60.8, 52.1, 37.2, 28.0, 24.1, 13.6; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₉H₂₄O₄: 436.1669, Found: 436.1673.

Ethyl-1,3-Dioxo-6a’-(Thiophen-2-yl)-1,3,3a’,5′,6′,6a’-Hexahydro-4′H-Spiro­[Indene-2,1′-Pentalene]-2′-Carboxylate (15h)

Purified by silica gel column chromatography eluting with Hexane/EA 20:1 to 10:1; 60% yield (26.0 mg); Yellow solid; m.p.: 137–138 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.00 (dt, J = 7.6, 1.0 Hz, 1H), 7.76 (td, J = 7.4, 1.1 Hz, 1H), 7.66 (td, J = 7.4, 1.1 Hz, 1H), 7.57 (dt, J = 7.6, 1.1 Hz, 1H), 7.13 (d, J = 2.2 Hz, 1H), 6.91 (d, J = 5.1 Hz, 1H), 6.68–6.66 (m, 1H), 6.52 (d, J = 3.6 Hz, 1H), 4.07 (dt, J = 9.7, 2.9 Hz, 1H), 4.03–3.93 (m, 2H), 2.74–2.69 (m, 1H), 2.08–2.03 (m, 1H), 1.93–1.88 (m, 1H), 1.84–1.73 (m, 2H), 1.43–1.36 (m, 1H), 1.0 (t, J = 7.1 Hz, 3H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 199.1, 198.9, 163.1, 153.3, 145.0, 143.2, 142.1, 135.1, 133.3, 126.5, 124.2, 122.9, 122.8, 72.2, 64.8, 60.8, 56.0, 38.5, 27.9, 24.7, 13.7; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₃H₂₁O₄S: 393.1155, Found: 393.1167.

Benzyl-(Z)-2-(5-Hydroxy-4-Methyl-4-Phenyl-4,5-Dihydroindeno­[1,2-b]­Pyran-2­(3H)-Ylidene)­Acetate ((Z)-16)

In a 7 mL glass vial, (Z)-11 (42 mg, 0.1 mmol) was dissolved in 2.0 mL MeOH and then NaBH₄ (113 mg, 0.3 mmol) was added at rt. The mixture was stirred for 24 h at room temperature. After the reaction completed (confirmed by TLC), the residue was diluted with saturated NH₄Cl solution, and the aqueous solution was extracted with DCM. The combined organic layers were dried over Na₂SO₄, and the solvent was removed in vacuo. The reaction mixture was purified by column chromatography (SiO₂, Hexanes: EtOAc, 20:1 to 10:1) to obtain the pure product 16 (28.4 mg, 67%).

dr > 20:1; Yellow oil; ¹H NMR (400 MHz, CDCl₃): δ 7.59–7.47 (m, 1H), 7.42–7.25 (m, 12H), 7.24–7.19 (m, 1H), 5.27 (s, 1H), 5.18 (s, 2H), 5.01 (d, J = 1.4 Hz, 1H), 2.75 (dd, J = 14.5, 1.5 Hz, 1H), 2.67 (d, J = 14.5 Hz, 1H), 1.80 (s, 3H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 164.2, 161.4, 150.1, 144.9, 144.1, 136.2, 135.0, 128.7, 128.5, 128.3, 128.0, 127.2, 126.9, 125.9, 123.4, 122.3, 118.3, 73.7, 65.8, 45.3, 37.8, 26.0; HRMS (ESI-TOF) m/z: [M + H]⁺ calcd. for C₂₈H₂₅O₄: 425.1747, Found: 425.1744.

Benzyl-2-(1′,3′-Dihydroxy-2-Phenyl-1′,3′-Dihydrospiro­[Cyclopentane-1,2′-Inden]-2-en-5-yl)­Acetate (17)

In a 7 mL glass vial, 13aa (42 mg, 0.1 mmol) was dissolved in 2.0 mL MeOH and then NaBH₄ (113 mg, 0.3 mmol) was added at rt. The mixture was stirred for 24 h at room temperature. After the reaction completed (confirmed by TLC), the residue was diluted with saturated NH₄Cl solution, and the aqueous solution was extracted with DCM. The combined organic layers were dried over Na₂SO₄, and the solvent was removed in vacuo. The reaction mixture was purified by column chromatography (SiO₂, Hexanes: EtOAc, 10:1 to 5:1) to obtain the pure product 17 (25.4 mg, 60%).

dr > 20:1; Yellow oil; ¹H NMR (400 MHz, CDCl₃): δ 7.37–7.17 (m, 9H), 7.01–6.98 (m, 1H), 6.97–6.90 (m, 2H), 6.73–6.71 (m, 2H), 6.16 (t, J = 2.6 Hz, 1H), 5.16 (s, 2H), 5.13 (s, 1H), 4.94 (s, 1H), 3.23–3.20 (m, 1H), 2.90–2.71 (m, 3H), 2.34 (ddd, J = 16.8, 7.6, 2.3 Hz, 1H), 1.95 (s, 2H); ¹³C­{¹H } NMR (101 MHz, CDCl₃): δ 172.8, 143.7, 142.6, 142.2, 137.9, 137.3, 135.7, 128.63, 128.57, 128.5, 128.3, 127.8, 126.9, 122.9, 122.7, 78.3, 75.4, 74.1, 66.5, 42.8, 37.1, 36.4; HRMS (ESI-TOF) m/z: [M-H]⁻ calcd. for C₂₈H₂₅O₄: 425.1747, Found: 425.1764.

The data underlying this study are available in the published article and its Supporting Information.

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.joc.6c00628.

• General information; preparation of starting materials; X-ray analysis data; NMR data; and NMR spectra of all compounds (PDF)

†.

W.D.Y. and I.T.C. contributed equally to this work.

The authors declare no competing financial interest.