Asymmetric [2+1] cycloaddition of difluoroalkyl-substituted carbenes with alkenes under rhodium catalysis: Synthesis of chiral difluoroalkyl-substituted cyclopropanes

Summary

Herein, we report a novel strategy for the synthesis of chiral difluoroalkyl-substituted cyclopropanes through enantioselective [2 + 1] cyclopropanation of alkenes and difluoroalkyl-substituted carbenes under rhodium catalysis, wherein the newly designed α, α-difluoro-β-carbonyl ketone N-triftosylhydrazones are used as the difluoroalkyl-substituted carbenes precursors. This approach represents the first asymmetric cyclopropanation of alkenes with difluoroalkyl carbenes, featuring high yield, high enantioselectivity, and broad substrate scope. Gram-scale synthesis and further interconversion of diverse functional groups demonstrate the usefulness of this protocol in the preparation of diverse functionalized chiral difluoroalkyl-substituted cyclopropanes.

Graphical abstract

Highlights

• •Chiral difluoromethylene cyclopropanes
• •Difluoroalkyl-substituted carbenes
• •Broad substrate scope

Catalysis; Organic synthesis; Organic compound

Introduction

The synthesis of partially fluorinated chiral organic molecules has drawn increasing attention, owing to the applications of such substrates in the design and development of bioactive molecules and drugs.^1,2,3,4 Difluoromethylene carbenes, which can considered as a suitable source of partially fluorinated moieties, have been widely used for the introduction of difluoroalkyl units into molecular skeletons.^5,6,7,8,9 However, in sharp contrast to the significant advances in the asymmetric reaction of perfluoroalkyl carbenes,^{5,6,7,8,9,10,11,12,13,14,15,16,17,18} the study on the enantioselective reactions involving difluoromethylene carbenes is still in its very early stage. To date, only three types of reactions are known in the prior art, namely the enantioselective cyclopropenation and aziridination reactions developed by Ma and coworkers^19,20 and our report of the asymmetric intramolecular C–H insertion of ethers (Scheme 1A).²¹ The [2 + 1] cyclopropanation represents one of the most typical reactions of carbenes; however, the analogous asymmetric reaction involving difluoroalkyl-substituted carbenes, which would allow for the synthesis of chiral difluoroalkyl-substituted cyclopropanes that have been found as the key structural unit of HIV inhibitors, remains undeveloped so far.^22,23 This may be due to the low reactivity of the available difluoroalkyl-substituted carbenes and to the lack of appropriate carbene precursors. Regarding the synthesis of chiral difluoroalkyl cyclopropanes, only one strategy has been disclosed, which involves the cycloaddition of difluoromethyl olefins with diazo compounds under, respectively, rhodium and enzyme catalysis.^24,25 On the other hand, the direct handling of hazardous diazo reagents remains until now the main disadvantage of this strategy. Consequently, an alternative strategy for asymmetric cyclopropanation of alkenes using difluoroalkyl-substituted carbenes is highly desirable.

Scheme 1.

Synthetic strategies for chiral difluoromethylene- or difluoromethyl-substituted molecules

As our continued interest in the chemistry of fluoroalkyl N-triftosylhydrazones,^{26,27,28,29,30} herein, we report the first enantioselective cyclopropanation of alkenes with difluoroalkyl-substituted carbenes in situ generated from α, α-difluoro-β-carbonyl ketone, which enables the successful application of difluoromethylene carbene in the asymmetric cyclopropanation. The use of N-triftosylhydrazones as difluoroalkyl-substituted carbenes surrogates avoids the need for direct manipulation of hazardous diazo reagents and, thus, reduces safety issues. It is worth mentioning that diverse alkenes, including aryl-alkyl, diaryl, and aryl terminal alkenes, are suitable in this protocol and have been proved to provide the chiral cyclopropanes in high yield and excellent enantioselectivity.^31,32,33 More importantly, N-triftosylhydrazones, with the advantage of easy decomposition at relatively low temperature, plays an essential role in the success of this kind of novel asymmetric [2 + 1] cycloaddition reaction.

Results and discussion

We began the study with the screening of chiral dirhodium catalyst for the cyclopropanation of suitable precursors in α-methyl-phenylethylene (2) with N-triftosylhydrazone (1). All the catalysts Rh₂(S-DOSP)₄, Rh₂(S-PTTL)₄, and Rh₂(S-PTAD)₄ afforded the desired difluoroalkyl-substituted cyclopropane in moderate yield at room temperature except with Rh₂(S-PTAD)₄ showing enantiocontrol up to 91% ee (Table 1, entry 1–3). Notably, the D2 symmetric catalyst Rh₂(S-BTPCP)₄ was found to be ineffective in this reaction (entry 4), whereas the C4 symmetric catalysts (Rh₂(S-DOSP)₄, Rh₂(S-PTTL)₄, and Rh₂(S-PTAD)₄) were more suitable for this [2 + 1] cycloaddition reaction.^34,35 Commonly used bases, such as K₂CO₃, Cs₂CO₃, and tBuOK, were not suitable for the cyclopropenation reaction (entries 5–7). Performing the reaction in other solvents, such as toluene, DCM, and DMF, led to lower yield or no reaction (entries 8–10). Subsequently, a decrease in enantioselectivity was found when the reaction temperature was increased, which indicated the advantage of N-triftosylhydrazone decomposable at low temperatures (room temperature or below) in such asymmetric reactions (room temperature or lower) (entry 11 and 12).^19,20,28 However, at low catalyst loadings (0.5 mol % of Rh₂(S-PTAD)₄), no significant changes in both yield and enantioselectivity were found (entry 13). Notably, low yield and enantioselectivity were observed when the reaction was run with 0.25 mol % of catalyst (entry 14). Surprisingly, when α-methyl-4-NO₂-phenylethylene was used instead of α-methyl-phenylethylene, the desired product was obtained in 93% yield with 95% ee (entry 15). Based on these results, we speculated that the electronic setup of the substrate might have a significant effect on the yield of this reaction. Finally, the reaction condition as stated in entry 9 [DIPEA (2.0 equiv), Rh₂(S-PTAD)₄ (0.5 mol %), benzotrifluoride (TFT, 3.0 mL) at room temperature] was identified as the optimal condition for investigating the scope of this reaction.

Table 1.

Optimization of the reaction conditions

Entry	Rh catalysta	Base	Solvent	Temp.	Yield	ee
1	Rh2(S-DOSP)4 (1 mol %)	DIPEA	TFT	25°C	58%	59%
2	Rh2(S-PTTL)4 (1 mol %)	DIPEA	TFT	25°C	66%	87%
3	Rh2(S-PTAD)4 (1 mol %)	DIPEA	TFT	25°C	61%	91%
4	Rh2(S-BTPCP)4 (1 mol %)	DIPEA	TFT	25°C	N.D.	–
5	Rh2(S-PTAD)4 (1 mol %)	K2CO3	TFT	25°C	N.R.	–
6	Rh2(S-PTAD)4 (1 mol %)	CsCO3	TFT	25°C	N.R.	–
7	Rh2(S-PTAD)4 (1 mol %)	tBuOK	TFT	25°C	N.R.	–
8	Rh2(S-PTAD)4 (1 mol %)	DIPEA	Toluene	25°C	53%	82%
9	Rh2(S-PTAD)4 (1 mol %)	DIPEA	DCM	25°C	47%	20%
10	Rh2(S-PTAD)4 (1 mol %)	DIPEA	DMF	25°C	Trace	–
11	Rh2(S-PTAD)4 (1 mol %)	DIPEA	TFT	40°C	73%	87%
12	Rh2(S-PTAD)4 (1 mol %)	DIPEA	TFT	0°C	21%	–
13	Rh2(S-PTAD)4 (0.5 mol %)	DIPEA	TFT	25°C	61%	92%
14	Rh2(S-PTAD)4 (0.25 mol %)	DIPEA	TFT	25°C	50%	74%
15b	Rh2(S-PTAD)4 (0.5 mol %)	DIPEA	TFT	25°C	93%	95%

N.D., Not detect.

^aReaction conditions: N-Triftosylhydrazone 1 (0.2 mmol), 1,1-diphenylethylene 2 (0.1 mmol), [Rh] catalyst (1 mol %), DIPEA (N, N-diisopropylethylamine) (0.2 mmol), TFT (benzotrifluoride, 3.0 mL), 12 h, under N₂.

^bα-Methyl-4-NO₂-phenylethylene was used.

With the optimized condition in hand, initially, we directed our studies toward exploring the scope of α-methyl-phenylethylenes in this asymmetric [2 + 1] cycloaddition reaction. Remarkably, under the reaction condition as shown in Scheme 2A, α-methyl-phenylethylenes bearing a wide range of functional groups, such as methyl (4), tert-butyl (5), methoxy (6), halogen (7; 8), phenyl (9), nitro (10), and cyano (11), were tolerated, leading to the desired chiral difluoroalkyl-substituted cyclopropanes (3–12) in moderate to high yield with excellent enantioselectivity. The substrates having electron-withdrawing and electron-donating substituents have no significant effect on enantioselectivity, albeit moderate yields were observed from the latter (3–6). The 3,4-dichloro phenyl and naphthyl-substituted α-methyl terminal alkenes were also found to be suitable coupling partners to afford the corresponding products in good yield and excellent enantioselectivity (13 and 14). By substituting methyl by cyclopropyl, the chiral difluoromethylene bicyclopropane (15) product was obtained in 94% ee with a moderate yield (50%; Scheme 2). Notably, such a bicyclopropane structural skeleton is present in a variety of protein inhibitors, antibiotic, and antifungal agents.^36,37,38,39 Both methyl- and nitro-containing α-ethylstyrene substrates (16 and 17) responded well under these conditions to afford good yields (72%, 75%; Scheme 2), but with a significant decrease in enantioselectivity (61%, 62%). Styrene was also found to be suitable for this transformation and provided the chiral difluoroalkyl-substituted cyclopropane in 63% yield with 4:1 diastereoisomer ratio (18), wherein the major configuration retained high enantioselectivity (90% ee). We subsequently screened several difluoromethylene N-triftosylhydrazones with various substituents such as Br, Cl, phenyl, naphthyl etc., and were pleased to find that all of them reacted with excellent enantioselectivity (19–23).

Scheme 2.

Reaction conditions: 1 (0.4 mmol), Rh₂(S-PTAD)₄ (0.5 mol %), 2 (0.2 mmol) and DIPEA (0.4 mmol) in TFT (3 mL) at rt

(A) The enantiomer ratio was determined by converting the compound to an alcohol.

(B) Rh₂(S-PTAD)₄ (0.25 mol %) was used.

(C) DCM (3 mL) used as solvent. Diastereoselective ratio >20:1.

Encouraged by these promising results, we envisioned that this strategy could be extended to the more sterically hindered 1,1-diarylethenes (Scheme 2B). After fine optimization of the reaction condition (for detail see Supplemental information), when the reaction was run under the catalysis of 0.25 mol % Rh₂(S-PTAD)₄ between 1,1-diphenylethylene and difluoromethylene hydrazone 1, chiral triaryl difluoroalkyl-substituted cyclopropane 24 was obtained with remarkable enantiocontrol and high yield (92% yield, 99% ee). Subsequently, various structurally diverse difluoromethylene hydrazones were proved to be effective reaction components without having affected by any electronic and substituent effects. Substituents such as methyl (25), tert-butyl (26), methoxy (27, 28), halogen (29–32), phenyl (33), trifluoromethyl (34), and ester (35) were well tolerated and the corresponding products were obtained in excellent yield and enantioselectivity. Multi-substituted aryl and naphthyl difluoromethylene hydrazones also underwent asymmetric cyclopropanation smoothly to provide the desired products (36, 37) in 98% and 97% ee, respectively. The absolute configuration of 37 was assigned by X-ray crystallographic analysis. In addition, chiral difluorocarbonyl cyclopropane 38 could also be prepared with high enantioselectivity (88% ee) starting from difluorocarbonyl phenyl N-triftosylhydrazone. However, difluoramide phenyl N-triftosylhydrazone is not compatible with this reaction, mainly due to its low solubility which renders it incapable releasing the diazo compound in the reaction medium (39). This transformation also proved its usefulness, affording excellent yield and high enantioselectivity using various 1,1-diphenylethylene derivatives, which illustrates the potential of this method for the synthesis of diverse optically pure triaryl difluoroalkyl substituted (40–46).

The same synthetic protocol was demonstrated to be robust and applicable also on gram-scale synthesis. As shown in Scheme 3A, the cyclopropanation of 1,1-diphenylethylene can be scaled up to 5 mmol, affording 24 in high yield (1.73 g, 88%) with excellent enantioselectivity (99% ee) even with low catalyst loading Rh₂(S-PTAD)₄ (0.25 mol %). It is also noteworthy that the use of sulfonyl hydrazones instead of diazo compounds can significantly reduce the safety risk during large-scale synthesis and simplify operational procedures. Taking into account the ester group interconversion, we subsequently carried out the functionality derivatization of the optically pure product 24. As demonstrated in Scheme 3B, diversely functionalized chiral difluoroalkyl-substituted cyclopropane derivatives were readily obtained from 24. The latter was converted into amide 47 (98% yield), alcohol 48 (96% yield), acid 49 (93% yield), and ketone (50, 70% yield) using appropriate reagents.⁴⁰

Scheme 3.

Gram-scale synthesis and functional-group transformations Reaction conditions

(A) 24 (0.2 mmol), Ammonia (7 M in methanol) (0.5 mL), 25°C, 16 h.

(B) 24 (0.5 mmol), LiAlH₄ (0.75 mmol), THF (3 mL), N₂, 0–25°C, 4 h.

(C) 24 (0.2 mmol), NaOH (0.4 mmol), EtOH (2 mL), 60°C, 2 h.

(D) 24 (0.2 mmol), ⁿBuLi (1.6 M in hexane, 0.25 mmol), THF (1 mL), N₂, -78°C, 2.5 h.

Experimental outcome has shown that the Rh₂(S-PTAD)₄ catalyst has a highly stereo-selectivity for this asymmetric [2 + 1] cycloaddition process. To better understand the origin for the stereo-selectivity, a plausible mechanism was proposed using the cycloaddition of N-triftosylhydrazone 1, which could be decomposed in situ to form the diazo compound under alkaline conditions,⁴¹ with 1,1-diphenylethylene as model and rationalized by density functional theory calculations at M06L/6-31G(d)-SDD(Rh) level of theory (for detailed computational methods, see Supplemental information). As shown in Scheme 4, the cycloaddition process is stepwisely owing to the geometric constraints derived from the body cavity of rhodium carbene. Firstly, the nucleophilic attack of 1,1-diphenylethylene to the carbene carbon can occur separately from the Si- or Re-plane of the carbene carbon, which determines the stereoselectivity of the product (ΔG^≠(Si-TS1) = 14.0 kcal/mol; ΔG^≠(Re-TS1) = 25.1 kcal/mol) (Scheme 4A). The non-covalent interactions analysis (Scheme 4B) shows that Si-TS1 displayed stronger hydrogen bond interactions (C-H···F, C-H···O) than Re-TS1, resulting in a more stable transition state and thus a lower kinetic energy barrier. Subsequently, the cyclization process from Si-int1 and Re-int1 to form the final enantioselective product via Si-TS2 (ΔG^≠ = 3.3 kcal/mol) and Re-TS2 (ΔG^≠ = 16.3 kcal/mol) occurred. The lower energy barrier for Si-TS2 may be derived from the more and stronger interactions exist in the configuration (See the part circled in red; Scheme 4C, upside), which renders the transition state more stable. Therefore, the formation of Si-pro is both kinetically and thermodynamically more favorable than Re-pro; this is in consistence with the experimental outcomes.

Scheme 4.

Theoretical research on proposed asymmetric [2 + 1] cycloaddition process at M06L/6-31G (d)-SDD(Rh) level of theory

The computed relative free energies are in kcal/mol and the values in (B) and (C) are in Å.

In summary, we have reported the first asymmetric [2 + 1] cycloaddition reaction of alkenes with difluoroalkyl-substituted carbenes, which were generated in situ from the easily decomposable α,α-difluoro-β-carbonyl ketone N-triftosylhydrazones. This protocol enables the enantioselective cyclopropanation of difluoroalkyl-substituted carbenes with alkenes, thereby providing a facile route to access enantioenriched difluoroalkyl-substituted cyclopropanes in high yield and excellent enantioselectivity. No doubt that the α, α-difluoro-β-carbonyl ketone N-triftosylhydrazones as the difluoroalkyl-substituted carbenes surrogates would find wide applications in asymmetric difluoroalkyl carbene transfer reactions in the near future.

Limitations of the study

This study is limited to the terminal alkenes, and it is still necessary to further develop an asymmetric catalytic system suitable for internally substituted alkenes.

STAR★Methods

Key resources table

REAGENT or RESOURCE	SOURCE	IDENTIFIER
Chemicals, peptides, and recombinant proteins
2-(Trifluoromethyl)benzenesulfonyl chloride	776-04-5	Energy Chemical
DIPEA	7087-68-5	Energy Chemical
Rh2(S-PTAD)4	909389-99-7	J&K Scientific
TFT(Benzotrifluoride)	98-08-8	Energy Chemical
Hydrazinium hydroxide solution	10217-52-4	Energy Chemical

Resource availability

Lead contact

Further information and requests for resources and reagents should be directed to and will be fulfilled by the lead contact, Xihe Bi (bixh507@nenu.edu.cn).

Materials availability

This study did not generate new unique reagents.

All reagents were purchased from commercial sources (Energy Chemical, Adamas-beta®, J&K Scientific, Sigma-Aldrich) and used without purification unless otherwise mentioned. The products were purified by column chromatography over silica gel (200–400 size). ¹H, ¹³C and ¹⁹F nuclear magnetic resonance (NMR) spectra were recorded at 25°C on a Bruker 600 MHz, 150 MHz and 565 MHz or Bruker 500 MHz, 125 MHz and 470 MHz (TMS was used as internal standard). High resolution mass spectra (HRMS) were recorded on Waters Premier GC-TOF MS by using EI method or Bruck microTof by using ESI method. High-pressure liquid chromatography (HPLC) was performed on Agilent 1220 Series chromatographs using a chiral column (25 cm) as noted for each compound. Enantiomer excess was determined by HPLC analysis employing Darcel Chiracel AD-H, OD-H, OJ-H, AS-H or IF column.

Method details

General procedure for the asymmetric cyclopropanation

In a nitrogen-filled glovebox, a flame-dried screw-cap reaction tube equipped with a Teflon-coated magnetic stir bar was charged with sulfonyl hydrazone 1 (0.8 mmol) and anhydrous TFT solvent (1.0 mL). The reaction mixture was stirred until complete dissolve, DIPEA (0.8 mmol) was added to the reaction system. The alkene 2 (0.4 mmol) was dissolved in 1.0 mL of anhydrous TFT and added to the reaction system. Rh₂(S-PTAD)₄ (0.5 mol%) was dissolved in anhydrous TFT (1 mL) and then added to the reaction system. The mixture was stirred at 25°C for 12 h until the reaction was complete as indicated by ¹H NMR. The reaction crude was filtered through a short silica gel eluting with DCM. The filtrate was evaporated under reduced pressure to leave a crude mixture, which was separated by flash column chromatography to afford the pure product.

Note: The yield of the reaction decreases as the dosage of DIPEA decreases, but the enantioselectivity remains unchanged.

Synthesis of racemate: The same procedure uses Rh₂(esp)₂ instead of Rh₂(S-PTAD)₄ and performs at room temperature.

General procedure for the synthesis of olefins

A sealed flask was charged with benzaldehyde (10 mmol), then THF (30 mL) was added and stirred at 0°C. Grignard reagent (15 mmol) was slowly added and the mixture was placed at room temperature for 4 h. When the reaction was complete (monitored by TLC), saturated NH₄Cl was added. The mixture was extracted with EA (30 mL × 3), then the organic phase was dried with anhydrous Na₂SO₄, concentrated under reduced pressure to give the pure compound.

Synthesis of benzophenones

A round-bottomed flask was charged with alcohol and dissolved in DCM (40 mL). Then Dess-Martin oxidant (1.5 equiv) was slowly added and stirred at room temperature overnight. After completion of the reaction (monitored by TLC), saturated NaHCO₃ and Na₂S₂O₃ solution were slowly added. Extracted with DCM (30 mL × 3) and washed the organic phases with brine, then dried with anhydrous Na₂SO₄. The residue was purified by flash column chromatography to give the corresponding benzophenone compound.

Synthesis of olefins

A sealed flask was charged with methyltriphenylphosphine bromide (1.5 equiv), THF (30 mL) was added and stirred at 0°C. Potassium tert-butoxide (1.5 equiv) and ketone (1.0 equiv) in THF (20 mL) was slowly added, the mixture was reacted at room temperature for 4 h. After completion of the reaction (monitored by TLC), NH₄Cl solution was slowly added. The mixture was extracted with EA (30 mL × 3) and dried with anhydrous Na₂SO₄. Then concentrated under reduced pressure to give the pure compound.perform flash column chromatography.

General procedure for the synthesis of compound 47

A sealed reaction tube was charged with 24 (0.2 mmol) and ammonia (7 M in methanol) (0.5 mL). The mixture was stirred at 25°C for 16 h. Then the mixture was concentrated under reduced pressure to give the pure compound.

General procedure for the synthesis of compound 48

A sealed reaction tube was charged with LiAlH₄ (0.3 mmol) under nitrogen atmosphere. 24 (0.2 mmol) in THF (3.0 mL) was added to the reaction tube under 0°C. Then the mixture was stirred at 25°C for 4 h. After the reaction was complete (monitored by TLC), aqueous NH₄Cl was added, and quenched with EA. The organic phase was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to give the pure compound.

General procedure for the synthesis of compound 49

A bottom flask was charged with 24 (0.2 mmol), NaOH (0.4 mmol) and EtOH (2.0 mL). The mixture was stirred at 60°C for 2 h. After the reaction was complete (monitored by TLC), aqueous NH₄Cl was added, and quenched with EA. The organic phase was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to give the pure compound.

General procedure for the synthesis of compound 50

A sealed reaction tube was replaced nitrogen three times, then 24 (0.2 mmol) in dry THF (3.0 mL) was added. The mixture was placed at −78°C, ⁿBuLi (1.6 M in hexane, 0.25 mmol) was added dropwise and stirred for 2.5 h. After the reaction was complete, aqueous NH₄Cl was added, and quenched with CH₃CO₂Et. The organic phase was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure and purified by column chromatography to give the pure compound.

Characterization data for the products

1a, White solid; m.p: 80–81°C; ¹H NMR (500 MHz, CDCl₃) δ 8.30–8.27 (m, 1H), 8.10 (s, 1H), 7.92–7.88 (m, 1H), 7.81–7.77 (m, 2H), 7.58–7.52 (m, 3H), 7.28–7.26 (m, 2H), 4.33 (q, J = 7.2 Hz, 2H), 1.35 (t, J = 7.2 Hz, 3H). ¹³C NMR (125 MHz, CDCl₃) δ 162.0 (t, J = 31.0 Hz), 146.8 (t, J = 27.5 Hz), 136.0, 133.9, 133.5, 132.5, 131.5, 129.9, 128.4 (q, J = 6.3 Hz), 128.2, 127.7 (q, J = 32.3 Hz), 124.9, 122.6 (q, J = 281.3 Hz), 111.9 (t, J = 250.9 Hz), 63.2, 13.9. ¹⁹F NMR (470 MHz, CDCl₃) δ −58.4, −104.0. HRMS (ESI) m/z calculated C₁₈H₁₅F₅N₂O₄S [M]⁺ 450.0567, found 450.0565.

1e, White solid; m.p: 83–84°C; ¹H NMR (500 MHz, CDCl₃) δ 8.30–8.26 (m, 1H), 8.13 (s, 1H), 7.91–7.87 (m, 1H), 7.80–7.76 (m, 2H), 7.34 (d, J = 8.0 Hz, 2H), 7.16 (d, J = 8.0 Hz, 2H), 4.32 (q, J = 7.2 Hz, 2H), 2.42 (s, 3H), 1.34 (t, J = 7.2 Hz, 3H). ¹³C NMR (125 MHz, CDCl₃) δ 162.1 (t, J = 30.9 Hz), 147.0 (t, J = 32.3 Hz), 142.0, 136.0, 133.9, 133.5, 132.5, 130.5, 128.4 (q, J = 6.3 Hz), 128.1, 127.7 (q, J = 34.3 Hz), 122.6 (q, J = 271.8 Hz), 121.9, 111.9 (t, J = 248.8 Hz), 63.2, 21.5, 13.9. ¹⁹F NMR (470 MHz, CDCl₃) δ −58.3, −104.0.

1f, White solid; m.p: 82–83°C; ¹H NMR (600 MHz, CDCl₃) δ 8.30–8.24 (m, 1H), 8.17 (s, 1H), 7.91–7.89 (m, 1H), 7.80–7.77 (m, 2H), 7.55–7.54 (m, 2H), 7.20 (d, J = 8.3 Hz, 2H), 4.32 (q, J = 7.2 Hz, 2H), 1.36 (s, 9H), 1.34 (t, J = 7.2 Hz, 3H). ¹³C NMR (150 MHz, CDCl₃) δ 162.1 (t, J = 30.9 Hz), 155.0, 147.0 (t, J = 32.3 Hz), 136.0, 133.9, 133.5, 132.5, 128.4 (q, J = 6.1 Hz), 127.9, 127.7 (q, J = 32.3 Hz), 126.8, 122.4 (q, J = 274.0 Hz), 121.9, 112.0 (t, J = 250.5 Hz), 63.2, 35.0, 31.0, 13.9. ¹⁹F NMR (564 MHz, CDCl₃) δ −58.3, −104.0. HRMS (ESI) m/z calculated C₂₂H₂₃F₅N₂O₄S [M]⁺ 506.1199, found 506.1191.

1g, White solid; m.p: 92–93°C; ¹H NMR (500 MHz, CDCl₃) δ 8.30–8.26 (m, 1H), 8.15 (s, 1H), 7.90–7.87 (m, 1H), 7.80–7.76 (m, 2H), 7.23 (d, J = 8.6 Hz, 2H), 7.03 (d, J = 8.6 Hz, 2H), 4.32 (q, J = 7.2 Hz, 2H), 3.87 (s, 3H), 1.34 (t, J = 7.2 Hz, 3H). ¹³C NMR (125 MHz, CDCl₃) δ 162.1 (t, J = 31.1 Hz), 161.8, 146.9 (t, J = 32.1 Hz), 136.0, 133.9, 133.5, 132.5, 129.9, 128.4 (q, J = 6.3 Hz), 127.7 (q, J = 33.4 Hz), 122.5 (q, J = 270.0 Hz), 116.6, 115.3, 112.1 (t, J = 250.4 Hz), 63.2, 55.4, 13.9. ¹⁹F NMR (470 MHz, CDCl₃) δ −58.3, −103.9. HRMS (ESI) m/z calculated C₁₉H₁₇F₅N₂O₅S [M]⁺ 480.0670, found 480.0671.

1h, White solid; m.p: 96–97°C; ¹H NMR (600 MHz, CDCl₃) δ 8.30–8.27 (m, 1H), 8.17 (s, 1H), 7.92–7.89 (m, 1H), 7.81–7.77 (m, 2H), 7.45 (t, J = 7.8 Hz, 1H), 7.09–7.07 (m, 1H), 6.82 (d, J = 7.8 Hz, 1H), 6.77–6.75 (m, 1H), 4.33 (q, J = 7.2 Hz, 2H), 3.83 (s, 3H), 1.35 (t, J = 7.2 Hz, 3H). ¹³C NMR (150 MHz, CDCl₃) δ 162.0 (t, J = 31.3 Hz), 160.5, 146.5 (t, J = 32.4 Hz), 136.0, 133.9, 133.5, 132.5, 131.1, 128.5 (q, J = 6.3 Hz), 127.7 (q, J = 33.3 Hz), 126.0, 122.5 (q, J = 274.6 Hz), 120.1, 117.5, 113.2, 111.9 (t, J = 250.6 Hz), 63.2, 55.4, 13.9. ¹⁹F NMR (564 MHz, CDCl₃) δ −58.3, −104.0. HRMS (ESI) m/z calculated C₁₉H₁₇F₅N₂O₅S [M]⁺ 480.0670, found 480.0671.

1i, White solid; m.p: 116–117°C; ¹H NMR (500 MHz, CDCl₃) δ 8.30–8.26 (m, 1H), 8.08 (s, 1H), 7.91–7.88 (m, 1H), 7.82–7.77 (m, 2H), 7.70 (d, J = 8.5 Hz, 2H), 7.17 (d, J = 8.5 Hz, 2H), 4.32 (q, J = 7.0 Hz, 2H), 1.35 (t, J = 7.0 Hz, 3H). ¹³C NMR (150 MHz, CDCl₃) δ 161.8 (t, J = 30.3 Hz), 145.4 (t, J = 32.7 Hz), 135.9, 134.0, 133.5, 133.3, 132.6, 129.9, 128.5 (q, J = 6.1 Hz), 127.7 (q, J = 30.3 Hz), 126.5, 123.7, 122.5 (q, J = 274.2 Hz), 111.7 (t, J = 250.8 Hz), 63.3, 13.9. ¹⁹F NMR (564 MHz, CDCl₃) δ −58.3, −103.8. HRMS (ESI) m/z calculated C₁₈H₁₄BrF₅N₂O₄S [M]⁺ 527.9684, found 527.9670.

1j, White solid; m.p: 96–97°C; ¹H NMR (500 MHz, CDCl₃) δ 8.30–8.26 (m, 1H), 8.07 (s, 1H), 7.91–7.88 (m, 1H), 7.81–7.78 (m, 2H), 7.55–7.53 (m, 2H), 7.24 (d, J = 8.5 Hz, 2H), 4.32 (q, J = 7.1 Hz, 2H), 1.35 (t, J = 7.1 Hz, 3H). ¹³C NMR (125 MHz, CDCl₃) δ 161.8 (t, J = 31.0 Hz), 145.4 (t, J = 32.7 Hz), 138.1, 135.9, 134.0, 133.5, 132.5, 130.3, 129.8, 128.5 (q, J = 6.3 Hz), 127.7 (q, J = 33.6 Hz), 123.2, 122.4 (d, J = 273.5 Hz), 111.8 (t, J = 250.8 Hz), 63.3, 13.9. ¹⁹F NMR (470 MHz, CDCl₃) δ −58.3, −103.8. HRMS (ESI) m/z calculated C₁₈H₁₄ClF₅N₂O₄S [M]⁺ 484.0180, found 484.0175.

1k, White solid; m.p: 127–128°C; ¹H NMR (600 MHz, CDCl₃) δ 8.30–8.26 (m, 1H), 8.11 (s, 1H), 7.92–7.90 (m, 1H), 7.82–7.78 (m, 2H), 7.56–7.54 (m, 1H), 7.50 (t, J = 7.8 Hz, 1H), 7.27 (t, J = 1.8 Hz, 1H), 7.18–7.16 (m, 1H), 4.33 (q, J = 7.2 Hz, 2H), 1.35 (t, J = 7.2 Hz, 3H). ¹³C NMR (150 MHz, CDCl₃) δ 161.7 (t, J = 31.1 Hz), 144.9 (t, J = 32.8 Hz), 136.1, 135.8, 134.1, 133.5, 132.6, 131.8, 131.2, 128.5 (q, J = 6.6 Hz), 128.4, 127.7 (q, J = 33.3 Hz), 126.6, 126.4, 122.5 (q, J = 274.0 Hz), 111.7 (t, J = 251.0 Hz), 63.4, 13.9. ¹⁹F NMR (564 MHz, CDCl₃) δ −58.3, −103.7. HRMS (ESI) m/z calculated C₁₈H₁₄ClF₅N₂O₄S [M]⁺ 484.0171, found 484.0175.

1l, White solid; m.p: 87–88°C; ¹H NMR (500 MHz, CDCl₃) δ 8.30–8.27 (m, 1H), 8.09 (s, 1H), 7.92–7.89 (m, 1H), 7.81–7.78 (m, 2H), 7.32–7.23 (m, 4H), 4.32 (q, J = 7.1 Hz, 2H), 1.35 (t, J = 7.1 Hz, 3H). ¹³C NMR (125 MHz, CDCl₃) δ 164.3 (d, J = 253.5 Hz), 161.8 (t, J = 30.9 Hz), 145.6 (t, J = 32.7 Hz), 135.9, 134.0, 133.5, 132.5, 130.7 (d, J = 8.6 Hz), 128.5 (q, J = 6.2 Hz), 127.7 (q, J = 33.0 Hz), 122.4 (q, J = 274.2 Hz), 120.8 (d, J = 3.5 Hz), 117.3 (d, J = 22.0 Hz), 111.8 (t, J = 250.5 Hz), 63.3, 13.9. ¹⁹F NMR (470 MHz, CDCl₃) δ −58.3, −103.8, (−106.6)-(-106.7) (m). HRMS (ESI) m/z calculated C₁₈H₁₄F₆N₂O₄S [M]⁺ 468.0471, found 468.0471.

1m, White solid; m.p: 97–98°C; ¹H NMR (600 MHz, CDCl₃) δ 8.31–8.29 (m, 1H), 8.21 (s, 1H), 7.92–7.89 (m, 1H), 7.81–7.78 (m, 2H), 7.76–7.73 (m, 2H), 7.62–7.60 (m, 2H), 7.50–7.48 (m, 2H), 7.44–7.41 (m, 1H), 7.36 (d, J = 8.2 Hz, 2H), 4.34 (q, J = 7.2 Hz, 2H), 1.36 (t, J = 7.2 Hz, 3H). ¹³C NMR (150 MHz, CDCl₃) δ 162.0 (t, J = 31.1 Hz), 146.5 (t, J = 32.3 Hz), 144.5, 139.5, 136.0, 133.9, 133.5, 132.5, 129.0, 128.7, 128.5, 128.4 (q, J = 6.1 Hz), 128.3, 127.7 (q, J = 33.2 Hz), 127.2, 123.5, 122.6 (q, J = 272.3 Hz), 112.0 (t, J = 250.7 Hz), 63.3, 13.9. ¹⁹F NMR (564 MHz, CDCl₃) δ −58.3, −103.8. HRMS (ESI) m/z calculated C₂₄H₁₉F₅N₂O₄S [M]⁺ 526.0886, found 526.0878.

1n, White solid; m.p: 111–112°C; ¹H NMR (600 MHz, CDCl₃) δ 8.29–8.24 (m, 2H), 8.19–8.16 (m, 2H), 7.92–7.89 (m, 1H), 7.82–7.78 (m, 2H), 7.39 (d, J = 8.1 Hz, 2H), 4.32 (q, J = 7.2 Hz, 2H), 3.94 (s, 3H), 1.34 (t, J = 7.2 Hz, 3H). ¹³C NMR (150 MHz, CDCl₃) δ 165.6, 161.7 (t, J = 30.7 Hz), 145.3 (t, J = 32.4 Hz), 135.8, 134.0, 133.4, 132.8, 132.5, 130.8, 129.3, 128.5, 128.4 (q, J = 6.2 Hz), 127.6 (q, J = 33.4 Hz), 122.5 (q, J = 274.0 Hz), 111.7 (t, J = 251.0 Hz), 63.3, 52.5, 13.8. ¹⁹F NMR (564 MHz, CDCl₃) δ −58.3, −103.6.

1o, White solid; m.p: 95–96°C; ¹H NMR (500 MHz, CDCl₃) δ 8.30–8.28 (m, 1H), 8.06 (s, 1H), 7.93–7.91 (m, 1H), 7.83–7.80 (m, 4H), 7.44 (d, J = 8.0 Hz, 2H), 4.33 (q, J = 7.2 Hz, 2H), 1.35 (t, J = 7.2 Hz, 3H). ¹³C NMR (125 MHz, CDCl₃) δ 161.6 (t, J = 30.9 Hz), 144.9 (t, J = 32.9 Hz), 135.8, 134.1, 133.6 (q, J = 32.5 Hz), 133.5, 132.6, 129.1, 128.7, 128.6 (q, J = 6.3 Hz), 127.7 (q, J = 33.2 Hz), 126.9 (q, J = 3.8 Hz), 123.2 (q, J = 271.3 Hz), 122.6 (q, J = 272.5 Hz), 111.7 (t, J = 250.9 Hz), 63.4, 13.9. ¹⁹F NMR (470 MHz, CDCl₃) δ −58.3, −63.3, −103.6. HRMS (ESI) m/z calculated C₁₉H₁₄F₈N₂O₄S [M]⁺ 518.0446, found 518.0439.

1p, ¹H NMR (500 MHz, CDCl₃) δ 8.29–8.27 (m, 1H), 8.12 (s, 1H), 7.94–7.92 (m, 1H), 7.84–7.78 (m, 2H), 7.57 (t, J = 1.9 Hz, 1H), 7.17 (d, J = 1.9 Hz, 2H), 4.33 (q, J = 7.2 Hz, 2H), 1.35 (t, J = 7.2 Hz, 3H). ¹³C NMR (150 MHz, CDCl₃) δ 161.5 (t, J = 31.1 Hz), 143.3 (t, J = 32.8 Hz), 137.0, 135.7, 134.2, 133.5, 132.6, 131.9, 128.6 (q, J = 5.6 Hz), 127.8 (q, J = 33.2 Hz), 127.7, 126.7, 122.5 (q, J = 273.5 Hz), 111.5 (t, J = 243.0 Hz), 63.5, 13.9. ¹⁹F NMR (564 MHz, CDCl₃) δ −58.3, −103.5.

1q, White solid; m.p: 96–97°C; ¹H NMR (500 MHz, CDCl₃) δ 8.27–8.25 (m, 1H), 8.21 (s, 1H), 7.93–7.90 (m, 1H), 7.83–7.77 (m, 2H), 7.62 (d, J = 8.2 Hz, 1H), 7.40 (d, J = 2.0 Hz, 1H), 7.14 (dd, J = 8.3, 2.0 Hz, 1H), 4.31 (q, J = 7.2 Hz, 2H), 1.33 (t, J = 7.2 Hz, 3H). ¹³C NMR (150 MHz, CDCl₃) δ 161.6 (t, J = 30.8 Hz), 143.7 (t, J = 32.8 Hz), 136.4, 135.7, 134.6, 134.1, 133.4, 132.6, 132.0, 130.4, 128.6 (q, J = 6.6 Hz), 127.7 (q, J = 32.2 Hz), 127.6, 124.6, 122.5 (q, J = 274.0 Hz), 111.6 (t, J = 251.2 Hz), 63.4, 13.8. ¹⁹F NMR (564 MHz, CDCl₃) δ −58.3, −103.6. HRMS (ESI) m/z calculated C₁₈H₁₃Cl₂F₅N₂O₄S [M]⁺ 517.9799, found 517.9785.

1r, White solid; m.p: 108–109°C; ¹H NMR (600 MHz, CDCl₃) δ 8.30–8.28 (m, 1H), 8.24 (s, 1H), 7.99 (d, J = 8.4 Hz, 1H), 7.90–7.87 (m, 3H), 7.81 (s, 1H), 7.80–7.76 (m, 2H), 7.62–7.57 (m, 2H), 7.31 (d, J = 8.4 Hz, 1H), 4.33 (q, J = 7.2 Hz, 2H), 1.35 (t, J = 7.2 Hz, 3H). ¹³C NMR (150 MHz, CDCl₃) δ 162.0 (t, J = 30.9 Hz), 146.7 (t, J = 32.4 Hz), 135.9, 134.1, 133.9, 133.4, 132.9, 132.5, 130.0, 129.0, 128.5, 128.4 (q, J = 6.5 Hz), 128.3, 127.9, 127.6 (q, J = 33.5 Hz), 127.4, 123.9, 122.5 (q, J = 272.3 Hz), 122.1, 112.1 (t, J = 250.7 Hz), 63.2, 13.8. ¹⁹F NMR (564 MHz, CDCl₃) δ −58.3, −103.5.

1s, White solid; m.p: 125–126°C; ¹H NMR (500 MHz, CDCl₃) δ 8.15 (s, 1H), 7.90–7.86 (m, 3H), 7.80 (d, J = 7.8 Hz, 1H), 7.65 (t, J = 7.7 Hz, 1H), 7.60–7.56 (m, 4H), 7.48 (t, J = 7.7 Hz, 1H), 7.41 (t, J = 7.8 Hz, 2H), 7.35–7.34 (m, 2H). ¹³C NMR (125 MHz, CDCl₃) δ 187.1 (t, J = 27.8 Hz), 148.0 (t, J = 31.9 Hz), 135.5, 134.0, 133.71, 133.65, 132.6, 132.4, 131.6, 123.0, 128.5, 128.2, 128.1 (q, J = 6.3 Hz), 127.4 (q, J = 32.5 Hz), 125.4, 122.5 (q, J = 278.8 Hz), 113.9 (t, J = 252.0 Hz). ¹⁹F NMR (470 MHz, CDCl₃) δ −58.4, −99.5.

3, Colorless oil; ¹H NMR (500 MHz, CDCl₃) δ 7.09–7.02 (m, 6H), 7.01–6.94 (m, 4H), 3.97 (q, J = 7.1 Hz, 2H), 2.17–2.14 (m, 1H), 1.87 (d, J = 2.1 Hz, 3H), 1.81–1.78 (m, 1H), 1.01 (t, J = 7.1 Hz, 3H). ¹³C NMR (125 MHz, CDCl₃) δ 163.8 (dd, J = 36.1, 34.9 Hz), 142.5, 134.6 (d, J = 6.8 Hz), 131.5, 128.0, 127.7, 127.5, 127.3, 126.0, 117.1 (t, J = 255.7 Hz), 62.3, 39.5 (dd, J = 26, 22.9 Hz), 32.7, 22.0 (d, J = 6.7 Hz), 20.7 (t, J = 5.0 Hz), 13.6. ¹⁹F NMR (470 MHz, CDCl₃) δ −97.9 (d, J = 249.6 Hz), (−103.5)-(-105.0) (m). IR (Film): 2963, 1772, 1497, 1450, 1260, 1100 cm^–1. [α]25 D = −10.3, (c = 1.00, CH₂Cl₂).

4, White solid; mp: 76–77°C; ¹H NMR (500 MHz, CDCl₃) δ 7.01 (d, J = 8.8 Hz, 2H), 6.96–6.94 (m, 2H), 6.86 (d, J = 7.9 Hz, 2H), 6.55–6.53 (m, 2H), 4.03–3.96 (m, 2H), 3.64 (s, 3H), 2.16 (s, 3H), 2.04–2.02 (m, 1H), 1.82–1.80 (m, 3H), 1.75–1.72 (m, 1H), 1.06 (t, J = 7.1 Hz, 3H). ¹³C NMR (125 MHz, CDCl₃) δ 163.9 (dd, J = 35.4, 34.4 Hz), 158.5, 139.7, 135.3, 132.7, 128.4, 127.8, 126.8 (d, J = 6.1 Hz), 117.3 (t, J = 256.3 Hz), 112.9, 62.3, 55.0, 38.8 (dd, J = 25.8, 22.0 Hz), 32.3, 22.2 (d, J = 6.8 Hz), 21.0 (t, J = 4.3 Hz), 20.9, 13.7. ¹⁹F NMR (470 MHz, CDCl₃) δ −97.8 (d, J = 248.2 Hz), −104.7 (d, J = 248.2 Hz). HRMS (ESI) m/z calculated C₂₂H₂₄F₂O₃ [M]⁺ 374.1587, found 374.1586. IR (Film): 2926, 2923, 1773, 1600, 1260, 1109, 1021 cm^–1. [α]25 D = −12.1, (c = 1.00, CH₂Cl₂).

5, Colorless oil; ¹H NMR (500 MHz, CDCl₃) δ 7.07–7.02 (m, 4H), 6.98–6.94 (m, 5H), 3.96 (q, J = 7.2 Hz, 2H), 2.11 (t, J = 5.0 Hz, 1H), 1.87 (s, 3H), 1.77 (d, J = 5.9 Hz, 1H), 1.15 (s, 9H), 1.01 (t, J = 7.2 Hz, 3H). ¹³C NMR (125 MHz, CDCl₃) δ 163.9 (dd, J = 35.4, 34.4 Hz), 148.7, 139.3, 134.8 (d, J = 6.0 Hz), 131.6, 127.4, 127.1, 124.4, 117.1 (t, J = 256.0 Hz), 62.3, 39.6 (dd, J = 26.4, 22.4 Hz), 34.1, 32.1, 31.2, 21.8 (d, J = 6.6 Hz), 20.9 (t, J = 5.0 Hz), 13.6. ¹⁹F NMR (470 MHz, CDCl₃) δ −97.9 (d, J = 248.5 Hz), −104.4 (d, J = 248.5 Hz). HRMS (ESI) m/z calculated C₂₄H₂₈F₂O₂ [M]⁺ 386.1948, found 386.1950. IR (Film): 2960, 1772, 1500, 1260, 1100 cm^–1. [α]25 D = −3.9, (c = 1.00, CH₂Cl₂).

6, White solid; mp: 80–81°C; ¹H NMR (500 MHz, CDCl₃) δ 7.09 (d, J = 7.2 Hz, 2H), 7.02–6.96 (m, 5H), 6.60–6.56 (m, 2H), 3.95 (q, J = 7.1 Hz, 2H), 3.65 (s, 3H), 2.09–2.07 (m, 1H), 1.83 (d, J = 1.5 Hz, 3H), 1.78–1.76 (m, 1H), 1.00 (t, J = 7.1 Hz, 3H). ¹³C NMR (125 MHz, CDCl₃) δ 163.8 (dd, J = 35.5, 33.9 Hz), 157.5, 134.8 (d, J = 6.0 Hz), 134.7, 131.5, 128.9, 127.6, 127.3, 117.1 (d, J = 255.8 Hz), 113.0, 62.3, 55.0, 39.5 (dd, J = 26.5, 22.8 Hz), 32.1, 22.3 (d, J = 6.6 Hz), 20.9 (t, J = 4.9 Hz), 13.5. ¹⁹F NMR (470 MHz, CDCl₃) δ −97.8 (d, J = 248.6 Hz), −104.2 (d, J = 248.6 Hz). HRMS (ESI) m/z calculated C₂₁H₂₂F₂O₃ [M]⁺ 360.1419, found 360.1429. IR (Film): 3021, 2959,1765, 1613, 1516 cm–1 [α]25 D = −15.5, (c = 1.00, CH₂Cl₂).

7, White solid; mp: 75–76°C; ¹H NMR (500 MHz, CDCl₃) δ 7.09–7.07 (m, 2H), 7.03–6.98 (m, 7H), 3.96 (q, J = 7.1 Hz, 2H), 2.10 (t, J = 5.4 Hz, 1H), 1.84–1.80 (m, 4H), 1.00 (t, J = 7.1 Hz, 3H). ¹³C NMR (150 MHz, CDCl₃) δ 163.6 (t, J = 34.7 Hz), 141.2, 134.3 (d, J = 5.8 Hz), 131.7, 131.2, 129.3, 127.8, 127.7, 127.6, 116.9 (t, J = 256.3 Hz), 62.4, 39.6 (dd, J = 26.1, 22.1 Hz), 32.1, 22.0 (d, J = 6.8 Hz), 20.8 (t, J = 5.2 Hz), 13.5. ¹⁹F NMR (564 MHz, CDCl₃) δ −97.9 (d, J = 250.7 Hz), −104.4 (d, J = 250.7 Hz). HRMS (ESI) m/z calculated C₂₀H₁₉ClF₂O₂ [M]⁺ 364.0927, found 364.0934. IR (Film): 3053, 2989, 2950, 1765, 1493 cm^–1. [α]25 D = −20.4, (c = 1.00, CH₂Cl₂).

8, Colorless oil; ¹H NMR (500 MHz, CDCl₃) δ 7.08–7.01 (m, 7H), 6.73 (t, J = 8.7 Hz, 2H), 3.97 (q, J = 7.1 Hz, 2H), 2.10 (t, J = 5.0 Hz, 1H), 1.84 (s, 3H), 1.80 (d, J = 6.1 Hz, 1H), 1.00 (t, J = 7.1 Hz, 3H). ¹³C NMR (150 MHz, CDCl₃) δ 163.7 (t, J = 34.2 Hz), 160.9 (d, J = 244.3 Hz), 138.4, 134.5 (d, J = 6.5 Hz), 131.3, 129.5 (d, J = 8.0 Hz), 127.7, 127.4, 117.0 (t, J = 255.8 Hz), 114.5 (d, J = 21.0 Hz), 62.4, 39.5 (dd, J = 25.7, 22.2 Hz), 32.1, 22.2 (d, J = 6.2 Hz), 20.9 (t, J = 5.0 Hz), 13.6. ¹⁹F NMR (564 MHz, CDCl₃) δ −97.9 (d, J = 249.8 Hz), −104.3 (d, J = 251.6 Hz), (−114.5)-(-120.9) (m). IR (Film): 2935, 1773, 1560, 1512, 1161 cm^–1. [α]25 D = −3.1, (c = 1.00, CH₂Cl₂).

9, White solid; mp: 65–66°C; ¹H NMR (500 MHz, CDCl₃) δ 7.46–7.44 (m, 2H), 7.37–7.33 (m, 2H), 7.30–7.26 (m, 3H), 7.13–7.11 (m, 4H), 7.01–6.95 (m, 3H), 3.97 (q, J = 7.1 Hz, 2H), 2.18 (t, J = 5.5, 1H), 1.90 (d, J = 1.4 Hz, 3H), 1.83 (d, J = 6.0 Hz, 1H), 1.01 (t, J = 7.1 Hz, 3H). ¹³C NMR (125 MHz, CDCl₃) δ 163.8 (dd, J = 35.4, 33.9 Hz), 141.7, 140.6, 138.5, 134.6 (d, J = 6.1 Hz), 131.5, 128.6, 128.3, 127.6, 127.4, 127.0, 126.8, 126.3, 117.1 (t, J = 257.1 Hz), 62.3, 39.7 (dd, J = 25.9, 22.5 Hz), 32.4, 22.0 (d, J = 5.6 Hz), 20.9 (t, J = 4.8 Hz), 13.6. ¹⁹F NMR (470 MHz, CDCl₃) δ −97.9 (d, J = 249.3 Hz), −104.4 (d, J = 249.9 Hz). HRMS (ESI) m/z calculated C₂₆H₂₄F₂O₂ [M]⁺ 406.1646, found 406.1637. IR (Film): 3054, 2985, 2306, 1767, 1421, 1264, 1118, 895, 731, 702 cm^–1. [α]25 D = −46.1, (c = 1.00, CH₂Cl₂).

10, White solid; mp: 110–111°C; ¹H NMR (600 MHz, CDCl₃) δ 7.90 (t, J = 1.9 Hz, 1H), 7.84–7.82 (m, 1H), 7.43 (d, J = 8.1 Hz, 1H), 7.22 (t, J = 8.0 Hz, 1H), 7.08 (d, J = 7.2 Hz, 2H), 7.02–6.97 (m, 3H), 4.00–3.97 (m, 2H), 2.22 (t, J = 5.2 Hz, 1H), 1.93–1.89 (m, 4H), 1.01 (t, J = 7.1 Hz, 3H). ¹³C NMR (150 MHz, CDCl₃) δ 163.4 (t, J = 34.1 Hz), 147.7, 144.9, 134.4, 133.7 (d, J = 6.3 Hz), 131.1, 128.6, 128.0, 127.8, 122.8, 121.2, 116.7 (t, J = 257.4 Hz), 62.5, 39.8 (dd, J = 25.8, 22.7 Hz), 32.2, 21.6 (d, J = 6.9 Hz), 20.9 (t, J = 4.7 Hz), 13.5. ¹⁹F NMR (564 MHz, CDCl₃) δ −98.0 (d, J = 251.1 Hz), −104.4 (d, J = 251.1 Hz). IR (Film): 3055, 2936, 2306, 1770, 6530, 1348, 1265, 1112, 909, 730, 704 cm^–1. [α]25 D = −19.0, (c = 1.00, CH₂Cl₂).

11, White solid; mp: 89–90°C; ¹H NMR (600 MHz, CDCl₃) δ 7.91 (d, J = 8.9 Hz, 2H), 7.23 (d, J = 8.9 Hz, 2H), 7.10–7.06 (m, 2H), 7.04–7.00 (m, 3H), 3.98 (q, J = 7.2 Hz, 2H), 2.23–2.21(m, 1H), 1.93–1.89 (m, 4H), 1.01 (t, J = 7.2 Hz, 3H). ¹³C NMR (150 MHz, CDCl₃) δ 163.4 (t, J = 34.0 Hz), 150.3, 146.0, 133.6 (d, J = 5.8 Hz), 131.0, 128.8, 128.0, 127.9, 123.0, 116.7 (t, J = 256.8 Hz), 62.5, 40.0 (t, J = 22.5 Hz), 32.4, 21.5 (d, J = 6.7 Hz), 21.1 (t, J = 4.7 Hz), 13.5. ¹⁹F NMR (564 MHz, CDCl₃) δ −98.1 (d, J = 251.0 Hz), −104.5 (d, J = 251.0 Hz). HRMS (ESI) m/z calculated C₂₀H₁₉F₂NO₄ [M]⁺ 375.1172, found 375.1174. IR (Film): 3060, 2990, 2939, 1771, 1599, 1518, 1345 cm^–1. [α]25 D = −32.2, (c = 1.00, CH₂Cl₂).

12, White solid; mp: 91–92°C; ¹H NMR (600 MHz, CDCl₃) δ 7.34–7.31 (m, 2H), 7.26–7.24 (m, 1H), 7.16 (t, J = 8.0 Hz, 1H), 7.09–6.99 (m, 5H), 3.98 (q, J = 7.1 Hz, 2H), 2.15 (t, J = 5.2 Hz, 1H), 1.88–1.85 (m, 4H), 1.01 (t, J = 7.1 Hz, 3H). ¹³C NMR (150 MHz, CDCl₃) δ 163.4 (t, J = 35.2 Hz), 144.2, 133.8 (d, J = 6.1 Hz), 132.7, 131.5, 131.1, 129.8, 128.5, 127.9, 127.8, 118.8, 116.7 (t, J = 256.4 Hz), 111.8, 62.5, 39.8 (dd, J = 26.4, 22.4 Hz), 32.1, 21.6 (d, J = 5.4 Hz), 20.6 (t, J = 4.8 Hz), 13.6. ¹⁹F NMR (564 MHz, CDCl₃) δ −98.0 (d, J = 251.2 Hz), −104.4 (d, J = 251.2 Hz). HRMS (ESI) m/z calculated C₂₁H₁₉F₂NO₂ [M]⁺ 355.1279, found 355.1276. IR (Film): 2940, 2255, 1559, 1502, 1160 cm^–1. [α]25 D = −21.1, (c = 1.00, CH₂Cl₂).

13, Colorless oil; ¹H NMR (500 MHz, CDCl₃) δ 7.15–7.05 (m, 7H), 6.89 (d, J = 7.1 Hz, 1H), 3.97 (q, J = 7.1 Hz, 2H), 2.08 (t, J = 5.3 Hz, 1H), 1.86–1.79 (m, 4H), 1.00 (t, J = 7.1 Hz, 3H). ¹³C NMR (150 MHz, CDCl₃) δ 163.5 (t, J = 34.6 Hz), 143.1, 133.9 (d, J = 5.9 Hz), 131.7, 130.1, 129.9, 129.6, 128.4 (d, J = 4.1 Hz), 127.9, 127.8, 127.5, 116.8 (t, J = 256.4 Hz), 62.5, 39.7 (dd, J = 25.2, 21.9 Hz), 31.9, 21.8 (d, J = 6.9 Hz), 20.9 (t, J = 4.8 Hz), 13.6. ¹⁹F NMR (564 MHz, CDCl₃) δ −98.0 (d, J = 250.7 Hz), −104.4 (d, J = 250.7 Hz). HRMS (ESI) m/z calculated C₂₀H₁₈Cl₂F₂O₂ [M]⁺ 398.0539, found 398.0544. IR (Film): 3066, 2963, 2937, 1773, 1654, 1102 cm^–1. [α]25 D = −10.7, (c = 1.00, CH₂Cl₂).

14, White solid; mp: 70–71°C; ¹H NMR (500 MHz, CDCl₃) δ 7.66–7.62 (m, 2H), 7.55 (d, J = 8.5 Hz, 1H), 7.44 (d, J = 1.9 Hz, 1H), 7.37–7.31 (m, 3H), 7.16 (d, J = 7.6 Hz, 2H), 6.96–6.86 (m, 3H), 3.97 (q, J = 7.2 Hz, 2H), 2.30–2.27 (m, 1H), 1.93 (d, J = 2.0 Hz, 3H), 1.89 (d, J = 6.0 Hz, 1H), 1.01 (t, J = 7.2 Hz, 3H). ¹³C NMR (150 MHz, CDCl₃) δ 163.8 (t, J = 34.7 Hz), 140.3, 134.4 (d, J = 6.7 Hz), 133.0, 131.8, 131.3, 127.62, 127.57, 127.4, 127.34, 127.27, 127.1, 126.0, 125.7, 125.4, 117.2 (t, J = 256.0 Hz), 62.4, 39.7 (dd, J = 26.0, 21.9 Hz), 33.1, 22.2 (d, J = 6.7 Hz), 20.9 (t, J = 4.9 Hz), 13.6. ¹⁹F NMR (564 MHz, CDCl₃) δ −97.9 (d, J = 249.4 Hz), −104.2 (d, J = 249.4 Hz). HRMS (ESI) m/z calculated C₂₄H₂₂F₂O₄ [M]⁺ 380.1471, found 380.1480. IR (Film): 3057, 3020, 2970, 2934, 1768, 1496, 1312,1107 cm^–1. [α]25 D = +2.3, (c = 1.00, CH₂Cl₂).

15, Colorless oil; ¹H NMR (500 MHz, CDCl₃) δ 7.15–6.90 (m, 10H), 3.98 (q, J = 7.2 Hz, 2H), 1.98 (t, J = 5.4 Hz, 1H), 1.92–1.85 (m, 1H), 1.79 (d, J = 6.2 Hz, 1H), 1.01 (t, J = 7.2 Hz, 3H), 0.91–0.81 (m, 1H), 0.77–0.71 (m, 1H), 0.62–0.55 (m, 1H), 0.50–0.46 (m, 1H). ¹³C NMR (125 MHz, CDCl₃) δ 164.0 (dd, J = 36.1, 33.8 Hz), 141.5, 134.7 (d, J = 6.1 Hz), 131.4, 128.7, 127.5, 127.4, 127.3, 125.8, 117.0 (t, J = 256.3 Hz), 62.3, 40.3 (t, J = 22.5 Hz), 38.7, 18.2 (d, J = 4.2 Hz), 15.1 (d, J = 3.8 Hz), 13.6, 8.5 (d, J = 7.2 Hz), 6.6 (d, J = 3.3 Hz). ¹⁹F NMR (470 MHz, CDCl₃) δ −98.8 (d, J = 251.4 Hz), −104.7 (d, J = 251.4 Hz). HRMS (ESI) m/z calculated C₂₂H₂₂F₂O₂ [M]⁺ 356.1489, found 356.1480. IR (Film): 1740, 1535, 1503, 1152 cm^–1. [α]25 D = −3.7, (c = 1.00, CH₂Cl₂).

16, Colorless oil; ¹H NMR (500 MHz, CDCl₃) δ 7.19–7.06 (m, 1H), 7.01–6.93 (m, 6H), 6.83 (d, J = 7.9 Hz, 2H), 3.93 (q, J = 7.1 Hz, 2H), 2.37–2.30 (m, 1H), 2.14 (s, 3H), 2.06–1.99 (m, 2H), 1.72 (d, J = 5.8 Hz, 1H), 0.98 (t, J = 7.1 Hz, 3H), 0.79 (t, J = 7.3 Hz, 3H). ¹³C NMR (150 MHz, CDCl₃) δ 163.8 (dd, J = 35.6, 33.8 Hz), 136.9, 135.4, 134.9 (d, J = 6.5 Hz), 131.2, 129.1, 128.3, 127.5, 127.1, 117.4 (t, J = 257.7 Hz), 62.3, 40.2 (dd, J = 26.4, 21.6 Hz), 39.4, 27.1 (d, J = 7.2 Hz), 20.9, 18.9 (t, J = 5.2 Hz), 13.5, 11.9. ¹⁹F NMR (564 MHz, CDCl₃) δ −96.2 (d, J = 248.4 Hz), (−102.6)-(-103.1) (m). HRMS (ESI) m/z calculated C₂₂H₂₄F₂O₂ [M]⁺ 358.1632, found 358.1637. IR (Film): 1726, 1540, 1513, 1135 cm^–1. [α]25 D = −2.0, (c = 1.00, CH₂Cl₂).

17, Colorless oil; ¹H NMR (500 MHz, CDCl₃) δ 7.90 (t, J = 2.0 Hz, 1H), 7.84–7.81 (m, 1H), 7.46–7.43 (m, 1H), 7.26 (s, 1H), 7.23 (t, J = 8.0 Hz, 1H), 7.03–6.95 (m, 4H), 3.96 (q, J = 7.1 Hz, 2H), 2.44–2.36 (m, 1H), 2.19–2.09 (m, 2H), 1.86 (t, J = 6.3 Hz, 1H), 0.99 (t, J = 7.1 Hz, 3H), 0.82 (t, J = 7.3 Hz, 3H). ¹³C NMR (125 MHz, CDCl₃) δ 163.4 (dd, J = 35.5, 34.1 Hz), 147.6, 142.7, 135.6, 133.9 (d, J = 6.1 Hz), 132.3, 128.6, 128.0, 127.7, 124.1, 121.3, 116.9 (t, J = 257.2 Hz), 62.5, 40.4 (dd, J = 26.1, 22.3 Hz), 39.2, 26.7 (d, J = 7.3 Hz), 18.9 (d, J = 5.1 Hz), 13.5, 11.9. ¹⁹F NMR (470 MHz, CDCl₃) δ −96.4 (d, J = 250.5 Hz), −102.9 (d, J = 250.5 Hz). HRMS (ESI) m/z calculated C₂₁H₂₁F₂NO₄ [M]⁺ 389.1324, found 389.1331. IR (Film): 1730, 1610, 1513, 1320, 1140 cm^–1. [α]25 D = +5.0, (c = 1.00, CH₂Cl₂).

18, Colorless oil; ¹H NMR (600 MHz, CDCl₃) δ 7.11–7.05 (m, 3H), 6.94 (d, J = 8.4 Hz, 2H), 6.82–6.79 (m, 2H), 6.63 (d, J = 8.4 Hz, 2H), 4.16 (q, J = 7.1 Hz, 2H), 3.70 (s, 3H), 2.91 (dd, J = 9.6, 6.6 Hz, 1H), 1.93 (dd, J = 9.0, 5.7 Hz, 1H), 1.61–1.57 (m, 1H), 1.20 (t, J = 7.2 Hz, 3H). ¹³C NMR (150 MHz, CDCl₃) δ 163.8 (t, J = 35.2 Hz), 159.2, 136.6, 133.6, 127.9, 127.7, 126.1, 124.1, 115.2 (t, J = 254.1 Hz), 113.4, 62.5, 55.0, 36.2 (t, J = 24.6 Hz), 25.1 (t, J = 3.4 Hz), 15.1 (t, J = 3.7 Hz), 13.9. ¹⁹F NMR (564 MHz, CDCl₃) δ −108.8 (d, J = 244.6 Hz), −110.7 (d, J = 244.6 Hz). HRMS (ESI) m/z calculated C₂₀H₂₀F₂O₃ [M]⁺ 346.1268, found 346.1273. IR (Film): 3057, 2253, 1766, 1610, 1515, 1265, 906, 721, 649 cm^–1. [α]25 D = +0.9, (c = 1.00, CH₂Cl₂).

19, Colorless oil; ¹H NMR (500 MHz, CDCl₃) δ 7.95 (d, J = 8.5 Hz, 2H), 7.23 (d, J = 8.5 Hz, 2H), 7.17 (d, J = 8.3 Hz, 2H), 6.97 (d, J = 8.2 Hz, 2H), 4.07–3.99 (m, 2H), 2.16 (t, J = 5.5 Hz, 1H), 1.92 (d, J = 6.4 Hz, 1H), 1.87 (s, 3H), 1.07 (t, J = 7.1 Hz, 3H). ¹³C NMR (125 MHz, CDCl₃) δ 163.2 (dd, J = 37.5, 34.5 Hz), 149.8, 146.2, 132.9 (d, J = 6.0 Hz), 132.7, 131.2, 128.8, 123.2, 122.3, 116.3 (t, J = 257.0 Hz), 62.8, 39.4 (dd, J = 25.8, 22.8 Hz), 32.6, 21.6 (d, J = 6.7 Hz), 21.1 (t, J = 4.9 Hz), 13.6. ¹⁹F NMR (470 MHz, CDCl₃) δ −98.2 (d, J = 253.1 Hz), −104.3 (d, J = 253.1 Hz). HRMS (ESI) m/z calculated C₂₀H₁₈BrF₂NO₄ [M]⁺ 453.0289, found 453.0279. IR (Film): 3078, 2926, 1766, 1516, 1346, 1104 cm^–1. [α]25 D = −40.8, (c = 1.00, CH₂Cl₂).

20, White solid; mp: 93–94°C; ¹H NMR (500 MHz, CDCl₃) δ 7.95 (d, J = 8.8 Hz, 2H), 7.23 (d, J = 8.8 Hz, 2H), 7.05–7.00 (m, 4H), 4.08–3.98 (m, 2H), 2.16 (t, J = 5.2 Hz, 1H), 1.92 (d, J = 6.4 Hz, 1H), 1.88 (s, 3H), 1.07 (t, J = 7.1 Hz, 3H). ¹³C NMR (150 MHz, CDCl₃) δ 163.2 (dd, J = 35.1, 33.0 Hz), 149.9, 146.2, 134.0, 132.5, 132.3 (d, J = 5.9 Hz), 128.8, 128.3, 123.2, 116.3 (t, J = 257.0 Hz), 62.7, 39.3 (dd, J = 25.4, 8.3 Hz), 32.6, 21.6 (d, J = 6.9 Hz), 21.1 (t, J = 4.5 Hz), 13.6. ¹⁹F NMR (564 MHz, CDCl₃) δ −98.2 (d, J = 252.7 Hz), −104.3 (d, J = 252.7 Hz). HRMS (ESI) m/z calculated C₂₀H₁₈ClF₂NO₄ [M]⁺ 409.0787, found 409.0785. IR (Film): 3078, 2986, 2940, 1769, 1757, 1517, 1370, 1126 cm^–1. [α]25 D = −20.3, (c = 1.00, CH₂Cl₂).

21, Colorless oil; ¹H NMR (500 MHz, CDCl₃) δ 7.93 (d, J = 8.9 Hz, 2H), 7.44–7.40 (m, 2H), 7.36 (t, J = 7.6 Hz, 2H), 7.31–7.26 (m, 5H), 7.15 (d, J = 8.1 Hz, 2H), 4.04–3.97 (m, 2H), 2.24 (t, J = 5.5 Hz, 1H), 1.96–1.90 (m, 4H), 1.01 (t, J = 7.1 Hz, 3H). ¹³C NMR (150 MHz, CDCl₃) δ 163.4 (t, J = 34.4 Hz), 150.3, 146.1, 140.5, 139.9, 132.7 (d, J = 5.8 Hz), 131.6, 128.9, 128.7, 127.5, 126.9, 126.5, 123.1, 116.7 (t, J = 257.1 Hz), 62.6, 39.7 (dd, J = 25.5, 24.1 Hz), 32.6, 21.7 (d, J = 6.7 Hz), 21.2 (t, J = 5.0 Hz), 13.6 (d, J = 8.1 Hz). ¹⁹F NMR (564 MHz, CDCl₃) δ −102.7 (d, J = 251.2 Hz), −109.2 (d, J = 251.2 Hz). HRMS (ESI) m/z calculated C₂₆H₂₃F₂NO₄ [M]⁺ 451.1485, found 451.1487. IR (Film): 3031, 2931, 1771, 1518, 1345, 1111 cm^–1. [α]25 D = −10.9, (c = 1.00, CH₂Cl₂).

22, White solid; mp: 98–99°C; ¹H NMR (500 MHz, CDCl₃) δ 7.99 (d, J = 8.8 Hz, 2H), 7.26 (d, J = 8.6 Hz, 2H), 7.20 (s, 1H), 7.11 (d, J = 8.4 Hz, 1H), 6.95 (d, J = 8.4 Hz, 1H), 4.09 (q, J = 7.1 Hz, 2H), 2.15 (t, J = 5.5 Hz, 1H), 1.94 (d, J = 6.5 Hz, 1H), 1.87 (s, 3H), 1.11 (t, J = 7.1 Hz, 3H). ¹³C NMR (150 MHz, CDCl₃) δ 163.0 (t, J = 34.1 Hz), 149.4, 146.4, 134.2 (d, J = 5.8 Hz), 133.0, 132.4, 132.2, 130.6, 130.0, 128.8, 123.4, 116.0 (t, J = 256.7 Hz), 62.9, 39.0 (dd, J = 26.1, 24.3 Hz), 32.8, 21.6 (d, J = 6.8 Hz), 21.1 (t, J = 4.7 Hz), 13.6. ¹⁹F NMR (564 MHz, CDCl₃) δ −98.2 (d, J = 253.8 Hz), −103.9 (d, J = 253.8 Hz). HRMS (ESI) m/z calculated C₂₀H₁₇Cl₂F₂NO₄ [M]⁺ 443.0385, found 443.0395. IR (Film): 3078, 2984, 2935, 1769, 1598, 1516 1370, 1110 cm^–1. [α]25 D = −77.7, (c = 1.00, CH₂Cl₂).

23, Colorless oil; ¹H NMR (600 MHz, CDCl₃) δ 7.85 (d, J = 8.9 Hz, 2H), 7.64–7.60 (m, 2H), 7.56 (s, 1H), 7.49 (d, J = 8.4 Hz, 1H), 7.40–7.36 (m, 2H), 7.29 (d, J = 8.8 Hz, 2H), 7.20 (d, J = 8.0 Hz, 1H), 3.89 (q, J = 7.1 Hz, 2H), 2.35 (t, J = 5.0 Hz, 1H), 2.00 (d, J = 6.3 Hz, 1H), 1.94 (s, 3H), 0.86 (t, J = 7.1 Hz, 3H). ¹³C NMR (150 MHz, CDCl₃) δ 163.4 (dd, J = 35.0, 33.5 Hz), 150.1, 146.0, 132.6, 132.5, 131.3, 128.8, 128.4, 127.7, 127.6, 127.5, 126.5, 126.2, 123.0, 116.8 (t, J = 257.1 Hz), 62.5, 40.1 (dd, J = 25.5, 22.1 Hz), 32.6, 21.7 (d, J = 6.5 Hz), 21.4, 13.5. ¹⁹F NMR (564 MHz, CDCl₃) δ −98.0 (d, J = 251.4 Hz), −104.2 (d, J = 251.4 Hz). HRMS (ESI) m/z calculated C₂₄H₂₁F₂NO₄ [M]⁺ 425.1322, found 425.1331. IR (Film): 3057, 2935, 1770, 1518, 1345, 1114, 749 cm^–1. [α]25 D = −36.9, (c = 1.00, CH₂Cl₂).

24, White solid; mp: 87–88°C; ¹H NMR (500 MHz, CDCl₃) δ 7.69 (d, J = 8.0 Hz, 2H), 7.36–7.29 (m, 4H), 7.24–7.19 (m, 1H), 7.15–7.06 (m, 5H), 6.98–6.94 (m, 2H), 6.90–6.86 (m, 1H), 3.96 (q, J = 7.0 Hz, 2H), 2.46–2.43 (m, 1H), 2.41–2.38 (m, 1H), 1.00 (t, J = 7.0 H z, 3H). ¹³C NMR (150 MHz, CDCl₃) δ 163.6 (dd, J = 35.7, 32.3 Hz), 141.6, 140.9, 133.4 (d, J = 5.7 Hz), 131.7, 130.2, 129.0, 128.1, 127.8, 127.74, 127.69, 126.7, 126.0, 116.4 (t, J = 255.5 Hz), 62.3, 42.7, 40.7 (dd, J = 26.4, 21.6 Hz), 20.4 (t, J = 3.8 Hz), 13.6. ¹⁹F NMR (564 MHz, CDCl₃) δ −102.8 (d, J = 249.5 Hz), −105.1 (d, J = 249.5 Hz). HRMS (ESI) m/z calculated C₂₅H₂₂F₂O₂ [M]⁺ 392.1485, found 392.1480. IR (Film): 3057, 2253, 1766, 1494, 1304, 1261, 1136, 906, 724, 649 cm^–1. [α]25 D = −51.2, (c = 1.00, CH₂Cl₂).

25, White solid; mp: 89–90°C; ¹H NMR (500 MHz, CDCl₃) δ 7.68 (d, J = 7.5 Hz, 2H), 7.31 (t, J = 7.5 Hz, 2H), 7.23–7.17 (m, 3H), 7.15 (d, J = 8.0 Hz, 2H), 6.98 (t, J = 7.5 Hz, 2H), 6.93–6.87 (m, 3H), 4.00–3.93 (m, 2H), 2.41–2.35 (m, 2H), 2.18 (s, 3H), 1.03 (t, J = 7.3 Hz, 3H). ¹³C NMR (150 MHz, CDCl₃) δ 163.6 (dd, J = 32.9, 3.6 Hz), 141.8, 141.1, 137.4, 131.5, 130.20 (d, J = 6.2 Hz), 130.16, 129.0, 128.6, 128.1, 127.7, 126.6, 126.0, 116.5 (t, J = 255.2 Hz), 62.3, 42.7, 40.4 (dd, J = 26.5, 20.9 Hz), 21.0, 20.6 (dd, J = 5.2, 3.6 Hz), 13.6. ¹⁹F NMR (564 MHz, CDCl₃) δ −102.7 (d, J = 248.3 Hz), −105.2 (d, J = 248.3 Hz). HRMS (ESI) m/z calculated C₂₆H₂₄F₂O₂ [M]⁺ 406.1642, found 406.1637. IR (Film): 3055, 2253, 1765, 1305, 1264, 1088, 906, 726, 649 cm⁻¹.

26, White solid; mp: 80–81°C; ¹H NMR (600 MHz, CDCl₃) δ 7.68 (d, J = 7.8 Hz, 2H), 7.32 (t, J = 7.5 Hz, 2H), 7.23–7.19 (m, 3H), 7.13–7.10 (m, 4H), 6.95 (t, J = 7.8 Hz, 2H), 6.87 (t, J = 7.5 Hz, 1H), 4.00–3.90 (m, 2H), 2.41–2.37 (m, 2H), 1.18 (s, 9H), 0.95 (t, J = 7.2 Hz, 3H). ¹³C NMR (150 MHz, CDCl₃) δ 163.7 (dd, J = 36.2, 32.7 Hz), 150.6, 141.7, 141.1, 131.3, 130.22, 130.16 (d, J = 9.8 Hz), 129.0, 128.1, 127.6, 126.6, 125.8, 124.7, 116.5 (t, J = 255.4 Hz), 62.2, 42.6, 40.4 (dd, J = 26.4, 20.8 Hz), 34.3, 31.1, 20.6 (t, J = 4.2 Hz), 13.5. ¹⁹F NMR (564 MHz, CDCl₃) δ −102.6 (d, J = 247.8 Hz), −105.6 (d, J = 247.8 Hz). HRMS (ESI) m/z calculated C₂₉H₃₀F₂O₂ [M]⁺ 448.2112, found 448.2106. IR (Film): 3057, 2957, 2923, 2859, 2358, 1761, 1459, 1378, 1265, 806, 736, 706 cm^–1. [α]25 D = −16.9, (c = 1.00, CH₂Cl₂).

27, White solid; mp: 106–107°C; ¹H NMR (500 MHz, CDCl₃) δ 7.67 (d, J = 8.0 Hz, 2H), 7.31 (t, J = 7.5 Hz, 2H), 7.23–7.19 (m, 3H), 7.15 (d, J = 7.5 Hz, 2H), 6.99 (t, J = 7.8 Hz, 2H), 6.90 (t, J = 7.3 Hz, 1H), 6.65 (d, J = 9.0 Hz, 2H), 3.99 (q, J = 7.3 Hz, 2H), 3.69 (s, 3H), 2.39–2.35 (m, 2H), 1.06 (t, J = 7.3 Hz, 3H). ¹³C NMR (150 MHz, CDCl₃) δ 163.6 (dd, J = 36.3, 33.0 Hz), 158.9, 141.7, 141.1, 132.8, 130.2, 129.0, 128.1, 127.7, 126.6, 126.0, 125.3 (d, J = 4.8 Hz), 116.5 (t, J = 256.9 Hz), 113.3, 62.3, 55.0, 42.7, 40.0 (dd, J = 26.4, 20.9 Hz), 20.7, 13.7. ¹⁹F NMR (470 MHz, CDCl₃) δ −102.6 (d, J = 249.0 Hz), −105.4 (d, J = 249.0 Hz). HRMS (ESI) m/z calculated C₂₆H₂₄F₂O₃ [M]⁺ 422.1590, found 422.1586. IR (Film): 3055, 2253, 1766, 1514, 1294, 1261, 905, 725, 649 cm^–1. [α]25 D = −32.5, (c = 1.00, CH₂Cl₂).

28, White solid; mp: 87–88°C; ¹H NMR (500 MHz, CDCl₃) δ 7.68 (d, J = 7.7 Hz, 2H), 7.32 (t, J = 7.7 Hz, 2H), 7.22 (t, J = 7.4 Hz, 1H), 7.16 (d, J = 7.6 Hz, 2H), 7.04 (t, J = 7.9 Hz, 1H), 6.98 (t, J = 7.7 Hz, 2H), 6.94–6.89 (m, 2H), 6.85 (s, 1H), 6.63 (dd, J = 8.0, 2.4 Hz, 1H), 4.02–3.97 (m, 2H), 3.68 (s, 3H), 2.44–2.41 (m, 1H), 2.39–2.36 (m, 1H), 1.04 (t, J = 7.1 Hz, 3H). ¹³C NMR (125 MHz, CDCl₃) δ 163.5 (dd, J = 35.9, 32.2 Hz), 159.0, 141.6, 140.9, 134.9 (d, J = 5.5 Hz), 130.2, 128.9, 128.7, 128.1, 127.7, 126.7, 126.1, 124.1, 117.7, 116.3 (t, J = 257.0 Hz), 113.2, 62.3, 55.1, 42.7, 40.8 (dd, J = 26.0, 21.1 Hz), 20.6 (t, J = 4.5 Hz), 13.6. ¹⁹F NMR (470 MHz, CDCl₃) δ −102.6 (d, J = 249.6 Hz), −104.8 (d, J = 249.6 Hz). HRMS (ESI) m/z calculated C₂₆H₂₄F₂O₃ [M]⁺ 422.1590, found 422.1587. IR (Film): 3055, 2923, 2841, 1753, 1580, 1493 cm^–1. [α]25 D = −54.9, (c = 1.00, CH₂Cl₂).

29, Colorless oil; ¹H NMR (500 MHz, CDCl₃) δ 7.66 (d, J = 7.5 Hz, 2H), 7.34–7.24 (m, 4H), 7.24–7.20 (m, 1H), 7.15–7.09 (m, 4H), 7.00 (t, J = 7.5 Hz, 2H), 6.94–6.90 (m, 1H), 4.01–3.96 (m, 2H), 2.43–2.38 (m, 2H), 1.05 (t, J = 7.3 Hz, 3H). ¹³C NMR (125 MHz, CDCl₃) δ 163.4 (dd, J = 36.3, 32.5 Hz), 141.3, 140.5, 133.8, 133.0, 132.2 (d, J = 5.0 Hz), 130.1, 128.9, 128.2, 128.1, 127.9, 126.8, 126.3, 116.1 (t, J = 255.6 Hz), 62.5, 42.9, 40.1 (dd, J = 26.3, 21.9 Hz), 20.5 (t, J = 5.0 Hz), 13.6. ¹⁹F NMR (470 MHz, CDCl₃) δ −102.7 (d, J = 250.5 Hz), −104.7 (d, J = 250.5 Hz). HRMS (ESI) m/z calculated C₂₅H₂₁ClF₂O₂ [M]⁺ 426.1086, found 426.1090. IR (Film): 3057, 2983, 2253, 1381, 1263, 908, 723, 649 cm^–1. [α]25 D = −33.5, (c = 1.00, CH₂Cl₂).

30, Colorless oil; ¹H NMR (500 MHz, CDCl₃) δ 7.67 (d, J = 8.0 Hz, 2H), 7.34–7.30 (m, 3H), 7.25–7.20 (m, 2H), 7.16–7.14 (m, 2H), 7.09–7.04 (m, 2H), 7.04–6.99 (m, 2H), 6.94–6.90 (m, 1H), 4.00 (q, J = 7.0 Hz, 2H), 2.44–2.39 (m, 2H), 1.05 (t, J = 7.0 Hz, 3H). ¹³C NMR (125 MHz, CDCl₃) δ 163.3 (dd, J = 35.6, 32.8 Hz), 141.2, 140.4, 135.7 (d, J = 5.5 Hz), 133.6, 131.7, 130.1, 129.1, 128.9, 128.2, 128.0, 127.9, 126.8, 126.3, 116.0 (t, J = 255.3 Hz), 62.5, 42.9, 40.4 (dd, J = 26.2, 21.8 Hz), 20.4 (t, J = 4.2 Hz), 13.6. ¹⁹F NMR (564 MHz, CDCl₃) δ −102.9 (d, J = 251.0 Hz), −104.7 (d, J = 251.0 Hz). HRMS (ESI) m/z calculated C₂₅H₂₁ClF₂O₂ [M]⁺ 426.1090, found 426.1090. IR (Film): 3055, 2253, 1767, 1449, 1304, 1265, 1137, 906, 726, 649 cm^–1. [α]25 D = −48.3, (c = 1.00, CH₂Cl₂).

31, White solid; mp: 113–114°C; ¹H NMR (500 MHz, CDCl₃) δ 7.67 (d, J = 8.0 Hz, 2H), 7.34–7.29 (m, 4H), 7.22 (t, J = 7.5 Hz, 1H), 7.13 (d, J = 7.5 Hz, 2H), 6.99 (t, J = 7.5 Hz, 2H), 6.91 (t, J = 7.5 Hz, 1H), 6.81 (t, J = 7.5 Hz, 2H), 3.99 (q, J = 7.2 Hz, 2H), 2.43–2.38 (m, 2H), 1.05 (t, J = 7.2 Hz, 3H). ¹³C NMR (125 MHz, CDCl₃) δ 163.5 (dd, J = 35.0, 32.5 Hz), 162.1 (d, J = 248.5 Hz), 141.4, 140.7, 133.4, 130.2, 129.4 (dd, J = 5.5, 3.4 Hz),128.9, 128.1, 127.9, 126.8, 126.2, 116.2 (t, J = 255.0 Hz), 114.8 (d, J = 22.5 Hz), 62.4, 42.8, 40.0 (dd, J = 27.5, 21.9 Hz), 20.6 (dd, J = 5.0, 3.8 Hz), 13.7. ¹⁹F NMR (470 MHz, CDCl₃) δ −102.8 (d, J = 249.1 Hz), −105.1 (d, J = 249.1 Hz), (−113.7)-(-113.8) (m). HRMS (ESI) m/z calculated C₂₅H₂₁F₃O₂ [M]⁺ 410.1394, found 410.1386. IR (Film): 3055, 2358, 2253, 1766, 1512, 1303, 1261, 1135, 905, 725, 649 cm^–1. [α]25 D = −50.2, (c = 1.00, CH₂Cl₂).

32, White solid; mp: 114–115°C; ¹H NMR (500 MHz, CDCl₃) δ 7.66 (d, J = 7.5 Hz, 2H), 7.32 (t, J = 7.5 Hz, 2H), 7.27–7.19 (m, 5H), 7.13 (d, J = 7.5 Hz, 2H), 7.00 (t, J = 7.5 Hz, 2H), 6.94–6.90 (m, 1H), 4.03–3.93 (m, 2H), 2.42–2.37 (m, 2H), 1.05 (t, J = 7.0 Hz, 3H). ¹³C NMR (125 MHz, CDCl₃) δ 163.3 (dd, J = 35.6, 32.8 Hz), 141.3, 140.5, 133.3, 132.7 (d, J = 5.6 Hz), 131.0, 130.1, 128.9, 128.1, 127.9, 126.8, 126.3, 122.1, 116.0 (t, J = 255.4 Hz), 62.5, 42.9, 40.2 (dd, J = 26.4, 21.4 Hz), 20.4 (t, J = 4.3 Hz), 13.6. ¹⁹F NMR (470 MHz, CDCl₃) δ −102.8 (d, J = 251.0 Hz), −104.7 (d, J = 251.0 Hz). HRMS (ESI) m/z calculated C₂₅H₂₁BrF₂O₂ [M]⁺ 470.0587, found 470.0585. IR (Film): 2986, 2253, 1766, 1491, 1264, 1136, 906, 726, 649 cm^–1. [α]25 D = −51.1, (c = 1.00, CH₂Cl₂).

33, Colorless oil; ¹H NMR (600 MHz, CDCl₃) δ 7.70 (d, J = 8.4 Hz, 2H), 7.50–7.47 (m, 2H), 7.40–7.36 (m, 6H), 7.35–7.28 (m, 3H), 7.24–7.21 (m, 1H), 7.19–7.17 (m, 2H), 6.99–6.96 (m, 2H), 6.90–6.87 (m, 1H), 4.01–3.95 (m, 2H), 2.48–2.46 (m, 1H), 2.44–2.42 (m, 1H), 1.01 (t, J = 6.9 Hz, 3H). ¹³C NMR (150 MHz, CDCl₃) δ 163.6 (dd, J = 35.9, 32.0 Hz), 141.6, 140.9, 140.3, 132.5 (d, J = 5.7 Hz), 132.0, 130.2, 129.0, 128.7, 128.1, 127.8, 127.4, 126.9, 126.7, 126.4, 126.1, 116.4 (t, J = 255.5 Hz), 62.4, 42.9, 40.5 (dd, J = 26.4, 20.9 Hz), 20.6, 13.6. ¹⁹F NMR (564 MHz, CDCl₃) δ −102.6 (d, J = 250.0 Hz), −104.9 (d, J = 250.0 Hz). HRMS (ESI) m/z calculated C₃₁H₂₆F₂O₂ [M]⁺ 468.1787, found 468.1793. IR (Film): 3057, 2253, 1766, 1424, 1265, 906, 722, 649 cm^–1. [α]25 D = −25.4, (c = 1.00, CH₂Cl₂).

34, White solid; mp: 97–98°C; ¹H NMR (500 MHz, CDCl₃) δ 7.68 (d, J = 8.0 Hz, 2H), 7.46 (d, J = 7.0 Hz, 2H), 7.38 (d, J = 8.5 Hz, 2H), 7.33 (t, J = 7.5 Hz, 2H), 7.23 (t, J = 7.3 Hz, 1H), 7.12 (d, J = 8.0 Hz, 2H), 6.98 (t, J = 8.0 Hz, 2H), 6.91 (t, J = 8.0 Hz, 1H), 4.01–3.90 (m, 2H), 2.49–2.44 (m, 2H), 1.00 (t, J = 7.3 Hz, 3H). ¹³C NMR (125 MHz, CDCl₃) δ 163.3 (dd, J = 35.4, 32.6 Hz), 141.1, 140.3, 137.8 (d, J = 5.1 Hz), 132.1, 130.0, 129.9 (q, J = 32.5 Hz), 128.8, 128.2, 128.0, 126.9, 126.4, 124.7 (q, J = 3.4 Hz), 123.7 (q, J = 270.6 Hz), 116.0 (t, J = 255.4 Hz), 62.6, 43.0, 40.5 (dd, J = 26.4, 21.9 Hz), 20.4 (t, J = 4.3 Hz), 13.5. ¹⁹F NMR (470 MHz, CDCl₃) δ −62.8, −102.8 (d, J = 251.5 Hz), −104.3 (d, J = 251.5 Hz). IR (Film): 3055, 2253, 1766, 1449, 1326, 1264, 1129, 907, 726, 649 cm^–1. [α]25 D = −27.8, (c = 1.00, CH₂Cl₂).

35, Colorless oil; ¹H NMR (600 MHz, CDCl₃) δ 7.81–7.78 (m, 2H), 7.68 (d, J = 7.8 Hz, 2H), 7.42 (d, J = 7.2 Hz, 2H), 7.33 (t, J = 7.5 Hz, 2H), 7.24–7.21 (m, 1H), 7.15–7.12 (m, 2H), 6.98–6.95 (m, 2H), 6.90–6.87 (m, 1H), 3.96 (q, J = 7.2 Hz, 2H), 3.84 (s, 3H), 2.51–2.48 (m, 1H), 2.45–2.42 (m, 1H), 1.02 (t, J = 7.2 Hz, 3H). ¹³C NMR (150 MHz, CDCl₃) δ 166.6, 163.3 (dd, J = 35.7, 32.2 Hz), 141.2, 140.4, 138.9 (d, J = 5.0 Hz), 131.6, 130.0, 129.4, 129.1, 128.9, 128.2, 127.9, 126.8, 126.3, 116.0 (t, J = 255.3 Hz), 62.5, 52.1, 43.1, 40.6 (dd, J = 26.6, 21.8 Hz), 20.4 (t, J = 4.5 Hz), 13.6. ¹⁹F NMR (564 MHz, CDCl₃) δ −102.8 (d, J = 251.4 Hz), −104.2 (d, J = 251.4 Hz). HRMS (ESI) m/z calculated C₂₇H₂₄F₂O₄ [M]⁺ 450.1538, found 450.1535. IR (Film): 3055, 2985, 1768, 1720, 1264, 1113, 731, 703, 601 cm^–1. [α]25 D = −33.4, (c = 1.00, CH₂Cl₂).

36, White solid; mp: 95–96°C; ¹H NMR (600 MHz, CDCl₃) δ 7.66 (d, J = 8.4 Hz, 2H), 7.32 (t, J = 8.1 Hz, 2H), 7.24–7.21 (m, 3H), 7.17–7.15 (m, 2H), 7.09 (t, J = 1.8 Hz, 1H), 7.07–7.03 (m, 2H), 6.98–6.94 (m, 1H), 4.08–4.01 (m, 2H), 2.40 (s, 2H), 1.10 (t, J = 7.2 Hz, 3H). ¹³C NMR (150 MHz, CDCl₃) δ 163.1 (dd, J = 35.9, 32.9 Hz), 140.8, 139.9, 137.3 (d, J = 5.3 Hz), 134.3, 130.3, 130.0, 128.7, 128.2, 128.1, 128.0, 127.0, 126.6, 115.7 (t, J = 255.5 Hz), 62.7, 43.1, 40.2 (dd, J = 26.7, 22.4 Hz), 20.4 (t, J = 3.9 Hz), 13.7. ¹⁹F NMR (564 MHz, CDCl₃) δ −102.9 (d, J = 253.0 Hz), −104.2 (d, J = 253.0 Hz). HRMS (ESI) m/z calculated C₂₅H₂₀Cl₂F₂O₂ [M]⁺ 460.0712, found 460.0701. IR (Film): 3086, 2984, 2253, 1768, 1264, 905, 726, 649 cm^–1. [α]25 D = −40.0, (c = 1.00, CH₂Cl₂).

37, White solid; mp: 122–123°C; ¹H NMR (500 MHz, CDCl₃) δ 7.77–7.71 (m, 3H), 7.70–7.67 (m, 2H), 7.60 (d, J = 8.5 Hz, 1H), 7.54 (s, 1H), 7.40–7.32 (m, 4H), 7.25–7.19 (m, 3H), 6.90 (t, J = 7.8 Hz, 2H), 6.79 (t, J = 7.3 Hz, 1H), 3.87 (q, J = 7.0 Hz, 2H), 2.58 (t, J = 4.0 Hz, 1H), 2.49 (d, J = 5.5 Hz, 1H), 0.85 (t, J = 7.0 Hz, 3H). ¹³C NMR (125 MHz, CDCl₃) δ 163.5 (dd, J = 35.8, 32.8 Hz), 141.7, 140.8, 132.8, 132.6, 131.2 (d, J = 4.8 Hz), 130.9, 130.2, 129.3, 129.0, 128.1, 127.8, 127.7, 127.44, 127.39, 126.7, 126.2, 126.1, 125.9, 116.5 (t, J = 255.7 Hz), 62.3, 42.9, 40.9 (dd, J = 26.4, 21.3 Hz), 20.8 (t, J = 4.3 Hz), 13.5. ¹⁹F NMR (470 MHz, CDCl₃) δ −102.4 (d, J = 249.1 Hz), −104.7 (d, J = 249.1 Hz). HRMS (ESI) m/z calculated C₂₉H₂₄F₂O₂ [M]⁺ 442.1641, found 442.1637. IR (Film): 3055, 2253, 1766, 1378, 1261, 1009, 907, 725, 649 cm^–1. [α]25 D = −2.1, (c = 1.00, CH₂Cl₂).

38, Colorless oil; ¹H NMR (500 MHz, CDCl₃) δ 7.75 (d, J = 7.7 Hz, 2H), 7.63 (d, J = 7.8 Hz, 2H), 7.47 (t, J = 7.5 Hz, 1H), 7.37–7.28 (m, 5H), 7.24–7.22 (m, 2H), 7.16–7.13 (m, 2H), 7.02–6.94 (m, 5H), 6.90–6.86 (m, 1H), 2.50–2.44 (m, 2H). ¹³C NMR (150 MHz, CDCl₃) δ 190.5 (dd, J = 33.6, 29.0 Hz), 141.9, 140.9, 133.7, 133.5 (d, J = 5.8 Hz), 133.3, 132.2, 130.4, 129.6, 129.0, 128.11, 128.09, 127.69, 127.65, 127.5, 126.6, 126.0, 119.5 (t, J = 260.1 Hz), 42.7, 41.1 (dd, J = 26.3, 20.9 Hz), 21.1 (d, J = 6.1 Hz). ¹⁹F NMR (564 MHz, CDCl₃) δ −96.0 (d, J = 264.6 Hz), −99.4 (d, J = 264.6 Hz). HRMS (ESI) m/z calculated C₂₉H₂₂F₂O [M]⁺ 424.1535, found 424.1531. IR (Film): 3087, 2253, 1710, 1449, 1264, 906, 726, 649 cm^–1. [α]25 D = −18.9, (c = 1.00, CH₂Cl₂).

40, Colorless oil; ¹H NMR (500 MHz, CDCl₃) δ 7.54 (d, J = 7.5 Hz, 2H), 7.39–7.29 (m, 2H), 7.15–7.07 (m, 5H), 7.00 (d, J = 8.0 Hz, 2H), 6.76 (d, J = 8.0 Hz, 2H), 3.95 (q, J = 7.1 Hz, 2H), 2.39–2.34 (m, 2H), 2.30 (s, 3H), 2.07 (s, 3H), 1.00 (t, J = 7.1 Hz, 3H). ¹³C NMR (125 MHz, CDCl₃) δ 163.6 (dd, J = 36.0, 32.8 Hz), 138.9, 138.3, 136.1, 135.4, 133.7 (d, J = 5.7 Hz), 131.7, 129.9, 128.81, 128.76, 128.4, 127.8, 127.7, 116.5 (t, J = 256.4 Hz), 62.3, 42.1, 40.7 (dd, J = 26.8, 20.9 Hz), 21.1, 20.7, 20.5 (t, J = 4.5 Hz), 13.6. ¹⁹F NMR (470 MHz, CDCl₃) δ −102.7 (d, J = 248.1 Hz), −105.0 (d, J = 248.1 Hz). HRMS (ESI) m/z calculated C₂₇H₂₆F₂O₂ [M]⁺ 420.1787, found 420.1789. IR (Film): 3060, 2245, 1705, 1435, 1260 cm^–1. [α]25 D = −18.9, (c = 1.00, CH₂Cl₂).

41, White solid; mp: 73–74°C; ¹H NMR (600 MHz, CDCl₃) δ 7.51 (d, J = 7.8 Hz, 1H), 7.45 (s, 1H), 7.38–7.28 (m, 2H), 7.21 (t, J = 7.8 Hz, 1H), 7.14–7.06 (m, 3H), 7.02 (d, J = 7.8 Hz, 1H), 6.96 (d, J = 7.8 Hz, 1H), 6.93 (s, 1H), 6.85 (t, J = 7.8 Hz, 1H), 6.68 (d, J = 7.8 Hz, 1H), 3.95 (q, J = 7.2 Hz, 2H), 2.41–2.38 (m, 1H), 2.37–2.34 (m, 4H), 2.09 (s, 3H), 1.00 (t, J = 7.2 Hz, 3H). ¹³C NMR (125 MHz, CDCl₃) δ 163.6 (dd, J = 35.6, 32.7 Hz), 141.6, 141.0, 137.5, 137.0, 133.5 (d, J = 5.6 Hz), 131.6, 130.8, 129.8, 127.8, 127.72, 127.68, 127.5, 127.4, 127.3, 126.7, 126.2, 116.4 (t, J = 255.3 Hz), 62.3, 42.7, 40.6 (dd, J = 26.4, 21.1 Hz), 21.5, 21.3, 20.5 (t, J = 4.4 Hz), 13.6. ¹⁹F NMR (470 MHz, CDCl₃) δ −102.7 (d, J = 248.6 Hz), −105.0 (d, J = 248.6 Hz). IR (Film): 3057, 2924, 2253, 1766, 1603, 1449, 1264, 1132, 906, 726, 649 cm^–1. [α]25 D = −19.8, (c = 1.00, CH₂Cl₂).

42, Colorless oil; ¹H NMR (500 MHz, CDCl₃) δ 7.65–7.60 (m, 2H), 7.34–7.26 (m, 2H), 7.16–7.09 (m, 3H), 7.08–6.99 (m, 4H), 6.69–6.63 (m, 2H), 3.97 (q, J = 7.1 Hz, 2H), 2.41–2.35 (m, 2H), 1.00 (t, J = 7.1 Hz, 3H). ¹³C NMR (150 MHz, CDCl₃) δ 163.4 (dd, J = 35.7, 32.5 Hz), 161.7 (d, J = 245.3 Hz), 161.0 (d, J = 245.5 Hz), 137.3, 136.7 (d, J = 3.1 Hz), 133.0 (d, J = 5.6 Hz), 131.6 (d, J = 7.9 Hz), 130.4 (d, J = 8.1 Hz), 128.04, 128.00, 118.0, 116.3 (d, J = 257.3 Hz), 115.1 (d, J = 21.7 Hz), 114.7 (d, J = 21.3 Hz), 62.4, 41.2, 40.9 (dd, J = 26.1, 21.0 Hz), 20.8 (t, J = 4.5 Hz), 13.6. ¹⁹F NMR (564 MHz, CDCl₃) δ −102.7 (d, J = 249.0 Hz), −105.2 (d, J = 249.0 Hz), (−115.7)-(-115.8) (m), (−116.3)-(-116.4) (m). HRMS (ESI) m/z calculated C₂₅H₂₀F₄O₂ [M]⁺ 428.1290, found 428.1292. IR (Film): 2926, 2360, 1751, 1511, 1230 cm^–1. [α]25 D = −22.6 (c = 1.00, CH₂Cl₂).

43, White solid; mp: 84–85°C; ¹H NMR (600 MHz, CDCl₃) δ 7.46 (d, J = 7.8 Hz, 1H), 7.36 (d, J = 10.2 Hz, 1H), 7.33–7.28 (m, 3H), 7.17–7.10 (m, 3H), 6.97–6.92 (m, 2H), 6.90 (d, J = 7.8 Hz, 1H), 6.83–6.81 (m, 1H), 6.63–6.60 (m, 1H), 3.98 (q, J = 7.2 Hz, 2H), 2.43–2.40 (m, 1H), 2.39–2.36 (m, 1H), 1.01 (t, J = 7.2 Hz, 3H). ¹³C NMR (150 MHz, CDCl₃) δ 163.3 (dd, J = 35.7, 32.0 Hz), 162.5 (d, J = 245.2 Hz), 162.2 (d, J = 246.3 Hz), 143.4 (d, J = 7.5 Hz), 142.9 (d, J = 7.0 Hz), 132.6 (d, J = 5.1 Hz), 131.5, 129.7 (d, J = 8.5 Hz), 129.2 (d, J = 8.2 Hz), 128.09 (d, J = 6.9 Hz), 128.07, 125.9, 124.6 (d, J = 3.3 Hz), 117.2 (d, J = 21.6 Hz), 116.1 (t, J = 255.5 Hz), 116.0 (d, J = 21.9 Hz), 114.0 (d, J = 20.9 Hz), 113.3 (d, J = 21.3 Hz), 62.5, 41.8, 41.1 (dd, J = 26.3, 20.9 Hz), 20.6 (t, J = 4.6 Hz), 13.6. ¹⁹F NMR (564 MHz, CDCl₃) δ −102.9 (d, J = 249.6 Hz), −105.5 (d, J = 249.6 Hz), (−113.1)-(-113.4) (m). HRMS (ESI) m/z calculated C₂₅H₂₀F₄O₂ [M]⁺ 428.1290, found 428.1292. IR (Film): 3065, 2963, 2925, 1753, 1587, 1487, 1261, 1183 cm^–1. [α]25 D = −38.1, (c = 1.00, CH₂Cl₂).

44, White solid; mp: 94–95°C; ¹H NMR (500 MHz, CDCl₃) δ 7.58 (d, J = 7.6 Hz, 2H), 7.33–7.27 (m, 4H), 7.17–7.13 (m, 3H), 7.02 (d, J = 8.7 Hz, 2H), 6.95 (d, J = 8.7 Hz, 2H), 3.97 (q, J = 7.1 Hz, 2H), 2.40–2.35 (m, 2H), 1.00 (t, J = 7.1 Hz, 3H). ¹³C NMR (150 MHz, CDCl₃) δ 163.3 (dd, J = 35.6, 30.5 Hz), 139.7, 139.2, 132.8, 132.7 (d, J = 5.5 Hz), 132.2, 131.4, 130.2, 128.5, 128.2, 128.1, 128.0, 116.2 (t, J = 257.3 Hz), 62.5, 41.4, 41.0 (dd, J = 26.3, 20.9 Hz), 20.6 (t, J = 4.5 Hz), 13.6. ¹⁹F NMR (564 MHz, CDCl₃) δ −102.6 (d, J = 249.5 Hz), −105.3 (d, J = 249.5 Hz). HRMS (ESI) m/z calculated C₂₅H₂₀Cl₂F₂O₂ [M]⁺ 460.0707, found 460.0701. IR (Film): 3055, 2985, 2253, 1422, 1263, 902, 719, 649 cm^–1. [α]25 D = −22.6, (c = 1.00, CH₂Cl₂).

45, Colorless oil; ¹H NMR (600 MHz, CDCl₃) δ 7.52 (d, J = 7.8 Hz, 2H), 7.45 (d, J = 8.6 Hz, 2H), 7.34–7.27 (m, 2H), 7.17–7.13 (m, 3H), 7.12–7.08 (m, 2H), 6.97–6.94 (m, 2H), 3.97 (q, J = 7.1 Hz, 2H), 2.39–2.34 (m, 2H), 1.00 (t, J = 7.1 Hz, 3H). ¹³C NMR (125 MHz, CDCl₃) δ 163.3 (dd, J = 35.6, 32.7 Hz), 140.2, 139.6, 132.7 (d, J = 5.4 Hz), 131.7, 131.4, 131.0, 130.6, 128.19, 128.17, 121.0, 120.4, 116.2 (t, J = 257.1 Hz), 62.5, 41.5, 41.0 (dd, J = 26.4, 21.0 Hz), 20.6 (t, J = 4.3 Hz), 13.6. ¹⁹F NMR (470 MHz, CDCl₃) δ −102.6 (d, J = 249.5 Hz), −105.3 (d, J = 249.5 Hz). IR (Film): 3052, 2985, 2253, 1767, 1491, 1421, 1264, 907, 728, 703, 649 cm^–1. [α]25 D = −27.6, (c = 1.00, CH₂Cl₂).

46, Colorless oil; ¹H NMR (500 MHz, CDCl₃) δ 7.56 (d, J = 7.9 Hz, 2H), 7.35–7.30 (m, 2H), 7.14–7.07 (m, 3H), 7.00 (d, J = 8.8 Hz, 2H), 6.85 (d, J = 8.8 Hz, 2H), 6.50 (d, J = 8.9 Hz, 2H), 3.95 (q, J = 7.1 Hz, 2H), 3.78 (s, 3H), 3.60 (s, 3H), 2.37–2.32 (m, 2H), 1.01 (t, J = 7.1 Hz, 3H). ¹³C NMR (125 MHz, CDCl₃) δ 163.7 (dd, J = 36.0, 32.6 Hz), 158.2, 157.5, 134.1, 133.7 (d, J = 5.7 Hz), 133.6, 131.7, 131.0, 129.8, 127.9, 127.7, 116.5 (t, J = 256.5 Hz), 113.5, 113.1, 62.3, 55.2, 55.0, 41.3, 40.9 (dd, J = 26.6, 21.1 Hz), 20.8 (t, J = 4.5 Hz), 13.6. ¹⁹F NMR (470 MHz, CDCl₃) δ −102.8 (d, J = 248.6 Hz), −104.8 (d, J = 248.6 Hz). HRMS (ESI) m/z calculated C₂₇H₂₆F₂O₄ [M]⁺ 452.1688, found 452.1691. IR (Film): 3046, 2253, 1766, 1512, 1264, 905, 726, 649 cm^–1. [α]25 D = −9.2 (c = 1.00, CH₂Cl₂).

47, White solid; mp: 98–99°C; ¹H NMR (500 MHz, CDCl₃) δ 7.67 (d, J = 7.6 Hz, 2H), 7.33–7.28 (m, 4H), 7.20 (t, J = 7.4 Hz, 1H), 7.11–7.03 (m, 5H), 6.94 (t, J = 7.6 Hz, 2H), 6.86 (t, J = 7.3 Hz, 1H), 5.73 (s, 1H), 5.64 (s, 1H), 2.47–2.44 (m, 1H), 2.38 (d, J = 6.0 Hz, 1H). ¹³C NMR (150 MHz, CDCl₃) δ 166.0 (dd, J = 33.2, 30.1 Hz), 141.7, 140.7, 133.7 (d, J = 4.9 Hz), 132.0, 130.2, 128.8, 128.0, 127.8, 127.6, 126.6, 125.9, 117.8 (t, J = 258.4 Hz), 41.8, 40.4 (dd, J = 26.7, 21.8 Hz), 20.6 (t, J = 4.2 Hz). ¹⁹F NMR (564 MHz, CDCl₃) δ −102.8 (d, J = 248.0 Hz), −105.1 (d, J = 248.0 Hz). HRMS (ESI) m/z calculated C₂₃H₁₉F₂NO [M]⁺ 363.1326, found 363.1327. IR (Film): 3035, 2250, 1740, 1501, 1151, 750, 637 cm^–1. [α]25 D = −15.3 (c = 1.00, CH₂Cl₂).

48, Colorless oil; ¹H NMR (500 MHz, CDCl₃) δ 7.69 (d, J = 7.6 Hz, 2H), 7.38–7.29 (m, 4H), 7.22–7.19 (m, 1H), 7.16–7.06 (m, 5H), 6.95 (t, J = 7.6 Hz, 2H), 6.86 (t, J = 7.3 Hz, 1H), 3.56–3.41 (m, 2H), 2.40 (t, J = 5.1 Hz, 1H), 2.14 (d, J = 5.7 Hz, 1H), 1.65 (s, 1H). ¹³C NMR (125 MHz, CDCl₃) δ 142.5, 141.1, 135.2 (d, J = 6.0 Hz), 131.1, 130.1, 129.0, 128.0, 127.6, 127.4, 126.4, 125.9, 123.0 (dd, J = 249.1, 246.3 Hz), 64.8 (dd, J = 34.4, 27.3 Hz), 41.8, 40.0 (dd, J = 25.9, 21.1 Hz), 19.8 (dd, J = 5.8, 3.7 Hz). ¹⁹F NMR (470 MHz, CDCl₃) δ −105.9 (dd, J = 247.7, 12.7 Hz), −109.4 (dt, J = 247.5, 16.8 Hz). IR (Film): 2237, 1421, 1209, 1150, 920 cm^–1. [α]25 D = −30.2, (c = 1.00, CH₂Cl₂).

49, White solid; mp: 90–91°C; ¹H NMR (500 MHz, CDCl₃) δ 8.33–8.10 (m, 1H), 7.67 (d, J = 7.7 Hz, 2H), 7.36–7.27 (m, 4H), 7.22 (t, J = 7.4 Hz, 1H), 7.12–7.09 (m, 5H), 6.97 (t, J = 7.5 Hz, 2H), 6.89 (t, J = 7.3 Hz, 1H), 2.45 (t, J = 5.1 Hz, 1H), 2.36 (d, J = 6.0 Hz, 1H). ¹³C NMR (125 MHz, CDCl₃) δ 167.2 (dd, J = 37.8, 33.5 Hz), 141.3, 140.6, 132.8 (d, J = 5.2 Hz), 131.7, 130.1, 128.9, 128.2, 128.0, 127.9, 127.7, 126.8, 126.1, 116.1 (t, J = 256.7 Hz), 42.8, 40.3 (dd, J = 25.9, 20.9 Hz), 20.5. ¹⁹F NMR (470 MHz, CDCl₃) δ −103.4 (d, J = 251.4 Hz), −105.4 (d, J = 251.4 Hz). IR (Film): 3023, 2267, 1420, 922 cm^–1. [α]25 D = −27.5, (c = 1.00, CH₂Cl₂).

50, Colorless oil; ¹H NMR (500 MHz, CDCl₃) δ 7.69 (d, J = 7.8 Hz, 2H), 7.35–7.20 (m, 5H), 7.14–7.05 (m, 5H), 6.96 (t, J = 7.6 Hz, 2H), 6.88 (t, J = 7.3 Hz, 1H), 2.46–2.42 (m, 1H), 2.39–2.35 (m, 1H), 2.31–2.23 (m, 1H), 1.90–1.82 (m, 1H), 1.31–1.13 (m, 2H), 1.06–0.95 (m, 2H), 0.70 (t, J = 7.3 Hz, 3H). ¹³C NMR (150 MHz, CDCl₃) δ 201.6 (dd, J = 35.8, 27.0 Hz), 141.8, 140.7, 133.3 (d, J = 5.8 Hz), 132.1, 130.3, 128.9, 128.1, 128.0, 127.71, 127.67, 126.6, 126.0, 118.2 (t, J = 259.5 Hz), 42.2, 40.3 (dd, J = 27.0, 21.4 Hz), 37.5, 24.3, 21.7, 20.5 (dd, J = 26.1, 22.2 Hz), 13.6. ¹⁹F NMR (564 MHz, CDCl₃) δ −102.4 (d, J = 250.4 Hz), −108.4 (d, J = 250.4 Hz). IR (Film): 3050, 2250, 1715, 1433, 1251, 922, 630 cm^–1. [α]25 D = −22.3, (c = 1.00, CH₂Cl₂).

Theoretical methodology

The quantum chemical calculations described in this work were carried out with Gaussian16 package.⁴² Geometry optimizations were conducted in the framework of the density functional theory (DFT) at the M06l⁴³ level. The effective core potential SDD⁴⁴ basis set was used to represent Rh atom, all the other atoms (C, H, O, F etc.) were described with 6-31G(d) basis set.^45,46,47 The nature of the local minima was established with analytical frequencies calculations. Intrinsic reaction coordinate (IRC)^48,49 calculations were carried out to ascertain the true nature of the transition states. 3D diagrams of the computed species were generated using CYLview visualization software.⁵⁰ All structures are optimized under gas phase conditions.

Published: January 11, 2023

Data and code availability

• •All original crystal structures have been deposited at CCDC and are publicly available as of the date of publication. Compound 37: CCDC 2117854. Compound 44: CCDC 2117853.
• •This paper does not report original code.
• •Any additional information required to reanalyze the data reported in this paper can be obtained from the lead contact upon request.