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Organocatalytic regioselective asymmetric Michael addition of azlactones to o-hydroxy chalcone derivatives† Shao-Yun Zhang, Gui-Yu Ruan, Zhi-Cong Geng, Nai-Kai Li, Ming Lv, Yong Wang* and Xing-Wang Wang* The regioselective and enantioselective Michael addition between azlactones and o-hydroxy chalcone derivatives is reported. Enantiomerically enriched N,O-aminals with two continuous stereogenic centers are exclusively obtained in moderate to good yields with excellent diastereoselectivities and good to

Received 21st January 2015, Accepted 12th April 2015

excellent enantioselectivities. The experimental results show that an o-hydroxy group on the cinnamenyl

DOI: 10.1039/c5ob00121h

motif of chalcone derivatives plays a crucial role at the reaction sites for the regioselective Michael addition. In addition, circular dichroism (CD) spectroscopy and density functional theory (DFT) are used to

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investigate the absolute configuration of N,O-aminals and the corresponding transition-state structures.

Introduction N,O-Subunits bearing all-carbon quaternary stereogenic centers1 are one important class of molecular structures presented in biological and pharmaceutical agents or natural products. As shown in the literature, some natural products,2 such as mycalamaide A, tallysomycin, spergualin, zampanolide, echinocandin B as well as the peredin family, all contain chiral N,O-subunits. Their significant biological activity related to allcarbon quaternary enantiomeric centers of N,O-motifs is evidenced by cytotoxicity studies against various human tumor cell lines.3 Although some elegant catalytic strategies have been reported to efficiently construct N,O-aminals with azlactones,4 asymmetric synthesis of optically active N,O-aminals with all-carbon quaternary stereogenic centers is still highly demanded and interesting. Azlactones,5 endowed with three different nucleophilic sites6 and one electrophilic site7 owing to their interconvertible keto and enol forms, have been widely investigated in the synthesis of chiral amino acids8 and N,O-aminals4 with quaternary stereogenic centers. In general, different nucleophilic reaction sites of 2,4-disubstituted azlactones were greatly affected by substituents on the azlactones, electrophiles, cata-

Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, P. R. China. E-mail: [email protected], [email protected]; Fax: +86 (0) 512 65880378; Tel: +86 (0) 512 65880378 † Electronic supplementary information (ESI) available: Characterization data and HPLC chromatograms for all compounds. CCDC 1032990. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c5ob00121h

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Scheme 1

Michael additions between azlactones and enones.

lysts, and reaction conditions.4b,c From 2008, several groups reported 1,4-addition reaction of azlactones to electrondeficient alkenes catalyzed by organocatalysis,4,9 in which chiral amino acids and N,O-aminals were selectively obtained by tuning the substituents on azlactones or by the use of electron-poor Michael acceptors. Among them, enantioselective Michael addition of 4-substituted azlactones to α,β-unsaturated ketones was reported by two groups with complete C-4 selectivity (Scheme 1).10 Based on the reported literature and our previous studies,11 we envisioned that whether the reaction of azlactones with o-hydroxy chalcone derivatives could proceed smoothly to give the regioselective Michael addition products. Finally, we found that enantiomerically enriched N,O-aminals with two contiguous stereogenic centers were generated for this transformation, in which the regioselective products were determined by the hydroxy group on the cinnamenyl group of chalcone derivatives (Scheme 2). Correspondingly, the C-2 regioselective

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Scheme 2 C-2 regio- and enantio-selective Michael addition of azlactones 3 to o-hydroxy chalcone derivatives 2. Scheme 4

Michael adducts were exclusively obtained in moderate to good yields with good to excellent enantioselectivities.

Results and discussion The Michael addition of 2,4-diphenyloxazol-5(4H)-one 3a to (E)-chalcone was investigated to explore the nucleophilic reaction sites of azlactones, which was carried out under standard reaction conditions in this study is as follows: 20 mol% of quinine derived bifunctional thiourea tertiary amine catalyst 1a with 150 mg of 4 Å molecular sieves at −30 °C in m-xylene. It was found that the mixture of both C-2 and C-4 products was obtained in 41% yield after 12 hours of reaction time, albeit with 99% ee for the minor C-2 product B. After the mixture products were treated with the TMSCl reagent in MeOH for 0.5 hour,11 the major product with the C-4 nucleophilic attack was converted into the ring-opening product A in 75% yield with 93% ee (Scheme 3). In order to probe whether the hydroxyl functional groups had a pronounced effect on the nucleophilic sites of azlactones for the regioselective Michael addition, the chalcone derivatives bearing o-, m-, p-hydroxyl groups on styryl motifs were respectively employed to react with 2,4-diphenyloxazol-5(4H)-one 3a under the above mentioned standard reaction conditions. It was found that o-hydroxy chalcone was a competent substrate to furnish the regioselective C-2 attack product in 81% yield with 81% ee. However, for the m- and p-hydroxy chalcones, the reactions processed very sluggishly to provide

Scheme 3

Separation of the mixture of C-2 and C-4 products.

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The influence of the hydroxyl substituent on the reaction.

mixture products even at room temperature. These controlling reactions indicate that an o-hydroxy group on the cinnamenyl group of chalcone derivatives plays a crucial role at the reaction sites for the regioselective Michael addition reaction (Scheme 4). Initially, the reaction between (E)-3-(5-chloro-2-hydroxyphenyl)-1-phenylprop-2-en-1-one 2a and 2,4-diphenyloxazol-5(4H)one 3a, derived from rac-phenylglycine, was selected as the model reaction to examine a series of bifunctional organic catalysts 1a–m (Fig. 1) at room temperature in toluene (Table 1, entries 1–13). Quinine, (1R,2R)-cyclohexane-1,2-diamine (DACH) and (1R,2R)-1,2-diphenylethane-1,2-diamine (DPEN) derived bifunctional thiourea tertiary amine catalysts 1a–1c were first investigated for this transformation (Table 1, entries 1–3). It was observed that the desired product 4a could be obtained in 85% yield, 15/1 dr and 76% ee, when the reaction was catalyzed by 20 mol% of 1a in toluene at room temperature (Table 1, entry 1). Chiral organocatalysts 1d–1f could not improve the enantioselectivities of the desired products (Table 1, entries 4–6). Subsequently, bifunctional thiourea tertiary amine catalysts 1g–1m were further investigated for this transformation (Table 1, entries 7–13). In comparison with catalyst 1a, catalyst 1h showed a slight increase of enantioselectivity albeit with relatively low reactivity (Table 1, entry 8 vs. entry 1). In consideration of the reactivity, diastereoselectivity and enantioselectivity, catalyst 1a gave the most promising catalytic results for this transformation. With 1a as an optimal chiral organocatalyst, the reaction conditions were further optimized by adjusting several reaction parameters, including reaction medium, substrate concentration, reaction temperature, catalyst loading and additives. The results are summarized in Table 2. Firstly, some common solvents were screened for this transformation (Table 2, entries 2–6). Only a trace product was obtained in THF (Table 2, entry 2). In view of both reactivity and enantioselectivity, m-xylene proved to be the optimal reaction medium (Table 2, entry 7 vs. entries 1–6). The yield could be improved to 95% by increasing the substrate concentration (Table 2, entry 10). When the reaction was carried out in m-xylene at −30 °C, 90% enantioselectivity was obtained (Table 2, entry 13). Further dropping the reaction temperature to −40 °C, the reaction was dramatically suppressed (Table 2, entry 14). Then, the molar ratio and catalyst loading were investigated (Table 2, entries 15–18). Finally, the highest enantioselectivity and a balanced yield

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Fig. 1

Table 1

Paper

Structures of bifunctional organocatalysts 1a–m.

Screening organocatalystsa

Entry

Cat.

Yieldb (%)

1 2 3 4 5 6 7 8 9 10 11 12 13

1a 1b 1c 1d 1e 1f 1g 1h 1i 1j 1k 1l 1m

85 51 92 74 48 83 96 68 88 80 79 32 94

Table 2

drc

eec (%)

15 : 1 4:1 7:1 8:1 7:1 3:1 13 : 1 17 : 1 12 : 1 14 : 1 5:1 4:1 >20 : 1

76 −33 −43 55 −20 −7 −74 84 −76 52 21 65 39

a Unless noted, reactions were carried out with 2a (0.1 mmol), 3a (0.1 mmol), and 1 (20 mol%) in toluene (1.0 mL) at rt. b Isolated yield of 4a. c Determined by chiral HPLC analysis.

were furnished as the reaction was performed with a 1/2 ratio of 2a to 3a in m-xylene at −30 °C, and the addition of activated 4 Å molecular sieves with a substrate concentration of 0.67 M in the presence of 20 mol% catalyst 1a (Table 2, entry 19).

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Optimization of the reaction conditionsa

Entry

Solv.

Con.

T (°C)

Yieldh (%)

1 2 3 4 5 6 7 8 9 10 11e 12e 13e 14e 15e, f 16e,g 17b,e, f 18c,e, f 19d,e, f

Toluene THF DCM MTBE CH3CN PhCl m-Xylene m-Xylene m-Xylene m-Xylene m-Xylene m-Xylene m-Xylene m-Xylene m-Xylene m-Xylene m-Xylene m-Xylene m-Xylene

1 1 1 1 1 1 1 0.5 0.33 0.67 0.67 0.67 0.67 0.67 0.67 0.67 0.67 0.67 0.67

25 25 25 25 25 25 25 25 25 25 −10 −20 −30 −40 −30 −30 −30 −30 −30

85 20 : 1 15 : 1 15 : 1 15 : 1 >20 : 1 >20 : 1 >20 : 1 — >20 : 1 >20 : 1 >20 : 1 — >20 : 1

76 — 59 65 65 60 75 74 75 75 82 87 90 — 90 89 86 — 90

i

a Unless noted, the reactions were carried out with 2a (0.1 mmol), 3a (0.1 mmol) and cat. 1a (20 mol%) at rt for 0.5 h. b 10 mol% cat. was added. c 5 mol% cat. was added. d 150 mg 4 Å MS was added. e The reaction was carried out for 12 h. f 0.2 mmol of 3a was added. g 0.3 mmol of 3a was added. h Isolated yield of 4a. i Determined by chiral HPLC analysis.

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Table 3

Organic & Biomolecular Chemistry Substrate scope for the C-2 regioselective Michael additiona

Table 4 Substrate scope for the C-2 regioselective Michael additiona

Entry

R

Yield [%]

dr

ee [%]

Entry

1 2 3d 4 5 6 7 8 9 10e 11 12e 13 14 15 f

C6H5 (2a) 4-FC6H4 (2b) 4-BrC6H4 (2c) 4-IC6H4 (2d) 4-CF3C6H4 (2e) 4-tBuC6H4 (2f) 4-C6H5C6H4 (2g) 4-(n-Pentyl) C6H4 (2h) 3-FC6H4 (2i) 3-ClC6H4 (2j) 2-FC6H4 (2k) 3,4-F2C6H3 (2l) 2-Furyl (2m) 2-Thienyl (2n) 2o

4a/75 4b/78 4c/98 4d/99 4e/89 4f/91 4g/92 4h/99 4i/67 4j/81 4k/91 4l/71 4m/95 4n/60 4o/25

>20/1 >20/1 >20/1 >20/1 >20/1 >20/1 >20/1 >20/1 >20/1 >20/1 >20/1 >20/1 >20/1 >20/1 >20/1

90 91 96 (>99) 99 95 90 97 91 93 81 89 89 90 90 12

1 2 3 4d 5d 6 7 8 9 10 11e

1

b

c

c

a Unless noted, reactions were carried out with 2 (0.1 mmol), 3a (0.2 mmol), 1a (20 mol%), and 4 Å MS (150 mg) in m-xylene (1.5 mL) at −30 °C for 12 h. b Isolated yield of 4. c Determined by chiral HPLC analysis. d After recrystallization, ee > 99%. e The reaction was carried out at −10 °C. f The reaction was carried out at rt. The substrate 2o was (E)-4-(2-hydroxyphenyl)but-3-en-2-one.

Having established the optimized reaction conditions, the substrate scope of the organocatalytic asymmetric addition of azlactone 3a to o-hydroxy chalcone derivatives 2 was then explored, and the results are summarized in Table 3. By the use of 3a as the nucleophilic reagent, o-hydroxy chalcone derivatives 2 were investigated to study the effects of the electronic properties and the steric hindrance of R1 groups on the catalytic results (Table 3, entries 1–15). For most aryl-substituted o-hydroxy α,β-unsaturated ketones 2 bearing electrondonating groups (4-tBu, 4-Ph, 4-n-amyl) or electron-withdrawing groups (4-F, 4-Br, 4-I, 4-CF3, 3-F, 2-F) on the benzoyl backbones, the reactions proceeded smoothly to provide the desired products in 67–99% yields with 89–99% ee (Table 3, entries 2–9, entry 11). Intriguingly, substrates 2j and 2l bearing 3-Cl and 3,4-2F-substituents on phenyl rings respectively gave the desired products 4j and 4l in 81% and 71% yields with 81% and 89% ee, when the reaction temperature climbed to −10 °C (Table 3, entries 10 and 12). Furthermore, α,β-unsaturated ketones 2m and 2n bearing heteroaromatic rings were also suitable substrates for this reaction, providing the desired products 4m and 4n in 95% and 60% yields with both 90% ee, respectively (Table 3, entries 13 and 14). In addition, for the alkyl-substituted o-hydroxy α,β-unsaturated ketone 2o, the reaction could not proceed under otherwise identical reaction conditions. But to our delight, when the reaction temperature was increased to room temperature, the desired product 4o was obtained in 25% yield with >20/1 dr and 12% ee.

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R1, R2

R3

Yieldb [%]

drc

eec [%]

H, H (2p) H, 4-Cl (2q) H, 4-Br (2r) 5-CH3, H (2s) 3-OCH3, H (2t) 5-Cl, H (2a) 5-Cl, H (2a) 5-Cl, H (2a) 5-Cl, H (2a) 5-Cl, H (2a) 5-Cl, H (2a)

C6H5 (3a) C6H5 (3a) C6H5 (3a) C6H5 (3a) C6H5 (3a) 4-FC6H4 (3b) 4-ClC6H4 (3c) 4-OCH3C6H4 (3d) 4-CH3C6H4 (3e) 3-CH3C6H4 (3f) t Bu (3g)

4p/73 4q/82 4r/94 4s/60 4t/87 4u/70 4v/76 4w/85 4x/74 4y/67 4z/54

>20/1 >20/1 >20/1 >20/1 >20/1 >20/1 >20/1 >20/1 >20/1 >20/1 >20/1

81 84 80 80 84 92 93 92 90 90 72

a Unless noted, reactions were carried out with 2 (0.1 mmol), 3 (0.2 mmol), 1a (20 mol%), and 4 Å MS (150 mg) in m-xylene (1.5 mL) at −30 °C for 12 h. b Isolated yield of 4. c Determined by chiral HPLC analysis. d The reaction was carried out at −20 °C. e The reaction was carried out at −10 °C.

The substrate scope of o-hydroxy chalcone derivatives 2 and the aryl substituted azlactones 3 were further investigated, as shown in Table 4. On the one hand, the reaction between o-hydroxy chalcone 2p and 3a afforded the desired adduct 4p in 73% yield with 81% ee. For o-hydroxy chalcones 2q and 2r bearing 4-Cl and 4-Br on benzoyl backbones, the reactions also performed well to furnish the expected products 4q and 4r in 82% and 94% yields with 84% and 80% ee, respectively (Table 4, entries 2 and 3). However, for o-hydroxy chalcones 2s and 2t, respectively attached electron-donating groups (5-CH3 and 3-OCH3), the reactions were quite sluggish at −30 °C. When the reaction temperature was increased to −20 °C, the desired products 4s and 4t were obtained in 60% and 87% yields with 80% and 84% ee, respectively (Table 4, entries 4 and 5). On the other hand, for the substrate azlactones 3 bearing both electron-donating groups (4-OCH3, 4-CH3, 3-CH3) or electron-withdrawing groups (4-F, 4-Cl) on the benzene rings at the R3 positions, the corresponding reactions all proceeded smoothly to provide the desired products in 67–85% yields with 90–93% ee (Table 4, entries 6–10). Notably, azlactone 3g with the −tBu alkyl group at the R3 position also afforded the desired product 4z in 54% yield and 72% ee, albeit a higher reaction temperature (−10 °C) was required (Table 4, entry 11). In all the above cases, excellent diastereoselectivities (>20 : 1 dr) were obtained for the desired products. After bromination of compound racemic 4a with 3.0 equiv. of NBS, the N,O-aminal derivative rac-5a was produced in 35% yield (Scheme 5). The structure of rac-5a in the crystalline solid state was finally determined by single crystal X-ray diffraction analysis (Fig. 2), which determined the relative configuration of the N,O-aminal 4 structure. Furthermore, based on the relative configuration obtained by X-ray diffraction of rac-5a, the

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Scheme 5

Fig. 2

Paper

The bromination reaction.

X-ray crystal structure of rac-5a.

Fig. 4 Experimental CD spectra and simulated spectra proving (a) the 1S,2R-4c absolute configuration catalyzed by 1a and (b) the 1R,2Sent-4c absolute configuration catalyzed by 1g.

Fig. 3

Optimization conformations of compound 4c.

experimental CD spectra of compound 4c and the optimization conformations of compound 4c (Fig. 3), the calculation of the CD spectra of a (4c) and b (ent-4c) was carried out using the m062x/6-31g(d) level, as shown in Fig. 4. Electronic excitation energies (nm) and rotational strengths (θ) were calculated for a and b. In order to cover the 230–400 nm range, 50 transitions were calculated. As shown in Fig. 4, the simulated spectra are in good agreement with the spectral data, and the 1S, 2R configuration could be reliably assigned to compound 4c, which was catalyzed by 1a. The 1R, 2S configuration of ent4c was in agreement with that catalyzed by 1g. In order to further understand the absolute structure of N,O-aminal 4 and the activation mechanism between the bifunctional thiourea tertiary amine catalyst and substrates, the transition-state structures, based on the relative configuration obtained by the X-ray diffraction of rac-5a in reactions between

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Fig. 5 Computed transition-state structures and relative free energies (kcal mol−1) of reactions between 2a and 3a catalyzed by 1a.

2a and 3a catalyzed by 1a, were located by DFT [oniom(b3lyp/ 6-31G**:b3lyp/3-21g)] calculations in Fig. 5. Accordingly, TS-bb is 3.28 kcal mol−1 higher in free energy than TS-aa. It is clearly seen that the 1S, 2R stereoisomer was the main product of our asymmetric Michael addition, which is consistent with the results of the calculation of the CD spectra. The hydrogen-

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bonding interaction between the hydrogen atom of the hydroxy group on the o-hydroxy chalcone derivatives 2 and the fluorine atom of the catalyst 1a (O–H⋯F) may account for the origin of the nucleophilic sites of C-4 aryl substituted azlactones for the regioselective Michael addition.

Optical rotations are reported as follows: [α]r.t. D (c in g per 100 mL, solvent). CD spectra were recorded on a circular dichroism spectrometer model 410 at 25 °C in chloroform solutions, using path lengths of 1.0 cm, in the range 220–300 nm; reported Δε values are expressed as L mol−1 cm−1. DFT calculations used Gaussian 03, Reversion B.04.

Conclusions

General procedure for the additive products 4a–4z

In summary, we have developed the regioselective asymmetric Michael addition of azlactones to o-hydroxy chalcone derivatives with complete C-2 regioselectivity by using quinine derived bifunctional thiourea tertiary amine as a catalyst. A series of optically active pseudooxazol-5-ones with all-carbon quaternary stereogenic centers were synthesized in moderate to good yields, excellent diastereoselectivities with moderate to excellent enantioselectivities. It was disclosed that the o-hydroxy group on the cinnamenyl group of chalcone derivatives plays a crucial role in the reaction sites for the regioselective Michael addition. In addition, circular dichroism (CD) spectroscopy and density functional theory (DFT) were used to investigate the absolute configuration of N,O-aminals and the corresponding transition-state structure between the bifunctional thiourea tertiary amine catalyst and substrates. Further exploration of the regioselective Michael addition reaction is under way in our laboratory.

Experimental section General information Unless otherwise stated, all reagents were purchased from commercial suppliers and used without further purification. All reactions were carried out in air and using an undistilled solvent, without any precautions to exclude moisture unless otherwise noted. Organic solutions were concentrated under reduced pressure on an EYELA N-1001 rotary evaporator. Reactions were monitored by thin-layer chromatography (TLC) on silica gel precoated glass plates (0.2 ± 0.03 mm thickness, GF-254, particle size 0.01–0.04 mm) from Yantai Chemical Industry Research Institute, P. R. China. Chromatograms were visualized by fluorescence quenching with UV light at 254 nm. Flash column chromatography was performed using silica gel ( particle size 0.04–0.05 mm). 1H and 13C NMR spectra were recorded in DMSO-d6 or CDCl3 on a Varian Inova (400 MHz and 100 MHz, respectively) spectrometer. 1H NMR data are reported as follows: chemical shift (δ, ppm), multiplicity (s = singlet, d = doublet, t = triplet, m = multiplet), coupling constants ( J) and assignment. Data for 13C NMR are reported in terms of chemical shift (δ, ppm). High-resolution mass spectra (HRMS) for all the compounds were determined on a Micromass GCT-TOF mass spectrometer with ESI or CI resource. High performance liquid chromatography (HPLC) was performed on Agilent 1200 Series chromatographs using a Daicel Chiralpak IA or AD-H column (0.46 cm × 25 cm). X-ray data were recorded on a Rigaku Mercury CCD/AFC diffractometer.

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To a stirred solution of o-hydroxy α,β-unsaturated ketones 2a–t (0.1 mmol) and catalyst 1a (0.02 mmol) in m-xylene (1.5 mL) was added azlactone 3a–g (0.2 mmol) at the given temperature. After stirring for about 12 hours, the desired additive product was purified by flash chromatography over silica gel ( petroleum ether/ethyl acetate = 9 : 1–10 : 1, v/v as eluents). (2R,3S)-Methyl 2-benzamido-5-oxo-2,3,5-triphenylpentanoate A. The title compound was isolated by column chromatography in 75% yield; 93% ee, dr > 20/1 [Daicel Chiralcel IA, hexane/i-PrOH (70 : 30), flow rate: 1.0 mL min−1, λ = 254 nm, t (major) = 7.336, t (minor) = 16.812]; [α]26 D = 44.50 (c 0.40, CHCl3); 1H NMR (400 MHz, CDCl3): δ 7.88–7.86 (m, 2H), 7.73–7.71 (m, 2H), 7.53–7.48 (m, 3H), 7.46–7.44 (m, 2H), 7.42–7.38 (m, 4H), 7.33–7.27 (m, 3H), 7.22–7.20 (m, 3H), 7.13–7.10 (m, 2H), 4.80 (dd, J = 4.0, 8.0 Hz, 1H), 3.79 (s, 3H), 3.73–3.71 (m, 2H); 13C NMR (101 MHz, CDCl3) δ 198.55, 171.88, 166.48, 138.96, 138.05, 136.92, 134.59, 133.27, 131.83, 129.38, 128.77, 128.65, 128.51, 128.32, 128.24, 127.98, 127.82, 127.25, 127.17, 68.81, 52.89, 47.69, 41.17; IR (KBr) νmax: 3410.3, 2923.9, 1733.5, 1670.7, 1598.9, 1580.8, 1480.7, 1363.9, 1294.7, 1235.2, 1184.2, 1022.6, 1002.4, 845.4, 798.5, 704.3, 589.1, 529.3 cm−1; HRMS-CI: [M]+ Calcd for C31H27NO4, 477.1940, found: 477.1940. (R)-2-((S)-3-Oxo-1,3-diphenylpropyl)-2,4-diphenyloxazol-5(2H)one B. The title compound was isolated by column chromatography in 20/1 [Daicel Chiralcel AD-H, hexane/i-PrOH (90 : 10), flow rate: 1.0 mL min−1, λ = 254 nm, t (major) = 10.424, t (minor) = 15.143]; [α]26 D = −126.80 (c 0.25, CHCl3); 1H NMR (400 MHz, CDCl3): δ 8.07–8.05 (m, 2H), 7.80–7.78 (m, 2H), 7.74–7.72 (m, 2H), 7.51–7.44 (m, 2H), 7.41–7.34 (m, 7H), 7.26–7.24 (m, 2H), 7.17–7.13 (m, 2H), 7.08–7.04 (m, 1H), 4.52 (dd, J = 4.0, 12.0 Hz, 1H), 3.81 (dd, J = 8.0, 16.0 Hz, 1H), 3.28 (dd, J = 4.0, 16.0 Hz, 1H); 13 C NMR (101 MHz, CDCl3) δ 196.95, 164.23, 155.44, 137.58, 136.79, 136.21, 133.28, 132.38, 129.72, 129.13, 128.76, 128.65, 128.62, 128.52, 128.31, 128.26, 128.05, 127.71, 126.59, 107.31, 50.75, 38.59; IR (KBr) νmax: 3446.1, 2927.0, 2850.1, 1778.8, 1684.3, 1655.5, 1634.9, 1384.4, 1267.9, 1171.8, 1005.3, 960.5, 749.1, 688.2, 531.3 cm−1; HRMS-ESI: [M + H]+ Calcd for C30H24NO3, 446.1678, found: 446.1744. (R)-2-((S)-1-(5-Chloro-2-hydroxyphenyl)-3-oxo-3-phenylpropyl)2,4-diphenyloxazol-5(2H)-one 4a. The title compound was isolated by column chromatography in 75% yield; 90% ee, dr > 20/1 [Daicel Chiralcel AD-H, hexane/i-PrOH (70 : 30), flow rate: 1.0 mL min−1, λ = 254 nm, t (major) = 14.217, t (minor) = 1 10.807]; [α]26 D = +20.40 (c 0.50, CHCl3); H NMR (400 MHz, CDCl3): δ 7.95 (d, J = 8 Hz, 2H), 7.72 (d, J = 8 Hz, 2H), 7.62–7.59 (m, 1H), 7.52–7.38 (m, 10H), 7.30–7.25 (m, 1H), 7.08–7.02

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(m, 2H), 6.87 (s, 1H), 5.44 (d, J = 8 Hz, 1H), 3.68 (d, J = 16 Hz, 1H), 3.54 (dd, J = 8.0, 20.0, 1H); 13C NMR (101 MHz, CDCl3): δ 196.43, 167.51, 166.70, 149.19, 136.08, 134.97, 133.82, 133.36, 132.34, 130.17, 129.39, 129.33, 128.87, 128.76, 128.35, 127.26, 127.06, 126.95, 126.84, 117.99, 64.26, 37.95, 37.46; IR (KBr) νmax: 3415.0, 1779.4, 1684.06, 1599.3, 1580.3, 1512.6, 1480.3, 1447.8, 1408.6, 1220.6, 689.0, 637.1, 619.2 cm−1; HRMS-CI: [M]+ Calcd for C30H22ClNO4, 495.1237, found: 495.1233. (R)-2-((S)-1-(5-Chloro-2-hydroxyphenyl)-3-(4-fluorophenyl)3-oxopropyl)-2,4-diphenyloxazol-5(2H)-one 4b. The title compound was isolated by column chromatography in 78% yield; 91% ee, dr > 20/1 [Daicel Chiralcel AD-H, hexane/i-PrOH (70 : 30), flow rate: 1.0 mL min−1, λ = 254 nm, t (major) = 13.994, t (minor) = 12.423]; [α]26 D = +48.33 (c 0.30, CHCl3); 1 H NMR (400 MHz, CDCl3): δ 7.96–7.88 (m, 2H), 7.71–7.69 (m, 2H), 7.54–7.50 (m, 1H), 7.46–7.40 (m, 4H), 7.36–7.35 (m, 3H), 7.25–7.22 (m, 1H), 7.12–7.04 (m, 3H), 6.96 (s, 1H), 6.73 (s, 1H), 5.38 (dd, J = 4.0, 8.0 Hz, 1H), 3.63 (dd, J = 4.0, 16.0 Hz, 1H), 3.46 (dd, J = 8.0, 16.0 Hz, 1H); 13C NMR (101 MHz, DMSO-d6): δ 195.76, 166.78, 165.33, 165.24 ( J = 250.0 Hz), 163.99, 149.11, 135.31, 133.40, 132.71, 131.78, 131.25 ( J = 10.0 Hz), 128.58, 128.47, 128.36, 128.25, 127.90, 127.75, 127.68, 127.28, 117.54, 115.69 ( J = 22.0 Hz), 62.69, 37.65, 37.15; IR (KBr) νmax: 3414.8, 1779.1, 1683.2, 1598.6, 1580.8, 1480.4, 1299.5, 1071.6, 968.7, 656.6, 593.0 cm−1; HRMS-CI: [M]+ Calcd for C30H21ClFNO4, 513.1143, found: 513.1140. (R)-2-((S)-3-(4-Bromophenyl)-1-(5-chloro-2-hydroxyphenyl)3-oxopropyl)-2,4-diphenyloxazol-5(2H)-one 4c. The title compound was isolated by column chromatography in 98% yield; 96% ee, dr > 20/1 [Daicel Chiralcel AD-H, hexane/i-PrOH (70 : 30), flow rate: 1.0 mL min−1, λ = 254 nm, t (major) = 12.748, t (minor) = 14.229]; [α]26 D = +33.70 (c 0.46, CHCl3); 1 H NMR (400 MHz, CDCl3): δ 7.76 (d, J = 8.0 Hz, 2H), 7.69 (d, J = 8.0 Hz, 2H), 7.57–7.49 (m, 3H), 7.48–7.39 (m, 4H), 7.35–7.30 (m, 3H), 7.24–7.22 (m, 1H), 7.04 (d, J = 8.0 Hz, 1H), 6.94 (s, 1H), 6.76 (s, 1H), 5.38 (d, J = 8.0 Hz, 1H), 3.62 (d, J = 16.0 Hz, 1H), 3.44 (dd, J = 8.0, 16.0 Hz, 1H); 13C NMR (101 MHz, DMSO-d6): δ 196.42, 166.74, 165.28, 149.03, 135.19, 134.91, 133.35, 131.78, 131.72, 130.19, 128.58, 128.47, 128.36, 128.23, 127.85, 127.65, 127.44, 127.20, 117.54, 62.67, 37.60, 36.96; IR (KBr) νmax: 3380.8, 1766.6, 1685.4, 1670.0, 1600.9, 1584.6, 1517.8, 1417.5, 1400.5, 984.0, 834.7, 730.6, 653.1 cm−1; HRMS-CI: [M]+ Calcd for C30H21ClBrNO4, 573.0342, found: 575.0322. (R)-2-((S)-1-(5-Chloro-2-hydroxyphenyl)-3-(4-iodophenyl)-3oxopropyl)-2,4-diphenyloxazol-5(2H)-one 4d. The title compound was isolated by column chromatography in 99% yield; >99% ee, dr > 20/1 [Daicel Chiralcel AD-H, hexane/i-PrOH (70 : 30) , flow rate: 1.0 mL min−1, λ = 254 nm, t (major) = 1 13.571]; [α]26 D = +25.71 (c 0.16, CHCl3); H NMR (400 MHz, DMSO-d6): δ 9.17 (s, 1H), 7.88 (d, J = 8.0 Hz, 2H), 7.72 (d, J = 8.0 Hz, 2H), 7.67 (d, J = 8.0 Hz, 2H), 7.58–7.51 (m, 3H), 7.44–7.40 (m, 2H), 7.37–7.34 (m, 4H), 7.21 (s, 1H), 7.13 (d, J = 8.0 Hz, 1H), 5.07 (d, J = 4.0 Hz, 1H), 3.67 (d, J = 12.0 Hz, 1H), 3.60 (d, J = 16.0 Hz, 1H); 13C NMR (101 MHz, DMSO-d6):

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δ 196.75, 166.72, 165.27, 149.03, 137.61, 135.19, 133.34, 131.78, 129.87, 128.61, 128.59, 128.47, 128.36, 128.24, 128.17, 127.84, 127.64, 127.44, 127.20, 117.54, 102.29, 62.64, 37.53, 36.96; IR (KBr) νmax: 3379.2, 1766.7, 1684.8, 1670.0, 1580.7, 1296.2, 1220.6, 1122.1, 1001.8, 982.6, 729.9, 687.9 cm−1; HRMS-CI: [M]+ Calcd for C30H21ClINO4, 621.0204, found: 621.0206. (R)-2-((S)-1-(5-Chloro-2-hydroxyphenyl)-3-oxo-3-(4-(trifluoromethyl)phenyl)propyl)-2,4-diphenyloxazol-5(2H)-one 4e. The title compound was isolated by column chromatography in 89% yield, 95% ee, dr > 20/1 [Daicel Chiralcel AD-H, hexane/ i-PrOH (70 : 30), flow rate: 1.0 mL min−1, λ = 254 nm, t (major) = 9.552, t (minor) = 13.048]; [α]26 D = +20.88 (c 0.45, CHCl3); 1 H NMR (400 MHz, CDCl3): δ 8.00 (d, J = 8.0 Hz, 2H), 7.70–7.66 (m, 4H), 7.51–7.49 (m, 1H), 7.42–7.35 (m, 7H), 7.23 (s, 1H), 7.05 (d, J = 4.0 Hz, 1H), 6.94 (s, 1H), 6.80 (s, 1H), 5.42 (d, J = 8.0 Hz, 1H), 3.70 (d, J = 16.0 Hz, 1H), 3.50 (dd, J = 8.0, 20.0 Hz, 1H); 13C NMR (101 MHz, DMSO-d6): δ 196.73, 166.80, 165.31, 149.02, 139.12, 135.11, 133.37, 131.80, 129.04, 128.64, 128.51, 128.42, 128.34, 128.25, 127.86, 127.67, 127.62, 127.17, 125.65, 125.62, 117.59, 62.75, 37.96, 36.78; IR (KBr) νmax: 3384.3, 1780.1, 1691.3, 1662.6, 1602.0, 1580.9, 1511.7, 1384.3, 1410.27, 1014.4, 989.5, 780.41, 647.5 cm−1; HRMS-CI: [M]+ Calcd for C31H21ClF3NO4, 563.1111, found: 563.1110. (R)-2-((S)-3-(4-(tert-Butyl)phenyl)-1-(5-chloro-2-hydroxyphenyl)3-oxopropyl)-2,4-diphenyloxazol-5(2H)-one 4f. The title compound was isolated by column chromatography in 96% yield, 90% ee, dr > 20/1 [Daicel Chiralcel AD-H, hexane/i-PrOH (70 : 30), flow rate: 1.0 mL min−1, λ = 254 nm, t (major) = 8.398, t (minor) = 7.545]; [α]26 D = +24.08 (c 0.49, CHCl3); 1 H NMR (400 MHz, CDCl3): δ 7.85 (d, J = 8.0 Hz, 2H), 7.69–7.67 (m, 2H), 7.52–7.50 (m, 1H), 7.48–7.47 (m, 1H), 7.46–7.43 (m, 2H), 7.42–7.41 (m, 1H), 7.40–7.37 (m, 2H), 7.36–7.33 (m, 3H), 7.22 (dd, J = 4.0, 12.0 Hz, 1H), 7.04 (d, J = 8.0 Hz, 1H), 7.00 (dd, J = 4.0, 8.0 Hz, 1H), 6.71 (s, 1H), 5.36 (dd, J = 4.0, 8.0 Hz, 1H), 3.60 (dd, J = 4.0, 16.0 Hz 1H), 3.48 (dd, J = 4.0, 16.0 Hz, 1H), 1.32 (s, 9H); 13C NMR (101 MHz, DMSO-d6): δ 196.63, 166.67, 165.28, 156.67, 149.10, 135.37, 133.44, 133.33, 131.77, 128.55, 128.43, 128.32, 128.23, 128.11, 127.86, 127.77, 127.65, 127.30, 125.48, 117.50, 62.56, 38.14, 37.70, 34.79, 30.70; IR (KBr) νmax: 3385.7, 2959.1, 1765.4, 1671.1, 1604.7, 1225.3, 1145.4, 1122.8, 985.4, 651.3, 570.6 cm−1; HRMS-CI: [M]+ Calcd for C34H30ClNO4, 551.1863, found: 551.1858. (R)-2-((S)-3-([1,1′-Biphenyl]-4-yl)-1-(5-chloro-2-hydroxyphenyl)3-oxopropyl)-2,4-diphenyloxazol-5(2H)-one 4g. The title compound was isolated by column chromatography in 92% yield; 97% ee, dr > 20/1 [Daicel Chiralcel AD-H, hexane/i-PrOH (70 : 30), flow rate: 1.0 mL min−1, λ = 254 nm, t (major) = 18.319, t (minor) = 22.501]; [α]26 D = +30.05 (c 0.48, CHCl3); 1 H NMR (400 MHz, CDCl3): δ 7.98 (d, J = 8.0 Hz, 2H), 7.70 (d, J = 8.0 Hz, 2H), 7.65–7.58 (m, 4H), 7.52–7.45 (m, 5H), 7.41–7.35 (m, 6H), 7.23 (dd, J = 4.0, 12.0 Hz, 1H), 7.06–7.03 (m, 2H), 6.76 (s, 1H), 5.41 (d, J = 8.0 Hz, 1H), 3.67 (d, J = 16.0 Hz, 1H), 3.53 (dd, J = 8.0, 16.0 Hz, 1H); 13C NMR (101 MHz, DMSO-d6): δ 196.72, 166.74, 165.32, 149.09, 144.94,

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138.79, 135.30, 134.74, 133.37, 131.81, 129.10, 128.93, 128.61, 128.50, 128.38, 128.27, 128.22, 127.89, 127.78, 127.68, 127.27, 127.00, 126.89, 117.56, 99.53, 62.66, 37.74, 37.13; IR (KBr) νmax: 3377.7, 1770.6, 1673.1, 1603.1, 1580.4, 1560.0, 1261.5, 983.1, 697.4, 561.8 cm−1; HRMS-ESI: [M + H]+ Calcd for C36H27ClNO4, 572.1550, found: 572.1606. (R)-2-((S)-1-(5-Chloro-2-hydroxyphenyl)-3-oxo-3-(4-pentylphenyl)propyl)-2,4-diphenyloxazol-5(2H)-one 4h. The title compound was isolated by column chromatography in 99% yield; 91% ee, dr > 20/1 [Daicel Chiralcel AD-H, hexane/i-PrOH (70 : 30), flow rate: 1.0 mL min−1, λ = 254 nm, t (major) = 1 9.991, t (minor) = 8.133]; [α]26 D = +26.17 (c 0.53, CHCl3); H NMR (400 MHz, CDCl3): δ 7.85 (d, J = 8.0 Hz, 2H), 7.72–7.70 (m, 2H), 7.53–7.48 (m, 3H), 7.44–7.37 (m, 4H), 7.24 (d, J = 8.0 Hz, 3H), 7.04 (d, J = 8.0 Hz, 1H), 7.03–7.01 (m, 1H), 6.72 (s, 1H), 5.38 (dd, J = 4.0, 8.0 Hz, 1H), 3.62 (dd, J = 4.0, 20.0 Hz, 1H), 3.50 (dd, J = 8.0, 16.0 Hz, 1H), 2.66 (t, J = 8.0 Hz, 2H), 1.67–1.59 (m, 2H), 1.36–1.29 (m, 4H), 0.91 (t, J = 8.0 Hz, 3H); 13 C NMR (101 MHz, DMSO-d6): δ 196.67, 166.75, 165.33, 149.16, 148.82, 135.43, 133.73, 133.38, 131.82, 128.65, 128.60, 128.48, 128.36, 128.32, 128.28, 128.19, 127.91, 127.82, 127.69, 127.36, 117.54, 62.59, 37.70, 37.33, 35.06, 30.78, 30.25, 21.93, 13.88; IR (KBr) νmax: 3367.2, 2954.5, 2927.7, 2856.4, 1780.6, 1682.3, 1604.8, 1580.4, 1092.3, 969.0, 657.4, 559.3 cm−1; HRMS-CI: [M]+ Calcd for C35H32ClNO4, 565.2020, found: 565.2007. (R)-2-((S)-1-(5-Chloro-2-hydroxyphenyl)-3-(3-fluorophenyl)3-oxopropyl)-2,4-diphenyloxazol-5(2H)-one 4i. The title compound was isolated by column chromatography in 72% yield; 93% ee, dr > 20/1 [Daicel Chiralcel AD-H, hexane/i-PrOH (70 : 30), flow rate: 1.0 mL min−1, λ = 254 nm, t (major) = 15.412, t (minor) = 10.609]; [α]26 D = +26.32 (c 0.48, CHCl3); 1 H NMR (400 MHz, CDCl3): δ 7.72–7.69 (m, 3H), 7.59 (d, J = 8.0 Hz, 1H), 7.54–7.50 (m, 1H), 7.43–7.35 (m, 7H), 7.29–7.22 (m, 2H), 7.05 (d, J = 8.0 Hz, 1H), 6.93 (s, 1H), 6.73 (s, 1H), 5.41 (d, J = 8.0 Hz, 1H), 3.64 (dd, J = 4.0, 20.0 Hz, 1H), 3.46 (dd, J = 8.0, 20.0 Hz, 1H); 13C NMR (101 MHz, DMSO-d6): δ 196.32, 166.80, 165.31, 162.13 ( J = 244.0 Hz), 149.04, 143.65, 138.18, 135.13, 133.38, 131.83, 130.89, 128.65, 128.57, 128.51, 128.41, 128.28, 127.90, 127.68, 127.19, 124.41, 120.46 ( J = 21.0 Hz), 117.60, 114.78 ( J = 22.0 Hz), 62.76, 37.77, 36.95; IR (KBr) νmax: 3393.4, 1779.1, 1685.8, 1601.3, 1588.5, 1512.8, 1444.9, 1001.9, 966.8, 639.2, 520.9 cm−1; HRMS-CI: [M]+ Calcd for C30H21ClFNO4, 513.1143, found: 513.1136. (R)-2-((S)-1-(5-Chloro-2-hydroxyphenyl)-3-(3-chlorophenyl)3-oxopropyl)-2,4-diphenyloxazol-5(2H)-one 4j. The title compound was isolated by column chromatography in 81% yield, 81% ee, dr > 20/1 [Daicel Chiralcel AD-H, hexane/i-PrOH (70 : 30), flow rate: 1.0 mL min−1, λ = 254 nm, t (major) = 16.262, t (minor) = 10.459]; [α]26 D = +37.5 (c 0.40, CHCl3); 1 H NMR (400 MHz, CDCl3): δ 7.87–7.86 (m, 1H), 7.79 (d, J = 8.0 Hz, 1H), 7.71–7.69 (m, 2H), 7.55–7.50 (m, 2H), 7.45–7.35 (m, 7H), 7.24 (dd, J = 4.0, 8.0 Hz, 1H), 7.05 (d, J = 8.0 Hz, 1H), 6.94–6.93 (m, 1H), 6.73 (s, 1H), 5.41 (dd, J = 4.0 Hz, J = 8.0 Hz, 1H), 3.63 (dd, J = 4.0, 16.0 Hz, 1H), 3.46 (dd, J = 4.0, 16.0 Hz, 1H); 13C NMR (101 MHz, DMSO): δ 196.28, 166.75, 165.29, 149.00, 137.79, 135.12, 133.63, 133.38, 133.19, 131.80, 130.65,

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Organic & Biomolecular Chemistry

128.64, 128.51, 128.38, 128.34, 128.25, 127.97, 127.94, 127.68, 127.15, 126.77, 117.57, 62.77, 37.71, 36.78; IR (KBr) νmax: 3384.0, 1767.5, 1673.5, 1518.1, 1444.6, 1190.8, 1001.1, 943.9, 786.8, 698.9, 574.9 cm−1; HRMS-CI: [M]+ Calcd for C30H21Cl2NO4, 529.0848, found: 529.0835. (R)-2-((S)-1-(5-Chloro-2-hydroxyphenyl)-3-(2-fluorophenyl)3-oxopropyl)-2,4-diphenyloxazol-5(2H)-one 4k. The title compound was isolated by column chromatography in 96% yield, 89% ee, dr > 20/1 [Daicel Chiralcel AD-H, hexane/i-PrOH (70 : 30), flow rate: 1.0 mL min−1, λ = 210 nm, t (major) = 12.729, t (minor) = 11.649]; [α]26 D = +10.40 (c 0.50, CHCl3); 1 H NMR (400 MHz, CDCl3): δ 7.82 (td, J = 4.0, 8.0 Hz, 1H), 7.76–7.74 (m, 2H), 7.54–7.51 (m, 2H), 7.45–7.38 (m, 4H), 7.35–7.33 (m, 3H), 7.24–7.10 (m, 3H), 7.06 (d, J = 8.0 Hz, 1H), 6.88–6.87 (m, 1H), 6.69 (s, 1H), 5.50 (d, J = 8.0 Hz, 1H), 3.70 (dt, J = 4.0, 20.0 Hz, 1H), 3.47 (ddd, J = 4.0, 12.0, 20.0 Hz, 1H); 13 C NMR (101 MHz, DMSO-d6): δ 195.12, 166.85, 165.37, 161.16 ( J = 253.0 Hz), 159.90, 149.16, 135.48, 135.39, 135.34, 133.36, 131.80, 130.28, 128.61, 128.45, 128.25, 127.74 ( J = 10.0 Hz), 127.56, 127.41, 124.76, 124.64, 117.55, 116.91 ( J = 23 Hz), 62.56, 42.27, 37.26; IR (KBr) νmax: 3423.7, 1780.7, 1684.7, 1609.1, 1580.0, 1511.3, 1479.9, 1410.2, 1384.4, 1280.5, 1239.3, 1001.7, 967.7, 869.4, 540.1 cm−1; HRMS-CI: [M]+ Calcd for C30H21ClFNO4, 513.1143, found: 513.1137. (R)-2-((S)-1-(5-Chloro-2-hydroxyphenyl)-3-(3,4-difluorophenyl)3-oxopropyl)-2,4-diphenyloxazol-5(2H)-one 4l. The title compound was isolated by column chromatography in 76% yield; 89% ee, dr > 20/1 [Daicel Chiralcel AD-H, hexane/i-PrOH (70 : 30), flow rate: 1.0 mL min−1, λ = 210 nm, t (major) = 13.436, t (minor) = 11.258]; [α]26 D = +25.71 (c 0.28, CHCl3); 1 H NMR (400 MHz, CDCl3): δ 7.71–7.70 (m, 4H), 7.52–7.36 (m, 8H), 7.26–7.23 (m, 2H), 7.05 (d, J = 8.0 Hz, 1H), 6.92 (s, 1H), 6.77 (s, 1H), 5.40 (d, J = 4.0 Hz, 1H), 3.62 (d, J = 16.0 Hz, 1H), 3.43 (dd, J = 8.0, 16.0 Hz, 1H); 13C NMR (101 MHz, DMSO-d6) δ 195.21, 166.80, 165.33, 149.05, 135.10, 133.46, 133.37, 131.83, 128.62, 128.49, 128.42, 128.27, 127.90, 127.69, 127.19, 126.22, 126.14, 126.09, 117.99, 117.81, 117.75, 117.59, 117.48, 62.80, 37.54, 37.01; IR (KBr) νmax: 3423.9, 1779.0, 1685.9, 1654.5, 1610.3, 1581.0, 1516.1, 1480.9, 1447.3, 1430.8, 1284.0, 1239.6, 1001.9, 968.5, 657.1, 561.3 cm−1; HRMS-CI: [M]+ Calcd for C30H20ClF2NO4, 531.1049, found: 531.1041. (R)-2-((S)-1-(5-Chloro-2-hydroxyphenyl)-3-(furan-2-yl)-3-oxopropyl)-2,4-diphenyloxazol-5(2H)-one 4m. The title compound was isolated by column chromatography in 95% yield, 90% ee, dr > 20/1 [Daicel Chiralcel AD-H, hexane/i-PrOH (70 : 30), flow rate: 1.0 mL min−1, λ = 254 nm, t (major) = 19.063, t (minor) = 1 17.389]; [α]26 D = +24.00 (c 0.42, CHCl3); H NMR (400 MHz, CDCl3): δ 7.73 (d, J = 8.0 Hz, 2H), 7.53–7.50 (m, 1H), 7.46–7.39 (m, 5H), 7.35–7.34 (m, 3H), 7.24–7.22 (m, 1H), 7.15 (d, J = 4.0 Hz, 1H), 7.07–7.04 (m, 2H), 6.75 (s, 1H), 6.48 (s, 1H), 5.38 (d, J = 4.0 Hz, 1H), 3.47 (d, J = 4.0, 16.0 Hz, 1H), 3.37 (dd, J = 8.0, 16.0 Hz, 1H); 13C NMR (101 MHz, DMSO-d6): δ 185.41 166.73, 165.19, 151.33, 149.11, 148.09, 135.29, 133.31, 131.81, 128.89, 128.58, 128.43, 128.26, 128.19, 127.84, 127.64, 127.50, 127.30, 118.97, 117.55, 112.68, 62.40, 37.41, 37.22; IR (KBr)

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νmax: 3370.0, 1778.9, 1671.0, 1601.9, 1568.1, 1513.8, 1480.6, 1466.7, 1447.3, 1409.4, 1286.5, 1200.3, 1002.2, 940.9, 653.1, 515.8 cm−1; HRMS-CI: [M]+ Calcd for C28H20ClNO5, 485.1030, found: 485.1024. (R)-2-((S)-1-(5-Chloro-2-hydroxyphenyl)-3-oxo-3-(thiophen2-yl)propyl)-2,4-diphenyloxazol-5(2H)-one 4n. The title compound was isolated by column chromatography in 60% yield, 90% ee, dr > 20/1 [Daicel Chiralcel AD-H, hexane/i-PrOH (70 : 30), flow rate: 1.0 mL min−1, λ = 254 nm, t (major) = 18.914, t (minor) = 13.918]; [α]26 D = +8.16 (c 0.24, CHCl3); 1 H NMR (400 MHz, CDCl3): δ 7.68–7.64 (m, 4H), 7.46–7.22 (m, 9H), 7.09–7.06 (m, 3H), 6.74 (s, 1H), 5.35 (d, J = 4.0 Hz, 1H), 3.56 (d, J = 16.0 Hz, 1H), 3.41 (dd, J = 8.0, 16.0 Hz, 1H); 13 C NMR (101 MHz, DMSO-d6) δ 190.08, 166.72, 165.14, 149.12, 142.75, 135.52, 135.29, 134.00, 133.33, 131.80, 128.79, 128.55, 128.42, 128.26, 128.08, 127.86, 127.63, 127.53, 127.33, 117.55, 62.45, 37.99, 37.66; IR (KBr) νmax: 3384.6, 2922.0, 1778.7, 1660.0, 1579.3, 1515.2, 1277.5, 1181.3, 965.7, 821.0, 642.2, 560.9, 492.6 cm−1; HRMS-CI: [M]+ Calcd for C28H20ClNO4S, 501.0802, found: 501.0809. (R)-2-((R)-1-(2-Hydroxyphenyl)-3-oxobutyl)-2,4-diphenyloxazol5(2H)-one 4o. The title compound was isolated by column chromatography in 25% yield; 12% ee, dr > 20/1 [Daicel Chiralcel AD-H, hexane/i-PrOH (70 : 30), flow rate: 1.0 mL min−1, λ = 210 nm, t (major) = 10.852, t (minor) = 15.559]; [α]26 D = −0.36 (c 0.6, CH2Cl2); 1H NMR (400 MHz, CDCl3): δ 7.74–7.72 (m, 2H), 7.54–7.50 (m, 1H), 7.44–7.42 (m, 2H), 7.39–7.37 (m, 1H), 7.29–7.25 (m, 4H), 7.10–7.05 (m, 2H), 6.97 (d, J = 8.0 Hz, 1H), 6.75 (s, 1H), 5.20 (dd, J = 4.0, 8.0 Hz, 1H), 3.11 (dd, J = 4.0, 16.0 Hz 1H), 2.93 (dd, J = 12.0, 16.0 Hz, 1H), 2.18 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 206.18, 167.77, 167.17, 150.58, 134.91, 133.73, 132.36, 129.22, 129.11, 129.02, 128.88, 127.24, 127.06, 126.37, 125.20, 124.81, 116.70, 64.76, 42.68, 37.95, 29.77; IR (KBr) νmax: 3446.9, 3067.9, 2859.7, 1770.4, 1719.5, 1647.2, 1575.4, 1516.0, 1484.4, 1450.6, 1384.3, 1261.2, 1210.3, 1067.2, 988.9, 761.9, 697.1, 473.6 cm−1; HRMS-CI: [M]+ Calcd for C25H21NO4, 399.1471, found: 399.1481. (R)-2-((S)-1-(2-Hydroxyphenyl)-3-oxo-3-phenylpropyl)-2,4diphenyloxazol-5(2H)-one 4p. The title compound was isolated by column chromatography in 73% yield; 81% ee, dr > 20/1 [Daicel Chiralcel AD-H, hexane/i-PrOH (70 : 30), flow rate: 1.0 mL min−1, λ = 254 nm, t (major) = 20.648, t (minor) = 1 18.834]; [α]26 D = +83.28 (c 0.33, CHCl3); H NMR (400 MHz, CDCl3): δ 7.91 (d, J = 8.0 Hz, 2H), 7.68 (d, J = 8.0 Hz, 2H), 7.58–7.48 (m, 5H), 7.45–7.37 (m, 5H), 7.33–7.30 (m, 3H), 7.09 (d, J = 8.0 Hz, 1H), 7.05 (d, J = 8.0 Hz, 1H), 6.77 (s, 1H), 5.31 (dd, J = 4.0, 8.0 Hz, 1H), 3.58–3.52 (m, 2H); 13C NMR (101 MHz, DMSO-d6): δ 197.26, 166.72, 165.93, 150.16, 136.04, 135.54, 133.54, 131.72, 128.75, 128.46, 128.36, 128.20, 128.07, 127.87, 127.71, 127.21, 125.50, 124.63, 115.67, 99.52, 63.04, 37.88, 36.98; IR (KBr) νmax: 3416.2, 2923.2, 1762.3, 1667.4, 1599.1, 1513.9, 1482.5, 1146.5, 1001.3, 971.2, 689.3, 562.3 cm−1; HRMS-CI: [M]+ Calcd for C30H23NO4, 461.1627, found: 461.1620. (R)-2-((S)-3-(4-Chlorophenyl)-1-(2-hydroxyphenyl)-3-oxopropyl)2,4-diphenyloxazol-5(2H)-one 4q. The title compound was

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isolated by column chromatography in 87% yield, 84% ee, dr > 20/1 [Daicel Chiralcel AD-H, hexane/i-PrOH (70 : 30), flow rate: 1.0 mL min−1, λ = 254 nm, t (major) = 16.638, t (minor) = 1 20.411]; [α]26 D = +26.47 (c 0.34, CHCl3); H NMR (400 MHz, CDCl3): δ 7.83 (d, J = 8.0 Hz, 2H), 7.67 (d, J = 4.0 Hz, 2H), 7.48–7.32 (m, 11H), 7.10–7.00 (m, 2H), 6.81 (s, 1H), 5.31 (d, J = 8.0 Hz, 1H), 3.62–3.47 (m, 2H); 13C NMR (101 MHz, DMSO-d6): δ 196.33, 166.73, 165.91, 150.12, 138.45, 135.42, 134.70, 133.53, 131.71, 130.04, 128.83, 128.47, 128.36, 128.19, 127.86, 127.70, 127.18, 125.41, 124.65, 115.68, 63.07, 37.77, 36.85; IR (KBr) νmax: 3377.0, 2922.3, 1759.1, 1670.2, 1589.2, 1514.2, 1400.5, 1011.7, 948.1, 756.4, 694.8, 564.0 cm−1; HRMS-CI: [M]+ Calcd for C30H22ClNO4, 495.1237, found: 495.1237. (R)-2-((S)-3-(4-Bromophenyl)-1-(2-hydroxyphenyl)-3-oxopropyl)2,4-diphenyloxazol-5(2H)-one 4r. The title compound was isolated by column chromatography in 94% yield; 80% ee, dr > 20/1 [Daicel Chiralcel AD-H, hexane/i-PrOH (70 : 30), flow rate: 1.0 mL min−1, λ = 254 nm, t (major) = 17.483, t (minor) = 1 22.023]; [α]26 D = +18.60 (c 0.43, CHCl3); H NMR (400 MHz, CDCl3): δ 7.75 (d, J = 8.0 Hz, 2H), 7.68 (d, J = 4.0 Hz, 2H), 7.55 (d, J = 8.0 Hz, 2H), 7.50–7.46 (m, 3H), 7.42–7.38 (m, 2H), 7.33–7.31 (m, 3H), 7.28–7.25 (m, 1H), 7.10–7.04 (m, 2H), 6.99 (d, J = 8.0 Hz, 1H), 6.78 (s, 1H), 5.31 (dd, J = 4.0, 8.0 Hz, 1H), 3.60 (dd, J = 4.0, 16.0 Hz, 1H), 3.50 (dd, J = 8 Hz, J = 16 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 196.08, 167.39, 167.15, 150.63, 135.18, 134.99, 133.55, 132.32, 132.15, 129.85, 129.19, 129.04, 128.95, 128.79, 127.24, 127.15, 126.63, 125.17, 124.80, 116.76, 64.45, 38.47, 37.63; IR (KBr) νmax: 3377.3, 1759.5, 1684.4, 1671.1, 1601.2, 1515.1, 1341.0, 1187.2, 1008.9, 983.9, 768.7, 561.9 cm−1; HRMS-CI: [M]+ Calcd for C30H22BrNO4, 539.0732, found: 539.0725. (R)-2-((S)-1-(2-Hydroxy-5-methylphenyl)-3-oxo-3-phenylpropyl)2,4-diphenyloxazol-5(2H)-one 4s. The title compound was isolated by column chromatography in 65% yield; 80% ee, dr > 20/1 [Daicel Chiralcel IA, hexane/i-PrOH (70 : 30), flow rate: 1.0 mL min−1, λ = 254 nm, t (major) = 17.141, t (minor) = 1 14.905]; [α]26 D = +41.60 (c 0.50, CHCl3); H NMR (400 MHz, DMSO-d6): δ 7.90 (d, J = 8.0 Hz, 2H), 7.67 (d, J = 8.0 Hz, 2H), 7.57–7.47 (m, 4H), 7.44–7.39 (m, 4H), 7.34–7.32 (m, 3H), 7.05–6.96 (m, 2H), 6.81 (s, 1H), 6.75 (s, 1H), 5.25 (dd, J = 4.0, 8.0 Hz, 1H), 3.61 (dd, J = 4.0, 16.0 Hz, 1H), 3.51 (dd, J = 8.0, 16.0 Hz, 1H), 2.23 (s, 3H); 13C NMR (101 MHz, DMSO-d6) δ 197.29, 166.74, 166.06, 148.06, 136.11, 135.57, 133.60, 133.50, 131.68, 128.74, 128.46, 128.45, 128.39, 128.20, 128.08, 127.88, 127.72, 127.33, 125.24, 115.48, 63.16, 37.91, 36.63, 20.53; IR (KBr) νmax: 3423.7, 3059.4, 2919.8, 1773.2, 1683.0, 1598.9, 1579.4, 1447.5, 1412.8, 1253.9, 1217.2, 1142.1, 1001.6, 972.4, 611.5, 562.0 cm−1; HRMS-CI: [M]+ Calcd for C31H25NO4, 475.1784, found: 475.1791. (R)-2-((S)-1-(2-Hydroxy-3-methoxyphenyl)-3-oxo-3-phenylpropyl)-2,4-diphenyloxazol-5(2H)-one 4t. The title compound was isolated by column chromatography in 87% yield; 84% ee, dr > 20/1 [Daicel Chiralcel IA, hexane/i-PrOH (70 : 30), flow rate: 1.0 mL min−1, λ = 254 nm, t (major) = 20.697, t (minor) = 1 32.395]; [α]26 D = −4.90 (c 0.53, CHCl3); H NMR (400 MHz, DMSO-d6): δ 9.15 (s, 1H), 7.92 (d, J = 4.0 Hz, 2H), 7.77

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(d, J = 4.0 Hz, 2H), 7.62–7.49 (m, 6H), 7.43–7.35 (m, 5H), 7.06–7.01 (m, 2H), 6.63 (s, 1H), 5.18 (s, 1H), 3.79 (s, 3H), 3.64 (s, 2H); 13C NMR (101 MHz, DMSO-d6) δ 197.26, 166.72, 165.66, 146.47, 138.85, 136.06, 135.39, 133.59, 131.72, 128.78, 128.52, 128.42, 128.22, 128.07, 127.90, 127.74, 126.48, 124.73, 118.14, 111.74, 62.97, 55.90, 37.82, 36.70; IR (KBr) νmax: 3361.7, 3058.7, 3003.6, 2852.2, 1770.8, 1685.6, 1616.6, 1580.7, 1510.5, 1447.2, 1283.7, 1126.4, 1001.1, 801.0, 763.9, 650.9, 551.0 cm−1; HRMS-CI: [M]+ Calcd for C31H25NO5, 491.1733, found: 491.1720. (R)-2-((S)-1-(5-Chloro-2-hydroxyphenyl)-3-oxo-3-phenylpropyl)2-(4-fluorophenyl)-4-phenyloxazol-5(2H)-one 4u. The title compound was isolated by column chromatography in 75% yield; 92% ee, dr > 20/1 [Daicel Chiralcel IA, hexane/i-PrOH (70 : 30), flow rate: 1.0 mL min−1, λ = 254 nm, t (major) = 14.650, 1 t (minor) = 10.781]; [α]26 D = +45.88 (c 0.34, CHCl3); H NMR (400 MHz, CDCl3): δ 7.91 (d, J = 8.0 Hz, 2H), 7.71 (dd, J = 4.0, 8.0 Hz, 2H), 7.59–7.56 (m, 1H), 7.45–7.42 (m, 4H), 7.36–7.34 (m, 3H), 7.23 (dd, J = 4.0, 12.0 Hz, 1H), 7.09–7.03 (m, 3H), 6.97 (s, 1H), 6.68 (s, 1H), 5.40 (dd, J = 4.0, 8.0 Hz, 1H), 3.63 (dd, J = 4.0, 16.0 Hz, 1H), 3.51 (dd, J = 8.0, 16.0 Hz, 1H); 13C NMR (101 MHz, DMSO-d6) δ 197.19, 165.70, 165.32, 164.19 ( J = 248.0 Hz), 148.98, 135.92, 135.06, 133.58, 130.44 (d, J = 9.0 Hz), 129.79 (d, J = 3.0 Hz), 128.71, 128.63, 128.48, 128.37, 128.25, 128.16, 127.85, 127.68, 127.11, 117.58, 115.24 (d, J = 21.0 Hz), 62.80, 37.55, 36.91; IR (KBr) νmax: 3414.6, 2923.3, 1777.8, 1684.4, 1602.8, 1526.6, 1481.3, 1158.3, 1001.6, 944.6, 762.7, 560.5 cm−1; HRMS-CI: [M]+ Calcd for C30H21ClFNO4, 513.1143, found: 513.1141. (R)-2-((S)-1-(5-Chloro-2-hydroxyphenyl)-3-oxo-3-phenylpropyl)2-(4-chlorophenyl)-4-phenyloxazol-5(2H)-one 4v. The title compound was isolated by column chromatography in 76% yield; 93% ee, dr > 20/1 [Daicel Chiralcel IA, hexane/i-PrOH (70 : 30), flow rate: 1.0 mL min−1, λ = 254 nm, t (major) = 19.811, 1 t (minor) = 12.582]; [α]26 D = +40.00 (c 0.31, CHCl3); H NMR (400 MHz, CDCl3): δ 7.91 (d, J = 8 Hz, 2H), 7.62 (d, J = 8 Hz, 2H), 7.57 (d, J = 8 Hz, 1H), 7.45–7.42 (m, 4H), 7.37–7.35 (m, 5H), 7.24–7.22 (m, 1H), 7.02 (d, J = 8 Hz, 1H), 6.97 (s, 1H), 6.70 (s, 1H), 5.39 (d, J = 4 Hz, 1H), 3.62 (d, J = 16 Hz, 1H), 3.51 (dd, J = 8 Hz, J = 8 Hz, 1H); 13C NMR (101 MHz, DMSO-d6) δ 197.18, 165.77, 165.29, 148.94, 136.68, 135.92, 134.94, 133.58, 132.04, 130.57, 129.64, 128.71, 128.68, 128.51, 128.38, 128.36, 128.16, 127.86, 127.66, 127.06, 117.61, 62.88, 37.50, 36.76; IR (KBr) νmax: 3355.5, 2924.0, 1765.6, 1682.6, 1672.4, 1594.9, 1527.4, 1308.6, 1296.4, 1001.0, 969.3, 690.1, 563.0, 527.3 cm−1; HRMS-CI: [M]+ Calcd for C30H21ClFNO4, 529.0848, found: 529.0843. (R)-2-((S)-1-(5-Chloro-2-hydroxyphenyl)-3-oxo-3-phenylpropyl)2-(4-methoxyphenyl)-4-phenyloxazol-5(2H)-one 4w. The title compound was isolated by column chromatography in 85% yield; 92% ee, dr > 20/1 [Daicel Chiralcel IA, hexane/i-PrOH (70 : 30), flow rate: 1.0 mL min−1, λ = 254 nm, t (major) = 17.393, t (minor) = 24.283]; [α]26 D = +20.43 (c 0.46, CHCl3); 1 H NMR (400 MHz, CDCl3): δ 7.91 (dd, J = 4.0, 12.0 Hz, 2H), 7.67 (d, J = 8.0 Hz, 2H), 7.57 (t, J = 8.0 Hz, 1H), 7.47–7.41 (m, 4H), 7.37–7.34 (m, 3H), 7.22 (dd, J = 4.0, 8.0 Hz, 1H), 7.04

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Organic & Biomolecular Chemistry

(d, J = 8 Hz, 1H), 6.97 (s, 1H), 6.89 (d, J = 8.0 Hz, 2H), 6.61 (s, 1H), 3.83 (s, 3H), 3.64 (dd, J = 4.0, 16.0 Hz, 1H), 3.47 (dd, J = 8.0, 16.0 Hz, 1H); 13C NMR (101 MHz, DMSO-d6) δ 197.24, 166.11, 165.45, 162.09, 149.15, 135.94, 135.54, 133.61, 130.98, 129.64, 128.74, 128.55, 128.46, 128.33, 128.16, 127.90, 127.82, 127.30, 117.52, 113.51, 62.51, 55.40, 37.81, 37.32; IR (KBr) νmax: 3385.3, 2898.8, 2838.8, 1763.2, 1676.0, 1658.3, 1605.8, 1480.4, 1255.6, 1000.7, 942.9, 685.9, 558.8, 478.2 cm−1; HRMS-CI: [M]+ Calcd for C31H24ClNO5, 525.1343, found: 525.1335. (R)-2-((S)-1-(5-Chloro-2-hydroxyphenyl)-3-oxo-3-phenylpropyl)4-phenyl-2-(p-tolyl)oxazol-5(2H)-one 4x. The title compound was isolated by column chromatography in 74% yield; 90% ee, dr > 20/1 [Daicel Chiralcel IA, hexane/i-PrOH (70 : 30), flow rate: 1.0 mL min−1, λ = 254 nm, t (major) = 15.426, t (minor) = 1 21.305]; [α]26 D = +26.60 (c 0.50, CHCl3); H NMR (400 MHz, CDCl3): δ 7.91 (d, J = 8.0 Hz, 2H), 7.60–5.58 (m, 3H), 7.45–7.43 (m, 4H), 7.43–7.42 (m, 3H), 7.25–7.18 (m, 3H), 7.03 (d, J = 8.0 Hz, 1H), 6.98 (s, 1H), 6.69 (s, 1H), 5.36 (d, J = 4.0 Hz, 1H), 3.64 (d, J = 20.0 Hz, 1H), 3.47 (dd, J = 12.0, 20.0 Hz, 1H), 2.37 (s, 3H); 13C NMR (101 MHz, DMSO-d6) δ 197.19, 166.53, 165.35, 149.12, 141.87, 135.93, 135.43, 133.59, 130.50, 128.94, 128.77, 128.72, 128.56, 128.46, 128.33, 128.15, 127.89, 127.80, 127.70, 127.29, 117.52, 62.53, 37.77, 37.18, 20.97; IR (KBr) νmax: 3387.1, 2921.2, 1767.2, 1676.0, 1611.1, 1578.6, 1523.2, 1261.2, 1144.0, 1001.2, 903.8, 643.0, 571.2, 504.0 cm−1; HRMS-CI: [M]+ Calcd for C31H24ClNO4, 509.1394, found: 509.1396. (R)-2-((S)-1-(5-Chloro-2-hydroxyphenyl)-3-oxo-3-phenylpropyl)4-phenyl-2-(m-tolyl)oxazol-5(2H)-one 4y. The title compound was isolated by column chromatography in 67% yield; 90% ee, dr > 20/1 [Daicel Chiralcel IA, hexane/i-PrOH(70 : 30), flow rate: 1.0 mL min−1, λ = 254 nm, t (major) = 8.907, t (minor) = 1 8.208]; [α]26 D = +36.67 (c 0.36, CHCl3); H NMR (400 MHz, CDCl3): δ 7.92 (d, J = 8.0 Hz, 2H), 7.57 (t, J = 8.0 Hz, 1H), 7.50–7.41 (m, 6H), 7.38–7.35 (m, 3H), 7.31–7.29 (m, 2H), 7.23–7.21 (m, 1H), 7.04 (d, J = 8 Hz, 1H), 6.98 (s, 1H), 6.71 (s, 1H), 5.39 (d, J = 4.0 Hz, 1H), 3.64 (dd, J = 4.0, 20.0 Hz, 1H), 3.49 (dd, J = 8.0, 16.0 Hz, 1H), 2.35 (s, 3H); 13C NMR (101 MHz, DMSO-d6) δ 197.15, 166.82, 165.29, 149.12, 137.54, 135.94, 135.37, 133.56, 133.40, 132.32, 128.70, 128.56, 128.46, 128.33, 128.21, 128.15, 127.92, 127.84, 127.30, 124.83, 117.54, 62.57, 37.76, 37.15, 20.83; IR (KBr) νmax: 3422.6, 1777.7, 1639.5, 1480.7, 1448.2, 1407.8, 1384.4, 1136.8, 1092.6, 688.1, 435.3 cm−1; HRMS-CI: [M]+ Calcd for C31H24ClNO4, 509.1394, found: 509.1397. (R)-2-(tert-Butyl)-2-((S)-1-(5-chloro-2-hydroxyphenyl)-3-oxo3-phenylpropyl)-4-phenyloxazol-5(2H)-one 4z. The title compound was isolated by column chromatography in 54% yield; 72% ee, dr > 20/1 [Daicel Chiralcel IA, hexane/i-PrOH (70 : 30), flow rate: 1.0 mL min−1, λ = 210 nm, t (major) = 5.883, 1 t (minor) = 5.537]; [α]26 D = +52.08 (c 0.24, CHCl3); H NMR (400 MHz, CDCl3): δ 7.94–7.91 (m, 2H), 7.59 (t, J = 8.0 Hz, 1H), 7.49–7.45 (m, 2H), 7.43–7.40 (m, 2H), 7.35–7.33 (m, 3H), 7.23–7.20 (m, 1H), 7.03–7.00 (m, 2H), 6.14 (s, 1H), 5.13 (dd, J = 4.0, 8.0 Hz, 1H), 3.50 (dd, J = 4.0, 20.0 Hz, 1H), 3.41

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(dd, J = 8.0, 16.0 Hz, 1H), 1.12 (s, 9H); 13C NMR (101 MHz, DMSO-d6) δ 197.18, 176.99, 165.03, 149.17, 136.08, 136.05, 135.88, 133.53, 128.71, 128.34, 128.15, 128.06, 127.98, 127.91, 127.38, 117.30, 61.56, 38.03, 37.94, 26.67; IR (KBr) νmax: 3393.6, 2962.1, 1773.2, 1679.0, 1597.0, 1580.5, 1260.7, 1191.0, 1001.2, 967.9, 945.0, 699.6, 616.4, 530.8 cm−1; HRMS-CI: [M]+ Calcd for C28H26ClNO4, 475.1550, found: 475.1544. 2-(1-(3-Bromo-5-chloro-2-hydroxyphenyl)-3-oxo-3-phenylpropyl)2,4-diphenyloxazol-5(2H)-one race-5a. The title compound was isolated by column chromatography in 35% yield, 1H NMR (400 MHz, CDCl3): δ 8.19 (d, J = 8.0 Hz, 2H), 7.83–7.81 (m, 2H), 7.69 (d, J = 8.0 Hz, 2H), 7.56–7.52 (m, 2H), 7.47–7.42 (m, 4H), 7.40–7.35 (m, 3H), 7.23 (d, J = 4.0 Hz, 1H), 7.08–7.06 (m, 1H), 4.93 (d, J = 12.0 Hz, 1H), 3.70 (dd, J = 12.0, 20.0 Hz, 1H), 3.29 (d, J = 20.0 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 196.01, 173.95, 163.70, 156.13, 145.71, 142.74, 137.04, 136.70, 136.23, 133.68, 133.08, 130.95, 129.58, 128.94, 128.90, 128.83, 128.77, 128.05, 126.58, 122.92, 106.39, 60.98, 41.33, 38.32; IR (KBr) νmax: 3446.1, 2969.5, 1737.6, 1448.3, 1392.8, 1365.5, 1287.4, 1228.5, 1123.3, 527.8, 515.8, 435.2 cm−1; HRMS-ESI: [M + H]+ Calcd for C30H22BrNO4, 574.0342, found: 574.0430.

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Acknowledgements We are grateful for the financial support from the National Natural Science Foundation of China (21272166), the Major Basic Research Project of the Natural Science Foundation of the Jiangsu Higher Education Institutions (13KJA150004), the Program for New Century Excellent Talents in University (NCET-12-0743), a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), and also the Project of Scientific and Technologic Infrastructure of Suzhou (SZS201207).

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Organocatalytic regioselective asymmetric Michael addition of azlactones to o-hydroxy chalcone derivatives.

The regioselective and enantioselective Michael addition between azlactones and o-hydroxy chalcone derivatives is reported. Enantiomerically enriched ...
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