Asymmetric epoxidation of α,β-unsaturated aldehydes catalyzed by a spiro-pyrrolidine-derived organocatalyst

Tetrahedron: Asymmetry xxx (2016) xxx–xxx

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Asymmetric epoxidation of a,b-unsaturated aldehydes catalyzed by a spiro-pyrrolidine-derived organocatalyst Ming-Hui Xu a, Yong-Qiang Tu a,b,⇑, Jin-Miao Tian a, Fu-Min Zhang a, Shao-Hua Wang a, Shi-Heng Zhang a, Xiao-Ming Zhang a a b

State Key Laboratory of Applied Organic Chemistry & College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, PR China School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai 200240, PR China

a r t i c l e

i n f o

Article history: Received 12 December 2015 Accepted 14 February 2016 Available online xxxx

a b s t r a c t The asymmetric epoxidation of a,b-unsaturated aldehydes, catalyzed by a spiro-pyrrolidine (SPD)derived organocatalyst, has been accomplished with good diastereoselectivities (up to dr >20:1) and with high to excellent enantioselectivities (up to 99% ee). Ó 2016 Elsevier Ltd. All rights reserved.

1. Introduction The a,b-epoxy aldehydes have been employed as important building blocks for the synthesis of natural products and bioactive molecules,1 such as (R)-methyl palmoxirate,2 epoxyisoprostanes,3 (+)-amphidinolide K4 and (+)-stagonolide C.5 Although a number of related studies for preparing enantiomerically pure epoxides have been documented,6 no method using organocatalysis had emerged until Jørgensen et al.’s pioneering work on the asymmetric epoxidation of a,b-unsaturated aldehydes using Jørgensen– Hayashi catalyst 3 in combination with hydrogen peroxide (Scheme 1).7 Afterwards, a variety of pyrrolidine-derived catalysts, such as 4,8 52,9 and 6,10 have been developed and successfully applied to this type of epoxidation for the purpose of enhanced enantioselectivities and better substrate scope. Additionally, other organocatalysts, such as chiral imidazolidinone 7,11 amine salts 812 and quinine-derived amine 9,13 have also found their exceptional utility in such epoxidation reactions. Despite these achievements in organocatalytic asymmetric epoxidations of a,b-unsaturated aldehydes, developing novel catalysts to further enhance the enantioselectivity and diastereoselectivity is still highly desirable. Considering the excellent a stereocontrol and extensive applications of catalysts with chiral spiro-backbone14 as well as the structural features of pyrrolidine-based catalysts 3–6, we have designed and prepared the spiro-pyrrolidine derived (SPD) organocatalyst 10 on a gram scale (Scheme 1). The catalytic efficiency of this type of catalyst has been supported by an asymmetric Michael reac-

⇑ Corresponding author. Fax: +86 931 8912973.

tion.1 To prove that this catalyst might be a beneficial complement for current secondary amine catalysts, we employed 10 to catalyze the asymmetric epoxidation of a,b-unsaturated aldehydes to prepare various enantiomerically pure a,b-epoxy aldehydes/alcohols with good to excellent diastereoselectivities and enantioselectivities (Scheme 1). 2. Results and discussion Initially, cinnamic aldehyde 1a was selected as a model substrate with hydrogen peroxide as the oxidant to test the catalytic efficiency of organocatalyst 10 in anhydrous MeOH. The desired epoxide 2a was obtained with excellent enantioselectivity (99% ee) and diastereoselectivity (dr >20:1), albeit with moderate yield (68%) after the in situ reduction of the aldehyde intermediate by NaBH4 (Table 1, entry 1). Encouraged by this result, we further optimized the reaction conditions to increase the reaction yield. Solvent screening (Table 1) showed that other aprotic solvents, such as anhydrous DCM, THF and MeCN, decreased the yield while maintaining the selectivity (entries 2–4). In contrast, non-polar solvents such as toluene prohibited the reaction (entry 5). Importantly, the direct use of commercially available MeOH without any treatment gave a much higher yield of 87% (entry 6 vs entry 1), which indicated the pivotal role of a small amount of water in enhancing the efficiency of the reaction. Next, other commonly used oxidants were examined (entries 8–10), but all of them gave poor results. Increasing the concentration (50%) of H2O2 also afforded a comparable result (entry 11 vs entry 6), while lowering the catalyst loading from 20 mol % to 10 mol % significantly decreased the yield (61%) (entry 12). Therefore, entry 6 was chosen

E-mail addresses: [email protected], [email protected] (Y.-Q. Tu). http://dx.doi.org/10.1016/j.tetasy.2016.02.009 0957-4166/Ó 2016 Elsevier Ltd. All rights reserved.

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M.-H. Xu et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx R1

O

O R1

organocatalst

oxidant

2

R

solvent

O

R2

1

2' R1 3 R = OTMS 4 Ar = Ph, R = OTMS 5 R = OSiMePh2 6 Ar = Ph, R = F

Ar Ar N H

R

Me

t-Bu

O

O

N

NH 2

N

O

H

Bn N H HX 7

N H

R3 N

P O

O

R1

8

H

R2

OTBDPS

MeO 10 N

SPD organocatalyst

9

Scheme 1. Organocatalytic asymmetric epoxidation of a,b-unsaturated aldehydes.

Table 1 Optimization for the asymmetric epoxidation of cinnamic aldehydea O 1. H 2O2 (3 equiv),10 (20 mol%) H

1 2 3 4 5 6 8 9 10 11 12f

OH

2. NaBH 4 (4 equiv) 0°C

1a

Entry

O

MeOH, rt, 48 h

Solvent b

MeOH DCMb THFb MeCNb Tolueneb MeOH (AR) MeOH (AR) MeOH (AR) MeOH (AR) MeOH (AR) MeOH (AR)

2a

Oxidant

drc

eed (%)

30% H2O2 30% H2O2 30% H2O2 30% H2O2 30% H2O2 30% H2O2 UHP m-CPBA TBHP 50% H2O2 30% H2O2

>20:1 >20:1 >20:1 >20:1 — >20:1 — — — >20:1 >20:1

99 99 99 99 — 99 — — — 98 99

Yielde (%) 68 40 62 59 <5 87 <5 <5 nd 86 61

AR = analytical reagent, UHP = urea hydrogen peroxide, m-CPBA = 3-chloroperbenzoic acid, TBHP = tert-butyl hydroperoxide. a Unless otherwise noted, the reaction was conducted in solvent (1.0 mL) with cinnamic aldehyde (0.3 mmol), oxidant (3 equiv), catalyst 10 (0.2 equiv) at room temperature for 48 h. The reaction was cooled to 0 °C followed by the addition of NaBH4 (4 equiv). Since the epoxy aldehyde is not stable during work-up, the dr and ee data of its corresponding primary alcohol compound 2a were determined. b Solvents were distilled by standard procedure. c Determined by NMR. d Determined by HPLC. e Isolated yield for two steps. f 10 mmol % catalyst were used.

as the general experimental conditions for subsequent substrate scope investigations. With the optimal conditions in hand, a series of a,b-unsaturated aldehydes bearing different b-aromatic substituents were applied to this reaction; most of them could be oxidized into the corresponding epoxides with good to excellent diastereoselectivities as well as enantioselectivities (up to dr >20:1 and 99% ee; Table 2, entries 1–8). Generally, substrates with electron deficient aromatic substituents gave better results in terms of both yields and enantioselectivities than those with electron rich aromatic substituents (entries 3, 6 vs entry 7). Meanwhile, the position of substituents slightly affected the diastereoselectivities; the ortho-substituted substrate gave the worst result (entries 3, 5, 6). In addition, a bulky aromatic group such as naphthyl could seriously decrease the diastereoselectivity and enantioselectivity (entry 8). It should be noted that substrates 1d–1g all gave better results than previously

reported under the current reaction conditions (entries 4–7);10a,12a these results further demonstrate the potential utility of catalyst 10 as a complement for known secondary amine catalysts. In addition, the aliphatic substituted a,b-unsaturated aldehydes are also amenable to this catalytic peroxidation system, which provided epoxides 2i–2n with good to excellent dr, ee and moderate to high yields after subsequent reduction and esterification of the aldehyde intermediates (entries 9–14). However, both the yields and enantioselectivities decreased considerably compared with the results of the aromatic substituted aldehydes. Generally, higher enantioselectivities were observed in the epoxidation of b-monosubstituted substrates (entries 1–11) than those of b-disubstituted ones (entries 12–14), which may be caused by the steric hindrance of the corresponding substrates 1l–1n. According to the experimental results, a possible mechanism is proposed for the SPD catalyzed asymmetric reaction (Scheme 2). Firstly, an iminium ion is formed from dehydration of an a,bunsaturated aldehyde with catalyst 10. Next, the iminium ion is attacked by H2O2, leading to an enamine intermediate. Finally, the formation of epoxide 20 takes place by the attack of the nucleophilic enamine carbon atom on the electrophilic oxygen atom. Due to the steric hindrance caused by the bulky silyl ether from the Si-face, the nucleophilic H2O2 could only approach the iminium ion from the Re-face, thus affording the (S,R)-epoxide. 3. Conclusion In conclusion, we have demonstrated that the SPD-derived organocatalyst 10 is able to catalyze the asymmetric epoxidation of a variety of a,b-unsaturated aldehydes with good to excellent dr and ee. Some examples give better results than previously reported ones. Overall, this is a complement to the field of enantioselective, organocatalytic epoxidation. Further studies on the catalytic efficiency of this type of catalysts towards other reactions are ongoing in our laboratory. 4. Experimental 4.1. General All reactions were carried out under an argon atmosphere. All solvents were purified and dried by standard techniques and distilled prior to use. All reactions under standard conditions were monitored by thin-layer chromatography (TLC) on gel GF254

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M.-H. Xu et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx

plates. Silica gel (200300 mesh), petroleum ether (bp 6090 °C) and ethyl acetate are used for product purification by flash column chromatography. The phosphate buffer used (1 M, PH = 7.0) was prepared from KH2PO4 (136 g), solid NaOH (23.3 g) and both were dissolved in H2O (1 L). 1H, 13C and 19F NMR spectra, which were recorded in CDCl3 solution, were acquired on a Bruker AM400 MHz spectrometer. Chemical shifts (d) are reported in ppm rel-

ative to residual solvent signals (CDCl3: 7.26 ppm for 1H NMR, 77.0 ppm for 13C NMR). The following abbreviations are used to indicate the multiplicity in NMR spectra: s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet. High-resolution mass spectral analysis (HRMS) data were determined on an APEXII 47e FT-ICR spectrometer by means of the ESI technique. IR spectra were recorded on a fourier transform infrared spectrometer. The enan-

Table 2 Scope of the epoxidation of a,b-unsaturated aldehydes with H2O2a R1

1. H 2 O2 (3 equiv), 10 (20 mol%)

O

R1

MeOH, rt, 48 h R2 1a-n

Entry

O

R2

H 2. NaBH4 (4 equiv) 0°C

OH 2a-n

Yieldb (%)

Product

drd

eee (%)

O OH

1

2a

87

99

2b

62

2c

78

2d

61

2e

60

2f

74

2g

36

2h

75

2i0

29c

2j0

37c

2k0

62c

2l0

15c

—

83

2m0

54c

—

75

>20:1

O OH

2

85

>20:1

Br O OH

3

99

>20:1

Cl O OH

4

18:1

98

F O OH

5

98

>20:1

F O OH

6

99

>20:1

F O OH

7

96

>20:1

O OH

8

10:1

92

O

O

9f

O

94

>20:1

NO 2 O

O f

O

10

98

>20:1

NO 2 O

O

11f

O

94

>20:1

NO2 O

O

12f

O NO2 O O

13

O NO2

(continued on next page)

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M.-H. Xu et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx

Table 2 (continued) Entry

Yieldb (%)

Product

drd

eee (%)

O

O O

14f

2n0

73c

>20:1

85

NO2

Unless otherwise noted, the reaction was conducted in MeOH (AR) (1.0 mL) with a,b-unsaturated aldehyde (0.3 mmol), H2O2 (30% in water, 3 equiv), catalyst 10 (0.2 equiv), at rt for 48 h. Then, NaBH4 (4 equiv) was added at 0 °C. The dr and ee of aldehydes 20 a–20 h were determined after they were reduced to the corresponding primary alcohols 2a–2h. The dr and ee of compounds 20 i–20 n were determined after they were reduced and then transformed into the corresponding p-nitrobenzoate ester 2i0 –2n0 due to the volatility of the resulting alcohol. For details, please see Supporting information. b Isolated yield for two steps. c Isolated yield for three steps. d The major dr was determined by NMR. e The major ee was determined by HPLC. f The solvent was TBME. a

H 2O

N OTBDPS R

R1

H

1

HO OH

O 1

path b H 2O 2

N

favored

N H

N

R1

OTBDPS

Ph

10 path a

H 2O 2

t

Bu

1

R

O

OH

disfavored

O R1

OTBDPS

Si

Ph

H

O 2'

N

H2 O

H2 O OTBDPS O R1

Scheme 2. The proposed mechanism of asymmetric epoxidation of a,b-unsaturated aldehydes.

tiomeric excess (ee) of the products was determined by high performance liquid chromatography (HPLC) analysis employing Daicel Chiralpak AD, IA-3, OJ and OD-H column. Optical rotations were detected on RUDOLPH A21202-J APTV/GW. Aldehydes 1a–l were commercially available and used as received. Organocatalyst 10 was prepared according to the published procedure.15 Substrates 1m–n were synthesized according to literature procedures.16 The analytical reagents (AR) were purchased from commercial suppliers and used without further purification unless stated otherwise. The oxidation H2O2 was degassed for 30 min by bubbling argon. Racemic epoxides were prepared by epoxidation of the corresponding a,b-unsaturated aldehydes with H2O2 through direct catalysis by the racemic catalyst 10. 4.1.1. General procedure for the enantioselective asymmetric epoxidation Catalyst 10 (22.8 mg, 0.06 mmol) was added at rt to a solution of the a,b-unsaturated aldehyde (0.3 mmol) in MeOH (1.0 mL). The mixture was stirred for 10 min at rt followed by the addition

of H2O2 (30% in H2O, 92 lL, 0.9 mmol). The reaction was stirred for 48 h under argon. After completion, the reaction was cooled to 0 °C (ice bath) followed by the addition of NaBH4 (45.6 mg, 1.2 mmol). The reaction mixture was then stirred for a further 30 min at 0 °C, and quenched with a pH = 7.0 phosphate buffer solution. The aqueous phase was extracted with CH2Cl2 (3  5 mL) and the combined organic extracts were dried over anhydrous MgSO4 and concentrated in vacuo after filtration. The crude product was purified by column chromatography (silica gel; petroleum ether/AcOEt = 8:1) to give target compounds 2a–h. The crude products 2i–n were dissolved in anhydrous CH2Cl2 and cooled to 0 °C followed by the continuous addition of Et3N (166 lL, 1.2 mmol), DMAP (7.2 mg, 0.06 mmol) and p-nitrobenzoyl chloride (167 mg, 0.9 mmol). The mixture was stirred for 15 min at 0 °C and then stirred for a further 1 h at rt. After completion, the mixture was quenched with NaHCO3 saturated solution. The aqueous phase was extracted with CH2Cl2 (3  5 mL), and the combined organic extracts were dried over anhydrous MgSO4 and concentrated in vacuo after filtration. Purification by column

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M.-H. Xu et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx

chromatography (silica gel; petroleum ether/AcOEt = 15:1) gave target compounds 2i0 –2n0 . 4.1.1.1. ((2S,3S)-3-Phenyloxiran-2-yl)methanol 2a6e. To confirm the configuration of the product, we compared the specific rotation of 2a0 with the literature values, [a]20 D = +53 (c 1.0, CHCl3), 99% ee, Lit. [a]D23 = +14.3 (c 0.48, CHCl3), 94% ee.6e The configuration of 20 a is (2R,3S), so the configuration of 2a is (2S,3S). All other absolute configurations were assigned by analogy. Compound 2a was prepared according to the general procedure in 87% yield as a white solid. 1H NMR (400 MHZ, CDCl3) d 7.25–7.37 (m, 5H), 4.05 (ddd, J = 2.4 Hz, 5.2 Hz, 12.8 Hz, 1H), 3.93 (d, J = 2 Hz, 1H), 3.77–3.84 (m, 1H), 3.21–3.24 (m, 1H), 1.86 (dd, J = 5.2 Hz, 7.6 Hz, 1H); 13C NMR (100 MHZ, CDCl3) d 136.6, 128.5, 128.3, 125.7, 62.3, 61.2, 55.5; HRMS (ESI) Calcd for C9H9O [MH2O+H]+: 133.0648, Found: 133.0646, Error: 1.5 ppm; IR (neat) cm1 3373, 2924, 2371, 1596, 1384, 1260, 1118, 869, 768, 698; [a]20 D = 47 (c 1.0, CHCl3). Enantiomeric excess is 99% determined by HPLC (Chiralpak OD-H, Hexane/ Isopropanol = 96:4, flow rate = 1.0 mL/min, 215 nm); major enantiomer: tR = 32.05 min; minor enantiomer: tR = 28.64 min. 4.1.1.2. ((2S,3S)-3-(4-Bromophenyl)oxiran-2-yl)methanol 2b. Compound 2b was prepared according to the general procedure in 62% yield as a white solid. 1H NMR (400 MHZ, CDCl3) d 7.47 (d, J = 8.4 Hz, 2H), 7.15 (d, J = 8.4 Hz, 2H), 4.04 (dd, J = 2.4 Hz, 13.2 Hz, 1H), 3.90 (d, J = 2 Hz, 1H), 3.80 (dd, J = 3.2 Hz, 12.8 Hz, 1H), 3.16–3.18 (m, 1H), 2.18 (s, 1H); 13C NMR (100 MHZ, CDCl3) d 135.8, 131.6, 127.3, 122.2, 62.4, 60.9, 54.9; HRMS (ESI) Calcd for C9H10Br1O2 [M+H]+: 228.9859, Found: 228.9858, Error: 0.4 ppm, IR (neat) cm1 3298, 2925, 2398, 1720, 1595, 1490, 1381, 1261, 1073, 766; [a]20 D = 32 (c 1.0, CHCl3). Enantiomeric excess is 85% determined by HPLC (Chiralpak OD-H, Hexane/Isopropanol = 98:2, flow rate = 1.0 mL/min, 220 nm); major enantiomer: tR = 55.75 min; minor enantiomer: tR = 51.36 min. 4.1.1.3. ((2S,3S)-3-(4-Chlorophenyl)oxiran-2-yl)methanol 2c. Compound 2c was prepared according to the general procedure in 78% yield as a colourless oil. 1H NMR (400 MHZ, CDCl3) d 7.31–7.33 (m, 2H), 7.20–7.23 (m, 2H), 4.05 (ddd, J = 2.4 Hz, 5.2 Hz, 12.8 Hz, 1H), 3.92 (d, J = 2 Hz, 1H), 3.78–3.84 (m, 1H), 3.17–3.19 (m, 1H), 2.03 (dd, J = 5.2 Hz, 7.6 Hz, 1H); 13C NMR (100 MHZ, CDCl3) d 135.2, 134.0, 128.7, 127.0, 62.4, 61.0, 54.9; HRMS (ESI) Calcd for C9H10Cl1O2 [M+H]+: 185.0364, Found: 185.0362, Error: 1.1 ppm; IR (neat) cm1 3391, 2924, 2373, 1720, 1600, 1493, 1383, 1260, 1086, 820. [a]20 D = 38 (c 1.0, CHCl3). Enantiomeric excess is 99% determined by HPLC (Chiralpak OJ, Hexane/Isopropanol = 99:1, flow rate = 1.0 mL/min, 230 nm): major enantiomer: tR = 74.4 min. 4.1.1.4. ((2S,3S)-3-(2-Fluorophenyl)oxiran-2-yl)methanol 2d. Compound 2d was prepared according to the general procedure in 61% yield as a colourless oil. 1H NMR (400 MHZ, CDCl3) d 7.03–7.26 (m, 4H), 4.21 (d, J = 2 Hz, 1H), 4.07 (ddd, J = 2.4 Hz, 5.6 Hz, 12.8 Hz, 1H), 3.82 (ddd, J = 4 Hz, 7.2 Hz, 8.4 Hz, 1H), 3.23– 3.25 (m, 1H), 2.23 (dd, J = 5.6 Hz, 7.2 Hz, 1H); 13C NMR (100 MHZ, CDCl3) d 161.3 (d, JF = 245 Hz), 129.5 (d, JF = 8 Hz), 126.2 (d, JF = 3 Hz), 124.3 (d, JF = 3 Hz), 124.0 (d, JF = 12 Hz), 115.2 (d, JF = 20 Hz), 61.7, 61.2, 50.2 (d, JF = 6 Hz); 19F NMR (376 MHZ, CDCl3) d 120.7 (m, 1F) ppm; HRMS (ESI) Calcd for C9H10F1O2 [M+H]+: 169.0659, Found: 169.0657, Error: 1.2 ppm; IR (neat) cm1 3368, 2924, 2371, 1720, 1588, 1458, 1260, 1075, 760. [a]20 D = 23 (c 1.0, CHCl3). Enantiomeric excess is 98% determined by HPLC (Chiralpak IA-3, Hexane/Isopropanol = 99:1, flow rate = 1.0 mL/min, 225 nm): major enantiomer: tR = 51.55 min; minor enantiomer r: tR = 59.73 min.

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4.1.1.5. ((2S,3S)-3-(3-Fluorophenyl)oxiran-2-yl)methanol 2e. Compound 2e was prepared according to the general procedure in 60% yield as a colourless oil. 1H NMR (400 MHZ, CDCl3) d 7.29–7.34 (m, 1H), 7.09 (d, J = 7.6 Hz, 1H), 6.97–7.03 (m, 2H), 4.05 (d, J = 12.8 Hz, 1H), 3.94 (d, J = 1.6 Hz, 1H), 3.82 (d, J = 12.8 Hz, 1H), 3.17–3.19 (m, 1H), 1.97 (s, 1H); 13C NMR (100 MHZ, CDCl3) d 163.0 (d, JF = 245 Hz), 139.5 (d, JF = 8 Hz), 130.1 (d, JF = 8 Hz), 121.4 (d, JF = 3 Hz), 115.2 (d, JF = 21 Hz), 112.4 (d, JF = 23 Hz), 62.5, 60.9, 54.8 (d, JF = 3 Hz); 19F NMR (376 MHZ, CDCl3) d 112.8 (m, 1F) ppm; HRMS (ESI) Calcd for C9H8F1O1 [MH2O+H]+: 151.0554, Found: 151.0553, Error: 0.7 ppm; IR (neat) cm1 3380, 2924, 2374, 1721, 1592, 1457, 1258, 1079, 788, 690. [a]20 D = 44 (c 1.0, CHCl3). Enantiomeric excess is 98% determined by HPLC (Chiralpak IA-3, Hexane/Isopropanol = 95:5, flow rate = 1.0 mL/min, 220 nm): major enantiomer: tR = 16.23 min; minor enantiomer: tR = 19.18 min. 4.1.1.6. ((2S,3S)-3-(4-Fluorophenyl)oxiran-2-yl)methanol 2f. Compound 2f was prepared according to the general procedure in 74% yield as a colourless oil. 1H NMR (400 MHZ, CDCl3) d 7.23–7.25 (m, 2H), 7.01–7.06 (m, 2H), 4.05 (d, J = 12.8 Hz, 1H), 3.92 (d, J = 2 Hz, 1H), 3.80 (d, J = 12.8 Hz, 1H), 3.18–3.20 (m, 1 H), 2.10 (s, 1H); 13C NMR (100 MHZ, CDCl3) d 162.5 (d, JF = 245 Hz), 132.3 (d, JF = 3 Hz), 127.4 (d, JF = 8 Hz), 115.5 (d, JF = 21 Hz), 62.4, 61.0, 54.9; 19F NMR (376 MHZ, CDCl3) d 113.5 (m, 1F) ppm; HRMS (ESI) Calcd for C9H8F1O1 [MH2O+H]+: 151.0554, Found: 151.0552, Error: 1.3 ppm; IR (neat) cm1 3396, 2959, 2374, 1722, 1607, 1513, 1224, 1076, 830, 557. [a]20 D = 35 (c 1.0, CHCl3). Enantiomeric excess is 99% determined by HPLC (Chiralpak OD-H, Hexane/Isopropanol = 99:1, flow rate = 1.0 mL/min, 220 nm): major enantiomer: tR = 65.78 min. 4.1.1.7. ((2S,3S)-3-(p-Tolyl)oxiran-2-yl)methanol 2g. Compound 2g was prepared according to the general procedure in 36% yield as a colourless oil. 1H NMR (400 MHZ, CDCl3) d 7.15– 7.20 (m, 4H), 4.05 (d, J = 12.8 Hz, 1H), 3.9 (d, J = 2 Hz, 1H), 3.77– 3.83 (m, 1H), 3.22–3.25 (m, 1H), 2.36 (s, 3H) 1.95 (t, J = 6 Hz, 1H); 13C NMR (100 MHZ, CDCl3) d 138.1, 133.5, 129.2, 125.6, 62.2, 61.2, 55.5, 21.1; HRMS (ESI) Calcd for C10H11O1 [MH2O +H]+: 147.0804, Found: 147.0803, Error: 0.7 ppm; IR (neat) cm1 3402, 2924, 2369, 1721, 1455, 1261, 1079, 1022, 815, 758. [a]20 D = 36 (c 1.0, CHCl3). Enantiomeric excess is 96% determined by HPLC (Chiralpak OD-H, Hexane/Isopropanol = 98:2, flow rate = 1.0 mL/min, 230 nm): major enantiomer: tR = 52.23 min; minor enantiomer: tR = 46.64 min. 4.1.1.8. ((2S,3S)-3-(Naphthalen-1-yl)oxiran-2-yl)methanol 2h. Compound 2i was prepared according to the general procedure in 75% yield as a light yellow oil. 1H NMR (400 MHZ, CDCl3) d 8.10–8.13 (m, 1H), 7.89–7.92 (m, 1H), 7.82 (d, J = 8 Hz, 1H), 7.45– 7.58 (m, 4H), 4.63 (dd, J = 4.4 Hz, 14.4 Hz 1H), 4.18 (dd, J = 1.6 Hz, 12.8 Hz, 1H), 3.98 (dd, J = 2 Hz, 12.6 Hz, 1H) 3.23–3.25 (m, 1H), 2.57 (s, 1H); 13C NMR (100 MHZ, CDCl3) d 133.1, 132.7, 131.1, 128.6, 128.1, 126.3, 125.8, 125.4, 122.7, 122.2, 61.6, 61.2, 53.8; HRMS (ESI) Calcd for C13H12O2Na1 [M+Na]+: 233.0730, Found: 233.0729, Error: 0.4 ppm; IR (neat) cm1 3400, 2925, 2372, 1721, 1395, 1261, 1085, 1022, 800, 778, 759. [a]20 D = 66 (c 1.0, CHCl3). Enantiomeric excess is 92% determined by HPLC (Chiralpak ODH, Hexane/Isopropanol = 96:4, flow rate = 1.0 mL/min, 215 nm): major enantiomer: tR = 57.57 min; minor enantiomer: tR = 42.29 min. 4.1.1.9. ((2S,3S)-3-Methyloxiran-2-yl) methyl 4-nitrobenzoate 2i0 . Compound 2i0 was prepared according to the general procedure in 29% yield as a light yellow oil. 1H NMR (400 MHZ, CDCl3) d 8.29–8.31 (m, 2H), 8.23–8.25 (m, 2H), 4.70 (dd, J = 2.8 Hz, 12 Hz,

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M.-H. Xu et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx

1H), 4.20 (dd, J = 6.4 Hz, 12 Hz, 1H), 3.08–3.11 (m, 1H), 3.01–3.06 (m, 1H), 1.40 (d, J = 5.2 Hz, 3H); 13C NMR (100 MHZ, CDCl3) d 164.4, 150.6, 135.0, 130.8, 123.5, 66.0, 56.0, 52.5, 17.1; HRMS (ESI) Calcd for C11H12N1O5 [M+H]+: 238.0710, Found: 238.0708, 1 Error: 0.8 ppm. [a]20 3432, D = 14 (c 1.0, CHCl3); IR (neat) cm 2926, 2373, 1726, 1608, 1527, 1449, 1273, 1102, 718. Enantiomeric excess is 94% determined by HPLC (Chiralpak AD, Hexane/Isopropanol = 90:10, flow rate = 1.0 mL/min, 230 nm): major enantiomer: tR = 13.01 min; minor enantiomer: tR = 17.41 min. 4.1.1.10. ((2S,3S)-3-Ethyloxiran-2-yl) methyl-4-nitrobenzoate 2j0 . Compound 2j0 was prepared according to the general procedure in 37% yield as a white solid. 1H NMR (400 MHZ, CDCl3) d 8.30 (dd, J = 2 Hz, 6.8 Hz, 2H), 8.24 (dd, J = 2 Hz, 6.8 Hz, 2H), 4.70 (dd, J = 2.8 Hz, 12 Hz, 1H), 4.20 (dd, J = 6.8 Hz, 12.4 Hz, 1H), 3.12– 3.15 (m, 1H), 2.92–2.95 (m, 1H), 1.61–1.70 (m, 2H), 1.02 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHZ, CDCl3) d 164.3, 150.6, 135.0, 130.8, 123.5, 66.1, 57.5, 54.7, 24.5, 9.6; HRMS (ESI) Calcd for C12H14N1O5 [M+H]+: 252.0866, Found: 252.0865, Error: 0.4 ppm; IR (neat) cm1 3367, 2962, 2368, 1727, 1528, 1270, 1103, 757, 505. [a]20 D = 23 (c 1.0, CHCl3). Enantiomeric excess is 98% determined by HPLC (Chiralpak AD, Hexane/Isopropanol = 95:5, flow rate = 1.0 mL/min, 220 nm): major enantiomer: tR = 16.01 min; minor enantiomer: tR = 22.12 min. 4.1.1.11. ((2S,3S)-3-Propyloxiran-2-yl) methyl-4-nitrobenzoate 2k0 . Compound 2k0 was prepared according to the general procedure in 62% yield as a light red oil. 1H NMR (400 MHZ, CDCl3) d 8.22–8.31 (m, 4H), 4.68 (dd, J = 2.8 Hz, 12 Hz, 1H), 4.21 (dd, J = 6.4 Hz, 12 Hz, 1H), 3.10–3.13 (m, 1H), 2.92–2.96 (m, 1H), 1.57–1.63 (m, 2H), 1.46–1.54 (m, 2H), 0.98 (t, J = 7.4 Hz, 3H); 13C NMR (100 MHZ, CDCl3) d 164.4, 150.6, 135.0, 130.8, 123.5, 66.1, 56.4, 54.9, 33.4, 19.1, 13.8; HRMS (ESI) Calcd for C13H16N1O5 [M +H]+: 266.1023, Found: 266.1018, Error: 1.9 ppm; IR (neat) cm1 3435, 2960, 1944, 1728, 1529, 1271, 1102, 720, 505. [a]20 D = 32 (c 1.0, CHCl3). Enantiomeric excess is 94% determined by HPLC (Chiralpak AD, Hexane/Isopropanol = 90:10, flow rate = 1.0 mL/ min, 220 nm): major enantiomer: tR = 11.24 min; minor enantiomer: tR = 13.65 min. 4.1.1.12. (S)-(3,3-Dimethyloxiran-2-yl)methyl-4-nitrobenzoate 2l0 . Compound 2l0 was prepared according to the general procedure in 15% yield as a white solid. 1H NMR (400 MHZ, CDCl3) d 8.23–8.31 (m, 4 H), 4.67 (dd, J = 4 Hz, 12 Hz, 1H), 4.31 (dd, J = 7.2 Hz, 12 Hz, 1H), 3.15 (dd, J = 4 Hz, 7.2 Hz, 1H), 1.40 (s, 6H); 13 C NMR (100 MHZ, CDCl3) d 164.5, 150.6, 135.1, 130.8, 123.5, 64.9, 60.2, 58.3, 24.5, 18.9; HRMS (ESI) Calcd for C12H14N1O5 [M +H]+: 252.0866, Found: 252.0863, Error: 1.2 ppm; IR (neat) cm1 3344, 2961, 2370, 1728, 1640, 1525, 1347, 1262, 1108, 758, 507. [a]20 D = 22 (c 1.0, CHCl3). Enantiomeric excess is 83% determined by HPLC (Chiralpak AD, Hexane/Isopropanol = 95:5, flow rate = 1.0 mL/min, 256 nm): major enantiomer: tR = 15.40 min; minor enantiomer: tR = 17.14 min. 4.1.1.13. (S)-1-Oxaspiro[2.4]heptan-2-ylmethyl-4-nitrobenzoate Compound 2m0 was prepared according to the general 2m0 . procedure in 54% yield as a white solid. 1H NMR (400 MHZ, CDCl3) d 8.24–8.32 (m, 4H), 4.69 (dd, J = 3.6 Hz, 12 Hz, 1H), 4.22 (dd, J = 7.2 Hz, 12 Hz, 1H), 3.40 (dd, J = 3.6 Hz, 7.6 Hz, 1H), 1.82–2.05 (m, 4H), 1.71 (m, 4H); 13C NMR (100 MHZ, CDCl3) d 164.5, 150.6, 135.1, 130.8, 123.5, 68.8, 66.0, 57.9, 33.5, 29.3, 25.1, 24.7; HRMS (ESI) Calcd for C14H14N1O4 [MH2O+H]+: 260.0917, Found: 260.0916, Error: 0.4 ppm; IR (neat) cm1 3430, 2925, 2372, 1945, 1727, 1529, 1265, 1102, 758, 502. [a]20 D = 17 (c 1.0, CHCl3). Enantiomeric excess is 75% determined by HPLC (Chiralpak AD, Hexane/

Isopropanol = 95:5, flow rate = 1.0 mL/min, 230 nm): major enantiomer: tR = 23.21 min; minor enantiomer: tR = 25.53 min. 4.1.1.14. ((2S,3R)-3-Heptyl-3-methyloxiran-2-yl)methyl 4nitrobenzoate 2n0 . Compound 2n0 was prepared according to the general procedure in 73% yield as a white solid. 1H NMR (400 MHZ, CDCl3) d 8.29–8.31 (m, 2H), 8.23–8.26 (m, 2H), 4.624.69 (m, 1H), 4.31-4.36 (m, 1H), 1.62–1.71 (m, 4H), 1.37–1.50 (m, 3H), 1.25–1.29 (m, 8H), 0.85-0.89 (m, 3H); 13C NMR (100 MHZ, CDCl3) d 164.5, 150.7, 135.1, 130.8, 123.5, 64.9, 60.9, 59.4, 38.2, 31.7, 29.4, 29.2, 25.0, 22.6, 16.9, 14.0; HRMS (ESI) Calcd for C18H25N1O5Na [M+Na]+: 358.1625, Found: 358.1622, Error: 0.8 ppm; IR (neat) cm1 3439, 2929, 2372, 1729, 1530, 1273, 1102, 720. [a]20 D = 11 (c 1.0, CHCl3). Enantiomeric excess is 85% determined by HPLC (Chiralpak OD-H, Hexane/Isopropanol = 98:2, flow rate = 1.0 mL/min, 230 nm): major enantiomer r: tR = 15.00 min; minor enantiomer: tR = 13.78 min. 4.1.1.15. Catalyst 10. Catalyst 10 was prepared according to the published procedure.15 1H NMR (400 MHZ, CDCl3) d 7.64– 7.68 (m, 4H),7.34–7.45 (m, 6H), 3.85 (t, J = 5.8 Hz, 1H), 2.76–2.84 (m, 2H), 2.24 (s, 1H), 1.53–1.86 (m, 6H), 1.32–1.49 (m, 4H), 1.08 (s, 9H); 13C NMR (100 MHZ, CDCl3) d 135.8, 134.4, 133.8, 129.6, 129.5, 127.6, 127.4, 78.2, 71.8, 45.8, 36.1, 34.8, 32.3, 27.0, 25.9, 19.4, 19.3; HRMS Calcd for C24H34N1O1Si1 [M+H]+: 380.2404, Found: 380.2400, Error: 1.1 ppm; IR (neat) cm1 3353, 2955, 2860, 1657, 1589, 1471, 1427, 1112, 739, 702, 508. [a]20 D = +6 (c 1.0, CHCl3). Acknowledgements This work was supported by the NSFC (No.: 21202073, 21290180, 21272097, 21372104 and 21472077), the ‘111’ Program of MOE, the Project of MOST (2012ZX 09201101–003) and the fundamental research funds for the central universities (lzujbky-2014K20 and lzujbky-2015-k12). Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.tetasy.2016.02. 009. References 1. (a) Jung, M. E.; D’Amico, D. C. J. Am. Chem. Soc. 1995, 117, 7379–7388; (b) Aldous, D. J.; Dalencüon, A. J.; Steel, P. G. Org. Lett. 2002, 4, 1159–1162; (c) Baldwin, J. E.; Bulger, P. G.; Marquez, R. Tetrahedron 2002, 58, 5441–5452; (d) Zou, Y.; Lobera, M.; Snider, B. B. J. Org. Chem. 2005, 70, 1761–1770; (e) Urano, H.; Enomoto, M.; Kuwahara, S. Biosci. Biotechnol. Biochem. 2010, 74, 152–157; (f) Volchkov, I.; Lee, D. J. Am. Chem. Soc. 2013, 135, 5324–5327; (g) Xuan, Y. N.; Lin, H. S.; Yan, M. Org. Biomol. Chem. 2013, 11, 1815–1817; (h) Zhu, Y.; Wang, Q.; Cornwall, R. G.; Shi, Y. Chem. Rev. 2014, 114, 8199–8256; (i) Davis, R. L.; Stiller, J.; Naicker, T.; Jiang, H.; Jorgensen, K. A. Angew. Chem., Int. Ed. 2014, 53, 7406–7426. 2. Bondzic, B. P.; Urushima, T.; Ishikawa, H.; Hayashi, Y. Org. Lett. 2010, 12, 5434– 5437. 3. Egger, J.; Bretscher, P.; Freigang, S.; Kopf, M.; Carreira, E. M. Angew. Chem., Int. Ed. 2013, 52, 5382–5385. 4. Williams, D. R.; Meyer, K. G. J. Am. Chem. Soc. 2001, 123, 765–766. 5. Shelke, A. M.; Rawat, V.; Suryavanshi, G.; Sudalai, A. Tetrahedron: Asymmetry 2012, 23, 1534–1541. 6. (a) Bougauchi, M.; Watanabe, S.; Arai, T.; Sasai, H.; Shibasaki, M. J. Am. Chem. Soc. 1997, 119, 2329–2330; (b) Katsuki, T.; Sharpless, K. B. J. Am. Chem. Soc. 1980, 102, 5974–5976; (c) Zhang, W.; Loebach, J. L.; Wilson, S. R.; Jacobsen, E. N. J. Am. Chem. Soc. 1990, 112, 2801–2803; (d) Irie, R.; Noda, K.; Ito, Y.; Matsumoto, N.; Katsuki, T. Tetrahedron Lett. 1990, 31, 7345–7348; (e) Nemoto, T.; Ohshima, T.; Shibasaki, M. J. Am. Chem. Soc. 2001, 123, 9474–9475; (f) Nemoto, T.; Ohshima, T.; Yamaguchi, K.; Shibasaki, M. J. Am. Chem. Soc. 2001, 123, 2725–2732; (g) Lane, B. S.; Burgess, K. Chem. Rev. (Washington, DC, U. S.) 2003, 103, 2457–2474; (h) Xia, Q. H.; Ge, H. Q.; Ye, C. P.; Liu, Z. M.; Su, K. X. Chem. Rev. (Washington, DC, U. S.) 2005, 105, 1603–1662.

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