Exploring Substrate Scope of Shi-Type Epoxidations

Abstract

Enantioselective epoxidations of alkenes (12 examples) were achieved using a Shi-type carbohydrate-derived hydrate and Oxone. The chiral platform provided by the catalyst tolerates a wide range of substituents providing high yields and enantioselectivities (80-95.5% ee). However, styrene derivatives were only converted with poor selectivities (11-26% ee).

Key words

alkenes - asymmetric catalysis - organocatalysis - ligands - epoxidations

References and Notes

• 1a Katsuki T. In Comprehensive Asymmetric Catalysis   Vol. 2:  Jacobsen EN. Pfaltz A. Yamamoto H. Springer; Heidelberg: 1999.  p.621-648  
• 1b Jacobsen EN. Wu MH. In Comprehensive Asymmetric Catalysis   Vol. 2:  Jacobsen EN. Pfaltz A. Yamamoto H. Springer; Heidelberg: 1999.  p.649-677  
• 1c Johnson RA. Sharpless KB. In Catalytic Asymmetric Synthesis   2nd ed.:  Ojima I. Wiley-VCH; New York: 2000.  p.231-285  
• 1d Katsuki T. In Catalytic Asymmetric Synthesis   2nd ed.:  Ojima I. Wiley-VCH; New York: 2000.  p.287-325  
• 2 Aziridines and Epoxides in Organic Synthesis   Yudin AK. Wiley-VCH; Weinheim: 2006. 
• See, for example:
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• For leading references on this transformation, see:
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• 13 Higher pH values were not considered since the background reaction could be significant. See: Kurihara M. Ito S. Tsutsumi N. Miyata N. Tetrahedron Lett.  1994,  35:  1577 
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8

Diacetate 2 is a very effective as epoxidation catalyst using 10 mol% of catalyst loading. Loading for Shi’s catalysts usually ranges from 20 mol% to 30 mol%. See refs. 4a-c.

11

Compound 4e (0.37 g, 46% yield) was obtained as a colourless oil. ^¹H NMR (400 MHz, CDCl₃): δ = 7.27-7.40 (m, 15 H), 6.48 (dt, 1 H, J = 16.0, 1.3 Hz), 6.28 (dt, 1 H, J = 16.0, 6.9 Hz), 5.42 (s, 1 H), 3.62 (t, 2 H, J = 6.9 Hz), 2.60 (qd, 2 H, J = 6.9, 1.3 Hz). ^¹³C NMR: δ = 142.4, 137.7, 131.6, 128.5, 128.4, 127.4, 127.3, 127.2, 127.0, 126.0, 83.7, 68.7, 33.6.
The asymmetric epoxidation of alkene 4e to give (+)-5e was carried out by the general procedure (see ref. 12).
Compound 5e (0.15 g, 52% yield); white solid; mp 56 ˚C; [α]_D ^²5 +28.53 (c 0.12, CH₂Cl₂). IR: 2871-3066, 1599, 1491, 1097, 1037, 855 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 7.12-7.36 (m, 15 H), 5.36 (s, 1 H), 3.69 (d, 1 H, J = 1.9 Hz), 3.65 (t, 2 H, J = 6.0 Hz), 3.13 (td, J = 5.6, 1.9 Hz), 2.02 (td, 2 H, J = 5.6, 6.0 Hz). ^¹³C NMR: δ = 142.3, 142.3, 137.8, 128.6, 128.5, 128.2, 127.6, 127.6, 127.3, 127.1, 127.0, 125.7, 84.0, 65.7, 61.1, 58.8, 33.1. HRMS: m/z calcd for C₂₃H₂₂O₂Na: 353.1517; found: 353.1520. Enantiomeric excess was determined by HPLC using a chiral stationary phase (Chiracel OD-H column), eluent: hexane-i-PrOH (95:5); flow: 0.8 mL/min; l = 216 nm; t _R (major) = 10.8 min; t _R (minor) = 11.7 min.

12

General Procedure for the Epoxidation of Alkenes: The corresponding alkene (2.22 mmol) and the required amount of catalyst 3 (10-30 mol%) were dissolved in MeCN-dimethoxymethane (44 mL, 1:2). A pH 6 buffer solution (8 mL), tetrabutylammonium hydrogen sulfate (35 mg, 0.10 mmol) was slowly added with stirring and the mixture was cooled to the desired temperature. The flask was equipped with two syringe pumps; one of them was filled with a solution of Oxone (3.62-6.82 mmol) in pH 6 buffer (14 mL) and the other one with a solution of K₂CO₃ (5.33-16.06 mmol) in H₂O (14 mL). The two solutions were added dropwise over a 2 h period (syringe pump). The solution was stirred at 0 ˚C for the corresponding reaction time. The mixture was diluted with H₂O (40 mL) and extracted with the appropriate organic solvent [5a and 5h: hexane (4 × 40 mL); 5b-g,i-l: CH₂Cl₂ (4 × 40 mL)]. The combined organic fractions were collected and washed with brine (50 mL), dried over Na₂SO₄, filtered and the solvents were removed under reduced pressure. The crude material was purified by flash chromatography on SiO₂˙Et₃N (2.5%). Enantioselec-tivity was determined by chiral chromatography and the configuration of epoxides was established by comparison with either reported elution order or optical rotation if reported data was available. For 5a, HPLC; Chiralpak AD.^¹4 For 5b,^¹5 5j,^¹6 and 5k,^¹7 GC: gamma dex. For 5c ^¹8 and 5h,^¹9 HPLC; Chiralcel OD. For 5d, HPLC; Chiralcel OD-H.^²0 For 5f,^²¹ HPLC: Chiralcel AD-H. For 5l GC: gamma dex.