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Synlett 2014; 25(6): 805-808
DOI: 10.1055/s-0033-1340825
letter
© Georg Thieme Verlag Stuttgart · New York

Concise Synthesis of Chiral N-Benzyl-α,α-Diarylprolinols through Shi Asymmetric Epoxidation

Jie Li
a   College of Chemistry and Materials Engineering, Quzhou University, Quzhou 324000, P. R. of China   Fax: +86(570)8015339   Email: gechengsheng@qzu.zj.cn
,
Hai Zhou
a   College of Chemistry and Materials Engineering, Quzhou University, Quzhou 324000, P. R. of China   Fax: +86(570)8015339   Email: gechengsheng@qzu.zj.cn
,
Jiangsen Weng
a   College of Chemistry and Materials Engineering, Quzhou University, Quzhou 324000, P. R. of China   Fax: +86(570)8015339   Email: gechengsheng@qzu.zj.cn
,
Mingwen Wang
b   ACS Scientific Inc., Metuchen, NJ 08840, USA
,
Chengsheng Ge*
a   College of Chemistry and Materials Engineering, Quzhou University, Quzhou 324000, P. R. of China   Fax: +86(570)8015339   Email: gechengsheng@qzu.zj.cn
,
Wujie Tu
a   College of Chemistry and Materials Engineering, Quzhou University, Quzhou 324000, P. R. of China   Fax: +86(570)8015339   Email: gechengsheng@qzu.zj.cn
› Author Affiliations
Further Information

Publication History

Received: 05 December 2013

Accepted after revision: 22 January 2014

Publication Date:
11 March 2014 (online)

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Abstract

A concise and practical synthesis of chiral N-benzyl-α,α-diaryl-2-prolinols was developed through Shi asymmetric epoxidation, followed by double nucleophilic substitution of bromo-containing olefins. A series of enantioenriched N-benzyl-α,α-diaryl-2-prolinols were obtained with excellent enantioselectivities (96% ee) in moderate to good yields (40–76% yield). For the first time, enantiopure N-benzyl-α,α-diphenyl-2-prolinol was obtained from bromo-containing olefin using this methodology.

Key words

synthesis - chiral N-benzyl-α,α-diaryl-2-prolinols - asymmetric epoxidation

Supporting Information

    for this article is available online at http://www.thieme-connect.com/ejournals/toc/synlett.
  • Supporting Information
 

  • References and Notes

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  • 11 General Experimental Procedure for the Synthesis of 4a–g A mixture solution of 5,5-diphenyl-4-pentenyl bromide (2a, 1 g, 3.3 mmol) in MeCN–DMM (1:2, v/v, 24 mL), and Na2B4O7·10H2O (0.62 g, 1.6 mmol), tetrabutylammonium hydrogen sulfate (45 mg, 0.13 mmol), and Shi catalyst (0.42 g, 1.65 mmol) in a buffer solution [4·10–4 M aq Na2(EDTA), 16 mL] was cooled to 0 °C in an ice bath. A solution of Oxone (5.06 g, 8.25 mmol) in 4·10–4 M aq Na2(EDTA) solution (20 mL) and a solution of K2CO3 (5 g, 36 mmol) in deionized water were, respectively, added dropwise through two separate addition funnels over a period of 3 h at 0 °C. After addition, the reaction was stirred for another 3 h at this temperature and then diluted with H2O (150 mL). The resulting solution was extracted with PE (2 × 150 mL), dried over Na2SO4, and concentrated to afford the crude 3a (1.56 g, >95% purity), which was applied to next step without purification. The mixture solution of the above obtained crude 3a (1.56 g, ca. 3.3 mmol), benzyl amine (0.706 g, 6.6 mmol), K2CO3 (0.91 g, 6.6 mmol), and freshly activated 4 Å MS (1.56 g) in MeCN (10 mL) was refluxed for 12 h. The resulting solution was filtered and evaporated to give the crude product which was purified over silica gel chroma-tography (EtOAc–PE = 1:20 to 1:10) to afford 0.86 g of 4a as a white solid. Compound 4a: yield 76%; 96% ee. [α]D 22 +91.5 (c 1.0, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 7.75 (d, J = 8 Hz, 2 H), 7.61 (d, J = 8 Hz, 2 H), 7.35–7.06 (m, 11 H), 4.03–3.99 (m, 1 H), 3.26 (d, J = 16 Hz, 1 H), 3.06 (d, J = 16 Hz, 1 H), 2.98–2.93 (m, 1 H), 2.43–2.35 (m, 1 H), 2.03–1.93 (m, 1 H), 1.84–1.63 (m, 3 H). Compound 4b: yield 70%; 96% ee. [α]D 22 +98.4 (c 1.0, CHCl3). IR (KBr): ν = 3400, 2975, 2887, 2808, 1649, 1600, 1502, 1223, 1037, 836 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.70–7.65 (m, 2 H), 7.56–7.51 (m, 2 H), 7.28 (m, 3 H), 7.08 (m, 6H), 3.96–3.92 (m, 1 H), 3.29 (d, J = 16 Hz, 1 H), 3.10 (d, J = 16 Hz, 1 H), 2.98–2.95 (m, 1 H), 1.99–1.90 (m, 1 H), 1.75 (m, 3 H). 13C NMR (100 MHz, CDCl3): δ = 128.2, 128.0, 127.0, 126.9, 126.9, 126.8, 126.8, 115.0, 114.8, 114.8, 114.6, 77.3, 70.6, 60.6, 55.5, 29.8, 24.1. HRMS: m/z calcd for C24H24F2NO: 380.1820 [M + H]+; found: 380.1797. Compound 4c: yield 40%; 96% ee. [α]D 22 +101.1 (c 1.0, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 7.58 (d, J = 8 Hz, 2 H), 7.45 (d, J = 8 Hz, 2 H), 7.24–7.21 (m, 3 H), 7.06 (d, J = 8 Hz, 2 H), 6.83–6.78 (m, 4 H), 4.85 (br, 1 H), 3.89–3.86 (m, 1 H), 3.75 (s, 1 H), 3.69 (s, 3 H), 3.30 (d, J = 12 Hz, 1 H), 3.02 (d, J = 12 Hz, 1 H), 2.37–2.30 (m, 1 H), 1.97–1.87 (m, 1 H), 1.78–1.71 (m, 1 H), 1.65–1.57 (m, 2 H). Compound 4d: yield 75%; 96% ee. [α]D 22 +94.5 (c 1.0, CHCl3). IR (KBr): ν = 3290, 3027, 2965, 2919, 2806, 1507, 1454, 1381, 1099, 1038, 803, 699 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.61 (d, J = 8 Hz, 2 H), 7.47 (d, J = 12 Hz, 2 H), 7.28–7.21 (m, 3 H), 7.13–7.08 (m, 6 H), 3.98–3.93 (m, 1 H), 3.33 (d, J = 16 Hz, 1 H), 3.04 (d, J = 16 Hz, 1 H), 2.96–2.90 (m, 1 H), 2.41–2.32 (m, 1 H), 2.30 (s, 3 H), 2.24 (s, 3 H), 2.04–1.94 (m, 1 H), 1.91–1.73 (m, 1 H), 1.69–1.59 (m, 2 H). 13C NMR (100 MHz, CDCl3): δ = 145.1, 143.9, 139.6, 135.5, 135.3, 128.7, 128.7, 128.5, 127.9, 126.6, 125.2, 77.6, 70.6, 60.6, 55.5, 29.8, 24.1, 20.9. HRMS: m/z calcd for C26H30NO: 372.2322 [M + H]+; found: 372.2292. Compound 4e: yield 76%; 96% ee. [α]D 22 +90.8 (c 1.0, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 7.55 (s, 1 H), 7.47 (d, J = 8 Hz, 1 H), 7.41 (s, 1 H), 7.36 (d, J = 8 Hz, 1 H), 7.30–7.13 (m, 5 H), 7.04 (d, J = 6 Hz, 1 H), 6.98 (d, J = 8 Hz, 1 H), 6.90 (d, J = 8 Hz, 1 H), 3.94–3.90 (m, 1 H), 3.18 (d, J = 12 Hz, 1 H), 3.02 (d, J = 12 Hz, 1 H), 2.93–2.91 (m, 1 H), 2.38–2.35 (m, 7 H), 2.03–1.94 (m, 1 H), 1.81–1.56 (m, 3 H). Compound 4f: yield 77%. 96% ee. [α]D 22 +88.8 (c 1.0, CHCl3). IR (KBr): ν = 3426, 2964, 2930, 1652, 1607, 1452, 1414, 1261, 1099, 1030, 818, 699 cm–1. 1H NMR (300 MHz, CDCl3): δ = 7.61 (d, J = 12 Hz, 2 H), 7.47 (d, J = 8 Hz, 4 H), 7.17–7.03 (m, 9 H), 4.85 (br s, 1 H), 3.96–3.91 (m, 1 H), 3.27 (d, J = 16 Hz, 1 H), 3.02 (d, J = 16 Hz, 1 H), 2.92–2.89 (m, 1 H), 2.62–2.51 (m, 4 H), 1.94–1.93 (m, 1 H), 1.76–1.74 (m, 1 H), 1.61–1.54 (m, 2 H), 1.21–1.10 (m, 6 H). 13C NMR (100 MHz, CDCl3): δ = 145.3, 144.1, 141.8, 141.6, 139.7, 128.5, 127.9, 127.4, 127.3, 126.6, 125.4, 125.2, 77.7, 70.8, 60.6, 55.6, 29.9, 28.4, 28.3, 24.2, 14.4, 15.4. HRMS: m/z calcd for C26H30NO: 400.2635 [M + H]+; found: 400.2611. Compound 4g: yield 68%. 96% ee. [α]D 22 +94.8 (c 1.0, CHCl3). IR (KBr): ν = 3333, 3061, 3028, 2963, 2871, 2804, 1488, 1403, 1092, 1012, 809, 699 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.66 (d, J = 12 Hz, 2 H), 7.51 (d, J = 12 Hz, 2 H), 7.30–7.22 (m, 7 H), 7.06 (d, J = 8 Hz, 2 H), 5.07 (br s, 1 H), 3.95–3.91 (m, 1 H), 3.33 (d, J = 20 Hz, 1 H), 3.10 (d, J = 16 Hz, 1 H), 2.98–2.94 (m, 1 H), 2.43–2.37 (m, 1 H), 1.98–1.92 (m, 1 H), 1.74–1.62 (m, 3 H). 13C NMR (100 MHz, CDCl3): δ = 146.6, 145.2, 139.4, 132.7, 132.5, 128.7, 128.7, 128.6, 128.5, 127.3, 127.3, 127.2, 77.4, 70.6, 60.8, 55.7, 30.0, 24.2. HRMS: m/z calcd for C24H24Cl2NO: 412.1229 [M + H]+; found: 412.1209.