Synlett 2005(4): 603-606  
DOI: 10.1055/s-2005-863710
LETTER
© Georg Thieme Verlag Stuttgart · New York

Asymmetric Michael Addition of Arylthiols to α,β-Unsaturated Carbonyl Compounds Catalyzed by Bifunctional Organocatalysts

Bang-Jing Lib, Lin Jianga, Min Liua, Ying-Chun Chen*a, Li-Sheng Dingb, Yong Wua
a Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu 610041, P. R. China
Fax: +86(28)85502609; e-Mail: ycchenhuaxi@yahoo.com.cn;
b Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, P. R. China
Further Information

Publication History

Received 10 December 2004
Publication Date:
22 February 2005 (online)

Abstract

Bifunctional chiral organocatalysts comprising thiourea and tertiary amine groups were synthesized. They act as efficient catalysts for asymmetric Michael addition of arylthiols to α,β-unsaturated carbonyl compounds. Enantioselectivity up to 85% has been achieved. Asymmetric α-protonation reaction (up to 60% ee) can be obtained in the presence of the bifunctional catalyst.

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HRMS data of new organocatalysts: 1a, 564.1770 (calcd 564.1782); 1b, 564.1781 (calcd 564.1782); 1f, 501.1853 (calcd 501.1861); 1g, 701.1728 (calcd 701.1734).

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General Experimental Procedure for ( S , S )-1d-Catalyzed Asymmetric Michael Addition. Phenylthiol (12 µL, 0.11 mmol) was added to the stirred solution of α,β-unsaturated imide 7a (25.1 mg, 0.1 mmol) and 1d (4.2 mg, 0.01 mmol) in 0.5 mL CH2Cl2 at -40 °C. The reaction was stirred for 72 h. Flash chromatography eluting with petroleum ether-EtOAc (10:1) gave the product as a white solid (35.3 mg, 98%). 1H NMR (400 MHz, CDCl3): δ = 9.47 (s, NH), 7.78-7.76 (m, 2 H), 7.62-7.59 (m, 1 H), 7.51-7.47 (m, 2 H), 7.36-7.32 (m, 4 H), 7.29-7.19 (m, 6 H), 4.85 (dd, J = 1.6, 8.4 Hz, 1 H), 3.77 (dd, J = 8.4, 15.6 Hz, 1 H), 3.62 (dd, J = 8.4, 15.6 Hz, 1 H). 13C NMR (100 MHz, CDCl3): δ = 173.3, 165.6, 140.8, 133.9, 133.3, 133.1, 132.4, 128.9, 128.8, 128.4, 127.8, 127.7, 127.6, 127.4, 48.2, 43.8. ESI-MS: m/z = 360.1 [M - H]-; ee was determined by HPLC on Daicel Chiralcel OD (20% 2-propanol in hexane, 0.5 mL/min, t S = 10.8 min, t R = 12.1 min, 75% ee).

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The absolute configuration was determined by the rotation after conversion to ethyl ester.8c