Enantioselective Evans-Tishchenko Reduction of b-Hydroxyketone Catalyzed by Lithium Binaphtholate.docVIP

Molecules 2011, 16, 5008-5019; doi:10.3390/moleculeOPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Enantioselective Evans-Tishchenko Reduction of β-Hydroxyketone Catalyzed by Lithium Binaphtholate Tomonori Ichibakase, Masato Nakatsu and Makoto Nakajima * Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan * Author to whom correspondence should be addressed; E-Mail: nakajima@gpo.kumamoto-u.ac.jp; Tel.: +81-96-371-4680; Fax: +81-96-362-7692. Received: 1 June 2011; in revised form: 10 June 2011 / Accepted: 15 June 2011 / Published: 17 June 2011 Abstract: Lithium diphenylbinaphtholate catalyzed the enantioselective Evans-Tishchenko reduction of achiral β-hydroxyketones to afford monoacyl-protected 1,3-diols with high stereoselectivities. In the reaction of racemic β-hydroxyketones, kinetic optical resolution occurred in a highly stereoselective manner. Keywords: Evans-Tishchenko reduction; lithium binaphtholate; β-hydroxyketone; 1,3-diol; enantioselectivity 1. Introduction Stereoselective synthesis of 1,3-diols is an important subject in synthetic organic chemistry because numerous biologically active compounds include such units [1,2]. One method to prepare chiral 1,3-diol is the reduction of β-hydroxyketones, and various metal hydride reagents have been applied to the syntheses of biologically active compounds using this method. Recently, acetalization of a β-hydroxy group with an aldehyde followed by a hydride shift to the carbonyl carbon, the so called Evans-Tishchenko reduction (Scheme 1) [3-5], has received much attention because it does not require the use of metal hydride reagents. Although the literature contains numerous examples using the Evans-Tishchenko reduction in the synthesis of biologically active compounds [6-13], the enantioselective Evans-Tishchenko reduction of an ach