Enantioselective α-hydroxylation of β-keto esters catalyzed by chiral S-timolol derivatives

A screen of aryloxy aminopropanol organocatalysts derived from the beta-blocker inhibitor S-timolol determined the most active catalyst of asymmetric alpha-hydroxylation of beta-keto esters. (R)-1-(tert-butylamino)-3-(3,4,5-trimethoxyphenoxy) propan-2-ol (3k) was the most effective derivative, enantioselectively catalyzing alpha-hydroxylation of beta-keto esters using tert-butyl hydroperoxide as the oxidant in hexane to afford the corresponding products in excellent yield and with good enantioselectivity (up to 96% yield, 88% ee). (C) 2012 Elsevier Ltd. All rights reserved.