The Rational Design of Modified Cinchona Alkaloid Catalysts. Application to a New Asymmetric Synthesis of Chiral Chromanes

A new asymmetric synthesis of 2-substituted chiral chromanes has been achieved. The key step is the intramolecular conjugate addition of a phenolic nucleophile on a alpha,beta-unsaturated ester catalyzed by Cinchona alkaloids. The high ee's obtained with cinchonine and its derivatives have been rationalized by ab initio quantum chemistry calculations of transition state structures. (C) 2004 Elsevier Ltd. All rights reserved.