First Highly Regio-and Diastereoselective [3+2] Cycloaddition of Chiral Nonracemic Fischer Carbene Complexes with Azomethine Ylides:An Enantioselective Synthesis of (+)-Rolipram

摘要

A new procedure for the synthesis of 1,3,4-trisubstituted and 1,4-disubstituted pyrrolidin-2-one defivatives in an enantioselective rashion is reported.The 1,3-dipolar cycloaddition of (+-)-menthol and (-)-8-phenylmenthol derived Fischer alkoxy alkenyl carbene complexes with in situ generated functionalized azomethine ylides gives the corresponding cycloadducts as chdlated tetracarbonyl Fischer carbene complexes.Only one regiosomer is detected in all cases,and the diastereoselectivity of the reaction is very high when(-)-8-phenylmenthol derived carbenes are dmployed.Oxidation and further transformation of the cycloadducts provide an easy access to pyrrolidin-2-ones.The anti-inflammatory and antidepressant drug(+)-Rolipram is readily prepared in four steps in a 20% overall yield by taking advantage of this newly developed methodology.