STEREOSPECIFICITY IN THE PICTET-SPENGLER REACTION - KINETIC VS THERMODYNAMIC CONTROL

The Pictet-Spengler reaction of N(b)-benzyl tryptophan methyl ester 4 with 5 in refluxing benzene yielded a mixture of cis and trans tetrahydro beta-carbolines in a ratio of 7a(23)/7b(77), whereas the analogous reaction of isopropyl ester 10 with 5 provided increased trans stereoselectivity [cis(13):trans(87)]. The implications in regard to the role of intermediates 1-3 in this condensation are described. Moreover, Pictet-Spengler reaction of 4 or 10 with aldehydes (Ph,DELTA) led to kinetic trapping of the cis/trans diastereomers, whereas reaction in TFA/CH2Cl2(25-degrees-C) provided tetrahydro beta-carbolines via thermodynamic control and increased trans diastereoselectivity in most cases.