Stereospecificity in the Pictet-Spengler reaction kinetic vs thermodynamic control

Article abstract of DOI:10.1016/0040-4039(91)80847-Y

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 β-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, Δ) led to kinetic trapping of the cis/trans diastereomers, whereas reaction in TFA/CH₂Cl₂(25°C) provided tetrahydro β-carbolines via thermodynamic control and increased trans diastereoselectivity in most cases.