Abstract
The Pictet-Spengler reaction of Nb-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.
The Pictet-Spengler reaction of tryptophan methyl ester with butyraldehyde (PhH, Δ) occurs with trans stereoselectivity (77/23); furthermore, use of the isopropyl ester 10 under the same conditions provides even higher trans stereoselectivity (87/13). These results imply that the trans stereoselectivity occurs (2b⪰3b) as illustrated.