A 4-hydroxypyrrolidine-catalyzed mannich reaction of aldehydes: Control of anti-selectivity by hydrogen bonding assisted by bronsted acids

摘要

An anti-selective Mannich reaction of aldehydes with N-sulfonyl imines has been developed by using a 4-hydroxypyrrolidine in combination with an external Br?nsted acid. The catalyst design is based on three elements: the ct-substituent of the pyrrolidine, the 4-hydroxy group, and the Br?nsted acid, the combination of which is essential for high chemical and stereochemical efficiency. The reaction works with aromatic aldehydederived imines, which have rarely been employed in previously reported enamine-based anti-Mannich reactions. Additionally, both N-tosyl and N-nosyl imines can be successfully used and the Mannich adducts can be easily reduced or oxidized, and after N-deprotection the corresponding ?-amino acids and ?-amino alcohols can be obtained with good yields. The results also show that this ternary catalytic system may be practical in other enamine-based reactions.