Catalytic Enantioselective Pictet-Spengler Reaction of α-Ketoamides Catalyzed by a Single H-Bond Donor Organocatalyst

The asymmetric Pictet-Spengler reaction (PSR) with aldehydes is well known. However, PSR involving ketones as electrophilic partners is far-less developed. We report herein the first examples of catalytic enantioselective PSR of tryptamines with alpha-ketoamides. A new class of easily accessible prolyl-urea organocatalysts bearing a single H-bond donor function catalyzes the title reaction to afford 1,1-disubstituted tetrahydro-beta-carbolines in excellent yields and enantioselectivities. The kinetic isotope effect using C2-deuterium-labelled tryptamine indicates that the rearomatization of the pentahydro-beta-carbolinium ion intermediate might be the rate- and the enantioselectivity-determining step.

Automated summary

This paper reports the first examples of catalytic enantioselective PSR of tryptamines with alpha-ketoamides, and a new class of easily accessible organocatalysts was developed to achieve excellent yields and enantioselectivities.