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

Andres, RémiWang, QiangZhu, Jieping2022-06-212022-06-212022-06-21202210.1002/anie.202201788https://infoscience.epfl.ch/handle/20.500.14299/188721The 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 α-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-β-carbolines in excellent yields and enantioselectivities. The kinetic isotope effect using C2-deuterium-labelled tryptamine indicates that the rearomatization of the pentahydro-β-carbolinium ion intermediate might be the rate- and the enantioselectivity-determining step.Asymmetric SynthesisOrganocatalysisPictet–Spengler ReactionTetrahydrocarbazoleα-OxoamidesCatalytic Enantioselective Pictet–Spengler Reaction of α‐Ketoamides Catalyzed by a Single H‐Bond Donor Organocatalysttext::journal::journal article::research article