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

ABSTRACT: 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 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.

SUBMITTER: Andres R

PROVIDER: S-EPMC9313548 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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

Andres Rémi R Wang Qian Q Zhu Jieping J

Angewandte Chemie (International ed. in English) 20220311 19

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 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 i ...[more]

PMID: 35225416

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