In recent years, cooperative approaches in which thiourea organocatalysts act in concert with Bronsted acid co-catalysts have garnered interest in the field of asymmetric catalysis. Internally chiral conjugate-base-stabilized Bronsted acid catalysts will be introduced as a generalizable concept for asymmetric catalysis and applied specifically to the enantioselective direct Pictet-Spengler reaction. These catalysts contain an acidic site and an anion receptor moiety; in our case, a carboxylic acid group and a thiourea moiety fulfills these roles. Substrate protonation by the catalyst results in the association of the conjugate base with the anion recognition site, resulting in the formation of a rigid substrate/catalyst ion pair. These new catalysts have facilitated the catalytic enantioselective Pictet-Spengler reaction with unmodified tryptamine. Past problems with reactivity have been alleviated as the corresponding tetrahydrobetacarbolines have been obtained in moderate to high yields with up to 92% ee in lower reaction times. The use of achiral Bronsted acid additives and in-situ Boc protection have also been explored to assist in catalyst turnover.

Chiral internally conjugate-base-stabilized Bronsted acids as catalysts in the enantioselective direct Pictet Spengler reaction

248th National Meeting (2014)

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