Replication of chiral α-hydroxy acids via induction and amplification through an enantioenriched cyanohydrin
Tsuneomi Kawasaki1, Naoya Takamatsu2, Shohei Aiba2
1Department of Applied Chemistry, Tokyo University of Science, Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan. tkawa@rs.tus.ac.jp.
Abstract:
A spontaneous absolute asymmetric synthesis of cyanohydrins has been developed without any external chiral source through the combination of conglomerate formation and solution-phase racemization. This method integrates HCN addition reaction to an aldehyde with subsequent Viedma ripening; consequently, spontaneous deracemization and enantioselective reactive crystallization of cyanohydrins are achieved for the first time. Importantly, the hydrolysis products of the cyanohydrin-namely, the corresponding α-hydroxy acid and hydroxyamide-serve as chiral inducers that direct the handedness of solid-state asymmetric amplification, leading to highly enantioenriched cyanohydrins with matching chirality. This feedback between product formation and asymmetric amplification establishes a reaction network in which chirality is propagated and reinforced across molecular transformations. In combination with cyanohydrin hydrolysis, this system constitutes a chemically coupled process that approaches the replication of chiral α-hydroxy acids and hydroxyamides, key products in abiotic Strecker-type synthesis, and is therefore relevant to the origin of biological homochirality.
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