Double Catalytic Kinetic Resolution (DoCKR) of Acyclic anti-1,3-Diols: The Additive Horeau Amplification

Jérémy Merad (1) , Prashant Borkar (1) , Frédéric Caijo , Jean-Marc Pons (1) , Jean-Luc Parrain (1) , Olivier Chuzel (1) , Cyril Bressy (1)

1 ISM2 - Institut des Sciences Moléculaires de Marseille

The concept of a synergistic double catalytic kinetic resolution (DoCKR) as described in this article was successfully applied to racemic acyclic anti-1,3-diols, a common motif in natural products. This process takes advantage of an additive Horeau amplification involving two successive enantioselective organocatalytic acylation reactions, and leads to diesters and recovered diols with high enantiopurities. It was first developed with C 2-symmetrical diols and then further extended to non-C 2-symmetrical anti diols to prepare useful chiral building blocks. The protocol is highly practical as it only requires 1 mol % of a commercially available organocatalyst and leads to easily separable products. This procedure was applied to the shortest reported total synthesis of (+ +)-cryptocaryalactone, a natural product with anti-germinative activity.

Mots clés: enantioselectivity; kinetic resolution; natural products; organocatalysis; diols

Domaines: Chimie organique

Jérémy Merad, Prashant Borkar, Frédéric Caijo, Jean-Marc Pons, Jean-Luc Parrain, et al.. Double Catalytic Kinetic Resolution (DoCKR) of Acyclic anti-1,3-Diols: The Additive Horeau Amplification. Angewandte Chemie International Edition, 2017, 56, pp.16052-16056. ⟨10.1002/anie.201709844⟩. ⟨hal-01687281⟩