Highly Enantioselective Acylation of Acyclic Meso 1,3-Diols through Synergistic Isothiourea-Catalyzed Desymmetrization/Chiroablative Kinetic Resolution

Jérémy Mérad (1) , Prashant Borkar (1) , Tracy Bouyon Yenda (1) , Christèle Roux (1) , Jean-Marc Pons (1) , Jean-Luc Parrain (1) , Olivier Chuzel (1) , Cyril Bressy (1)

1 ISM2 - Institut des Sciences Moléculaires de Marseille

A general and highly efficient organocatalyzed desymmetrization of acyclic meso 1,3-diols through acyl transfer using chiral isothioureas is described. The introduction of π-systems in the acyclic substrates provided new opportunities in terms of reactivity, enantioselectivity and synthetic potential. To reach this high level of enantioselectivity (up to er >99:1), the reaction proceeds through a synergistic mechanism involving a desymmetrization reaction and a chiroablative kinetic resolution process. This methodology was used with success as the sole enantioselective catalytic step (developed on a gram scale) to achieve the total synthesis of the antiosteoporotic diarylheptanoid (−)-diospongin A (7 steps).

Mots clés: Desymmetrization; meso compounds; Organocatalysis; Amplification; Diospongin A; 1; 3-diols

Domaines: Chimie organique

Jérémy Mérad, Prashant Borkar, Tracy Bouyon Yenda, Christèle Roux, Jean-Marc Pons, et al.. Highly Enantioselective Acylation of Acyclic Meso 1,3-Diols through Synergistic Isothiourea-Catalyzed Desymmetrization/Chiroablative Kinetic Resolution. Organic Letters, 2015, 17, pp.2118. ⟨10.1021/acs.orglett.5b00707⟩. ⟨hal-01224270⟩