Catalytic Enantioselective Desymmetrization of Meso Compounds in Total Synthesis of Natural Products: Towards an Economy of Chiral Reagents

International audienceMeso compounds represent a particular family of achiral molecules bearing elements of chirality. Their desymmetrization through enantioselective catalytic methods usually leads to elaborate chiral building blocks containing several stereogenic elements, which can be a very useful and elegant approach in the context of total synthesis. In the present review, the power of this strategy is illustrated through the different possibilities of catalytic enantioselective desymmetrization. From the combination of the hidden symmetry detection and the catalytic enantioselective transformations a new type of economy emerges: the economy of chiral reagents

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

International audienceA 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)