We have developed one-step procedures for the synthesis of enantioenriched O-acylated cyanohydrins and hydroxyphosphonates from aldehydes and acyl cyanides or acyl phosphonates, respectively. The desired transformations were achieved by dual catalytic activation using chiral Lewis acids in combination with achiral Lewis bases. Figure 1. <img src='https://acs-archive-assets2.s3.amazonaws.com/241nm/uploads/70553_silole2.jpg' alt='' />The stereoselectivity of the acylcyanations were improved, without compromising the yields, by a novel methodology for asymmetric synthesis: the undesired minor stereoisomers from a stereoselective reaction are recycled back to the prochiral starting reagent, thereby giving it another chance in the reaction. The catalytic system consists of a titanium salen dimer which catalyzes the forward reaction between an aldehyde and an acyl cyanide in the organic phase, and a biocatalyst that in the aqueous phase hydrolyzes the minor stereoisomers. We have demonstrated the utility of this system in the total synthesis of �-adrenergic antagonists and in the preparation of a range of 4-amino-2(5H)-furanones. Current efforts are focused on expanding the procedure to other reactions.

Dual activation and minor enantiomer recycling: Asymmetric synthesis of O-acylated cyanohydrins and hydroxyphosphonates

248th National Meeting (2014)

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