Abstract
The use of chiral enol silanes in fundamental transformations such as Mukaiyama aldol, Michael, and Mannich reactions as well as Saegusa–Ito dehydrogenations has enabled the chemical synthesis of enantiopure natural products and valuable pharmaceuticals. However, accessing these intermediates in high enantiopurity has generally required the use of either stoichiometric chiral precursors or stoichiometric chiral reagents. We now describe a catalytic approach in which strongly acidic and confined imidodiphosphorimidates (IDPi) catalyze highly enantioselective interconversions of ketones and enol silanes. These “silicon–hydrogen exchange reactions” enable access to enantiopure enol silanes via tautomerizing σ-bond metatheses, either in a deprotosilylative desymmetrization of ketones with allyl silanes as the silicon source or in a protodesilylative kinetic resolution of racemic enol silanes with a carboxylic acid as the silyl acceptor.
Highlights
The use of chiral enol silanes in fundamental transformations such as Mukaiyama aldol, Michael, and Mannich reactions as well as Saegusa−Ito dehydrogenations has enabled the chemical synthesis of enantiopure natural products and valuable pharmaceuticals
We found that, under certain conditions, enol silanes can form as side products in Mukaiyama aldol and Hosomi−Sakurai reactions via silylium asymmetric counteranion-directed catalysis (Si-ACDC).[15−17] Inspired by these observations, we became intrigued by the opportunity to develop asymmetric silicon−hydrogen exchange reactions toward enantiopure enol silanes
We envisioned a catalytic cycle in which, upon the formation of a chiral silylium ion-equivalent (R3SiX*) and propene, via protodesilylation of an allylsilane by the strong acid HX*, a siloxocarbenium ion intermediate could be reversibly generated from the starting ketone (Scheme 1C)
Summary
Generous support from the Max Planck Society, the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), Leibniz Award to B.L. and under Germany’s Excellence Strategy−EXC 2033−390677874−RESOLV, and the European Research Council (ERC, European Union’s Horizon 2020 research and innovation program “C−H Acids for Organic Synthesis, CHAOS” Advanced Grant Agreement No 694228) is gratefully acknowledged. The authors thank Benjamin Mitschke for his help during the preparation of this manuscript and several members of the group for crowd reviewing. We thank the technicians of our group and the members of our NMR, MS, and chromatography groups for their excellent service
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