Direct enantio-convergent transformation of racemic substrates without racemization or symmetrizatio

Abstract

Asymmetric reactions that transform racemic mixtures into enantio-enriched products are in high demand, but classical kinetic resolution produces enantiopure compounds in <50% yield even in an ideal case. Many deracemization processes have thus been developed including dynamic kinetic resolution and dynamic kinetic asymmetric transformation, which can provide enantio-enriched products even after complete conversion of the racemic starting materials. However, these dynamic processes require racemization or symmetrization of the substrates or intermediates. We demonstrate a direct chemical enantio-convergent transformation without a racemization or symmetrization process. Copper(I)-catalysed asymmetric allylic substitution of a racemic allylic ether afforded a single enantiomer of an α-chiral allylboronate with complete conversion and high enantioselectivity (up to 98% enantiomeric excess). One enantiomer of the substrate undergoes an anti-SN2′-type reaction whereas the other enantiomer reacts via a syn-SN2′ pathway. The products, which cannot be prepared by dynamic procedures, have been used to construct all-carbon quaternary stereocentres. Processes that convert racemic chiral compounds into enantioenriched chiral products are highly sought after. Here, in a copper-catalysed borylation reaction one enantiomer of a cyclic allylic ether reacts with anti-stereoselectivity and the other reacts with syn-stereoselectivity. The starting material is not easily racemized and this new process is dubbed an enantioconvergent reaction.

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Ito, H., Kunii, S. & Sawamura, M. Direct enantio-convergent transformation of racemic substrates without racemization or symmetrization. Nature Chem 2, 972–976 (2010). https://doi.org/10.1038/nchem.801

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