Enantioselective preparation and chemoselective cross-coupling of 1,1-diboron compounds

Abstract

The simplicity, efficiency and generality of the transition-metal-catalysed Suzuki–Miyaura cross-coupling reaction has led to its application in the preparation of a wide variety of organic compounds. Cross-coupling of alkylboron derivatives, however, remains a major challenge, in particular with regard to stereochemical control. Here, we describe the preparation and reaction of highly optically enriched 1,1-diboron compounds. A catalytic asymmetric conjugate borylation of β-boronylacrylates provided geminal diboronate products that feature two distinct boronyl units, in 99% enantiomeric excess. Chemoselective cross-coupling of one-boronyl unit, a trifluoroborate salt, occurred stereospecifically via inversion of its configuration to generate enantioenriched benzylic or allylic boronates. The difficult transmetallation in the Suzuki–Miyaura catalytic reaction cycle is believed to be facilitated by a stabilization effect from the second boronyl unit, and internal coordination by the oxygen of the proximal carboxyester. We also explored subsequent functionalization of the second boronyl unit. Stereoselective Suzuki–Miyaura cross-coupling reactions involving non-benzylic secondary alkylboronates are notoriously challenging. Here, an enantioselective synthesis of 1,1-diboronyl compounds using asymmetric conjugate borylation, followed by chemoselective mono cross-coupling with inversion at the diboron centre, is used to produce highly enantioenriched benzylic or allylic boronates, which themselves are useful reagents for a number of processes.

Cite this article

Lee, J., McDonald, R. & Hall, D. Enantioselective preparation and chemoselective cross-coupling of 1,1-diboron compounds. Nature Chem 3, 894–899 (2011). https://doi.org/10.1038/nchem.1150

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