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.
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This research was generously funded by the Natural Sciences and Engineering Research Council (NSERC) of Canada, and the University of Alberta. J.C.H.L. thanks the University of Alberta for a Queen Elizabeth II Graduate Scholarship. The authors are grateful to M. Ferguson of the X-ray Crystallographic Laboratory (analysis of 2a) and to the Spectral Services staff at the University of Alberta, Department of Chemistry. The authors thank Solvias AG (H. Steiner and H.-U. Blaser) for a generous gift of chiral ligands.
The authors declare no competing financial interests.
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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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