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

A Corrigendum to this article was published on 20 June 2013

This article has been updated

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.

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Figure 1: Suzuki–Miyaura cross-coupling reactions with enantioenriched secondary alkyl boronate derivatives.
Figure 2
Figure 3: Proposed transition state for the stereospecific cross-coupling reaction of 3,3-diboronyl carboxyester 9 and applications of mono cross-coupled products 10.

Change history

  • 10 May 2013

    In the version of this Article originally published, in Table 1, the ferrocene-based ligands 4, 5, 7 and 8 should have had 1,2-substituted cyclopentadienyl rings rather than 1,3-substituted. This error has been corrected in the HTML and PDF versions of this Article.

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Acknowledgements

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.

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J.C.H.L. performed the experiments. R.M. performed the X-ray crystallographic analysis of 2b. D.G.H. directed the project. The manuscript was co-written by J.C.H.L. and D.G.H.

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Correspondence to Dennis G. Hall.

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Crystallographic data for compound 2a (CIF 17 kb)

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Crystallographic data for compound 2b (CIF 32 kb)

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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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