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Beyond Benzyl Grignards: Facile Generation of Benzyl Carbanions from Styrenes

Authors

  • R. David Grigg,

    1. Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI 53706 (USA), Fax: (+1) 608-265-4534
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  • Jared W. Rigoli,

    1. Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI 53706 (USA), Fax: (+1) 608-265-4534
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  • Ryan Van Hoveln,

    1. Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI 53706 (USA), Fax: (+1) 608-265-4534
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  • Samuel Neale,

    1. Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI 53706 (USA), Fax: (+1) 608-265-4534
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  • Prof. Jennifer M. Schomaker

    Corresponding author
    1. Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI 53706 (USA), Fax: (+1) 608-265-4534
    • Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI 53706 (USA), Fax: (+1) 608-265-4534
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Abstract

Benzylic functionalization is a convenient approach towards the conversion of readily available aromatic hydrocarbon feedstocks into more useful molecules. However, the formation of carbanionic benzyl species from benzyl halides or similar precursors is far from trivial. An alternative approach is the direct reaction of a styrene with a suitable coupling partner, but these reactions often involve the use of precious-metal transition-metal catalysts. Herein, we report the facile and convenient generation of reactive benzyl anionic species from styrenes. A CuI-catalyzed Markovnikov hydroboration of the styrenic double bond by using a bulky pinacol borane source is followed by treatment with KOtBu to facilitate a sterically induced cleavage of the C[BOND]B bond to produce a benzylic carbanion. Quenching this intermediate with a variety of electrophiles, including CO2, CS2, isocyanates, and isothiocyanates, promotes C[BOND]C bond formation at the benzylic carbon atom. The utility of this methodology was demonstrated in a three-step, two-pot synthesis of the nonsteroidal anti-inflammatory drug (±)-flurbiprofen.

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