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Beyond Benzyl Grignards: Facile Generation of Benzyl Carbanions from Styrenes
Author(s) -
Grigg R. David,
Rigoli Jared W.,
Van Hoveln Ryan,
Neale Samuel,
Schomaker Jennifer M.
Publication year - 2012
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201200642
Subject(s) - carbanion , chemistry , pinacol , steric effects , combinatorial chemistry , electrophile , benzyl bromide , organic chemistry , medicinal chemistry , catalysis
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 Cu I ‐catalyzed Markovnikov hydroboration of the styrenic double bond by using a bulky pinacol borane source is followed by treatment with KO t Bu to facilitate a sterically induced cleavage of the CB bond to produce a benzylic carbanion. Quenching this intermediate with a variety of electrophiles, including CO 2 , CS 2 , isocyanates, and isothiocyanates, promotes CC 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.