19950-47-1Relevant academic research and scientific papers
Beyond benzyl grignards: Facile generation of benzyl carbanions from styrenes
Grigg, R. David,Rigoli, Jared W.,Van Hoveln, Ryan,Neale, Samuel,Schomaker, Jennifer M.
, p. 9391 - 9396 (2012/08/29)
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-B bond to produce a benzylic carbanion. Quenching this intermediate with a variety of electrophiles, including CO2, CS2, isocyanates, and isothiocyanates, promotes C-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. Make or break: The facile generation of benzyl anion equivalents from styrenes has been achieved by using a Cu-catalyzed hydroboration in conjunction with sterically induced cleavage of the C-B bond with tBuOK. Quenching this reactive intermediate with heteroallene electrophiles yields benzylic C-C bond formation (see scheme), and the utility of this methodology has been demonstrated by a synthesis of the nonsteroidal anti-inflammatory drug (±)-flurbiprofen. Copyright
