Enantioselective Dearomatization of Pyridines with Styrene-Derived Nucleophiles
Asymmetric Cu-Catalyzed 1,4-Dearomatization of Pyridines and Pyridazines without Preactivation of the Heterocycle or Nucleophile.
J. Am. Chem. Soc. 2018;
18. Juni 2018 (online)
Dearomatization of heteroaromatics is a valuable transformation in organic chemistry to create new carbon–carbon bonds. Herein, Buchwald and co-workers report the dearomatization of pyridines with a chiral benzylic copper species generated through an enantioselective copper hydride addition to the corresponding styrene.
The intermediate dihydropyridine could be oxidized to regenerate the pyridine or reduced to give the piperidine scaffold. A variety of substituents could be tolerated on either the styrene or pyridine, including halogens and alkyl or alkynyl groups. The alkene could also be a β-substituted styrene containing a heteroatom in the alkyl chain.