Nickel-Catalyzed Esterification of Aliphatic Amides.
Recent studies have demonstrated that amides can be used in nickel-catalyzed reactions that lead to cleavage of the amide C-N bond, with formation of a C-C or C-heteroatom bond. However, the general scope of these methodologies has been restricted to amides where the carbonyl is directly attached to an arene or heteroarene. We now report the nickel-catalyzed esterification of amides derived from aliphatic carboxylic acids. The transformation requires only a slight excess of the alcohol nucleophile and is tolerant of heterocycles, substrates with epimerizable stereocenters, and sterically congested coupling partners. Moreover, a series of amide competition experiments establish selectivity principles that will aid future synthetic design. These studies overcome a critical limitation of current Ni-catalyzed amide couplings and are expected to further stimulate the use of amides as synthetic building blocks in C-N bond cleavage processes.
Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Liana
L
Hie
Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Emma L
EL
Baker
Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Sarah M
SM
Anthony
Department of Chemical Development US, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, 06877, USA.
Jean-Nicolas
JN
Desrosiers
Department of Chemical Development US, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, 06877, USA.
Chris
C
Senanayake
Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Neil K
NK
Garg
D000577:Amides / Q000737:chemistry*; D002384:Catalysis; D004952:Esters / Q000138:chemical synthesis* / Q000737:chemistry; D008968:Molecular Conformation; D009532:Nickel / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry*
D000577:Amides; D004952:Esters; D009942:Organometallic Compounds; D009532:Nickel
aliphatic amides; cross-coupling; esterification; homogeneous catalysis; nickel