title: Novel alpha,alpha-difluorohomophthalimides via copper-catalyzed tandom cross-coupling-cyclization of 2-halobenzamides with alpha,alpha-difluoro Reformatskii reagent.
abstract: Novel alpha,alpha-difluorohomophthalimides 2 were prepared by reacting N-substituted 2-halobenzamides with the alpha,alpha-difluoro Reformatskii reagent BrZnCF2CO2Et (3) in the presence of CuBr at room temperature. The synthesis involves a CuBr-mediated cross-coupling of 3 with aryl iodides or activated aryl bromides, followed by a spontaneous cyclization of the ethyl 2-benzamido-alpha,alpha-difluoroacetate intermediates at room temperature. N-unsubstituted alpha,alpha-difluorohomophthalimides 2 (R' = H), bearing an acidic imide proton capable of acting as a carboxylic acid bioisostere, were also prepared by reacting 3 equiv of 3 with the parent 2-iodobenzamides. Other aryl iodides such as 3-iodo-imidazo[1,2-alpha]pyridine were also used for the tandem coupling-cyclization reaction.
authors.affiliation: Affymax, Inc., 4001 Miranda Ave., Palo Alto, California 94304, USA.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Pan
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Holmes
authors.forename: David
authors.initials: D
authors.lastname: Tumelty