Synthesis and Evaluation of 5-Phenyl-1H-1,4-benzodiazepin-2(3H)-one-Based Palladium Complexes as Precatalysts in C−C Bond Forming Reactions

The C−H activation of C-3-unsubstituted 1,4-benzodiazepin-2(3H)-ones (LH = 2a−c) (2a = 1-methyl-5-phenyl-1H-1,4-benzodiazepin-2(3H)-one, 2b = 1-benzyl-5-phenyl-1H-1,4-benzodiazepin-2(3H)-one, 2c = benzyl-2-(2,3-dihydro-2-oxo-5-phenyl-1,4-benzodiazepin-1-yl)acetate) with Na2PdCl4 afforded the insoluble palladacycles [(L)PdCl]2 3a−c. Treatment of the latter with triphenylphosphine afforded the soluble monomeric triphenylphosphine analogues [(L)Pd(PPh3)Cl] 4a−c. 1-Methyl-3-(2-(methylthio)ethyl)-5-phenyl-1H-1,4-benzodiazepin-2(3H)-one (LH = 2d) reacted with Na2PdCl4 or with PdCl2(MeCN)2 to afford the monomeric cis-S−N-coordinated complex 5d of the type [(LH)PdCl2]. 3-((tert-Butylthio)methyl)-1-methyl-5-phenyl-1H-1,4-benzodiazepin-2(3H)-one, 2e, reacted with Pd(OAc)2 in acetic acid and, following LiCl metathesis, yielded the monomeric cis-S−N-bound pincer palladacycle 6f. X-ray structures of 5d and 4a have been determined. 3a and 6f were found to be effective precatalysts for Suzuki coupling reactions, and 3a, 3c, and 4a were effective precatalysts in Heck couplings across a range of substrates.