Functionalization of Methyl (R)-Phenylglycinate Through Orthopalladation: C−Hal, C−O, C−N, and C−C Bond Coupling

Abstract

The ortho functionalization of methyl R-phenylglycinate has been easily achieved using the known orthopalladated complex [Pd(mu-Cl){R-C(6)H(4)(CH(CO(2)Me)NH(2))-2}](2) (1) as synthetic tool. Different functional groups have been introduced at the ortho position of the aryl ring. The reaction of (R)-1 with X(2) or PhI(OAc)(2) gives XC(6)H(4)(CH(CO(2)Me)NH(2))-2 (X = I, Br, OMe, OEt) through oxidative coupling, while the reaction with CO gives an isoindolone. (R)-1 also reacts with one, two, or three alkyne molecules to give different metal-containing or metal-free heterocycles. The resulting functionalized amino esters or heterocycles retain the chirality of (R)-1, according with the values of the optical rotation and the obtained ee values ranging from 22%-87%. The X-ray structures of six representative compounds have also been determined.