Pd-Catalyzed Oxidative Functionalizations.

Abstract

A traditional Pd(0/II) mechanism is commonly evoked for a number of well-known cross-coupling reactions (i.e. Heck, Suzuki, Negishi, etc). In recent years, there has been great interest in developing Pd-catalyzed oxidative functionalizations. This dissertation describes efforts to address several challenges in Pd-catalyzed oxidative reactions. The transformations studied are: (1) olefin difunctionalization via interception of Pd(ll)-alkyl Heck intermediates, (2) the use of pyridine ligands as promoters for C-H olefination reactions, and (3) ligand-directed Pd-catalyzed cyclopropane oxidative functionalizations. The strategy behind the first project was to oxidatively intercept Pd(ll)-alkyl intermediate, resulting from migratory insertion of alkenes into Pd-Ar bond, and reductively eliminate an X-type ligand to form a new C-X bond. This methodology was developed for Pd-catalyzed aryloxygenation and arylamination of terminal olefins. The transformation was made feasible by utilizing Pd(ll) catalysts, arylstannanes as transmetallating reagents providing the aryl functionality, and iodobenzene dicarboxylates for oxidant and oxygen source or in conjunction with bis-benzene sulfonimide for amine source. In the second project, several of the limitations of currently available C-H olefination reactions were addressed using catalyst control by employing equimolar amount of Pd(OAc)2 and pyridine as a ligand. The challenges associated with C-H olefination include lack of reactivity from alpha-olefins and electron deficient arenes as well as poor site-selectivity of C-H activation when substituted arenes are utilized. With the use of (pyr)Pd(OAc)2 catalyst system, the scope of the reaction was broadened to include allyl acetate (alpha-olefin) and several electron deficient arenes. Also, preliminary studies show that pyridine-based ligands do affect site-selectivity of the C-H activation as well. In the last project, cyclopropane substrates were studied under known Pd-catalyzed C-H activation/functionalization conditions in hopes to gain a better understanding of C-H activation at 2° sp3 C-H bonds, which are known to be challenging. These studies showed that cyclopropanes are extremely sensitive to ligand choice, substrate structure, and reaction conditions. Most reactions, if any reactivity was present, resulted in C-C bond activation to form the ring-opened products instead of the desired C-H activation product.