| Description |
Transition metal-catalyzed cross-coupling reactions have become a widely-used method for the formation of a seemingly endless array of carbon-carbon bonds. As Chapter 1 will describe, the extension of Pd-catalyzed cross-coupling technology to include sp3-sp3 bonds has been more slowly realized, primarily due to facile P-hydride elimination of Pd-alkyl intermediates. A close examination of pioneering studies in ligand-controlled sp3-sp3 cross-coupling reactions is the focus of the first section of Chapter 1. The chapter then details alternative methods, developed by the Sigman laboratory, to form new carbon-carbon bonds using substrate-controlled selective alkene hydrofunctionalization. Chapter 2 details the development of a Pd-catalyzed hydroalkylation reaction of nonconjugated terminal alkenes. This entails reaction optimization, the evaluation of substrate scope, and mechanistic studies. This research ultimately led to a selective Pdcatalyzed anti-Markovnikov hydroalkylation of terminal allylic alkenes and alkylzinc reagents. Mechanistic insights suggest that this reductive coupling delivers the anti- Markovnikov product selectively by slowing P-hydride elimination at the allylic position, in conjunction with a much faster rate of transmetallation of the primary Pdalkyl intermediate. Chapter 3 describes an unrelated project, namely the investigation of site-selectivity in intermolecular Rh-catalyzed aliphatic C-H sulfamatations of isoamylbenzene. The chapter details the design of a sulfamate ester library used to interrogate steric and electronic features important for isomeric product distribution. Linear regression modeling was used to unveil the influence that both the IR stretching frequencies of the sulfamate ester, as well as the Hammett o+ value of the isoamylbenzene substrates, impart on the benzylic-to-tertiary selectivity in these C-H sulfamatation reactions. Ultimately, the insight gained from this study led to the rational design of a new sulfamate ester that delivered the most selective intermolecular benzylic sulfamatation selectivity to date for this system. |
