| Description |
The Heck reaction is an important tool in target-directed syntheses, but its full potential has yet to be realized due to limited substrate compatibility. This limitation arises from poor behavior of the selectivity-determining steps of migratory insertion and β-hydride elimination when using electronically nonbiased substrates. The inability to accommodate nonbiased alkenes is due to chemist's poor understanding of the controlling factors in these two key mechanistic steps. Herein are described Pd0 and PdII catalysts that exhibit unique selectivity in these electronically nonbiased molecular systems. Chapter 1 describes the use of an electrophilic PdII catalyst to install two identical aryl groups upon terminal aliphatic olefins. The use of the same system, with a different aryl source, led to the discovery that electrophilic PdII catalysts are capable of selectively delivering (E)-styrenyl products from electronically nonbiased olefins. Chapter 2 details optimization of the PdII system to selectively deliver traditionally inaccessible (E)-styrenyl products, and evaluation of substrate scope. Mechanistic experiments are performed, suggesting that the unique selectivity observed is attributable to the cationic nature of the catalyst, that the ligand on Pd is required for catalyst stability, and that the catalyst distinguishes between β-hydrogens on the basis of C−H bond strength. These findings are applied to rational design of a Pd0-catalyzed Heck reaction of similar substrates. The Pd0-catalyzed system exhibits greater functional group tolerance than the oxidative system, is operationally simple, and requires no added stabilizing ligand. The design and study of this reaction is the subject of Chapter 3. Mechanistic studies suggest that solvent choice is crucial in allowing the metal center to distinguish between β-hydrogens on the basis of their relative hydridic nature. The insight gained in the work described in Chapters 2 and 3 allowed for the rational design of a system enabling enantioselective Heck reactions using acyclic substrates. This methodology, described in Chapter 4, was intended to deliver optically active β-aryl ketones from allylic alcohol substrates. After establishing that the reaction performs as anticipated, it was applied to the unprecedented single-step enantioselective synthesis of γ-aryl ketones, and aldehydes, and a δ-aryl aldehyde. |
