Cross-couplings that proceed via C–H bond activation streamline the synthesis of complex molecules. Rhodium complexes are promising catalysts for these reactions and they readily activate aldehyde C–H bonds to generate acyl-Rh-hydrides. Developing strategies to control the reactivity of these oxidative addition products enables developments in hydroacylation.

Chapter 1 describes the development of a cobalt-catalyst that can couple aldehydes and dienes selectively to make new ketone products. Our Co-catalyzed hydroacylation circumvents migratory deinsertion pathways by avoiding formation of an acyl-metal-hydride intermediate. This work spurred renewed interest in base metal-catalysis in the development of new hydroacylation reactions.

Chapter 2 describes the synthesis of dienyl aldehydes that can be cycloisomerized into a variety of scaffolds by careful choice of the Rh-catalyst system employed. One substrate can be derivatized into cyclopentanones, cyclohexenals, [2.2.1]-bicycloheptanones, and bis(acyl)octanone scaffolds. The details regarding asymmetric cyclopentanones containing an all-carbon quaternary center will be described. Included will be our mechanistic understanding of the reaction and its ability to reach the other scaffolds.

Chapter 3 describes the complementary use of Co-catalysis to cyclize dienyl aldehydes into strained cyclobutanones. This takes advantage of unique properties of cobalt- versus rhodium-catalysis. Furthermore, the evaluation of the catalyst system using a robustness evaluation as well as further mechanistic probes will be described.