UCLA

A method is reported for synthesis of synthetically-valuable borylated pyridines via a Lewis acid promoted C-H activation approach. The transformation involves BF3 or BH3 Lewis-acid precomplexation followed by Ir-catalyzed borylation. The method’s development was guided by computational studies, culminating in the development of a reaction with several advantages over existing methods, including enhanced reactivity, improved regioselectivity, novel formation of trifluoroborate salts and an operationally simple purification procedure. During the reaction discovery process, we also devised a convenient and rapid synthesis of isotopically enriched 10B-pinacolborane, which was used to probe the reaction mechanism.

The synthesis and screening of various π-base ligands for use in a copper-promoted coupling reaction of alcohols and vinyl boronates are also highlighted. While alkenes and alkynes are frequently used as π–bond ligands in transition-metal promoted reactions, allenes have long been underutilized for this purpose despite possessing excellent π–bond donor characteristics. Several alkynes and allenes were synthesized and tested as π–bond ligands in a copper-mediated oxidative vinyl ether synthesis. Cyclonona-1,2-diene was identified as an ideal allene additive for the reaction.

Next, building upon our previous work on palladium-catalyzed oxidative couplings of vinyl boronates, we describe our efforts towards translating this chemistry to a nickel-catalyzed manifold. Central to the success of this new method was the serendipitous discovery that nitroarenes act as a terminal oxidant for nickel, enabling the synthesis of biaryls and butadienes. To the best of our knowledge, this is the first example of nitroarenes used as oxidants in a nickel-catalyzed coupling reaction.

The final part of this work chronicles the design and synthesis of a new class of carbon-monoxide releasing molecules. While carbon monoxide is a pervasive environmental toxin, it’s also an endogenously-produced, essential signaling molecule in all vertebrates. In order to better study the physiological effects of CO, we synthesized molecules which are activated by the presence of genetically programmable β-galactosidase enzyme. This chapter represents an important first step towards the realization of a useful biochemical tool and perhaps even a unique therapeutic compound.