Synthetic Organic Chemistry, Organometallic Chemistry

Mechanism-based design of new catalytic reactions
Catalysts play a critical role in synthetic organic chemistry. The right catalyst can control a reaction’s chemoselectivity and stereoselectivity, providing an efficient route to the required product. Many elegant syntheses of biologically active compounds rely on highly selective catalytic transformations for streamlined assembly of the required functional groups. The focus of our research interests is the development of new reactions using organometallic catalysts, and application of these transformations in complex target-oriented synthesis. In addition to providing valuable synthetic methods, these studies test and deepen our understanding of the fundamental principles that underlie reactivity.

Base metal catalysts for stereospecific C–C bond construction
Nickel-catalyzed stereospecific reactions are powerful transformations for diverse applications including cross-coupling and cascade reactions. There are many challenges that must be addressed as part of development of such transformations; one major challenge is suppressing the inherent one-electron reactivity of the organonickel catalyst. We have identified nickel-catalyzed cross-coupling reactions of alkyl electrophiles that are stereospecific and proceed with inversion at the electrophilic carbon. This stereochemical outcome is unusual for nickel catalysts: alkyl electrophiles are typically thought to react with nickel catalysts via radical intermediates that racemize rapidly.  We have begun to demonstrate the broad applicability of stereospecific cross-coupling reactions by developing new strategies to accelerate coupling of unactivated electrophiles and expanding the range of nucleophiles that participate in cross-coupling reactions. We have also begun to identify new transformations that can be initiated by a stereospecific oxidative addition step.

Silver-catalyzed enantioselective propargylation reactions of electrophiles
As part of our long-term interest in enantioselective reactions of organometal intermediates, we have identified silver catalysts ligated by bidentate phosphines in the Walphos family that provide highly enantioselective propargylation reactions of a range of carbonyl derivatives.

Umpolung approaches to C–C, C–N, and C–S bond formation
We have developed nucleophilic allylpalladium complexes, and used these complexes to develop catalytic allylation reactions and a series of cascade reactions for carbocycle and heterocycle synthesis.  We have developed a series of transformations employing electrophilic N-chloroamines and sulfenyl chlorides for synthesis of of amines and thioethers.

umpolung molecules

Collaboration to test compounds for selective activity against cancer cell lines
Many of the compounds that we synthesize over the course of developing new catalytic reactions are structurally related to medicinal agents with proven biological activity.  We are members of the Chao Family Comprehensive Cancer Center at UC Irvine, and collaborate with the research group of Professor Zi, UC Irvine Medical School, and Professor Morrissette, UC Irvine MB&B, to test our new compounds for growth inhibitory effect against prostate, bladder, and ovarian cancer cell lines.

For detailed information on each project, please see the publications page.