Synthesis • Methods • Catalysis

The overarching goal of our research program is to discover, develop, and study new chemical reactions within the context of natural product total synthesis. Over the last century, natural products have played an essential role not only in medicine, but also in advancing the field of synthetic organic chemistry. Their complex architectures, reactive functional groups, and issues of stereochemistry provide a fertile setting for reaction development while exerting strict demands for selectivity and efficiency. Endeavors in natural product synthesis drive advances in the state-of-the-art in organic chemistry, and in so doing, impact a variety of research areas that integrate synthetic tools, from catalysis and materials science to biology.  

Natural Product Synthesis

Our total synthesis efforts focus on structurally complex, stereochemically-rich targets that require innovative synthetic solutions, and that provide opportunities to engage in biological collaborations. We embrace opportunities to develop new chemistry, with the goal of contributing new reaction methods and fundamental studies of chemical reactivity that transcend the scope of a given synthesis project. Although a new reaction may be discovered in the context of a very specific synthetic transformation, we ultimately hope to expand upon the general principles of reactivity through mechanistic studies in order to develop widely applicable chemistry.  The syntheses of these molecules can enable further study of biological modes of action and provide us with an opportunity to explore exciting reactions that expand the synthetic chemist's toolbox.

Methods Development

Our lab prides itself on the fluidity with which we move between natural product total synthesis and synthetic methods development. Many of our reaction development efforts seek to address gaps in the existing technology as revealed by a complex target. These efforts have resulted in new methods for the preparation of pyrroloindolines and unnatural tryptophan derivatives, the development of arene cyclopropanation reactions, and most recently, the discovery of new Ni-catalyzed asymmetric reductive cross-coupling reactions.

Nickel Catalysis

Within our methods development program, the discovery of new nickel-catalyzed asymmetric reductive cross-coupling reactions is of particular interest. While traditional transition metal-catalyzed cross-coupling reactions typically employ the use of pre-formed organometallic coupling partners, reductive cross-coupling reactions allow us to join two readily available electrophiles under mild conditions. These studies are enabled by our collaboration with the Caltech Center for Catalysis and Chemical Synthesis (3CS), which is equipped with liquid- and solid-dispensing robots for parallel screening and extensive analytical equipment.