Research

General Research Approach

Our research goal is to rapidly and efficiently synthesize complex organic molecules of interest and utility while creating powerful synthetic methodologies. Transformations using the benefits of organoboronates as well as transition-metal catalysts that stabilize carbene and ylide-like intermediates are sought to form densely functionalized bonds with chemo- and stereoselectivity. Furthermore, cascade reactions allow for a variety of bond forming and bond breaking events to occur in one reaction setup, providing significant chemical transformation with high efficiency.

Target molecules are principally complex natural products that exhibit a challenging architecture and intriguing biological properties, designer ligands for controlled organometallic catalysis, and small organic molecules to serve as pharmaceutical leads. Our strategy for synthetic planning incorporates efficiency and practicality so the result is a synthesis that can be utilized for reliable access to the target and its analogues. Other molecular targets include recognition motifs for directed chemical reactions or molecular biology applications, with value for therapeutic target identification, pharmaceutical development, protein sequencing, and chemical biology.

Research Areas

Natural Product Synthesis

We have achieved a three-step biomimetic synthesis of the antimalarial alkaloids isolated from the genus Flindersia. Thus, tryptamine is transformed in two steps to the natural product borrerine, which is then treated with acid. The resulting cascade sequence results in the selective formation of flinderole A and desmethylflinderole C or isoborreverine depending on the conditions used. If borrerine is first treated with a methylating agent and then acid, flinderole B, flinderole C, and dimethylisoborreverine can be obtained.

Methods Development

We have developed an enantioselective conjugate addition of vinylboronic acids to β-indolyl enones. Though these enones are deactivated by the electron-rich heterocycle, and indoles are well known for their ease of acidic and oxidative decomposition, this approach provides indoles with adjacent stereocenters in high yields and excellent enantioselectivities. Further catalyst development has now enabled the transformation to efficiently occur with a wide range of heteroaryl-appended enones, allowing us to build a library of alpha-chiral heterocyclic compounds.

Cascade & Carbene Chemistry

Our work with carbenes has afforded a powerful cascade reaction that builds bridged bicyclic motifs common to biologically active natural products. The connectivity and ring size in the product can be controlled and predicted. Heterocyclic products readily rearrange to prepellanes. This strategy is now allowing the synthesis of multiple natural products.