New Approaches to Stereospecific Alkyl Transfer in Metal-Catalyzed Reactions: Synthetic and Mechanistic Investigations

Cuny City College, New York NY

Investigators

Abstract

With the award, the Chemical Synthesis Program of the NSF Division of Chemistry is supporting the research of Professor Biscoe, whose laboratory develops new synthetic strategies for use in organic and medicinal chemistry. Two molecules that have the same composition and structure but are mirror images of each other can elicit drastically different biological responses. Consequently, synthetic methods that enable precise control of three-dimensional molecular structure are essential. Metal-catalyzed cross-coupling reactions are routinely employed by medicinal chemists in efforts to produce biologically active compounds. However, these reactions are most reliable for the preparation of flat molecular units, and not for the preparation of three-dimensionally branched molecular structures. Professor Biscoe’s research investigates new strategies towards the preparation of individual mirror images of a branched molecule. From these studies, new chemical reactions are developed that expedite the synthesis of chiral molecules and contribute to the improved safety and efficacy of pharmaceutical and other biologically-relevant compounds emerging from the discovery process. Dr. Biscoe is active in projects that are designed to increase the diversity of students participating in the STEM fields. As part of these outreach activities, Dr. Biscoe is initiating a joint research program between CCNY and the High School for Math, Science, and Engineering (HSMSE) of City College. The goal of this program is to create a mechanism through which high school students can gain exposure to cutting-edge academic research, thereby facilitating a career path in scientific research. With this NSF award, Professor Biscoe is investigating the transfer of stereodefined alkyl units in palladium-catalyzed cross-coupling reactions. This research focuses on the use of enantioenriched alkylcarbastannatranes in cross-coupling reactions. The factors that influence stereochemical transfer from the alkyl unit of the carbastannatrane backbone are explored in these studies. As alkyl transfer can occur with retention or inversion of three-dimensional geometry, a variety of mechanistic probes are employed to elucidate the underlying chemical factors most influential in determining the pathway of alkyl transfer. Because alkyl transfer to palladium is a fundamental step in the catalytic cycle of cross-coupling reactions, these studies facilitate the development of new stereospecific cross-coupling reactions, which can be used to generate non-racemic molecules enantio- or diastereoselectively. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.