Prof. Patricia Musacchio
Title: A Redesigned Approach to Accessing Cationic Intermediates
Abstract:
Efforts in the Musacchio research group are on the development of enabling chemical transformations to accessing valuable cationic intermediates using mild catalysis from unconventional functional groups. In the past few years, we have successfully established a visible-light photoredox catalysis platform to orchestrate the generation of carbocations directly from C(sp3)–H bonds to avoid the harsh requirements of classical SN1 conditions from organohalides, protected alcohols, etc. The key mechanistic strategy is the combination of two steps: a hydrogen atom transfer (HAT) followed by a radical-polar crossover (RPC), to ultimately provide a net hydride removal from a C–H bond. A recent discovery in our lab demonstrates that this platform can also be used to generate alkene radical cations from homobenzylic C–X motifs (i.e. alkyl halides, protected and unprotected alcohols, and alkyl azides). Computational studies reveal a concerted HAT and spin-center shift (SCS) process to access the radical cation intermediate. We leverage this mechanism to establish a 1,2-difunctionalization of C(sp³)–X motifs. This photocatalytic platform allows us to develop a suite of transformations that depart from current conventional synthetic logic for which alkyl C–X scaffolds are confined to single-site substitutions, now transforming them into nonintuitive precursors for building vicinal complexity. Incorporation of the spin-center shift process in the platform ultimately allows for transfer of electrophilic reactivity from one carbon to another, allowing for the establishment of a new synthetic concept – ‘electrophilic shuttling.’
Keywords: photocatalysis, carbocation, alkene radical cation, synthetic methods
Bio:
Patricia Z. Musacchio is originally from Sandy, Utah (USA) and is currently an Assistant Professor at University at Buffalo, the State University of New York (SUNY). She was previously an assistant professor at Worcester Polytechnic Institute in central Massachusetts. Her group specializes in developing new organic transformations that expedite the synthesis of valuable small molecules. She obtained her undergraduate degree from the University of Texas, Austin (USA) where she worked in the area of total synthesis with Prof. Stephen F. Martin. To pursue her passion in organic chemistry, Patti then went to Princeton University (USA) to study with Nobel Laureate Prof. David W. C. MacMillan for her graduate work where she developed a silyl radical-mediated cross-electrophile coupling with metallaphotoredox catalysis. Afterward, she joined Prof. F. Dean Toste’s group at U.C. Berkeley (USA) for her postdoctoral studies to develop bioconjugation strategies and covalent drug design. Notable achievements include an NIH MIRA R35 award, ACS PRF DNI, and Thieme Journal Chemistry Award. She is currently the Marjorie E. Winkler Assistant Professor of Chemistry at UB.
Faculty Host: Prof. Tehshik Yoon