Vicinal disubstitution of alkyl C–X synthons via alkene radical cation generation

Y Yufei Zhang (Department of Chemistry, Natural Sciences Complex, University at Buffalo, The State University of New York, Buffalo, NY, USA.) T Tamal Das (Department of Chemistry, Binghamton University, Binghamton, NY, USA.) Z Zi Xuan (Department of Chemistry, Worcester Polytechnic Institute, Worcester, MA, USA.) M Mrinmoy Das (Department of Chemistry, Worcester Polytechnic Institute, Worcester, MA, USA.) H Hammed O. Bisiriyu (Department of Chemistry, Natural Sciences Complex, University at Buffalo, The State University of New York, Buffalo, NY, USA.) A Alon Nudler (Department of Chemistry, Natural Sciences Complex, University at Buffalo, The State University of New York, Buffalo, NY, USA.) B Ben D. Parasch (Department of Chemistry, Natural Sciences Complex, University at Buffalo, The State University of New York, Buffalo, NY, USA.) M Matthew D. Resmini A Aubrey E. Graham (Department of Chemistry, Worcester Polytechnic Institute, Worcester, MA, USA.) D David F. Watson (Department of Chemistry, Natural Sciences Complex, University at Buffalo, The State University of New York, Buffalo, NY, USA.) J Jennifer S. Hirschi (Department of Chemistry, Binghamton University, Binghamton, NY, USA.) P Patricia Z. Musacchio (Department of Chemistry, Natural Sciences Complex, University at Buffalo, The State University of New York, Buffalo, NY, USA.)

Abstract

In organic chemistry, functionalization of two adjacent carbons often starts from alkenes or already disubstituted precursors. Herein, we report an exergonic activation mode that directly generates alkene radical cation intermediates from monofunctional C(sp 3 )–X handles through a photoredox-triggered hydrogen-atom abstraction (HAT) and spin-center shift (SCS) process. Computations show that electron delocalization and a network of hydrogen-bonding solvent molecules facilitate a concerted [HAT+SCS] mechanism. The catalytic platform was used to design a transfer of electrophilic reactivity (C–X) from one carbon to another, which we refer to as electrophilic shuttling. Thus, two nucleophiles can be used in the construction of 1,2-difunctionalization adducts from homobenzylic C–X synthons, delivering bisazole architectures and demonstrating compatibility with other nucleophile classes. A suite of transformations is developed that departs from 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.

Article Details

Journal Science
Volume / Issue Vol. 1, Issue 1
Published July 09, 2026
ISSN 0036-8075
Publisher American Association for the Advancement of Science

Journal Info

Science

American Association for the Advancement of Science

ISSN: 0036-8075 Social Sciences

Authors (12)

Y

Yufei Zhang

Department of Chemistry, Natural Sciences Complex, University at Buffalo, The State University of New York, Buffalo, NY, USA.

T

Tamal Das

Department of Chemistry, Binghamton University, Binghamton, NY, USA.

Z

Zi Xuan

Department of Chemistry, Worcester Polytechnic Institute, Worcester, MA, USA.

M

Mrinmoy Das

Department of Chemistry, Worcester Polytechnic Institute, Worcester, MA, USA.

H

Hammed O. Bisiriyu

Department of Chemistry, Natural Sciences Complex, University at Buffalo, The State University of New York, Buffalo, NY, USA.

A

Alon Nudler

Department of Chemistry, Natural Sciences Complex, University at Buffalo, The State University of New York, Buffalo, NY, USA.

B

Ben D. Parasch

Department of Chemistry, Natural Sciences Complex, University at Buffalo, The State University of New York, Buffalo, NY, USA.

M

Matthew D. Resmini

A

Aubrey E. Graham

Department of Chemistry, Worcester Polytechnic Institute, Worcester, MA, USA.

D

David F. Watson

Department of Chemistry, Natural Sciences Complex, University at Buffalo, The State University of New York, Buffalo, NY, USA.

J

Jennifer S. Hirschi

Department of Chemistry, Binghamton University, Binghamton, NY, USA.

P

Patricia Z. Musacchio

Department of Chemistry, Natural Sciences Complex, University at Buffalo, The State University of New York, Buffalo, NY, USA.