Single Atom Logic for Skeletal Editing

Abstract:

Reactions which can manipulate the connectivity of the molecular skeleton are underexplored as tools for late-stage functionalization, in part because their implementation has been hindered by their often nonintuitive retrosynthetic logic. This presentation will cover selected transformations discovered in our laboratory which address this challenge by enabling single-atom changes to aliphatic and aromatic systems through the insertion and deletion of single heavy atoms (C,N,O, etc.), as well as more complex manipulations leveraging combinations of these elementary transformations. Our approach to this problem is modality-agnostic, drawing from a wide range of reactive species and synthetic disciplines (organometallic chemistry, reagent design, photochemistry). Applications to late-stage functionalization and diversification of complex pharmaceutically relevant compounds as well as unique opportunities for synthesis will be presented alongside mechanistic findings.