C–C BOND FORMATION REALIZED BY AMIDYL-RADICAL-MEDIATED CHAIN REACTIONS

I. X–H Functionalization as a Means for Achieving C–C Bond Formation An overview of the benefits and challenges related to site-selective, intermolecular C(sp3)–H and carboxylic acid O–H functionalizations are discussed, particularly as they pertain to enabling C–C bond formation. II. Strategic Introduction of Carbon Fragments Onto Building Blocks and Late-Stage Molecules The development of an amidyl-radical-mediated chain reaction to convert aliphatic C(sp3)–H bonds into a variety of C–C bonds is discussed. The methods disclosed include (a) C–H functionalizations of tertiary alkylamines and (b) α-heteroatom C–H thioetherification followed by alkylation with an organometallic species. III. Decarboxylative Homologation Using a Radical–Polar Conjunctive Reagent The development of one-carbon homologation of aliphatic carboxylic acids is discussed. Particular attention is paid to the iterative design of a two-carbon SOMOphile that was critical to achieving the desired synthon for the overall transformation. IV. Rapid Access to Α-Ketoesters via C–H and Decarboxylative Pyruvylation Alpha-ketoesters are regarded as highly diversifiable intermediates in organic synthesis, with numerous applications ranging from unnatural amino acid construction to heterocycle formation. A late-stage approach to installing these functional handles onto C(sp3)–H and carboxylic acid-containing molecules is discussed.