Accessing α-Amino Ketyl Radicals from β-Amino Alcohols via Chemoselective Hydrogen Atom Transfer Catalysis

Abstract

The selective activation of a given C−H bond in complex molecules possessing bonds of similar polarity and strength remains one of the foremost challenges in hydrogen atom transfer (HAT) catalysis. Herein, we present the combination of photoredox and HAT catalysis with an oxophilic boron-based catalyst to achieve the chemoselective abstraction of α-hydroxy C−H bonds in β-amino alcohols. This enables us to access α-amino ketyl radicals, which are exploited for the direct synthesis of γ-oxo-δamino esters�a prominent scaffold in biologically active molecules.

Photocatalytic Late-Stage C–H Functionalization

“…Gómez-Suárez and co-workers combined quinuclidine and 4CzIPN to generate α-amino ketyl-radicals from α-amino alcohols that undergo Giese-type alkylation with α,β-unsaturated carbonyl compounds . A variety of α-amino alcohols, derived from natural and unnatural amino acids, were tolerated in the reaction.…”

“…Goḿez-Suaŕez and co-workers combined quinuclidine and 4CzIPN to generate α-amino ketyl-radicals from α-amino alcohols that undergo Giese-type alkylation with α,β-unsaturated carbonyl compounds. 348 A variety of α-amino alcohols, derived from natural and unnatural amino acids, were tolerated in the reaction. As shown by MacMillan 346 and Taylor, 349,350 both hydrogen bond 351 and covalent interactions, respectively, can weaken α-oxygen bonds and facilitate the hydrogen abstraction.…”

Metal‐Free Visible‐Light Induced Oxidative Cleavage of C(sp3)−C, and C(sp3)−N Bonds of Nitriles, Alcohols, and Amines

“…In this context, hydrogen atom transfer (HAT) catalysis is a highly attractive strategy for functionalization of inert CÀ H bonds. [40][41][42][43] Continuing our quest for the development of milder, and sustainable oxidation protocol, we introduce here a visible light induced transition metal-free method for the oxidative cleavage of CÀ CN, CÀ C(OH) and CÀ N bond to access carboxylic acids and aldehydes respectively. To the best of our knowledge, this is the first report for the metal-free photocatalytic cleavage of unstrained CÀ CN, CÀ C(OH) as well as CÀ N bonds using one single system.…”

“…The direct C−H bond activation is a potentially challenging step. In this context, hydrogen atom transfer (HAT) catalysis is a highly attractive strategy for functionalization of inert C−H bonds [40–43] …”

Selective N-α-C–H alkylation of cyclic tertiary amides via visible-light-mediated 1,5-hydrogen atom transfer

“…10 Although excellent works have been reported, most of these approaches are restricted to certain electrophilic alkenes. 11 Therefore, the development of efficient, step-economical, and practical strategies with a broad scope for the α-functionalization of nitrogen-containing systems is still of great significance.…”