A General Amino Acid Synthesis Enabled by Innate Radical Cross‐Coupling

Abstract

The direct union of primary, secondary, and tertiary carboxylic acids with a chiral glyoxylate-derived sulfinimine provides rapid access into a variety of enantiomerically pure α-amino acids (>85 examples). Characterized by operational simplicity, this radical-based reaction enables the modular assembly of exotic α-amino acids, including both unprecedented structures and those of established industrial value. The described method performs well in high-throughput library synthesis, and has already been implemented in three distinct medicinal chemistry campaigns.

Ni-catalyzed deaminative cross-electrophile coupling of Katritzky salts with halides via C─N bond activation

“…However, forging sp 3 -hybridized carbon centers remains a great challenge mainly due to the weak nucleophilic reactivity of sp 3 carbon centers and their innate difficulties in coordination with metals (4)(5)(6)(7). In recent years, various alkyl radical precursors including halides (4,(8)(9)(10)(11), silicones (12), dihydropyridine (13), carboxylic acids (14)(15)(16), sulfones (17), and others (18)(19)(20) have been used for radical cross-coupling reactions (Fig. 1A).…”

Nickel-catalyzed allylic defluorinative alkylation of trifluoromethyl alkenes with reductive decarboxylation of redox-active esters

“…Reductive cross-coupling reactions represent a versatile tool for accurate construction of C–C bonds from cheap, abundant, and stable electrophiles as compared with methods using the corresponding organometallic reagents 8. Recently, reductive decarboxylative coupling has been exploited for generating alkyl radicals from alkanoic acids, complementing the use of alkyl halides beneficially 9. As part of our ongoing interest in alkene functionalization reactions9b,10 and fluorinated olefin synthesis,11 we set out to take advantage of allylic defluorination and reductive decarboxylation for the radical alkylation of trifluoromethyl alkenes (Fig.…”

A General Amino Acid Synthesis Enabled by Innate Radical Cross‐Coupling

“…[27] Angewandte Chemie Zuschriften hydrolysis,a nd, of course,t oxic reagents. A) Decarboxylative coupling to access enantioenriched amino acids.…”