Electron donor–acceptor complex offers a diverse approach for carbonyl alkylative amination
Hrishikesh Paul, A. CHAKRABORTY, Animesh Mandal, Dibyangshu Das, Sanat Kumar Mahapatra, Lisa Roy, Indranil Chatterjee
Abstract
The synthesis of α-tertiary amino acids and amines is crucial in biochemistry and medicinal chemistry. However, creating tertiary carbon centers has traditionally been challenging due to the lack of effective, sustainable, and straightforward mild protocols. This current work presents a method for creating α-tertiary carbon centers that leverages the formation of an electron donor-acceptor (EDA) complex, where electron-poor imines act as the acceptor and electron-rich 1,4-dihydropyridine serves as the donor. This interaction facilitates the generation of α-amino radicals through a charge transfer phenomenon. In the presence of a suitable radical trapping reagent, these α-amino radicals can forge C-C bonds, where H-DHP acts solely as a reductant. Additionally, a radical cross-coupling process between an alkyl radical generated from 4-alkylated 1,4-dihydropyridine and the α-amino radical also produces reductive alkylation products. In this later scenario, 4-alkylated 1,4-dihydropyridine functions both as a reductant and as a source of alkyl radicals. Interestingly, both processes yield amino acids and amine derivatives having α-tertiary centres under mild reaction conditions, avoiding the need for photocatalysts or transition metals.