Access to Deuterated Unnatural α-Amino Acids and Peptides by Photochemical Acyl Radical Addition

Abstract

A visible-light-enabled, photocatalyst-free conjugate addition reaction of dehydroamino acids is disclosed. Employing 4acyl-1,4-dihydropyridines as both a radical reservoir and reductant, various β-acyl α-amino acids and their deuterated analogues were obtained in good results. Both late-stage peptide modification and stereoselective synthesis of chiral oxazolidinones are successfully achieved. The protocol is characterized by mild conditions and efficient derivatization, thus unlocking a novel blueprint to access unnatural amino acid derivatives, important building blocks with potential application in the peptidomimetic toolbox.

Enantioselective Radical Hydroacylation of α,β-Unsaturated Carbonyl Compounds with Aldehydes by Triplet Excited Anthraquinone

“…Various acyl radical precursors have been developed, such as α-keto acids, carboxylic acids, anhydrides, acyl chlorides, acyl silanes, 4-acyl-1,4-dihydropyridines, and acyl oximes . However, beyond all that, inexpensive and readily available aldehydes are the especially attractive ones due to the highly atom-economical property .…”

Photoinduced carbamoylation reactions: unlocking new reactivities towards amide synthesis

“…Additionally, some DHPs can be homolitically cleaved when exposed to light of a determined wavelength. 69 The main feature of this approach over the 2e- pathway is the possibility of the transference of radical species (alkyl, acyl, and carbamoyl radicals) besides hydrogen atoms, allowing for DHPs to be directly applied in C–C couplings and, so that expanding dramatically the chemical space accessed by these species (Scheme 11).…”

Photoredox-Catalyzed Site-Selective Generation of Carbanions from C(sp3)–H Bonds in Amines

“…Labeled amino acids are essential for biological in vivo and in vitro studies. The installation of deuterium in the α-position of amino acids can reduce the rate of epimerization and enhance the efficacy for elucidating biosynthetic pathways. , As these factors are of crucial interest for scientists in research and development, broadening the toolbox for the preparation of deuterated amino acids and peptides in a facile one-pot synthesis remains an urgent and ongoing challenge. ,, In this regard, we herein describe a practically simple protocol for the site-selective generation of carbanions from α-amino C­(sp 3 )–H bonds via a reductive radical-polar crossover, without a HAT catalyst. This method was successfully implemented in a site-specific deuteration, tritiation, and 1,2-amino alcohol synthesis (Figure a).…”