Modulable Photocatalyzed Strategies for the Synthesis of α- C-Glycosyl Alanine Analogues via the Giese Reaction with Dehydroalanine Derivates

Org Lett. 2023 Jul 7;25(26):4862-4867. doi: 10.1021/acs.orglett.3c01660. Epub 2023 Jun 22.

Abstract

Herein, we present the α-selective Giese reaction between pyranosyl/furanosyl bromides and dehydroalanine analogues, which provides access to a library of highly valuable α-C-glycosyl alanines. The key C-glycosyl radical is generated through photocatalysis by either the new generation copper(I) complex [(DPEPhos)(bcp)Cu]PF6 or [Ru(bpy)3](BF4)2. The reactions proceed smoothly, affording the desired α-C-glycosyl alanines in up to 99% yield when diethyl 1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate [Hantzsch ester (HE)] is used as an additive. N,N-Diisopropylethylamine (DIPEA) has been selected as a reductant in both protocols. A mechanistic study by means of transient absorption spectroscopy unveils a halogen-atom transfer (XAT) process in C-glycosyl radical formation.

MeSH terms

  • Alanine*

Substances

  • dehydroalanine
  • Alanine