Synthesis of α-Hydroxy and α-Alkoxy Esters Enabled by a Visible-Light-Induced O–H Insertion Reaction of Diazo Compounds

Abstract

A visible light-induced O−H insertion reaction of diazo compounds is herein reported. This developed synthetic method, which is different from traditional pathways that rely on transition metals, Lewis acids or Brønsted acids, does not use any catalyst and produces valuable α-hydroxy and α-alkoxy esters in good yields (up to 98%). This protocol exhibits a broad substrate scope and good functional group tolerance. Notably, a gram-scale synthesis in continuous photo flow fashion has been performed.

Visible photons as ideal reagents for the activation of coloured organic compounds

“…The protocol was optimized under both batch and continuous flow conditions. In particular, by using a mesoflow photoreactor, the product 84.2a was isolated on a multigram scale in 91% yield with a residence time of 4 h. 288 Cyclic diazoamides have been also employed as photoactivatable substrates in the preparation of α-hydroxy and α-alkoxy amides by using (fluorinated) alcohols and phenols as oxygenated partners. 289 Analogously, O -, S - and N -alkylated phenylacetate esters have been prepared in good to satisfactory yields by using 2-pyridones (phenols), 2-mercaptopyridine and anilines, respectively, as the coupling agents.…”

Visible Light-Induced Reactions of Diazo Compounds and Their Precursors

“…In 2022, the groups of Yang and Xia further extended the scope of alcohols (Scheme 27b). 77 In the same report, the authors also utilized water for O−H insertions targeting α-hydroxy esters 27.11 and 27.12 (Scheme 27c). The use of oximes 27.13 in photochemical O−H insertion reactions with aryl diazoacetates was independently developed by the groups of Xuan, 78 Wang, 79 and Jurberg 80 (Scheme 27d).…”

“…In contrast, the metal carbene underwent nucleophilic attack by the azirine nitrogen in the presence of a gold catalyst. In 2022, the groups of Yang and Xia further extended the scope of alcohols (Scheme b) . In the same report, the authors also utilized water for O–H insertions targeting α-hydroxy esters 27.11 and 27.12 (Scheme c).…”

Visible light-mediated photolysis of organic molecules: the case study of diazo compounds

“…52 N-H insertions were reported with amines, 15,43 indoles, 43,53 carbazoles, 43,54,55 pyrazoles, 55 1,2,3-triazoles, 55 amides, 56 sulfonamides, 56 imides, 56 and isatines. 56 O-H insertions were also successfully accomplished with carboxylic acids, 15 perfluorinated alcohols, 57,58 alcohols, 15,59 phenols, 60 oximes, [61][62][63] hydroxamic acids (generated in situ from a NHC catalyst, aldehydes and nitroso compounds) 64 and phosphinic acids (generated in situ presumably from the air oxidation of H-phosphine oxides). 65 Intriguingly, Koenigs and co-authors had initially proposed that the O-H insertion of more acidic compounds would proceed via a photoinduced proton transfer mechanism, 57,60 which would be an alternative not involving the formation of free carbene intermediates.…”