Access to α-Hydroxy Amides via a Practical Metal-Free “One-Pot” Tandem Reaction Involving Aerobic C(sp³)–H Hydroxylation and C(sp²)–C(sp³) Cleavage

Abstract

A flexible metal-free cascade reaction involving aerobic C(sp 3 )−H hydroxylation and decarbonylation with high regioselectivity and functional group tolerance has been established. Moreover, this indirect hydroxylation approach of N-aryl amides could enable the construction of a wide range of valuable secondary alcohols at α-position of N-aryl amides. It provides a supplementary strategy for direct α-hydroxylation of simple amides.

Recent Advances in Carbon‐Nitrogen/Carbon‐Oxygen Bond Formation Under Transition‐Metal‐Free Conditions

“…In a latest report, Li and co-workers developed a DBUpromoted hydroxylation protocol for α-hydroxylation of β-keto amides (224) via a CÀ C bond cleavage process under aerobic conditions (Scheme 46b). [130] In this protocol, the metal-free hydroxylation and decarbonylation cascade reaction were achieved by the combination of DBU, DMSO and O 2 , and various αhydroxyl N-aryl amides were obtained in moderate to good yields with high chemoselectivity and good functional group compatibility. To conclude, this indirect hydroxylation of N-aryl amides enabled the facile construction of valuable secondary alcohols at the α-position of N-aryl amides.…”

“…After careful mechanistic studies, a plausible reaction mechanism involving a SET process was proposed. In a latest report, Li and co‐workers developed a DBU‐promoted hydroxylation protocol for α‐hydroxylation of β‐keto amides ( 224 ) via a C−C bond cleavage process under aerobic conditions (Scheme 46b) [130] . In this protocol, the metal‐free hydroxylation and decarbonylation cascade reaction were achieved by the combination of DBU, DMSO and O 2 , and various α‐hydroxyl N‐aryl amides were obtained in moderate to good yields with high chemoselectivity and good functional group compatibility.…”

Transition-metal-free access to benzyl ethers via aerobic cross-dehydrogenative coupling of benzylic C(sp3)–H bonds with alcohols

“…However, more economical and environmentally benign base-catalyzed dehydrogenative cross-couplings with molecular oxygen as the sole oxidant are scarce. Herein, to continue our research on transition metal-free catalysis 12 and oxidative functionalization reactions, 13 we report a straightforward approach for the construction of substituted p -hydroxybenzyl ethers, which are valuable intermediates in the synthesis of drug molecules and perfumes (Scheme 1d). 14 Furthermore, this practical method enables direct alkoxylation of benzylic C(sp 3 )–H bonds of numerous substituted 4-alkylphenols to desired products in moderate to high yields in the presence of catalytic equivalents of base by employing molecular oxygen as the sole oxidant.…”