Visible Light-Mediated Carbamoylation of para-Quinone Methides

Abstract

We report a photocatalytic approach for the installation of the amide moiety onto para-quinone methides. This transformation features a net reductive approach for the generation of carbamoyl radicals from amidesubstituted Hantzsch ester derivatives under transition metal-free conditions. This protocol exhibits wide scope and allows access to diarylacetamides employing a C−C bond formation approach.

Cascade Cyclizations Triggered by Photochemically Generated Carbamoyl Radicals Derived from Alkyl Amines

“…39−43 Among other strategies for cyclization of acrylamide precursors, phosphorylation, 44,45 trifluoromethylation, 46 difluoromethylation, 40,47 azidation, 48 thiomethylation, and silylation 49 are methods 50 that have been well received by the scientific community. Our group has reported the visible light-mediated functionalization of C�C and C�N bonds 33,46,51 including the addition of carbamoyl radicals to quinone methides (Scheme 1b). We contemplated that photochemical carbamoylation represents several advantages over peroxide-promoted generation and use of carbamoyl radicals, such as application to aliphatic amines, 21 use of precursors with other functionalities such as olefins and alkynes, and applicability to acrylamides containing other heteroatoms and flanking groups, ultimately resulting in a significantly greater product diversity (Scheme 1c).…”

“…The ortho -cyano-substituted acrylamide motif is being actively studied by the synthetic community as it leads to the quinoline dione substructure, which is present in a plethora of important biologically active molecules. ,− Among methods that provide access to different derivatives of quinoline diones, a sulfonylative cyclization was reported by Yu and Li groups wherein the Yu group demonstrated a metal-free sulfonylative cyclization, and the Li group utilized Cu-catalyzed sulfonylation under conditions that were applicable to a larger selection of radicals for the annulation of 2-cyanoacrylamides. − Among other strategies for cyclization of acrylamide precursors, phosphorylation, , trifluoromethylation, difluoromethylation, , azidation, thiomethylation, and silylation are methods that have been well received by the scientific community. Our group has reported the visible light-mediated functionalization of CC and CN bonds ,, including the addition of carbamoyl radicals to quinone methides (Scheme b). We contemplated that photochemical carbamoylation represents several advantages over peroxide-promoted generation and use of carbamoyl radicals, such as application to aliphatic amines, use of precursors with other functionalities such as olefins and alkynes, and applicability to acrylamides containing other heteroatoms and flanking groups, ultimately resulting in a significantly greater product diversity (Scheme c).…”

“…Hong and co-workers have reported a photocatalyst-free carbamoylation of pyridinium salts . Our group has recently reported the photochemical carbamoylation of para -quinone methides using carbamoylated Hantzsch esters …”

“…14 Our group has recently reported the photochemical carbamoylation of para-quinone methides using carbamoylated Hantzsch esters. 33…”

A single-pot synthesis of 4-hydroxybenzophenones via acid-catalyzed alkoxylation of p-quinone methides followed by DDQ-assisted oxo-demethoxylation

“…p-QMs serve as vinylogous Michael acceptors in the 1,6-conjugate addition of various nucleophiles due to their versatile carbonyl and methide groups. [44][45][46][47][48] However, in most cyclization protocols, p-QMs generate structurally intricate final products, which may limit their probable applicability as substrates in the synthesis of active pharmaceutical ingredients. 49,50 Li et al recently developed a protocol for directly converting p-QMs to 3,5-ditertiarybutyl-4-HBP via radical oxidation using elemental sulphur as the redox reagent and KOH as the base in DMSO at 120-140 1C after 8-12 hours (Scheme 3(a)).…”