Tertiary Alcohols as Radical Precursors for the Introduction of Tertiary Substituents into Heteroarenes

Abstract

Despite many recent advances in the radical alkylation of electron-deficient heteroarenes since the seminal reports by Minisci and coworkers, methods for the direct incorporation of tertiary alkyl substituents into nitrogen heteroarenes are limited. This report describes the use of tert-alkyl oxalate salts, derived from tertiary alcohols, to introduce tertiary substituents into a variety of heterocyclic substrates. This reaction has reasonably broad scope, proceeds rapidly under mild conditions, and is initiated by either photochemical or thermal activation. Insights into the underlying mechanism of the higher yielding visible-light initiated process were obtained by flash photolysis studies, whereas computational studies provided insight into the reaction scope.

Recent advances in photoredox and nickel dual-catalyzed cascade reactions: pushing the boundaries of complexity

“…Alkyltrifluoroborates, 4m , 5 alkylsilicates, 4l , 6 carboxylic acids, 4n , 7 alkyl oxalates, 8 4-alkyl-1,4-dihydropyridines (DHPs), 4e , 9 and THF 10 have been demonstrated as readily available carbon radical precursors in photochemistry. Using photoredox and nickel dual-catalyzed cascade reactions as a platform, a series of protocols for the difunctionalization of alkynes and alkenes have been established using these radical precursors.…”

Synthesis of Alkyl Fluorides by Silver‐Catalyzed Radical Decarboxylative Fluorination of Cesium Oxalates

“…With this aim in mind, we kept on investigating the radical deoxyfluorination of oxalate derivatives. Although such alkyl radical precursors have been successfully used in various visible‐light‐mediated transformations, [14,15] they have long been known to undergo non‐light‐mediated radical decarboxylative transformations [14k,16,17] …”

Radical Deoxyfunctionalisation Strategies

“…In 2019, Overman expanded his work on light-mediated generation of tertiary alkyl radicals to realise the alkylation of basic heteroarenes via a Minisci-type reaction (Scheme 16B). [31] This protocol can be promoted via either photochemical or thermal methods, benefiting from mild conditions, fast reaction times, and reasonable functional group tolerance, e.g. cyano, amides, esters and trifluoromethyl.…”