Synthesis using aromatic homolytic substitution—recent advances

Abstract

This critical review aims at presenting recent developments in intramolecular aromatic homolytic substitution which has become one of the common methodologies in modern synthesis. The application of Bu3SnH-mediated cyclisations have proved especially useful. The critical review illustrates the mechanistic considerations required for planning synthetic applications and a wide range of synthetic protocols and natural product syntheses are shown. The latest evidence for the mechanisms involved in aromatic homolytic substitution are presented. (152 references).

The frequently overlooked importance of solvent in free radical syntheses

“…Alternatively, when the halide yields a highly reactive carboncentered radical, such as an aryl radical, intramolecular H-atom abstraction can occur even from unactivated C-H bonds (radical translocation). The new radical center can then generate the desired C-C bond by effecting an intramolecular homolytic aromatic substitution 45 and cyclizing onto the aromatic ring, see e.g., Scheme 13. 46 The observation that tin hydride reductions of alkyl halides were retarded by unsaturated compounds was made during the first kinetic experiments designed to measure the absolute (as opposed to the relative) rate constants for chain propagation Scheme 11 Mechanism of cumene autoxidation initiated by Fe(II) and mechanism of its inhibition by phenol that can be formed from its hydroperoxide by Lewis acid catalysts.…”

A new era for homolytic aromatic substitution: replacing Bu3SnH with efficient light-induced chain reactions

“…1 The difficulties in carrying out net oxidation in the presence of a Group 14 metal hydride reductant are rationalized along with an overview of recent synthetic examples. Over the last five years however there has been a renascence with more efficient and green chain reactions invented with the most prominent being visible light photoredox catalysis and base-promoted HAS.…”

Palladium and radical routes to phenanthridines

“…The mechanism for the formation of the phenanthridines is that of homolytic aromatic substitution. 19 The t-BuO⋅ radical abstracts the imine-H forming the imidoyl radical, which then adds to the phenyl ring. The homolytic aromatic substitution is then terminated by H-atom abstraction by another radical such as a t-BuO⋅ radical.…”