This tutorial review outlines the evolution of methods for radical generation with applications in total synthesis, starting from classical methods towards greener methods that utilize recent advances in electrochemistry and photoredox catalysis.

The field of strain-driven, radical formal cycloadditions is experiencing a surge in activity motivated by a renaissance in free radical chemistry and growing demand for sp 3 -rich ring systems. The former has been driven in large part by the rise of photoredox catalysis, and the latter by adoption of the "Escape from Flatland" concept in medicinal chemistry. In the years since these broader trends emerged, dozens of formal cycloadditions, including catalytic, asymmetric variants, have been developed that operate via radical mechanisms. While cyclopropanes have been studied most extensively, a variety of strained ring systems are amenable to the design of analogous reactions. Many of these processes generate lucrative, functionally decorated sp 3 -rich ring systems that are difficult to access by other means. Herein, we summarize recent efforts in this area and analyze the state of the field.

The field of strain-driven, radical formal cycloadditions is experiencing a surge in activity motivated by a renaissance in free radical chemistry and growing demand for sp 3 -rich ring systems. The former has been driven in large part by the rise of photoredox catalysis, and the latter by adoption of the "Escape from Flatland" concept in medicinal chemistry. In the years since these broader trends emerged, dozens of formal cycloadditions, including catalytic, asymmetric variants, have been developed that operate via radical mechanisms. While cyclopropanes have been studied most extensively, a variety of strained ring systems are amenable to the design of analogous reactions. Many of these processes generate lucrative, functionally decorated sp 3 -rich ring systems that are difficult to access by other means. Herein, we summarize recent efforts in this area and analyze the state of the field.

A simple method for accessing trans-2,3-diaryl-dihydrobenzofurans is reported. This approach leverages a persistent radical equilibrium between quinone methide dimers and the persistent phenoxyl radicals derived therefrom. This equilibrium is disrupted by phenols that yield transient phenoxyl radicals, leading to cross-coupling between persistent and transient radicals. The resultant quinone methides with pendant phenols rapidly cyclize to dihydrobenzofurans (DHBs). This putatively biomimetic access to dihydrobenzofurans provides superb functional group tolerance and a unified approach for the synthesis of resveratrol-based natural products.

A simple method for accessing trans‐2,3‐diaryl dihydrobenzofurans is reported. This approach leverages the equilibrium between quinone methide dimers and their persistent radicals. This equilibrium is disrupted by phenols that yield comparatively transient phenoxyl radicals, leading to cross‐coupling between the persistent and transient radicals. The resultant quinone methides with pendant phenols rapidly cyclize to form dihydrobenzofurans (DHBs). This putative biomimetic access to dihydrobenzofurans provides superb functional group tolerance and a unified approach for the synthesis of resveratrol‐based natural products.