Radical di- and multi-functionalization of alkenes: recent advances in diverse reaction modes utilizing TBHP as reactants

Abstract

In recent years, radical-mediated functionalization of olefins has gradually become a research hotspot in the field of organic synthesis due to its high reactivity, excellent regioselectivity, and wide substrate applicability. Compared to traditional ionic pathways, radical strategies effectively avoid compatibility issues with some functional groups through modes, such as photocatalysis, electrocatalysis, or chemical initiation, and provide new pathways for the diversified conversion of olefins, such as bifunctional, hydrogen functionalization, and cyclization reactions. Among them, tert-butyl hydroperoxide (TBHP) plays multiple roles in synthetic chemistry as an efficient and inexpensive oxidant and radical precursor: it is not only a classic initiator of radical chain reactions but also a source of tert-butyl peroxide, tert-butyl oxygen, methyl, oxygen, hydrogen, or hydroxyl groups. The unique capacity to generate controllable radical species establishes TBHP as an indispensable platform for advancing green synthetic methodologies, empowering pharmaceutical innovation and deciphering fundamental reaction mechanisms. In this review, we summarize the recent progress in TBHP-enabled transformations of alkenes, which are categorized as peroxidation, carbonylation, epoxidation, etherification, hydrogenation, and hydroxylation. Within each category, representative studies are presented and discussed in terms of mechanistic insights and substrate scope expansion.