Radical retrosynthesis: a powerful strategy for modern assembly of terpenoid natural products

Abstract

Radical retrosynthesis has emerged as a powerful strategy for the modern assembly of complex natural products, offering a one-electron logic that complements traditional polar disconnections. This review highlights recent advances—particularly developed over the past decade—in radical methodologies and their strategic applications in the total synthesis of terpenoid natural products. Emphasis is placed on how various radical precursors, including alkenes, carboxylic acids, halides, alcohols, carbonyl compounds, and alkanes, have been transformed through innovative processes such as photoredox catalysis, metal–hydride hydrogen atom transfer (MHAT), redox-active ester (RAE) chemistry, cross-electrophile couplings (XEC), and HAT-based C–H functionalization. By organizing the discussion around precursor classes and corresponding reaction modes, we illustrate how radical-based synthetic strategies enable efficient construction of quaternary stereocenters and modular assembly of complex polycyclic scaffolds.