Research Progress on the Radical-Polar Crossover Reaction in Total Synthesis of Natural Products

doi:10.6023/cjoc202410003

Abstract

Radical-polar crossover (RPCO) reactions are a class of cascade transformations that link radical and ionic intermediates, enabling the formation of multiple chemical bonds in a single step and thereby facilitating rapid increases in molecular complexity. Over the past few decades, a number of research groups have utilized RPCO reactions as key steps in the total synthesis of natural products, including terpenoids, alkaloids, lignans, and steroids. Despite these advances, compre- hensive reviews focusing on RPCO reactions remain limited. Applications of RPCO reactions in the total synthesis of natural products are systematically highlighted according to three categories: reduction type, oxidation type, and redox neutral type.

Key words: total synthesis of natural product, radical chemistry, cascade reaction, radical-polar crossover

Cite this article

Tao Long, Shuzhong He, Chao Li. Research Progress on the Radical-Polar Crossover Reaction in Total Synthesis of Natural Products[J]. Chinese Journal of Organic Chemistry, 2025, 45(3): 748-763.

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Fig. & Tab. 16

Scheme 1. Three types of RPCO reactions

Figure 1. Some representative natural products synthesized via RPCO reactions

Scheme 2. Constructionof a quaternary carbon via a reductive RPCO by Castle’s group

Scheme 3. Total synthesis of acutumine via a reductive RPCO achieved by Castle’s group

Scheme 4. Total synthesis of nodulisporic acid C via a reductive RPCO achieved by Pronin’s group

Scheme 5. Total synthesis of forskolin via a reductive RPCO achieved by Pronin’s group

Scheme 6. Total synthesis of quassin via a reductive RPCO achieved by Pronin’s group

Scheme 7. Construction of bicyclo[3.2.1]octanes via a reductive RPCO achieved by Li’s group

Scheme 8. Total synthesis of 11 diterpenoids via a reductive RPCO achieved by Li’s group

Scheme 9. Total synthesis of marcocalyxoformin B via a reductive RPCO achieved by Li’s group

Scheme 10. Total synthesis of 14-epiupial via an oxidative RPCO achieved by Paquette’s group

Scheme 11. Total synthesis of abifarine B via an oxidative RPCO achieved by Heretsch’s group

Scheme 12. Total synthesis of spirochensilide A/B via an oxidative RPCO achieved by Heretsch’s group

Scheme 13. Total synthesis of aspidospermidine via a redox-neutral RPCO achieved by Murphy’s group

Scheme 14. Total synthesis of cephalosporolide E/F via a redox-neutral RPCO achieved by Sartillo-Piscil’s group

Scheme 15. Total synthesis of DBCODs via a redox-neutral RPCO achieved by Lumb’s group

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