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Recent Advances in Base-Mediated [5 + 1] Annulation Reactions.

Created on 01 Sep 2026

Authors

Yao Jiang, Yue Wang, Teck-Peng Loh

Published in

Chemical record (New York, N.Y.). Pages e70243. Aug 31, 2026. Epub Aug 31, 2026.

Abstract

The [5 + 1] annulation is a highly efficient strategy for constructing six-membered carbocycles, heterocycles, and spiro/fused ring skeletons, playing a crucial role in the synthesis of natural products, pharmaceuticals, and functional molecules. Traditional transition-metal-catalyzed methods often suffer from limitations such as metal contamination, high costs, and tedious workup procedures. In contrast, base-mediated/catalyzed systems have emerged as a prominent research hotspot owing to their metal-free nature, mild conditions, excellent functional group tolerance, and green economy. This review systematically summarizes the recent advances in base-mediated [5 + 1] cycloadditions over the past two decades. Based on the catalytic systems, the reactions are categorized into organic bases (tertiary amines, N-heterocyclic carbenes, organophosphines) and inorganic bases (potassium tert-butoxide, carbonates, and potassium methoxide). The cyclization modes involving various five-atom synthons with one-carbon/one-nitrogen synthons are discussed in detail. This review aims to provide a comprehensive theoretical reference for the future design of novel base-mediated cycloadditions and the construction of complex cyclic pharmaceutical skeletons.

PMID:
42675917
Bibliographic data and abstract were imported from PubMed on 01 Sep 2026.

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