Construction of Benzo‐Fused Heterocycles by Epoxide–Heteronucleophile Cyclization: Applications in the Synthesis of Natural Products and Designed Molecules

Construction of benzo‐fused heterocycles, specifically which have one or more sp3 stereogenic carbon atoms on the heterocyclic ring, by intramolecular ring‐opening cyclization of epoxides with O‐ and N‐nucleophiles is a powerful synthetic tool in organic synthesis. In this Review, we analyze the efficiency of such a heterocyclization approach in natural product synthesis and synthetic methodologies published since the year 2000. In addition to briefly discussing the synthetic methods of accessing the requisite epoxide substrates, important aspects of the subsequent cyclization reaction, such as reaction conditions, endo‐ versus exo‐regioselectivity, protecting or functional group compatibility, and enantio‐ and distereoselectivity are surveyed. Although the literature of organic chemistry in the last four decades has witnessed a large number of reviews/book chapters on the epoxide ring‐opening chemistry, the title topic has never been reviewed. Herein, we have systematized it as a dedicated review for the first time. The construction of benzo‐fused heterocycles by intramolecular ring‐opening cyclization of epoxides with O‐ and N‐nucleophiles, en route to the synthesis of natural products and designed molecules has been reviewed for the first time.