Bicyclo[4.1.0]heptane derivatives have broad application prospects in the fields of biomedicine and agrochemistry. This review systematically summarizes the methods for constructing the bicyclo[4.1.0]heptane framework, based on two types of cyclization reactions: intramolecular and intermolecular cyclizations.

Abstract

Bicyclo[4.1.0]heptanes and their nitrogen- and oxygen-containing derivatives represent an important class of fused bicyclic scaffolds with significant biological activities, commonly found in natural products and pharmaceutical agents. In recent years, considerable progress has been made in the development of efficient synthetic strategies targeting these structures. Various approaches, including transition-metal catalysis, organic catalysis, and free radical-mediated cyclization reactions, have been successfully applied for the precise construction of bicyclo[4.1.0]heptane frameworks. In this review, systematically summarized are two major types of cyclization strategies—intramolecular and intermolecular cyclizations—based on their reaction mechanisms. Particular emphasis is placed on recent advances in the synthesis of bicyclo[4.1.0]heptanes, azabicyclo[4.1.0]heptanes, and oxabicyclo[4.1.0]heptanes. This paper aims to highlight key developments and inspire further innovation in the construction of these valuable frameworks.