Unlocking Oxetane Potential: Modular Synthetic Platform for the Concise Synthesis of Acyclic Oligo‐Isoprenoids and Terpenoids

Abstract Terpenes occupy a unique place among the secondary metabolites due to their broad utility and extraordinary structural diversity. Their synthesis via polyene cyclization, either biomimetic or enzymatic, represents the cutting edge of modern synthetic chemistry. However, these endeavors have been inherently tied to the availability of natural and non‐natural acyclic polyene starting materials. Herein, we report an oxetane‐based platform for the modular construction of oxygenated polyolefins with precise geometric control. This “tail‐to head” iterative method leverages the site‐selective cross‐metathesis of terminal olefins to form an alkylidene oxetane moiety and the regioselective ring opening of alkenyl‐oxetanes for chain elongation. In addition, the unique and peculiar propensity of alkylidene oxetane fragment in various reactions was also revealed and exploited for site‐selective functionalization, cyclization, and as a protecting group in polyenes.