Hydrazide‐Catalyzed Polyene Cyclization: Asymmetric Organocatalytic Synthesis of cis‐Decalins

Polyene cyclizations offer rapid entry into terpenoid ring systems. Although enantioselective cyclizations of (E)‐polyenes to form trans‐decalin ring systems are well precedented, highly enantioselective cyclizations of (Z)‐polyenes to form the corresponding cis‐decalins have not been reported. Here, we describe the first application of iminium catalysis to the initiation of polyene cyclizations. Ethyl 1,2‐diazepane‐1‐carboxylate catalyzes the cyclization of polyenes bearing enal initiators. Moreover, chiral bicyclic hydrazides catalyze the cyclizations of (Z)‐polyene substrates to form cis‐decalins with enantioselectivities of up to 97:3 er. DFT calculations suggest the catalysts promote the reaction by stabilizing positive charge as it develops during the bicyclization. Remote stabilization: Chiral bicyclic hydrazides catalyze cyclizations of (Z)‐polyenes to cis‐decalins by means of iminium‐ion catalysis. High enantioselectivity results from remote stabilization of the developing cationic charge in the transition state by the hydrazide carbonyl.