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

Abstract

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.

Asymmetric Total Synthesis of Dankasterones A and B and Periconiastone A Through Radical Cyclization

“…Nonetheless,all attempts along this line met with diminished yields and enantioselectivities until very recently,the Gleason group described the asymmetric formation of cis-decalin 14 from (Z)-polyene substrate (13)t hrough iminium ion catalyzed polyene cyclization (Scheme 2b). [12] Although great progress has been made,alternative methods are still demanding partly because elaborations of the phenyl group to other functional species are challenging and require harsh conditions.Eschenmoser disclosed that enantiomerically enriched 15 could be converted into racemic trans-decalin 16 under thermodynamic control (Scheme 2c). It was presumed isomerization of the exocyclicd ouble bond of 15 to tetrasubstituted alkene occurred at first, thus eliminating the stereochemical information, prior to diastereospecific carbocyclization.…”

A Three-Step Process to Facilitate the Enantioselective Assembly of Cis-Fused Octahydrophenanthrenes with a Quaternary Stereocenter

“…Just recently, one-step catalytic asymmetric methods have been achieved. In 2020, Gleason et al 10 reported a highly enantioselective synthesis of a series of cis-fused octahydrophenanthrenes bearing a methylated quaternary stereocenter by chiral bicyclic hydrazide-catalyzed asymmetric polyene cyclization of Zpolynenes (Figure 1b). Subsequently, by employing an elegant rhodium-catalyzed asymmetric intramolecular carboacylation of olefins with benzocyclobutanones, 11 Dong et al 8c achieved the enantioselective construction of cis-fused octahydrophenanthrene ring systems in one step and completed the first total synthesis of (−)-thebainone (Figure 1b).…”