Synthesis of Sulfur-Containing Exo-Bicyclic Dienes and Their Diels–Alder Reactions To Access Thiacycle-Fused Polycyclic Systems

Abstract

The stereocontrolled synthesis of unprecedented sulfur-containing exo-bicyclic 1,3-dienes is reported through a palladium-catalyzed reductive cyclization of sulfur-linked 2-bromoenynes. The fused bicyclic structure provides a better stability to the thiacyclic diene compared to the simple 3,4-dimethylenetetrahydrothiophene. Their reactivity toward several dienophiles has been investigated, and various original thiacycle-fused polycyclic systems have been obtained with high or total diastereoselectivity. Moreover, they are the first exo-bicyclic dienes used in Diels-Alder reactions. The relative configurations of four cycloadducts have been unambiguously assigned by X-ray crystallographic analysis. Mechanistic details of the cycloadditions have been examined by computational means.

Synthesis of Medium-Sized Heterocycles by Transition-Metal-Catalyzed Intramolecular Cyclization

“…The synthesis of sulfur-containing heterocycles via palladium-catalyzed reactions is a less-common method than for the other heterocycles, because sulfur species are known to deactivate the Pd catalyst and make the reaction difficult. Our group was interested in this aspect, and since 2014 has published several papers dealing with the use of intramolecular carbopalladation of propargyl or alkynyl sulfides to access 5-and 6-membered S-heterocycles [39][40][41]. Then, we decided to extend the method to more challenging compounds, such as the medium-sized rings, and focused on N,S-heterocycles as target compounds.…”