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

T. Castanheiro , A. Schoenfelder (1) , M. Donnard (2) , Isabelle Chataigner (3, 4) , M. Gulea (2)

1 Institut Gilbert-Laustriat : Biomolécules, Biotechnologie, Innovation Thérapeutique
2 LIT - Laboratoire d'Innovation Thérapeutique
3 COBRA - Chimie Organique et Bioorganique : Réactivité et Analyse
4 LCT - Laboratoire de chimie théorique

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.

Domaines: Chimie

T. Castanheiro, A. Schoenfelder, M. Donnard, Isabelle Chataigner, M. Gulea. Synthesis of Sulfur-Containing Exo -Bicyclic Dienes and Their Diels-Alder Reactions to Access Thiacycle-Fused Polycyclic Systems. Journal of Organic Chemistry, 2018, 83 (8), pp.4505-4515. ⟨10.1021/acs.joc.8b00213⟩. ⟨hal-02024483⟩