A straightforward hetero Diels-Alder approach to (2-ambo, 4'R,8'R) alpha-, beta-, gamma- and delta-4-thiatocopherol

A simple and original inverse electron demand hetero-Diels- Alder reaction has been successfully applied to the synthesis of (2-ambo,4'R,8'R)-alpha/beta/gamma/delta-4-thiatocopherol. Commercially available methyl hydroquinones and (2E,7R,11R)-(+)-phytol were exploited for the preparation of the ortho-thioquinones, acting as electron-poor dienes, and of the proper 1,3-diene used as dienophile, respectively. The benzoxathiine cycloadducts, with the required tocopherol-like skeleton, were obtained with complete control of regio and chemoselectivity. The antioxidant activity of 4-thiatocopherols was measured and rationalized in comparison with that of the corresponding natural components of Vitamin E