Intramolecular [2+2]‐Cycloaddition in the Synthesis of Polycyclic Tetrahydrothiopyran Derivatives Bearing a Cyclobutane Scaffold

Abstract

In the manuscript the synthesis of polycyclic tetrahydrothiopyrans incorporating cyclobutane and cyclopentane moieties is described. The developed reaction sequence takes advantage of the functionalization of the dihydrothiopyran ring via a recently disclosed enantioselective ortho-regioselective inverse-electron-demand hetero-Diels-Alder reaction between thiochalcones and α,β-unsaturated aldehydes. It was found that when dihydrothiopyrans thus obtained were subjected to Wittig olefination, the resulting products participated in the Lewis-acid-promoted intramolecular [2 + 2]-cycloaddition. The one-pot reaction sequence proceeded efficiently and with the introduction of four new stereogenic centers with excellent diastereocontrol. Scheme 8. Intramolecular [2 + 2]-cycloaddition -mechanistic considerations.