Substituted oxabicyclo derivatives bearing two quaternary carbon centers and five contiguous stereocenters have been synthesized from C3‐thioester/‐ester substituted dienones, a simple and linear pluripotent molecular platform. The conversion proceeds from neat reactants, possibly via a thermally‐driven pericyclic cascade manifold involving sequential (E)‐s‐trans to (E)‐s‐cis isomerization, oxa‐6π‐electrocyclization, and intermolecular, regioselective [4π+2π] cycloaddition. The proposed mechanism has been substantiated by intermediate trapping experiments and DFT studies. Such dienones have also been exploited to effect stereoselective cross Diels‐Alder cycloadditions with olefins and sequential Diels‐Alder/retro‐Diels‐Alder reactions with activated alkynes. The reaction is greatly influenced by the substituent effect exerted by the C3‐thioester/‐ester group.

α‐Ketothioesters undergo triphenylphosphine (PPh3)‐catalyzed cyclization with acetylenedicarboxylate esters smoothly, in contrast to α‐ketooxoesters which require more drastic conditions with the limited substrate scope. The reaction works well with a wide range of α‐ketothioesters, delivering highly functionalized α,β‐unsaturated γ‐butyrolactones in moderate to excellent yields. The higher reactivity of the thioester derivatives is seemingly due to a favourable intramolecular non‐bonding electrostatic 1,4‐interaction involving C−S σ* orbital on the sulphur atom and the lone pair of electrons in the electron‐donating oxygen atom. This is apparent from the X‐ray crystallographically determined internuclear distance between the sulphur and ketone (C=O) oxygen atoms (2.71–2.85 Å), which is significantly less than the sum of their van der Waals radii (3.25–3.30 Å). The substitution on the S atom is oriented diametrically away from the ketone O atom to maximize the interaction between them. The trend is also seen in the 1,4‐S⋅⋅⋅O contact between the S and furan O atoms (2.70 Å) in the γ‐butyrolactone products.