ZnI₂‑Catalyzed Diastereoselective [4 + 2] Cycloadditions of β,γ‑Unsaturated α‑Ketothioesters with Olefins

The potential of β,γ-unsaturated α-ketothioesters participating in hetero-Diels–Alder reaction has remained unexplored. We report herein the first study of a ZnI2-catalyzed highly diastereoselective inverse electron demand hetero-Diels–Alder reaction of β,γ-unsaturated α-ketothioesters with olefins to access highly substituted 3,4-dihydro-2H-pyrans. All the reactions proceed with cis-selectivity in moderate to excellent yields. Under similar reaction conditions, terminal alkynes undergo direct conjugate 1,4-addition to yield δ,ε-acetylenic α-ketothioesters. Furthermore, the utility of these cycloadducts has been demonstrated by an NBS-MeOH mediated stereospecific efficient access to fully substituted pyran rings. The product bromoethers undergo E2 elimination with DBU, resulting in substituted 3,6-dihydro-2H-pyrans. In addition, the thioester moiety of the products has been used for further transformations, such as amidations and Fukuyama coupling reactions.β,γ-不饱和α-酮硫酯（β,γ-unsaturated α-ketothioesters）参与杂Diels-Alder（hetero-Diels–Alder）反应的潜力至今尚未得到探索。本文首次报道了碘化锌（ZnI₂）催化的β,γ-不饱和α-酮硫酯与烯烃的高非对映选择性逆电子需求杂Diels-Alder反应，以制备高度取代的3,4-二氢-2H-吡喃类化合物。所有反应均以顺式选择性进行，产率从中等到优异不等。在相似反应条件下，端基炔烃可直接发生共轭1,4-加成，生成δ,ε-炔基α-酮硫酯。此外，通过NBS-MeOH介导的立体专一性高效合成全取代吡喃环的反应，验证了此类环加合物的应用价值：所得溴代醚可与DBU发生E2消除，得到取代的3,6-二氢-2H-吡喃。除此之外，产物中的硫酯基团还可用于进一步转化，例如酰胺化反应和Fukuyama偶联反应。