Stereoselective Sequential Spirocyclopropanation/Cloke–Wilson Rearrangement Reactions for Synthesis of <i>trans</i>-β,γ-Disubstituted γ‑Butyrolactones Using Alkylidene Meldrum’s Acid and Benzyl Halides

The stereoselective sequential spirocyclopropanation/Cloke–Wilson rearrangement reactions have been developed to synthesize γ-butyrolactones using alkylidene Meldrum’s acids and benzyl halides. The DBU-promoted spirocyclopropanation was carried out efficiently at room temperature to generate trans-isomeric spirocyclopropyl Meldrum’s acid, and the following stereospecific thermal decarboxylative Cloke–Wilson rearrangement afforded trans-γ-butyrolactones. A variety of aromatic and aliphatic Meldrum’s acid derived olefins and benzyl halides were tolerated. Various trans-β,γ-disubstituted γ-butyrolactones were produced with moderate to good overall yields from 46 to 96% and excellent diastereoselectivities.本研究开发了立体选择性串联螺环丙烷化/Cloke-Wilson重排反应，以亚烷基麦氏酸（alkylidene Meldrum’s acids）与卤化苄为原料合成γ-丁内酯。该反应以DBU为碱促进剂，在室温下高效完成螺环丙烷化步骤，得到反式构型的螺环丙基麦氏酸中间体；随后经立体专一性热脱羧Cloke-Wilson重排，生成反式γ-丁内酯产物。该反应对多种芳基及烷基来源的麦氏酸衍生烯烃与卤化苄均具有良好的底物兼容性。最终可得到一系列反式-β,γ-二取代γ-丁内酯产物，总收率介于46%至96%之间，表现出中等至优异的整体收率，且具有极佳的非对映选择性。