Studies On Semipinacol Rearrangement-Based Cascade Reaction

Development of a general method for quickly generating structural complex organic molecules in step-and atom-ecnomical manners has always been a ideal goal for synthetic chemistry. Among the "ideal synthesis" methods achieved, the cascade reaction has been proved to be one of the most powerful methods and played growing roles in organic synthesis. Chapter1of this thesis introduced different kinds of cascade reactions and semipinacol-based cascade reactions developed in this group; Chapter2introduced recent progress on synthesis of2-oxindoles and3-oxindoles and our studies on constructing2-spirocyclo-3-oxindoles through a cascade oxidative dearomatization/semipinacol rearrangement of indol-2-yl cyclobutanol with N-sulfonyloxaziridine as oxidant; Chapter3introduced electrophile induced semipinacol rearrangement and our studies on constructing complex polycyclic structures through a novel carbon electrophile induced intermolecular oxa-Diels-Alder/semipinacol rearrangement/aldol cascade reaction.Chapter1:Cascade reactions were classified and illustrated depending on the nature of the reaction. Semipinacol rearrangement and pinacol rearrangement reaction was introduced briefly. Semipinacol rearrangement has been extensively studied as one of the powerful quaternary carbon constructing reactions. When it was combined with cascade reaction, polycyclic structures could be obtained efficiently.Chapter2:Although numerous approaches have been developed for the synthesis of the oxindole derivatives, most of them focus on the synthesis of3-spirocyclo-2-oxindoles. In fact, the2-spirocyclo-3-oxindoles also exist widely in natural products. However, since the general electrophilic reaction of indole occurs favorably at C3position instead of C2, methods on the synthesis of2,2-disubstituted (or2-spirocyclo)3-oxindoles are still rare, and generally based on a Michael addition of indolin-3-ones to unsaturated carbonyl compounds and nitroolefins. We have developed a cascade oxidative dearomatization/semipinacol rearrangement of indol-2-yl cyclobutanol with N-sulfonyloxaziridine as oxidant, which provided a direct route of2-spirocyclo-3-oxindoles from N-alkyl substituted indoles. This reaction might be useful in the synthesis of indole-based alkaloids and pharmaceutical molecules.Chapter3:Series of semipinacol rearrangement have been developed in the past few decades, however, most of the electrophiles used previously is based on heteroatoms such as oxygen, nitrogen and halogen. In contrast, carbon electrophile is a much more direct and efficient method compared to heteroatom to provide complex carbon frameworks. A novel carbon electrophile induced intermolecular oxa-Diels-Alder/semipinacol rearrangement/aldol cascade reaction of allylic silylethers with β,γ-unsaturated a-ketoester has been developed under the promotion of SnCl4. This highly efficient transformation enables the quick construction of polycyclic architectures with up to five contiguous stereogenic centers in a single operation with good to excellent yields as well as high diastereoselectivity, and would provide versatile short approaches to frameworks and/or analogues of numerous biologically important polycyclic natural products.