芳基砜自由基/正离子参与烯烃的串联环化反应构建芳基烷基砜类化合物

Aryl alkyl sulfones are an important class of bioactive compounds and synthetic intermediates that have widespread applications in pharmaceutical chemistry, organic synthesis and material science. As a consequence, the exploitation of efficient method to construct aryl alkyl sulfones has become the hot-topic area in modern organic synthesis. Recently, the chemist has made great progress in the synthesis of aryl alkyl sulfones, However, few reports were published about the construction of heterocyclic aryl alkyl sulfones by hetero-sulfonylation or spiro cyclization through the tandem cyclization strategy of alkenes with aryl sulfone radical/cation. For the project, we have done some preliminary exploration, and have successfully constructed the sulfone-substituted isoxazolines through a tandem oxysulfonylation of alkenyl oximes with sodium sulfonates. Inspired by this result we intend to develop more efficient and concise methods to construct aryl alkyl sulfone skeleton by using the above strategy. The specific research includes the following contents: (1) tandem cyclization and aminosulfonylation of alkenes with aryl sulfone reagents. (2) tandem cyclization and hetero-sulfonylation of three-component reaction. (3) tandem spiro cyclization of alkenes with aryl sulfone reagents. The implementation of this project will contribute to the study for the reaction of building aryl alkyl sulfone compounds.

芳基烷基砜作为一类重要的生物活性物质和合成中间体，被广泛应用于药物化学、有机合成以及材料科学，所以此类化合物的制备已成为有机合成领域的热点研究课题之一。虽然目前有关合成芳基烷基砜的研究已经取得了很大的进展，但是通过芳基砜自由基/正离子参与烯烃底物的串联环化反应策略，实现杂砜双官能团化或螺环化，构建杂环类芳基烷基砜的报道还很少。针对本项目我们做了一些前期探索，利用芳基亚磺酸钠和烯基肟通过串联氧砜化反应成功构建了砜代异噁唑啉类化合物。受此鼓舞我们拟利用上述策略发展更多高效、简洁的构建芳基烷基砜骨架的新方法。具体的研究内容如下：(1)烯烃化合物和芳基砜试剂的串联环化、胺砜双官能团化反应。(2) 三组分参与的串联环化、杂砜双官能团化反应。(3) 烯烃化合物和芳基砜试剂的串联螺环化反应。该项目的实现将会对构建芳基烷基砜化合物的反应研究做出贡献。

设计了一系列砜自由基诱导的串联环化反应，建立了一种构建砜代杂环骨架的绿色、简洁新方法，实现了串联胺砜化和砜代串联螺环化反应。我们深入研究了这类反应的反应条件、反应机理和反应体系对该类型反应的影响，对反应的机理有了深刻理解。此外，在本项目探索中还拓展实现了一系列的“铜催化/介导 β,γ-不饱和烯基腙类化合物的氨基功能化环化反应”和“铜/DTBP 促进下炔丙基胺、二硒醚和二氧化碳的三组分亲电串联环化合成硒基 2-恶唑烷酮类化合物反应”。这些工作为相关复杂有机化合物分子和天然产物的高效合成奠定了基础。