Zhang Guanqun, Alshreimi Abdullah S, Alonso Laura, Antar Alan, Yu Hsien-Cheng, Islam Shahidul M, Anderson Laura L
Department of Chemistry, University of Illinois at Chicago, 845 W Taylor St. MC 111, Chicago, IL, 60607, USA.
Angew Chem Int Ed Engl. 2021 Jun 1;60(23):13089-13097. doi: 10.1002/anie.202101511. Epub 2021 Apr 28.
The synthesis of 1-pyrrolines from N-alkenylnitrones and alkynes has been explored as a retrosynthetic alternative to traditional approaches. These cascade reactions are formal [4+1] cycloadditions that proceed through a proposed dipolar cycloaddition and N-alkenylisoxazoline [3,3']-sigmatropic rearrangement. A variety of cyclic alkynes and terminal alkynes have been shown to undergo the transformation with N-alkenylnitrones under mild conditions to provide the corresponding spirocyclic and densely substituted 1-pyrrolines with high regio- and diastereoselectivity. Mechanistic studies provide insight into the balance of steric and electronic effects that promote the cascade process and control the diastereo- and regioisomeric preferences of the 1-pyrroline products. Diastereoselective derivatization of the 1-pyrrolines prepared by the cascade reaction demonstrate the divergent synthetic utility of the new method.
探索了由N-烯基硝酮和炔烃合成1-吡咯啉作为传统方法的逆合成替代方法。这些串联反应是形式上的[4+1]环加成反应，通过提出的偶极环加成和N-烯基异恶唑啉[3,3']-σ迁移重排进行。已表明多种环状炔烃和末端炔烃在温和条件下与N-烯基硝酮发生转化，以高区域和非对映选择性提供相应的螺环和密集取代的1-吡咯啉。机理研究深入了解了促进串联过程并控制1-吡咯啉产物的非对映和区域异构体偏好的空间和电子效应的平衡。通过串联反应制备的1-吡咯啉的非对映选择性衍生化证明了新方法的不同合成效用。
