Premium
Nitrone and Alkyne Cascade Reactions for Regio‐ and Diastereoselective 1‐Pyrroline Synthesis
Author(s) -
Zhang Guanqun,
Alshreimi Abdullah S.,
Alonso Laura,
Antar Alan,
Yu HsienCheng,
Islam Shahidul M.,
Anderson Laura L.
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202101511
Subject(s) - pyrroline , chemistry , cycloaddition , alkyne , nitrone , steric effects , combinatorial chemistry , allene , cascade , pyrrolidine , sigmatropic reaction , stereochemistry , organic chemistry , catalysis , chromatography
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.