Nitrone and Alkyne Cascade Reactions for Regio‐ and Diastereoselective 1‐Pyrroline Synthesis

Abstract

The synthesis of 1-pyrrolines from N-alkenylnitrones and alkynes has been explored as ar etrosynthetic alternative to traditional approaches.T hese cascade reactions are formal [4 + 1] cycloadditions that proceed through ap roposed dipolar cycloaddition and N-alkenylisoxazoline [3,3']sigmatropic rearrangement. Av ariety 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.M echanistic 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.D iastereoselective derivatization of the 1-pyrrolines prepared by the cascade reaction demonstrate the divergent synthetic utility of the new method.Scheme 1. N-Alkenylisoxazoline approach to 1-pyrroline synthesis.LG = leaving group. EWG = electron-withdrawing group.

Substituent and Solvent Effect Studies of N‐Alkenylnitrone 4π Electrocyclizations**

“…No evidence of cycloreversion was observed (Scheme 5B). To test for reversibility with trapping experiments, we turned to a cascade reaction established previously in our group [28] . As shown in Scheme 5C, when 1 b is treated with phenylacetylene at 70 °C, mixtures of azetidine nitrone 2 b and pyrroline 9 b are isolated by competitive electrocyclization and a cycloaddition/rearrangement process, respectively.…”

The Stannum–Ene Reactions of Benzyne and Cyclohexyne with Superb Chemoselectivity for Cyclohexyne

“…and our group, respectively. In 2021, Anderson and co‐workers reported a cascade transformation between cyclohexyne and N ‐alkenylnitrones toward the preparation of spirocyclic 1‐pyrrolines [3n] . Very recently, Wang et al.…”