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Updated: Sep 25, 2026

Efficient Construction of Drug-like Bispirocyclic Scaffolds Via Organocatalytic Cycloadditions of α-Imino γ-Lactones and Alkylidene Pyrazolones
Published on: February 7, 2019
Preparation, structure, and unique thermal [2+2], [4+2], and [3+2] cycloaddition reactions of
Yoshikazu Horino1, Masanari Kimura, Shuji Tanaka
1Department of Applied Chemistry, Faculty of Engineering, Nagasaki University, 1-14 Bunkyo-Machi, Nagasaki 852-8521, Japan.
Abstract:
The terminal allene C(alpha)=C(beta) bonds of 4vinylidene-2-oxazolidinone (2) readily undergo [2+2] cycloaddition with a wide variety of terminal alkynes, alkenes, and 1,3-dienes irrespective of their electronic nature under strictly thermal activation conditions (70-100 degrees C) and provide 3substituted (Z)-methylenecyclobutenes 6, 3substituted methylenecyclobutanes 7 and 8, and 3vinylmethylenecyclobutanes 9, respectively, in good to excellent yields. Alkenes react with 2 with complete retention of configuration. The [2+2] cycloaddition is concluded to proceed via a concerted [(pi(2s)+pi(2s))(allene) + pi(2s)] Hückel transition state on the basis of experimental evidences and quantum mechanical methods. Some highly polarized enones and nitrile oxide, on the other hand, react with 2 selectively at the internal C(4)=C(alpha) double bonds and give spiro compounds 10 and 11, respectively. The bent allene bonds (173-176 degrees) and the unique reactivity associated with 2 are attributed to a low-lying LUMO (C(alpha)=C(beta)) that is substantiated by a through-space sigma*(N-SO(2))-pi*(C(alpha)=C(beta)) orbital interaction.
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