Transition-metal-catalyzed cycloaddition of cyclopropane with π-unsaturated compound has emerged as a powerful tool for the construction of cyclic structural units during the past decades. However, their cycloaddition reaction still remains an elusive challenge. Different from highly strained cyclopropanes bearing fused π-unsaturation, lessstrained cyclopropanes bearing adjacent π-unsaturation prove quite inert in transition metal-catalyzed cloaddition reactions.

Herein, Prof. Ye’s group reported a Ni-Al bimetallic synergism to facilitate the cycloaddition reaction of cyclopropyl carboxamide with alkyne for the first time, in which the ligand-Ni-Al combination probably played a triple role: activating cyclopropane substrate, directing nickel oxidative addition and stabilizing the in situ formed nickellacycle. In addition, a successful enantioselective control of this reaction was also achieved by the use of taddol-derived chiral phosphine oxide ligand with up to 94% ee.

To demonstrate the applicability of the amide group, further transformation of products was conducted. When subjected to acidic conditions, cyclopentene was easily transformed into the corresponding acid, a versatile synthetic intermediate, in 85% yield but with partial racemization. Cyclopentene was treated by oxidation conditions to deliver a dearylated amide in 81% yield.

In summary, this work has demonstrated the first example of nickelcatalyzed enantioselective cycloaddition reaction of unreactive cyclopropyl carboxamide with alkyne. A series of synthetically useful cyclopentenyl carboxamides are obtained in up to 99% yield and 94% ee. The cooperation of ligand with Ni and Al may provide new insights into the C-C bond activation of unreactive substrates.

This research was published in the Journal of the American Chemical Society. The first author is PhD. Qi-Sheng Liu and the joint first author is PhD. De-Yin Wang.

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https://pubs.acs.org/doi/abs/10.1021/jacs.7b09947