Asymmetric Synthesis of Azepine-Fused Cyclobutanes from Yne-Methylenecyclopropanes Involving Cyclopropanation/C-C Cleavage/Wagner-Meerwein Rearrangement and Reaction Mechanism.

Abstract

Ring expansion of in situ generated cyclopropylmethyl cations via Wagner-Meerwein rearrangement to cyclobutanes is widely used in synthesis. However, the cyclopropylmethyl cations generated are planar, which would lead to loss of chiral information in the case of chiral precursors, making an asymmetric version of such ring expansion difficult. In the present work, a gold(I)-catalyzed asymmetric cyclopropanation/C-C cleavage/Wagner-Meerwein rearrangement of easily affordable yne-methylenecyclopropanes (1,6-yne-MCPs) has been developed to synthesize 3-azabicyclo[5.2.0]nonadiene, a bicyclic 7/4 ring (azepine fused with cyclobutane) with a bridgehead aryl substituent. This reaction overcomes the challenging loss of chirality from the Wagner-Meerwein rearrangement. Density functional theory calculations indicate that the chirality of the final product comes from the first cyclopropanation step in this reaction. The chirality in the resultant cyclopropane is lost in the following C-C cleavage step, generating rigid, planar cyclopropylmethyl carbocation intermediate. Then, only one carbon of the cyclopropyl group in the cyclopropylmethyl carbocation intermediate can migrate via ring expansion in the Wagner-Meerwein rearrangement process, and consequently, the chirality in the cyclopropane generated in the first step is transferred to the final product.