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

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.