Asymmetric Synthesis of Azepine-Fused Cyclobutanes from Yne-Methylenecyclopropanes Involving Cyclopropanation/C-C Cleavage/Wagner-Meerwein Rearrangement and Reaction Mechanism
Asymmetric Synthesis of Azepine-Fused Cyclobutanes from Yne-Methylenecyclopropanes Involving Cyclopropanation/C-C Cleavage/Wagner-Meerwein Rearrangement and Reaction Mechanism
复制标题
涉及环丙烷化/C-C裂解/Wagner-Meerwein重排的炔-亚甲基环丙烷不对称合成氮杂环庚烷稠合环丁烷及反应机制
DOI：
10.1021/acs.joc.9b01071
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发表时间：
2019
影响因子：
3.6
通讯作者：
Yu Zhi Xiang
中科院分区：
文献类型：
--
作者：
Li Chen Long;Yu Zhi Xiang
通过 Wagner-Meerwein 重排原位生成的环丙基甲基阳离子环扩展为环丁烷被广泛用于合成中。然而，产生的环丙基甲基阳离子是平面的，这会导致手性前体的手性信息丢失，使得这种环扩展的不对称版本变得困难。在目前的工作中，开发了一种金（I）催化的不对称环丙烷化/C-C裂解/Wagner-Meerwein重排，用于合成3-氮杂双环[5.2.0]壬二烯，这是一种带有桥头芳基的双环7/4环（与环丁烷稠合的吖庚因）。取代基。该反应克服了瓦格纳-梅尔温重排造成的手性损失。密度泛函理论计算表明，最终产物的手性来自该反应的第一个环丙烷化步骤。所得环丙烷的手性在接下来的 C-C 裂解步骤中消失，生成刚性的平面环丙基甲基碳阳离子中间体。然后，在Wagner-Meerwein重排过程中，环丙基甲基碳阳离子中间体中环丙基中只有一个碳可以通过扩环迁移，因此第一步生成的环丙烷中的手性转移到了最终产物中。
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.