Dept. of Organic Chemistry, Stockholm University, Arrhenius Laboratory, 10691, Stockholm, Sweden.
Cardiovascular, Renal and Metabolism IMED Biotech Unit, AstraZeneca Gothenburg, 43183, Mölndal, Sweden.
Angew Chem Int Ed Engl. 2019 Apr 23;58(18):5930-5935. doi: 10.1002/anie.201814123. Epub 2019 Feb 15.
Asymmetric cyclopropane synthesis currently requires bespoke strategies, methods, substrates, and reagents, even when targeting similar compounds. This approach slows down discovery and limits available chemical space. Introduced herein is a practical and versatile diazocompound and its performance in the first unified asymmetric synthesis of functionalized cyclopropanes. The redox-active leaving group in this reagent enhances the reactivity and selectivity of geminal carbene transfer. This effect allowed the asymmetric cyclopropanation of various olefins, including unfunctionalized aliphatic alkenes, that enables the three-step total synthesis of (-)-dictyopterene A. This unified synthetic approach delivers high enantioselectivities that are independent of the stereoelectronic properties of the functional groups transferred. Our results demonstrate that orthogonally differentiated diazocompounds are viable and advantageous equivalents of single-carbon chirons.
不对称环丙烷合成目前需要定制的策略、方法、底物和试剂，即使是针对相似的化合物也是如此。这种方法减缓了发现速度，并限制了可用的化学空间。本文介绍了一种实用且通用的重氮化合物及其在第一个功能化环丙烷的统一不对称合成中的性能。该试剂中的氧化还原活性离去基团增强了偕二甲基卡宾转移的反应性和选择性。这种效应使得各种烯烃的不对称环丙烷化成为可能，包括未官能化的脂肪族烯烃，从而实现了(-)-dictyopterene A 的三步全合成。这种统一的合成方法提供了高对映选择性，与所转移的官能团的立体电子性质无关。我们的结果表明，正交差异的重氮化合物是单碳手性的可行且有利的等价物。
