Lu Liguo, Chen Shuhan, Kong Weiyu, Gao Ben, Li Yangyang, Zhu Lei, Yin Guoyin
The Institute for Advanced Studies, Wuhan University, Wuhan, Hubei 430072, P. R. China.
Hubei Key Laboratory of Quality Control of Characteristic Fruits and Vegetables, Hubei Engineering University, Wuhan, Hubei 430072, P. R. China.
J Am Chem Soc. 2024 Jun 9. doi: 10.1021/jacs.4c03700.
Aminoboronic acids represent a class of significant compounds that have attracted significant attention in the fields of drug discovery and organic synthesis. Despite notable progress in their synthesis, the efficient construction of chiral β-aminoboronic acids with alkyl side chains remains a challenging endeavor. Here, we introduce an unprecedented nickel-catalyzed asymmetric borylalkylation of enamides, employing a simple chiral diamine ligand, readily available Bpin, and alkyl halides as coupling partners. This reaction serves as an efficient platform for assembling a diverse range of β-aminoboronic acid derivatives with flexible alkyl side chains, displaying exceptional regio-, stereo-, and enantioselectivities. Moreover, this transformation exhibits a broad substrate scope and remarkable tolerance toward various functional groups. Theoretical calculations demonstrate that the benzyl group on the ligand is the key to the high enantiocontrol in this transformation. Additionally, we exemplify the practical application of this strategy through the concise synthesis of complex bioactive molecules.
氨基硼酸是一类重要的化合物，在药物发现和有机合成领域引起了广泛关注。尽管它们的合成取得了显著进展，但具有烷基侧链的手性β-氨基硼酸的高效构建仍然是一项具有挑战性的工作。在此，我们报道了一种前所未有的镍催化烯酰胺的不对称硼烷基化反应，该反应使用简单的手性二胺配体、易于获得的Bpin和卤代烃作为偶联伙伴。该反应为组装具有灵活烷基侧链的各种β-氨基硼酸衍生物提供了一个高效平台，表现出优异的区域选择性、立体选择性和对映选择性。此外，这种转化具有广泛的底物范围和对各种官能团的显著耐受性。理论计算表明，配体上的苄基是该转化中高对映选择性控制的关键。此外，我们通过简洁合成复杂的生物活性分子例证了该策略的实际应用。
