铑催化环丙醇类化合物基于C—C键断裂的胺化和烷基化反应研究

Rh(Ⅲ)-catalyzed amidation and alkylation of cyclopropanols via C—C bond cleavage and redox-neutral coupling

本文将环丙醇C—C键活化与乃春/卡宾的迁移插入相结合,发展了一种简单高效的铑催化环丙醇开环官能化体系,实现了环丙醇的胺化和烷基化反应,构建了一系列重要的β-官能化的酮类化合物.该体系以易于制备的二恶唑酮和重氮化合物为乃春/卡宾前体,以水为溶剂,生成的副产物为CO2和N2.该反应条件温和,操作简单且底物的适用范围宽泛,为β-官能化的酮类化合物的合成提供新途径.

Strain-driven ring-opening coupling of cyclopropanols plays an important role in synthesis of structurally diversified β-functionalized ketones.Herein,Rh (Ⅲ) -catalyzed ring-opening amidation and alkylation of cyclopropanols have been realized by integrating C—C activation andα-insertion of nitrenes and carbenes,where readily available 1,4,2-dioxazol-5-ones and diazo compounds serve as the nitrene/carbene precursor.The reaction proceeded under mild and operationally simple conditions in water with good functional group tolerance(47 examples,up to 95% yield),providing an efficient route to access structural diversifyβ-functionalized ketones.Additionally,the coupling was carried out in low catalyst loading without any additives,affording CO2 or N2 as the only byproduct.Scale-up synthesis and transformations of aminating product demonstrated the potential utilities of this coupling system.On the basis of mechanistic studies(control and deuteration experiments)and literature precedents,aplausible mechanism for the reaetion is proposed.Cp*Rh (Ⅲ) is effective to induce the cyclopropanol C—C activation viaβ-carbon elimination to generate a reactive Rh (Ⅲ) alkyl intermediate.1,4,2-dioxazol-5-one readily replaces a ligand of Rh (Ⅲ) homoenolate,followed by release of CO2 to give a Rh nitrenoid intermediate.Migratory insertion of the Rh-alkyl bond into the nitrenoid followed by protonolysis furnishes the final product with the regeneration of the catalyst.A similar mechanism is followed for the coupling of cyclopropanols with diazo compounds.Efforts to expand the utility of other strained rings are underway in our laboratories.