Remote, Diastereoselective Cobalt-Catalyzed Alkene Isomerization-Hydroboration: Access to Stereodefined 1,3-Difunctionalized Indanes
Remote, Diastereoselective Cobalt-Catalyzed Alkene Isomerization-Hydroboration: Access to Stereodefined 1,3-Difunctionalized Indanes
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DOI：
10.1021/acscatal.9b03444
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发表时间：
2019-10-01
期刊：
影响因子：
12.9
通讯作者：
Chirik, Paul J.
中科院分区：
文献类型：
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作者：
Leonard, Nadia G.;Palmer, W. Neil;Chirik, Paul J.
用2,2':6',2"-三吡啶钴烷基预催化剂对2-和3-取代茚进行远端非对映选择性硼氢化反应，与烯烃起始位置无关，该反应保持了高的区域选择性和立体选择性。得到了几种1,2-和1,3-二取代硼酸茚酮酯，对反式非对映体具有独家（>20:1 dr）选择性，包括合成的多用途，立体定义的二硼衍生物。假定的钴氢化中间体的烯烃异构化先于碳硼键的形成，导致观察到硼在未取代的C(sp(3))-H苯基上的选择性结合。甲基取代茚的三个同分异构体的硼化反应证明了该转化的区域选择性和非对映选择性与烯烃的起始位置无关。氘标记实验支持快速可逆的插入和β -氢化物消除，以异构化3-亚甲基和1-外置亚甲基-吲哚，解释了在产物中观察到的同位素分布。机理研究，包括化学计量实验、密度泛函理论计算和动力学分析，支持2,3-烯烃插入氢化钴中间体决定催化反应的区域选择性和非对映选择性的机理。通过对几个1,3-二取代的吲哚烷（在药理学和生物活性分子中都是重要的碳环结构基序）的产物的详细分析，证明了吲哚烷硼酸酯的合成应用。
The remote, diastereoselective hydroboration of 2- and 3-substituted indenes with a 2,2':6',2"-terpyridine cobalt alkyl precatalyst is described that maintains high regio- and stereoselectivity independent of the starting position of the alkene. Several 1,2- and 1,3-disubstituted indanyl boronate esters were obtained with exclusive (>20:1 dr) selectivity for the trans diastereomer including synthetically versatile, stereodefined diboron derivatives. Alkene isomerization by a putative cobalt hydride intermediate precedes carbon-boron bond formation, leading to the observed regioselectivity for boron incorporation at the unsubstituted C(sp(3))-H benzylic site. The regio- and diastereoselectivity of the transformation were maintained independent of the starting position of the alkene, as demonstrated by hydroboration of three isomers of methyl-substituted indene. Deuterium-labeling experiments support rapid and reversible insertion and beta-hydride elimination to isomerize 3-methylindene and 1-exo-methylene-indane, accounting for the isotopic distribution observed in the products. Mechanistic studies, including stoichiometric experiments, density functional theory calculations, and kinetic analysis, support a mechanism in which 2,3-alkene insertion into a cobalt hydride intermediate determines both the regio- and diastereoselectivity of the catalytic reaction. Synthetic applications of the indanyl boronate esters were demonstrated through the elaboration of the products to several examples of 1,3-disubstituted indanes, important carbocyclic structural motifs in both pharmacological and bioactive molecules.