Department of Chemistry, Princeton University , New Jersey 08544, United States.
J Am Chem Soc. 2017 Feb 22;139(7):2825-2832. doi: 10.1021/jacs.6b13346. Epub 2017 Feb 10.
Cobalt catalysts with electronically enhanced site selectivity have been developed, as evidenced by the high ortho-to-fluorine selectivity observed in the C(sp)-H borylation of fluorinated arenes. Both the air-sensitive cobalt(III) dihydride boryl 4-Me-(PNP)Co(H)BPin (1) and the air-stable cobalt(II) bis(pivalate) 4-Me-(PNP)Co(OCBu) (2) compounds were effective and exhibited broad functional group tolerance across a wide range of fluoroarenes containing electronically diverse functional groups, regardless of the substitution pattern on the arene. The electronically enhanced ortho-to-fluorine selectivity observed with the cobalt catalysts was maintained in the presence of a benzylic dimethylamine and hydrosilanes, overriding the established directing-group effects observed with precious-metal catalysts. The synthetically useful selectivity observed with cobalt was applied to an efficient synthesis of the anti-inflammatory drug flurbiprofen.
开发出电子增强位选择性的钴催化剂，在氟化芳烃的 C(sp)-H 硼化反应中观察到高邻位到氟的选择性即可证明这一点。空气敏感的钴(III)二氢化物硼基 4-Me-(PNP)Co(H)BPin（1）和空气稳定的钴(II)双（新戊酸酯）4-Me-(PNP)Co(OCBu)（2）化合物都是有效的，并且在含有电子不同的各种官能团的广泛范围内的氟代芳烃中表现出广泛的官能团耐受性，无论芳烃上的取代模式如何。在存在苄基二甲胺和硅烷的情况下，钴催化剂观察到的电子增强的邻位到氟的选择性得以保持，这超过了与贵金属催化剂观察到的既定导向基团效应。钴表现出的有用的合成选择性被应用于抗炎药物氟比洛芬的有效合成。
