Ambler Brett R, Peddi Santosh, Altman Ryan A
Department of Medicinal Chemistry, The University of Kansas, Lawrence, Kansas 66045, United States.
Org Lett. 2015 May 15;17(10):2506-9. doi: 10.1021/acs.orglett.5b01027. Epub 2015 Apr 24.
"Cu-CF3" species have been used historically for a broad spectrum of nucleophilic trifluoromethylation reactions. Although recent advancements have employed ligands to stabilize and harness the reactivity of this key organometallic intermediate, the ability of a ligand to differentiate a regiochemical outcome of a Cu-CF3-mediated or -catalyzed reaction has not been previously reported. Herein, we report the first example of a Cu-catalyzed trifluoromethylation reaction in which a ligand controls the regiochemical outcome. More specifically, we demonstrate the ability of bipyridyl-derived ligands to control the regioselectivity of the Cu-catalyzed nucleophilic trifluoromethylation reactions of propargyl electrophiles to generate (trifluoromethyl)allenes. This method provides a variety of di-, tri-, and tetrasubstituted (trifluoromethyl)allenes, which can be further modified to generate complex fluorinated substructures.
“Cu-CF3”物种历来被用于广泛的亲核三氟甲基化反应。尽管最近的进展采用了配体来稳定和利用这种关键有机金属中间体的反应活性，但配体区分Cu-CF3介导或催化反应的区域化学结果的能力此前尚未见报道。在此，我们报道了第一例配体控制区域化学结果的铜催化三氟甲基化反应。更具体地说，我们展示了联吡啶衍生配体控制铜催化的亲电炔丙基亲核三氟甲基化反应区域选择性以生成（三氟甲基）丙二烯的能力。该方法提供了多种二取代、三取代和四取代的（三氟甲基）丙二烯，它们可进一步修饰以生成复杂的氟化亚结构。
