Scheidt Felix, Schäfer Michael, Sarie Jérôme C, Daniliuc Constantin G, Molloy John J, Gilmour Ryan
Organisch Chemisches Institut, Westfälische Wilhelms-Universität Münster, Corrensstraße 40, 48149, Münster, Germany.
Angew Chem Int Ed Engl. 2018 Dec 10;57(50):16431-16435. doi: 10.1002/anie.201810328. Epub 2018 Nov 8.
The enantioselective, catalytic vicinal difluorination of alkenes is reported by I /I catalysis using a novel, C -symmetric resorcinol derivative. Catalyst turnover via in situ generation of an ArI F species is enabled by Selectfluor oxidation and addition of an inexpensive HF-amine complex. The HF:amine ratio employed in this process provides a handle for regioselective orthogonality as a function of Brønsted acidity. Selectivity reversal from the 1,1-difluorination pathway (geminal) to the desired 1,2-difluorination (vicinal) is disclosed (>20:1 in both directions). Validation with electron deficient styrenes facilitates generation of chiral bioisosteres of the venerable CF unit that is pervasive in drug discovery (20 examples, up to 94:06 e.r.). An achiral variant of the reaction is also presented using p-TolI (up to >95 % yield).
报道了使用一种新型的C对称间苯二酚衍生物通过I/I催化实现烯烃的对映选择性催化邻位二氟代反应。通过Selectfluor氧化和添加廉价的HF-胺络合物，能够通过原位生成ArI F物种实现催化剂周转。该过程中使用的HF:胺比例提供了一种根据布朗斯特酸度实现区域选择性正交性的方法。公开了从1,1-二氟代途径（偕二氟）到所需的1,2-二氟代（邻位）的选择性反转（两个方向均>20:1）。用缺电子苯乙烯进行验证有助于生成在药物发现中普遍存在的经典CF单元的手性生物电子等排体（20个实例，高达94:06的对映体比例）。还展示了使用对甲苯基碘（产率高达>95%）的该反应的非手性变体。
