Laboratoire d'Innovation Moléculaire et Applications (UMR 7042), Université de Strasbourg, Université de Haute-Alsace, CNRS, 67000, Strasbourg, France.
Department of Chemical Science and Engineering, School of Materials and Chemical Technology, Tokyo Institute of Technology, O-okayama, Meguro-ku, 152-8552, Tokyo, Japan.
Angew Chem Int Ed Engl. 2023 Mar 1;62(10):e202215899. doi: 10.1002/anie.202215899. Epub 2023 Jan 31.
The deprotonative functionalization of α,α-difluoromethyl ketones is described herein. Using a catalytic organosuperbase and a silane additive, the corresponding difluoroenolate could be generated and trapped with aldehydes to deliver various α,α-difluoro-β-hydroxy ketones in high yields. This new strategy tolerates numerous functional groups and represents the access to the difluoroenolate by direct deprotonation of the difluoromethyl unit. The diastereoselective version of the reaction was also investigated with d.r. up to 93 : 7. Several transformations were performed to demonstrate the synthetic potential of these α,α-difluoro-β-hydroxy ketones. In addition, this method has been extended to the use of other electrophiles such as imines and chalcogen derivatives, and a difluoromethyl sulfoxide as nucleophile, thus leading to a diversity of difluoromethylene compounds.
本文描述了 α,α-二氟甲基酮的去质子官能化反应。使用催化有机超强碱和硅烷添加剂，可以生成相应的二氟烯醇盐，并与醛捕获，以高收率得到各种 α,α-二氟-β-羟基酮。这种新策略可以容忍许多官能团，并且代表了通过直接去质子化二氟甲基单元来获得二氟烯醇盐的方法。还研究了反应的非对映选择性版本，对映体过量值高达 93 : 7。进行了几种转化以证明这些 α,α-二氟-β-羟基酮的合成潜力。此外，该方法已扩展到其他亲电试剂的使用，如亚胺和硫属元素衍生物，以及二氟甲基砜作为亲核试剂，从而得到了多种二氟亚甲基化合物。
