Room-temperature enantioselective C–H iodination via kinetic resolution

Abstract

The development of asymmetric C–H activation reactions through metal insertions remains in its infancy. The commonly used approach is the desymmetrization of prochiral C–H bonds on the same or different carbons of one achiral molecule using a chiral catalyst. Herein, we report a Pd-catalyzed enantioselective C–H activation reaction via kinetic resolution in which one of the enantiomers of the racemic substrates undergoes faster C–H insertion with the chiral catalysts thereby producing enantioenriched C–H functionalization products that are not accessible via desymmtrization of prochiral C–H bonds. The exceedingly high relative rate (kfast/kslow up to 244) and the subsequent iodination of the remaining enantiomerically enriched starting material using a chiral ligand with the opposite configuration allows for the conversion of both enantiomers of amines into enantiomerically pure iodinated amines.

Modern Transition-Metal-Catalyzed Carbon–Halogen Bond Formation

“…142 This method represents a highly selective and nonenzymatic approach to chiral iodinated amide derivatives. When the D-Bz-MPAA ligand is employed, an efficient kinetic resolution occurs to give a mixture of recovered starting material (S)-65 and the desired iodinated products (R)-66 which are both present in highly enantioenriched form.…”

Advances in Enantioselective C–H Activation/Mizoroki-Heck Reaction and Suzuki Reaction

“…A chiral carbon-Pd intermediate could be formed, followed by olefination to give the corresponding chiral product. Based on the recent development of enantioselective C-H iodination using Pd II /MPAA catalysts for kinetic resolution through C-H hydroxylation and iodination [82,83], Yu and coworkers developed a kinetic resolution method to achieve enantioselective C-H olefinations of α-hydroxy and α-amino phenylacetic acids utilizing Pd II -catalyzed system in 2016 (Scheme 27) [84]. Yu also proposed a possible transition state for this enantioselective C-H olefination ( Figure 5).…”

“…A chiral carbon-Pd intermediate could be formed, followed by olefination to give the corresponding chiral product. Based on the recent development of enantioselective C-H iodination using Pd II /MPAA catalysts for kinetic resolution through C-H hydroxylation and iodination [82,83], Yu and coworkers developed a kinetic resolution method to achieve enantioselective C-H olefinations of α-hydroxy and α-amino phenylacetic acids utilizing Pd II -catalyzed system in 2016 (Scheme 27) [84]. Based on the recent development of enantioselective C-H iodination using Pd II /MPAA catalysts for kinetic resolution through C-H hydroxylation and iodination [82,83], Yu and coworkers developed a kinetic resolution method to achieve enantioselective C-H olefinations of α-hydroxy and α-amino phenylacetic acids utilizing Pd II -catalyzed system in 2016 (Scheme 27) [84].…”

Recent Advances on Transition-Metal-Catalyzed Halogenation of Unactivated C-H Bonds

“…另外, 以恶唑啉为导向基团, 也可以实现 六元环或者七元环过渡态的远程碘代反应 [26] (图 7, 式 2). 随后, Yu 课题组 [27,28] 进一步将反应体系进行拓展, 实现了羧基(图 8, 式 1)、三氟甲磺酰胺(NHTf) [29] (图 8, 式 2)、单齿配位酰胺(CONHAr F ) [30] (图 8, 式 3)的导向的 Figure 7 Pd(II)-catalyzed C-H iodination directed by oxazoline [33] (图 9, 式 2).…”