Kinetic Resolution of α-Tertiary Propargylic Amines through Asymmetric Remote Aminations of Anilines

Several valuable biologically active molecules can be obtained through C-H activation processes. However, the use of expensive and not readily accessible catalysts complicates the process of pharmacological application of these compounds. A plausible way to overcome this issue is developing and using cheaper, more accessible, and equally effective catalysts. First-row transition (3d) metals have shown to be important catalysts in this matter. This review summarizes the use of 3d metal catalysts in C-H activation processes to obtain potentially (or proved) biologically active compounds.

https://www.beilstein-journals.org/bjoc/content/pdf/1860-5397-17-126.pdf

On the application of 3d metals for C-H activation toward bioactive compounds: The key step for the synthesis of silver bullets.

The direct difunctionalization of alkenes is an effective way to construct multiple C-C bonds in one-pot using a single functional group. The regioselective dicarbofunctionalization of alkenes is therefore an important area of research to rapidly obtain complex organic molecules. Herein, we report a palladium-catalyzed γ,γ'-diarylation of free alkenyl amines through interrupted chain walking for the synthesis of Z-selective alkenyl amines. Notably, while 1,3-dicarbofunctionalization of allyl groups is well precedented, the present disclosure allows 1,3-dicarbofunctionalization of highly substituted allylamines to give highly Z-selective trisubsubstituted olefin products. This cascade reaction operates via an unprotected amine-directed Mizoroki-Heck (MH) pathway featuring a β-hydride elimination to selectively chain walk to furnish a new terminal olefin which then generates the cis-selective alkenyl amines around the sterically crowded allyl moiety. This operationally simple protocol is applicable to a variety of cyclic, branched, and linear secondary and tertiary alkenylamines, and has a broad substrate scope with regard to the arene coupling partner as well. Mechanistic studies have been performed to help elucidate the mechanism, including the presence of a likely unproductive side C-H activation pathway.

Palladium-Catalyzed γ,γ'-Diarylation of Free Alkenyl Amines.

Recent advances in palladium-catalyzed (hetero)annulation of CC bonds with ambiphilic organo(pseudo)halides

Asymmetric Synthesis of Hydroquinazolines Bearing C4-Tetrasubstituted Stereocenters via Kinetic Resolution of α-Tertiary Amines.

Enantioenriched, six-membered azacycles are essential structural motifs in many products of pharmaceutical or agrochemical interest. Here we report a simple and practical method for enantioselective assembly of tetrahydropyridines, which is paired to a kinetic resolution of α-branched allyltriflamides. The reaction consists of a formal (4+2) cycloaddition between the allylamine derivatives and allenes and is initiated by a palladium(II)-catalyzed C-H activation process. Both the chiral allylamide precursors and the tetrahydropyridine adducts were successfully obtained in high yields, with excellent enantioselectivity (up to 99% ee) and selectivity values of up to 127.

José Manuel Pereira González

Papers

Kinetic Resolution of Allyltriflamides through a Pd-Catalyzed C-H Functionalization with Allenes: Asymmetric Assembly of Tetrahydropyridines