Tunable Silver-Catalyzed Nitrene Transfer: From Chemoselectivity to Enantioselective C–H Amination

Abstract

Transition-metal-catalyzed C–H aminations via nitrene transfer processes are powerful synthetic methods to construct valuable amines. Over the past decade, significant efforts in the field have resulted in an expansion in the utility of nitrene transfer chemistry, enabling the use of these carbon–nitrogen bond-forming reactions in complex organic molecule syntheses. This Perspective highlights efforts in silver-catalyzed nitrene transfer reactions that achieve chemo-, site-, and enantioselective transformations using simple N-dentate ligands that can serve as stepping stones for future investigations of other tunable C–H functionalizations.

Regio- and Enantioselective Catalytic δ-C–H Amidation of Dioxazolones Enabled by Open-Shell Copper-Nitrenoid Transfer

“…In general, singlet acylnitrenoids favor a concerted C­(sp 3 )–H insertion pathway, where this closed-shell reactivity of the key intermediate has a high kinetic preference toward the six-membered chair-like transition state, thus leading to γ-lactam formation (Scheme b, left). , However, in the case of access to δ-lactams via the metal-acylnitrenoid pathway, there is no guiding mechanistic principle leading to the site-selective δ-C–H functionalization. Based on the assumption that the open-shell character of metal-nitrenoids may invoke a stepwise amidation process consisting of hydrogen atom abstraction (HAA) followed by radical rebound, ,, we hypothesized to develop a new mechanistic motif to access δ-lactams (Scheme b, right). Furthermore, we desired to further enable an asymmetric version of this intramolecular δ-lactam synthesis by leveraging the critical step of asymmetric C–N bond-forming radical rebound while addressing a potentially stereoablative interconversion of carbon-centered radical intermediates (vide infra).…”

Silver-Exchanged Zeolite Y Catalyzes a Selective Insertion of Carbenes into C–H and O–H Bonds

“…We will show here that the resulting zeolites catalyze representative carbene-mediated reactions in organic synthesis, such as the Buchner reaction and acetate insertion in methylene and hydroxyl bonds. , The Ag-zeolite enables the reaction of C–H and C–O bonds without requiring prefunctionalized substrates or leaving groups (such as halides, etc. ), and not only the catalytic activity but also the selectivity of the reaction is dictated by the counter cation of the zeolite.…”

Silver Catalyzed Site-Selective C(sp3)−H Bond Amination of Secondary over Primary C(sp3)−H Bonds

“…To date, the selective amination of aliphatic C(sp 3 )–H bonds has mainly been limited to the site-selectivity of unactivated substrates (e.g., tertiary alkyl C–H bonds and benzylic γ-C–H bonds) and activated substrates (e.g., allylic and benzylic C–H bonds)23, [ 25 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 ]. Due to the similar high bond-dissociation energy of aliphatic C-H bonds, only a handful of studies have been conducted to identify the selective amination of aliphatic C(sp 3 )–H bonds.…”