Tunable, Chemoselective Amination via Silver Catalysis

Abstract

Organic N-containing compounds, including amines, are essential components of many biologically and pharmaceutically important molecules. One strategy for introducing nitrogen into substrates with multiple reactive bonds is to insert a monovalent N fragment (nitrene or nitrenoid) into a C–H bond or add it directly to a C=C bond. However, it has been challenging to develop well-defined catalysts capable of promoting predictable and chemoselective aminations solely through reagent control. Herein, we report remarkable chemoselective aminations that employ a single metal (Ag) and a single ligand (phenanthroline) to promote either aziridination or C–H insertion by manipulating the coordination geometry of the active catalysts.

Chemoselective silver-catalyzed nitrene insertion reactions

“…Simultaneously with the mechanistic studies described by Perez, the Schomaker group applied silver(I) catalysis to the intramolecular aziridination of homoallenic and homoallylic carbamates [14][15][16]. Schomaker found that typical dinuclear Rh(II) catalysts for nitrene insertion gave poor chemoselectivity and limited substrate scope in the amination of homoallenic carbamates 7a and 7b (Table 3, entries 1-2 and 6-7).…”

“…The Schomaker group has recently described an interesting solution to this problem by harnessing the unique ability of silver complexes to adopt different coordination geometries in response to minor changes in the reaction conditions (Table 6) [18]. A simple change in the metal:ligand ratio diverts the reaction pathway to favor either aziridination or C-H insertion [14,15]. These complementary Ag(I) catalyst systems employ AgOTf as the silver source and 1,10-phenanthroline (phen) as the ligand.…”

“…5). Employing excess ligand favors Ag(phen) 2 OTf in solution and leads to exclusive preference for C-H insertion over aziridination [15]. NMR titration experiments using 4,4′-di-tert-butylbipyridine ( t Bu 2 bipy) and AgOTf showed a continuous shift in the ligand proton as the metal:ligand was varied, suggesting that a dynamic equilibrium exists in solution between Ag(I), Ag:ligand complex and ligand.…”

Silver-Mediated Direct sp3 C–H Bond Functionalization

“…In 2013, Schomaker and coworkers reported highly chemoselective amidation of C¼C and sp 3 C-H bonds by silver catalyst (Scheme 7) [29]. AgOTf was used as the catalyst with phenanthroline as ligand set in the presence of PhIO as the oxidant and 4 Å molecular sieves as additive in DCM.…”

Substrate Specific Silver(I)-Catalyzed Cycloisomerization of Diene Involving Alkyl Rearrangements: Syntheses of 1,2,5,6-Tetrahydrocuminic Acid, <i>p</i>-Menth-3-en-7-ol, and <i>p</i>-Menth-3-en-7-al

“…In comparison with the catalytic reaction using a triple bond, the silver catalyzed reactions of simple alkene moieties are limited. [35][36][37][38][39][40][41][42] However, for example, the silver cation is often used in ion chromatography to separate a mixture of unsaturated fatty acids containing similar multiple double bond units. [43][44][45][46][47][48][49][50] Thus, we hypothesized that the coordination of the silver ion with two intramolecular alkenes might cause a novel cyclization under high temperature.…”