A General Catalyst for Site-Selective C(sp³)–H Bond Amination of Activated Secondary over Tertiary Alkyl C(sp³)–H Bonds

Abstract

The discovery of transition metal complexes capable of promoting general, catalyst-controlled and selective carbon-hydrogen (C-H) bond amination of activated secondary C-H bonds over tertiary alkyl C(sp(3))-H bonds is challenging, as substrate control often dominates when reactive nitrene intermediates are involved. In this letter, we report the design of a new silver complex, [(Py5Me2)AgOTf]2, that displays general and good-to-excellent selectivity for nitrene insertion into propargylic, benzylic, and allylic C-H bonds over tertiary alkyl C(sp(3))-H bonds.

Chemo‐ and Enantioselective Intramolecular Silver‐Catalyzed Aziridinations

“…This is not an issue in Ag catalysts with fewer open coordination sites on the metal. [12,13] Attempts to utilize [Cu(MeCN) 4 ]PF 6 with carbamates gave no reaction (entry 2), while sulfamates were successful as previously reported (entry 4). [10] These results highlight the impact of differences in metal identity and nitrogen transfer reagent on reaction behavior and point to the importance of further studies to better understand such effects.…”

“…This was surprising, as we have previously shown sulfamates to be effective in other Ag-catalyzed nitrene transfers. [12,13] Closer examination by 1 H NMR showed formation of an iminoiodinane intermediate, which eventually furnished the aziridine over a period of days (Figure S2 for details). We propose this arises from either increased Lewis acidity of Ag(I) compared to Cu(I), or more likely, the increased size of the Ag(I) cation (115–126 pm) vs. a Cu(I) ion (96 pm).…”

Catalyst-Controlled and Tunable, Chemoselective Silver-Catalyzed Intermolecular Nitrene Transfer: Experimental and Computational Studies

“…13–15 Changes to the ligand, the AgOTf/ligand ratio, and the nitrene precursor all influence the coordination geometry and reactivity of the putative nitrene. For example, preference for aziridination or C‒H bond insertion in a homoallylic carbamate can be controlled by simply changing the ratio of 1,10-phenanthroline (phen) to AgOTf (Scheme 1A).…”

Chemo‐ and Enantioselective Intramolecular Silver‐Catalyzed Aziridinations

“…This result was surprising,a sw eh ave previously shown sulfamates to be effective in other silver-catalyzed nitrene transfers. [12,13] Closer examination by 1 HNMR spectroscopy showed formation of an iminoiodinane intermediate,w hich eventually furnished the aziridine over aperiod of days (see Figure S2). We propose that this arises from either increased Lewis acidity of silver(I) compared to copper(I), or more likely,the increased size of the silver(I) cation (115-126 pm) versus acopper(I) ion (96 pm).…”

“…Our group has reported tunable,chemo-and site-selective nitrene transfers catalyzed by silver(I) complexes supported by diverse N-chelating ligands. [11][12][13][14][15][16] We wondered if the flexibility exhibited by these catalysts might improve both the scope and the ee value of intramolecular alkene and allene aziridinations.S uch studies would provide corroboration of our hypothesis that lower-coordination silver(I) complexes favor aziridination, while higher coordination at the metal prefers C À Hb ond amination instead. [11] In light of the need to favor low-coordinate silver(I) complexes,p reliminary studies focused on bidentate asymmetric ligands using AgClO 4 as the metal salt (see the Supporting Information for full details).…”