Chemo- and enantioselective intramolecular silver-catalyzed aziridinations of carbamimidates

Abstract

Transition metal-catalyzed asymmetric nitrene transfer is a powerful method to generate enantioenriched amines found in natural products and bioactive molecules.

Chemoselective Silver-Catalyzed Nitrene Transfer: Tunable Syntheses of Azepines and Cyclic Carbamimidates

“…However, the carbamimidate furnished an 86% yield and 94% ee of the aziridine. These observations, coupled with other works from our group showing divergent site selectivity in C–H amidation that can be achieved by using either a carbamate or sulfamate in tandem with the optimal ligands, highlight our ability to “match” the steric bulk of the nitrene precursor with that of the ligand to influence the reaction outcome …”

“…9 Interestingly, large differences in the ee of the product aziridine were noted based on the identity of the nitrene precursor. 9,10 When a carbamate was employed, the use of (S,S)-indanBOX (A; Scheme 2A) resulted in only 32% ee of the aziridine. 10 However, the carbamimidate furnished an 86% yield and 94% ee of the aziridine.…”

“…These observations, coupled with other works from our group showing divergent site selectivity in C−H amidation that can be achieved by using either a carbamate or sulfamate in tandem with the optimal ligands, 8i highlight our ability to "match" the steric bulk of the nitrene precursor with that of the ligand to influence the reaction outcome. 9 We were intrigued by the potential to achieve a unique example of a tunable and chemoselective NT using carbamimidates, which are underexplored as nitrene precursors; indeed, prior to our work, only one example of aziridination was reported by the Dauban group. 11 We were curious whether the steric bulk of a Tces-protected carbamimidate, combined with the appropriate ligands, might enable selective tuning for either amination at a benzylic C−H bond or dearomative NT via an aza-Buchner reaction (Scheme 2C) to generate a transient fused aziridine.…”

“…For example, simple changes to the ratio of 1,10-phenanthroline (phen):AgOTf (Scheme A) enabled tuning for aziridination vs C–H amination using carbamates as nitrene precursors . More recently, we reported a highly chemo- and enantioselective intramolecular aziridination catalyzed by a silver catalyst supported by an indan-based bis(oxazoline) (BOX) ligand A (Scheme A) . Interestingly, large differences in the ee of the product aziridine were noted based on the identity of the nitrene precursor. , When a carbamate was employed, the use of ( S,S )-indanBOX ( A ; Scheme A) resulted in only 32% ee of the aziridine .…”