Ligand-Controlled Synthesis of Azoles via Ir-Catalyzed Reactions of Sulfoxonium Ylides with 2-Amino Heterocycles

Abstract

An iridium-catalyzed method was developed for the synthesis of imidazo-fused pyrrolopyrazines. The presence or absence of a nitrogenated ligand controlled the outcome of the reaction, leading to simple β-keto amine products in the absence of added ligand and the cyclized 7- and 8-substituted-imidazo[1,2-a]pyrrolo[2,3-e]pyrazine products in the presence of ligand. This catalyst control was conserved across a variety of ylide and amine coupling partners. The substrate was shown to act as a ligand for the iridium catalyst in the absence of other ligands via NMR spectroscopy. Kinetic studies indicated that formation of the Ir-carbene was reversible and the slow step of the reaction. These mechanistic investigations suggest that the β-keto amine products form via an intramolecular carbene N-H insertion, and the imidazopyrrolopyrazines form via an intermolecular carbene N-H insertion.

Sulfoxonium Ylide Derived Metal Carbenoids in Organic Synthesis

“…In 2016, the group of Schomaker and Shekhar studied the iridium-catalyzed N-H insertion of sulfoxonium ylides for the synthesis of imidazo-fused pyrrolopyrazines 46 (Scheme 19). 43 The authors found that the outcome of the reaction was greatly controlled by the addition of a bidentate N,N-ligand. When [Ir(cod)Cl] 2 was employed as catalyst without ligand, N-H insertion of 44 afforded the -keto amine 45.…”

Enantioselective S−H Insertion Reactions of α‐Carbonyl Sulfoxonium Ylides

“…To date, efforts have typically focused on transition metal catalyzed insertion chemistry of sulfoxonium ylides (Scheme A). Select transition metal catalyst systems (e.g., [Ir(cod)Cl] 2 , [Pt(cod)Cl] 2 , [AuCl(SMe 2 )]) enable non‐enantioselective N−H, S−H, and O−H insertion reactions of a range of substrates in high yield . To the best of our knowledge, excluding the contributions employing diazocarbonyls, no examples of enantioselective insertion reactions of sulfoxonium ylides have been reported.…”

Ruthenium(II)-Catalyzed Homocoupling of α-Carbonyl Sulfoxonium Ylides Under Mild Conditions: Methodology Development and Mechanistic DFT Study

“…2-(dimethyl(oxo)-λ 6 -sulfanylidene)-1-(naphthalen-2yl)ethan-1-one(1y) (Phelps et al, 2016). 1 H NMR (400 MHz, CDCl 3 ) δ 8.33 (s, 1H), 8.01-7.75 (m, 4H), 7.58-7.42 (m, 2H), 5.13 (s, 1H), 3.56 (s, 6H).…”

“…)benzoate(1m)(Phelps et al, 2016). 1 H NMR (400 MHz, CDCl 3 ) δ 8.06 (d, J = 8.4 Hz, 2H), 7.84 (d, J = 8.4 Hz, 2H), 5.04 (s, 1H), 3.93 (s, 3H), 3.54 (s, 6H).2-(dimethyl(oxo)-λ 6 -sulfanylidene)-1-(4-(trifluoromethyl)phenyl)ethan-1-one(1n)(Jiang H. F. et al, 2019).…”