Synthesis of Cyanide‐Functionalized Imidazo[1,5‐a]quinolines via Copper‐Mediated Aerobic Three‐Component Cyclizations

Abstract

A three-component cyclization of 2methylquinolines, trimethylsilyl cyanide, and alkylamines or a-amino acids mediated by CuSO 4 was developed. By employing oxygen as the clean oxidant, cyanated imidazo[1,5-a]quinolines were constructed with high efficiency for the first time. The loading of CuSO 4 could be lowered to 20 mol% with a slightly diminished yield. The synthetic utility of this method is further highlighted by the gram-scale synthesis and tolerance of sensitive functional group.

Copper Mediated Chemo‐ and Stereoselective Cyanation Reactions

“…[29] Copper sulfate/ N-methyl morpholine (NMP) was used as a cheap and readily available catalytic material for the aerobic three-component reaction involving reaction of 2-methylquinolines, trimethylsilyl cyanide, and alkylamines or α-amino acids. Cyanated imidazo[1,5-a]quinolines were synthesized with high yields and excellent functional group tolerance (See Figure 19) [30] Cu(OAc) 2 /CuF 2 was used as the catalytic system for the aerobic CÀ H cyanation 2-arylpyridine with moderate to good yield at 130 °C using TMSCN asnitrile source (See Figure 20). [31] Cu(CH 3 CN) 6 BF 4 /TMSCN and 10-phenyl-10H-phenothiazine (Ph-PTZ) based duel copper, and photoredox catalytic system was used the cyanation of the asymmetric propargylic radical.…”

“…Copper sulfate/ N‐methyl morpholine (NMP) was used as a cheap and readily available catalytic material for the aerobic three‐component reaction involving reaction of 2‐methylquinolines, trimethylsilyl cyanide, and alkylamines or α‐amino acids. Cyanated imidazo[1,5‐a]quinolines were synthesized with high yields and excellent functional group tolerance (See Figure 19) [30] …”

Alkene carboamination/oxidative denitrogenation of 3-allyl-3-hydrazinylindolin-2-ones: one-pot entry to spirocyclopropyloxindoles

“…Most of the reported methodologies rely on the use of sulfur ylides, such as the recent protocol developed by Hajra and co-workers, in which isatin undergoes a domino Corey–Chaykovsky reaction to give unsubstituted spirocyclopropyloxindoles, 13 and the protocols described by Feng and co-workers and by Yuan and co-workers, in which activated 3-alkenyl oxindoles undergo a formal [2 + 1] annulation with sulfur and sulfoxonium ylides, both by metal catalysis and under metal-free conditions. 14,15 Besides sulfur ylides, phenyliodonium ylides can be employed as C-1 synthons in [2 + 1] annulations, as recently demonstrated by Feng and co-workers, 16 as well as Morita–Baylis–Hillman carbonates, as reported by Warghude and co-workers. 17 A domino reaction of M–B–H carbonates of isatins and sulfur ylides was exploited by Zheng and co-workers to synthesize complex oxospiro[bicyclo[3.1.0]hexane-6,3′-indoline] scaffolds.…”

Electrochemical synthesis of CN-substituted imidazo[1,5-a]pyridines via a cascade process using NH4SCN as both an electrolyte and a non-trivial cyanating agent

“…53 Related cyanide-functionalized imidazo [1,5-a] quinolones were prepared via Cu-mediated oxidative cyclization of 2-methylquinolines, trimethylsilyl cyanide, and alkylamines applying oxygen as the oxidant. 54 However, the use of transition metal compounds and the need for stoichiometric amounts of non-recyclable oxidants remain constraints to these methods. Considering the great attention given to the electrochemical synthesis of heterocyclic structures, [55][56][57][58][59][60][61][62][63][64] which have always been basic scaffolds in organic chemistry, efficient electrochemical approaches for in situ construction and modification of heterocycles are highly desirable.…”