Metal‐Free Catalyst‐Controlled Chemoselective Synthesis of Aryl α‐Ketoesters and Primary α‐Ketoamides from Aryl Acetimidates

Abstract

A simple and chemoselective method has been developed for the divergent synthesis of aryl α‐ketoesters and primary α‐ketoamides from pre‐functionalized arylacetimidates under metal‐free conditions. The chemoselective outcome is controlled by the subtle catalyst. This methodology features operational simplicity with broad substrate scope, metal‐free catalyst, and usage of easy to handle reagents. Based on a series of control experiments, a plausible reaction mechanism is also proposed.

Two‐Step One‐Pot Synthesis of Unsymmetrical (Hetero)Aryl 1,2‐Diketones by Addition‐Oxygenation of Potassium Aryltrifluoroborates to (Hetero)Arylacetonitriles

“…Taking the above results and previous reports into consideration, we then proposed a possible reaction mechanism (Scheme ). First, arylpalladium species A is generated by transmetalation with the potassium aryltrifluoroborate.…”

“…Despite tremendous progress, arylacetonitriles have never been used as the starting material for the direct synthesis of diaryl 1,2‐diketones. With this understanding and our interest in copper‐catalyzed oxidative functionalizations of benzylic C–H bonds for the synthesis of functionalized organic molecules, we herein report a general and practical one‐pot procedure for the synthesis of unsymmetrical 1,2‐diketones 3 . The reaction between arylacetonitriles 1 and potassium aryltrifluoroborates 2 proceeds through a Pd‐catalyzed nucleophilic addition reaction followed by a Cu‐catalyzed/O 2 benzylic C–H oxygenation without the need to isolate the deoxybenzoin intermediate (Scheme d).…”

Metal-Free Oxidative Esterification of Ketones and Potassium Xanthates: Selective Synthesis of α-Ketoesters and Esters

“…26 Yellow liquid (73 mg, 74% yield); R f = 0.48 (petroleum ether/ethyl acetate = 20:1); 1 H NMR (500 MHz, CDCl 3 ) δ 8.10−8.05 (m, 2H), 7.19 (dd, J = 11.9, 5.2 Hz, 2H), 4.44 (q, J = 7.1 Hz, 2H), 1.42 (t, J = 7.2 Hz, 3H); Ethyl 2-Oxo-2-(3-(trifluoromethyl)phenyl)acetate (3l). 29 Yellow liquid (77 mg, 63% yield); R f = 0.51 (petroleum ether/ethyl acetate = 20:1); 1 H NMR (400 MHz, CDCl 3 ) δ 8.32 (s, 1H), 8.24 (d, J = 7.8 Hz, 1H), 7.91 (d, J = 7.8 Hz, 1H), 7.67 (t, J = 7.8 Hz, 1H), 4.48 (q, J = 7.0 Hz, 2H), 1.44 (t, J = 7.2 Hz, 3H); 13 Ethyl 2-(3,4-Dichlorophenyl)-2-oxoacetate (3n). 30 Yellow liquid (103 mg, 86% yield), R f = 0.61 (petroleum ether/ethyl acetate = 20:1); 1 H NMR (500 MHz, CDCl 3 ) δ 8.14 (d, J = 2.0 Hz, 1H), 7.88 (dd, J = 8.4, 2.0 Hz, 1H), 7.59 (d, J = 8.4 Hz, 1H), 4.45 (q, J = 7.2 Hz, 2H), 1.43 (t, J = 7.2 Hz, 3H); 13 Ethyl 2-(Benzo [d][1,3]dioxol-5-yl)-2-oxoacetate (3o).…”

Palladium-Catalyzed Regioselective C–H Alkenylation of Arylacetamides via Distal Weakly Coordinating Primary Amides as Directing Groups

“…The substantial advantage of this distal and weakly coordinating directing group is due to the presence of a free amide moiety, which can be easily manipulated into different functional groups. In our continued efforts to synthesize multifunctionalized arenes, herein we disclose an efficient Pd­(II)-catalyzed mono-ortho-olefination of phenylacetamide derivatives via distal C–H bond activation (Scheme c). The generality of this protocol is demonstrated by preparing a commendable set of E -alkenylated compounds.…”