Copper-Catalyzed Aerobic Oxidative Amidation of Benzyl Alcohols

Abstract

A Cu-catalyzed synthesis of amides from alcohols and secondary amines using the oxygen in air as the terminal oxidant has been developed. The methodology is operationally simple requiring no high pressure equipment or handling of pure oxygen. The commercially available, nonprecious metal catalyst, Cu(phen)Cl, in conjunction with di-tert-butyl hydrazine dicarboxylate and an inorganic base provides a variety of benzamides in moderate to excellent yields. The pK of amine conjugate acid and electronics of alcohol were shown to impact the selection of base for optimal reactivity. A mechanism consistent with the observed reactivity trends, KIE, and Hammett study is proposed.

Tandem Photoredox Catalysis: Enabling Carbonylative Amidation of Aryl and Alkylhalides

“…Multiphoton excitation catalysis has emerged as new strategy to overcome the thermodynamic limitations of visible light photoredox catalysis to generate high energy photoreductants. 14 Recently our group disclosed a method for the in-situ generation of a second highly reducing iridium photocatalyst from [Ir(ppy)2(dtbpy)] + via a 2-photon tandem photoredox cycle 15 ( Figure 2a) and Nicewicz uncovered similar behaviour with organophotoredox catalysts. 16 This strategy has been successfully applied to the reductive protodehalogenation of unactivated organohalides and showcases the ability common photoredox catalysts to yield a potent excited-state donors via multiphoton excitation.…”

“…We elected to use morpholine as the amine coupling partner with triethylamine (TEA) as sacrificial reductant and the catalyst [Ir(ppy)2(dtb-bpy)]PF6 on the basis of previously established conditions for the reduction of aryl halides by the tandem photoredox system. 15 A mixture of these reagents in acetonitrile was pumped through the gas−liquid reactor, enriched with CO at 25 bar, then irradiated inside the photoreactor with 54W blue LEDs. The photoreactor residence time was initially set to 5 min.…”

“…The flow chemistry platform consists of a Knauer ® Smartline pump (although any syringe or HPLC pump capable of high pressure handling can be deployed), an Upchurch ® 6 port injection valve, a tube-in-tube gas/liquid reactor assembled and bespoke flow photoreactor fabricated in our laboratory ( Supplementary Fig S3 and Fig S4). The method was reoptimized for the carbonylative amidation of alkyl iodides and the synthesis of cyclohexylamide (43) using iodocyclohexane (Ep red = -2.15 V vs SCE) 15 as a representative alkyl iodide substrate. In line with the aryl halides, we selected morpholine as the amine coupling partner, DIPEA as sacrificial reductant and the [Ir(ppy)2(dtb-bpy)]PF6 photocatalyst.…”

Mechanism of atom economical conversion of alcohols and amines to amides using Fe(ii) pincer catalyst. An outer-sphere metal–ligand pathway or an inner-sphere elimination pathway?

“…5 Alternatively they can also be synthesized by using transition metal catalyzed dehydrogenation of alcohols with amines which is doubtlessly an efficient and atom economical method of synthesis. [6][7][8][9][10][11][12][13][14][15][16][17][18][19] The rst transition metal catalyst (Ru-PNN pincer catalyst) for direct amide synthesis was proposed by Milstein which operates through metal-ligand cooperation by aromatization and dearomatization of the pyridine ring. 8 Since then a lot of attention has been paid to direct amide formation from alcohols and amines.…”

“…8 Since then a lot of attention has been paid to direct amide formation from alcohols and amines. 6,7,[9][10][11][12][13][14][15][16][17][18][19] The atom economic strategy of amide synthesis faces lot of challenges such as limited substrate scope, long reaction timings and harsh reaction temperatures needed for the reaction to carry out. To circumvent these problems some efforts are being made to develop the transition-metal catalysts for the dehydrogenative coupling of alcohols with amines to form amides.…”