Direct ortho‐Acylation of Azoxybenzenes with Aldehydes via Palladium‐Catalyzed Regioselective CH Bond Activation

Abstract

A highly efficient and convenient palladium catalyzed the ortho-acylation of azoxybenzenes has been developed. Easily available aldehydes were used as a cheap and ideal aroyl sources. This method provides a practical and direct pathway to synthesize 2-acylated azoxybenzenes in chemo-and regioselective manners via palladium-catalyzed CÀH bond activation. Various substituents on both coupling partners are tolerated well.Current interest in azoarenes and their derivatives is increasing dramatically due to their wide applications in the fields of pharmaceuticals, analytic chemistry, functional materials, organic synthesis, and the dye industry. [1] As a result of their importance, a number of methods have been established to build such a structural skeleton. Transition-metal-catalyzed direct CÀH bond activation and functionalization of azobenzenes has been extensively investigated and proved to be a powerful protocol, such as for ortho-acyloxyation, [2] ortho-arylation, [3] ortho-halogenation, [4] ortho-acylation, [5] ortho-alkoxylation, [6] and ortho-amination. [7] However, a mixture of mono-, diand multisubstituted products [3, 5a] are always obtained because of poor regioselective CÀH bond activation of azobenzenes. Recently, azoxy groups with two kinds of potential CÀH bonds as directing groups have been studied to control the regioselective CÀH bond activation of azobenzenes in view of N being a stronger coordination atom than O with transition-metal centers. [8] Introduction of azoxy group into the substrates can not only bring a high level of regiocontrol, but also enhance the reactivity of the target CÀH bond. Recently, Wang and coworkers developed the palladium-catalyzed regioselective ortho-acylation [9] of azoxybenzenes with a-oxocarboxylic acids and Ru III -catalyzed ortho-alkenylation [10] of azoxybenzenes.Additionally, ortho-acylated azoxybenzenes are important building blocks for preparing medicines, dyes, fragrances, and natural products. [9, 11] Therefore, a facile protocol to form orthoacylated azoxybenzenes via the oxidative coupling of two CÀH bonds from two coupling partners is highly worthy in terms of atom economy. Because of our ongoing interest in CÀH activa-Supporting information for this article is available on the WWW under http://dx.Scheme 3. ortho-Acylation of azoxybenzene with benzaldehydes. Reaction conditions: azoxybenzene (0.2 mmol), benzaldehyde derivatives (4 equiv.), Pd(OAc) 2 (5 mol %), TBHP (4 equiv.), DCE (1.5 mL), at 80 8C under an air atmosphere for 12 h. Figure 1. X-ray single-crystal structure for acylated azoxybenzene 3 ab. The structure of 3 ab was determined by X-ray diffraction. Recrystallized from CH 2 Cl 2 /pentane. CCDC-1023470 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via http://www.ccdc.cam.ac.uk/ data%5Frequest/cif. Scheme 4. Control experiments.Scheme 5. Proposed reaction mechanism.

Recent Advances in Radical C–H Activation/Radical Cross-Coupling

“…A similar procedure was later developed by Cui, Wu, and co-workers using Pd­(OAc) 2 as the catalyst at 80 °C. As compared to Sun’s procedure, aliphatic aldehydes gave lower yields and heteroaryl aldehydes could not be applied, which showed the importance of reaction temperature . Wang and co-workers also reported the acylation of azobenzenes to the desired acylated azobenzenes with aldehydes in good yields (Scheme ).…”

Oxidative Coupling between Two Hydrocarbons: An Update of Recent C–H Functionalizations

“…Triazoles 192 , isoxazoles 193 , pyridine 194 , and azoxy 195 have also been used as the N -containing directing groups for the oxidative cross-coupling between arenes and aldehydes (Scheme ). Pd­(OAc) 2 /TBHP was still the general catalyst/oxidant combination for those transformations with DCE as the solvent.…”

Acylation of (Hetero)Arenes through CH Activation with Aroyl Surrogates

“…Various aldehydes were applied as the coupling partner in the presence of palladium catalysts, and good to excellent yields of the desired products were formed with good functional group tolerance (Scheme ). In the same period, a similar procedure was developed by Cui, Wu, and co‐workers with Pd(OAc) 2 as the catalyst at 80 °C 12b. Compared with Sun’s procedure, aliphatic aldehydes gave lower yields and heteroaryl aldehydes could not be applied, which shows the importance of reaction temperature.…”