A range of environmentally friendly solvents was evaluated in the Suzuki−Miyaura coupling of amides in an attempt to provide the first solvent selection guide for the powerful C−C coupling by amide bond cleavage. Of the 14 solvents and 10 Pd−NHC catalysts (NHC = N-heterocyclic carbene) considered, i-PrOAc was identified as the recommended, environmentally friendly solvent for the coupling. The obtained data permit an overall ranking of the recommended solvents in the Suzuki−Miyaura coupling of amides, with methyl t-butyl ether (MTBE), cyclopentyl methyl ether (CPME), diethyl carbonate (DEC), p-cymene, dimethylcarbonate (DMC), and anisole as alternative recommended solvents in terms of health, safety, and environmental ranking for the coupling. The data should facilitate the replacement of hazardous solvents with green organic solvents in the biorelevant manifold of amide bond coupling for the further implementation of amide bond activation methods.

The selection of solvents is essential as a suitable reaction milieu in chemical processes of industrial and academic impact. We present an evaluation of a range of green solvents for acyl Buchwald–Hartwig cross-coupling of amides to provide the first green-solvent selection guide for this powerful C–N to C–N′ cross-coupling interconversion engaging typically inert amide bonds, resulting in a net transamidation process of historically challenging amide bonds. Of the solvents considered, methyl tert-butyl ether (MTBE) and 2-methyltetrahydrofuran (2-MeTHF) were identified as the preferred alternative solvents for the acyl-Buchwald–Hartwig cross-coupling using well-defined and robust Pd­(II)–NHC (NHC = N-heterocyclic carbene) precatalysts. MTBE and, in particular, 2-MeTHF are superior solvents in this cross-coupling manifold and recommended in terms of safety, health, biodegradability, and environmental score. The results indicate the replacement of hazardous solvents with green organic solvents in the biorelevant C–N to C–N′ cross-coupling manifold of amides to further the burgeoning chemical repertoire of amide-bond activation methods.

As a continuous effort toward developing novel and highly efficient agrochemicals for integrated management of crop pathogens, two series of oxime ester derivatives from indole and tetrahydroquinoline natural scaffolds were prepared. Guided by the preliminary inhibition rates against ubiquitous and representative fungi, the antifungal profile of the target compounds against Valsa mali was intensively and extensively studied. The tetrahydroquinoline-based derivatives 12a−12r exerted a promising inhibition effect, especially against V. mali. The remarkable compounds 12p (R = 4-OCF 3 ) and 12r (R = 4-OBn) with EC 50 values of 0.81 and 0.47 μg/mL, respectively, have a far more prominent activity than commercial fungicide trifloxystrobin. The biochemistry and physiology responses of V. mali after treatment with target compound 12p was examined, and the fruit body production, hyphae morphology, and organelles were profoundly affected. Moreover, the curative effects of compound 12p on apple detached branches and leaves were 57.69 and 64.84% at 100 μg/mL, respectively, which were even superior to that of trifloxystrobin. Meanwhile, the three-dimensional quantitative structure−activity relationship model [comparative molecular field analysis (CoMFA): q 2 = 0.823, r 2 = 0.924, F = 189.781, and standard error of estimation (SEE) = 0.138 and comparative molecular similarity index analysis (CoMSIA): q 2 = 0.795, r 2 = 0.904, F = 145.644, and SEE = 0.156] indicated that the antifungal activity of target compounds was facilitated by crucial structural factors, which would render inspiration for further design and discovery of novel fungicidal candidates.