Piperidine-1-carbonitrile

Synthesis of aryl amidines¹⁾: To a vial Pd(O₂CCF₃)₂ (13.3 mg, 0.04 mmol), 6-methyl-2,2’-bipyridyl (10.2 mg, 0.06 mmol) and methanol (3.0 mL) are added and the mixture is stirred for 5 min before addition of piperidine-1-carbonitrile (1 mmol), trifluoroborate (1.1 mmol) and trifluoroacetic acid (228 mg, 2 mmol) is added to the reaction mixture and the vial is instantly capped under air and then heated using microwave irradiation at 120 °C for 20 min. The reaction mixture is then diluted with 20 mL NaHCO₃ aq. and washed with 20 mL DCM. The organic phase is further extracted with 2 x 20 mL NaHCO₃ aq. The combined aqueous phases are basified to pH ~ 14 by the addition of NaOH and extracted with 3 x 60 mL DCM. The combined organic phases are dried and concentrated to provide the pure isolated product.

Synthesis of 2-aminopyridines by the [2+2+2] cycloaddition²⁾: FeI₂ (7.8 mg, 0.025 mmol) and dppp (21.2 mg, 0.05 mmol) are weighed in the glovebox and placed in a dried Schlenk tube. Subsequenly, distilled THF (2 mL) is added. The resulting mixture is stirred at room temperature for 30 min to afford an orange-yellow clear solution, at which time Zn dust (3.3 mg, 0.05 mmol) is added. After an additional 30 min of stirring, diyne 1 (0.5 mmol) is added followed by piperidine-1-carbonitrile (2.5 mmol), and the mixture is stirred for 24 h. The solvent is evaporated, and the crude product is directly purified by silica gel flash column chromatography to give 2 in 86% yield.