C–H functionalization of amines with aryl halides by nickel-photoredox catalysis

A redox-neutral method for α-amino C(sp3)–H arylation is described using nickel and photoredox catalysis.

Paragon 500 and are reported in terms of frequency of absorption (cm -1 ). Reversed-phase liquid chromatography/mass spectrometry (LC/MS) was performed on an Agilent 1260 Infinity analytical LC and Agilent 6120 Quadrupole LC/MS system using electrospray ionization/atmospheric-pressure chemical ionization (ESI/APCI) and UV detection at 254 nm and 280 nm. High-performance liquid chromatography (HPLC) was performed on an Agilent 1200 series instrument with a binary pump and a diode array detector. The optical rotation was taken with a Jasco P-1010 polarimeter Na/Hal lamp with a 0.5 dm/1 mL cell in spectral grade chloroform.
Light Sources. Screening scale reactions (0.10 mmol) and scaled-up reactions (0.40 mmol) were carried out using Blue Kessil H150 LED Grow Lights. Standard  to keep the reaction at 25 °C). After 24 hours, the reaction was exposed to air and shaken. 1,3bis(trifluoromethyl)-5-bromobenzene (17.2 μL, 1.0 equiv) was added to the reaction as external standard. A 1 mL aliquot was taken, diluted with water (3 mL) and diethyl ether (3 mL), and shaken. An aliquot was taken from the ether layer, diluted in acetone-d6, and analyzed by 1 H NMR spectroscopy.

IV. Emission and Absorption Spectra
Arb = arbitrary units (spectra not to scale).
2-(pyrrolidin-1-yl)pyridine. Prepared according to a known procedure. 6 Spectroscopic data matched those previously reported. 7 To a 25-mL conical flask fitted with a reflux condenser was added 2-bromopyridine (2.00 mL, 21.0 mmol, 1.0 equiv) and pyrrolidine (3.88 mL, 47.2 mmol, 2.25 equiv). The reaction was heated to 120 °C for 20 minutes. Upon cooling to room temperature, the reaction mixture was diluted with dichloromethane (75 mL) and washed with 1 M Na2CO3 (75 mL), water (75 mL), and brine (75 mL). The organic layer was dried over MgSO4, filtered, and the solvent was removed in vacuo to afford the desired compound as a colorless oil (2.39 g, 77% yield).

S10
To a 100-mL conical flask fitted with a reflux condenser were added chloroform (33 mL), Nmethyl-N-phenylacetimide (5.00 g, 33.5 mmol, 1.0 equiv), InBr3 (594 mg, 1.68 mmol, 0.050 equiv), and triethylsilane (21.4 mL, 134 mmol, 4.0 equiv). The reaction was heated to 60 °C for 16 hours, during which period the solution turned from colorless to yellow and then to orange. After cooling to room temperature, 1 M HCl (200 mL) was added to the mixture, which was then basified with 1 M NaOH and extracted with dichloromethane (3 × 200 mL). The combined organic layer was dried over MgSO4, filtered, and the solvent was removed in vacuo. Purification of the crude reaction mixture was carried out using automated chromatographic separation on silica gel using a gradient of 1% EtOAc/Hex  10% EtOAc/Hex to afford a colorless oil, which was then distilled to deliver the desired compound as a colorless oil (3.48 g, 77% yield).
Purification of the crude reaction mixture by preparative thin layer chromatography (TLC) using the indicated solvent system provided the desired product.