Nickel-catalyzed transamidation of aliphatic amide derivatives

We report a two-step approach to achieve the transamidation of secondary aliphatic amides using non-precious metal catalysis.

equiv). The resulting mixture was stirred at 23 °C for 12 h, and then diluted with deionized water (50 mL) and EtOAc (50 mL). The layers were separated and the organic layer was washed successively with 1.0 M HCl (50 mL), saturated aqueous NaHCO 3 (50 mL), and brine (50 mL).
The organic layer was dried over Na 2 SO 4 and concentrated under reduced pressure. The resulting crude solid material was used in the subsequent step without further purification.
To a flask containing the crude material from the previous step was added DMAP (105 mg, 0.86 mmol, 0.1 equiv) followed by acetonitrile (43 mL, 0.2 M). Boc 2 O (2.30 g, 10.3 mmol, 1.2 equiv) was added in one portion and the reaction vessel was flushed with N 2 . The reaction mixture was allowed to stir at 23 °C for 24 h. The reaction mixture was diluted with EtOAc (50 mL) and then washed with saturated aqueous NaHCO 3 (2 x 50 mL) and brine (50 mL). The combined organic layers were dried over Na 2 SO 4  Acid chloride SI-13 (1.08 mL, 8.08 mmol, 1.0 equiv) was then added dropwise (1 drop/sec) at -78 °C and stirred for an additional 1 h. This mixture was then warmed to 0 °C and stirred for an additional 1 h. The reaction was warmed to 23 °C before quenching with saturated aqueous NaHCO 3 (30 mL). This biphasic solution was transferred to a separatory funnel with brine (10 mL) and EtOAc (30 mL). The layers were separated and the aqueous layer was extracted with EtOAc (3 x 30 mL). The combined organic layers were dried over Na 2 SO 4 and concentrated under reduced pressure. The resulting crude residue was purified by flash chromatography

B. Reaction Discovery, Optimization, and Relevant Control Experiments
Representative procedure for ligand screening (coupling of amide 7 and cyclohexylamine (8) is used as an example). Amide 9 (Table S1,  Optimization efforts that deviate from the above conditions are indicated below.

D. Scope of Amine Nucleophiles
Representative and toluene (0.133 mL, 1.5 M) were added. The vial was sealed with a Teflon-lined screw cap, removed from the glove box, and stirred at 60 °C for 18 h. After cooling to 23 °C, the mixture was diluted with hexanes (0.5 mL) and filtered over a plug of silica gel (10 mL of EtOAc eluent).
The volatiles were removed under reduced pressure and the crude residue was purified by flash chromatography Any modifications of the conditions shown in the representative procedure above are specified in the following schemes, which depict all of the results shown in Figure 4.
For each of the nickel-catalyzed reactions described herein, control experiments were performed concurrently where Ni(cod) 2 and both Ni(cod) 2

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To obtain an authentic sample of the product, to a flame dried scintillation vial containing the  The volatiles were removed under reduced pressure. Yields were determined by 1 H NMR analysis with hexamethylbenzene (HMB). Spectral data match those previously reported for amides 30 and 9 (see pages S20 and S14, respectively).  Amide rac-40 ( Figure 6). rac-40 was prepared using the known procedure described for (-)-    Table S2 below.