One-Pot Synthesis of Amides from Aldehydes and Amines via C–H Bond Activation

Roberta Cadoni , Andrea Porcheddu , Giampaolo Giacomelli , and Lidia De Luca

http://pubs.acs.org/doi/abs/10.1021/ol302175v 

This is a nice way to make amides from aldehydes in one step -- it avoids a two-step sequence of chromium-based oxidation  followed by EDCI/DCC/HATU/HBTU etc coupling.

General procedures for amides 4a-q: An amine (0.5 mmol) was added to a solution of N- chlorosuccinimide (0.55 mmol) in 7 mL of acetonitrile under N2 atmosphere and at room temperature. After 3 hour were added an aldehyde (2.5 mmol), TBHP (2.5 mmol, 0.34 mL of a 70 wt% in water) and Cu(OAc)2 . H2O (0.068 mmol) under N atmosphere.

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The reaction mixture was heated in an oil bath at 82°C for 50 min (the reaction was monitored by

TLC until disappearance of N-chloroamine). Then the reaction mixture was quenched with 40 mL of a saturated solution of Na2SO3 (for removal of excess TBHP) and extracted three times with 20 mL of diethyl ether. The combined organic phases were dried over anhydrous Na2SO4 and the solvent was evaporated under reduced pressure. The crude product was purified by silica gel column chromatography to provide the desired amide.