TfO- and Cu(OTf)-Assisted Acylamination Reaction of Unactivated Alcohols with Nitriles: A One-Pot P(IV) Activation, Stereoretention in Cycloalkanols and Deprotection Approach.

Described herein is a simple, novel, one-pot acylamination reaction of unactivated alcohols. This reaction employs the combination of PCl and triflic anhydride (TfO) or copper triflate Cu(OTf), which serves as a source of P(IV)-activated complex for nitriles to react under the Ritter-type mechanism. The synthetic utility of TfO-promoted reactions was demonstrated by its effectiveness to generate different acylaminated products. By employing Cu(OTf), this method represents a rare example of α-selective acylamination reaction. With chiral cycloalkanols, using the Cu(OTf)-promoted procedure, acylaminated products are formed with complete retention of configuration. The synthetic utility of the copper-assisted reaction in acetonitrile was readily demonstrated as a mild deprotection strategy.