Alkylation of amines with allylic alcohols and deep eutectic solvents as metal-free and green promoters

Abstract

A novel approach for the allylic alkylation of anilines, hydrazides, indole derivatives and additional interesting nucleophiles is described, which involves the direct use of a variety of allylic alcohols under very mild conditions, such as room temperature, and the use of sustainable deep eutectic solvents (DESs). The search for the optimum DES to be used in the reaction revealed that a simple mixture of choline chloride (ChCl) and lactic acid provides excellent results for a wide range of substrates with high isolated yields. This methodology represents a significant improvement compared to other procedures described in the literature, for which high temperatures, stronger reaction conditions or metal catalysts are usually required. In some cases, this protocol provides the first examples of trapping allylic carbocations with indole derivatives. In addition, challenging nucleophiles such as amides, carbamates, azides or sulfonamides, among others, have also been successfully used. All these features render this procedure an appealing and green alternative compared to other examples reported in the literature on the alkylation of amines by allylic alcohols. Preliminary mechanistic studies using unsymmetrically substituted alcohols support that the reaction could proceed via an S_N1 pathway.