Microwave-assisted alkylation reactions employing O-alkylisoureas

In recent years, the use of microwave irradiation to accelerate chemical reactions has become increasingly popular. A protocol for the synthesis of esters via reaction of carboxylic acids with O-alkylisoureas under microwave heating was studied. Efficient processes were developed using pre-formed O-alkylisoureas or via an in-situ formation sequence starting from primary and secondary alcohols. It was demonstrated that under these microwave conditions ester formation with primary and secondary alcohols proceeded in good yields and, in the latter case, with clean inversion of configuration of the esters. O-alkylisoureas were used as reactive intermediate also in the alkylation of substituted phenols. A PASP procedure was also developed by employing pre-formed polymer-supported isoureas, and by an efficient “catch and release” esters formation procedure in which alcohols are caught on resin as isoureas by reaction with immobilised carbodiimide, and released as ester by subsequent treatment with a carboxylic acid. Polymer-supported isoureas were also employed in the synthesis of 2-oxazolines.