Benzotriazole-mediated arylalkylation and heteroarylalkylation

Abstract

N-(Arylmethyl)benzotriazoles, containing in the aryl ring an ortho or para electron-donating group such as amino, hydroxy, or methoxy, undergo lithiation at the methylene carbons to give anions which react with a variety of electrophiles. The benzotriazole groups in the parent derivatives as well as those obtained via lithiation, have been displaced by Grignard reagents and reductively removed with LiAlH4 or Na/piperidine, to give alkylsubstituted aromatic compounds. These N-(arylmethyl)- and N-(arylalkyl)benzotriazoles are also efficient arylalkylating reagents for electron-rich aromatic and heteroaromatic compounds, alcohols, thiols, amines, and active methylene compounds. This general methodology has also been extended to heteroaryl analogues in which the ring heteroatom acts as the electron-donating group. In general, the reactions proceed in good to excellent yields and isolation and purification of the products was simple. In many instances this new methodology represents the method of choice for the preparation of whole classes of compounds.