The synthetic versatility of the Tiffeneau–Demjanov chemistry in homologation tactics

Abstract

Abstract The Tiffeneau–Demjanov rearrangement can be regarded as an interesting alternative to the more common semi-pinacol transposition. It is usually employed for ring extension but, under specific conditions, it can also be used for ring contraction. Compared to other techniques, such as the Demjanov rearrangement or homologations with diazo compounds, the Tiffeneau–Demjanov pathway presents attractive features including high yielding and selective processes. Ring enlargements follow very strict and simple rules, such as the movement of the less substituted carbon and retention of the configuration. The rearrangement process is mainly affected by steric factors, due to presence of neighbouring groups, rather than electronic ones. The ring contraction may be achieved positioning the amine within the ring, thus achieving a high level of control. Unfortunately, applications of the reaction in modern homologation chemistry are rare; therefore, the aim of the review is re-proposing to the synthetic community the versatility of this venerable reaction and thus, spurring its employment for tackling challenging homologations processes. Graphic abstract