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

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

Oxidative rearrangement of 1,1-disubstituted alkenes to ketones

“…Because terminal alkenes 5 are easily prepared from ketones 10 , the realization of the planned transformation represents a two-step, one-carbon homologation or ring expansion of ketones, a transformation of high synthetic importance. Previously, the Tiffeneau-Demjanov reaction has most often been used for this purpose ( 24 ). However, three to four steps are needed to accomplish this sequence with moderate overall synthetic efficiency.…”

Annulated carbamates are precursors for the ring contraction of the adamantane framework

“…In this work, we focus on the triflic acid promoted decarboxylation of N -unsubstituted carbamates, which leads to the ring contraction of the adamantane framework by nucleophilic 1,2-alkyl shift 16 producing noradamantane carbaldiminium salts, and the one-pot reduction of the resulting iminium salts to noradamantane methylene amines was performed in the same pot subsequently using LiAlH 4 ( Fig. 2 ).…”

Acid-catalyzed ring-expansion of 4-(1-hydroxycyclobutyl)-1,2,3-triazoles

“…It is known that the denitrogenative rearrangement of diazo compounds as a variant of the semipinacol rearrangement, 12 such as the classical Tiffeneau–Demjanov rearrangement, 13 is an efficient method for the construction of structurally unique ketone-containing frameworks. 14 However, it is generally not easy to prepare α -diazo-ol precursors.…”