Recent Advances in Stetter Reaction and Related Chemistry: An update

Abstract

The Stetter reaction is actually a special CÀ C bond forming reaction through a 1,4-addition reaction in the presence of nucleophilic catalyst. It involves a reaction between aldehydes and Michael acceptors catalyzed by Nheterocyclic carbenes (NHC's) leading to preparation of 1,4dicarbonyl compounds via carbon-carbon bond formation. It offers a powerful approach to access 1,4-dicarbonyl compounds which are significant starting materials and inter-mediates in the synthesis of several heterocyclic systems, and bioactive heterocyclic framework which are present in natural products. In this review we try to underscore the recent advances in Stetter reaction and its applications from 2015 till date. Notably, we focused on the applications of Stetter reaction in the synthesis of various heterocyclic systems and total synthesis of natural products, which have largely been overlooked, previously.

A Highly EfficientN‐Mesityl Thiazolylidene for the Aliphatic Stetter Reaction: Stereoelectronic Quantification for Comparison of N‐Heterocyclic Carbene Organocatalysts

“…Recent mechanistic studies have focused mainly on asymmetric triazolylidene‐catalyzed inter‐ or intramolecular Stetter reactions [71,75–79] . The Stetter reaction and variations thereof have been recently reviewed [80–82] . Although asymmetric intra molecular variants have been successfully developed, [60,83] asymmetric inter molecular Stetter reactions (largely mediated by chiral triazolylidene NHCs) remain limited in scope and efficiency, tolerating only chalcones (Figure 1B) [57,84,85] or highly activated non‐ketone Michael acceptors [65,66,80,81,86–91] .…”

“…[71,[75][76][77][78][79] The Stetter reaction and variations thereof have been recently reviewed. [80][81][82] Although asymmetric intramolecular variants have been successfully developed, [60,83] asymmetric intermolecular Stetter reactions (largely mediated by chiral triazolylidene NHCs) remain limited in scope and efficiency, tolerating only chalcones (Figure 1B) [57,84,85] or highly activated non-ketone Michael acceptors. [65,66,80,81,[86][87][88][89][90][91] At present, poor reactivity of aliphatic aldehyde substrates remains a major limitation of intermolecular Stetter approaches to access 1,4diketones for synthesis, with the few reported examples employing only sterically trivial aldehydes.…”

“…[80][81][82] Although asymmetric intramolecular variants have been successfully developed, [60,83] asymmetric intermolecular Stetter reactions (largely mediated by chiral triazolylidene NHCs) remain limited in scope and efficiency, tolerating only chalcones (Figure 1B) [57,84,85] or highly activated non-ketone Michael acceptors. [65,66,80,81,[86][87][88][89][90][91] At present, poor reactivity of aliphatic aldehyde substrates remains a major limitation of intermolecular Stetter approaches to access 1,4diketones for synthesis, with the few reported examples employing only sterically trivial aldehydes. [66,92,93] The sila-Stetter variant addresses some of these issues (Figure 1C) [46,56] although preparation of the requisite acylsilane limits the efficiency and substrate scope for this approach.…”

Synthesis of indole derivatives as prevalent moieties present in selected alkaloids

“…36 Owing to the importance of the indole as a scaffold in natural products and biologically active compounds, a plethora of reviews and several chapters have been published in this eld. In a continuation of our interest in heterocyclic chemistry [65][66][67] and the applications of named reactions in the total synthesis of natural products, [68][69][70][71][72][73][74][75] in this review we aim to highlight the synthesis of indoles as a moiety in selected alkaloids.…”

Steroid-Functionalized Imidazolium Salts with an Extended Spectrum of Antifungal and Antibacterial Activity

“…NHCs are a very useful tool in modern organic synthesis, mainly due to their ability to bind most transition metals. Metal complexes with NHCs are homogeneous catalysts for many reactions (mainly as ruthenium and palladium complexes) [27,28]; additionally, NHCs themselves can be used as organocatalysts [29][30][31]. Moreover, it has been shown that NHC-metal complexes exhibit antibacterial and antitumor activity, especially when the NHCs are silver-or gold-bound ligands [32,33].…”