One-Pot Synthesis of 2-Cyano-1,4-diketones: Applications to Synthesis of Cyanosubstituted Furans, Pyrroles, and Dihydropyridazines

Abstract

A convenient synthetic route for the construction of functionalized 2-cyano-1,4-diketones has been established from the nucleophilic substitution of 2-bromoacetophenones with NaCN via the in situ-generated β-ketonitriles. This method was further applied to the synthesis of cyanosubstituted furans, pyrroles, or dihydropyridazines, which were obtained in good to excellent yields using Bi(OTf)3, NH4OAc, or N2H4. The key structures were confirmed by X-ray single crystal diffraction analysis.

Bismuth(III) triflate: An Efficient Catalyst for the Synthesis of Diverse Biologically Relevant Heterocycles

“…In Bi(OTf) 3 this Lewis acidic property being enhanced by the presence of the strong electron‐withdrawing group which make it superior than the other triflate salts as a catalyst. Therefore such beneficial features as a whole motivated the organic chemists to explore the catalytic applicability of bismuth(III) triflate in more heights and as a results, in the recent past, there were immense applications of bismuth(III) triflate as catalyst for the diverse organic synthesis . The catalytic applicability of this mild catalyst is well documented in the literature especially in various name reactions that include aldol reactions, Michael‐type reactions, Ene reaction, Diels Alder reaction, Friedel‐Crafts reaction,, Fries rearrangement, Beckmann rearrangements, Claisen rearrangement, Mannich reaction,, Prins reaction, Baeyer‐Villiger oxidation, and many more .…”

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

“…In contrast to 1,4‐dicarbonyls in general, the synthesis of 1,4‐diketones poses a greater challenge, often requiring use of an excess of one coupling partner and/or significant pre‐functionalisation of substrates to achieve the desired heterocoupling. Reported methods include oxidative homocoupling [23–27] or heterocoupling of ketone enolates, [7,24,28–34,35,36] alkylation of enolates, [9,14,37–42] alkylation of acyl anion equivalents [43–47] or acyl radicals, [11,48] acylation of homoenolate equivalents, [12,13,49–52] or multicomponent strategies [53,54] . Only a subset of methods have been reported that tolerate aliphatic substrates for both reaction partners: addition of silyl enolates to oxyallyl zwitterions [10] and the aldehyde umpolung‐based Stetter reaction [4,5,45,55] …”

“…[8,[15][16][17][18][19][20][21][22] In contrast to 1,4-dicarbonyls in general, the synthesis of 1,4-diketones poses a greater challenge, often requiring use of an excess of one coupling partner and/or significant pre-functionalisation of substrates to achieve the desired heterocoupling. Reported methods include oxidative homocoupling [23][24][25][26][27] or heterocoupling of ketone enolates, [7,24,[28][29][30][31][32][33][34]35,36] alkylation of enolates, [9,14,[37][38][39][40][41][42] alkylation of acyl anion equivalents [43][44][45][46][47] or acyl radicals, [11,48] acylation of homoenolate equivalents, [12,13,[49][50][51][52] or multicomponent strategies. [53,…”

One-Pot Tandem Approach to Functionalized 3-Hydroxy-2-furanyl-acrylamides

“…One of the core concepts involves the Wittig reaction between α-substituted chalcones (generated from aldehydes) and acyl chlorides using a combination of reagents (Scheme 1a). 8 In an effort to develop such a system, we hypothesized that the reaction of aroylacetonitrile 1 with 2-oxoaldehydes (OAs) 2 under triethylamine (TEA)– tert -butyl hydroperoxide (TBHP) combination in one pot will result in the synthesis of 3-cyanofurans, through an in situ generated 1,4-dione A (Scheme 1b). 9 However, an unprecedented reaction between 1 and 2 under TEA–TBHP resulted in the synthesis of Z-selective highly functionalized polysubstituted furans that are difficult to be accessed by other protocols (Scheme 1c).…”