aza-Wittig Reaction Research Articles

Mechanochemical synthesis of β-cyclodextrin urea derivatives under reactive CO2 atmosphere by Staudinger aza-Wittig reaction

Easily synthesize various ureido β-cyclodextrins with minimal environmental impact using a fast and solvent-free mechanochemical process under carbon dioxide reactive atmosphere.

Aza-Wittig reaction of (β-diazo-α,α-difluoroethyl)phosphonates with aldehydes for the synthesis of difluoromethylphosphonate-containing arylidene hydrazones

An aza-Wittig reaction of in situ generated difluoroalkyl diazo analog, (β-diazo-α,α-difluoroethyl)phosphonates, with aldehyde under mild conditions has been developed to afford difluoromethylphosphonate-containing arylidene hydrazones up to 99 % yields. The reaction was carried out under mild conditions with a broad substrate scope and was suitable for scale-up application. This reaction provides an efficient method for the facile construction of a series of difluoromethylphosphonate-containing arylidene hydrazones and is also a useful supplement to the transformation of (β-diazo-α,α-difluoroethyl)phosphonates.

Isoquinoline-Forming Staudinger–aza-Wittig Reaction Enabled by Atroposelective PIII/PIV=O Redox Catalysis

Isoquinoline-Forming Staudinger–aza-Wittig Reaction Enabled by Atroposelective PIII/PIV=O Redox Catalysis

N-Silylimine of Trifluoropyruvate in the Asymmetric Synthesis of Trifluoroalanine Derivatives

Aim. To develop a preparative method for the synthesis of N-trimethylsilylimine of trifluoropyruvate, and study its interaction with acetone under organocatalytic conditions.Results and discussion. A simple preparative approach to the first representative of N-silylimines of trifluoropyruvate was developed based on the interaction of triphenylphosphinimide and trifluoropyruvic acid methyl ester by the aza-Wittig reaction. It was found that the addition of acetone to N-silylimine occurred in the presence of L- or D-proline and led to the formation of enantiomerically enriched α-amino-γ-oxocarboxylates. The hydrolysis of the ester function resulted in (R)-α-trifluoromethyl aminocarboxylic acid, and the cyclocondensation with isocyanates or 2,5-dimethoxytetrahydrofuran yielded nitrogen-containing heterocycles containing pyrimidine or pyrrolizine nuclei.Experimental part. The synthetic procedures for the N-silylimine of trifluoropyruvate and its reaction with acetone are provided, along with the transformations of obtained α-amino-γ-oxocarboxylates (hydrolysis, cyclocondensations with isocyanates and 2,5-dimethoxytetrahydrofuran). The structures of the compounds synthesized were proven by 1H, 13C, 19F NMR spectroscopy methods, as well as by the elemental analysis.Conclusions. A convenient method for the synthesis of N-silylimine of trifluoropyruvate has been developed. Using the example of the Mannich reaction with acetone, it has been demonstrated that N-silylimine of trifluoropyruvate is a convenient substrate for the synthesis of optically active 3,3,3-trifluoroalanine derivatives.

A Cobalt Mediated Nitrene Transfer aza-Wittig Cascade Reaction To Access 1,3,4-Oxadiazole Scaffolds.

A cobalt(II) mediated three-component synthesis of 5-substituted-N-sulfonyl-1,3,4-oxadiazol-2(3H)-imines using sulfonyl azides, N-isocyaniminotriphenylphosphorane (NIITP), and carboxylic acids has been developed. This one-pot tandem reaction starts with a nitrene transfer to NIITP, followed by addition of the carboxylic acid to the in situ formed carbodiimide and subsequent intramolecular aza-Wittig reaction. Both the steric constraints of carboxylic acid and the stoichiometry of the employed cobalt salt determine the selectivity toward the two products, i.e. 5-substituted-N-sulfonyl-1,3,4-oxadiazol-2(3H)-imine versus 5-substituted-4-tosyl-2,4-dihydro-3H-1,2,4-triazol-3-one.

Investigating the Mechanism of the Catalytic Intramolecular Aza-Wittig Reaction Involved in the Synthesis of 2-Methylbenzothiazole from the Perspective of Bonding Evolution Theory

AbstractBonding evolution theory has been used at the density functional theory level [ωB97X-D exchange-correlation functional, 6-311G(d,p) basis set, and solvent (toluene) effects with polarizable continuum model] to unravel the reaction mechanism of the intramolecular aza-Wittig reaction of 2-(acetylthio)phenyl isocyanate (1) catalyzed by 3-methyl-1-phenyl-2-phospholene 1-oxide (2) to form 2-methylbenzothiazole (3). The reaction involves four steps (transition states) corresponding to (1) the formation of a cycloadduct (O–C then P–N bonds), (2) a decarboxylation leading to the formation of an iminophosphorane, and (3) an intramolecular [2+2] cycloaddition (N–C then P–O bonds) followed by (4) a retro [2+2] cycloaddition (cleavage of the P–N then O–C bonds) to get the product and regenerate the catalyst. Step 1 is the rate-determining step with an activation Gibbs free enthalpy of 21 kcal mol–1 and it is favored with respect to a competitive pathway leading to the formation of another cycloadduct (P–C then O–N bonds). The whole reaction is exergonic with a Gibbs free energy decrease of 31 kcal mol–1, associated with the liberation of a CO2 molecule and the formation of the aromatic benzothiazole. Following the scale of Domingo, the successive steps of the reaction have a polar nature.

Spotlight on the Winners of the DCO‐SCF 2021 Awards – An Ever Valuable Collaboration with EurJOC

Spotlight on the Winners of the DCO‐SCF 2021 Awards – An Ever Valuable Collaboration with EurJOC

Enantioselective Synthesis of Quaternary Oxindoles: Desymmetrizing Staudinger-Aza-Wittig Reaction Enabled by a Bespoke HypPhos Oxide Catalyst.

This paper describes a catalytic asymmetric Staudinger-aza-Wittig reaction of (o-azidoaryl)malonates, allowing access to chiral quaternary oxindoles through phosphine oxide catalysis. We designed a novel HypPhos oxide catalyst to enable the desymmetrizing Staudinger-aza-Wittig reaction through the PIII/PV═O redox cycle in the presence of a silane reductant and an IrI-based Lewis acid. The reaction occurs under mild conditions, with good functional group tolerance, a wide substrate scope, and excellent enantioselectivity. Density functional theory revealed that the enantioselectivity in the desymmetrizing reaction arose from the cooperative effects of the IrI species and the HypPhos catalyst. The utility of this methodology is demonstrated by the (formal) syntheses of seven alkaloid targets: (-)-gliocladin C, (-)-coerulescine, (-)-horsfiline, (+)-deoxyeseroline, (+)-esermethole, (+)-physostigmine, and (+)-physovenine.

A convenient E-diastereoselective synthesisof NH-isatin N′-arylimines via the aza-Wittig reaction

A general synthesis of NH-isatin N′-arylimines involves the aza-Wittig reaction of isatin and aryl azides, providing higher E-diastereoselectivity as compared to previously described methods. The procedure is applicable even to anilines which do not directly react with isatins.

Multicomponent synthesis of substituted pyridines via a catalytic intermolecular aza-Wittig/Diels-Alder sequence.

A three-component synthesis of polysubstituted pyridines has been developed, based upon the synthesis of 2-azadienes by a redox-neutral catalytic intermolecular aza-Wittig reaction and their subsequent Diels–Alder reactions. The two-pot process has been demonstrated using a range of aryl and heteroaromatic aldehydes, substituted α,β-unsaturated acids and push–pull enamines, to give rapid access to diverse tri- and tetrasubstituted pyridines.

Synthesis and Discovery of Schiff Base Bearing Furopyrimidinone for Selective Recognition of Zn2+ and its Applications in Cell Imaging and Detection of Cu2.

A simplefuro [2,3-d]pyrimidinone-based Schiff base FPS was synthesized via aza-Wittig reaction and structure elucidation was carried out by spectroscopic studies FT-IR, 1H NMR, and 13C NMR and mass spectrometry. FPS showed weak fluorescence emission in methanol and the selectivity of FPS to different metal ions (Mn2+, Ca2+, Fe2+, Fe3+, Mg2+, Al3+, Ba2+, Ag+, Co2+, Na+, K+, Cu2+, Zn2+, Pb2+, Bi3+) were studied by absorption and fluorescence titration. The results show that FPS has selective fluorescence sensing behavior for Zn2+ ions and the limit of detection (LOD) was calculated to be 1.19 × 10–8 mol/L. Moreover, FPS-Zn2+ acts as a metal based highly selective and sensitive new chemosensor for Cu2+ ions and the LOD was calculated to be 2.25 × 10–7 mol/L. In accordance with the results and theoretical calculations, we suspected that the binding mechanisms of FPS to Zn2+ and Cu2+ were assigned to be the cooperative interaction of Zn2+(Cu2+)-N.

Recent Advances in the Synthesis of Heterocycles by the Aza-Wittig Reaction

AbstractThe formation of the C=N bond in recent studies on heterocyclic compounds via the aza-Wittig reaction is reviewed. Furthermore, two different strategies for the formation of heterocyclic compounds, including intermolecular and intramolecular aza-Wittig reactions are described. The primary aim of this review is to provide up-to-date information on the application of the aza-Wittig reaction in the synthesis of a wide range of N-containing heterocyclic compounds in the chemical literature since 2010.1 Introduction2 Mechanism of the Staudinger and Aza-Wittig Reactions3 Intramolecular Aza-Wittig Reaction4 Intermolecular Aza-Wittig Reaction5 Conclusion

Interrupted aza-Wittig reactions using iminophosphoranes to synthesize 11C-carbonyls.

A direct CO2-fixation methodology couples structurally diverse iminophosphoranes with various nucleophiles to synthesize ureas, carbamates, thiocarbamates, and amides, and is amenable for 11C radiolabeling. This methodology is practical, as demonstrated by the synthesis of >35 products and isolation of the molecular imaging radiopharmaceuticals [11C]URB694 and [11C]glibenclamide.

Computational Study on the Kinetics and Mechanisms of Unimolecular Reactions of (Z)-(Z)-N-(λ5-phosphanylidene) Formohydrazonic Formic Anhydride: Intramolecular aza-Wittig Reaction in Competition with Mumm Rearrangement

For (Z)-(Z)-N-(λ5-phosphanylidene) formohydrazonic formic anhydride, Aza-Wittig reaction and Mumm rearrangement are studied using both density functional and coupled cluster theories. For this purpose, two different products starting from one substrate are considered that are competing with each other. The obtained products, P1 and P2, are thermodynamically favorable. The product of the aza-Wittig reaction, P1, is more stable than the product of Mumm rearrangement (P2). For the mentioned products, just one reliable pathway is separately proposed based on unimolecular reaction. Therefore, the rate constants based on RRKM theory in 300-600 K temperature range are calculated. Results show that the P1 generation pathway is a suitable path due to low energy barriers than the path P2. The first path has three steps with three transition states, TS1, TS2, and TS3. The P2 production path is a single-step reaction. In CCSD level, the computed barrier energies are 14.55, 2.196, and 10.67 kcal/mol for Aza-Wittig reaction and 42.41 kcal/mol for Mumm rearrangement in comparison with the corresponding complexes or reactants. For final products, the results of the computational study are in a good agreement with experimental predictions.

Acetylenes and nitriles as unconventional reactants for aza-Wittig reactions

The classic version of aza-Wittig reactions, namely, reactions between phosphazenes and compounds with polar double bonds, is widely employed in organic synthesis to produce C=N bonds. However, only a limited number of aza-Wittig reactions between phosphazenes and compounds with triple bonds is known, which has a lot to do with certain structural features of the reactants, wherein additional activation is required. This review provides a guide to those rare examples of aza-Wittig reactions with acetylenes and nitriles. A unique trait of these atom-economic processes is that they afford Wittig or new aza-Wittig reagents, respectively, which offers new opportunities for employing these reactions in organic syntheses, especially those of N-heterocyclic compounds.

Concise Diastereoselective Total Synthesis of (±)-Parvistemonine A

AbstractWe have developed a concise diastereoselective total synthesis of (±)-parvistemonine A. By using a Mukaiyama–Michael addition, an aza-Wittig reaction, a Paal–Knorr pyrrole synthesis, an acid-mediated annulation, and a Mitsunobu reaction as key steps, we achieved a total synthesis in which the longest linear sequence was ten steps and the overall yield was 19.6%. Additionally, the relative stereochemistry of parvistemonine A was confirmed by X-ray crystallographic analysis for the first time.

A facile synthesis of polysubstituted furo[2,3-d]pyrimidinones and 1,2,4-triazole-fused derivatives

In this paper, a series of polysubstituted furo[2,3- d]pyrimidinones, including 1,2,4-triazole-fused derivatives, are synthesized via aza-Wittig reactions of iminophosphoranes, under mild conditions.

Reactive & Efficient: Organic Azides as Cross-Linkers in Material Sciences.

The exceptional reactivity of the azide group makes organic azides a highly versatile family of compounds in chemistry and the material sciences. One of the most prominent reactions employing organic azides is the regioselective copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition with alkynes yielding 1,2,3-triazoles. Other named reactions include the Staudinger reduction, the aza-Wittig reaction, and the Curtius rearrangement. The popularity of organic azides in material sciences is mostly based on their propensity to release nitrogen by thermal activation or photolysis. On the one hand, this scission reaction is accompanied with a considerable output of energy, making them interesting as highly energetic materials. On the other hand, it produces highly reactive nitrenes that show extraordinary efficiency in polymer crosslinking, a process used to alter the physical properties of polymers and to boost efficiencies of polymer-based devices such as membrane fuel cells, organic solar cells (OSCs), light-emitting diodes (LEDs), and organic field-effect transistors (OFETs). Thermosets are also suitable application areas. In most cases, organic azides with multiple azide functions are employed which can either be small molecules or oligo- and polymers. This review focuses on nitrene-based applications of multivalent organic azides in the material and life sciences.

Synthesis of 3-methylthio-1-phenyl-pyrazolo[3,4-d][1,2,4]triazolo[1,5-a]pyrimidin-4-one derivatives via tandem aza-Wittig reaction

An efficient and convenient procedure for the synthesis of 3-methylthio-1-phenyl-pyrazolo[3,4-d][1,2,4]triazolo[1,5-a]pyrimidin-4-one derivatives (4a–m) via tandem aza-Wittig and annulation reactions with iminophosphoranes 1, aryl isocyanate, and substituted 2-phenoxyacetohydrazide is described. This protocol provides a simple and facile approach to synthesize pyrazolo[3,4-d][1,2,4] triazolo[1,5-a]pyrimidine derivatives under mild conditions.

Expansion of diazepine heterocyclic chemical space via sequential Knoevenagel condensation-intramolecular aza-Wittig reaction: 2-acyl-4-aryl-5H-pyrrolo[1,2-d][1,4]diazepines.

A highly efficient synthetic route to a new 1,4-diazepene skeleton, 2-acyl-4-aryl-5H-pyrrolo[1,2-d][1,4]diazepine, was established where Knoevenagel condensation of readily available two fragments, N-substituted pyrrole-2-carboxaldehyde and α-azidoketone, followed by intramolecular aza-Wittig reaction under Staudinger azide reduction conditions permitted facile access to a poly-substituted 1,4-diazepine ring system for the first time. Successful application of this protocol to construct new 1-alkoxy-3-acylisoquinolines and 1-alkoxy-3-acyl-β-carbolines is also demonstrated.