Intramolecular aza-Wittig Reaction Research Articles

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.

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

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.

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.

Phosphazenomalonates as Catalysts and Reactants in (4+3) Annulation to Acrolein.

The concept of combining a catalyst and an activated center in one molecule was implemented in Michael donors functionalized with phosphazene units. First, the phosphazene group catalyzes Michael addition and then acts as a reactant in an intramolecular aza-Wittig reaction. The viability of this strategy was demonstrated by our development of a one-pot method for azepane core construction starting from functionalized azides, triphenylphosphine and acrolein.

Facile Synthesis of 3-Arylidene-3H-1,4-benzodiazepines by a Sequential Ugi/Staudinger/Aza-Wittig Reaction

N -[2-(Alkylamino)-1-(2-azidophenyl)-2-oxoethyl]- N -(3-oxoprop-1-en-2-yl)amides, obtained from the Ugi reaction of a vinyliminophosphorane, 2-azidobenzaldehyde, a carboxylic acid, and an alkyl isocyanide, reacted with triphenylphosphine to give various 3-arylidene-3 H -1,4-benzodiazepine in good yields via sequential Staudinger and intramolecular aza-Wittig reaction.

Synthesis of 2H-pyrrolo[3,4-C]quinoline via an Aldol/Van Leusen/Staudinger/aza-Wittig sequence

ABSTRACTAn aldol/van Leusen/Staudinger/aza-Wittig reaction for the preparation of the derivatives of 2H-pyrrolo[3,4-c]quinolines from 2-azidobenzaldehyde, acetyl compounds, and tosylmethyl isocyanide was developed. The process involves an aldol condensation of 2-azidobenzaldehyde with acetyl compound in base, a van Leusen reaction to form the key pyrrole intermediates, and then a Staudinger and intramolecular aza-Wittig reaction occurred with the addition of triphenylphosphine to complete the formation of pyrrolo[3,4-c]quinoline ring in high yields.

Synthesis of 1,3,4-oxadiazoles from the reaction of N-isocyaniminotriphenylphosphorane (NICITPP) with cyclohexanone, a primary amine and an aromatic carboxylic acid via intramolecular aza-Wittig reaction of in situ generated iminophosphoranes

GRAPHICAL ABSTRACT

ChemInform Abstract: New Efficient Synthesis of 1,4‐Benzodiazepin‐5‐ones by Catalytic Aza‐Wittig Reaction.

1,4-Benzodiazepin-5-ones were synthesized in 71–89% yields from 2-isocyanato-N-(2-oxoalkyl)benzamides via a new catalytic intramolecular aza-Wittig reaction. Starting from easily accessible phthalic anhydride and α-arylamino ketones, the corresponding 2-{[(2-oxoalkyl)amino]carbonyl}benzoic acids underwent sequential formation of the acid azide and Curtis rearrangement to give 2-isocyanato-N-(2-oxoalkyl)benzamides that were reacted directly to give the final 2,4-diaryl-3,4-dihydro-5H-1,4-benzodiazepin-5-ones and 4-aryl-2-tert-butyl-3,4-dihydro-5H-1,4-benzodiazepin-5-ones.

N-Isocyanimino-Triphenylphosphorane (Ph3Pnnc) as an Efficient Reagent for the Preparation of Fully Substituted 1,3,4-Oxadiazoles via Intramolecular Aza-Wittig Reaction in Water

GRAPHICAL ABSTRACT

New Efficient Synthesis of 1,4-Benzodiazepin-5-ones by Catalytic Aza-Wittig Reaction

1,4-Benzodiazepin-5-ones were synthesized in 71–89% yields from 2-isocyanato-<i>N</i>-(2-oxoalkyl)benzamides via a new catalytic intramolecular aza-Wittig reaction. Starting from easily accessible phthalic anhydride and α-arylamino ketones, the corresponding 2-{[(2-oxoalkyl)amino]carbonyl}benzoic acids underwent sequential formation of the acid azide and Curtis rearrangement to give 2-isocyanato-<i>N</i>-(2-oxoalkyl)benzamides that were reacted directly to give the final 2,4-diaryl-3,4-dihydro-5<i>H</i>-1,4-benzodiazepin-5-ones and 4-aryl-2-<i>tert</i>-butyl-3,4-dihydro-5<i>H</i>-1,4-benzodiazepin-5-ones.

ChemInform Abstract: One‐Pot Synthesis of 3‐Acetyl‐2‐aryl‐3,4‐dihydroquinazolines from N‐[2‐(Azidomethyl)phenyl]benzamides Utilizing Intramolecular Aza‐Wittig Reaction.

A new and convenient method for the preparation of 3,4-dihydroquinazolines 5 with aryl and Ac groups at C(2) and N(3), respectively, has been developed. The key sequence is the formation of aza-phosphorane intermediates by the reaction of N-[2-(azidomethyl)phenyl]benzamides 1 with Ph3P, followed by intramolecular aza-Wittig reaction and 3-acetylation, which can be conducted in one-pot.

Sequential multicomponent synthesis of α-ketoimides, from acyl chlorides, isocyanides, and silver salts of carboxylic acids

A sequential multicomponent synthesis among acyl chlorides, isocyanides, and silver salts of carboxylic acids was developed to synthesize α-ketoimides. The latter undergo an intramolecular aza-Wittig reaction to afford 2-acylquinazolinones.

Facile Synthesis of 4-Arylidene-1H-imidazol-5(4H)-ones by an Ugi–Aza-Wittig Sequence

Vinyl azides, obtained from the Ugi-type reaction of 2-azido-3-arylacrylic acid, secondary amine, aldehyde, and isocyanide, react with triphenylphosphine to give a variety of 4-arylidene-1H-imidazol-5(4H)-ones in high yields via sequential Staudinger and intramolecular aza-Wittig reaction.

ChemInform Abstract: Four‐Component Synthesis of Disubstituted 1,3,4‐Oxadiazoles from N‐Isocyaniminotriphenylphosphorane, Phenylacetylenecarboxylic Acid, Chloroacetone Derivatives, and Primary Amines.

Abstract The 1:1 imine intermediate generated by the addition of primary amine to chloroacetone derivatives is trapped by N-isocyaniminotriphenylphosphorane in the presence of phenylacetylenecarboxylic acid, leading to the formation of the corresponding iminophosphorane intermediate. Disubstituted 1,3,4-oxadiazole derivatives are formed via intramolecular aza-Wittig reaction of the iminophosphorane intermediate. The reactions were completed in neutral conditions at room temperature. The disubstituted 1,3,4-oxadiazole derivatives were prepared in excellent yields. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.

Model support studies toward the total synthesis of the stemona alkaloid stemocurtisine

Herein we report the results of a furan-based approach toward the synthesis of the Stemona alkaloid, stemocurtisine 1 via the linearly fused tricyclic intermediate 3, representing the key A,B,C-ring structural feature of the target molecule. A highly diastereoselective synthesis of compound 3 was achieved starting from 3-furfural 6, in a synthetic sequence that involved; (1) a rapid in situ conversion of an O-mesylate to the corresponding chloride with inversion of configuration from assistance of the neighbouring 3-furanyl group; (2) an intramolecular aza-Wittig reaction to prepare the azepine ring; and (3) a base promoted lactam ring forming step. While methods were established to oxidize the furan ring of 3 to the corresponding γ-hydroxy-α,β-unsaturated lactone we were unable to affect cyclization of the lactam ring hydroxyl group to the γ-position of the lactone to create the cyclic ether feature of the natural product. Model studies were also unsuccessful.

The Reaction of N-Isocyaniminotriphenylphosphorane With Biacetyl in the Presence of (E)-Cinnamic Acids: Synthesis of Fully Substituted 1,3,4-Oxadiazole Derivatives via Intramolecular AZA-Wittig Reactions of in Situ Generated Iminophosphoranes

Reaction of N-isocyaniminotriphenylphosphorane with biacetyl in the presence of (E)-cinnamic acids proceeds smoothly at room temperature and under neutral conditions to afford sterically congested 1,3,4-oxadiazole derivatives in high yields. The reaction proceeds smoothly and straightforward under mild conditions and no side reactions are observed.

Facile synthesis of benzothiadiazine 1,1-dioxides, a precursor of RSV inhibitors, by tandem amidation/intramolecular aza-Wittig reaction

Reaction of o-azidobenzenesulfonamides with ethyl carbonochloridate afforded the corresponding amide derivatives, which gave 3-ethoxy-1,2,4-benzothiadiazine 1,1-dioxides through an intramolecular aza-Wittig reaction. The reaction was found to be general through the synthesis of a number of benzothiadiazine 1,1-dioxides. Acid-catalyzed hydrolysis of 3-ethoxy-1,2,4-benzothiadiazine 1,1-dioxides furnished the 2-substituted benzothiadiazine-3-one 1,1-dioxides in good yields and high purity, which is the core moiety of RSV inhibitors.

Four-Component Synthesis of Disubstituted 1,3,4-Oxadiazoles from N-Isocyaniminotriphenylphosphorane, Phenylacetylenecarboxylic Acid, Chloroacetone Derivatives, and Primary Amines

The 1:1 imine intermediate generated by the addition of primary amine to chloroacetone derivatives is trapped by N-isocyaniminotriphenylphosphorane in the presence of phenylacetylenecarboxylic acid, leading to the formation of the corresponding iminophosphorane intermediate. Disubstituted 1,3,4-oxadiazole derivatives are formed via intramolecular aza-Wittig reaction of the iminophosphorane intermediate. The reactions were completed in neutral conditions at room temperature. The disubstituted 1,3,4-oxadiazole derivatives were prepared in excellent yields. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.