New efficient synthesis of 4-aminocarbonyl substituted 4H-3,1-benzoxazines by a Passerini 3CC/Staudinger/aza-Wittig sequence

α-Acyloxy-carboxamide azides 1, obtained from Passerini reaction of easily accessible o-azidobenzaldehyde with isocyanides and carboxylic acids, reacted with triphenylphosphine to give various 4-aminocarbonyl substituted 4H-1,3-benzoxazines 3 in moderate to high yields via sequential Staudinger and intramolecular aza-Wittig reaction. However, α-hydroxy carboxamide azides 5 were obtained in moderate yields when pyruvic acid was used in the Passerini reaction. Further sequential reaction of azides 5 with triphenylphosphine and isocyanates produced 2-amino-4-aminocarbonyl substituted 4H-1,3-benzoxazines 8 via a tandem Staudinger/aza-Wittig/heterocumulene-mediated annulation.     

New efficient synthesis of pyrimido[1,6-c]quinazolin-4-ones by a Biginelli 3CC/Staudinger/aza-Wittig sequence

Dihydropyrimidinone azides 1, obtained from trimethylsilyl chloride-catalyzed Biginelli reaction of 2-azidobenzaldehyde, ethyl acetoacetate, and urea (or thiourea) at room temperature, reacted with triphenylphosphine to give iminophosphorane 2. A tandem aza-Wittig reaction of iminophosphorane 2 with isocyanate, acyl chloride or CS₂ in the presence of K₂CO₃ or NEt₃ generated pyrimido[1,6-c]quinazolin-4-ones 4, 6 or 8 in moderate to good yield.     

One-pot and regioselective synthesis of polysubstituted 3,4-dihydroquinazolines and 4,5-dihydro-3H-1,4-benzodiazepin-3-ones by sequential Ugi/Staudinger/aza-Wittig reaction

An efficient one-pot and regioselective synthesis of 3,4-dihydroquinazolines and 4,5-dihydro-3H-1,4-benzodiazepin-3-ones by Ugi/Staudinger/aza-Wittig sequence has been developed. The Ugi reactions of 2-azidobenzylamines, aldehydes, acids (or α-keto acids) and isocyanides produced the azide intermediates, which were then treated with tributylphosphine or triphenylphosphine to give polysubstituted 3,4-dihydroquinazolines or 4,5-dihydro-3H-1,4-benzodiazepin-3-ones in moderate to good yields by tandem Standinger/aza-Wittig reactions.     

New efficient synthesis of 1,2,4-trisubstituted imidazoles and imidazo[1,2-c]quinazolines by a tandem aza-Wittig/electrocyclic ring-closure process

A series of 1,2,4-trisubstituted imidazoles 5 were synthesized efficiently by a tandem aza-Wittig/1,5-electrocyclic ring-closure reaction of vinyliminophosphoranes 3 with aldehydes. Reactions of 5s,t with triphenylphosphine produced iminophosphoranes 7. A tandem aza-Wittig reaction of iminophosphorane 7 with isocyanate generated imidazo[1,2-c]quinazolines 9 in high yields.     

Synthesis of pseudopeptidic [(5H)-6-oxodibenzo[b,f][1,5]diazocine-5-yl]arylglycinamides by an Ugi 4CC/Staudinger/aza-Wittig sequence

Sequential Ugi reaction between p-substituted benzaldehydes, 2-acetyl or 2-benzoylanilines, cyclohexyl or benzyl isocyanides, and 2-azidobenzoic acid, followed by a Staudinger/aza-Wittig cyclization in the presence of triphenylphosphine afforded pseudopeptidic [(5H)-6-oxodibenzo[b,f][1,5]diazocine-5-yl]arylglycinamides.     

Synthesis of pseudopeptidic (S)-6-amino-5-oxo-1,4-diazepines and (S)-3-benzyl-2-oxo-1,4-benzodiazepines by an Ugi 4CC Staudinger/aza-Wittig sequence

Sequential Ugi reaction between p-substituted arylglyoxals, alkylamines, cyclohexyl isocyanide and 3-azido-(S)-2-(tert-butoxycarbonylamino)propanoic acid, followed by a Staudinger/aza-Wittig cyclization in the presence of triphenylphosphine, gave rise to enantiomerically pure N-cyclohexyl 4-alkyl-2-aryl-5-oxo-(S)-6-(tert-butoxycarbonylamino)-4,5,6,7-tetrahydro-1H-1,4-diazepine-3-carboxamides, that can be useful for new drug design. By the same sequence, p-substituted benzaldehydes, 2-aminobenzophenone, cyclohexyl isocyanide and (S)-3-phenyl-2-azidopropionic acid gave rise to N-cyclohexyl 2-((S)-3-benzyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-1-yl)-(R/S)-2-arylacetamides.     

New efficient synthesis of 1H-imidazo-[4,5-c]quinolines by a sequential Van Leusen/Staudinger/aza-Wittig/carbodiimide-mediated cyclization

A new efficient synthesis of multisubstituted 1H-imidazo-[4,5-c]quinoline derivatives via sequential van Leusen/Staudinger/aza-Wittig/carbodiimide-mediated cyclization was developed. Azides 4, obtained from Van Leusen reaction of 2-azidobenzaldehyde 1, amine 2 and TosMIC (tosylmethyl isocyanide) 3, reacted with triphenyl phosphine to produce iminophosphorane 5. A tandem aza-Wittig reaction of iminophosphorane 5 with isocyanate generated 1H-imidazo-[4,5-c]quinoline 7 through carbodiimide intermediate 6 in moderate to good yield.     

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

An 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.     

Stereoselective synthesis of 2,3,4-trisubstituted tetrahydrothiophenes

We describe an efficient new approach for the synthesis of highly substituted chiral tetrahydrothiophenes, based on the oxidation of a chiral furan substrate with singlet oxygen, followed by intramolecular hetero Michael addition.     

Microwave-assisted synthesis of dinucleoside analogues containing a thiazolidin-4-one linkage via one-pot tandem Staudinger/aza-Wittig/cyclization

Dinucleosides containing a thiazolidin-4-one linkage were prepared by one-pot tandem Staudinger/aza-Wittig/intermolecular cyclization under microwave irradiation and their structures were confirmed. Preliminary examination of HIV-RT inhibition showed that the dinucleosides containing (R)-thiazolidin-4-one linkage are significantly more active than those containing (S)-thiazolidin-4-one linkage.     

A diastereoselective synthesis of pseudopeptidic hydantoins by an Ugi/cyclization/Ugi sequence

A diastereoselective synthesis of helix-forming pseudopeptidic hydantoins by an Ugi 4CC/cyclization/reduction/Ugi 4CC sequence of reactions, giving mainly the l-adduct when benzoic acids were used, is described.     

Efficient Synthesis of Quinolines via a Knoevenagel/Staudinger/aza-Wittig Sequence

A simple and efficient method for the construction of quinoline derivatives from 2-azidobenzaldehyde and various carbonyl compounds was developed. The process involves a Knoevenagel condensation of 2-azidobenzaldehyde with carbonyl compound and subsequently an intramolecular normal Staudinger/aza-Wittig reaction to form the quinolone ring in satisfactory yields.     

De novo synthesis of sugar-aza-crown ethers via a domino Staudinger aza-Wittig reaction

A short and highly efficient route to sugar-aza-crown (SAC) ethers has been developed. The key step of the transformation is a one-pot cyclodimerization of C-glycosyl azido aldehydes via a domino Staudinger aza-Wittig reaction. This process allows the preparation of various orthogonally protected SAC ethers, from both alpha- and beta-C-glycosyl azido aldehydes.     

Synthesis of 3-oxo-1,4-diazepine-5-carboxamides and 6-(4-oxo-chromen-3-yl)-pyrazinones via sequential Ugi 4CC/Staudinger/intramolecular nucleophilic cyclization and Ugi 4CC/Staudinger/aza-Wittig reactions

An efficient approach for the assembly of 1,4-diazepine-based and 6-(4-oxo-chromen-3-yl)-pyrazinone-based frameworks has been developed that involves the Ugi four-component reaction (U-4CR) followed by Staudinger/nucleophilic cyclization and Staudinger/Aza-Wittig reactions, respectively. This convergent approach exhibits a high bond-forming efficiency, involving the use of readily available commercial reagents and is an example of the reconciliation of structural complexity with operational simplicity in a time- and cost-effective manner.     

Unexpected synthesis of 2,4,5-trisubstituted oxazoles via a tandem aza-Wittig/Michael/isomerization reaction of vinyliminophosphorane

2,4,5-Trisubstituted oxazoles 6 were unexpectedly prepared from a tandem reaction of vinyliminophosphorane 3 with various acyl chlorides in a one-pot fashion.     

Ring-opening cyclization of alkylidenecyclopropyl ketones with amines. An efficient synthesis of 2,3,4-trisubstituted pyrroles

[STRUCTURE: SEE TEXT] An efficient synthesis of 2,3,4-trisubstituted pyrroles via intermolecular cyclization of alkylidenecyclopropyl ketones with amines was observed. The addition of anhydrous MgSO4 improved the yields of the products 3. A possible mechanism involving the distal cleavage of the C-C bond of cyclopropane ring was proposed.     

Synthesis of cyclopropa[c]indeno[1,2-b]quinolines through a MCR/Staudinger/aza-Wittig sequence

Spirocyclopropanes were prepared from aromatic aldehydes, 1,3-indandione and acetophenones through a halogenation/S_N2-displacement/Michael-initiated ring-closing sequence by a pyridinium-ylide-assisted multicomponent reaction, and their further use was also researched in the construction of cyclopropa[c]indeno[1,2-b]quinolines through subsequent Staudinger/aza-Wittig reactions.     

Stereoselective synthesis of 3,4-disubstituted tetrahydrofurans and 2,3,4-trisubstituted tetrahydrofurans using an intramolecular allylation strategy employing allylsilanes

A Brønsted acid-mediated intramolecular allylation involving an allylsilane and an aldehyde has been used as the key step in a stereoselective synthesis of 3,4-disubstituted tetrahydrofurans and 2,3,4-trisubstituted tetrahydrofurans.     

Solid-phase synthesis of 3-alkyl-2-arylamino-3,4-dihydroquinazolines

The solid-phase synthesis of 3-alkyl-2-arylamino-3,4-dihydroquinazolines using an N-Fmoc-β-amino-2-nitrobenzenepropanoic acid scaffold is described. The resin-bound scaffold was reductively alkylated with aldehydes or ketones after Fmoc deprotection, followed by reduction of the nitro group with tin(II) chloride. Subsequent cyclization of the 1,3-diamine intermediates with aryl isothiocyanates in the presence of 1,3-diisopropylcarbodiimide (DIC) afforded the desired products in high purity with moderate to good yield after trifluoroacetic acid (TFA) cleavage.     

Formation of the BC ring system of upenamide via a Staudinger/aza-Wittig reaction

The BC ring system of upenamide was assembled using a stereoselective Diels-Alder reaction followed by a Staudinger/aza-Wittig/imine hydrolysis reaction. Stereoselective aldol coupling with an aldehyde that incorporates the DE ring system led to an advanced synthetic intermediate en route to the marine alkaloid upenamide.