[3+2] Cycloaddition of metal-containing azomethine ylides for highly efficient synthesis of mitosene skeleton

Efficient synthesis of tricyclic indole derivatives bearing a substituent at the 3-position of the indole nucleus was achieved by the [3+2] cycloaddition reaction of transition metal-containing azomethine ylides derived from N-(o-alkynylphenyl)imines with vinyl ethers. Third-row transition metal complexes, especially PtCl₂, turned out to be highly efficient for the reaction of internal alkynes and imidate substrates with wide generality. Moreover, as strong support for the reaction mechanism, the intermediate Pt-carbene complex was found to undergo intramolecular C-H bond insertion reaction to give tetracyclic indoline derivatives when benzyl vinyl ether was employed as a dipolarophile. This protocol provided a facile synthesis of highly functionalized tricyclic indole derivatives found as the basic skeleton of the mitosene family, such as mitomycin C.     

A convenient procedure for the synthesis of fused fluoro isoquinolines

A base-promoted conversion of ortho-trifluoromethyl benzyl derivatives of NH-heterocycles into a respective fluorinated isoquinolines (38-57% isolated yields) is reported. The reaction is general for the benzylated derivatives of the electron-rich NH-heterocycles and the respective derivatives of pyrazole. The outcome of the reaction could be explained by an intermediate formation of a highly reactive quinone methide species.     

Three component reaction of aryl diazonium salt with sulfonamide & actonitrile to synthesize N-sulfonyl amidine

A new method was developed to prepare N-sulfonyl amidine compounds through three-component reaction of aryl diazonium salts with sulfonamides and acetonitrile, in which, nitrilium ion intermediate, generated from the reaction of aryldiazonium salt with nitrile, was subsequently trapped by sulfonamides. A series of N-sulfonyl amidine derivatives were synthesized by using various types of aryl diazonium salts, sulfonamides and nitriles. In addition, indolyl imine products could also be prepared by using indole as the nucleophile to trap nitrilium ion intermediate.     

Mild and rapid method for the generation of o-quinone methide intermediates. Synthesis of puupehedione analogues

A route to simpler analogues to bioactive puupehedione derivatives involving a hetero Diels-Alder cycloaddition of a o-quinone methide is described. These intermediate species are generated via fluoride-induced desilylation of silyl derivatives of o-hydroxybenzyl iodides. Remarkable short reaction times and very mild experimental conditions are the main features of this method.     

Synthesis of 1-thio-phytosphingolipid analogs by microwave promoted reactions of thiols and aziridine derivatives

A practical and versatile method for the synthesis of 1-thio-phytosphingolipid analogs through regioselective nucleophilic ring-opening reactions of phytosphingosine aziridine derivatives with thiols is described. The reactions were carried out with N-acylaziridines and a variety of thiol compounds. Microwave irradiation highly improved the yield of the ring-opening reaction and the intermediate N-acyl adducts were converted into 1-S-phytosphingolipid analogs, such as phytoceramide and phytosphingosine derivatives.     

Reaction of N-fluoropyridinium fluoride with isonitriles: a convenient route to picolinamides

Reaction of N-fluoropyridinium fluoride generated in situ with a series of isonitriles led to the formation of the corresponding picolinamides in good yields. A similar reaction sequence for quinoline yielded the respective derivatives of 2-quinoline carboxylic acid. The proposed reaction mechanism involves the intermediate formation of a highly reactive carbene species.     

Enantioselective construction of biaryl part in the synthesis of stegane related compounds

A Pd-mediated intramolecular aryl-aryl coupling reaction of phenyl benzoate derivatives were examined to form benzo[c]chromen-6-ones, and then enantioselective lactone-opening reaction with a borane-oxazaborolidine combination was carried out. The resulting biphenyl was transformed into a key intermediate for the stegane related compounds. The absolute configuration of the biphenyl is also discussed.     

One-pot synthesis of functionalized furamide derivatives via a three-component reaction between an amine, diketene and dibenzoylacetylene in the presence of triphenylphosphine

An effective route to functionalized furamide derivatives is described. This involves reaction of N-alkyl-3-oxobutanamides, derived from the addition of amines to the diketene, and dibenzoylacetylene in the presence of triphenylphosphoine. The reactive 1:1 intermediate obtained from the addition of triphenylphosphine to dibenzoylacetylene was trapped by OH-acids such as N-alkyl-3-oxobutanamide to produce functionalized furamide derivatives.     

Pd(II)-catalyzed cascade Heck/intramolecular C(sp2)–H amidation reaction: An efficient route to 4-aryl-2-quinolinones

A Pd(II)-catalyzed cascade Heck/intramolecular C(sp²)–H amidation reaction is described for the synthesis of 4-aryl-2-quinolinone derivatives. Substituted cinnamamide containing 2-(pyridin-2-yl)ethanamine unit reacts with aryl iodide to form intermediate by Heck reaction. Then, the intermediate takes place intramolecular amidation via C(sp²)–H activated process promoted by orientation group.     

Synthesis of novel rhodanine based functionalized furans from the reaction of tert-butyl isocyanide with acetylenic esters in the presence of rhodanine acetic acid derivatives

The reactive 1:1 intermediate produced from the reaction of tert-butyl isocyanide and dialkyl acetylenedicarboxylates was trapped by rhodanine-N-acetic acid derivatives to generate polyfunctionalized furan rings in fairly good yields.     

Reaction of N-fluoropyridinium fluoride with isonitriles and TMSN3: a convenient one-pot synthesis of tetrazol-5-yl pyridines

Reaction of N-fluoropyridinium fluoride generated in situ with a series of isonitriles and TMSN₃ led to the formation of the corresponding tetrazol-5-yl pyridines in good yields (37-84%). A similar reaction sequence for quinoline yielded the respective derivatives of 2-quinoline. The proposed reaction mechanism involves the intermediate formation of a highly reactive carbene species.     

Copper-catalyzed acylations of o-vinylbenzylzirconocene intermediate and synthetic application toward steroid skeleton

Benzylzirconocene intermediate, which was readily prepared by a reaction of o-alkoxymethylstyrene with `Cp₂Zr' under mild conditions, reacted with acyl chlorides in the presence of a catalytic amount of CuBr-SMe₂ to give ketone derivatives in moderate to good yields.     

Enantioselective aza-Diels-Alder reaction of Brassard’s diene with aldimines catalyzed by chiral N,N′-dioxide-Yb(OTf)3 complex

The chiral N,N′-dioxide-Yb(OTf)₃ complex-catalyzed enantioselective aza-Diels-Alder reaction of Brassard’s diene with aldimines has been developed, giving the corresponding α,β-unsaturated δ-lactam derivatives in moderate yields with good enantioselectivities (up to 81% ee and up to 99% ee by single recrystallization) under mild conditions. Isolation of the reaction intermediate indicates that this asymmetric aza-Diels-Alder reaction proceeds through a stepwise Mannich-type pathway.     

Short and efficient synthesis of 2H-pyrroles from 7-oxanorbornadiene derivatives

A microwave-assisted tandem [3+2] cycloaddition/retro-Diels-Alder reaction of azomethine ylides derived from imines of α-amino esters to dimethyl 7-oxabicyclo[2.2.1]hepta-2,5-diene-2,3-dicarboxylate derivatives is described. The procedure delivers, in a short reaction time, pyrrolines in high yields. In a such sequence, the oxanorbornadiene derivatives behave as masked forms of dimethyl acetylenedicarboxylate. Subsequent oxidation of the synthesized 3-pyrrolines with DDQ affords 2H-pyrroles with yields in the 76-88% range. If this three-step sequence is run on the non-substituted 7-oxabicycloheptadienedicarboxylate, purification of the intermediate 3-pyrrolines is avoided to afford 2H-pyrroles in less than 2 h.     

A new modular and flexible approach to [1,2,3]triazolo[1,5-a][1,4]benzodiazepines

A new synthetic route for the access to [1,2,3]triazolo[1,5-a][1,4]benzodiazepines and other derivatives is described. This strategy is based on the cycloaddition of 2-oxoalkylidenephosphoranes to o-functionalized aryl azides followed by the reaction of the corresponding triazole intermediate with amines. This new approach presents unique properties such as regioselectivity, modularity, mild reaction conditions, and high yields.     

Intramolecular hydrogen abstraction promoted by N-radicals: synthesis of chiral 7-oxa-2-azabicyclo[2.2.1]heptane and 8-oxa-6-azabicyclo[3.2.1]octane ring systems

Homochiral 7-oxa-2-azabicyclo[2.2.1]heptane and 8-oxa-6-azabicyclo[3.2.1]octane ring systems can be synthesized by reaction of specifically protected phosphoramidate derivatives of carbohydrates with (diacetoxyiodo)benzene or iodosylbenzene and iodine. The reaction mechanism goes through homolytic fragmentation of a hypothetical iodoamide intermediate. The N-radicals so generated participate in an intramolecular hydrogen abstraction reaction (IHA) to give the aforementioned bicycles.     

1,3-Dipolar Cycloaddition of Difluoro-Substituted Azomethine Ylides. Synthesis and Transformations of 2-Fluoro-4,5-dihydropyrroles

2-Fluoro-4,5-dihydropyrrole-3,4-dicarboxylic acid derivatives were obtained by reaction of difluorocarbene with N-substituted ketone imines in the presence of fumaronitrile, maleonitrile, or dimethyl maleate. The reaction involves intermediate formation of azomethine ylides and their subsequent cycloaddition at the double bond. 11H-Dibenz[b,e]azepine and 3,4-dihydroisoquinolines react with difluorocarbene in the presence of fumaronitrile to give fluoro-substituted dibenzo[c,f]pyrrolo[1,2-a]azepine and pyrrolo[2,1-a]-isoquinoline derivatives. Treatment of 2-fluoro-4,5-dihydropyrrole-3,4-dicarbonitrile with amines and alkoxides affords the corresponding 2-amino- and 2-alkoxy derivatives, while its reactions with hydrazine hydrate and benzimidamide lead to formation of substituted pyrrolo[2,3-c]pyrazole and pyrrolo[2,3-d]-pyrimidine derivatives.     

A convenient synthesis of chiral amino acid derived 3,4-dihydro-2H-benzo[b][1,4]thiazines and antibiotic levofloxacin

A series of 3,4-dihydro-2H-benzo[b][1,4]thiazine derivatives 8a-g were synthesized via- a copper-catalyzed intramolecular N-aryl amination reaction on substituted 2-(2-bromophenylthio)-ethanamines which were synthesized by the nucleophilic substitution reaction of 2-bromobenzenethiol with Boc-protected amino alcohol derivatives. This strategy provides a short and an efficient entry to (S)-3-methyl-1,4-benzoxazine 12, an advanced synthetic intermediate for the synthesis of levofloxacin.     

Efficient one-pot synthesis of spiro[indoline-3,4′-pyrazolo[3,4-e][1,4]thiazepine]dione via three-component reaction

An efficient one-pot synthesis of spiro[indoline-3,4′-pyrazolo[3,4-e][1,4]thiazepine] dione derivatives via three-component reaction of 5-amino-3-methylpyrazole, isatin, and thioacid is described. This new protocol produces novel heptacyclic spirooxindole derivatives in good yields in comparison to conventional pentacyclic compounds. This method proceeds through a 3-(5-aminopyrazol-3-yl)-3-hydroxy-2-oxindoline intermediate (Baylis-Hillman type adduct), unlike 3-indolylimine (the intermediate like Shiff-Bases) as in conventional methods. The structure of one representative compound has been confirmed by X-ray diffraction analysis.     

Tandem one-pot synthesis of α-(aminomethylene)-γ-butyrolactones via regioselective epoxide ring-opening with the Blaise reaction intermediate

A novel tandem one-pot method for the synthesis of α-aminomethylene-γ-butyrolactone derivatives has been developed through the regioselective epoxide opening reactions with the Blaise reaction intermediates, generated by the reaction of a Reformatsky reagent with nitriles. Formation of a modified Blaise reaction intermediate by the addition of a stoichiometric amount of n-BuLi followed by slow addition of epoxide is required for the good yield of γ-butyrolactones.