Synthesis of 2-(1-Arylcarbonyl-1-arylazomethylidene)-imidazolidines by the Reaction of 2-(Arylcarbonyl-methylidene)imidazolidines with Diazobenzenes

A variety of 2-(1-arylcarbonyl-1-arylazomethylidene)-imidazolidines 3 were prepared by the reaction of 2-(arylcarbonylmethylidene)-imidazolidines 1 with diazobenzenes 2 in moderate to excellent yields.     

Synthesis of 2-(1-Arylcarbonyl-1-arylazomethylidene)-thiazolidines by the Reaction of 2-(Arylcarbonyl-methylidene)thiazolidines with Diazobenzenes

A variety of 2-(1-arylcarbonyl-1-arylazomethylidene)-thiazolidenes were synthesized in excellent yields by the reaction of 2-(arylcarbonylmethylidene)thiazolidines with diazobenzenes.     

Nucleophilic amination of 2-iodo-3-nitro-1-(phenylsulfonyl)indole

The reaction of 2-iodo-3-nitro-1-(phenylsulfonyl)indole (2) with amines affords the corresponding 2-amino-3-nitroindoles in excellent yields via nucleophilic aromatic substitution.     

AuCl(3)-catalyzed synthesis of highly substituted furans from 2-(1-alkynyl)-2-alken-1-ones

Highly substituted furans have been synthesized by the reaction of 2-(1-alkynyl)-2-alken-1-ones and various nucleophiles under very mild reaction conditions in good to excellent yields. Gold and some other transition metals are efficient catalysts for this reaction.     

2-Alkylindoles via palladium-catalyzed reductive cyclization of ethyl 3-(o-trifluoroacetamidophenyl)-1-propargyl carbonates

The reaction of ethyl 3-(o-trifluoroacetamidophenyl)-1-propargyl carbonates with formate anions in the presence of Pd(PPh₃)₄ affords 2-alkylindoles in good to excellent yields.     

Synthesis of spiro[4.5]trienones by intramolecular ipso-halocyclization of 4-(p-methoxyaryl)-1-alkynes

A wide variety of 3-halospiro[4.5]trienones are readily prepared in good to excellent yields by the intramolecular ipso-halocyclization of 4-(p-methoxyaryl)-1-alkynes under mild reaction conditions. ICl, I2, and Br2 are all effective electrophiles for this process under carefully optimized reaction conditions.     

A new route to the improved synthesis of 1-(alkoxymethyl)-5-alkyl-6-(arylselenenyl)uracils

A new route to C-6-selenenyl analogs of compound 1a from 5-alkyl-6-chlorouracils 6a-b has been described. A mild and highly efficient synthesis of 1-(alkoxymethyl)-5-alkyl-6-(arylselenenyl)uracils 8a-e has been accomplished from 6a-b in good yields using a two step procedure. Silylation of 5-alkyl-6-chlorouracils 6a-b using N,O-bis(trimethylsilyl)acetamide followed by regioselective alkylation of the silylated intermediate with ethyl or benzyl chloromethyl ether in dichloromethane afforded the desired 1-(alkoxymethyl)-5-alkyl-6-chlorouracils 7a-d in 88–94% yields. Compounds 7a-d readily underwent addition-elimination reaction with an appropriate arylselenol in the presence of ethanolic sodium hyroxide to produce the corresponding 1-(alkoxymethyl)-5-alkyl-6-(arylselenenyl)uracils 8a-e in excellent yields (94–99%).     

A stereoselective route to alkenyl sulfides through the palladium-catalyzed cross-coupling reaction of 9-alkyl-BBN with 1-bromo-1-phenylthioethene or (E)- and (Z)-2-bromo-1-phenylthio-1-alkenes

The reaction of 9-alkyl-9-BBNs with 1-bromo-1-phenylthioethene or (E)- and (Z)-2-bromo-1-phenylthio-1-alkenes takes place readily in the presence of Pd(PPh₃)₄ and sodium hydroxide to afford stereodefined vinylic sulfides in excellent yields.     

Efficient preparation of highly optically active (S)-(-)-2,3-allenols and (R)-(+)-2,3-allenyl acetates by a clean novozym-435-catalyzed enzymatic separation of racemic 2,3-allenols

Novozym-435 has been found to be an effective biocatalyst for the kinetic resolution of a series of racemic 2,3-allenols, affording highly optically active (S)-(-)-2,3-allenols and (R)-(+)-2,3-allenyl acetates in high yields and with excellent ee values. The reaction of 3-(n-butyl)-3,4-pentadien-2-ol (1 a) was successfully performed on a 10 g scale to afford the corresponding (S)-(-)-2,3-allenol (1 a) and (R)-(+)-2,3-allenyl acetate (2 a) in synthetically useful amounts and with high ee values. The advantages of this reaction are the ready availability of the starting materials, high stereoselectivities for both (-)-2,3-allenols and (+)-2,3-allenyl acetates, the use of a relatively high substrate concentration, and a lower catalyst loading. The resulting (S)-(-)-2,3-allenol 1 a can be converted into the corresponding chiral 2,5-dihydrofuran and the vinylic epoxide.     

Addition of Cl2C: to (-)-O-menthyl acrylate under sonication-phase-transfer catalysis. Efficient synthesis of (+)- and (-)-(2-chlorocyclopropyl)methanol

[reaction: see text] Dichlorocyclopropanation of (-)-O-menthyl acrylate under conditions of phase-transfer catalysis (CHCl3, KOH, tetramethylammonium bromide), with sonication, gives excellent yields (85-94%) of the corresponding dichlorocyclopropanecarboxylate ester compared to thermal conditions (90 degrees C, 56%). No diastereoselectivity was observed, but one isomer was isolated pure by fractional crystallization. The measured kinetic isotope effect (initial rate (CHCl3)/rate (CDCl3) approximately 1.7) suggests deprotonation of CHCl3 as the rate-limiting step.     

1-(2-Iodophenyl)-1H-tetrazole as a ligand for Pd(II) catalyzed Heck reaction

1-(2-Iodophenyl)-1H-tetrazole 2 was synthesized by the reaction of 2-iodoaniline, sodium azide and triethyl orthoformate in acetic acid. The newly synthesized ligand 2 was successfully used in Heck reaction to give the cross-coupled products in excellent yields.     

Isoprene-catalyzed lithiation of imidazole: synthesis of 2-(hydroxyalkyl)- and 2-(aminoalkyl)imidazoles

2-Lithioimidazole was prepared by means of a new protocol, which consists of a slight excess of lithium metal in the presence of a substoichiometric amount of isoprene (20 mol%) in THF at room temperature. By reacting this organolithium with carbonyl electrophiles 2-(hydroxyalkyl)imidazoles 3 were obtained, in good yields. As a result of the reaction of the mentioned lithium intermediate with imines 4, the corresponding 2-(aminoalkyl)imidazoles 5 were isolated in excellent yields.     

A multi-component synthesis of 3-aryl-1-(arylmethylideneamino)pyrrolidine-2,5-diones

A multi-component synthesis of 3-aryl-1-(arylmethylideneamino)pyrrolidine-2,5-diones is described. A mixture of N-isocyaniminotriphenylphosphorane, an aldehyde, and Meldrum's acid undergo a 1:2:1 addition reaction under mild conditions to afford the title compounds in good to excellent yields.     

Phosphomolybdic Acid: An Efficient and Recyclable Solid Acid Catalyst for the Synthesis of 4,4′-(Arylmethylene)bis(1H-pyrazol-5-ols)

An efficient and environmentally friendly method has been developed for synthesis of 4,4′-(arylmethylene)bis(1H-pyrazol-5-ols) by condensation reaction of aromatic aldehydes with 3-methyl-l-phenyl-5-pyrazolone in the presence of phosphomolybdic acid as a recyclable catalyst in ethanol at ambient temperature in excellent yields.     

Synthesis of 4-halophosphaisocoumarins via halocyclization of 2-(1-alkynyl)phenylphosphonates

A series of 4-halophosphaisocoumarins were prepared with high regioselectivity in good to excellent yields under mild conditions by the reaction of 2-(1-alkynyl)phenylphosphonic acid diesters with I₂ in CHCl₃ or ICl in CH₂Cl₂, or by the reaction of 2-(1-alkynyl)phenylphosphonic acid monoesters with NBS or NCS in DMF. Whether the alkynylphosphonates could cyclize or not was affected by the substituents, reaction solvents and electrophiles. A rationale for this reaction is discussed.     

Syntheses of 4-(2-hydroperoxy-2,2-diarylethyl)-3,5-dimethylpyrazoles, 4-(2-hydroxy-2,2-diarylethyl)-3,5-dimethylpyrazoles and the related compounds

The reactions of 1,1-disubstituted ethenes with 2,4-pentanedione in the presence of manganese(III) acetate and atmospheric oxygen yielded 4-acetyl-6,6-diaryl-3-methyl-1,2-dioxan-3-ols. The latter gave 4-(2-hydroperoxy-2,2-diarylemyl)-3,5-dimethylpyrazoles by the reaction with hydrazines in methanol-acetic acid (1:1 v/v) at 50° in 15-77% yields, or 4-(2-hydroxy-2,2-diarylethyl)-3,5-dimethylpyrazoles by the reaction with hydrazines in methanol in 2-78% yields. The acid-catalyzed reaction of 4-(2-hydroperoxy-2,2-diarylethyl)-3,5-dimethylpyrazoles yielded 4-(aroylmethyl)-3,5-dimethylpyrazoles (15-55%) and 4-(2,2-diarylethenyl)-3,5-dimethylpyrazoles (9-29%).     

Unexpected formation of (Z)-3-(halomethylene)isoindolinones from gem-dihalovinylbenzonitriles: efficient synthesis of enyne-containing isoindolinones

An efficient one-pot procedure for the regioselective synthesis of (Z)-3-(halomethylene)-isoindolin-1-ones was developed from easily accessible 2-(2,2-dihalovinyl)benzonitriles. From this key intermediate, a variety of isoindolinones containing an enyne moiety were synthesized in good to excellent yields via palladium-catalyzed Sonogashira reaction. The generated enyne-containing isoindolinones could be further manipulated by iodide induced cyclization reaction to afford a versatile synthetic intermediate 5H-pyrrolo[2,1-a]isoindolol-5-one in high yield and could be further elaborated.     

CU2O-Catalyzed C(SP3)-H/C(SP3)-H Cross-Coupling Using TEMPO: Synthesis of 3-(2-Oxoalkyl)-3-hydroxyoxindoles

A simple, convenient, and efficient oxidative cross-coupling reaction of oxindoles with ketones toward a variety of 3-(2-oxoalkyl)-3-hydroxyoxindoles in moderate to excellent yields has been developed. This transformation proceeds via a tandem oxidative cross-coupling by using 2,2,6,6-tetramethylpiperidine N-oxyl (TEMPO) in air as an environmentally benign oxidant. This methodology provides an alternative approach for the direct generation of all-carbon quaternary centers at the C3 position of oxindoles.     

Syntheses of 4-(1-alkynyl)-2(5H)-furanones and coumarins via the palladium catalyzed cross-coupling reactions of potassium alkynyltrifluoroborates

An efficient synthesis of 4-(1-alkynyl)-2(5H)-furanones has been developed utilizing a palladium catalyzed coupling reaction of β-tetronic acid bromide with potassium alkynyltrifluoroborates in the absence of base. 4-Alkynylcoumarins were also synthesized using this method. The reactions are straightforward and the yields are excellent.     

Novel one-pot multicomponent synthesis of (E)-2-(benzylideneamino)-5-mercapto-4H-1,2,4-triazol-3-yl)-2,3-dihydrophthalazine-1,4-dione derivatives

Abstract

An expeditious, one-pot multicomponent reaction has been developed for the synthesis of (E)-2-(benzylideneamino)-5-mercapto-4H-1,2,4-triazol-3-yl)-2,3-dihydrophthalazine-1,4-dione derivatives. Condensation of 4-amino-5-hydrazino-4H-1,2,4-triazole-3-thiol with phthalic anhydride and aromatic aldehyde afforded the (E)-2-(benzylideneamino)-5-mercapto-4H-1,2,4-triazol-3-yl)-2,3-dihydrophthalazine-1,4-diones in acetic acid medium with excellent yields. All the synthesized compounds were characterized by their analytical and spectral data.