Synthesis and Crystal Structure of (Z)-Ethyl 5-(phenylamino)-3-(phenylimino)-3H-1,2-dithiole-4-carboxylate

The compound (Z)-ethyl 5-(phenylamino)-3-(phenylimino)-3H-1,2-dithiole-4-carboxylate 3 has been synthesized by the reaction of ethylacetoacetate 1 and phenylisothiocyanate 2. Its structure has been established by ¹H NMR, ¹³C NMR, infrared, mass spectra, and x-ray crystallography.      

Stereoselective Synthesis and Characterization of (Z)-(−)-4-(1′-Alkoxyl-1′-alkyloxycarbonyl-methylidene)-5(R)-[(1R)-menthyloxy]-γ-butyrolactones

Abstract

A series of enantiomerically pure (Z)-(?)-4-(1′-alkyloxy-1′-alkyloxycarbonyl-methylidene)-5(R)-[(1R)-menthyloxy]-γ-butyrolactones were synthesized and characterized in good to excellent yields via O-alkylation of (4R,5R)-(?)-4-ethoxyoxalyl-5-[(1R)-menthyloxy]-γ-butyrolactone with alkyl halides in the presence of K₂CO₃ in acetone at room temperature.     

Sonogashira Coupling Offers a New Synthetic Route to Thieno[2,3-c]pyrazoles

Abstract

1,3-Disubstituted-5-chloro-4-iodopyrazoles are selectively coupled with phenylacetylene under typical Sonogashira reaction conditions [PdCl₂(PPh₃)₂, CuI, Et₃N, dimethylformamide (DMF)] to obtain the corresponding 5-chloro-4-(phenylethynyl)pyrazoles in good yield. The latter are smoothly cyclized with Na₂S in DMF into the corresponding thieno[2,3-c]pyrazoles. Detailed spectroscopic investigations (¹H, ¹³C, and ¹⁵N NMR, mass, and infrared) of all compounds are reported.     

Synthesis of Heterocyclic Compounds Using Amidines as Their Ene-1,1-diamine Tautomers,IV: Synthesis of N-Bridged Heterocycles 1,2,3,4-Tetrahydropyrido[1,2-a]pyrimidin-6-ones and Methyl 1,2,3,4-Tetrahydropyrrolo[1,2-a]pyrimidin-7-ylideneacetates

2-Benzyl-1,4,5,6-tetrahydropyrimidines 1 (as ene-1,1-diamine N,C-tautomers) in diglyme reacted with ethyl benzoylacetate at 160 °C in an oil bath to give 1,2,3,4-tetrahydropyrido[1,2-a]pyrimidin-6-ones 3 and with dimethyl acetylenedicarboxylate in methanol at room temperature, leading to methyl 1,2,3,4-tetrahydropyrrolo[1,2-a]pyrimidin-7-ylideneacetates 5, respectively.      

A New Approach to the Efficient Method for the Asymmetric Synthesis of (S)-O-, M-, P-Fluorophenylalanines and Their 2-Methyl-substituted Analogs

Abstract

The reactions of asymmetric C-alkylation of glycine and alanine in Ni^II complexes of their Schiff's bases with modified chiral auxiliaries (S)-2-N-[(N′-2-chlorobenzylprolyl)amino]benzophenone and (S)-2-N-[N′-(3,4-dimethylbenzylprolyl)amino]benzophenone by fluorine-substituted benzyl halogenides have been studied. As a result, a highly stereoselective and relatively rapid method for the asymmetric synthesis of (S)-o-, m-, p-fluorophenylalanines and their 2-methyl substituted analogs has been developed.     

Stannous Chloride–Promoted Synthesis of S-Allyl-N-aryl Dithiocarbamates under Solvent-Free Conditions

Abstract

A highly efficient method of synthesis of S-allyl-N-aryl dithiocarbamates using SnCl₂ as a catalyst under solvent-free conditions is described. The mild reaction conditions, high yields, and shorter reaction period illustrate the good synthetic utility of this method.     

Sigmatropic Rearrangement of Ammonium Ylides—Key Step in the Synthesis of Methyl 2-Formylphenyl Acetate

N-Cyanomethyl-N,N-dimethyl-N-(α-methoxycarbonyl)benzylammonium salts 5 were synthesized and treated with different base/solvent systems, giving the products of sigmatropic rearrangements [2,3] 7 and [1,2] 8. In reactions carried out in liquid ammonia, [2,3] rearrangement definitively prevailed. Pure 7(or mixture of 7 and 8) were deprotected to afford methyl 2-formylphenyl acetate (9) in good yield.      

Synthesis of the Precursor of K252a and Its Analogs

A practical and efficient asymmetric synthesis of the key precursor furanose 3 for the synthesis of K252a and CEP-701 has been achieved in nine steps with an overall yield of 12.8% from (R)-methyl β-hydroxytetradecanoate 5, an industrial intermediate for production of orlistat.      

Regioselective Intramolecular Carbon-Hydrogen Insertion in Copper-Catalyzed Carbenoid Decompositions of cis-1-Methyl-3-Arylcyclohexane-1-Diazomethyl Ketones : Some Synthetic Applications

Recently, we have developed¹ a new route for the stereo-specific introduction of an angular carboxyl or functionalized methyl groups² in a rigid hydrophenanthrene moiety. The key step in this approach is a regioselective intramolecular α-keto carbenoid insertion across the benzylic C-H bond (at C-4a) in CuSO₄-catalyzed thermal decomposition of the diazoketones and to the corresponding tetracyclic ketones and in moderate to good yields. A modified procedure³ of carbenoid decomposition of these diazoketones, in the presence of Cu₂O under irradiation with tungsten filament lamp, improves the yields of the desired C-H insertion products. Thus, the ketones and have been prepared now in consistently higher yields (53-55%) from the pure diazoketones , m.p. 125-127°, and , m.p.     

Water-Promoted,Silver–Phosphine Complex–Catalyzed Stereoselective Cyclization of 2-(1-Hydroxy-3-arylprop-2-ynyl)phenols Leading to a Highly Efficient Approach to Aurones

Silver–phosphine complexes can be utilized as highly efficient catalysts for the cyclization of 2-(1-hydroxy-3-arylprop-2-ynyl)phenols (1) to give product 2, key intermediates to synthesize aurones (4), with good yields and stereoselectivities in water–toluene mixed solvent. With fluoride as the counteranion, complete E- or Z- stereoselectivities were achieved at high temperature or room temperature, respectively. Furthermore, after removing water from the reaction mixtures, the toluene solution containing crude products 2 can be treated by MnO₂ directly without further purification, to give aurones 4 in good yields.      

Task-Specific Ionic Liquid as the Recyclable Catalyst for the Rapid and Green Synthesis of Dihydropyrano[3,2-c]chromene Derivatives

Abstract

A task-specific ionic liquid, [H₃N⁺–CH₂–CH₂–OH][CH₃COO^?], was successfully applied as an efficient and reusable catalyst for the one-pot domino to approach to dihydropyrano[3,2-c]chromene derivatives with atom economy in a condensation reaction of 4-hydroxycoumarin, aldehydes, and malononitrile in a combinatorial fashion. The reaction gave excellent yields within short reaction times at room temperature under solvent-free grinding conditions. The products and ionic liquid could be conveniently separated from the reaction mixture, indicating that the whole process was performed as a green chemical transformation.      

The Reaction of 2-Arylvinamindinium Perchlorates with Sodium Borohydride and Sodium Cyanoborohydride

In the last few years, numerous efforts have been directed to the development of acetonylation methods¹. Recent works in this laboratory have shown that O, O-t-butyl and O-isopropenyl peroxycarbonate 1 can be regarded as a good acetonylation reagent; its decomposition in solution results in the substitution of an hydrogen atom by an acetonyl group on each compound Σ-H able to undergo free radical addition reactions to alkenes². The following free radical chain reaction mechanism has been proposed:      

Excellent Synthesis of Adipic Acid

Abstract

A simple, straightforward, and environmentally benign protocol for the synthesis of adipic acid from oxidation of cyclohexanone with Oxone® in the presence of 0.5 mol% RuCl₃ · nH₂O is reported. The reaction completes within a very short time even at room temperature. The generality of the method is shown successfully for synthesis of other C-5 to C-8 dicarboxylic acids.     

L-Proline-Catalyzed Synthesis of Novel 5-(1H-Indol-3-yl-methylene)-thiazolidine-2,4-dione Derivatives as Potential Antihyperglycemic Agents

Knoevenagel condensation between indole-3-aldehyde 1 and an active methylene group containing 2,4-thiazolidinedione 2 in refluxing toluene using L-proline as a catalyst yielded 3, which on alkylation using 2 equivalents of alkylating agent under phase-transfer-catalyzed (PTC) conditions using K₂CO₃ as a base in dimethylformamide gave N,N^I-symmetrically disubstituted 5-(1H-indol-3ylmethylene)-thiazolidine-2,4-diones 4. Alternately, 4 can be synthesized by condensing 5 and 6 in a single step. Using this synthetic strategy, N,N^I-unsymmetricallydisubstituted derivatives 9a–f were prepared either by condensing 6 with N-substituted-2,4-thiazolidinedione 5 to obtain 7 followed by alkylation under PTC conditions or condensing 6 with N-unsubstituted- 2,4-thiazolidinedione 2 to yield 8 followed by alkylation under PTC conditions. The latter are the dehydro analogs of the dihydro-N-substituted-5-(1H-indol-3-yl-methylene)-thiazolidine-2,4-diones, which are potential antihyperglycemic agents.

Efficient,Stereoselective Approach to the Synthesis of 3-(1-Phenyl-2-(Z-styrylsulfonyl)-1H-imidazol-4-yl)-2H-chromen-2-ones

Reaction of phenyl acetylene with 3-(1-aryl-2-mercapto-4-imidazolyl)-2H-1-benzopyran-2-ones (4) in the presence of sodium hydroxide in absolute ethanol led to the formation of 3-(1-phenyl-2-(Z-styrylthio)-1H-imidazol-4-yl)-2H-chromen-2-ones (6) in excellent yields. These, on further oxidation with H₂O₂/AcOH, gave the corresponding sulfones (7) with retention of stereochemistry.