Enantioselective gem-chlorofluorination of active methylene compounds using a chiral spiro oxazoline ligand

Highly enantioselective gem-chlorofluorination of active methylene compounds was carried out by using a copper(II) complex of a chiral spiro pyridyl monooxazoline ligand. This reaction yielded α-chloro-α-fluoro-β-keto esters and α-chloro-α-fluoro-β-keto phosphonates with up to 92% ee. The resulting dihalo β-keto ester was converted into various α-fluoro-α-heteroatom-substituted carbonyl compounds via nucleophilic substitution without loss of optical purity. A fully protected β-amino acid with a gem-chlorofluoromethylene function was also synthesized.     

Synthesis of novel cyclic sulfone dihydropyridines facilitated by a selective ethyl diazoacetate ring expansion

A series of novel cyclic sulfone dihydropyridines with five to nine membered rings have been synthesized. Anomalous intermediates isolated from the Hantzch condensation were found to vary depending on the sulfone ring size and aromatic substitution. Tin tetrachloride has been shown to be a superior Lewis acid catalyst for ethyl diazoacetate ring expansion of the requesite β-keto cyclic sulfone precursors.     

Influence of β-cyclodextrin on the protolytic and complexing ability of p-aminobenzoic acid

UV spectroscopy was used to study the protolytic properties and determine the ionization constants of p-aminobenzoic acid in the presence of β-cyclodextrin. Formation of supramolecular structures of 1: 1 composition was established. Stability constants of the β-cyclodextrin-p-aminobenzoic acid inclusion complex were calculated, as were the thermodynamic parameters (ΔG°, ΔH°, and ΔS°) of its formation. The complexing process between β-cyclodextrin and p-aminobenzoic acid was found to occur spontaneously in the temperature range under investigation while being accompanied by energy liberation and leading to a reduction in the system’s entropy.     

Lewis acid-catalyzed one-pot sequential reaction for the synthesis of α-halogenated β-keto esters

A Lewis acid-catalyzed one-pot sequential transformation of β-keto esters, aromatic aldehydes, and NCS/NBS was reported. The reaction proceeds by way of Knoevenagel condensation/Nazarov cyclization/halogenation to give α-chloro- and α-bromo-β-keto esters in moderate yields with high diastereoselectivities. However, several aromatic aldehydes with electron-withdrawing substituents afforded unexpected α,β′-dichloro-β-keto esters in good to high yields.     

Efficient sulfonylation of ketones with sodium sulfinates for the synthesis of β-keto sulfones

The oxidative sulfonylation of ketones with sodium sulfinates as the sulfone source and DMSO as the oxidant is reported. A series of β-keto sulfones were obtained in good to excellent yields. The advantages of this efficient protocol include the low cost of DMSO and HBr, and a broad scope.     

Favorskii Rearrangement in the Reaction of 3-(1-Adamantyl)-1-chloro-2-propanone with Amines

The reaction of 3-(1-adamantyl)-1-chloro-2-propanone with amines [diethylamine, (1-adamantyl)methylamine, p-toluidine, and piperidine] in diethyl ether at room temperature involves the Favorskii rearrangement and yields N,N-disubstituted amides of 3-(1-adamantyl)propanoic acid.     

Film Composites of polyimide with polyaniline and poly(aniline-<Emphasis Type="Italic">co</Emphasis>-anthranilic acid)

New two-component composite polymer films are prepared and studied in terms of thermal stability and stress-strain properties. The matrix component of the composite is polyimide based on 3,3′,4,4′-(1,3-diphenoxybenzene)tetracarboxylic dianhydride and 4,4′-bis(4″-aminophenoxy)diphenyl sulfone. Another component is polyaniline or the copolymer poly(aniline-co-2-aminobenzoic acid). Composite films are cast from mixed solutions of individual polymers in N-methyl-2-pyrrolidone. Interpolymer interactions in polyimide composites with polyaniline or the copolymer of aniline and 2-aminobenzoic acid are investigated via viscometry and IR spectroscopy. The thermal treatment of composite films with poly(aniline-co-2-aminobenzoic acid) results in decarboxylation of the copolymer and formation of polyimide-polyaniline composite films. The morphology, microphase structure, and porosity of the composite films are different from those of the films cast from solutions of polyimide-polyaniline mixtures.     

Synthesis of 1-aryl-5-arylazo-3-phenylsulfonylpyrazol-4-ols from 1-chloro-3-phenylsulfonyl-2-propanone

Treatment of 1-chloro-3-phenylsulfonyl-2-propanone (2) with arenediazonium chlorides gave 1-arylhydrazono-3-chloro-1-phenylsulfonyl-2-propanones 4 , which were cyclized in the presence of sodium acetate to 1-aryl-3-phenylsulfonylpyrazol-4-ols 5B. Further treatment of 5B with arenediazonium chlorides yielded 1-aryl-5-arylazo-3-phenylsulfonylpyrazol-4-ols.     

An easy preparation of per- and poly-fluoroalkyl propenyl sulfones

Sodium tridecafluorohexanesulfinate (1a) and sodium 1-chloro-2,2,2-trifluoroethanesulfinate (1b) were prepared by the treatment of 1-iodo-tridecafluorohexane and 1-bromo-1-chloro-2,2,2-trifluoroethane with sodium dithionite in a water-acetonitrile solution. Prolonged reaction of 1a with allyl bromide in DMF afforded tridecafluorohexane 1-propenyl sulfone 2 as the only product in good yield. A similar treatment of 1b gave exclusively 1-chloro-2,2,2-trifluoroethane 3-propenyl sulfone 4. Bromination of 4 followed by dehydrobromination with Et₃N resulted in a mixture of 1-chloro-2,2,2-trifluoroethane 3-bromo-1-propenyl sulfone 6 and 1-chloro-2,2,2-trifluoroethane 2-bromo-3-propenyl sulfone 7, while dehydrobromination with pyridine gave sulfone 6 practically as the only product. α,β-Unsaturated sulfones 2 and 6 were shown to be active dienophiles.     

General and systematic synthetic entry to carotenoid natural products

A general synthetic method of carotenoid natural products has been developed, in which the systematic chain extension and termination processes were applied. The syntheses of the chain extension and termination units were greatly improved by the use of the common intermediate, 1-bromo-4-chloro-3-methyl-2-butene (8), in a short and highly efficient way. The C₁₀ chain initiation β-cyclogeranyl sulfone (3) was coupled with the C₅ chain extension unit to give the C₁₅ chain-extended allylic sulfone after chemoselective sulfide oxidation. This chain-extended C₁₅ allylic sulfone underwent the Julia olefination reaction with the C₅ and the C₁₀ chain termination units to give retinol (1) and β-carotene (2), respectively.     

Enhanced dissolution of copolymers bearing photobase- or photoacid-generating groups in polar solvents by photochemical formation of ionic pairs

Solubility changes in the irradiation of copolymers bearing photoacid- or photobase-generating groups and low molecular weight photobase generators (PBGs) or photoacid generators (PAGs) were investigated. Copolymers bearing acyloxyimino (AOI) groups were used as those generating pendant amino groups photochemically. Copolymers bearing o-nitrobenzyloxycarbonyl and imino sulfonate groups were used as those generating carboxy and sulfo groups, respectively. The solubility of copolymers bearing AOI groups into polar solvents was enhanced by added PAGs such as β-keto sulfones or imino sulfonates after irradiation. A similar enhancement was observed in copolymers bearing o-nitrobenzyloxycarbonyl groups in the presence of PBGs such as oxime esters or o-nitrobenzyl carbamates. These results showed that the formation of acid–base pairs on irradiation was effective for dissolution into polar solvents. Copolymers bearing imino sulfonate groups showed a high solubility, and no such enhancement was observed by PBG. Films of copolymers bearing β-keto sulfone groups became insoluble because of crosslinking. © 2001 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 39: 1708–1715, 2001     

Quinolactacin Biosynthesis Involves Non-Ribosomal-Peptide-Synthetase-Catalyzed Dieckmann Condensation to Form the Quinolone-γ-lactam Hybrid

Quinolactacins are novel fungal alkaloids that feature a quinolone-γ-lactam hybrid, which is a potential pharmacophore for the treatment of cancer and Alzheimer's disease. Herein, we report the identification of the quinolactacin A2 biosynthetic gene cluster and elucidate the enzymatic basis for the formation of the quinolone-γ-lactam structure. We reveal an unusual β-keto acid (N-methyl-2-aminobenzoylacetate) precursor that is derived from the primary metabolite l -kynurenine via methylation, oxidative decarboxylation, and amide hydrolysis reactions. In vitro assays reveal two single-module non-ribosomal peptide synthetases (NRPs) that incorporate the β-keto acid and l -isoleucine, followed by Dieckmann condensation, to form the quinolone-γ-lactam. Notably, the bioconversion from l -kynurenine to the β-keto acid is a unique strategy employed by nature to decouple R*-domain-containing NRPS from the polyketide synthase (PKS) machinery, expanding the paradigm for the biosynthesis of quinolone-γ-lactam natural products via Dieckmann condensation.     

Synthesis of 1-aryl-5-chloro-3-(phenylsulfonyl)pyrazol-4-ols from 1,1-dichloro-3-phenylsulfonyl-2-propanone

1,1-Dichloro-3-phenylsulfonyl-2-propanone was treated with arenediazonium chlorides to give 1-arylhydrazono-3,3-dichloro-1-phenylsulfonyl-2-propanones, which were cyclized to 1-aryl-5-chloro-3-(phenylsulfonyl)pyrazol-4-ols on treatmemt with base.     

Amine-induced rearrangements of 2-bromo-1-(1H-indol-3-yl)-2-methyl-1-propanones: A new route to α-substituted indole-3-acetamides, β-substituted tryptamines, α-substituted indole-3-acetic acids and indole β-aminoketones

The reaction of 2-bromo-1-(1H-indol-3-yl)-2-methyl-1-propanone ( 1 ) and 2-bromo-1-(1-methyl-1H-indol-3-yl)-2-methyl-1-propanone ( 2 ) with primary amines proceeds in good yields to produce rearranged amides by a proposed pseudo-Favorskii mechanism. These amides in turn can either be reduced to produce β-substituted tryptamines or hydrolyzed to produce substituted indole-3-acetic acids. When the reaction is carried out using bulky primary or secondary amines, β-aminoketones are produced by elimination of hydrogen bromide followed by Michael addition. When hindered secondary amines or tertiary amines are used, elimination to the α,β-unsaturated ketones occurs.     

An efficient synthesis of 6-formyl-1,2-dihydro-2-oxo-3-pyridinecarboxylic acid and some carbonyl derivatives of it and its 6-acetyl homologue

Starting with 1,1-dimethoxy-2-propanone ( 1 ), 6-formyl-1,2-dihydro-2-oxo-3-pyridinecarboxylic acid ( 5a ) has been prepared in large quantities by a highly efficient, 4-step synthesis. This compound, along with its one carbon homologue, 6-acetyl-1,2-dihydro-2-oxo-3-pyridinecarboxylic acid ( 5b ) has been reacted with several carbonyl derivative forming reagents to provide a series of side chains for β-lactams. Among these carbonyl derivatives are styrylamides which were prepared from Wittig and Horner-Emmons reagents. The preparation of the phosphonium salts and phosphonate esters is also described.     

Palladium(II)-assisted conversion of a 2-alkenyl sulfone into a 3-acetoxy(or chloro)-1-alkenyl sulfone

2-alkenyl p-tolyl sulfone was converted into the corresponding 3-acetoxy-1-alkenyl p-tolyl sulfone via a π-allyl palladium complex which underwent regiospecific attack of a nucleophile, acetate ion, and the reaction conditions for predominant formation of 3-chloro-1-alkenyl p-tolyl sulfone are also described.     

m-Aminobenzoic acid inserted β-turn in acyclic tripeptides: a peptidomimetic design

X-ray diffraction studies show that peptides Boc-Leu-Aib-m-ABA-OMe (I) (Aib, α-aminoisobutyric acid; m-ABA, meta-aminobenzoic acid) and Boc-Phe-Aib-m-ABA-OMe (II) adopt a type-II β-turn conformation, solely stabilized by co-operative steric interactions amongst the amino acid residues. This type of β-turn without any intramolecular hydrogen bonding is generally referred to as an open turn. Although there are some examples of constrained cyclic peptides in which o-substituted benzenes have been inserted to mimic the turn region of the neurotrophin, a nerve growth factor, peptides I and II present novel two examples where m-aminobenzoic acid has been incorporated in the β-turn of acyclic tripeptides. The result also demonstrates the first crystallographic evidence of a β-turn structure containing an inserted m-aminobenzoic acid, which can be considered as a rigid γ-aminobutyric acid with an all-trans extended configuration.     

Differentiation effect of solvents on the keto-enol equilibrium of heterocyclic β-dicarbonyl compounds

The differentiation effect of a solvent on the equilibrium of five- and six-membered heterocyclic β-keto esters and β-diketones containing =O, =S, =SO, =NR, =NRHC1, and -S-C(R)₂-S-fragments and, for comparison, on the equilibrium of aliphatic and carbocyclic β-keto esters and β-diketones was studied. The differentiating effect of a solvent is explained by different kinds of solvation of the heteroatomic fragments in the ketone and enol forms of heterocyclic β-dicarbonyl compounds.     

Synthesis of 5-polyfluoroalkyl-4-( p -tolyl-sulfonyl)pyrazoles and 4-polyfluoroalkyl-5-( p -tolylsulfonyl)pyrimidines from 1-dimethylamino-2-( p -tolylsulfonyl)-polyfluoro-1-alken-3-ones

1-Dimethylamino-2-(p-tolylsulfonyl)polyfluoro-1-alken-3-ones were obtained from hydrates of 3,3,3-trifluoro-1-(p-tolylsulfonyl)-2-propanone and 3,3,4,4,5,5-hexafluoro-1-(p-tolylsulfonyl)-2-pentanone under conditions of the Vilsmeier-Haack-Arnold reaction. The analogous reaction of 3,3-difluoro-1-(p-tolylsulfonyl)-2-propanone hydrate leads to 3-chloro-1-dimethylamino-4,4-difluoro-2-(p-tolylsulfonyl)-1,3-butadiene. The feasibility of using 1-dimethylamino-2-(p-tolylsulfonyl)-polyfluoro-1-alken-3-ones in reactions with nitrogen binucleophiles has been demonstrated for the regioselective synthesis of pyrazoles and pyrimidines. The structure of 1-phenyl-4-(p-tolylsulfonyl)-5-trifluoromethyl-1H-pyrazole was confirmed by X-ray diffraction structural analysis. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1052–1058, July, 2007.