Preparation of β-fluoro- and β,β-difluoro-histidinols

Nucleophilic attack of azide on 2-bromo-3-fluoro-3-(1-trityl-1H-imidazol-4-yl)-propan-1-ol (1a) in aprotic solvent occurs on the 2-position to give the 2-azido derivative (2a). Reduction of azide and removal of the trityl group produces β-fluorohistidinol (6a). Elimination of HBr from 1a followed by “FBr” addition to the resulting double bond gives 2-bromo-3,3-difluoro-3-(1-trityl-1H-imidazol-4-yl)-propan-1-ol (1b). Nucleophilic attack of azide followed by reduction and removal of the trityl group, as for the preparation of 6a, gives β,β-difluorohistidinol (6b). Initial attempts, under a variety of conditions, to oxidize the fluorinated histidinol precursors to carboxylic acids have not been successful.     

A Convenient Synthesis of β-Chloro, β-Methylthio α,β-Unsaturated Ketones from β-Oxodithioesters

The reaction of β-oxodithioesters with the Vilsmeier-Haack reagent prepared from POCl₃ and DMF provide β-chloro, β-methylthio α,β-unsaturated ketones in good yields.     

Syntheses of carbocyclic analogues of α-D-glucosamine, α-D-mannose, α-D-mannuronic acid, β-L-idosamine, and β-L-gulose

A versatile synthesis of orthogonally protected derivatives of carba-α-D-glucosamine, carba-α-D-mannose, carba-α-D-mannuronic acid, carba-β-L-idosamine, and carba-β-L-gulose from methyl α-D-mannoside is described. Our synthetic strategy utilizes the palladium-promoted Ferrier carbocyclization and persistent butane-2,3-diacetal protection to produce a key chiral cyclohexanone intermediate, from which all five carbasugar derivatives can readily be obtained.     

Synthesis of β,β‘-Difluorinated and β,β’-F-Dialkylated Acetals

Using the phase transfer catalysis technique, a series of fluorinated acetals has been prepared, in basic medium, by action of dicholromethane on 2-mononfluorinated alcohols or 1-F-alkyl 2-fluoroethanols. The identification of these new acetals has been achived by the study cf their ¹H, 19F NMR and their mass spectra.     

Mechanistic comparison of β-H elimination, β-OH elimination, and nucleophilic displacement reactions of β-hydroxy alkyl rhodium porphyrin complexes

This article reports on kinetic studies for three alternate pathways, including β-hydrogen elimination, β-hydroxy elimination, and intramolecular nucleophilic displacement reactions, for rhodium porphyrin β-hydroxy alkyl reactions in water and DMSO to form ketone, alkene, and epoxide, respectively. Comparisons of activation parameters for these processes indicate that the β-hydroxy elimination process has the lowest activation enthalpy in water, but the intramolecular nucleophilic displacement pathway predominates in DMSO.     

Metal-free,PTSA catalyzed facile synthesis of β-ketoacetal from β-chlorocinnamaldehyde

A toluene solution of β-chlorocinnamaldehyde and dihydroxy alcohols in the catalytic presence of para-toluenesulphonic acid (PTSA) yield the β-ketoacetal in good to outstanding amount. The catalyst (PTSA), first selectively protect the aldehydic group to form the β-chloroacetal and the subsequent dechlorination by H₂O result the β-ketoacetal. Significant transformation was achieved with electron donating substituent attached at the para-position of cinnamaldehyde. The selective formation of β-keto-1,3-acetal was also obtained with a mixture of 1, 2- and 1, 3- diol. The present reaction consists of a metal-free, economical, robustly feasible, sizeable functional group tolerance and high yield properties. Moreover, the use of different dihydroxy alcohols made this process more benign and valuable towards the metal-free development of ketones. First, of its kind, a rare and unusual multitasking nature of PTSA is observed.     

Stereoselective preparation of β,γ-methano-GABA derivatives

The Kulinkovich-de Meijere reaction between an unsaturated Grignard reagent and a chiral amide takes place with a high trans stereoselectivity and provides a convenient access to non-racemic trans cyclopropylamines. These compounds are transformed in four steps into the corresponding N-protected β,γ-methano-GABA derivatives, which are obtained for the first time in enantiomerically pure form. The corresponding transformations of the cis cyclopropylamine adducts are also described.     

Synthesis of phenols by the intramolecular condensation of β, β' ,δ ,δ'-tetraoxoalkanedioates a novel BF3 -promoted claisen condensation of

The aromatization process of β, β', δ , δ'-tetraoxoalkanedioates, which were synthesized by the BF₃-promoted Claisen condensation, was examined.     

The Synthesis of Substituted α, β-Butenolides from γ-Hydroxy-α, β-Acetylenic Esters

Abstract

The α, β-butenolide ring system is found in a number of physiologically important natural products² and there has been recent interest in the development of methods of synthesis of compounds of this type.³ It is well known that α, β-unsubstituted butenolides may be prepared by catalytic hydrogenation of γ-hydroxy acetylenic acids.^4,5b Recently, an excellent route of γ-hydroxy acetylenic esters which involves the addition of the lithium acetylide salts of propiolic esters to aldehydes⁵ and ketones⁶ has become available. We have carried out the addition of ethyl lithiopropiolate (1) to cyclohexanone (2) and 4-t-butylcyclohexanone (3) and wish to report the conversion of these adducts into corresponding β-methyl or β-methyl-α-allyl-α, β-butenolides.     

Crystal structures of layered zirconium pentafluorides of methylammonium,glycinium, and β-alanine

For the first time, new hybrid organic-inorganic layered zirconium pentafluorides of methylammonium, glycinium, and β-alanine with the composition (CH₃NH₃)ZrF₅·0.5H₂O, (H₃NCH₂COOH)ZrF₅·2H₂O, and (H₃N(CH₂)₂COOH)ZrF₅ are synthesized and their structures are analyzed. In the studied compounds, CN of the Zr atom is 8, and its coordination polyhedron represents a dodecahedron sharing its 6 vertex with three neighboring Zr polyhedra. The Zr dodecahedra are joined with each other in planar netlike anion layers of the composition _∞²[ZrF₅]⁻. The anion layers are hydrogen bonded into a three-dimensional structure by H₂O cations and molecules.     

Spectral studies of heterocyclic β-diketonates of actinide,lanthanide, and transition metals

The results of absorption spectral studies of the 1-phenyl-3-methyl-4-benzoyl-5-pyrazolone chelates of thorium, uranyl, neodymium, gadolinium, gallium, and iron are presented. These neutral chelates exhibit u.v. spectra very similar to that of the ligand, with slight bathochromic or hypsochromic shifts. The solution stability of the complexes in acetonitrile, ethanol, and chloroform was also studied and the lanthanide complexes were found to be the least stable. Sinha's parameter is calculated for the neodymium chelate to determine the relative degree of covalency upon complexation.     

Rapid, one-pot synthesis of β-siloxy-α-haloaldehydes

The Mukaiyama cross-aldol reaction of α-fluoro-, α-chloro-, and α-bromoacetaldehyde-derived (Z)-tris(trimethylsilyl)silyl enol ethers is described, furnishing anti-β-siloxy-α-haloaldehydes. A highly diastereoselective, one-pot, sequential double-aldol process is developed, affording novel β,δ-bissiloxy-α,γ-bishaloaldehydes. Reactions are catalyzed by C(6)F(5)CHTf(2) and C(6)F(5)CTf(2)AlMe(2) (0.5-1.5 mol %) and provide access to halogenated polyketide fragments.     

Highly Enantioselective Hydrogenation of β,β-Disubstituted Nitroalkenes

Building the building blocks: A highly enantioselective hydrogenation of β-aryl-β-alkyl disubstituted nitroalkenes 1 has been developed. This method results in enantiomerically pure nitroalkanes 2, which are versatile precursors for chemical synthesis.     

Iron-catalyzed asymmetric epoxidation of β,β-disubstituted enones

The combination of Fe(OTf)(2) and novel phenanthroline ligands enables the catalytic asymmetric epoxidation of acyclic β,β-disubstituted enones, which have been a heretofore inaccessible substrate class. The reaction provides highly enantioenriched α,β-epoxyketones (up to 92% ee) that can be further converted to functionalized β-ketoaldehydes with an all-carbon quaternary center.     

Triphenylphosphine-Catalyzed,Novel, One-Pot,Multicomponent Synthesis of Functionalized β-Acetamido Carbonyls

An efficient triphenylphosphine-catalyzed synthesis of β-acetamido carbonyls via multicomponent reaction of aromatic aldehydes, enolizable ketones or β-keto esters, acid chlorides and acetonitrile at room temperature is described. The process is remarkably simple, environmentally benign, and uses Lewis base for the first time in such type of reaction.     

Synthesis of pyridine derivatives by the three-component condensation of a β-dicarbonyl compound, β-enaminocarbonyl compound, and ethyl orthoformate

The major products of the three-component condensation of a -dicarbonyl compound, -enaminocarbonyl compound, and ethyl orthoformate are pyridine derivatives. The reaction of 1,3-cyclohexanedione or dimedone, the enamino ketones obtained from these diones, and ethyl orthoformate gives octahydroacridinediones, while the reaction of dimedone, ethyl -aminocrotonate, and ethyl orthoformate gives a tetrahydroquinoline derivative. The structures of the minor products were established in some cases. The reduction of 3,3,6,6-tetramethyl-1,2,3,4,5,6,7,8-octahydro-1,8-acridinedione by LiAlH₄ proceeds with retention of the pyridine ring and leads to the corresponding octahydroacridinediol.Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, 220141 Minsk, Belarus Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 774–781, June, 1999.     

Protecting group free, stereocontrolled synthesis of β-halo-enamides

Enamides, dienamides, and enynamides are important building blocks in synthetic, biological, and medicinal chemistry as well as materials science. Despite the extensive breath of their potential utility in synthetic chemistry, there is a lack of simple, high-yielding methods to deliver them efficiently and as single isomers. In this paper, we present a novel, protecting group free, efficient, and stereoselective approach to the generation of β-halo-enamides. The methodology presented provides a robust synthetic platform from which E- or Z-enamides can be generated in good yields and with complete stereocontrol.     

Expedient synthesis of β,β-disubstituted α-methylenepropionates

Baylis-Hillman alcohols are excellent sources of the allylic halides ArCHCH(CH₂X)(CO₂R) (X=Br, Cl; R¹=Me, Et, Bu^t). The Z double bond isomers are attained in high isomeric purity (>14:1, Z/E). The halides are chemo- and regiospecifically transformed into the acrylates (ArCHR²)C(CH₂)(CO₂R¹) on treatment with Zn(R²)₂ (R²=Me, Et, CH₂TMS, CH₂SiMe₂OMe) or PrZnBr in the presence of catalytic amounts of copper(I) salts (0.5-20 mol%) in high yield.     

Regioselective synthesis of β-fluoro-α,β-unsaturated ketones by the reaction of β-diketones with DFMBA

The deoxyfluorination reaction of β-diketones with N,N-diethyl-α,α-difluoro-m-methylbenzylamine (DFMBA) gave β-fluoro-α,β-unsaturated ketones in good yields. The reaction proceeded regioselectively, and only one regioisomer was obtained from the unsymmetrical 1-aryl-1,3-diketones. The reaction is applicable to diketones with a trifluoromethyl group, obtaining good yields of 3,4,4,4-tetrafluorobutenones. We used the resulting β-fluoro-α,β-unsaturated ketones for the reaction with lithium dialkyl cuprates.