Investigation of the selective reduction of isatin derivatives. Synthesis of α-hydroxyacetophenone derivatives and ethyl spiro-3,3-(ethylenedioxy)-2-hydroxyindoline carboxylates

The product from the reduction of ethyl spiro-3,3-(ethylenedioxy)-2-oxindole carboxylates (1) using borohydride salts has been found to be dependant upon both solvent and metal ion. With polar solvents and lithium bromide/sodium borohydride, spiro-3,3-(ethylenedioxy)-2-hydroxyindole carboxylates (2) are obtained in high yields whilst [2-(2-hydroxymethyl-[1,3]dioxolan-2-yl)-phenyl]-carbamic acid ethyl esters (3) are obtained using sodium borohydride in less polar solvents.     

An efficient synthesis of cholanic acids from 20-ketopregnanes

An efficient synthesis of 3β-hydroxy-5-cholanic acid (8) and 3β-hydroxy-Δ⁵-cholanic acid (16) was carried out starting from 5-dihydropregnenolene (1) and pregnenolone (9). The monoacetates (3 and 11), prepared by Grignard reaction of 1 and 9 with 3,3-ethylenedioxypropylmagnesium bromide followed by acetylation, were dehydrated selectively to give the Δ²⁰⁽²²⁾-compounds (4 and 12) which on hydrogenation followed by acid treatment and Jones oxidation yielded 8 and 16, respectively.     

On the Diastereoselectivity of the Aqueous-Acid-Catalyzed Intramolecular Aldol Condensation of 3-Oxocyclohexaneacetaldehydes

The factors responsible for the diastereoselective formation of the 6-endo-hydroxybicyclo[2.2.2]octan-2-one by acid-catalyzed intramolecular aldol reaction of 3-oxocyclohexaneacetaldehydes have been investigated. This study, carried out on (1SR,4RS,6RS)-6-hydroxybicyclo[2.2.2]octan-2-one 1a , (1SR,4RS,6SR)-6-hydroxybicyclo[2.2.2]octan-2-one 1b , and 3,3-(ethylenedioxy)cyclohexaneacetaldehyde 2a , allowed to demonstrate the absence of intramolecular H-bonding in 1a as a stabilizing factor, and to ascertain the presence of unfavorable steric interactions in 1b .     

Lipase-catalysed resolution of 3,3′-bi-indolizines: The first preparative access to enantiomerically pure samples

The lipase-catalysed kinetic resolution of the axially chiral 3,3′-bis[1-(2-hydroxyethyl)-2-phenylindolizine] [(±)-1a] and the corresponding 3-hydroxypropyl derivative (±)-1b by acylation with vinyl acetate in the presence of lipases from different origins has been investigated. For the first time, enantiomerically pure 3,3′-biindolizine derivatives were obtained on a preparative scale by careful monitoring of the conversion.     

Chains, ladders and sheets of d metal–organic polymers generated from the flexible bipyridyl ligands

By use of the three-layer diffusion method, reactions of flexible bipyridyl ligands (4,4′-bpp or 3,3′-bpp) with M(II) salts (M = Zn, Cd) and multi-carboxylate ligands resulted in the formation of four interesting d¹⁰ metal–organic coordination polymers: [Zn(μ-4,4′-bpp)Br₂]_n (1), [Zn(μ-4,4′-bpp)(1,2-bdc)]_n · nH₂O (2), [Zn(μ-3,3′-bpp)(1,3-bdc)]_n · nCH₃OH · 2nH₂O (3) and [Cd(μ-3,3′-bpp)(C₄H₂O₄)]_n · 3nH₂O (4) (4,4′-bpp = 2,2′-bis(4-pyridylmethyleneoxy)-1,1′-biphenylene; 3,3′-bpp = 2,2 ′-bis(3-pyridylmethyleneoxy)-1,1′-biphenylene; bdc=benzenedicarboxylate, C₄H₄O₄ = fumaric acid). Complex 1 has a 2D sheet structure consisting of two unusual zigzag Zn(II) chains which are nearly perpendicular to each other. Complex 2 is comprised of two-leg ladders, in which [Zn(4,4′-bpp)] chains serve as the side rails and 1,2-bdc ligands serve as the cross rungs. In complex 3, every two 1,3-bdc ligands connect the neighbouring Zn(II)-3,3′-bpp dimetallic rings in η¹ coordination modes into an interesting chain structure. Complex 4 consists of an anionic macrocycle-containing cadmium dicarboxylate sheets that are separated by 3,3′-bpp. These d¹⁰ metal complexes exhibit high thermal stabilities and strong luminescence efficiencies.     

New atropisomeric N-N ligands for CO/vinyl arene copolymerization reaction

New atropisomeric bidentate bipyridine-based ligands (3,3'-(ethylenedioxy)-2,2'-bipyridine 4; 3,3'-(propylenedioxy)-2,2'-bipyridine 4; 3,3'-(butylenedioxy)-2,2'-bipyridine 5) containing a bridge between the 3,3' positions of the aromatic rings have been prepared. Together with the previously reported analogous ligands ((R)-3,3'-(1-methylethylenedioxy)-2,2'-bipyridine) 1and ((S,S)-3,3'-(1,2-dimethylethylenedioxy)-2,2'-bipyridine) 2, they were used to synthesize the corresponding bis-chelated dicationic complexes [Pd(N-N)2][PF6]2. Crystal structures and comparison of the data obtained by X-ray analysis on four of these complexes is reported. These palladium compounds were used as precatalysts in the CO/styrene and CO/4-Me-styrene copolymerization reactions, where they showed that small variations in the ligand backbone remarkably affects the productivity of the catalytic system.     

Oligomeric flavanoids. Part 13. Synthesis of profisetinidins based on (−) robinetinidol and (+) -epifisetinidol

Acid-catalyzed condensation of (+)-mollisacacidin-[(2R, 3S, 4R)-2, 3-trans-3, 4-trans-flavan-3,3′,4,4′,7-pentaol] with an excess of (−)-robinetinidol[(2R,3S)-2,3-trans-flavan-3,3′,4′,5′,7-pentaol] afforded a novel series of bi-, tri-, and tetraflavanoid profisetinidins. They are accompanied by (−)-fisetinidol-(4,2′)-(−)-robinetinidol which results from the pyrogallol B-ring of (−)-robinetinidol serving as nucleophile competing with its resorcinol A-ring in coupling with a C-4 carbocationic intermediate. Similar condensation with (+)-epifisetinidol[(2S,3S)-2,3-cis-flavan-3,3′,4′,7-tetraol] led to the exclusive formation of [4,6]-interflavanyl bonds, these units being ‘linearly’ arranged in the tetraflavanoid analogue in contrast to the ‘branched’ nature of the (−)-robinetinidol homologue.     

3-acyl-1,5-benzodiazepines in the reactions of 5,5-dimethyl-2-formylcyclohexane-1,3-dione with certain 1,2-diaminobenzenes

Reaction of 5,5-dimethyl-2-formylcyclohexane-1,3-dione with 4-methyl-, 4-benzoyl-, and 4-nitro-1,2-diaminobenzenes gave the corresponding 2-(2-amino-4-methylphenylaminomethylene)-, 2-(2-amino-5-benzoylphenylaminomethylene)-, and 2-(2-amino-5-nitrophenylaminomethylene)-5,5-dimethylcyclohexane-1,3-diones. When treated with hydrochloric acid, they cyclize to 7-methyl-, 8-benzoyl-, and 8-nitro-3,3-dimethyl-2,3,4,5-tetrahydro-1H-dibenzo[b,e][1,4]diazepinon hydrochlorides. Under hydrolytic conditions the salts of 3,3,7-trimethyl-2,3,4,5-tetrahydro-1H-dibenzo[b,e][1,4]diazepinone and 3,3-dimethyl-2,3,4,5-tetrahydro-1H-dibenzo[b,e][1,4]diazepinone undergo the C₁₁−N₁₀ bond cleavage to give N-(2-aminophenyl)- and N-(2-amino-5-methylphenyl)-substituted 3-amino-2-formyl-5,5-dimethylcyclohex-2-enones. Ring opening of the hydrochlorides of 8-benzoyl-, and 3,3-dimethyl-8-nitro-2,3,4,5-tetrahydro-1H-dibenzo[b,e][1,4]diazepinones occurs at the C−N₅ bond and gives the starting enamines. Riga Technical University, Riga LV-1658, Latvia; Translated from Khimiya Geterotsiklicheskikh Soedinenii, N. 5, pp. 696–700, May, 1999.     

一类新型的双β-氨基醇的合成及催化硼烷对芳酮的不对称还原反应

以L-半胱氨酸盐酸盐出发，经与二卤代烷偶联，成酯和格氏反应制得三种双手性β-氨基醇，1,2-双[R-2-氨基-3-羟基-3,3-二苯基丙硫基]乙烷(4a)，1,3-双[R-2-氨基-3-羟基-3,3-二苯基丙硫基]丙烷(4b)，1,4-双[R-2-氨基-3-羟基-3,3-二苯基丙硫基]丁烷(4c)。将此类双手性β-氨基醇与硼烷在THF溶液中反应，in situ制备双手性恶唑硼烷催化硼烷对芳酮的不对称还原，产物苯乙醇的光学收率达72.8%、α-溴代苯乙醇的光学收率达91.4%。     

Furan ring as masked 3-acylacrylate moiety. Practical synthesis of racemic (E)4,4(ethylenedioxy)-7-hydroxy 2-octenoic acid,the c-8 subunit of pyrenophorin

Furfural and acetone are the starting materials for a new practical synthesis of racemic (E)4,4(ethylenedioxy)-7-hydroxy-2-octenoic acid, the protected C-8 subunit of Pyrenophorin. Furan ring has been used as masked 3-acylacrylate moiety.     

Interaction between β-cyclodextrin and ionic liquids in aqueous solutions investigated by a competitive method using a substituted 3H-indole probe

We report herein the interaction of three kinds of ionic liquids, i.e., 1-butyl-3-methylimidazolium hexafluorophosphate (bmimPF₆), 1-butyl-3-methylimidazolium tetrafluoroborate (bmimBF₄) and 1-butyl-3-methylimidazolium chloride (bmimCl) with β-cyclodextrin (β-CD) using 2-(p-aminophenyl)-3,3-dimethyl-5-carboethyoxy-3H-indole (1) as a fluorescent probe through a competitive method. The formation of the 1:1 (guest:host) inclusion complex was suggested and the association constants at different temperatures were estimated, from which the thermodynamic parameters ΔG^Θ, ΔH^Θ and ΔS^Θ were also obtained. The negative entropy and enthalpy changes indicated that the formation of above inclusion complexes was entropically unfavorable and enthalpy-driven. Conductivity measurements were also employed to study above systems. The results showed agreement with those based on the competitive method. Furthermore, through NMR, the location of anions in the system of ILs and β-CD was investigated. We suggested that the anion was accommodated to a great extent by the cavity forming ion pair with imidazolium cation which was totally in the cavity of β-CD. The above work demonstrated that molecule 1 is a very sensitive fluorescence probe for studying the interaction of a non-fluorescent guest with cyclodextrins.     

Structures of 3,3′-dicarbometoxy-2,2′-bipyridine complexes with silver(I) and copper(II) cations

The structures of 3,3′-dicarbometoxy-2,2′-bipyridine (dcmbpy) complexes with copper(II) and silver(I) cations have been determined using single crystal X-ray-diffraction. The crystals of Cu(dcmbpy)Cl₂ are monoclinic, C2/c, a = 16.966(3), b = 18.373(3), c = 13.154(2) Å, β = 126.543(3)°. The crystals of Ag(dcmbpy)NO₃ · H₂O are also monoclinic, C2/c, a = 16.7547(13), b = 11.0922(9), c = 18.7789(18) Å, β = 100.228(7)°. The results have been compared with the literature data on the complexes of dcmbpy and its precursors: 2,2′-bipyridine (bpy) and 3,3′-dicarboxy-2,2′-bipyridine (dcbpy). Two types of complexes of 3,3′-carboxy derivatives of bpy are distinguished: (1) with metal atom bonded to two N atoms of the same molecule and (2) with metal atom bonded to two N atoms of two different molecules. The Cu(dcmbpy)Cl₂ complex belongs to the first type, whereas Ag(dcmbpy)NO₃ · H₂O belongs to the second type.     

A novel method of highly enantioselective synthesis of γ-hydroxy-β-keto phosphonates via allene oxides

Optically active γ-hydroxy-β-keto phosphonates 8 (96–97% ee) were obtained starting from 1-trimethylsilyl-1 -alkynes 1 by employing chiral allene oxides for introduction of -hydroxy carbonyl functionality.     

Synthesis of enantiomerically pure (S)-(−)-propranolol from sorbitol

Synthesis of enantiomerically pure (S)-(−)-propranolol, the most active optical isomer of the widely used β-Sympatholyticum, was achieved in high optical yield starting from sorbitol, an inexpensive and easily accessible carbohydrate. Via regioselective protection and coupling of -naphthol, the key intermediate 5 was obtained. Deprotection of the intermediate acetals and successive oxidative degradation followed by some simple conversion steps lead to the formation of (S)-(−)-propranolol with high optically purity.     

3-Trifluoromethyl- and 3-difluoromethyl-thalidomides

Syntheses of racemic 3-trifluoromethyl- and 3-difluoromethyl-thalidomide starting from 2-(tert-butyloxycarbonylimino)-3,3,3-trifluoropropionate or -3,3-difluoropropionate as fluorine-containing building blocks are described.     

Some intramolecular rearrangements when pentofuranoses are treated with diethylaminosulphur trifluoride (DAST)

Treatment of methyl 2,3-O-isopropylidene-β- -ribofuranoside with DAST gave a goodyield of 2,3-O-isopropylidene-5-O-methyl-β- -ribofuranosyl fluoride in which the methoxygroup had migrated from C-1 → C-5 and been replaced with retention of configurationby fluorine. The corresponding aldehyde when treated under similar conditions underwenta similar migration to give 5-deoxy-5-fluoro-2,3-O-isopropylidene-5-O-methyl-β- -ribofuranosylfluoride. A similar migration occurred with methyl 2′,3′-di-O-acetyl-β- -ribofuranosideand with acetyl 2,3-O-isopropylidene - -ribofuranose but not with 1,2,3-tri-O-acetyl- -ribofuranose. Thus the migration depends upon the migratory aptitude of thesubstituent at C-1 and the conformation of the furanose ring. Two ribofuranosyl fluorideswere used as starting materials from which to make nucleosides by the method of Noyoriand Hayoshi.     

Synthesis of heterocyclic steroids—IV Synthesis of dl-B-nor-6-oxaequilenin

The synthesis of dl-B-nor-6-oxaequilenin starting from 7-methoxy-4-oxo-1,2,3,4-tetrahydrobinzofuran is described. The latter compound was prepared from the known γ-(2,4-diydroxybenzoyl)-butyric acid.     

H, C, N NMR, ESI mass spectral and single crystal X-ray structural characterization of three spiro[pyrrolidine-2,3′-oxindoles]

Three spiro[pyrrolidine-2,3′-oxindoles], 1,1′,2,2′,5′,6′,7′,7′a-octahydro-2-oxo-1′-phenyl-spiro[3H-indole-3,3′-[3H]-pyrrolizine]-2′-carboxylic acid methyl ester (1), 1,1′,2,2′,5′,6′,7′,7′a-octahydro-2-oxo-1′-nitro-2′-phenyl-spiro[3H-indole-3, 3′-[3H]-pyrrolizine] (2) and 1,1′,2,2′,5′,6′,7′,7′a-octahydro-2-oxo-1′-nitro-2′-(4″-chlorophenyl)-spiro[3H-indole-3,3′-[3H]-pyrrolizine] (3) have been synthesized and their ¹H, ¹³C and ¹⁵N spectra assigned. The chemical shift assignments are based on Pulsed Field Gradient (PFG) Double Quantum Filter (DQF) ¹H, ¹H correlation spectroscopy (COSY), PFG ¹H, ¹³C Heteronuclear Multiple Quantum Coherence (HMQC) and PFG ¹H,X (X = ¹³C and ¹⁵N) Heteronuclear Multiple Bond Correlation (HMBC) experiments. The single crystal X-ray structures of 1–3 have been determined. Compounds 1 and 2 crystallized in monoclinic space group C2/c and compound 3 in monoclinic space group P2₁/c, respectively. Also the ESI-TOF MS data of 1–3 are given.     

Reactions of metalloalkynes VII. Protonation of ruthenium ethyne-1,2-diyl complexes

The acid–base chemistry of some ruthenium ethyne-1,2-diyl complexes, [{Ru(CO)₂(η-C₅H₄R)}₂(μ₂-CC)] (R=H, Me) has been investigated. Initial protonation of [{Ru(CO)₂{η-C₅H₄R}}₂(μ₂-CC)] gave the unexpected complex cation, crystallised as the BF₄ salt, [{Ru(CO)₂(η-C₅H₄R}}₃(μ₃-CC)][BF₄] (R=Me structurally characterised). This synthesis proved to be unreliable but subsequent, careful protonation experiments gave excellent yields of the protonated ethyne-1,2-diyl complexes, [{Ru(CO)₂{η-C₅H₄R)}₂(μ₂-η¹:η²-CCH)](BF₄) (R=Me structurally characterised) which could be deprotonated in high yield to return the starting ethyne-1,2-diyl complexes.     

New C2 symmetrical and semisymmetrical substituted imidazolium ribonucleoside. Imidazolic nucleosides analogues

New C₂ symmetrical imidazolium ribonucleosides have been synthesized. The silyl Hilbert Johnson-Vorbrügen method was used. Subsequent coupling of trimethylsilylimidazole with the peracylated D-ribofuranose 1, followed by removal of the protecting groups, afforded 1,3-bis(β-D -ribofuranosyl)imidazolium 7 and 1-(β-D-ribofuranosyl)imidazole 8. In a similar synthetic sequence, 4(5)-substituted bis-ribofuranosylimidazolium 14 was also prepared. For the selective preparation of the monoglycosylated imidazole 15, the classical method starting from 2,3,5-tri-O-benzoyl-D-ribofuranosyl bromide in acetonitrile and using Hg(CN)₂ was employed. These new base modified nucleosides were devoid of activity against HIV and cytotoxicity.