New N-acyl, N-alkyl, and N-bridged derivatives of rac-6,6′,7,7′-tetramethoxy-1,1′,2,2′,3,3′,4,4′-octahydro-1,1′-bisisoquinoline

The preparation of potential new ligand systems based on the rac-1,1′,2,2′,3,3′,4,4′-octahydro-6,6′,7,7′-tetramethoxy-1,1′-bisisoquinoline skeleton has been investigated. Syntheses of N-(2-bromobenzyl), N-(3-acetoxybenzyl), N-acetyl, N-chloroacetyl, N-chlorocarbonyl, N-ethoxycarbonyl and N-tert-butyloxycarbonyl derivatives and five macrocyclic, polyether containing derivatives are described.     

Novel chiral C1-1′,2′,3′,4′-tetrahydro-1,1′-bisisoquinolines: synthesis, resolution, and applications in catalytic enantioselective reactions

A straightforward synthesis of a structurally constrained C₁-1′,2′,3′,4′-tetrahydro-1,1′-bisisoquinoline 1 is described. Resolution of this compound has been achieved successfully. The preparation of chiral N-alkyl, urea, and thiourea derivatives as potential new chiral ligands, based on the parent compound 1, is reported. Chiral compound 1 induced very good selectivity and yield in the addition of either Et₂Zn (85% ee, 96% yield) or nitromethane (85% ee, 60% yield) to benzaldehyde.     

5,5′-二甲基-2,2′-二茚满-1,1′,3,3′-四酮的合成及结构表征

本文以4-甲基邻苯二甲酸酐为原料, 成功地合成了5,5′-二甲基-2,2′-二茚满-1,1′,3,3′-四酮(2). 通过元素分析、核磁共振、红外光谱及质谱等测试手段, 确定了化合物2的结构与存在形式, 通过ESR测试发现化合物2具有顺磁性.     

Facile acid-catalyzed condensation of 2-hydroxy-2,2′-biindan-1,1′,3,3′-tetrone with phenols, methoxyaromatic systems and enols

Various phenols, methoxy aromatic compounds, 3- and 4-hydroxycoumarins and enols smoothly condense with 2-hydroxy-2,2′-biindan-1,1′,3,3′-tetrone 1 in an acid medium producing 2-aryl/alkyl-2,2′-biindan-1,1′,3,3′-tetrones in high yields. The adducts of resorcinol, 1,3,5-trihydroxybenzene and α- and β-naphthols of 1 preferably remain in the intramolecular hemi-ketal form, confirmed by X-ray diffraction studies. On the other hand para and meta substituted phenols condense with 1 in an acid medium to produce 6 or 7 substituted 2′,4-spiro(1′,3′-indanedion)-indeno[3,2-b]chromenes in good yields.     

Diastereoselective addition of dimethyl phosphite to 3,3′,4,4′-tetramethyl-1,1′-diphosphaferrocene-2-carboxaldehyde

Addition of dimethyl phosphite to racemic 3,3′,4,4′-tetramethyl-1,1′-diphosphaferrocene-2-carboxaldehyde gives almost exclusively one diastereomer of the corresponding α-hydroxyphosphonate (d.r. ?96:4). Its absolute configuration (S, R_p)-(R, S_p) was established by X-ray diffraction.     

Difluorocarbene chemistry: synthesis of gem-difluorocyclopropenylalkynes and 3,3,3′,3′-tetrafluorobicyclopropyl-1,1′-dienes

A series of gem-difluorocyclopropenylalkynes are easily obtained in good yields by the Sonogashira reaction of 3,3-difluoro-1-iodocyclopropenes with terminal alkynes. Onto these new alkynes addition of difluorocarbene, generated from the decomposition of FSO₂CF₂COOTMS in diglme in the presence of 10 mol% anhydrous NaF at 120 °C, gives 3,3,3′,3′-tetrafluorobicyclopropyl-1,1′-dienes. Acid hydrolysis of gem-difluorocyclopropenylalkynes in refluxing CH₃OH affords the corresponding methoxycarbonylenynes.     

A new route to 2,2′,3,3′-tetrasubstituted binaphthyls

Based on an ortho-lithiation protocol of 2,2′-dibromo-1,1′-binaphthyl four tetrasubstituted binaphthyls, 2,2′-dibromo-3,3′-diiodo-, 3,3′-dibromo-2,2′-diiodo-, 2,2′,3,3′-tetrabromo-, and 2,2′,3,3′-tetraiodo-1,1′-binaphthyls have been prepared in excellent yield which in turn proved to be versatile key intermediates in the synthesis of various 2,2′,3,3′-tetrasubstituted 1,1′-binaphthyl derivatives.     

Rapid atropisomerization of 1,1′:5′,1″-ternaphthalene-2,2′,6′,2″-tetrol (TERNOL) and its inhibition by tethering at positions 7 and 7″

Atropisomerization of 1,1′:5′,1″-ternaphthalene-2,2′,6′,2″-tetrol (TERNOL) is very fast under basic conditions. The stereochemical instability is attributed to the nature of oxide anion of the central 2,6-naphthodiol moiety. Ring-closing metathesis of 7,7″-diallyloxy TERNOL results in intramolecular tethering in a high yield, which intrinsically inhibits the rapid isomerization. Bidentate sites in the tethered TERNOL are proved to have enough structural flexibility as an axial chiral ligand.     

A simple synthetic approach to homochiral 6- and 6′-substituted 1,1′-binaphthyl derivatives

Various homochiral binaphthyl derivatives having functional groups at the 6-position are important key intermediates for the immobilization of binaphthyl compounds on various solid-supports and have been prepared from commercially available 1,1′-bi-2-naphthol via controlled monopivalation of the 2-hydroxyl group and electrophilic aromatic substitution at the 6-position. (S)-2,2′-Bis-((S)-4-alkyloxazol-2-yl)-6-(2-methoxycarbonyl)ethyl-1,1′-binaphthyls (6-functionalized (S,S)-boxax)) were prepared and immobilized on various polymer supports including PS-PEG, PS, PEGA and MeO-PEG resin.     

Highly efficient synthesis of 2′,3′-didehydro-2′,3′-dideoxy-β-nucleosides through a sulfur-mediated reductive 2′,3′-trans-elimination. From iodomethylcyclopropanes to thiirane analogs

Taking into account the thiophilic properties of iodine, a very simple methodology to achieve 2′,3′-didehydro-2′,3′-dideoxy-β-nucleosides in high yield was performed, using mild, and inexpensive conditions, by means of the treatment of 2′-deoxy-3′,5′-dibenzoyl-2′-iodo-β-nucleoside derivatives with NaHS. The process has shown to be highly dependent of the relative geometry between the iodine atom and the adjacent leaving group. In this way, different essays carried out with pyranose derivatives have concluded in no reaction when the vicinal groups to eliminate do not adopt a trans-diaxial disposition. In addition, the treatment of 2-iodomethyl-cyclopropane-1,1-dicarboxylic acid diethyl ester under the same conditions softly and readily leads to the obtention of a mixture of the expected 2-allyl-malonic acid diethyl ester (as the minor product) and the thiirane derivative 2-thiiranylmethyl-malonic acid diethyl ester (as the major product). In this case, the responsible of the reaction progress are the nucleophilic properties of the sulfur atom rather than the thiophilic character of the iodine atom.     

Diastereoselective synthesis of 1-alkyl-2,4,6-trioxoperhydropyrimidine-5-spiro-3′-(1′,2′,3′,4′-tetrahydroquinolines)

Knoevenagel products formed by the condensation of N-monoalkyl barbituric acids with o-tert-amino benzaldehydes undergo tert-amino effect reactions (T-reactions) yielding 1-alkyl-2,4,6-trioxoperhydropyrimidine-5-spiro-3′-(1′,2′,3′,4′-tetrahydroquinoline) derivatives as a mixture of (S^∗,S^∗)- and (S^∗,R^∗)-diastereomers. Mostly, the major diastereomer has the S^∗,S^∗-configuration. According to X-ray diffraction data in the solid form and NOE data in solution, diastereoselectivity of the T-reactions can be associated with the structure of the Knoevenagel products whose conformation is fixed by the strong intramolecular C-H?π interaction.     

1,1′,1′′-(2,4,6-Trihydroxybenzene-1,3,5-triyl)triethanone tautomerism revisited

It has recently been suggested that 1,1′,1′′-(2,4,6-trihydroxybenzene-1,3,5-triyl)triethanone may be tautomeric. Using ¹³C NMR chemical shifts and deuterium isotope effects on ¹³C chemical shifts, it is demonstrated that this is not the case. This compound occurs as a strongly hydrogen bonded benzene structure with hydrogen bonds between OH groups and the acetyl groups in both non-polar and hydrogen donating solvents. Quantum-chemical calculations using MP2 and M06-2X methods show substantial preference for the phenol structure in both the gas phase, and in cyclohexane and methanol. In addition, conventional UV–vis spectroscopy data suggest not tautomeric, but aggregation behaviour of the molecule in methanol and acetonitrile.     

2′,3′,4′,5′-Tetraacetyl-N(3)-carboxymethylriboflavin derivatives: synthesis and fluorescence studies

The hitherto not described 2′,3′,4′,5′-tetraacetyl-N(3)-carboxymethylriboflavin (1) could be prepared starting from 2′,3′,4′,5′-tetraacetylriboflavin by alkylation with tert-butyl α-bromoacetate and benzyl α-bromoacetate, followed by deprotection reaction. The results of fluorescence studies are described.     

Enantiospecific synthesis of 5′,5′,5′-trifluoro-5′-deoxyneplanocin A

(−)-(1S,4R)-4-Hydroxy-2-cyclopenten-1-yl acetate provided a convenient entry point for a 12-step chiral preparation of 5′,5′,5′-trifluoro-5′-deoxyneplanocin A.     

Synthesis of substituted 1,1′-diaminoferrocenes from cyclo-2-pentene imines

Condensation of anilines and primary aliphatic amines with 3,4-diphenylcyclo-2-pentenone leads to the corresponding diphenylcyclopentene imines in good yields of 72-90%. Deprotonation of these aminocyclopentadiene tautomers and reaction with FeCl₂ leads to the synthesis of the respective 1,1′-diamino-3,3′,4,4′-tetraphenylferrocenes. Yields increase from 33% to 65% with a decrease in the steric bulk of the amine substituent. The observation that a successful conversion requires two equivalents of base is conceived on the basis of the discussed reaction mechanism. The molecular structure of 1,1′-dianilino-3,3′,4,4′-tetraphenylferrocene (3a), which was determined by single crystal X-ray analysis reveals a trans coordination of the two amine moieties with respect to the central Cp-Fe-Cp axis of the ferrocenyl backbone.     

Straightforward synthesis of 3′-deoxy-3′,4′-didehydronucleoside-5′-aldehydes via 2′,3′-O-orthoester group elimination: a simple route to 3′,4′-didehydronucleosides

Straightforward, high-yielding syntheses of 3′-deoxy-3′,4′-didehydronucleoside-5′-aldehydes and 3′-deoxy-3′,4′-didehydronucleosides starting from 2′,3′-O-orthoester derivatives of ribonucleosides are described.     

The highly regiospecific synthesis and crystal structure determination of 1,1′-2,5′ substituted ring-locked ferrocenes

1,1′-Ferrocene biscarboxaldehyde (1) has been prepared and the aldehyde groups were subsequently protected with acetal groups to produce 1,1′-bisacetalferrocene (2). A ring-locked ferrocene was synthesised by further derivatisation of the cyclopentadiene rings at the 2,2′ positions with phosphine substituents to produce 2,2′-bis-(acetal)-1,1′-diphenylphosphinoferrocene (3), which was subsequently coordinated to either a nickel chloride (5) or nickel bromide (6) metal centre. The ring-locked ferrocene complexes produced 2,5′-bis-(acetal)-1,1′-diphenylphosphinoferrocene substitution patterns. The acetal protecting groups of 2,2′-bis-(acetal)-1,1′-diphenylphosphinoferrocene were removed to produce 1,1′-bis-carboxaldehyde-2,2′-diphenylphosphinoferrocene (4). The Cp rings of 1,1′-bisacetalferrocene were also further derivatised at the 2,2′ positions with a silane to produce the ring-locked 1,1′-siloxane-2,5′-bisacetalferrocenophane (7). The acetal protecting groups were removed from this to produce 1,1′-siloxane-2,5′-ferrocenophanecarboxaldehyde (8). For both the phosphine and siloxane electrophiles, the substitution on the Cp rings gives chiral products (obtained as racemic mixtures). Due to the highly regioselective nature of the reaction and diastereoselectivity in the products only C₂-symmetric compounds were observed without the presence of meso diastereoisomers. Subsequent ring-locking forced the Cp rings to rotate, leading to 1,1′-ring-locked ferrocenes with 2,5′-arrangement of the acetal groups (i.e. on opposite faces of the ferrocene unit).     

Novel and efficient syntheses of 3′,5′-diamino derivatives of 2′,3′,5′-trideoxycytidine and 2′,3′,5′-trideoxyadenosine. Protonation behavior of 3′,5′-diaminonucleosides

High yielding synthetic routes to 3′,5′-diamino-2′,3′,5′-trideoxycytidine and 3′,5′-diamino-2′,3′,5′-trideoxyadenosine are described. In addition, the protonation behavior of 3′,5′-diamino-2′,3′,5′-trideoxycytidine, 3′,5′-diamino-2′,3′,5′-trideoxyadenosine, 3′,5′-diamino-3′,5′-dideoxythymidine, and 3′,5′-diamino-2′,3′,5′-trideoxyuridine has been studied by means of pH-metric measurements and NMR spectroscopy. The ionization constants and the sequence of protonation sites have been determined.     

Synthesis and anti-HIV activities of phosphate triester derivatives of 3′-fluoro-2′,3′-dideoxythymidine and 3′-azido-2′,3′-dideoxythymidine

Fatty acyl-glycol phosphate triester conjugates of 3′-fluoro-2′,3′-dideoxythymidine (FLT) were prepared in three steps from the reaction of diisopropylphoramidous dichloride with fatty acyl-substituted glycols, followed by a coupling reaction with FLT and oxidation with tert-butyl hydroperoxide (t-BuOOH). Additionally, a number of fatty alcohols were reacted with diisopropylphoramidous dichloride to produce the phosphitylating intermediates, which underwent coupling reactions with 3′-azido-2′,3′-dideoxythymidine (AZT) and FLT followed by oxidation with t-BuOOH to yield fatty alcohol phosphate triester derivatives of AZT and FLT.     

Synthesis, crystal and molecular structure of gold(I) thiophenolate with 4′-ferrocenyl[1,1′]biphenylisocyanides

The syntheses of ferrocenylbiphenylisocyanide gold(I) thiophenolato complexes are described. The preparative route starts from ferrocenylphenylbromide and proceeds in six steps to yield the desired gold(I) complexes, (thiophenolato)gold{(4′-ferrocenyl[1,1′]biphenyl-4-yl)isocyanide} (11) and (thiophenolato)gold{(4′-ferrocenyl-3,5-dimethyl[1,1′]biphenyl-4-yl)isocyanide} (12) in good yields. The synthetic pathways were developed as a first step toward realizing the goal of preparing metallomesogens based on ferrocenyl-polyphenylenes coordinated to gold(I) thiophenolates, in which long chain alkoxy groups are substituted para to sulfur on the phenyl ring. The crystal structures of (chloro)gold{(4^′-ferrocenyl[1,1′]biphenyl-4-yl)isocyanide} (9) and 12 are reported. Complex 9 crystallizes in the space group P2₁/c and 12 crystallizes in P2₁/n. Complexes 9 and 12 show short intermolecular Au-Au contacts of 3.3765(7) Å and 3.3334(3) Å, respectively.