Synthesis of enantiomeric bridgehead substituted bisnoradamantane derivatives

The preparation of (+)- and (−)-12 by resolution of (±)-12 with (R)-N-phenylpantolactam, (R)-13, is described. From (+)- and (−)-12 a series of chiral bisnoradamantane derivatives, whose chirality stems from substitution at the bridgehead positions, have been obtained in both enantiomeric forms.     

Synthesis of functionalized tetracene dicarboxylic imides

For the first time, a synthesis of tetracene dicarboxylic imides was established with 1,2,3,4-tetrahydrotetracene (1) instead of tetracene as the starting material. Mono-bromination of 1 by CuBr₂ followed by a Friedel-Crafts reaction, oxidation, and imidization gave the tetrahydrotetracene carboxylic imides 5a-b. Subsequent oxidative dehydrogenation of 5a-b with DDQ afforded the functional tetracene dicarboxylic imide monobromides 6a-b, which can be further functionalized to provide functional materials such as the ‘donor-acceptor’ type compounds 7a-b.     

Facile synthesis of chiral 2-formyl-1,1′-binaphthyl via lipase-catalyzed acylation and hydrolysis of 1,1′-binaphthyl oximes

Lipase-catalyzed acylation of 2-hydroxyiminomethyl-1,1′-binaphthyl [(±)-1] and hydrolysis of 2-acetoxyiminomethyl-1,1′-binaphthyl [(±)-2] yielded optically active oximes 1 and 2 with high enantiomeric excess. Successful synthesis of the optically active aldehyde 4 from chiral O-acetyl oxime 2 occurred without a decrease of enantiomeric excess.     

Diastereoselective schenck ene reaction of singlet oxygen with chiral allylic alcohols; access to enantiomerically enriched 1,2,4-trioxanes

A series of antimalarial chiral 1,2,4-trioxanes (1-8) were synthesised in high enantiomeric purities. Enantioselective addition of R₂Zn reagent to 3-methyl-2-butenal catalysed by (+)-MIB or (−)-MIB yielded both the enantiomers of the chiral allylic alcohols 9-11 (90-98% ee), which were subjected to diastereoselective photooxygenation in the presence of tetraphenylporphine (TPP) to obtain (R,R)-threo- or (S,S)-threo-β-hydroperoxy alcohols (12-14). Reaction of β-hydroperoxy alcohols (12-14) with different cyclic ketones produced optically active trioxanes 1-8.     

Synthesis and pharmacological evaluation of 5-carboxamide-substituted tetrahydrochromeno[7,8-d]imidazoles

A fast access to novel 5-carboxamide-substituted tetrahydrochromeno[7,8-d]imidazoles 4 was developed using the readily available preclinical candidate BYK 405879 (1) as starting material. The 5-amino function was installed by the Curtius rearrangement of carboxylic acid 2 or by the Hofmann rearrangement of carboxamide 8 furnishing benzimidazole 3 as key intermediate. In the Ghosh Schild rat, some of the target compounds 10-14 showed noteworthy activity as potassium-competitive acid blockers.     

Regioselective Baeyer-Villiger lactonization of 2-substituted pyrrolidin-4-one. Synthesis of statine

Nine 2-substituted pyrrolidin-4-ones 4a-i were obtained via a series of functional group transformation of known prolinol 5 by facile six kinds of methodologies. The target structure of 1,3-amino alcohols 2a-i was constructed in the regioselective Baeyer-Villiger lactonization of ketones 4a-i and reduction of the resulting 4-substituted tetrahydro-1,3-oxazin-6-ones 3a-i. A new and straightforward synthesis of (3S,4S)-statine (6) has been established starting from trans-(2S,4R)-4-hydroxyproline (1).     

Salen-ligands based on a planar-chiral hydroxyferrocene moiety: Synthesis, coordination chemistry and use in asymmetric silylcyanation

Condensation of the O-protected hydroxyferrocene carbaldehyde (S_p)-1 with suitable diamines, followed by liberation of the hydroxyferrocene moiety leads to a new type of ferrocene-based salen ligands (3). While the use of ethylenediamine in the condensation reaction yields the planar-chiral ethylene-bridged ligand [(S_p,S_p)-3a], reaction with the enantiomers of trans-1,2-cyclohexylendiamine gives rise to the corresponding diastereomeric cyclohexylene-bridged systems [(S,S,S_p,S_p)-3b and (R,R,S_p,S_p)-3c], which feature a combination of a planar-chiral ferrocene unit with a centrochiral diamine backbone. Starting with the ferrocene-aldehyde derivative (R_p)-1, the enantiomeric ligand series (3d/e/f) is accessible via the same synthetic route.The (S_p)-series of these newly developed N₂O₂-type ligands was used for the construction of the corresponding mononuclear bis(isopropoxy)titanium (4a/b/c), methylaluminum (5a/b/c) and chloroaluminum-complexes (6a/b/c), which were isolated in good yields and identified by X-ray diffraction in several cases. The aluminum complexes (5/6) were successfully used in the Lewis-acid catalyzed addition of trimethylsilylcyanide to benzaldehyde, yielding the corresponding cyanohydrins in 45-62% enantiomeric excess.     

Substituted coumarin amidines: useful building blocks for the preparation of [1]benzopyrano[4,3-b]pyridin-5-one and [1]benzopyrano[4,3-d]pyrimidin-5-one derivatives

The synthesis of [1]benzopyrano[4,3-b]pyridin-5-ones 4a-f and 4g-j starting from 3-formylcoumarin and 3-cyanocoumarin N-functionalized amidines 3a-f and 3g-j, respectively, was reported. The ring-closure reaction mechanism, under basic or acidic media, was proposed. Furthermore, the reaction of 3-formylamidines 3a,c-f with ammonium acetate gave good yields of 2-substituted [1]benzopyrano[4,3-d]pyrimidin-5-ones 7.     

Chemoenzymatic syntheses of the linear triquinane-type sesquiterpenes (+)-hirsutic acid and (−)-complicatic acid

Formal total syntheses of the natural enantiomeric forms of the title sesquiterpenes 1 and 2 have been achieved using, as starting material, the readily available and enantiomerically pure cis-1,2-dihydrocatechol 4 derived from the whole-cell biotransformation of toluene.     

Gallic esters of 4,5-dinitrocatechol as potential building blocks for thermotropic liquid crystals

A series of unsubstituted and 1,4-disubstituted gallic catecholates 1, 6 and 7 as possible candidates for wedge-shaped mesogens were prepared starting from the respective benzene derivatives 2a-c and gallic esters 5a-h. The mesomorphic properties were investigated by DSC. However, only the 4,5-dinitro derivatives 1d,f-h with C₈H₁₇ and C₁₀H₂₁ to C₁₂H₂₅ alkyl side chains displayed mesophases, as evaluated by fluidity and optical anisotropy.     

Investigation of hydrazine addition to functionalized furans: synthesis of new functionalized 4,4′-bipyrazole derivatives

The addition of hydrazine to functionalized furans 2a-d leads to a variety of 4,4′-bipyrazoles 4a-c depending on the structure of the starting materials. In one example, compound 2c was first converted to an intermediate, furo[3,4-d]pyridazine 3c which was then transformed into 4,4′-bipyrazole 4c on reacting with hydrazine.     

Electrochemical synthesis of 1,3,4-thiadiazol-2-ylthio-substituted catechols in aqueous medium

Anodic oxidation of catechols 1a-e in the presence of 5-methyl-2-mercapto-1,3,4-thiadiazole 2 has been studied in acetate buffer solution by cyclic voltammetry and controlled-potential electrolysis techniques. The effects of various electrolytic conditions (amount of passed charge, anodic materials, pH of the electrolytic solution, applied potential, and concentration of substrates) on the yield have also been investigated. The results showed that the position of the initial substituent of the starting catechol derivatives dominated the formation of monothiadiazol-2-ylthio-substituted or/and dithiadiazol-2-ylthio-substituted products. For 4-substituted catechols 1a-b, monothiadiazol-2-ylthio-substituted products (3a-b) were exclusively produced in high to excellent yields. However, in the cases of catechol itself (1c) and 3-substituted catechols (1d-e), both monothiadiazol-2-yl-substituted (3c-e and 5d-e) and dithiadiazol-2-ylthio-substituted products (4c-e) were isolated. In addition, the nature of the initial substituent of the starting 3-substituted catechols (1d and 1e) affected the relative ratio of the two monothiadiazol-2-ylthio-substituted isomers (3d-e vs 5d-e).     

Amphiphilic perfluoroalkylated sulfones and sulfonate betaines

Two types of perfluoro alkyl-containing amphiphilic sulfones 7-9 and 13-15, respectively, and sulfonate betaines 23-32 were prepared using 2-[(perfluoroalkyl)methyl]oxiranes (1-3, R_F = C₄F₉, C₆F₁₃, C₈F₁₇) or 3-(perfluoroalkyl)propyl iodides (16 and 17, R_F = C₆F₁₃, C₈F₁₇) as the starting compounds. The overall yields of two-step syntheses were above 90%. The compounds 7-9 were prepared by the reaction of oxiranes 1-3 with 2-sulfanylethan-l-ol and subsequent oxidation of intermediate sulfides. Similarly, the amphiphiles 13-15 were obtained by analogous reaction of oxiranes 1-3 with thiomorpholine and subsequent oxidation of the sulfur atom in the morpholine ring. In the syntheses of betaines 23-32, the starting compounds 1-3 or 16 and 17 were first reacted with dimethylamine followed by the ring-opening reaction of the intermediate fluoroalkyl(dimethyl)amines with propane-1,3- or butane-1,4-sultones.     

Photo- and electroluminescent properties of cyano-substituted styryl derivatives and synthesis of CN-PPV model compounds containing an alkoxy spacer for OLEDs

The series of cyano-substituted model compounds 18-20 for organic light emitting diodes (OLEDs) was prepared through Knoevenagel condensation reactions between the dialdehydes 3,6,9 and the differently substituted acetonitrile derivatives 11,16,17. The influence of the different substituents on the optical properties of the resulting α-cyanostyryl compounds 18-20 was investigated. Another series of dimeric cyano-substituted styryl compounds 26-28 were prepared, in which a flexible, nonconjugated spacer is present between the two cyanostyryl moieties. The spacer isolates the π-conjugated portions of dimeric compounds 26-28, improves their solubility in common organic solvents, and decreases their tendency to crystallize. These features are favorable for producing efficient luminescent films in OLEDs devices.     

Total synthesis of phytoprostane F1 and its 16 epimer

The first synthesis of the two enantiomers of phytoprostane F₁ methyl ester 1 and 2 is described using the syn-anti-syn alcoxy ester 3 as starting material.     

Chemoenzymatic approaches to the montanine alkaloids: a total synthesis of (+)-nangustine

The synthesis of (+)-nangustine [(+)-2] has been achieved, for the first time, using the enantiomerically pure cis-1,2-dihydrocatechol 3 as starting material. The latter compound is available, in multi-gram quantities, through a whole-cell-mediated biotransformation of chlorobenzene using genetically engineered organisms that over-express the responsible enzyme, namely toluene dioxygenase. Since the enantiomer of compound 3 is available by related means, the present work also represents a formal total synthesis of the montanine alkaloid (−)-nangustine [(−)-2]. Single-crystal X-ray analyses of compounds 13 and (+)-2 are reported.     

Ti(III)-promoted cyclizations. Application to the synthesis of (E)-endo-bergamoten-12-oic acids. Moth oviposition stimulants isolated from Lycopersicon hirsutum

The Ti(III)-promoted radical cyclization of epoxyenone 8 is described as the key step to access the diol 10 as a convenient starting material of the target molecules. The synthesis of β-(E)-endo-bergamoten-12-oic acid 2a from (+)-8,9-epoxycarvone 8 was successfully achieved by Suzuki-Miyaura coupling of the terminal alkene 20 with β-iodomethacrylate 21c, followed by deprotection and dehydration processes. Moreover, synthesis of the α-(E)-endo-1-hydroxy-bergamoten-12-oic acid derivative 34 was achieved by iterative elongation processes of the diol 10 lateral chain.     

Columnar/smectic metallomesogens derived from heterocyclic benzoxazoles

The synthesis, mesomorphic behavior, and optical properties of two new series of metal complexes 1a,b-M (M=Pd, Cu, Zn) derived from benzoxazoles 2a,b are reported. The crystal and molecular structures of mesogenic 5-decyloxy-2-(6-decyloxybenzooxazol-2-yl)phenol and nonmesogenic bis[5-octyloxy-2-(6-octyloxybenzooxazol-2-yl) phenol]Pd(II) were determined by means of X-ray structural analysis. Two benzoxazoles 2a exhibited monotropic SmA phases, and all benzoxazoles 2b were nonmesogenic. On the other hand, metal complexes 1a-M exhibited distinctly different mesomorphism from complexes 1b-M. Complexes 1a-Pd formed SmC phases; complexes 1a-Cu and 1a-Zn formed crystal phases. In contrast, complexes 1b-Zn exhibited columnar phases, and complexes 1b-Cu and 1b-Pd were nonmesogenic. The difference of the mesomorphism in 1a-M and 1b-M was probably attributed to the geometry and/or the overall molecular shape created by 2a and 2b. The electronic configuration of metal ion might play an important role in forming the mesophases. The fluorescent properties of these compounds were also examined.     

Synthesis of l-cyclopentenyl nucleosides using ring-closing metathesis and palladium-mediated allylic alkylation methodologies

The enantiomeric synthesis of l-cyclopentenyl nucleosides is described. The key intermediate (+)-cyclopentenyl alcohol (8) was prepared from methyl-α-d-galactopyranoside 1 using a ring closing metathesis reaction. Transformation of the allylic alcohol 8 into the allylic acetate (9) or carbonate (10), allows their coupling with purine and pyrimidine bases under Pd(0)-catalyzed Tsuji-Trost allylic alkylation's to yield 12a-c. The Pd catalyzed reaction was found to require the use of AlEt₃.     

The absolute configuration determination of naturally occurring diacetylenic spiroacetal enol ethers from Artemisia lactiflora

Six new naturally occurring diacetylenic spiroacetal enol ethers, Lactiflodiynes A-F (1-6), together with five known congeners (7-11), were isolated from the whole plant of Artemisia lactiflora (Compositae). The structures were elucidated by extensive spectroscopic methods, X-ray crystallography, chemical transformations, and CD. The absolute configuration of Lactiflodiyne A (1) was determined to be 2R, 5S, 6S, and 7R by an X-ray crystallographic diffraction experiment using Mo Kα radiation with the absolute parameter of 0.01(8). In combination with CD, the absolute configurations of compounds 2-11 were confirmed by chemical transformations using 1 as the starting material.