Angelika Baro

Quaternary stereocenters : challenges and solutions for organic synthesis

Foreward. Preface. List of Contributors. Symbols and Abbreviations. 1 Important Natural Products (Hirokazu Arimoto and Daisuke Uemura). 1.1 Introduction. 1.2 Alkylation of Tertiary Carbon Centers. 1.3 Cycloaddition to Alkenes. 1.4 Rearrangement Reactions. 1.5 Carbometallation Reactions. 1.6 C-H Functionalization Reactions. 1.7 Asymmetric Modification of Enantiotopic/Diastereotopic Substituents of Quaternary Carbon Centers. 1.8 Summary. 2 Important Pharmaceuticals and Intermediates (Johannes G. de Vries). 2.1 The Chirality of Drugs and Agrochemicals. 2.2 Steroids. 2.3 Pharmaceuticals and Agrochemicals Based on a-Dialkylated Amino Acids. 2.4 Azole Antimycotics. 2.5 Alkaloids. 2.6 HIV Inhibitors. 2.7 &beta -Lactam Antibiotics. 2.8 The Tetracyclines. 2.9 Summary and Outlook. 3 Aldol Reactions (Bernd Schetter and Rainer Mahrwald). 3.1 Introduction. 3.2 Metal Enolates. 3.3 Catalytic Aldol Additions. 3.4 Conclusions. 3.5 Note Added in Proof 79 4 Michael Reactions and Conjugate Additions (Angelika Baro and Jens Christoffers). 4.1 Introduction. 4.2 Chiral Bronstedt Bases. 4.3 Chiral Metal Complexes. 4.4 Chiral Auxiliaries. 5 Rearrangement Reactions (Annett Pollex and Martin Hiersemann). 5.1 Introduction. 5.2 Applications. 5.3 Summary. 6 Cycloaddition Reactions (Giovanni Desimoni and Givseppe Faita). 6.1 Introduction. 6.2 [2+1] Cycloaddition Reactions. 6.3 [2+2] Cycloaddition Reactions. 6.4 1,3-Dipolar Cycloaddition Reactions. 6.5 Diels-Alder Reactions. 6.6 Hetero-Diels-Alder Reactions. 6.7 Consecutive Cycloaddition Reactions. 7 Asymmetric Cross-coupling and Mizoroki-Heck Reactions (Louis Barriault and Effiette L. O. Sauer). 7.1 The Asymmetric Heck Reaction. 7.2 Metal-catalyzed Cross-coupling Reactions. 7.3 Summary. 8 Alkylation of Ketones and Imines (Diego J. Ramon and Miguel Yus). 8.1 Introduction. 8.2 Diastereoselective Additions. 8.3 Enantioselective Additions by Modulated Processes. 8.4 Enantioselective Additions by Promoted Processes. 9 Asymmetric Allylic Alkylation (Manfred Braun). 9.1 Introduction. 9.2 Electrophilic Allylic Alkylation. 9.3 Nucleophilic Allylic Alkylation. 9.4 Miscellaneous Methods. 9.5 Outlook. 10 Phase-Transfer Catalysis (Takashi Ooi and Keiji Maruoka). 10.1 Introduction. 10.2 Carbon-Carbon Bond Formation Through PTC. 10.3 Carbon-Heteroatom Bond Formation Through PTC. 10.4 Conclusion. 11 Radical Reactions (Kalyani Patil and Mukund P. Sibi). 11.1 Introduction. 11.2 Radical Cyclization. 11.3 Atom- and Group-transfer Cyclizations. 11.4 Intermolecular Radical Allylations. 11.5 Other Metallic Reagents. 11.6 Radical Reactions in the Solid State. 11.7 Conclusion. 11.8 Experimental. 12 Enzymatic Methods (Uwe T. Bornscheuer, Erik Henke, and Jurgen Pleiss). 12.1 Introduction. 12.2 Strategies for the Kinetic Resolution of Sterically Demanding Substrates. 12.3 Conclusion. Index.

Counterion Effects on the Columnar Mesophases of Triphenylene‐Substituted [18]Crown‐6 Ethers: Is Flatter Better?

The twisted lateral tetraalkyloxy ortho-terphenyl units in dibenzo[18]crown-6 ethers 1a-f were readily converted into the flat tetraalkyloxytriphenylene systems 2a-f by oxidative cyclization with FeCl(3) in nitromethane. Reactions of the latter with potassium salts gave complexes KX.2, which displayed mesomorphic properties. The aromatization increased both the clearing and melting points; the mesophase stabilities, however, were mainly influenced by the respective anions upon complexation with various potassium salts. In contrast, the alkyl chain lengths played only a secondary role. Among the potassium complexes of triphenylene-substituted crown ethers KX.2, only those with the soft anions I(-) and SCN(-) displayed mesophases with expanded phase temperature ranges of 93 degrees C and 132 degrees C (for KX.2e), respectively, as compared to the corresponding o-terphenyl-substituted crown ether complexes KI.1e (DeltaT=51 degrees C) and KSCN.1e (plastic crystal phase). Anions such as Br(-), Cl(-), and F(-) decreased the mesophase stability, and PF(6)(-) led to complete loss of the mesomorphic properties of KPF(6).2 although not for KPF(6).1. For crown ether complexes KX.2 (X=F, Cl, Br, I, BF(4), and SCN), columnar rectangular mesophases of different symmetries (c2mm, p2mg, and p2gg) were detected. In contrast to findings for the twisted o-terphenyl crown ether complexes KX.1, the complexation of the flat triphenylene crown ethers 2 with KX resulted in the formation of organogels. Characterization of the organogel of KI.2e in CH(2)Cl(2) revealed a network of fibers.

Columnar Mesophases Controlled by Counterions in Potassium Complexes of Dibenzo[18]crown-6 Derivatives

Dibenzo[18]crown-6 derivatives 1 with two lateral tetraalkyloxy o-terphenyl units were prepared and converted to the corresponding complexes KX1 (X = halide, BF(4), PF(6), SCN) and NH(4)PF(6)1. Complexation was probed by MALDI-TOF spectrometry and NMR spectroscopy. Downfield shifts of (1)H NMR signals for complexes with soft anions Br, I, SCN, and PF(6) indicated the presence of tight ion pairs, whereas complexes with hard anions F, Cl, or BF(4) showed no or little shifts. In (13)C NMR spectra, upfield shifts were detected for soft anions. The character of the anion also influenced the mesomorphic properties of complexes MX1 (M = K, NH(4)), which were investigated by differential scanning calorimetry (DSC), polarizing optical microscopy (POM), and XRD in comparison to neat 1. Hard anions slightly stabilize or even destabilize the mesophase. Soft anions, however, improve the mesomorphic properties yielding mesophases with up to 70 degrees C phase widths in the case of KI1, KPF(6)1, and NH(4)PF(6)1. For complexes KSCN1 with a soft and bridging anion, the balance between mesophase stabilization and high order is shifted in favor of the plastic crystal phase.

p-Alkoxybiphenyls with guanidinium head groups displaying smectic mesophases

Novel calamitic guanidinium salts with p-alkoxybiphenyl or p-alkoxyphenyl core unit (7, 11, 12) have been synthesised, utilising the corresponding nitro compounds as synthetic intermediates. Differential scanning calorimetry (DSC), polarising optical microscopy (POM) and temperature-dependent X-ray diffraction studies reveal smectic A (SmA) mesophases for all series. Whereas the p-alkoxybiphenyl guanidinum chlorides 7 display SmA phases with a minimum chain lengths of C8 and broad mesophase width from 80°C (for C8 derivative 7b) up to 180°C (for C16 derivative 7g), the corresponding p-alkoxyphenyl guanidinium chlorides 11 display much smaller mesophase width from 4°C (for C10 derivative 11c) up to 72°C (for C16 derivative 11e). For the series 12 a large influence of the anion on the clearing point is observed, with clearing points ranging from 209°C for the guanidinium chloride 7f down to 127°C for guanidinium hexafluorophosphate 12d.

Synthesis and Biological Properties of Cylindramide Derivatives : Evidence for Calcium-Dependent Cytotoxicity of Tetramic Acid Lactams

To gain insight into the biological properties of tetramic acid lactam cylindramide 1, the analogues 4 a–d bearing a cyclopentane ring instead of the pentalene unit were prepared by tandem conjugate addition/enolate trapping of cyclopentenone 10; a Sonogashira or Stille coupling, followed by a Julia–Kocienski olefination, macrolactamisation and Lacey–Dieckmann cyclisation were the key steps. The previous NMR structure of cylindramide 1, which was based on NOE and J coupling restraints, could be refined by including residual dipolar coupling data measured for a sample of cylindramide that was aligned in polyacrylonitrile (18 %). Biological screening of cylindramide 1 and its analogues 2‐epi‐1, 20 and 4 revealed promising antiproliferative activity against several tumour cell lines. It turned out that the activity is strongly correlated to the functionalised pentalene system. The configuration of the cyclopentane ring and an intact tetramic acid lactam with the correct configuration seem to play an equal role in the cytotoxicity. The antiproliferative activity was found to be calcium dependent. Phenotypic characterisation of the mode of action showed vacuolisation and vesicle formation in the endoplasmic reticulum.

Crown ethers with lateral ortho-terphenyl units: effect of ester groups and sodium salts on the mesomorphic properties

Unsymmetrical crown ether derivatives 7 and 12 with one lateral o-terphenyl unit bearing different ester substituents were synthesized starting from methoxymethyl (MOM) protected bromobenzenes 3 and 8 by conversion into the respective borolanes 4 and 9, twofold Suzuki coupling with dibromobenzo[15]crown-5, acidic deprotection and finally esterification either with various alkanoic chlorides or gallic acids. Reaction with NaI provided the complexes [NaI·(7a–g)] and [NaI·(12a–d)], respectively. Uncomplexed crown ethers as well as their complexes [NaI·7a–c] and [NaI·12a–d] are non-mesogenic. In the case of [NaI·(7d–g)], however, the complexation induced a mesophase formation. As exemplarily shown for [NaI·7d], different textures were observed upon cooling, a fan-shaped texture, which is typical for a columnar hexagonal mesophase, and a striped fan-shaped texture, indicating a second mesophase Colx at low-temperature. From the SAXS diffraction pattern this mesophase was assigned to be columnar rectangular. For [NaI·7g] a different diffraction pattern was found, from which the low-temperature mesophase might be attributed to a soft crystal or a highly ordered columnar mesophase with orthorhombic symmetry.

Saddle-shaped tetraphenylenes with peripheral gallic esters displaying columnar mesophases

Summary Tetraphenylenes 2 with eight peripheral gallic esters were prepared in two steps from octamethoxytetraphenylene 1 in 19–72% yield. Investigation of the mesomorphic properties of 2 by DSC, POM and X-ray diffraction revealed that derivatives 2a–d with short alkoxy chain lengths (C5–C8) did not show any mesomorphic properties, whereas compounds 2e–i with C9–C13 chains displayed rectangular columnar mesophases and compounds 2j–l with C14–C16 chains displayed hexagonal columnar mesophases. Furthermore an anomalous odd-even effect of the clearing points of compounds 2e–l versus chain length was detected.

Triphenylene silanes for direct surface anchoring in binary mixed self-assembled monolayers.

New triphenylene-based silanes 2-(ω-(chlorodimethylsilyl)-n-alkyl)-3,6,7,10,11-penta-m-alkoxytriphenylene 4 (Tm-Cn) with n = 8 or 9 and m = 7, 8, 9, 10, or 11 were synthesized, and their self-assembly behavior in the liquid state and at glass and silicon oxide surfaces was investigated. The mesomorphic properties of triphenylene silanes 4 (Tm-Cn) and their precursors 3 (Tm-Cn) were determined by differential scanning calorimetry (DSC), polarizing optical microscopy (POM), and X-ray diffraction. From the small-angle X-ray scattering (SAXS) regime, a preferential discotic lamellar mesophase can be deduced, and wide-angle X-ray scattering (WAXS) highlights the liquid-like characteristics of the alkyl side chains. To transfer these bulk structural properties to thin films, self-assembled monolayers (SAMs) were obtained by adsorption from solution and characterized by water contact angle measurements, null ellipsometry, and atomic force microscopy (AFM). Employing the concentration as an additional degree of freedom, binary SAMs of 2-(ω-(chlorodimethylsilyl)-undecyl)-3,6,7,10,11-penta-decyloxytriphenylene 4 (T10-C11) were coassembled with chlorodecyldimethylsilane or chlorodimethyloctadecylsilane, and their capability as model systems for organic templating was evaluated. The structure of the resulting binary mixed SAMs was analyzed by water contact angle measurements, null ellipsometry, and X-ray reflectivity (XRR) in combination with theoretical modeling by a multidimensional Parratt algorithm and AFM. The composition dependence of film thickness and roughness can be explained by a microscopic model including the steric hindrance of the respective molecular constituents.

Tetraphenylenes as novel saddle-shaped building blocks of columnar and smectic liquid crystals

We report the synthesis and liquid crystalline properties of novel mesogenic octaalkyloxytetraphenylenes. Starting from 4-bromoveratrol, the saddle-shaped target tetraphenylenes were obtained in five steps. Compounds with shorter C7–C12 alkyl chain lengths displayed enantiotropic hexagonal columnar mesophases. For the decyloxy derivative a lattice constant d=27.4 Å was determined by X-ray diffraction. The compounds with longer C13–C16 alkyl chains exhibited enantiotropic mesophases, which are most probably smectic in nature. X-ray diffraction of the R=C14H29 derivative indicated a phase transition within the smectic mesophases.

Columnar liquid crystals derived from crown ethers with two lateral ester-substituted ortho-terphenyl units: unexpected destabilisation of the mesophase by potassium iodide

Gallic acid substituted ortho-terphenyl dimers linked by a central [18]crown-6 ether and their KI complexes were synthesised and characterised by differential scanning calorimetry, polarising optical microscopy and X-ray diffraction. With one exception, all salt free derivatives were liquid crystalline. They formed hexagonal columnar mesophases, whose columnar order is retained even upon cooling to room temperature. An odd–even effect of the clearing temperatures was observed with higher clearing points for compounds bearing even-numbered side chains as compared to odd-numbered ones. The calculation of molecules per unit cell resulted in Z ∼ 2, thus a disc with a dimeric subunit of two molecules oriented perpendicular to each other is assumed. In contrast, all KI complexes were non-mesomorphic.