High kinetic resolution in the addition of a racemic allenylzinc onto enantiopure N-tert-butanesulfinimines: concise synthesis of enantiopure trans-2-ethynylaziridines

Enantiopure trans-ethynyl N-tert-butanesulfinylaziridines (R(S))-6 were prepared in good to excellent yields by the condensation of the racemic allenylzinc species 1 derived from 3-chloro-1-trimethylsilylpropyne onto the corresponding enantiopure N-tert-butanesulfinimines (R(S))-5. The absolute stereochemistry of enantiopure N-tert-butanesulfinylaziridines (R(S))-6 was shown to be (R(S),2R,3R) and results from a chelate-type transition state in which the zinc atom of allenylzinc 1 is coordinated by both the nitogen and the oxygen atoms of the imine. Further removal of the N-tert-butanesulfinyl auxiliary of alkyl 3-substituted and 3,3-disubstituted ethynyl N-tert-butanesulfinylaziridines (R(S))-6 could be achieved by treatment with HCl in MeOH affording the corresponding deprotected aziridines (2R,3R)-9 and (2R)-9 respectively as enantiomerically pure compounds.     

Carboxylic acid derivatives of tetrathiafulvalene: key intermediates for the synthesis of redox-active calixarene-based anion receptors

A series of calixarene-TTF (TTF=tetrathiafulvalene) receptors incorporating amide binding units for anion recognition have been synthesized and characterized. For this purpose, two synthetically versatile new TTF carboxylic acid derivatives were prepared and characterized by X-ray diffraction, these structures demonstrating the critical role of the carboxylic function in the solid-state organization. Some of the calixarene-amide-TTF assemblies exhibit strong binding of various anions, as shown by ¹H NMR titration studies, and one receptor is able to electrochemically respond in the presence of H₂PO₄⁻, C₆H₅CO₂⁻ or CH₃CO₂⁻ anion.     

Templating Schiff-base lateral macrobicycles: an experimental and theoretical structural study of the intermediates

In this paper, we report a structural study both in the solid state and in solution of barium complexes with the diamine N,N'-bis(2-aminobenzyl)-4,13-diaza-18-crown-6 (L(2)), that allows us to rationalize the template effect of the metal ion in the synthesis of Schiff-base lateral macrobicycles resulting from the condensation of L(2) with different dicarbonyl compounds. The X-ray crystal structures of [Ba(L(2))(ClO(4))](ClO(4)) (3) [triclinic space group P1 with Z = 2, a = 10.467(2) A, b = 10.4755(2) A, c = 16.9911(3) A, alpha = 85.075(1) degrees, beta = 80.907(1) degrees, and gamma = 61.627(4) degrees ] and [Ba(L(2))(NCS)(H(2)O)](SCN) (4) [monoclinic space group P2(1)/n with Z = 4, a = 9.954(5) A, b = 29.193(5) A, c = 11.313(5) A, and beta = 91.371(5) degrees ] demonstrate that in the solid state the barium(II) ion induces an anti conformation of the receptor in the complexes. Variable temperature (1)H and (13)C NMR data point out that in solution compounds 3 and 4 exist as a mixture of syn and anti isomers. The presence of the syn isomer in solution, independent of the counterion employed (perchlorate or thiocyanate), accounts for the effectiveness of the barium(II) ion as a template agent in the synthesis of the lateral macrobicycles resulting from the condensation of L(2) with different dicarbonyl compounds. Density functional theory calculations (at the B3LYP/LanL2DZ level) for [Ba(L(2))](2+) predict the syn conformation to be more stable both in vacuo and in solution (PCM model). In order to asses which of the two isomers predominates in acetonitrile solution, the (13)C NMR shielding tensors of the two isomers of [Ba(L(2))](2+) were calculated for the in vacuo optimized structures by using the GIAO method, and the results were compared with the experimental ones. According to these analyses, a syn stereochemistry is assigned to the major species in solution.     

Intermolecular radical addition reactions of alpha-iodo cycloalkenones and a synthetic study of the formal synthesis of enantiopure fawcettimine

The generation of alpha-carbonyl vinyl radicals from alpha-iodo cycloalkenones, the scope of their participation in intermolecular addition reactions with electron-withdrawing olefins are studied and a synthetic study of the formal synthesis of enantiopure fawcettimine using this reaction is described.     

Nucleoside h-phosphonates: Valuable intermediates in the synthesis of deoxyoligonucleotides

Nucleoside H-Phosphonates are used directly in the synthesis of H-phosphonate linked deoxyoligonucleotides. A rapid and simplified procedure for the synthesis of deoxyoligonucleotides is described.     

Catalytic asymmetric synthesis of enantiopure isoprenoid building blocks: application in the synthesis of apple leafminer pheromones

The first catalytic asymmetric procedure capable of preparing all 4 diastereoisomers (ee > 99%, de > 98%) of a versatile saturated isoprenoid building block was developed and the value of this new method was demonstrated in its application to the concise total synthesis of two pheromones.     

Unexpected solids from enantiopure cationic palladium complexes and racemic anions: A structural study of chiral non-discrimination

Enantiomerically pure cationic complexes were obtained via cyclopalladation of primary amines and subsequent addition of a chelating ethylendiamine ligand. No diastereomeric resolution was observed upon combining these cations with racemic mandelate or hydratropate anions, but four less popular products, namely three double salts and a solid solution, were obtained and structurally characterized. For one of the double salts, the alternative ionic compounds based on different stereoisomers of the same residues were synthesized independently: The conventional racemic solid and both diastereomeric salts formed by enantiopure cations and anions were studied by single crystal X-ray diffraction. Lattice energy calculations confirm that the diastereomeric salts differ significantly; formation of the partially racemic double salt, however, is energetically favourable and precludes resolution.     

A study on the synthesis of structural analogs of bis-indole alkaloid caulerpin: a step-by-step synthesis of a cyclic indole-tetramer

The syntheses of structural isomers of bis-indole alkaloid caulerpin are investigated. Construction of the caulerpin skeleton is based on the Fisher indolization reaction of the appropriate cyclooctane-diones or cyclooctanone. In addition, a step-by-step synthesis of one isomer from possible four cyclic indole-tetramers has first been described.     

Two intermediates in the synthesis of deca­hydro­iso­quinolines with NMDA and AMPA receptor antagonist activity

In 6‐methyl‐N‐(4‐nitro­benzoyl)‐5,6‐di­hydropyridin‐2(1H)‐one, C₁₃H₁₂N₂O₄, (I), the piperidone ring is in a distorted half‐chair conformation. In 8‐methoxy‐3‐methyl‐N‐(4‐nitro­benzoyl)‐1,2,3,4,5,6,7,8‐octa­hydro­iso­quinoline‐1,6‐dione, C₁₈H₂₀N₂O₆, (II), the heterocyclic ring is in a slightly distorted half‐boat conformation, while the other six‐membered ring is in a distorted chair conformation. Compound (II) presents a strong intramolecular C—H?O hydrogen bond. In both (I) and (II), the mol­ecules interact through C—H?O interactions.     

Boron trifluoride-induced reactions of phenylglycidyl ethers: a convenient synthesis of enantiopure, stereodefined fluorohydrins

Ring-opening hydrofluorination of enantiomerically pure (2S,3S)-3-arylglycidyl ethers (aryl = phenyl, 4-trifluoromethylphenyl) by boron trifluoride-diethyl ether under mild conditions provides β-fluoro alcohols in good yield in a stereospecific manner with complete regiocontrol.     

Reactive intermediates in the H-phosphonate synthesis of oligonucleotides

The formation of H-phosphonate diesters is an important step in the synthesis of oligonucleotides. Using diphenylchlorophosphate as the activator for the coupling step is often accompanied by side reactions as a result of self 'capping' and other reactions of the reactive intermediate. In the absence of base, the activation of ethyl H-phosphonate with diphenylchlorophosphate probably occurs through the intermediate formation of bis diethyl pyro-di-H-phosphonate rather than the expected diphenyl ethyl pyro-H-phosphonate. Pyridine acts as a nucleophilic catalyst converting diphenylchlorophosphate to its pyridinium adduct. Several side and unwanted reactions are quantified so that conditions to minimise these can be identified.     

Solid phase synthesis of 4-hydroxycinnamic acid and its derivatives for potential use in combinatorial chemistry: a novel route for the synthesis of 4-hydroxycinnamoyl coenzyme A and NMDA receptor antagonists

Synthesis of 4-hydroxycinnamic acid 6 and its N-hydroxysuccinimide ester 8 has been carried out in high yield on solid support. Further development allowed the synthesis of 4-hydroxycinnamoyl CoA 1 in excellent overall yield. The utility of solid phase as a method for the synthesis of 4-hydroxycinnamic acid derivatives was demonstrated by the synthesis of a number of compounds including the NMDA receptor antagonists, N-(phenylalkyl)cinnamides 9 and 10.     

Convenient route to enantiopure substituted butyrolactones: application in a formal synthesis of both enantiomers of enterolactone

A simple route for the synthesis of enantiopure substituted γ-butyrolactones involving a highly diastereoselective alkylation of an enantiomerically pure substituted latent succinate ester is described. This route provides entry into both enantiomers of 3,4-disubstituted butyrolactones from a single enantiomer, 2,3-di-O-cyclohexylidine-R-(+)-glyceraldehyde. The synthetic potential of this methodology has been demonstrated by a formal synthesis of both enantiomers of enterolactone.     

Shifting the equilibrium of a biocatalytic cascade synthesis to enantiopure epoxides using anion exchangers

Hydroxide-loaded anion exchangers have been successfully employed to shift the equilibrium of a one-pot, two-step, two-enzyme cascade reaction affording enantiopure epoxides starting from prochiral α-chloroketones. The α-chloroketones were asymmetrically reduced employing an alcohol dehydrogenase and then transformed further to the corresponding epoxides employing halohydrin dehalogenases. Each epoxide enantiomer could be obtained with up to 93% conversion in enantiomerically pure form (>99% ee). In contrast to previous studies the amount of hydride donor (2-propanol) could be reduced due to favoured halohydrin formation in the reduction of α-chloroketones.     

4-tetrahydropyranthioazetidinyl phosphoranes: Versatile intermediates in the synthesis of 2-penems

The total synthesis of four racemic $\text{trans}$-6-ethyl-2-penems has been developed using the 4-tetrahydropyranthioazetidinyl phosphorane $\text{10}$ as a common precursor.     

1,4-Benzodiazepine N-nitrosoamidines: useful intermediates in the synthesis of tricyclic benzodiazepines

1,4-Benzodiazepine N-nitrosoamidines have been used as scaffolds for the preparation of different tricyclic derivatives. Replacement of the N-nitrosoamidine moiety through treatment with the nucleophiles acetylhydrazine, aminoacetaldehyde dimethylacetal and 1-amino-2-propanol, followed by an acid-catalyzed cyclization step, afforded triazolo and imidazobenzodiazepines 1, 6, and 7, respectively, in good yields. When acetylhydrazine is used as a nucleophile, the overall process provides an alternative route to alprazolam (1b) and triazolam (1c), respectively.     

Possible intermediates in the discharge synthesis of diboron tetrahalides

When boron trichloride and tribromide are passed through a radiofrequency discharge to prepare the corresponding sub-halides, BCl and BBr can be detected spectroscopically. It is suggested that they are intermediates in the formation of B₂Cl₄, B₄Cl₄ and B₂Br₄. By the same technique, good yields of B₂I₄ are obtained from BI₃, although no BI could be detected because of the presence of much free I₂. Using a microwave discharge, although no known BI bands were observed, four new bands assigned to BI were found in an emission spectrum once again largely dominated by I₂.     

The synthesis of key intermediates in cembranolides

Two key intermediates of cembranolides- (2E,6E,10E)-3,7,11,15-tetramethyl-9-phenylsulfonyl-2,6,10,14-tetraen-1-hexadecanol (1) and (2E,6E,10E,14E)-2,6,10,14-tetramethyl-8-phenylsulfonyl-2,6,10,14-tetraen-1,16-hexadecanediol (2) were synthesized starting from geraniol and linalool and some improved synthetic methods were used.