Push-pull amino-nitro helicenes: synthesis, (chir)optical properties and self-assembly into thin films.

A series of regioisomeric push-pull amino-nitro [6]helicenes and a related [7]helicene derivative were prepared and their racemates resolved into enantiomers. Compared to the parent helicenes, they exhibit red-shifted UV-Vis spectra, pronounced dipole moments, altered chiroptical properties such as remarkable optical rotatory power, and can form nanocrystalline Langmuir-Blodgett films.

Synthesis of Racemic, Diastereopure, and Enantiopure Carba- or Oxa[5]-, [6]-, [7]-, and -[19]helicene (Di)thiol Derivatives.

A series of carba- or oxa[5]-, [6]-, [7]-, and -[19]helicene (di)thiols was prepared. The Miyazaki-Newman-Kwart rearrangement of (dimethylcarbamothioyl)oxy (oxa)helicenes in a flow reactor or nucleophilic substitution of dichloro (oxa)helicenes with alkanethiolates were used in the sulfanylation step. Despite the high temperatures employed in this key step, no conformational scrambling was observed during the asymmetric synthesis of the diastereo- and enantiopure oxahelicenes. Single-molecule conductivity of the longest oxa[19]helicene dithiol derivative was studied by the scanning tunneling microscopy break-junction method.

[2+2+2] Cycloisomerisation of Aromatic Cyanodiynes in the Synthesis of Pyridohelicenes and Their Analogues.

We have developed a methodology for the synthesis of pyridohelicenes and their analogues based on the Ni(0) -, Co(I) - or Rh(I) -mediated intramolecular [2+2+2] cycloisomerisation of cyanodiynes. It allows for folding the linear precursors into the corresponding helical backbones comprising the newly formed pyridine unit in their central part. Along with racemic pyrido[n]helicenes (n=5,6,7) and their derivatives, both enantio- and diastereomerically pure pyrido[n]helicene-like molecules (n=5,6) were prepared by employing the chiral substrate-controlled cyclisation of the corresponding enantiopure cyanodiynes.

Rapid access to dibenzohelicenes and their functionalized derivatives.

Spiraling up: Easy access to dibenzo[5]-, dibenzo[6]-, and dibenzo[7]helicenes as well as their functionalized derivatives includes Sonogashira and Suzuki-Miyaura couplings, desilylation, and [2+2+2] alkyne cycloisomerization. The simplicity of this non-photochemical approach combined with the potential for helicity control favors dibenzohelicenes over the parent helicenes for practical applications.

A Ferrier-type allylic rearrangement of 3'-deoxy-3',4'-didehydronucleosides mediated by DMF dimethyl acetal: direct access to 4'-alkoxy-2',3'-didehydro-2',3'-dideoxynucleosides.

A straightforward synthesis of epimeric 4'-alkoxy-substituted 2',3'-didehydro-2',3'-dideoxynucleosides via a DMF dimethyl acetal mediated allylic rearrangement of 3'-deoxy-3',4'-didehydronucleosides is described.

Synthesis of α-carboxyphosphinopeptides derived from norleucine.

In the present study, we describe in detail the synthesis of a relatively rare class of phosphorus compounds, α-carboxyphosphinopeptides. We prepared several norleucine-derived α-carboxyphosphinic pseudopeptides of the general formula Nle-Ψ[PO(OH)]-Gly. These compounds could have important applications as transition state-mimicking inhibitors for methionine or leucine aminopeptidases or other enzymes. For the preparation of the key α-carboxyphosphinate protected precursors, we investigated, compared and improved two different synthetic methods described in literature: the Arbuzov reaction of a silylated N-protected phosphinic acid with a bromoacetate ester and the nucleophilic addition of a mixed O-methyl S-phenyl N-protected phosphonic acid or a methyl N-protected phosphonochloridate with tert-butyl lithioacetate. We also prepared two N-Fmoc protected synthons, Fmoc-Nle-Ψ[PO(OH)]-Gly-COOH and Fmoc-Nle-Ψ[PO(OAd)]-Gly-COOH, and demonstrated that these precursors are suitable building blocks for the solid-phase synthesis of α-carboxyphosphinopeptides.

Acidity of ortho-substituted benzoic acids: an infrared and theoretical study of the intramolecular hydrogen bonds.

The structures of ortho-substituted benzoic acids with substituents bearing hydrogen atoms (OH, NH2, COOH and SO2NH2) were investigated by means of IR spectroscopy and of density functional theory at the B3LYP/6-311 + G(d,p) level. All possible conformations, hydrogen bonds, tautomeric forms and zwitterions were taken into consideration and particular attention was given to intramolecular H-bonds and their effect on acidity. Strong H-bonds in the anions of all four acids, were revealed by calculations. In three cases they were confirmed by the IR spectra of the tetrabutylammonium salts in tetrachloromethane solution, while the salt of 1,2-benzenedicarboxylic acid was not sufficiently soluble. The H-bonds are of different strengths but in all cases they are the main cause of the strengthened acidity of these acids in the gas phase and also in solution, although their effect is opposed by weaker H-bonds present in the undissociated acid molecules. The substituent effect on the acidity was evaluated in terms of isodesmic reactions, separately in the acid molecules and in the anions. While the acidity of the 2-OH and 2-NH2 acids is determined essentially by the H-bonds, that of the 2-COOH and 2-SO2NH2 acids is strengthened by the polar effect operating in the undissociated molecule in addition to the H-bond in the anion. The steric inhibition of resonance (SIR), estimated from model conformations with fixed torsional angles, is of little importance. This analysis goes significantly beyond the classical explanation obtained from the acidities in solution but essentially conforms with it.

N,O-diacylhydroxylamines-structures in crystals and solutions.

The structures of four N,O-diacylhydroxylamines (RCOHNOCOR', R, R'= Me, Ph) were determined in the solid state by X-ray diffraction and studied by NMR and IR spectroscopies in solution. The interpretation of the results was supported by ab-initio calculations of various tautomers and conformers, rotational barriers and chemical shifts. The results indicate the absence of OH tautomers (R-C(OH)=N-O-C(O)-R', N-acyloxyimidic acid); the NH tautomers (R-C(O)-NH-O-C(O)-R', O-acylhydroxamic acid) are present in DMSO solutions as equilibrium mixtures of a few conformers, their exchange being the likely source of 15N and 13C NMR line broadening.

Synthesis of 3-hexahelicenol and its transformation to 3-hexahelicenylamines, diphenylphosphine, methyl carboxylate, and dimethylthiocarbamate.

A nonphotochemical synthetic route to 3-hexahelicenol is reported. It involves a key [2+2+2] cycloisomerization of CH(3)O-substituted triyne that is readily available from 1-methoxy-3-methylbenzene and 1-bromo-2-(bromomethyl)naphthalene. Further functional group transformations led to 3-CO(2)CH(3), 3-NH(2), 3-PPh(2), and 3-SC(O)N(CH(3))(2) substituted hexahelicenes.

Synthesis of [5]-, [6]-, and [7]helicene via Ni(0)- or Co(I)-catalyzed isomerization of aromatic cis,cis-dienetriynes.

An original approach to helicene frameworks exploiting atom economic isomerization of appropriate energy-rich aromatic cis,cis-dienetriynes has been developed. The new paradigm provides nonphotochemical syntheses of helicenes based on the easy, convergent, and modular assembly of key cis,cis-dienetriynes and their nickel(0)-catalyzed [2+2+2] cycloisomerization. The potential of the methodology is underlined by the syntheses of the parent [5]helicene (2), 7,8-dibutyl[5]helicene (23), [6]helicene (24), and [7]helicene (25). The approach can be adapted to prepare functionalized helicenes as exemplified by the eight-step synthesis of 7,8-dibutyl-2,3-dimethoxy[6]helicene (34). Density functional theory (DFT) calculations showed that bis[2-((1Z)-1-buten-3-ynyl)phenyl]acetylene (1) and isomeric [5]helicene (2) differ enormously in the Gibbs energy content (DeltaG = -136.6 kcal x mol(-1)) to favor highly the devised intramolecular simultaneous construction of three aromatic rings.

Conformation and Steric Effects in Mono- and Dimethoxybenzoic Acids.

The conformation of mono- and dimethoxybenzoic acids in solution was determined from their IR spectra and (13)C and (1)H NMR spectra. The main feature is a strong intramolecular hydrogen bond in all 2-methoxy derivatives that persists even in polar aprotic solvents but not in methanol. The methyl groups are mostly coplanar with the ring plane, the two planar conformations are almost equally abundant, and their conformation is not responsible for some enhanced values of the enthalpy of formation. The hydrogen bond (and possibly dimerization) is the reason for differences in the relative acidities (deltapK = pK - pK(H)) measured either in dimethyl sulfoxide or in methanol and also for the differences between deltapK values of methoxybenzoic acids and corresponding methylbenzoic acids. Nevertheless, it was possible to separate with good approximation the polar and steric effects on the acidity. The steric effects in methanol are then parallel for methyl- and methoxybenzoic acids despite variable conformation of the latter. Steric effects in dimethyl sulfoxide are smaller and less regular. The acidity enhancement by ortho substituents is better described as electrostatic induction in the anion rather than a steric hindrance.