Aminocatalytic enantioselective 1,6 additions of alkyl thiols to cyclic dienones: vinylogous iminium ion activation

Remote transmission: In the presence of chiral amines, 2,4-dienones are activated toward the attack of a nucleophile at the δ?position, a mode of activation that is termed vinylogous iminium?ion catalysis. Specifically, the 1,6?addition of alkyl thiols to β-substituted cyclic dienones was catalyzed by a cinchona-based primary amine; the reaction was highly stereoselective and displayed high selectivity for reaction at the δ?position.     

High regioselectivity in electrochemical α-methoxylation of N-protected cyclic amines

N-Protecting groups of α-substituted cyclic amines strongly affected the regioselectivity in electrochemical methoxylation of these compounds. Namely, N-acyl derivatives were transformed into α′-methoxylated compounds, while N-cyano derivatives changed into α-methoxylated derivatives. Furthermore, Lewis acid catalyzed nucleophilic substitution of the α-methoxylated compounds protected with cyano group afforded α,α-disubstituted cyclic amines.     

Ru/C catalyzed cyclization of linear α,ω-diamines to cyclic amines in water

A facile and convenient way to prepare cyclic amines in water was achieved by the catalyst system composed of Ru/C and Al powder. The α,ω-diaminoalkanes, 1,4-diaminobutane, 1,5-diaminopentane, and 1,6-diamino-heptane were converted to corresponding cyclic amines in good yields. The use of D₂O provided a novel route to obtain deuterated cyclic amines in good yields.     

Synthesis of some new α,α-dioxoketene-N,S- and -N,N-acetals derived from secondary aliphatic amines

A total of 11 new α,α-dioxoketene- N,S -acetals (2a–2k) and two new α,α-dioxoketene- N,N -acetals (3j and 3k) have been synthesised by treating 3-[bis(methylthiol)methylene]pentane-2,4-dione (1) with increasing mole ratios of secondary aliphatic amines at room temperature, in either toluene or ethanol. Eight non-cyclic N -methylalkyl and N -ethylalkyl amines and the azacyclopentane of pyrrolidine yielded exclusively mono-substituted N,S -acetals (2a–2i), while the azacyclohexanes of piperidine and morpholine yielded the mono-substituted N,S -acetals 2j and 2k and the double-substituted N,N -acetals 3j and 3k. The conversion yields for the reactions in ethanol are considerably higher than those in toluene. Furthermore, the secondary aliphatic amines with an N -methylalkyl moiety, which have one primary α-carbon and less steric crowding around the nucleophilic nitrogen, appear to be more reactive towards 1 than those with the N -ethylalkyl group, which have two primary α-carbons; further, the latter amines are more reactive than the amines with secondary α-carbons.     

Asymmetric synthesis of allylic secondary alcohols: a new general approach for the preparation of α-amino acids

A new general approach for the synthesis of optically active α-amino acids has been developed. The key steps involve a ruthenium catalysed cross-coupling reaction to give a range of α,β-unsaturated ketones, which were then reduced to allylic secondary alcohols in the presence of a chiral CBS oxazaborolidine. A thermal Overman rearrangement was used to prepare a series of allylic trichloroacetimidates and these were converted under standard conditions to the target α-amino acids in good overall yields.     

The α-effect of oximate ions and solvent effect in the transfer of the toluenesulfonyl group in aqueous dimethylsulfoxide

The kinetic behaviour of oximate ions was studied in the transfer of the toluenesulfonyl group in aqueous dimethylsulfoxide (0–95 vol.% DMSO). The solvation effects of the solvent are a factor controlling the nucleophilicity and magnitude of the α-effect of the oximate ions. L. M. Litvinenko Institute of Physical Organic and Coal Chemistry, National Academy of Sciences of Ukraine, 70 R. Lyuksemburg ul., Donetsk 340114, Ukraine. Translated from Teoreticheskaya i éksperimental'naya Khimiya, Vol. 36, No. 1, pp. 30–35, January–February, 2000.     

On the mechanism of ion exchange in zirconium phosphates—XXI Intercalation of amines by α-zirconium phosphate

The intercalation of n-propylamine, n-butylamine and ethylenediamine by the layered compound α-zirconium phosphate has been examined. Each of the amines forms a number of phases whose interlayer spacings are indicative of the orientation of the amines within the layers. At low uptakes of the n-alkyl amines, they appear to lie parallel to the layers. At higher contents a double layer forms with the carbon chain backbone roughly inclined at a 60° angle to the plane of the layer. A maximum of one n-alkyl amine molecule per phosphate group is intercalated. Half as much ethylenediamine is intercalated which constitutes the same number of amine-groups. The interlayer spacings indicate, however, that the ethylenediamine chain always lies parallel to the layer but in at least four different orientations, giving rise to as many phases.     

The efficient consecutive β-carboxylation and α-alkylation of cyclic α,β-enones; a new route to sarkomycin

Sequential one-pot introduction of a carboxy group equivalent and an alkyl group at the respective β- and α-positions of cyclic enones has been achieved through a 1,4-addition reaction of [methoxy(phenylthio)(trimethylsilyl)methyl] lithium followed by direct trapping of the resulting enolate with alkyl halides. The present method proved to be applicable to a simple synthesis of sarkomycin.     

β-Trimethylsilylethanesulfonyl chloride (SES-Cl): A new reagent for protection of amines

The title compound, easily prepared in two steps from vinyltrimethylsilane, is a useful reagent for the protection of primary and secondary amines as their sulfonamides, which are cleaved by fluoride ion.     

Acetals: a new organocatalysis chemotype for one-pot enantioselective α-amination

Conditions are described for one-pot Brønsted acid and organocatalysed enantioselective α-amination of acetals and associated functionalities. Of the organocatalysts screened, proline tetrazole gave the highest ee, while aqueous monochloroacetic acid proved to be the best Brønsted acid activator regarding minimizing racemization and maximizing product yield. The reaction opens up the way for using masked carbonyl functionalities in organocatalysis.     

The use of ∝-diazo-γ-butyrolactone in the Büchner-Curtius-Schlotterbeck reaction of cyclic ketones: A facile entry into spirocyclic scaffolds

The first example of the Büchner-Curtius-Schlotterbeck reaction of cyclic ketones with a stabilized cyclic diazo compound partner is described. The approach towards spirocyclic scaffolds has been exemplified with readily available ∝-diazo-γ-butyrolactone. The reaction proved to be viable with BF₃?OEt₂ as the preferred catalyst and displayed substantial sensitivity to the size of the cyclic ketone.     

A new “hydrophobic template” method detects segments forming transmembrane α-helical bundles in ion channels

We present a “hydrophobic template” method enabling recognition of α-helix bundles in membrane channels from sequence analysis. Inspection of hydrophobic properties of pore-forming helices in proteins with known structure (A-B₅ toxins) permits delineation of a common polarity motif: two hydrophobic surface stretches separated by polar areas. The bundles are stabilized by nonpolar interhelical contacts. A number of transmembrane segments were checked for presence of this motif, and it was detected for pore-forming helices of several ion transporters (segments M2 of acetylcholine and GABA_A receptors, α5 peptide of δ-endotoxin), which reveal five α-helix bundle architecture. Applications of the method to modeling of membrane channels are discussed. Received: 24 April 1998 / Accepted: 3 September 1998 / Published online: 7 December 1998     

N-Methylanilinium trifluoroacetate-promoted Prins reaction of α-methylene-α-tetralone dimers: generation of new molecular scaffolds

α-Methylene-α-tetralone dimers (8-10) are shown to undergo a diastereoselective Prins reaction with paraformaldehyde in the presence of N-methylanilinium trifluoroacetate resulting in 2, 4, and 5. The structure of the new scaffold 2 was confirmed by X-ray crystallographic analysis.     

The efficient preparation of α-substituted serine scaffolds as the chiral building blocks for the synthesis of SPT inhibitors

An efficient stereoselective synthesis of unusual substituted serine synthons 7, 10, 12 is reported. It was shown that highly functionalized furanose 6 has the suitable structure for further synthetic manipulations toward the inhibitors of SPT.     

Trichloroacetonitrile–hydrogen peroxide: a simple and efficient system for the selective oxidation of tertiary and secondary amines

A variety of tertiary and secondary amines were efficiently oxidized to their corresponding N-oxides and nitrones, respectively, using the trichloroacetonitrile–hydrogen peroxide system. The in situ generated trichloromethylperoxyimidic acid is the active reagent for the oxidation processes.     

Helical secondary structures in 2:1 and 1:2 α/γ-peptide foldamers

Oligomers containing both α- and γ-amino acid residues in a 1:1 alternating pattern have recently been shown by several research groups to adopt helical secondary structures. We have begun to explore the folding behavior of oligomers with different α-residue/γ-residue backbone patterns. Previously we reported that the γ-amino acids bearing a cyclohexyl constraint at the C_β–C_γ bond and a variable side chain at C_α strongly promote a helical conformation containing 12-atom CO(i)?H–N(i+3) hydrogen bonds for 1:1 α:γ backbones. Here we report synthesis and crystallographic analysis of 2:1 and 1:2 α/γ-peptides that adopt CO(i)?H–N(i+3) hydrogen-bonded helical conformations.     

The susceptibility of α-helical secondary structure to steric strain: Coarse-grained simulation of dendronized polypeptides

The propensity of a peptide chain for adopting helical secondary structure can be modulated not only through the solvation properties of its side chains but also through their size and shape. Here we examine a coarse-grained model for dendronized polypeptides that focuses on the susceptibility of α-helical structure to the steric strain exerted by hydrophilic pendant groups. Undecorated molecules exhibit a pronounced transition from random coil to helix upon cooling [J. P. Kemp and J. Z. Y. Chen, Biomacromolecules 2, 389 (2001)]. As gauged by specific heat and by order parameters characterizing helicity at several length scales, this transition is quite robust to the introduction of first- and second-generation dendron side chains. More highly branched side chains, however, reduce the entropy of compact states so severely that helical ordering is undetectable over the entire temperature range accessible to our importance sampling methods. Consistent with experimental observations for side chains comparable to those of our model in volume-excluding size and shape, we find the backbone of these third-generation molecules to assume a distended rodlike state that is both stiff and achiral.     

A new insight into ortho-(dimesitylboryl)diphenylphosphines: applications in Pd-catalyzed Suzuki-Miyaura couplings and evidence for secondary π-interaction

ortho-(Dimesitylboryl)phenylphosphines 1 and 2 were applied in Pd-catalyzed Suzuki-Miyaura C-C couplings. Coordination studies were performed in order to rationalize the relationship between structure and reactivity. Full characterization of a Pd(0) complex derived from 1 has evidenced a new coordination mode for phosphine-arylboranes involving secondary π-interaction between one of the mesityl groups at boron and the metal centre.     

The Compton continuum: Nuisance or new information in NAA?

The Compton continuum in large sample neutron activation analysis has a measurable contribution from scattering of gamma-rays in the sample itself besides from scattering in the detector. The continuum, therefore, contains information on the sample’s composition, which may be made available by chemometrics. This hypothesis was tested on four types of animal fodder with similar amounts of mineral supplements. First results indicate indisputable discrimination of the sample types if using peakless parts of the gamma-ray spectra of the natural radioactivity of the materials as well as of those obtained after neutron activation of 1 kg samples. It indicates that the valuable information on differences in, e.g., organic constituents may be obtained by analyzing the Compton continuum.