Sigitas Stončius

Asymmetric reduction of imines with trichlorosilane, catalyzed by sigamide, an amino acid-derived formamide: scope and limitations

Enantioselective reduction of ketimines 6-10 with trichlorosilane can be catalyzed by the N-methyl valine-derived Lewis-basic formamide (S)-23 (Sigamide) with high enantioselectivity (< or = 97% ee) and low catalyst loading (1-5 mol %) at room temperature in toluene. The reaction is efficient with ketimines derived from aromatic amines (aniline and anisidine) and aromatic, heteroaromatic, conjugated, and even nonaromatic ketones 1-5, in which the steric difference between the alkyl groups R(1) and R(2) is sufficient. Simple nitrogen heteroaromatics (8a,b,d) exhibit low enantioselectivities due to the competing coordination of the reagent but increased steric hindrance in the vicinity of the nitrogen (8c,e) results in a considerable improvement. Cyclic imines 32d-d exhibited low to modest enantioselectivities.

Dynamic Kinetic Resolution in the Asymmetric Synthesis of β‐Amino Acids by Organocatalytic Reduction of Enamines with Trichlorosilane

A new methodology based on the organocatalytic asymmetric hydrosilylation of enamines that allows a direct access to a range of β and β -amino acid derivatives was presented. The results show a successful reduction of aromatic substrates, a sterically more hindered ortho-substituted derivatives, and the thiophenyl analogue exhibiting lower reactivity. Fast enamine-imine equilibration is crucial as imines are chiral but racemic, while α-alkyl β-amino acids can be accessed by the symmetrical Mannich reaction. The α-alkyl derivatives have relative and absolute configuration due to their reduction with LiAlH into a known amino alcohols. Predominant formation of the anti isomer in 3o is consistent with conformation of the imine intermediate in the catalytic reduction.

Mechanistic Dichotomy in the Asymmetric Allylation of Aldehydes with Allyltrichlorosilanes Catalyzed by Chiral Pyridine N‐Oxides

Detailed kinetic and computational investigation of the enantio- and diastereoselective allylation of aldehydes 1 with allyltrichlorosilanes 5, employing the pyridine N-oxides METHOX (9) and QUINOX (10) as chiral organocatalysts, indicate that the reaction can proceed through a dissociative (cationic) or associative (neutral) mechanism: METHOX apparently favors a pentacoordinate cationic transition state, while the less sterically demanding QUINOX is likely to operate via a hexacoordinate neutral complex. In both pathways, only one molecule of the catalyst is involved in the rate- and selectivity-determining step, which is supported by both experimental and computational data.

Synthesis and chiroptical properties of enantiopure tricyclo[4.3.0.03,8]nonane-4,5-dione (twistbrendanedione)

Abstract The synthesis of chiral tricyclo[4.3.0.0 3,8 ]nonane-4,5-dione was accomplished starting from enantiomerically pure (+)-(1 S ,5 S )-bicyclo[3.3.1]nonane-2,6-dione 1 . Ring contraction of the latter with thallium(III) nitrate proceeded with high stereoselectivity giving exclusively methyl (+)-(1 S ,4 S )-(+)- exo , exo -bicyclo[2.2.1]heptan-2,5-dicarboxylate 2 . Inversion of the configuration of this diester to the required di- endo derivative was realized via the following reaction sequence. Bromination of the corresponding acid dichloroanhydride and subsequent reduction with zinc in acetic acid gave a diastereoisomeric mixture of esters, from which the endo , endo -ester 5 was isolated by column chromatography. Acyloin condensation of the latter with trimethylchlorosilane in toluene led to intramolecular ring closure, and subsequent oxidation of the enol silyl ether 7 in situ gave tricyclo[4.3.0.0 3,8 ]nonane-4,5-dione 8 . The chiroptical properties of this cage molecule were studied by electronic and vibrational circular dichroism spectroscopy. The (1 R ,3 R ,6 R ,8 R ) absolute configuration of the title structure was also unambiguously proved.

Enantiomer separation and absolute configuration of densely functionalized 2-oxatricyclo[4.3.1.03,8]decanes by CD spectroscopy and chemical correlation

Abstract Enantiomer separation by HPLC on a swollen microcrystalline triacetylcellulose column of highly substituted 2-oxatricyclo[4.3.1.0 3,8 ]decane (2-oxaprotoadamantane) structures afforded enantiomers of this molecule. Application of the octant rule to the carbonyl chromophore to establish the absolute configuration of the enantiomers did not lead to an unequivocal conclusion. The enantioselective synthesis of 4-bromo-3-methoxy-oxaprotoadamantanone was performed from homochiral (+)-(1 S ,5 S )-bicyclo[3.3.1]nonane-2,6-dione thus permitting the assignment of the (1 R ,3 S ,4 S ,6 R ,8 R )-configuration to the title structures.

Mapping lipid and detergent molecules at the surface of membrane proteins

Electron-density maps for the crystal structures of membrane proteins often show features suggesting binding of lipids and/or detergent molecules on the hydrophobic surface, but usually it is difficult to identify the bound molecules. In our studies, heavy-atom-labelled phospholipids and detergents have been used to unequivocally identify these binding sites at the surfaces of test membrane proteins, the reaction centres from Rhodobacter sphaeroides and Blastochloris viridis. The generality of this method is discussed in the present article.

Synthesis of Diastereomeric Bicyclo[3.3.1]nonane Dibenzoyl Esters and Study of Their Chiroptical Properties

A synthesis of diastereomeric bicyclic dibenzoyl esters derived from enantiomerically pure (1S,5S)-bicyclo[3.3.1]nonane-2,6-dione was accomplished. Molecules containing two benzoyl chromophores with different configuration in the bicyclic framework were obtained. Chiroptical properties of the synthesized enantiomerically pure molecules were studied. Diastereomeric esters exhibited exciton couplets in the circular dichroism (CD) spectra because of transannular interaction between non-conjugated benzoate chromophores. The conformational effects and solvent impact on the exciton coupling were examined by CD spectroscopy. Theoretical computation of the CD spectra of diastereomers correctly reproduced the sign of the exciton couplets in the studied molecules, however, no major solvent dielectric constant influence and conformational effects per se on the exciton coupling was observed.

Intramolecular ring closure via ether bond in reaction of α,α′-halogeno bicyclo[3.3.1]nonanediones under basic conditions

The stereoselectivity of halogenation of bicyclo[3.3.1]nonan-2-one 1 and bicyclo[3.3.1]nonane-2,6-dione 2 with molecular bromine and chlorine was studied. The transformation of α-bromo- and chloro-bicyclo[3.3.1]nonanones 3–5 under Favorskii reaction conditions was studied. The reaction of α,α′-dihalogeno diones in the presence of sodium methoxide, ethoxide, propoxide and potassium cyanide led to the intramolecular ring closure via C–O bond formation giving the highly functionalized chiral 2-oxatricyclo[4.3.1.03,8]decane (2-oxaprotoadamantane) structure. Enantiomers of this cage structure were resolved by chiral GLC. The intramolecular ring closure pathway involving the intermediate alkoxybicyclo[3.3.1]nonanolate structure was proposed.

Homoconjugation vs. Exciton Coupling in Chiral α,β-Unsaturated Bicyclo(3.3.1)nonane Dinitrile and Carboxylic Acids

The chiroptical properties of enantiomerically pure bicyclo[3.3.1]nona-2,6-diene-2,6-dicarbonitrile and related acids were studied by circular dichroism spectroscopy and theoretical computations. A consideration of the molecular structure of the synthesized difunctional compounds revealed that chromophores are predisposed to transannular through-space interaction due to a favourable conformation of the bicyclic skeleton and a rather small interchromophoric distance. Evidence for non-exciton-type coupling between the two acrylonitrile and acrylate moieties in 3 and 4, respectively, was obtained by chiroptical spectroscopy and DFT calculations.

Stereoselective Baeyer–Villiger oxidation of some bridged bicyclic diketones

The regioselectivity of the Baeyer–Villiger oxidation of bicyclo[3.3.1]nonane and bicyclo[2.2.2]octane ketones 1–7 with carbonyl groups located at different positions and bearing other substituents in the bicyclic ring is studied. The impact of the formation of the tetrahedral intermediate and the ring-bond migratory aptitude are considered as major factors governing the reactions regioselectivity. The distortion from sp2-hybridization of the valence angle of the C-9 carbonyl group is found to be considerably greater than that at the C-2 carbonyl in bicyclo[3.3.1]nonane-2,9-dione structures according to semiempirical calculations. Highly regioselective oxygen insertion leading to the functionalized oxabicyclic keto lactones is accounted for by kinetic and stereoelectronic factors.