Novel optically active 1,3-aminoalcohols derived from D-glucal

A series of ethyl(phenyl) 6-amino-2,3,6-trideoxy--D-glucopyranosides (amino=piperidino (Pip), pyrrolidino (Pyr), azetidino (Az), Bu₂N) have been prepared from tri-O-acetyl-D-glucal to obtain catalysts for asymmetric synthesis and the starting compounds for the syntheses of other bidentate ligands.Published in Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 45–52, January, 2000.     

Preparation of chiral annulated indenes derived from nopinone, verbenone and menthone

A three-step procedure for the synthesis of chiral annulated indenes is described in which nopinone, verbenone and menthone are converted to their enolate form, alkylated with 2-bromomethylbromobenzene, ring-closed with CrCl₂/cat. NiCl₂ and dehydrated with catalytic acid.     

Stereoselective synthesis of enantiopure γ-aminoalcohols by reduction of chiral β-enaminoketones

The results of the reduction of chiral β-enamino ketones with sodium borohydride in acetic acid are reported. The reaction is convenient, stereoselective and high yielding and allows the preparation of enantiopure γ-amino alcohols in syn diastereoselectivity. The reaction is easy to perform and does not require expensive or hazardous chemicals. A mechanistic hypothesis is presented. The absolute configuration of the products obtained is attributed by correlating ¹H NMR spectral data with conformational analysis performed by molecular modelling, and confirmed by X-ray analysis.     

Highly enantioselective carbonyl reduction with borane catalyzed by chiral spiroborate esters derived from chiral 1,2-aminoalcohols

Novel spiroborate esters derived from nonracemic 1,2-amino alcohols were examined as chiral catalysts in the borane reduction of acetophenone and other aromatic ketones at room temperature. The optically active alcohols were obtained in excellent chemical yields and enantioselectivities up to 99% ee with 10% of catalyst.     

New chiral 1,2-aminoalcohols derived from biomass and their application in diethyl zinc additions

A convenient procedure for the preparation of chiral 1,2-aminoalcohols starting from levoglucosenone, a biomass derivative, is described. The 1,2-aminoalcohols, bearing primary, secondary, and tertiary amino groups, were tested as chiral catalysts in the asymmetric addition of diethyl zinc to benzaldehyde.     

Stereoselective synthesis and transformations of pinane-based 1,3-diaminoalcohols

A library of pinane-based 1,3-diaminoalcohols and 5-aminomethyloxazolidin-2-ones was developed from commercially available (1R)-(?)-myrtenol which was transformed to N-trichloroacetyl protected allyl amine via Overmann rearrangement followed by stereoselective epoxidation with mCPBA resulting in key intermedier epoxy-amine. In order to obtain the diaminoalcohol moiety, aminolysis and azidolysis of the oxirane ring was performed. The cleavage of the oxirane ring proceeded regioselectively, affording N-trichloroacetyl protected 1,3-diaminoalcohols and oxazolidin-2-ones, which were obtained also via a thermal cyclisation. Since N deprotection of diaminoalcohols was unsuccessful under varied conditions, the protecting group was changed and Boc-protected analogues were synthesised. In this case, removal of the Boc protecting group was successful resulting in the planned diamino alcohols. An unexpected extreme δ Me_α-9 value (0.11 ppm) was measured for the dibenzylaminomethyl-substituted oxazolidine-2-one, and the stereostructure was refined by means of DFT geometry optimization. The obtained potential catalysts were applied in the test reaction of benzaldehyde and diethylzinc with low to moderate enantioselectivities (up to 74% ee).     

Stereoselective 1,3-dipolar cycloadditions of a chiral nitrone derived from erythrulose. An experimental and DFT theoretical study

We have investigated several 1,3-dipolar cycloadditions of a chiral nitrone prepared from L-erythrulose. While cycloadditions to carbon-carbon multiple bonds of dipolarophiles such as ethyl acrylate, ethyl propiolate, or dimethyl acetylenedicarboxylate were poorly stereoselective, reaction with acrylonitrile provided predominantly one diastereomeric adduct. Furthermore, the regioselectivity exhibited by the two structurally similar dipolarophiles ethyl acrylate and ethyl propiolate was found to be opposite. The molecular mechanisms of these cycloadditions have thus been investigated by means of density functional theory (DFT) methods with the B3LYP functional and the 6-31G and 6-31+G basis sets. A simplified achiral version of nitrone 1 as the dipole, and methyl propiolate or acrylonitrile as the dipolarophiles, were chosen as computational models. The cycloadditions have been shown to take place through one-step pathways in which the C-C and C-O sigma bonds are formed in a nonsynchronous way. For the reaction with methyl propiolate, DFT calculations predict the experimentally observed meta regioselectivity. For the reaction with acrylonitrile, however, the predicted regioselectivity has been found to depend on the computational level used. The calculations further indicate the exo approach to be energetically favored in the case of the latter dipolarophile, in agreement with experimental findings. The main reason for this is the steric repulsion between the nitrile function and one of the methyl groups on the nitrone that progressively develops in the alternative endo approach.     

Facile syntheses, structural characterizations, and isomerization of disiloxane-1,3-diols

In the hydrolysis reaction of dichlorosilanes having an intramolecular coordinating atom, dcisiloxane-1,3-diols, [(OH){o-(CH₃)₂NCH₂-C₆H₄}RSi]₂O(R=CH₂CH (1), C₆H₅ (2), o-(CH₃)₂NCH₂C₆H₄ (3), Me (4)), were obtained in high yields. The results of the crystal structure analyses of meso-2, rac-2a, rac-2b and 3 are reported. They showed strong intramolecular hydrogen bondings between the hydroxy group and the nitrogen atom. We have also found that the diastereomeric isomerization of meso-2 to rac-2 in CDCl₃ solvent containing moisture occurred to result in the 55:45 equilibrium mixtures of the isomers and vice versa.     

Stereoselective Michael-alkylation and Michael-oxidation reactions of chiral 1,3-dioxolanones

A highly diastereoselective Michael-alkylation/oxidation methodology has been developed for the synthesis of optically active α-hydroxy-1,5-diester subunits. Inverse stereochemistry at the C_2′ position could be achieved by using a Michael acceptor equipped with a suitable group followed by a highly stereoselective protonation. This methodology has been applied to the enantioselective synthesis of the upper fragment of (+)-retusine.     

A chiral auxiliary derived from levoglucosenone in asymmetric Diels-Alder transformations

The Diels-Alder reaction of the acrylate derived from levoglucosenone with cyclopentadiene was studied under several conditions, in the presence and absence of a Lewis acid. The results showed satisfactory diastereomeric excess and the ratio of cycloadducts was found to depend on the reaction conditions. A reversal in stereoselectivity was observed when EtAlCl₂ or Et₂AlCl were employed as Lewis acids.     

NMR determination of the absolute configuration of chiral 1,2- and 1,3-diols

Each of the chiral 1,2- and 1,3-diols examined was derivatized exclusively to a single diastereomeric acetal by the use of a new axially chiral reagent, 2′-methoxy-1,1′-binaphthalene-8-carbaldehyde (MBC). The absolute configuration of the original 1,2- and 1,3-diols was determined by the NOE correlation between the proton signals of the reagent moiety and those of the diol moiety in the acetals.     

Stereoselective syntheses of pinane-based 1,3-diamines and their application as chiral ligands in the enantioselective addition of diethylzinc to benzaldehyde

A library of 1,3-difunctionalized pinane derivatives was synthesized and applied as chiral catalysts in the addition of diethylzinc to benzaldehyde. The key intermediate β-lactam 2 was prepared regio- and stereoselectively from (?)-apopinene 1. The treatment of 2 with di-tert-butyl dicarbonate afforded N-Boc β-lactam 3, while acid-catalyzed ring opening of 2 resulted in amino acid 4. Nucleophilic ring opening of 3 with dimethylamine, followed by deprotection and benzylation, furnished β-amino amides 5, 8, and 11, which were transformed in two steps into the corresponding N-tosyldiamines 7, 10, and 13, respectively. Since the use of other amines, such as diethylamine, to study the influence of dialkyl substitution was unsuccessful, an alternative synthetic route was applied. Amidation of tosylated β-amino acid 14 furnished amides 15–25. Reduction of 15, 16, 19, 20, and 24 resulted in N-tosyl diamines 26–30. The β-amino amides and N-tosylated diamines were used as chiral ligands in the enantioselective alkylation of benzaldehyde with diethylzinc, resulting in (R)- and (S)-1-phenyl-1-propanol. The (R)-enantiomer was predominant except when 17, 22, 23, and 25 were used as ligands, in which case the opposite stereochemistry was observed. The best ee values (up to 83%) were obtained when 17, 20, 23, and 25 were used as catalysts.     

Stereoselective reduction of β hydroxyketones to 1,3-diols highly selective 1,3-asymmetric induction via boron chelates

Highly selective asymmetric induction can be achieved in the reduction of acyclic β-hydroxyketones via boron chelates. Treatment of β-hydroxyketones (1) with tributyl or tri-isobutylborane and successively with sodium borohydride afforded syn-1,3-diols (3) in highly stereo-selective manner, Syn -α-substituted-β -hydroxyketones (8) were also reduced to give syn, syn-1,3-diols (9) exclusively. The reaction was further applied to the convenient preparation of 3-deoxy-hexoses.     

Efficient synthesis of chiral β-and γ-N-tosylaminoalcohols from 1-aryl-2-aminopropane-1,3-diols

(1S,2S)-1-Aryl-2-tozylaminopropan-1-ols were synthesized by cyclization of 1-aryl-2-aminopropane-1,3-diol to aryl(1-tosylaziridin-2-yl)methanols, followed by hydride reduction of the latter. Reduction of the aza-Payne rearrangement products of intermediate aryl(1-tosylaziridin-2-yl)methanols gave (1S)-1-aryl-3-tosylaminopropan-1-ols. Published in Zhurnal Organicheskoi Khimii, 2006, Vol. 42, No. 4, pp. 514–518. The text was submitted by the authors in English.     

Stereoselective multimodal transformations of planar chiral 9-membered diallylic amides

Intermolecular reactions of planar chiral 9-membered diallylic amides provide a variety of bicyclic compounds with central chiralities in a stereospecific fashion with high group selectivity. Lewis-acid-promoted intramolecular reactions of the obtained bicyclic compounds provide transannular products in a stereospecific fashion. Furthermore, a direct transannular reaction of diallylic amide involving sequential intermolecular-intramolecular reactions has been developed.     

Synthesis of chiral 1-ferrocenylaldols and 1-ferrocenyl-1,3-diols via asymmetric reductions

The asymmetric transfer hydrogenation promoted by the (R,R)-(Ts-DPEN)–Ru complex of some 1-ferrocenyl-1,3-diketones was investigated and in all the cases only the carbonyl group distant to the metallocene moiety was reduced with variable selectivity depending on the C-3 substituent. The CBS-catalyzed reduction of 1-ferrocenyl-β-hydroxy-1-ketones, previously protected as acetates, was also found effective, giving both the corresponding syn- and anti-1,3-diols in satisfactory enantiomeric purity.     

Enantiopure 1,4-diols and 1,4-aminoalcohols via stereoselective acyclic sulfoxide-sulfenate rearrangement

Treatment of acyclic α-hydroxy and α-tosylamino sulfinyl dienes with amines affords enantiopure 1,4-diol or 1,4-hydroxysulfonamide derivatives in good yields and diastereoselectivities. This one-pot procedure entails a conjugate addition that triggers a diastereoselective sulfoxide-sulfenate [2,3]-sigmatropic rearrangement.     

Enantioselective addition of organometallics to aldehydes using camphor derived chiral 1,4-aminoalcohols as ligands

(+)-Camphor derived enantiomerically pure 1,4-aminoalcohols have been used as ligands in the addition reactions of n-BuLi and n-BuMgBr to benzaldehyde and in the reaction of diethylzinc with benzaldehyde and hexanal. All chiral secondary alcohols were obtained in good chemical yields and enantioselectivities were up to 87% ee in the addition of diethylzinc.