Short asymmetric syntheses of homoallylic, homopropargylic and allenic silylated primary amines

Amino alcohols derived from phenylglycinol and having vinyl-, alkynyl- or allenylsilane moieties were transformed in the corresponding primary amines in two steps: oxidative cleavage of phenylglycinol and transimination with phenylhydrazine. This methodology gave general access to enantiomerically enriched amines without loss of enantioselectivity.     

Chiral separation of amino-alcohols using extractant impregnated resins

The performance of extractant impregnated resin (EIR) technology for chiral separation of amino-alcohols has been investigated. Phenylglycinol was selected as an archetype model enantiomer and azophenolic crown ether was used as a versatile enantioselective extractant. 1-Phenyloctane was selected as a suitable solvent for this application because of its very low solubility in water. The extraction system was first evaluated by liquid-liquid equilibrium experiments. It was shown that crown ether dissolved in 1-phenyloctane has an intrinsic selectivity of 11.5. However, due to very low solubility of phenylglycinol in 1-phenyloctane, the overall capacity of the crown ether solution in 1-phenyloctane is limited. The extractant solution was immobilized in macroporous polypropylene particles. Competitive sorption isotherms were obtained from batch experiments and successfully described with a predictive model based on the complexation constants and partitioning ratios, either obtained from literature or from independent experiments. The equilibrium selectivity of these EIRs approaches the intrinsic selectivity for low phenylglycinol concentrations. The dynamic behaviour and stability of the system were examined in column experiments. Breakthrough profiles as well as the elution curves of the R enantiomer are less sharp than those of the S enantiomer proving that the R enantiomer is strongly retained on the column. Separation of phenylglycinol enantiomers is favoured by using lower feed flow rates. The column was regenerated by water with only atmospheric carbon dioxide dissolved which proved to be sufficient. After several cycles the breakthrough profiles remain unchanged suggesting that these EIRs will be sufficiently stable.     

Enantioselective borodeuteride reduction of aldimines catalyzed by cobalt complexes: preparation of optically active deuterated primary amines

[reaction: see text] The enantioselective borodeuteride reduction catalyzed by optically active beta-ketoiminato cobalt complexes was applied to N-(di(o-tolyl)phosphinyl)aldimines to afford the corresponding optically active deuterated primary amines in high yields with high enantiomeric excesses after simple deprotection. The present deuteride reduction of aldimines is in the opposite sense of the enantioselective for the previously reported borohydride reduction of ketones or diphenylphosphinyl aldimines. The stereochemical course in these enantioselective reductions is discussed.     

Synthesis of Chiral Crownophanes Having Two Phenolic Groups via Tandem Claisen Rearrangement and Their Chiral Recognition

Asymmetric crownophanes having a chiral binaphthyl unit and two phenolic hydroxyl groups were thermally synthesized from the corresponding macrocyclic ethers via tandem Claisen rearrangement. Circular dichroism (CD) spectroscopic studies and HPLC experiments confirmed that little racemization of these crownophanes occurred during the thermal rearrangement. The association constants for the interaction of the chiral crownophanes with the enantiomers of phenylethylamine, phenylglycinol, and phenylalaninol were determined by a ¹H NMR titration method in CD₂Cl₂. As a result, the 27 membered crownophane has some chiral recognition for phenylglycinol.     

Synthesis of New Schiff Bases and Assessment of Their in vitro Biological Effects on Acetylcholinesterase and Carbonic Anhydrase Isoenzymes Activities

Russian Journal of Organic Chemistry - In this study, three new Schiff bases have been synthesized by the reactions of commercially available phenylglycinol, phenylalaninol, and leuicinol with...     

A novel reductive dimerization/oxidative dehydrogenation of aldimines mediated by lanthanoid metals.

A lanthanoid metal-mediated novel reductive dimerization/oxidative dehydrogenation of a variety of aldimines has been achieved. Aromatic aldimines (1) were dimerized in the presence of 0.5 mol of ytterbium metal (Yb) and 1-naphthaldehyde (1-NpCHO) to give the corresponding vicinal diimines (2) in good to high yields. Samarium metal (Sm) or samarium(II) diiodide (SmI2) gives unsatisfied yields under the same reaction conditions. As an oxidant, 1-NpCHO gives the best result. In addition, HMPA plays an important role as a cosolvent in this reaction. Reaction of various aldimines with Yb metal is discussed in detail. Moreover, it has been found that the electron-donating substitutents on the benzene ring promote the reaction and that the electron-withdrawing substitutents retard the reaction. The reaction of deuterated N-benzylideneaniline with Yb metal confirmed that transformation of the hydride occurred from aldimines to the oxidant aldehyde. The mechanism of the reaction was discussed.     

Reactivity of α-chloro-aldimines

A series of secondary N-1-(2-chloroalkylidene)amines has been prepared by condensation of disubstituted acetaldehydes with primary amines followed by chlorination with N-chlorosuccinimide in carbontetrachloride. A study of the reactivity of these N-homologues of α-chloroaldehydes is described. Treatment of the title compounds with sodium methoxide in methanol gave high yields of α,β-unsaturated aldimines. However, N-1-(2-chloro-2-methylpropylidene)amines afforded a mixture of elimination and rearrangement products, which proceeded via an aziridine intermediate. On the other hand, α-phenyl-substituted α-chloro aldimines on treatment with methoxide in methanol underwent α-substitution, consistent with an S_N1 mechanism. Powerful nucleophiles such as sodium thiophenolate in methanol and sodium azide in acetone caused α-substitution. Reaction of α-chloro aldimines with Grignard reagents produced coupling of two aldimine units or α-alkylation. Finally the reactivity of α-chloro aldimines was compared with the reactivity of the corresponding oxygen-analogues, i.e. α-chloro aldehydes.     

Highly selective fluorescent recognition of amino alcohol based on chiral calix[4]arenes bearing L-tryptophan unit

Four two-armed chiral calix[4]arenes (1a–1d) functionalised at the lower ring with amino acid units have been synthesised and the structures of these compounds were characterised by IR, MS, ¹H NMR, ¹³C NMR spectra and elemental analysis. Their molecular recognition abilities towards amino alcohol were examined by fluorescence titration experiment in three kinds of solution. The results indicated that these receptors exhibited excellent fluorescent response to phenylglycinol and could distinguish phenylglycinol from phenylalaninol rapidly through the obvious difference in the fluorescent response. Solvent comparative experiments also indicated that acetonitrile was the best solvent to detect these phenomena.     

A practical procedure for the removal of the phenylethanol moiety from phenylglycinol-derived lactams

Chiral non-racemic bicyclic lactams derived from phenylglycinol have been appointed as key building blocks for the preparation of enantiopure nitrogen compounds. The removal of the chiral inductor leading to substituted piperidones by using air or oxygen in basic media is presented.     

3+2] cycloaddition reactions of cyclopropyl imines with enones

A nickel-catalyzed [3+2] cycloaddition of cyclopropyl aldimines and enones has been developed. The process provides direct access to trisubstituted cyclopentanes, and the scope exceeds that of the corresponding reactions involving cyclopropyl ketones. A basis for the improved performance of cyclopropyl aldimines compared with cyclopropyl ketones is provided.     

Magnesium Aldimines Prepared by Addition of Organomagnesium Halides to 2,4,6-Trichlorophenyl Isocyanide: Synthesis of 1,2-Dicarbonyl Derivatives

The selective addition of organomagnesium reagents to 2,4,6-trichlorophenyl isocyanide leading to magnesiated aldimines is reported. These aldimines react with Weinreb amides, ketones, or carbonates to provide the corresponding carbonyl derivatives after acidic cleavage. This allows for an efficient synthesis of 1,2-dicarbonyl compounds and α-hydroxy ketones.     

A General Approach for the Enantioselective Synthesis of anti-β-Hydroxy-α-Amino Acids: Preparation of an Oxazolidine-Functionalized Chiral Glycine Equivalent

The preparation of 2,4-disubstituted oxazolidine-functionalized glycine ester 3a derived from phenylglycinol is described.

     

Etude des aldimines lithiees: II. Preparation d'aldehydes a groupement halogenovinylique. Application a la synthese d'oxo-3 cyclopentenes et d'aldehydes γ acetyleniques

The condensation of metallated aldimines, prepared from activated lithium dialkylamides, with different dihalogenoalkenes gives aldehydes with a halogenovinylic group. Acidic hydrolysis of these aldehydes leads directly to cyclopentenones. When treated with an excess of activated amide, halogenovinylic aldimines give γ-acetylenic aldehydes.     

Über die Hydrierung α-cyanoäthylierter Aldimine

The catalytic hydrogenation of α-mono- and bis-cyanoethylated aldimines The catalytic hydrogenation of α-mono- and -bis-cyanoethylated aldimines using nickel catalysts was studied. Piperidine derivatives are formed in intramolecular cyclization reactions. The hydrogenation products of α-bis-cyanoethylated ketones, the decahydro-1, 8-naphthyridines, are observed here only as by-products.     

An efficient method for the phosphonation of C=X compounds

Reaction of trialkyl phosphites with C=X electrophiles (aldehydes, ketones, ketophosphonates, aldimines, ketimines, isocyanates, isothiocyanates, and activated olefins) in the presence of amines and anilines hydrohalides was studied. We found that pyridine hydrohalides effectively activate the reaction of tralkyl phosphites with various C=X electrophiles: aldehydes, ketones, ketophosphonates, aldimines, ketimines, isocyanates, isothiocyanates, and activated olefins. Particularly high activity showed pyridine hydroiodide. This reaction is a convenient method of synthesis of hydroxyphosphonates, aminophosphonates, carbamoylphosphonates, carbamoylthiophosphonates, and methylenebisphosphonates.     

Zinc-mediated highly α-regioselective prenylation of imines with prenyl bromide

A highly α-regioselective prenylation of imines has been successfully developed. The efficiency of this approach is confirmed by a wide range of imines including N- and C-aryl aldimines, N-alkyl aldimines, C-alkyl aldimines, and N- and C-aryl ketimines. The approach uses prenyl bromide as the prenyl source and inexpensive and convenient zinc as the mediator as well as environmentally benign 1,3-dimethyl-2-imidazolidinone (DMI) as the solvent.     

Reaction of singlet oxygen with α,β-unsaturated aldimines

The reaction of singlet oxygen with N-1-(2-alkenylidene)-t- butylamines ( and ) gives the unsaturated hemiperacetal derivatives ( and 4) of the hydroperoxy aldimines ( and ). Several α, β-unsaturated aldimines which are held in the s-trans conformation failed to react with singlet oxygen.     

Asymmetric Mannich-Type Reactions of Aldimines with a Chiral Acetate

We introduce here a strategy that enables effective addition of lithium enolates of acetates to aldimines. The new method depends strongly on the use of o-alkoxy (or o-fluoro) aniline-derived aldimines which have been found to have a potential effect on the enolate addition. This scope was expanded to the asymmetric process using the chiral acetate. A Lewis acid additive has a complementary role in the pronounced activation of imine functionalities.     

Synthesis of thiazole aminophosphine oxides, aminophosphonic and aminophosphinic acids and Cu(II) binding abilities of thiazole aminophosphonic acids

A series of new aminophosphine oxides, aminophosphonic and aminophosphinic acids derived from thiazole was synthesized by addition of phosphine oxides or silylated phosphorus esters to the corresponding thiazole aldimines. The thiazole aldimines were obtained from 2-thiazole aldehyde and primary amines by a standard procedure. The corresponding phosphine oxides were obtained by alkylation of diethyl phosphite or ethyl phenylphosphinate with the appropriate Grignard reagents. The silylated phosphorus esters were prepared from trimethyl phosphite and from methyl- or phenylphosphinic ethyl ester by treatment with bromotrimethylsilane. The coordination ability towards Cu(II) ions are described for two obtained aminophosphonate ligands.     

Asymmetric radical addition of ethers to enantiopure N-p-toluenesulfinyl aldimines, mediated by dimethylzinc-air

Asymmetric radical addition of ethers to enantiopure aromatic N-p-toluenesulfinyl aldimines has been achieved. The requisite radicals were generated by dimethylzinc-air. Lewis acid activation of the N-p-toluenesulfinyl aldimines followed by radical addition gives a mixture of sulfinamide and sulfonamide products. Subsequent treatment of the mixture with dry m-CPBA affords the sulfonamide product in enantiomerically enriched form. [reaction: see text]