Showing papers in "Tetrahedron-asymmetry in 1994"

Enantiomerically pure guanidine-catalysed asymmetric nitroaldol reaction

Abstract: Enantiomerically pure guanidines with and without C 2 symmetry have been prepared and used as catalysts in the addition of nitromethane to aldehydes (Henry reaction). The influence of the structure and amount of the guanidine, the solvent and the temperature in the enantioselectivity of the nitroaldol reaction has also been studied.

Enantioselective hydrogenation reactions with a full set of preformed and prepared in situ chiral diphosphine-ruthenium (II) catalysts.

Abstract: The new class of 2-methylallyl ruthenium chiral diphosphines 1 are efficient in asymmetric hydrogenation of α,β unsaturated acids and allylic alcohols. The related chiral halogen-containing ruthenium catalysts 2 are prepared from 1 or in situ from (COD)Ru(η) 3 -(CH 2 ) 2 CHCH 3 ) 2 by ligand exchange with the chelating diphosphine followed by protonation (HX) in acetone. This procedure allows rapid screening of chiral phosphines, such as Diop, Chiraphos, Cbd, Bppm, Binap, β-glucophos, Biphemp, MeO-Biphep, Me-Duphos, in ruthenium mediated hydrogenations of prochiral substrates. A high efficiency is displayed by Ru-catalysts having atropisomeric ligands (e.e. up to 99%), and a C 2 symmetric bis(phospholane) has also emerged as a valuable ligand (Me-Duphos, e.e. up to 87% not optimized). Asymmetric hydrogenation of β-keto esters can be conducted under quite mild conditions (4 atm. of H 2 , 50°C, e.e. up to 99%), β-keto esters having a disubstituted double bond are also hydrogenated chemoselectively to unsaturated chiral alcohols under controlled conditions with excellent optical purities.

Enantioselective allylic amination with chiral (phosphino-oxazoline)pd catalysts

Abstract: Chiral (phosphinophenyl-oxazoline)palladium complexes have been studied as enantioselective catalysts for allylic amination using benzylamine or the sodium salts of p-toluenesulfonamide, benzoylhydrazine, and (Boc) 2 NH as nucleophiles. In the reactions with 1,3-diphenyl- and 1,3 -dialkyl-2-propenyl acetates, carbonates, or phosphates, moderate to high enantiomeric excesses of up to 97% have been obtained.

α-Phenylethylamine based chiral phospholidines; new agents for the determination of the enantiomeric excess of chiral alcohols, amines and thiols by means of 31P NMR

Abstract: The synthesis and application of two new trivalent phosphorus derivatizing agents, based upon (S)-α-phenylethylamine, for the enantiomeric excess determination of alcohols, amines and thiols using 31P NMR, is presented.

Synthetic peptide receptor mimics: highly stereoselective recognition in non-covalent molecularly imprinted polymers

Abstract: Ligand-receptor recognition has been studied in a molecularly imprinted polymer (MIP) prepared against N -Ac-L-Phe-L-Trp-OMe. The non-ionic non-covalent interaction based recognition was evaluated using the polymers as chiral HPLC stationary phases. Marked regio-, enantio- and diastereo- ligand selectivity were demonstrated with enantiomer separation factors of up to 17.8. The interaction of a series of related structures with the MIP receptor site has provided insight concerning its nature and the recognition mechanisms.

Novel atropisomeric phosphorus ligands : 4,5-dihydro-3H-dinaphtho[2,1-c;1',2'-e]phosphepine derivatives

Abstract: Atropisomerically pure (S)-4-phenyl-4,5-dihydro-3H-dinaphtho[2,1-c;1′,2′-e]phosphepine 2b has been obtained by resolution of the racemic compound with an enantiopure palladium complex and its absolute configuration has been determined by X-ray analysis; it is an effective chiral ligand for the asymmetric hydroformylation of styrene with rhodium catalysts.

Enantioselective ester hydrolysis catalyzed by imprinted polymers

Abstract: Thefirst imprinted polymers with enantioselective catalytic activity are reported.

Novel, general synthesis of the chiral catalysts diphosphine-ruthenium (II) diallyl complexes and a new practical in situ preparation of chiral ruthenium (II) catalysts

Abstract: A general and new synthesis of hexacoordinate chiral 1-[2-methylallyl]Ru II 2 complexes is presented. This synthesis uses the very accessible CODRu(2-methylallyl) 2 complex as starting material. These complexes (P*P)Ru(η 3 -(CH 2 ) 2 CCH 3 ) 2 (e.g. P*P=DIOP, CBD, DEGUPHOS, BINAP, BIPHEMP, CHIRAPHOS, PROPHOS, DIMPC, BPPM, BDPP, DIPAMP, DIPAMPSi, β-PO-OP) have been characterized spectroscopically. X-Ray structures were obtained for (S,S)-DIOP and (S,S)-CHIRAPHOS. They are suitable for the preparation of chiral dihalide ruthenium (II) catalysts. In addition, we have found that it was possible to prepare these same catalysts directly in situ from (COD)Ru(η 3 -(CH 2 ) 2 CCH 3 ) 2 by adding 1-1.3 equiv. of the appropriate chiral ligand in the presence of HX in acetone at room temperature.

Use of simultaneous face to face and face to edge π-π interactions to facilitate chiral recognition

Abstract: A recendy developed HPLC chiral stationary phase exhibits a general ability to resolve the enantiomers of compounds possessing both an electron rich conjugated π-system and a hydrogen bond acceptor located near the stereogenic center

Origins of the high stereoselectivity in the conjugate addition of lithium(α-methylbenzyl)benzylamide to t-butyl cinnamate

Abstract: A model for the stereoselective conjugate addition of lithium (α-methylbenzyl) benzylamide, to t-butyl cinnamate has been devised, using molecular modelling techniques.

Enantioselective palladium catalysed allylic substitution. Electronic and steric effects of the ligand.

Abstract: Ligands containing an enantiomerically pure oxazoline and a sulfur-containing tether have been examined for their ability to provide asymmetric induction in palladium catalysed allylic substitution reaction. The enantioselectivity obtained was found to be highly dependent upon the stereochemistry at sulfur (for sulfoxides), and also somewhat dependent upon the nature of the aryl group attached to the sulfur.

Enantioselective synthesis of diethyl 1-hydroxyalkylphosphonates via oxazaborolidine catalyzed borane reduction of diethyl α-ketophosphonates

Abstract: Reduction of diethyl α-ketophosphonates 1 with borane and B-butyloxazaborolidine 2 as catalyst afforded diethyl (S)- or (R)-1-hydroxyalkylphosphonates 3a-d or 3e-f respectively in good yields and moderate to good enantiomeric excess (53–83 ee%). Respective diethyl (R)- and (S)-1-amino-alkylphosphonates 6 were obtained in a one-pot transformation, by the Mitsunobu reaction of 1-hydroxyphosphonates 3 with hydrazoic acid, and subsequent treatment of the intermediate azides 4 , with triphenylphosphine, followed by hydrolysis of the iminophosphoranes 5 with water.

Gold(I)-catalyzed asymmetric aldol reactions of fluorinated benzaldehydes with an α-isocyanoacetamide

Abstract: The use of N,N-dimethyl-α-isocyanoacetamide instead of methyl α-isocyanoacetate in the gold(I)-catalyzed asymmetric aldol reactions with polyfluorinated benzaldehydes was found to improve both diastereo- and enantioselectivity in the formation of trans-oxazolines.

Synthesis of the oxindole alkaloid (−)-horsfiline

Abstract: A synthesis of (-)-horsfiline ((-)- 1 ), a metabolite isolated recently from Horsfieldia superba , is described. The diastereoface selectivity of the crucial oxidative rearrangement of chiral tetrahydro-β-carboline precursors into the corresponding oxindoles was investigated in some detail and found to depend critically on the substitution pattern of the aliphatic amino group. These findings were exploited for the preparation of (-)- 1 , as well as of the unnatural optical antipode (+)- 1 , starting from 5-hydroxy-L-tryptophan as the single source from the chiral pool.

Efficient ligands, chiral 2-[2,2-dimethyl-1-(2-pyridyl)propoxy]-1,1-diarylethanols for highly enantioselective addition of alkynylzinc reagents to various aldehydes

Abstract: Formation of optically active secondary alkynyl alcohols ( 3 ) (up to 95% e.e.) by the catalysed asymmetric addition of alkynylzinc reagents to aromatic and aliphatic aldehydes in the presence of the tridentate title ligands ( 1a-c ) is described. Interestingly, enantioselectivity in the reaction was proved to be remarkably dependent on the structures of alkynylzinc reagents.

Asymmetric 1,3-dipolar cycloadditions to 5-(R)-menthyloxy-2(5H)-furanone

Abstract: Various diazo compounds, nitrile oxides, nitrones and azomethine ylides were examined in 1,3-dipolar cycloadditions to enantiomerically pure 5-(R)-menthyloxy-2(5H)-furanone 1a. Pyrazoline 9 was obtained in 100% c.y. as a mixture of 2 diastereoisomers in ratios up to 72 : 28, whereas pyrazoline 16 was obtained in 100 % c.y. as a single enantiomer. Photochemically pyrazolines 9 and 10 have been converted to cyclopropanes 11 and 13. Under thermal conditions pyrazoline 9 is converted to 4-methyl-5-menthyloxy-2(5H)-furanone. Isoxazoles 21a-24a were obtained enantiomerically pure via nitrile oxide addition to 1a in 64-67% yield. Nitrone addition afforded isoxazolidines 27, 28 and 34 with complete anti-facial- and regiochemistry, but with endo-exo selectivities up to 76%. Enantiomerically pure isoxazolidines were obtained in 25-75% yield. Pyrrolidine 36 was obtained diastereomerically pure in 81% c.y. Pyrrolidines 42 and 45, however, were obtained as diastereomeric mixtures in 37% resp. 6% yield.

Biocatalytic resolution of β-fluoroalkyl-β-amino acids

Abstract: N -Phenylacetyl derivatives of β-fluoroalkyl-β-alanines 6 were synthesized and biocatalytically resolved to the corresponding enantiopure β-amino acids 7,9 with the aid of penicillin acylase (EC 3.5.1.11) from Escherichia coli . In substrates 6 the enantioselectivity of the biocatalytic process was practically uninfluenced by the nature of the fluoroalkyl chain. Thus, β-fluoroalkyl-β-alanines 7,9 bearing short (R = CF 3 , CHF 2 ) or long [C 3 F 7 , H(CF 2 )4] chains were prepared in high enantiomeric parity. The ( R )-enantiomer was the fast-reacting enantiomer in all cases.

New fluorinated chiral synthons

Abstract: the syntheses of new optically pure poly-halo and poly-fluoro oxiranes 5b-e by addition of diazomethane on the corresponding β-ketoγ-fluorosubstituted sulphoxide intermediates, both in keto 3 , hydrate 4 or in keto/ hydrate form are described. Syntheses of sulphur-free fluorinated oxiranes 18b-e , β-hydroxy-β-trifluoromethyl amine 21d , α- acid 25d and β,γ-dihydroxy-β-trifluoro- and -chlorodifluoromethyl amines 26c and 26d are shown as examples of their chemical versatility

Chemo-enzymatic approach to the synthesis of each of the four isomers of α-alkyl-β-fluoroalkyl-substituted β-amino acids

Abstract: Starting from easily available ethyl 2-methyl-4,4,4-trifluoroacetoacetate and benzylamine each of the four stereoisomers of α-methyl-β-trifluoromethyl-β-alanine have been synthesized in optically pure form via stereocontrolled chemo-enzymatic procedure including diastereoselective base-catalyzed [1,3]-proton shift reaction and enantioselective penicillin acylase-catalyzed resolution.

Catalysed asymmetric reaction of aldehydes with dialkylzinc in the presence of chiral pyridyl alcohols as ligands

Abstract: The synthesis of homochiral pyridyl alcohols (1,2,3a-c) and a catalytic asymmetric addition of dialkylzinc to various aldehydes using 1-3 as ligands are described. Although the reaction of benzaldehyde with Et2Zn in the presence of (S)-1 and (R,R)-2 gave (S)- and (R)-1-phenyl-1-propanol, respectively, in moderate enantiomeric excess (e.e.), tridentate ligands (3a-c) accelerated the reaction to produce the corresponding alcohols in high e.e. Particularly, (S)-3b was found to be the most efficient catalyst, for which asymmetric reactions of various aldehydes with dialkylzinc gave the corresponding alcohols in good to high e.es. (up to 95% e.e.).

Catalytic enantioselective deprotonation of meso-epoxides by the use of chiral lithium amide

Abstract: Catalytic enantioselective deprotonation of meso-compound is achieved for the first time by the combined use of a catalytic amount of chiral lithium amide, lithium (S)-2-(pyrrolidin-1-ylmethyl)pyrrolidide, and excess lithium diisopropylamide in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene.

Mild stereoselective syntheses of thioglycosides under PTC conditions and their use as active and latent glycosyl donors

Abstract: Mild and stercoselective arylthio glycoside syntheses were accomplished by inversion of configuration of glycosyl halides under phase transfer catalyzed conditions. Under such conditions, aryl α-thiosialosides having electron donating and withdrawing substituents were evaluated as active and latent thioglycosyl donors. A sialyl-α-(2→6)-galactoside was prepared in good yield using the above strategy.

Sulfur derivatives of ephedra alkaloids - new and highly efficient chiral catalysts

Abstract: Sulfur derivatives of ephedrine catalyze the 1,2-addition of diethylzinc to benzaldehyde in high enantiomeric excess. Disulfides and cyclic sulfide derivatives of these compounds serve the purpose very well, and the actual catalytically active species, containing zinc, has been extracted from the reaction mixture.

Synthesis of optically pure (R)- and (S)-α-trifluoromethyl-alanine

Abstract: (+)-(R)- and (−)-(S)-3,3,3-trifluoro-2-methyl-alanine (1) were synthesized from (+)-(R)-methyl-p-tolyl-sulphoxide (5) and N-alkoxycarbonylimino derivatives 4 of methyl 3,3,3-trifluoropyruvate (3) The absolute configuration was determined by X-ray analyses of two synthetic intermediates (2S,RS)-6a and (2R,RS-6c

Oxazaborolidine catalyzed borane reductions of ketones: a significant effect of temperature on selectivity

Abstract: The effect of temperature on the selectivity of oxazaborolidine catalyzed borane reductions of ketones has been studied. For two model ketones, acetophenone ( 2a ) and cyclohexylmethyl ketone ( 2b ), and two different oxazaborolidine catalysts [derived from n-butyl -and phenyl boronic acids with (S)-diphenylprolinol], these reductions were carried out over a range of temperatures in THF and toluene. Our results show that in general there is an increase in selectivity with increasing temperature until 30–50°C where the selectivity then begins to decrease. As a result of these findings, the amount of catalyst for the reduction of acetophenone was reduced from 10 % to 1% with only a small decrease in selectivity (96 % and 94 % respectively). We obtained the highest selectivity ever reported for the reduction of acetophenone by a borane-phenyl substituted diphenylprolinol derived catalyst (98 % ee using the catalyst 1c at 40°C). In addition, we obtained the highest reported selectivity for the reduction of cyclohexylmethyl ketone by a diphenylprolinol derived catalyst (89 % ee using n-butyl-substituted borane catalyst 1b at 50°C).

Chiral recognition of olefins by 1H NMR spectroscopy in the presence of a chiral dirhodium complex

Abstract: A new NMR method using 1 for chiral recognition of olefins is presented and compared with Mannschreck's method using Yb(hfc) 3 /Ag(fod). It was found that the spectroscopic results are comparable but the new rhodium reagent is much easier to handle and can readily be recovered.

An asymmetric synthesis of (−)-carbovir

Abstract: Enantioselective deprotonation of trans -4- t -butyldimethylsiloxymethyl-1,2-epoxycyclopentane ( trans - 4 ) by a chiral lithium amide, lithium ( S )-2-(pyrrolidin-1-ylmethyl)pyrrolidide ( 1 ), afforded (1 S ,4 S )- trans -4- t -butyldimethylsiloxymethyl-2-cyclopenten-1-ol ( trans - 7 ) in 83 %ee. Alcohol trans - 7 was easily transformed to (−)-carbovir, an anti-HIV carbocyclic nucleoside.

Chiral pool synthesis of trans-(2S3S)-3-hydroxyproline and castanodiol from S-pyroglutamic acid.

Abstract: The Pyroglutamic acid derivative 1 was converted through several steps into Castanodiol 9 and 2S,3S-3-Hydroxyproline 11. Key steps of the reaction sequence were the stereoselective epoxidation of 1 to 2 and the regioselective ring opening of 2 to 3. BH 3S(CH3)2 reduction of the amide group of 3 and 4 resulted in a concomitant transformation of the acetal moiety into the N-benzyl protecting group. The air sensitive 5 and 6, were transformed to the stable N-Boc prolinol derivatives 7 and 8. Deprotection of 8 provided 9, white oxidation of 8 gave the protected proline derivative 10. Deprotection of 10 furnished enantiopure 2S,3S-3-Hydroxyprotine 11.

Cyclodextrins, cyclomannins, and cyclogalactins with five and six (1→4)-linked sugar units: A comparative assessment of their conformations and hydrophobicity potential profiles1

Abstract: A molecular modeling study of the (1→4)-linked cyclooligosaccharides containing five and six α- D -glucose, α- D -mannose, and β- D -galactose units, respectively, provide a clear conception of their overall conformations, their contact surfaces, and their cavity proportions. A MOLCAD-based generation of their molecular lipophilicity potential (MLP's) gives a lucid picture of their hydrophobic and hydrophilic surface areas, and hence, a first estimation of their inclusion properties.

Asymmetric synthesis of (2S,3R)-3-amino-2-hydroxydecanoic acid: The unknown amino acid component of microginin

Abstract: 3-Amino-2-hydroxydecanoic acid (AHDA) is an unusual amino acid purported to occur in the recently isolated angiotensin-converting enzyme inhibitor microgipin. In order to elucidate the stereochemistry of the naturally occurring material, and thus complete the structural assignment of microginin, both the (2 R ,3 R )- anti -diastereoisomer and the (2 S ,3 R ) syn -diastereoisomer of AHDA have been prepared. Comparison of the 1 H and 13 C nmr spectroscopic data of the synthetic amino acids with that reported for the naturally occurring material indicates that the relative stereochemisuy of the AHDA found in microginin is syn . The absolute stereochemistry of the natural amino acid is shown to be (2 S ,3 R ) by comparison of its reported CD spectrum with that recorded for the synthetic material prepared herein.