Showing papers in "Tetrahedron-asymmetry in 1993"
TL;DR: In this paper, a multistep synthesis of the title compound was developed based on the Pd-catalysed coupling of 1-chloroisoquinoline and 2-methoxy-1-naphthylboronic acid.
Abstract: A multistep synthesis resulting in a good yield of the title compound has been developed based on the Pd-catalysed coupling of 1-chloroisoquinoline and 2-methoxy-1-naphthylboronic acid (5). The product is converted into the corresponding trifluoromethanesulphonate (10) by successive demethylation and treatment with (CF3CO)2O, followed by a further Pd-catalysed coupling with Ph2P(O)H. The resulting phosphine oxide (11) was cleanly reduced with HSiCl3. Resolution of the phosphinamine (4) was carried out with the Pd complex derived from (R)-(+)-dimethyl(1-(1-naphthyl)ethyl)amine and PdCl2; the diastereomers were of different stabilities and solubilities and were therefore readily separated. The resolved phosphinamine, [α]D22 ± 153 (c = 1, CHCl3), was enantiomerically stable on heating to 65°C for 24h. X-ray crystal structures of the adduct (16) and the Pd dimer (7) isolated during the initial coupling reaction are presented.
238 citations
234 citations
TL;DR: In this paper, it was found that both enantiomeric excess and regioselectivity to the branched aldehyde strongly depend on the hydroformylation reaction conditions.
Abstract: Chiral diphosphites have been synthesised starting from 1,2:5,6-diisopropylidene- D -mannitol, L -α,α,α,α,-tetramethyl-1,3-dioxolan-4,5-dimethanol and L -diethyltartrate. The diols react in moderate to good yields with 2,2′-bisphenoxyphosphorus chloride and 4,4′,6,6′,-tetra- t -butyl-2,2′-bisphenoxyphosphorus chloride (32–92%) to the corresponding chiral diphosphites. These compounds all exhibit C 2 symmetry and have been used as ligands in the rhodium catalysed asymmetric hydroformylation of styrene. The catalytic activity of the diphosphites strongly depends on the bulkyness of the ligand. With a bulky ligand enantiomeric excesses up till 20% have been obtained under mild reaction conditions (25–40°C, 40 bar syngas). It was found that both enantiomeric excess and regioselectivity to the branched aldehyde strongly depend on the hydroformylation reaction conditions.
162 citations
TL;DR: 3-Alkyl substituted cyclohexanones are obtained in essentially optically pure form and the same chiral ligand, associated with CuI, in catalylic amount (10%), allows the asymmetric conjugate addition of Et2Zn to 2-cyclohexen-1-one.
Abstract: The asymmetric conjugate addition of medium order alkyl cuprate reagents. R5Cu3Li2, to 2-cyclohexen-1-one. 2-cyclopenten-1-one and 2-cyctohepten-1-one, with the help of phosphorus ligand B*, is described. 3-Alkyl substituted cyclohexanones are obtained in essentially optically pure form. The same chiral ligand, associated with CuI, in catalylic amount (10%), allows the asymmetric conjugate addition of Et2Zn to 2-cyclohexen-1-one.
138 citations
TL;DR: In this article, improved processes for the enantioselective synthesis of α-amino acids are described, which involve combinations of solvents, highly-mixed and low-temperature reaction conditions, and novel catalysts.
Abstract: Described are improved processes for the enantioselective synthesis of α-amino acids which involve combinations of solvents, highly-mixed and low-temperature reaction conditions, and novel catalysts. Also described are novel catalysts and precursors to α-amino acid derivatives.
121 citations
TL;DR: In this article, the enantioselective hydrophosphonylation of aromatic aldehydes with silylphosphite (1 ) or diethyl phosphonate (5a ) assisted by chiral titanium alkoxides as catalyst is examined.
Abstract: The enantioselective hydrophosphonylation of aromatic aldehydes with silylphosphite ( 1 ) or diethyl phosphonate ( 5a ) assisted by chiral titanium alkoxides as catalyst is examined. Titanium alkoxide ( 7 ), derived from L -tratrate and Ti(O-iPr) 4 , was found to be an effective catalyst and induce modest enantioselectivity in the reaction.
115 citations
TL;DR: In this paper, the electronic properties of para-substituents were investigated for α-hydroxyphosphonates in the presence of La-BINOL complex.
Abstract: Hydrophosphonylation of aromatic aldehydes with diethyl phosphite in the presence of catalytic amount of La-BINOL complex ( 2 ) proceeded enantioselectively to give the corresponding α-hydroxyphosphonates in good yield. Enantioselectivity was found to depend on the electronic nature of para -substituents.
107 citations
TL;DR: In this article, the room temperature and atmospheric pressure hydrogenation of ethyl pyruvate over Pt/Al2O3 catalysts modified by varying amounts of dihydrocinchonidine was examined.
Abstract: The room temperature and atmospheric pressure hydrogenation of ethyl pyruvate over Pt/Al2O3 catalysts modified by varying amounts of dihydrocinchonidine was examined. Data were obtained which showed that the hydrogenation occurred on the corner atoms and adatoms on the Pt crystallites in the catalyst. The formation of (S) ethyl lactate was observed when very low concentrations of the alkaloid modifier were used while at higher modifier concentrations the (R) lactate was produced. The formation of the (R) lactate was accompanied by an increase in the hydrogenation rate. A working hypothesis was formulated to explain these results and to serve as a model for the design of future experiments. This model suggested that the initial adsorption of the dihydrocinchonidine takes place on the face atoms adjacent to the corner atoms on the metal crystallite. This will place the chiral portion of the alkaloid close to the corner atom active site. Enantioselective pyruvate adsorption would be facilitated by a hydrogen bond between the C9 OH of the alkaloid and the ethoxy oxygen of the pyruvate and hydrogenation of the keto group will lead to (S) lactate formation. In order to place the chiral portion of the modifier near an adatom it is proposed that the alkaloid is adsorbed in an edge-on manner on the face near the adatom active site. In this way the modifier can interact directly with the pyruvate to change its adsorption characteristics. This will lead to an increase in reaction rate and the formation of the (R) lactate.
106 citations
TL;DR: While the two enzymes obtained act on different enantiomers of the lactam, either can be used in scaleable processes to obtain synthons for carbocyclic nucleosides having the natural configuration.
Abstract: For the resolution of the bicyclic lactam 2-azabicyclo[2.2.1]hept-5-en-3-one, efficient whole cell biocatalysts have been identified and from these, enzymes (lactamases) have been isolated. While the two enzymes obtained act on different enantiomers of the lactam, either can be used in scaleable processes to obtain synthons for carbocyclic nucleosides having the natural configuration.
102 citations
TL;DR: In this paper, eight lipases as well as pig liver esterase were tested as catalysts for enantioselective hydrolyses of α-(acyloxy)phosphonates in a biphasic system.
Abstract: α-Hydroxyphosphonates (±)- 3 were prepared and transformed into esters (±)- 5 . Eight lipases as well as pig liver esterase were tested as catalysts for enantioselective hydrolyses of α-(acyloxy)phosphonates in a biphasic system. Two of them proved to be useful. The highest enantioselectivity was obtained with lipase F-AP 15 and α-(acetyloxy)phenylmethylphosphonates(±)- 5a and (±)- 5b as substrates. The (S)-enantiomers were exclusively hydrolyzed to give optically pure alcohols (S)-(−)- 3a and (S)-(−)- 3b . Lipases AP 6 and F-AP 15 were used to prepare phosphonates (S)-(−)- 3b , (S)-(+)- 3d and (S)-(−)- 3e on a preparative scale with an enantiomeric excess of 81%, 87%, and 89%, respectively. The absolute configurations ofthe α-hydroxyphosphonates were assigned by Horeau's method and 1 H-NMR spectroscopy of Mosher's derivatives.
87 citations
TL;DR: A homochiral chiral 6,6′-bis(oxazolinyl)-2,2′-bipyridine ligand, bipymox (1), and its rhodium complex were synthesized to examine the enantioselectivity in the asymmetric hydrosilylation of ketones as mentioned in this paper.
Abstract: A homochiral chiral 6,6′-bis(oxazolinyl)-2,2′-bipyridine ligand, bipymox (1), and its rhodium complex were synthesized to examine the enantioselectivity in the asymmetric hydrosilylation of ketones in comparison to other chiral oxazoline ligands such as bis-(oxazolinyl)pyridine, pybox(2), and mono(oxazolinyl)pyridine, pymox(3). The bipymox-rhodium catalyst gave the (S)-absolute configuration of the product 1-phenylethanol (90 %ee) in the reduction of acetophenone with diphenylsilane the same as the pybox-rhodium system but opposite to the pymox-rhodium system. The reduction of 4-tert-butylcyclohexanone was also described.
TL;DR: Chiral resolutions of racemic 3-hydroxy esters were performed in organic phases with lipases from Pseudomonas cepacia, Chromobacterium viscosum and Porcine pancreas and found solvent type, lipase type and acylating agent acting as tools for changing the enantioselectivity.
Abstract: Chiral resolutions of racemic 3-hydroxy esters were performed in organic phases with lipases from Pseudomonas cepacia , Chromobacterium viscosum and Porcine pancreas. The reaction conditions have been optimized with 3-hydroxy octanoic acid methyl ester. Different organic solvents have been tested showing a tendentious correlation with the hydrophobicity of the solvents expressed as log P. The reaction time was shortened six fold by using irreversible acylating agents. We have found solvent type, lipase type and acylating agent acting as tools for changing the enantioselectivity. Lipase from Pseudomonas cepacia was lyophilized at different pH and the influence of the amount of water added was investigated, resulting in the highest activity at the pH optimum and a denaturation of the lipase above 1 % water (w/w lipase ). The water activity was measured on-line with a humidity sensor. Water activities greater than 0.4 led to a decrease in enantioselectivity and reaction rate. In the optimized system the resolutions of other 3-hydroxy esters were tested. Aliphatic compounds reacted with lower enantioselectivity, only the substrates could be isolated in high enantiomeric purity. In contrast, aromatic 3-hydroxy esters were acylated by lipases with high stereoselectivity. A model of the active site of lipase from Pseudomonas sp . explained these experimental observations.
TL;DR: A study of the enzymatic Baeyer-Villiger oxidation of a number of 4-substituted cyclohexanones utilizing the enzyme cyclo hexanone oxygenase (E.C.14.13.-), isolated from the bacteria Acinetobacter NCIB 9871, is described.
Abstract: A study of the enzymatic Baeyer-Villiger oxidation of a number of 4-substituted cyclohexanones utilizing the enzyme cyclohexanone oxygenase (E.C.1.14.13.-), isolated from the bacteria Acinetobacter NCIB 9871, is described.
DSM1
TL;DR: The scope and limitations of the enzymatic resolution of α,α-disubstituted α-amino acid amides by an amino acid amidase from Mycobacterium neoaurum and of the corresponding ethyl esteis with Pig liver estetase (PLE) have been studied.
Abstract: The scope and limitations of the enzymatic resolution of α,α-disubstituted α-amino acid amides by an amino acid amidase from Mycobacterium neoaurum and of the corresponding ethyl esteis with Pig liver estetase (PLE) have been studied. Moderate enantiomeric excesses were obtained with PLE, with only a narrow substrate specificity. Mycobacterium neoaurum on the contrary yields a broad range of S-α,α-disubstituted α-amino acids 1 and the corresponding R-amides 2.
TL;DR: Chloroperoxidase catalysed epoxidadon of styrene derivatives by t -BuOOH preferentially gives (R) oxides with ee values between 28 and 68%.
Abstract: Chloroperoxidase catalysed epoxidadon of styrene derivatives by t -BuOOH preferentially gives (R) oxides with ee values between 28 and 68%. The data support the view of oxygen delivery from the ferryl oxygen directly to the substrate.
TL;DR: Short and practical syntheses of (R )-(−)-carnitine and (R ǫ)-γ-amino-β-hydroxybutyric acid have been developed, both commencing with the catalytic asymmetric dihydroxylation of allyl bromide.
Abstract: Short and practical syntheses of ( R )-(−)-carnitine and ( R )-(−)-γ-amino-β-hydroxybutyric acid have been developed, both commencing with the catalytic asymmetric dihydroxylation of allyl bromide
TL;DR: Water Activity Influences Enantioselectivity in a Lipase Catalysed Resolution by Esterification in an Organic Solvent using a H2O/O2 mixture.
Abstract: Water Activity Influences Enantioselectivity in a Lipase Catalysed Resolution by Esterification in an Organic Solvent
TL;DR: The stereoselective reduction of racemic 2-keto-3-(N-benzoylamino)-3-phenylpropionic acid ethyl ester 1 to the corresponding alcohol 2 was carried out using microbial cultures and among microorganisms evaluated, Hansenula polymorpha SC 13865 and Hansenula fabianii SC 13894 effectively reduced compound1 to the desired syn diastereomer 2a.
Abstract: The chiral intermediate (2R,3S)-(−)-N-benzoyl-3-phenyl isoserine ethyl ester 2a , a potential taxol 5 side-chain synthon, was prepared by microbial and enzymatic processes. Taxol 5 is an anticancer compound recently approved by FDA for the treatment of ovarian cancer. The stereoselective reduction of racemic 2-keto-3-(N-benzoylamino)-3-phenylpropionic acid ethyl ester 1 to the corresponding alcohol 2 was carried out using microbial cultures. Among microorganisms evaluated, Hansenula polymorpha SC 13865 and Hansenula fabianii SC 13894 effectively reduced compound 1 to the desired syn diastereomer 2a . Reaction yields of >80% and enantiomeric excesses of >98% were observed for these bioreduction process. About 10–20% of anti diastereomers ( 2c,2d ) were produced during bioreduction.
TL;DR: N-Urethane protected, peracetylated glucosamine is converted into its 1-thio (1-bromo) derivative and used for glycosylation of a variety of protected serine or threonine derivatives as acceptors.
Abstract: A new approach to O-glycopeptides of the glucosamine type is described. N-Urethane protected, peracetylated glucosamine is converted into its 1-thio (1-bromo) derivative and used for glycosylation of a variety of protected serine or threonine derivatives as acceptors. The urethane group is easily exchanged for the natural N-acetyl moiety and O-deacetylation is achieved with hydrazine/methanol. The resulting O-GlcNAc derivatives are subjected to an enzymatic galactosylation procedure using β-1,4-galactosyltransferase (EC 2.4.1.22) to furnish O-glycopeptides of the neolactosamine type.
TL;DR: An immobilised whole cell Rhodococcus sp.
Abstract: An immobilised whole cell Rhodococcus sp. (SP 361) has been shown to be an effective catalyst for the stereoselective hydrolysis of both racemic and prochiral nitrile containing compounds. 2-Alkyl-arylacetonitriles 6a - 8a were hydrolysed to ( S )-acids and ( R )amides whereas the closely related substrate 9a gave the ( R )-acid. A series of prochiral dinitriles 10 a- 13a were hydrolysed to the corresponding ( S )-acids with e.e.'s 22–84%. Models to account for the stereoselectivity of the enzymic hydrolyses have been proposed.
TL;DR: Several bicyclic [n.2.0] ketones were submitted to enzymatic Baeyer-Villiger oxidation and provided the corresponding regioisomeric lactones showing high enantiopurities as discussed by the authors.
Abstract: Several bicyclic [n.2.0] ketones were submitted to enzymatic Baeyer-Villiger oxidation and provided the corresponding regioisomeric lactones showing high enantiopurities. These products could be used as interesting chirons for the synthesis of various natural compounds. The absolute configurations of the obtained lactones were assigned using circular dichroism measurements.
TL;DR: In this paper, an asymmetric synthesis of 2-alkyl-1-tetralones was achieved in up to 91% e.g. by enantioselective protonation of their corresponding achiral lithium enolates.
Abstract: Asymmetric synthesis of 2-alkyl-1-tetralones ( 2 ) was achieved in up to 91% e.e. by enantioselective protonation of their corresponding achiral lithium enolates ( 4 ) using a chiral amine (( R )- 1 ) as a chiral source in the presence of lithium bromide. Enantioselective alkylation using ( R )- 1 was also carried out, and it is found that the alkyl halide prefers the si -face of the lithium enolate 6 as oppose to the re -face preference of 4a in case of protonation.
TL;DR: A rhodium complex of a boron analog of DIOP, which is a model for a tailored bimetallic catalyst possessing dual functions, is an active catalyst for hydrogenation and hydrosilylation as mentioned in this paper.
Abstract: A rhodium complex of a boron analog of DIOP, which is a model for a tailored bimetallic catalyst possessing dual functions, is an active catalyst for hydrogenation and hydrosilylation.
TL;DR: In this article, a kilogram scale enantiomerically pure alkyl-aryl secondary alcohols were obtained from their racemic mixtures by enzymatic acylation with succinic anhydride in organic solvents.
Abstract: Enantiomerically pure alkyl-aryl secondary alcohols were conveniently obtained on a kilogram scale from their racemic mixtures by enzymatic acylation with succinic anhydride in organic solvents. A major advantage of this acylation method is the ease of separating the ester from the unreacted alcohol. This is achieved by extracting the organic solution with aqueous NaHCO 3 after the enzymatic reaction is completed.
TL;DR: In this paper, the enantioselective reduction of ketones by borane in the presence of catalytic amounts of (S )-(−)-proline or ( S )-(+)-prolinol as chiral auxiliaries has been investigated.
Abstract: The enantioselective reduction of ketones by borane in the presence of catalytic amounts of ( S )-(−)-proline or ( S )-(+)-prolinol as chiral auxiliaries has been investigated. The alcohols possess all the ( R ) configuration, and are obtained in good enantiomeric excess. A mechanistic rationale is proposed, involving an oxazaborolidine formed from ( S )-(+)-prolinol and borane.
TL;DR: The highly diastereoselective synthesis of β-amino-α-hydroxyphosphonic acid derivatives was achieved by Lewis acid mediated hydrophosphonylation of α-dibenzylamino aldehyde as discussed by the authors.
Abstract: The highly diastereoselective synthesis of β-amino-α-hydroxyphosphonic acid derivatives was achieved by Lewis acid mediated hydrophosphonylation of α-dibenzylamino aldehyde. Diastereofacial differentiation could be controlled in either a chelation or a non-chelation manner by simple tuning of the nature of phosphoric nucleophiles.
TL;DR: Syntheses of both title compounds have been achieved on a multigram scale by enzymic synthesis by optimization of reaction conditions led to simplified downstream processing.
Abstract: Syntheses of both title compounds have been achieved on a multigram scale by enzymic synthesis. For multiple use the enzymes were recovered by means of ultrafiltration. 5-Azido-neurammic acid was obtained by enzymic aldol condensation starting from 2-azido-2-deoxy-D-mannose and pyruvic acid with N -acetylneuraminic acid aldolase. 15 N-L-glutamic acid was obtained by reductive animation with glutamate dehydrogenase and regeneration of the cofactor. For both systems optimization of reaction conditions led to simplified downstream processing. HPLC-analysis was used to follow the reactions and to verify optical purity.
TL;DR: In this paper, an overview is presented on the various biological methods available and some strong and weak points of these systems are considered, as well as a review of some of the properties of these methods.
Abstract: Optically pure epoxides are valuable building blocks in organic synthesis which may be produced either chemically or biologically. In this review an overview is presented on the various biological methods available and some strong and weak points of these systems are considered.
TL;DR: Stereocontrolled syntheses of the title compounds from (R)-2,3,isopropylidene glyceraldehyde, (S)-O-THP-lactaldehyde and 1,2:5,6-Di-O-isopricidene-α-D-glucofuranose (diacetone-Dglucose) are described in this paper.
Abstract: Stereocontrolled syntheses of the title compounds from (R)-2,3-isopropylidene glyceraldehyde, (S)-O-THP-lactaldehyde and 1,2:5,6-Di-O-isopropylidene-α-D-glucofuranose (“diacetone-D-glucose”) are described.
TL;DR: In this paper, a chiral metallocyclic Lewis acid based catalyst system derived from norephedrine is reported, where a key stereodirective element emanates from a tricarbonyl chromium (0) group complexed to the aryl ring.
Abstract: A chiral metallocyclic Lewis acid based catalyst system derived from norephedrine is reported. A key stereodirective element emanates from a tricarbonyl chromium (0) group complexed to the aryl ring. The catalysts mediate the addition of dialkyl zinc species to a variety of aldehydes with high enantioselectivity.