Showing papers in "Tetrahedron-asymmetry in 2011"

Advances in the chemistry of proline and its derivatives: an excellent amino acid with versatile applications in asymmetric synthesis

Abstract: Non-proteinogenic prolines have been acknowledged as an important pool for the synthesis of conformationally rigid bioactive peptides, angiotensin converting enzyme inhibitors and as pharmacological probes. Proline and its derivatives are often used as asymmetric catalysts in organic reactions, such as CBS reductions and proline catalyzed aldol reactions, Mannich reactions, and so on. Furthermore l -proline is an osmoprotectant and is therefore frequently used in many pharmacological as well as biotechnological applications. The wide range of chemical and biological applications associated with l -proline has prompted researchers to develop new methodologies for the synthesis of prolines and substituted prolines and to further explore their chemical and biological applications. The present article is an attempt to discuss all the major advances available till date, describing the use of proline in organic asymmetric synthesis, the synthesis of various bioactive molecules or proline as a constituent part of bioactive molecules.

Carbohydrate-derived alcohols as organocatalysts in enantioselective aldol reactions of isatins with ketones

Abstract: The catalytic activity of carbohydrate-derived amino alcohols in the enantioselective aldol reaction of ketones with isatin and its derivatives has been examined for the first time. The carbohydrate-derived amino alcohols 5 were found to be efficient organocatalysts for asymmetric aldol reactions. A variety of isatins were used as substrates and the corresponding aldol products were obtained in high yields (up to 99%) and with moderate enantioselectivities (up to 75%).

Enantioselective α-tosyloxylation of ketones catalyzed by spirobiindane scaffold-based chiral iodoarenes

Abstract: Enantiomerically pure iodoarene (S)-2 and its derivatives (S)-3 to (S)-18 with a spirobiindane scaffold have been synthesized. The evaluation of these new chiral iodoarenes as catalysts in the enantioselective α-tosyloxylation of ketones was performed using m-CPBA as a stoichiometric oxidant, and the synthetically useful α-tosyloxylated ketones were obtained in up to 58% enantiomeric excess (ee).

Catalytic asymmetric carbon–carbon bond-forming reactions in aqueous media

Abstract: The development of enantioselective transformations has been the subject of numerous research efforts. In recent years, a variety of efficient asymmetric catalysts for different organic reactions in aqueous media have been introduced. This review summarizes an analysis of chiral metal complex reactions catalyzed as well as organocatalyzed reactions in aqueous media. The applications of a variety of chiral ligands alone, or in association with metal complexes, in water alone, as well as other conditions such as reactions in water in the presence of surfactants or in mixtures of water and organic solvents are described. Complete up to date results concerning asymmetric aldol reactions, 1,4-conjugate addition reactions, Mannich reactions, Diels–Alder reactions, Friedel–Craft reactions and so on have appeared in the literature.

Recyclable Merrifield resin-supported thiourea organocatalysts derived from l-proline for direct asymmetric aldol reaction

Abstract: Four Merrifield resin-supported thiourea organocatalysts derived from l -proline were synthesized and found to be efficient catalysts for the direct asymmetric aldol reaction between ketone and aromatic aldehydes. The catalysts exhibited high catalytic activity, diastereoselectivity and excellent enantioselectivity at room temperature with a low loading (only 2 mol %). They also retained unchanged enantioselectivities even after being reused for at least four cycles.

A highly efficient large-scale asymmetric Michael addition of isobutyraldehyde to maleimides promoted by a novel multifunctional thiourea

Abstract: A novel class of chiral multifunctional thioureas bearing a chiral lipophilic beyerane scaffold and a primary amino group were designed and prepared. The thioureas were proven to be effective for catalyzing the asymmetric Michael addition between isobutyraldehyde and maleimides with only 0.5 mol % catalyst loading, and exhibited double asymmetric induction. Both of the catalysts afforded the corresponding adduct with high to excellent yields (up to 98%) and excellent enantioselectivities (up to 99%). Furthermore, this catalytic system can be used efficiently in large-scale reactions with the yields and enantioselectivities being maintained at the same level.

Chiral phosphine–phosphite ligands in the enantioselective 1,4-addition of Grignard reagents to α,β-unsaturated carbonyl compounds

Abstract: A library of chiral phosphine–phosphite ligands was evaluated in the Cu-catalyzed asymmetric 1,4-addition of Grignard reagents to cyclopentenone, cycloheptenone and 5,6-dihydro-2 H -pyran-2-one. TADDOL-based ligands 1a and 1b with a bulky substituent at the ortho -position to the chiral phosphite moiety gave rise to the 1,4-addition products with high enantioselectivities (up to 93% ee). In addition to ethyl-MgBr (as a standard alkyl nucleophile) phenyl- and isopropenyl-MgBr could also be employed. In the case of cyclopentenone, the use of chlorotrimethylsilane as an additive led to improved regio- and enantioselectivities.

Enantioselective synthesis of (R)-salmeterol employing an asymmetric Henry reaction as the key step

Abstract: A practical synthesis of (R)-salmeterol has been accomplished from 3-bromo salicylaldehyde, which involved a Cu(II)–sparteine complex catalyzed asymmetric Henry reaction as the key step. (R)-Salmeterol can be obtained in 39% overall yield and 95% ee.

Catalytic enantioselective C-H functionalization of indoles with α-diazopropionates using chiral dirhodium(II) carboxylates : asymmetric synthesis of the (+)-α-methyl-3-indolylacetic acid fragment of acremoauxin A

Abstract: An enantioselective C–H functionalization of N -methoxymethyl (MOM)-protected 2,3-unsubstituted indoles with α-diazopropionates has been effected via catalysis by dirhodium(II) tetrakis[ N -phthaloyl-( S )-triethylalaninate], Rh 2 (( S )-PTTEA) 4 , providing α-methyl-3-indolylacetates in high yields and with enantioselectivities of up to 86% ee. The effectiveness of this protocol was demonstrated by the first catalytic asymmetric synthesis of the (+)-α-methyl-3-indolylacetic acid fragment of acremoauxin A, a potent plant-growth inhibitor. Furthermore, the Fujioka protocol using a combination of TMSOTf and 2,2′-bipyridyl was shown to be superior for the removal of the N -MOM group.

Asymmetric Michael reactions of α,α-disubstituted aldehydes with maleimides using a primary amine thiourea organocatalyst

Abstract: Primary amine thiourea organocatalyst 8 was used to promote Michael additions of bulky α,α-disubstituted aldehydes, such as isobutyraldehyde with maleimides to afford the corresponding adducts in high to excellent yields and with up to 91% ee.

Lewis acid- and Bronsted acid-catalyzed stereoselective rearrangement of epoxides derived from himachalenes: access to new chiral polycyclic structures

Abstract: The acid-catalyzed rearrangement of two enantiomerically pure epoxides derived from sesquiterpernic himachalenes, which are the main components of the essential oil of the Atlas cedar, has been studied using various Lewis and Bronsted acids. Several new polycyclic compounds have been obtained with different selectivities depending upon the catalysts used and the reaction conditions, and were fully characterized by spectroscopic methods. Mechanisms to explain the formation of the different compounds observed in the reaction mixture have also been proposed.

Synthesis of phosphorylated sulfoximines and sulfinamides and their application as ligands in asymmetric metal catalysis

Abstract: Starting from inexpensive materials and following simple protocols various N-phosphorylated sulfoximines and sulfinamides have been synthesized. The newly prepared compounds were then applied as chiral ligands in asymmetric transition metal catalysis. Phosphorus triamide-type ligands derived from (S)-glutamic acid were found to be the most efficient stereoselectors in enantioselective palladium-catalyzed allylic substitutions (up to 97% ee). On the other hand, diamidophosphite-type structures stemming from (S)-proline were the best ligands in rhodium-catalyzed hydrogenation reactions (up to 84% ee).

Catalytic enantioselective Steglich rearrangements using chiral N-heterocyclic carbenes

Abstract: The evaluation of a range of enantiomerically pure NHCs, prepared in situ from imidazolinium or triazolium salt precatalysts, to promote the catalytic enantioselective Steglich rearrangement of oxazolyl carbonates to their C-carboxyazlactones, is reported. Modest levels of enantioselectivity (up to 66% ee) are observed using oxazolidinone derived NHCs.

Screening of simple N-aryl and N-heteroaryl pyrrolidine amide organocatalysts for the enantioselective aldol reaction of acetone with isatin

Abstract: We have screened a range of simple N -aryl and N -heteroaryl pyrrolidine amide organocatalysts incorporating N -pyridyl and N -quinolinyl groups in the synthetically useful aldol reaction of isatin with acetone. The ‘reverse amide’ N -pyridyl pyrrolidinylmethyl amide catalysts proved highly catalytically active but gave disappointing enantioselectivities. However, an N -3-pyridyl prolinamide catalyst gave the aldol adduct in high yields and high enantioselectivity with up to 72% ee of the ( S )-isomer . Conditions were optimised for this catalyst and in particular an additive screen identified a link between the p K a of the acid additive and the yield and enantioselectivity. An N -arylsulfonamide prolinamide was also identified as a catalyst for this reaction giving the ( R )-enantiomer in 68% ee.

Simple and inexpensive threonine-based organocatalysts for the highly diastereo- and enantioselective direct large-scale syn-aldol and anti-Mannich reactions of α-hydroxyacetone

Abstract: Simple and inexpensive threonine-based organocatalysts that promote syn -aldol reactions and three-component asymmetric anti -Mannich reactions of α-hydroxyacetone achieving a respectable level of enantioselectivities are reported The syn -aldol products could be obtained with up to a 99:1 syn / anti ratio and >99% ee while the anti -Mannich products could be obtained with up to a 96:4 anti / syn ratio and >99% ee Catalyst 1c can be used efficiently on a large-scale with the enantioselectivities of the syn -aldol and anti -Mannich reactions being maintained at the same level, which offers a great possibility for application in industry

Total synthesis of crispine A enantiomers through a Burkholderia cepacia lipase-catalysed kinetic resolution

Abstract: Both enantiomers of the antitumour-active alkaloid crispine A (ee = 95%) were synthesised through the Burkholderia cepacia lipase-catalysed acylation of the primary hydroxy group of N -Boc-protected 1-(3-hydroxypropyl)-6,7-bis(methyloxy)-1,2,3,4-tetrahydroisoquinoline (±)- 3 and the enantioselective hydrolysis of the corresponding O -decanoate (±)- 4 [R = (CH 2 ) 8 Me] with a remote, four-atom distant stereogenic centre. High enantioselectivities were observed for the ( S )-selective O-acylation with vinyl decanoate in the presence of Et 3 N and Na 2 SO 4 in t -BuOMe at 45 °C ( E = 68), and for the ( S )-selective hydrolysis with H 2 O in t -BuOMe at 45 °C ( E = 52). The enzymatic resolutions, performed in two steps, afforded the key alcohol and ester enantiomers with high enantiomeric excesses (ee ⩾ 94%). Ring-closure reactions of alcohol enantiomers (+)- 3 and (−)- 3 with thionyl chloride afforded the desired crispine A enantiomers (+)- 1 and (−)- 1 (ee ⩾ 95%).

Axially chiral N-heterocyclic carbene gold(I) complex catalyzed asymmetric Friedel–Crafts/cyclization reaction of nitrogen-tethered 1,6-enynes with indole derivatives

Abstract: A class of axially chiral NHC–Au(I) complexes has been applied to the asymmetric Friedel–Crafts/cyclization reaction of nitrogen-tethered 1,6-enynes 14 with indole derivatives 15, affording the corresponding Friedel–Crafts and intramolecular cyclization products 16 in good yields and with moderate ee values under mild conditions.

Stereoselective synthesis of carane-based aminodiols as chiral ligands for the catalytic addition of diethylzinc to aldehydes

Abstract: Key intermediate epoxy alcohol 4 was prepared regio- and stereoselectively from (+)-3-carene 1 via carene oxide 2 and (−)- trans -allyl alcohol 3 . The lithium perchlorate-catalysed ring opening of 4 with secondary and primary achiral and chiral amines resulted in primary, secondary and tertiary aminodiols. Aminodiols 5 – 14 were applied as chiral catalysts in the enantioselective addition of diethylzinc to benzaldehyde, resulting in ( R )- and ( S )-1-phenyl-1-propanol with moderate enantioselectivity. N -Benzyl, N -methyl, and ( S )- and ( R )- N -methylbenzyl derivatives 7 and 10 – 13 were transformed into 1,3-oxazines 17 – 21 via highly regioselective ring closures. When 17 – 21 were applied as chiral catalysts in the addition of diethylzinc to aromatic and aliphatic aldehydes, high chiral induction in the tricyclic catalysts was observed. The effects of the substituents on the nitrogen of the aminodiols and 1,3-oxazines were studied in detail; the best enantioselectivity was observed in the case of N -methylbenzyl-substituted oxazine 19 .

Asymmetric synthesis of syn- and anti-α-deuterio-β3-phenylalanine derivatives

Abstract: The conjugate addition of lithium (S)-N-benzyl-N-(α-methylbenzyl) amide to a range of aryl substituted tert-butyl cinnamate esters followed by reaction of the resultant lithium β-amino enolates with D2O provides access to anti configured α-deuterio-β-aminocinnamate esters in high dr. The corresponding syn configured diastereoisomers were also obtained with high diastereoselectivity via the conjugate addition of lithium (S)-N-benzyl-N-(α-methylbenzyl)amide to a range of tert-butyl α-deuteriocinnamate esters followed by reaction of the resultant lithium β-amino enolates with 2-pyridone. After deprotection both the syn- and anti-diastereoisomers of the corresponding α-deuterio-β3- amino acids can be isolated in high dr. © 2011 Elsevier Ltd. All rights reserved.

Lipase-mediated resolution of substituted 2-aryl-propanols: application to the enantioselective synthesis of phenolic sesquiterpenes

Abstract: A comprehensive study of the lipase-mediated resolution of substituted 2-aryl-propanols is reported. The latter alcohols were submitted to the irreversible acetylation catalyzed either by PPL, CRL, or lipase PS. The enantioselectivity of these transformations was dependent on the type of lipase used. The type of substituents and particularly their position on the aromatic ring strongly affected the selectivity of the reaction. The experiments described prove that PPL is the more versatile lipase catalyzing the acetylation with an enantiomeric ratio (E) value that ranges from 1 up to 144, depending on the substrate used. Conversely, the same transformations were catalyzed by CRL and lipase PS with an enantiomeric ratio value, which is always less than 5. The remarkable behavior of PPL was exploited in the large scale resolution of some substituted 2-aryl-propanols whose enantiomeric forms are relevant building blocks in the enantioselective synthesis of phenolic sesquiterpenes. By these means, the synthesis of (S)-turmeronol B and the formal syntheses of (R)-curcumene, (R)-curcuphenol, (R)-xanthorrhizol, and (R)-curcuhydroquinone were accomplished.

A chiral pyrrolidine-pyrazole catalyst for the enantioselective Michael addition of carbonyls to nitroolefins

Abstract: An enantioselective Michael reaction of carbonyl compounds to nitroolefins has been accomplished using a novel chiral pyrrolidine-pyrazole catalyst. This newly prepared catalyst was found to be very effective in providing good yields as well as good diastereo- and enantio-selectivities. The mechanism of the reaction has also been substantiated by mass spectral studies.

tert-Butanesulfinylthioether ligands: synthesis and application in palladium-catalyzed asymmetric allylic alkylation

Abstract: A class of novel chiral SO-S-type bidentate ligands based on the tert-butylsulfinyl moiety as the sole chiral source were designed and synthesized through a simple and efficient pathway. These ligands are effective catalyst precursors for the palladium-catalyzed allylic alkylation of 1,3-diphenyl-2-propenyl acetate and moderate to good stereoselectivities (up to 84% ee) were obtained. (C) 2011 Elsevier Ltd. All rights reserved.

Asymmetric Mannich reactions catalyzed by cinchona alkaloid thiourea: enantioselective one-pot synthesis of novel β-amino ester derivatives

Abstract: An efficient one-pot synthesis of novel β-amino ester derivatives containing a benzoxazol moiety has been developed by using cinchona alkaloid thioureas as the organocatalyst. The adducts were isolated in high enantiomeric excess and high yield.

Chiral 1,1′-binaphthylazepine derived amino alcohol catalyzed asymmetric Henry reaction

Abstract: The catalytic asymmetric Henry reaction of nitromethane to various aldehydes has been developed using a chiral binaphthylazepine derived amino alcohol and Cu(OAc) 2 ·H 2 O as the catalyst. High yields and good enantioselectivities (up to 97% ee) were obtained for both aromatic and aliphatic aldehydes. Moreover, this catalytic system also works well for the diastereoselective Henry reaction to afford the corresponding adducts in up to 95:5 syn / anti selectivity and 95% enantioselectivity.

Amino alcohol based chiral solvating agents: synthesis and applications in the NMR enantiodiscrimination of carboxylic acids

Abstract: Four optically active amino alcohols were synthesized via the ring opening of ( R )- N -(2,3-epoxypropyl)phthalimide with ( R )-2-phenyl glycinol, (1 R ,2 S )- cis -1-amino-2-indanol, ( R )-2-amino-1-butanol and ( S )-phenyl ethylamine in 73–93% yields. The enantioselective recognition of these receptors towards the enantiomers of racemic carboxylic acids was studied by 1 H NMR spectroscopy. The molar ratio and the association constants of the chiral compounds with each of the enantiomers of the guests were determined by using Job plots and a non-linear least-squares fitting method, respectively. Large non-equivalent chemical shifts (up to 30.0 Hz) can be achieved in the presence of chiral amino alcohols 2 and 5 . Amongst the chiral receptors used, compound 5 was found to be the best chiral shift reagent, and was effective in the determination of the enantiomeric excess of chiral carboxylic acids.

Asymmetric Henry reaction catalyzed by a chiral Cu(II) complex: a facile enantioselective synthesis of (S)-2-nitro-1-arylethanols

Abstract: A catalytic asymmetric Henry reaction has been developed using a novel chiral Cu(II) complex derived from (R)-2-(diphenylmethanol)-l-(2-pyridylmethyl)pyrrolidine and copper(II) acetate in ethanol under mild conditions. The corresponding chiral 2-nitro-1-arylethanol derivatives were obtained in high yields with moderate to good enantiomeric excess (up to 86% ee). The results indicate that the coordination of a metal atom to the nitrogen of the pyridine ring is essential in determining the stereochemistry of the process.

Asymmetric epoxidation of styrene derivatives by styrene monooxygenase from Pseudomonas sp. LQ26: effects of α- and β-substituents

Abstract: Recombinant Escherichia coli expressing a styrene monooxygenase, StyAB2, from Pseudomonas sp. LQ26 was applied to synthesize a range of chiral epoxides from conjugated styrene derivatives with excellent (>99%) enantioselectivity in most cases. The substrate preference was studied with a special focus on the steric effect of α- and β-substituents.

The Ru-catalyzed enantioselective preparation of chiral halohydrins and their application in the synthesis of (R)-clorprenaline and (S)-sotalol

Abstract: The asymmetric transfer hydrogenation of a series of halo-substituted aryl methyl ketones, including those substituted in both α-methyl and aryl rings, was studied for the preparation of chiral halohydrins. Up to 99.7% ee was obtained with 2-chloro-1-(2-chlorophenyl)ethanone as the substrate and Ru-CsDPEN as the catalyst in an HCOONa/H 2 O system. ( R )-Clorprenaline , a drug used in the treatment of respiratory disorders, such as bronchitis and asthma, and ( S )-sotalol, a class-III antiarrhythmic compound, were prepared with these chiral halohydrins.

Synthesis of planar chiral imidazo[1,5-a]pyridinium salts based on [2.2]paracyclophane for asymmetric β-borylation of enones

Abstract: Novel planar chiral pseudo-geminal and pseudo-ortho-oxazoline substituted [2.2]paracyclophanyl imidazo[1,5-a]pyridinium triflates were synthesized. During the synthesis of a pseudo-ortho imidazo[1,5-a]pyridinium triflate based on [2.2]paracyclophane, the diastereoisomers of 4-amino-12-oxazolinyl[2.2]paracyclophane were separated. The imidazo[1,5-a]pyridinium triflates were used as carbene precursors in Cu-catalyzed enantioselective conjugate β-borylation of enones. In preliminary tests of a series of ligands and substrates, we obtained up to 84% enantioselectivity.

Asymmetric Henry reaction of aldehydes catalyzed by recyclable an MCM-41 supported copper(II) salen complex

Abstract: A chiral modified MCM-41-Cu(salen) complex has been prepared and characterized by SEM, powder XRD, and EDX techniques as well as FT-IR and EPR spectroscopic methods. This new catalytic system was examined in the asymmetric Henry reaction between various aldehydes and nitromethane at room temperature. Aromatic, aliphatic, and heterocyclic aldehydes have been converted into the corresponding nitro alcohols in 60−92% yields with 60−90% ee. Several factors concerning the reactivity and enantioselectivity are also discussed. This catalyst was separated by filtration and reused several times without a significant loss of reactivity or enantioselectivity.