Ketones 1a Research Articles

Synthesis of new ( R)-secondary carbinols with different structures via enzymatic resolution

The present study deals with the biocatalytic enantioselective synthesis of 19 new chiral alcohols with alkyl (C 11–C 19) and phenyl, substituted phenyl, heteroaromatic, and naphthyl groups 4a– 4z with an ( R)-configuration and high enantiomeric excess (∼100%). The corresponding ketones 1a– 1z were synthesized and then reduced with NaBH 4 to their racemic alcohols 2a– 2z, which were converted into their racemic acetyl derivatives 3a– 3z. Enzymes of four different types were used for the enantioselective hydrolysis of these acetyl compounds 3a– 3z. The optimal reaction conditions for these four enzymes were established by investigating the enantiomeric excesses by chiral HPLC. Amano lipase from Burkholderica cepacia ( Pseudomonas cepacia) AL-PS was determined as the best enzyme in this work. This study presents an environmentally friendly and green chemistry method for the synthesis of these new ( R)-chiral carbinols 4a– 4z.

Chlorodifluoromethyl aryl ketones and sulfones as difluorocarbene reagents: The substituent effect

We have investigated the different chlorodifluoromethyl aryl ketones 1a– 1g and sulfones 2a– 2h as difluorocarbene reagents for O- and N-difluoromethylations. It was found that the sulfone reagents 2 were generally more efficient in difluoromethylation than the ketone reagents 1. Furthermore, while the different substituents on ketone reagents 1 did not show a remarkable impact on the difluoromethylation reaction, the substituent effect on the sulfone reagents 2 was much more significant. Finally, we found that p-chlorophenyl chlorodifluoromethyl sulfone 2d and p-nitrophenyl chlorodifluoromethyl sulfone 2h were among the most powerful difluorocarbene reagents in this category for O-difluoromethylations.

Palladium‐Catalyzed Carbocyclization of Alkynyl Ketones Proceeding through a Carbopalladation Pathway

Palladium‐Catalyzed Carbocyclization of Alkynyl Ketones Proceeding through a Carbopalladation Pathway

Asymmetric Reduction of Heteroaryl Methyl Ketones Using <i>Daucus carota</i>

Asymmetric reduction of the heteroaryl prochiral ketones to corresponding chiral alcohols by Daucus carota was studied. The study highlights selective bioreduction of different substituted heteroaryl ketones (1a - 1j) to their respective chiral alcohols (2a - 2j) using plant dehydrogenase enzymes present in Daucus carota in good yields (60% - 95%) and enantioselectivity (76% - 99%) with S-form configuration. The results obtained confirm that the membrane bound dehydrogenase enzyme has broad substrate specificity and selectivity in catalyzing both six and five membered heteroaryl methyl ketones. The present methodology demonstrates promising and alternative green route in the synthesis secondary chiral alcohols of biologically importance in a simple, inexpensive and eco-friendly process.

Novel synthetic protocol toward pyrazolo[3,4‐h]‐[1,6]naphthyridines via Friedlander condensation of new 4‐aminopyrazolo[3,4‐b]pyridine‐5‐carbaldehyde with reactive α‐methylene ketones

AbstractNovel pyrazolo[3,4‐h][1,6]naphthyridine derivatives 6, 8, 9, 11, 13, and 15 have been synthesized by Friedlander condensation of new 4‐amino‐3‐methyl‐1‐phenyl‐1H‐pyrazolo[3,4‐b]pyridine‐5‐carbaldehyde (o‐aminoaldehyde) 4 with active methylene ketones, such as symmetric acetone 5a, monoalkylketones 5b, 5c, 5d, 5e, 5f, 5g, 5h, 5i, 5j, 5k, unsymmetrical dialkyl ketones 7a, 7b, p‐bromophenylacetonitrile 10, β‐ketoester 12a, β‐ketoamide 12b, or diethyl malonate 14, respectively. J. Heterocyclic Chem., (2011).

Asymmetric synthesis of new chiral long chain alcohols

Sixteen new chiral alcohols with alkyl (C11–C19) and aryl, substituted aryl, hetero aryl and biaryl groups 2a–2t were synthesized by three different asymmetric reduction methods from their corresponding ketones 1a–1t. Chiral NaBH4 (method A), chiral BH3 (method B) and chiral AIP (method C) were used as asymmetric reduction catalysts. Chiral NaBH4 was modified by four different ligands 3a–3d, chiral BH3 and chiral AIP by four different ligands 4a–4d. Ligand 4c was synthesized for the first time in this work. Chiral NaBH4 generated chiral alcohols of (R)-configuration and chiral BH3 and chiral AIP of (S)-configuration with high enantiomeric excesses, were analysed by chiral HPLC. In order to determine the ee values by chiral HPLC, sixteen corresponding racemic alcohols, synthesized by reducing their corresponding ketones via NaBH4, were used for chiral resolution on a Daicel OD HPLC column. The sixteen starting ketones were synthesized in this study by Friedel–Craft acylation. The new chiral alcohols were characterized by IR, NMR, (1H and 13C), MS, elemental analyses and specific rotation. The reduction methods A, B and C were applied to these ketones for the first time in this study and were compared with each other. The relationship between the structure of the ketone and the yield and the enantiomeric excess was discussed.

ChemInform Abstract: Diels-Alder Reactions in Aqueous Solutions. Enforced Hydrophobic Interactions Between Diene and Dienophile.

Second-order rate constants and isobaric activation parameters for the intermolecular Diels-Alder reactions of cyclopentadiene with alkyl vinyl ketones (2a,b) and 5-substituted-1,4-naphthoquinones (3a-c) as well as for the intramolecular Diels-Alder reaction of N-furfuryl-N-methylmaleamic acid (4) were determined in water, monohydric alcohols, and highly aqueous solutions containing monohydric alcohols and other organic cosolvents. The intermolecular as well as the intramolecular Diels-Alder reaction are characterized by large rate accelerations upon going from an organic solvent to water as the reaction medium. A model for solvation effects on rate constants for Diels-Alder reactions in aqueous solutions is developed. The typical, huge rate enhancements for Diels-Alder reactions in water and in highly aqueous binary mixtures are significantly sensitive to substituent effects and are discussed in terms of enforced pairwise hydrophobic interactions between diene and dienophile.

ChemInform Abstract: A Highly Efficient and Straightforward Stereoselective Synthesis of Novel Chiral α-Acetylenic Ketones.

Abstract A very efficient and straightforward synthesis of novel chiral α-acetylenic ketones of type 3 has been developed. Starting from commercially available l -(−)-serine 4, and through the Garner's aldehyde 5, ethynyloxazolidine 2 was formed in good overall yield. Condensation of the corresponding lithium acetylide 7 with different aliphatic and aromatic aldehydes 5 and 8a–h at low temperatures yielded the respective propargylic alcohols 9a–i. Subsequent mild oxidation of 9a–i with 10-I-4-iodinane oxide (IBX) 12 afforded chiral α-acetylenic ketones 3a–i almost quantitatively.

Michael Addition for the Synthesis of Octahydroindole Natural Products

Pansare and co-workers report an enantioselective route toward the aryloctahydro­indole core of several natural products. Their approach is based on the highly enantio- and dia­stereoselective Michael addition between ketones 1 and nitroalkenes 2 using the triamine salt catalyst 3. The resulting γ-nitro ketone 4a was diastereoselectively transformed into the cis-octahydro-indole 7 in five steps. This intermediate was further functionalized to tetracycle 8, thus completing a formal synthesis of (-)-pancracine.

Heteroaromatic Trapping of Tricyclic 2-Oxidocyclopentenyl Cations: A Surprisingly Efficient Example of Intermolecular Interrupted Nazarov Reaction

Bis(cycloalkenyl) ketones 2a and 2f underwent Nazarov cyclization and intermolecular trapping by electrophilic aromatic substitution with furans, thiophenes, pyrroles, indoles and dimethoxybenzene. Only the cis-anti-cis diastereomer was isolated with dicyclopentenyl ketone 2a, whereas a mixture of diastereomers was seen with 2f (albeit with complete regioselectivity). Comparable interrupted Nazarov trapping was not seen with acyclic dienones 2b-e, indicating the possible involvement of conformation effects in the polycyclic intermediates derived from 2a and 2f.

4 + 2] Cycloaddition Reactions Involving 2-Arylmethylidene-1-thiooxoindan Intermediates and Antimicrobial Activity Evaluation of Some Products

2-(4-Fluorophenyl)methylidene-1-thiooxoindane-, 2-(4-methoxyphenyl) methylidene-1-thiooxoindane-, 2-(4-N,N-dimethyaminophenyl)methylidene-1-thiooxoindane dimers 5a–c were prepared by the reaction of the corresponding α,β -unsaturated ketones 3a–c with Lawesson' Reagent (LR) in refluxing benzene. When these dimers were refluxed with LR in xylene, the 1,2-thiaphospholene-2-sulfides 7a–c were obtained. On the other hand, the thermolysis of the dimers 5a–c in the presence of acrylamide or dichloromaleic anhydride gave the corresponding cycloadducts of Diels-Alder type 8a–c, and 10a–c, respectively. The 3-carbamoyl thiapyran derivatives 8a–c showed good antimicrobial activity.

Preparation of 5‐nitro‐2‐amino[b]thiophenes and 1‐(2‐amino‐5‐nitrophenyl)ethanones via microwave irradiation

Abstract magnified image1‐(2‐Chloro‐5‐nitrophenyl)ethanone) reacts with various amines in the presence of sulfur under microwave radiation to give the corresponding 2‐aminobenzo[b]‐thiophenes 3a, 3b, 3c, 3d, 3e, 3f in good yields. The yields of 3a, 3b, 3c, 3d, 3e, 3f are vastly superior to those obtained using conventional heating. Additionally, 1‐(2‐amino‐5‐nitrophenyl)ethanones 4a, 4b, 4c, 4d, 4e, 4f were also obtained. A mechanism is proposed in which 2‐amino thiophenes 3a, 3b, 3c, 3d, 3e, 3f are formed by a SNAr mechanism involving an intramolecular addition of sulfur of the intermediate thioamide to the 2‐substituted carbon to give a Meisenheimer complex, which collapses to 2‐aminothiophenes 3a, 3b, 3c, 3d, 3e, 3f, and 2‐amino ketones (4a, 4b, 4c, 4d, 4e, 4f) are formed by a parallel pathway involving nucleophilic addition amine to the 2‐chloro position of 1 to form a Meisensheimer complex, which collapses to the amino ethanones. J. Heterocyclic Chem., (2009).

Convenient Access to β‐Substituted Chiral Phenones

Abstractmagnified imageA highly enantioselective approach towards the synthesis of β‐substituted chiral ketones by utilizing Grignard reagents was achieved. The (R)‐ and (S)‐antipodes of the target chiral ketones 2a–2k were obtained with up to 100% ee from chiral N‐alkanoylcamphorsultams 1 (Scheme, Table 2). This simple, catalyst‐free, direct procedure for the formation of chiral ketones is a fascinating method for the practical syntheses of chiral synthons as valuable building blocks and important medicinal intermediates.

Hydroacylation of 2-butyne from the alcohol or aldehyde oxidation level via ruthenium catalyzed C–C bond forming transfer hydrogenation

Under the conditions of ruthenium catalyzed transfer hydrogenation, 2-butyne couples to alcohols 1a– 1j to deliver α,β-unsaturated ketones 3a– 3j in good to excellent isolated yields with complete E-stereoselectivity. Under identical conditions, aldehydes 2a– 2j couple to 2-butyne to provide an identical set of α,β-unsaturated ketones 3a– 3j in good to excellent isolated yields with complete E-stereoselectivity. Nonsymmetric alkyne 4a couples to alcohol 1d or aldehyde 2d in good yield to deliver enone 3k as a 5:1 mixture of regioisomers. Thus, intermolecular alkyne hydroacylation is achieved from the alcohol or aldehyde oxidation level. In earlier studies employing the same ruthenium catalyst under slightly different conditions, alkynes were coupled to carbonyl partners from the alcohol or aldehyde oxidation level to furnish allylic alcohols. Therefore, under the conditions of C–C bond forming transfer hydrogenation, all oxidation levels of substrate (alcohol or aldehyde) and product (allylic alcohol or α,β-unsaturated ketone) are accessible.

Dancing of the Second Aromatic Residue around the 6,8-Diazabicyclo[3.2.2]nonane Framework: Influence on σ Receptor Affinity and Cytotoxicity

A series of 6,8-diazabicyclo[3.2.2]nonane derivatives bearing two aromatic moieties was prepared, the affinity toward sigma(1) and sigma(2) receptors was investigated, and the growth inhibition of six human tumor cell lines was determined. The enantiopure bicyclic ketones 5a ((+)-(1S,5S)-6-allyl-8-(4-methoxybenzyl)-6,8-diazabicyclo[3.2.2]nonane-2,7,9-trione) and 5b ((+)-(1S,5S)-6-allyl-8-(2,4-dimethoxybenzyl)-6,8-diazabicyclo[3.2.2]nonane-2,7,9-trione) as well as their enantiomers ent-5a and ent-5b served as chiral building blocks, which were derived from (S)- and (R)-glutamate, respectively. Structure-affinity relationships revealed that 11a (K(i) = 154 nM), ent-11a (K(i) = 91 nM), and ent-17a (K(i) = 104 nM) are the most potent sigma(1) ligands. High sigma(2) affinity was achieved with 17b (K(i) = 159 nM) and 8b (K(i) = 400 nM). The bicyclic sigma ligands showed a selective growth inhibition of the small cell lung cancer cell line A-427 with the benzyl ethers 11 and the benzylidene derivatives 17 being the most potent compounds. 11a has a cytotoxic potency (IC(50) = 0.92 muM), which exceeds the activity of cisplatin and interacts considerably with both sigma(1) and sigma(2) receptors.

Synthesis of 1,4-Diazabicyclo[3.3.1]nonan-6-ones

1,4-Diazabicyclo[3.3.1]nonanes (aza-morphans) represent conformationally constrained piperazine derivatives. Herein, we report a six-step synthesis of the benzyl and allyl substituted bicyclic ketones 3a and 3b, which represent interesting building blocks for the synthesis of conformationally restricted receptor ligands. The key steps of the synthesis are the regioselective addition of ethyl acrylate to the piperazine 8, the sodium hexamethyldisilazide-induced Dieckmann cyclization of the diesters 10, and the decarboxylation of the enol esters 11 with dilute HCl. The complete sequence is only successful when a benzyl (10a) or allyl moiety (10b) is attached to N-1, since the tosyl derivative 10f failed to give a Dieckmann cyclization product, and the decarboxylation failed with the acyl derivatives 11c and 11d.

A FACILE SYNTHESIS OF 6,7-FUSED STEROIDAL THIAZOLES VIA 1,3-INTRAMOLECULAR MIGRATION OF BROMINE/ALLYLIC DISPLACEMENT OF BROMINE

ABSTRACT A facile synthesis of an array of 6,7-fused steroidal thiazoles (4-9) is reported. Replacement of lachrymatory 7-bromosteroidal ketones (4a) with readily accessible 5-bromosteroidal ketones (1-3), as a starting material, on simple condensation with thiourea or phenylthiourea gives the thiazole fused ring products. The products have been characterized on the basis of microanalytical and spectral data, which find support in some cases from comparison with previously known samples. A rationalization for the routes of conversion is given, based on current and previous results. Keywords: Steroidal thiazoles, lachrymatory, phenylthiourea, IR spectroscopy.INTRODUCTIONThiazole is an important heterocycle found in various natural products, notably thiamine (vitamin B). 1 Therefore, thiazole derivatives have been isolated and synthesized in view of their pharmacological activities viz antibacterial, antifungal, anti-inflammatory and antiviral. 2-6 These are also employed as antiallergic,

Singlet oxygen addition to homoallylic substrates in solution and microemulsion: novel secondary reactions

The photooxygenation of three homoallylic substrates, the γ,δ-unsaturated ketone 1a, nitrile 2a, and the γ,δ-unsaturated ester 3a was investigated in homogeneous solution and in microemulsion (for 1a). Two secondary reaction pathways were detected for the allylic hydroperoxides of type b and c, respectively. The cyclization reactions of 1b and 2b to the 1,2-dioxanes 1d and 2d followed well-known reaction patterns, whereas the base-catalyzed epoxide ( 1e– 3e) formation from the tertiary allylic hydroperoxides 1c– 3c is a unprecedented reaction type.

Stabilization of Ketone and Aldehyde Enols by Formation of Hydrogen Bonds to Phosphazene Enolates and Their Aldol Products

Solution properties of enolates generated using the phosphazene (Schwesinger) base P4-tBu were investigated by NMR spectroscopy. With a full equivalent of base the benzyl ketones 1a and 1b, the acetophenone 2, the arylacetaldehyde 1c, and the methyl arylacetate 1d formed the expected "naked" (P4H+) enolates 3 and 7. However, at a half-equivalent of base the ketones 1a and 1b as well as the aldehyde 1c formed solutions of stable hydrogen-bonded dimeric (enol-enolate) structures (4). The acetophenone 2, on the other hand, forms only traces of the H-bonded dimer 8 during deprotonation of 2. The thermodynamic product was the isomeric self-aldol condensation product 12. The mechanism of this condensation was elucidated by low temperature rapid-injection (RI) NMR spectroscopy. Solutions of 8 stable enough for NMR characterization could be transiently generated by semiprotonation of the enolate 7 with HCl.OEt2 at -130 degrees C using RINMR. The ester enolate 1d gave no trace of 4d even on a time scale as short as a few seconds at -130 degrees C either during the semideprotonation of 1d, or during semiprotonation of the enolate 3d. Long-lived solutions of the enols derived from 1a, 1b, 1c, and 2 (but not 1d) could be produced by full protonation of the phosphazene enolates with HCl.OEt2 at low temperature.

Study of the reaction of 1,1-bis(trimethylsilyl)-2-phenylethylene with some acyl chlorides in the presence of AlCl 3

1,1-Bis(trimethylsilyl)-2-phenylethylene ( 1), which has been synthesized from the Peterson reaction between (Me 3Si) 3CLi and benzaldehyde, reacts with various acyl chlorides (RCOCl, R = Me, Et, iso-Pr, n-Bu, iso-Bu, iso-C 5H 11, PhCH 2, PhCH 2CH 2) in the presence of AlCl 3 to give α-silyl-α,β-unsaturated enones 3a– 3h with high E stereoselectivity along with trans-α,β-unsaturated ketones 4a– 4h. The enones 3 can be partially converted into the ketones 4 with an excess of AlCl 3. Reaction of 1 with RCOCl, (R = Ph, CH 3CH=CH) afforded only the ketones 4. Yields were dependent on time and the amounts of AlCl 3 used.