Kishner Reduction Research Articles

Synthesis and intramolecular hydrogen bonding of syn-9-hydroxy-18-substituted [3.3]metacyclophanes

Various anti-9-methoxy[3.3]metacyclophane-2,11-diones are exclusively obtained by the coupling reaction of the corresponding 1,3-bis(bromomethyl)benzenes and 2,6-bis[2-isocyano-2-(tolylsulfonyl)ethyl]-4-tert-butylanisole in dimethylformamide (DMF) with an excess of sodium hydride, from which the corresponding syn-[3.3]metacyclophanes (MCPs) are synthesized via anti/syn-isomerization during the Wolff–Kishner reduction. Demethylation of syn-9-methoxy[3.3]MCPs with BBr3 afforded the corresponding syn-9-hydroxy[3.3]MCPs in good yields. The existence of the strong intramolecular hydrogen bonding between the 9-hydroxy group and the 18-substituents, such as F, OH, and OMe groups at the opposing aromatic rings, are observed in solution and in the solid state. A distinct low-field shift of the phenolic OH proton was observed in the 1H NMR spectrum compared with that of the 18-unsubstituted analog. Furthermore, O–H···F through-space coupling was observed.

Synthesis and Conformational Studies of 9-Methoxy[3.3]Metacyclophanes and 9-Methoxy[3]Metacyclo[3](2,6)Pyridinophane

anti-9-Methoxy[3]metacyclo[3](2,6)pyridinophan-2,11-dione is obtained by the coupling reaction of 2,6-bis (bromomethyl)pyridine and 2,6-bis[2-isocyano-2-(tolylsulfonyl)ethyl]-4-tert-butylanisole in dimethylformamide (DMF) with an excess of sodium hydride, from which the corresponding syn-9-methoxy[3]metacyclo[3](2, 6)pyridinophane is synthesised via anti–syn-isomerisation during the Wolff–Kishner reduction in good yield.

Alternative Synthesis of 5-Chloromethyl-2,3-Dimethoxy-6-Methyl-1,4-Benzoquinone: A Key Intermediate for Preparing Coenzyme Q Analogues

The title compound, a key intermediate for preparing Coenzyme Qn family, was prepared in high yield by a reaction sequence starting from the commercially available 3, 4, 5-trimethoxy-benzadehyde via Wolff–Kishner reduction, Vilsmeier–Haack reaction, Blanc chloromethylation reaction, Dakin reaction and oxidation.

A Green and Efficient Synthesis of 1-Chloromethyl -2,3,4,5-Tetramethoxy-6-Methylbenzene

The title compound, a key intermediate for preparing coenzyme Q analogues, was prepared in excellent yield by a reaction sequence starting from the commercially available 3,4,5-trimethoxybenzadehyde via Wolff–Kishner reduction, selective bromination, methoxylation and Blanc chloromethylation reaction.

ChemInform Abstract: The Synthesis of Nor- and Bisnorlupanes.

In the course of our studies on geochemical biomarkers we required a series of lupane standards. We report here an efficient synthesis of lupane (1) in three steps from betulin (3) in an overall yield of 47.2%. 17β(H)-28-Norlupane (2) was obtained in 90% purity employing Barton's method for the decarboxylation of 3-oxolupan-28-oic acid (10). 24,28-Bisnorlupane (4) and 24-norlupane (5) were obtained by a series of reactions involving formation of the oxime, the seconitrile, the epoxynitrile, ring closure, and finally a Wolff–Kishner reduction of the C3 carbonyl to the methylene. Also, to aid in the quantitative determination of these lupanes from oil shales and geological samples, 3-deuterolupane (6) and 2,3-dideuterolupane (7) were needed, and a method for their preparation is reported. Key words: lupane, 24-norlupane, 28-norlupane, 24,28-bisnorlupane, 3-deuterolupane, 2,3-dideuterolupane.

Synthesis and Process Optimization of Amtolmetin: An Antiinflammatory Agent

Efforts toward the synthesis and process optimization of amtolmetin guacil 1 are described. High-yielding electrophilic substitution followed by Wolf−Kishner reduction are the key features in the novel synthesis of tolmetin 2 which is an advanced intermediate of 1.

An Asymmetric Total Synthesis of Brevisamide

An enantioselective synthesis of marine alkaloid brevisamide was accomplished in a convergent manner. The synthesis utilized an enantioselective hetero-Diels-Alder reaction which sets three chiral centers in compound 11. The synthesis also features a modified Wolff-Kishner reduction, Rubottom oxidation, and Suzuki-Miyaura coupling to furnish brevisamide.

A Practical, Kilogram-Scale Implementation of the Wolff−Kishner Reduction

A safe and practical strategy has been developed for the large-scale preparation of imidazole 7. The key transformation involved the Wolff−Kishner reduction of the sterically demanding neopentyl-trifluoromethylcyclopropyl imidazole ketone 8. The described process provided the desired product in 74% overall yield without recourse to chromatographic purification. Safety considerations which allowed for the reaction to be conducted safely on kilogram scale are discussed.

7α- and 12α-Hydroxysteroid dehydrogenases from Acinetobacter calcoaceticus lwoffii: a new integrated chemo-enzymatic route to ursodeoxycholic acid

We report the very efficient biotransformation of cholic acid to 7-keto- and 7,12-diketocholic acids with Acinetobacter calcoaceticus lwoffii. The enzymes responsible of the biotransformation (i.e. 7α- and 12α-hydroxysteroid dehydrogenases) are partially purified and employed in a new chemo-enzymatic synthesis of ursodeoxycholic acid starting from cholic acid. The first step is the 12α-HSDH-mediated total oxidation of sodium cholate followed by the Wolf–Kishner reduction of the carbonyl group to chenodeoxycholic acid. This acid is then quantitatively oxidized with 7α-HSDH to 7-ketochenodeoxycholic acid, that was chemically reduced to ursodeoxycholic acid (70% overall yield).

A New Synthetic Route of 2-Aroyl- and 2-Benzyl-Benzofurans and their Application in the Total Synthesis of a Metabolite Isolated from Dorstenia gigas

The Lewis acid-catalyzed cyclization of the (Z)-3-(dimethylamino)-2-aryloxy-1-arylprop-2-en-1-ones 4a–h leads to a regioselective and short synthesis of 2-aroylbenzofurans 2a–h. The Wolff–Kishner reduction of the latter yielded a series of substituted 2-benzylbenzofurans 3a–h. This methodology was applied in the first total synthesis of the metabolite 2-(4-hydroxybenzyl)-6-methoxybenzofuran 1, which was isolated from the tropical plant Dorstenia gigas, and obtained through a six-step route and in a 24% overall yield.

The synthesis of the insect pheromone (2 S,3 R,7 R)-3,7-dimethyltridec-2-yl acetate from racemic 3,4-dimethyl-γ-butyrolactone by diastereoselective chiral resolution

The insect pheromone (2 S,3 R,7 R)-3,7-dimethyltridec-2-yl acetate 1- Ac was prepared from diastereomerically enriched (2 S ∗,3 R ∗,7 R)- 1, which in turn was obtained by the coupling of racemic 3,4-dimethyl-γ-butyrolactone with (7 S)-2-methyloctyllithium, followed by a Wolff–Kishner reduction of the resulting ketone. Conversion of (2 S ∗,3 R ∗,7 R)- 1 to the corresponding alkyl hydrogen phthalate and diastereomer salt formation with ( S)-PhCHMeNH 2 provided after several crystallizations individual diastereomer, which was later transformed into target 1- Ac after hydrolysis and acylation.

Reductive Deoximation of Aryloximes into Hydrocarbons by Hydrazine/KOH: A Novel Application of the Wolff—Kishner Reduction.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Practical Synthesis of 2,3,4,5‐Tetramethoxytoluene.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

New Practical Synthesis of Indazoles via Condensation of o-Fluorobenzaldehydes and Their O-Methyloximes with Hydrazine

The reaction of o-fluorobenzaldehydes and their O-methyloximes with hydrazine has been developed as a new practical synthesis of indazoles. Utilization of the methyloxime derivatives of benzaldehydes (in the form of the major E-isomers) in this condensation effectively eliminated a competitive Wolf-Kishner reduction to fluorotoluenes, which was observed in the direct preparations of indazoles from aldehydes. Reaction of Z-isomers of methyloximes with hydrazine resulted in the formation of 3-aminoindazoles via a benzonitrile intermediate.

Practical Synthesis of 2,3,4,5‐Tetramethoxytoluene

The title compound, a key material for synthesis of coenzyme Q10, was effectively prepared in high yield by a reaction sequence starting from 3,4,5‐trimethoxybenzadehyde via Wolff–Kishner reduction, Vilsmeier–Haack reaction, Dakin reaction, and methylation.

Reductive Deoximation of Aryloximes into Hydrocarbons by Hydrazine/KOH: A Novel Application of the Wolff–Kishner Reduction

We report the reductive deoximation of different substituted aryl, diaryl, and aralkyloximes into the respective methyl or methylene derivatives by hydrazine hydrate/KOH at reflux in satisfactory yields.

Phosphorinanes as Ligands for Palladium‐Catalyzed Cross‐Coupling Chemistry.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Synthesis of Multiwalled Carbon Nanotubes through a Modified Wolff−Kishner Reduction Process

We report the synthesis of highly crystallized multiwalled carbon nanotubes through a modified Wolff-Kishner reduction process at a low temperature of 180 degrees C without adding the conventional catalysts of Fe/Co/Ni into the reaction vessel. The as-synthesized carbon nanotubes are about 10-40 nm in diameter and several tens of micrometers in length. The experimental results indicate that a high concentration of NaOH is essential to the formation of carbon nanotubes. This technique opens a new route for the synthesis of CNTs and other carbon nanostructured materials.

Synthesis of Eburnamine, Isoeburnamine, and Eburnamonine via a Spirocyclic Intermediate

AbstractRacemic eburnamonine (1) was synthesized via 6, an intermediate possessing local symmetry. Cleavage of the cyclopentene subunit led to pentacyclic aldehydes 8a/8b which on subsequent borohydride and Wolff–Kishner reductions gave 12. The final steps included a RuCl3‐catalyzed periodate oxidation and pyridinium chlorochromate (PCC) oxidation. The penultimate intermediates were racemic eburnamine (2) and racemic isoeburnamine (3).

Kishner′s Reduction of 2‐Furylhydrazone Gives 2‐Methylene‐2,3‐dihydrofuran, a Highly Reactive Ene in the Ene Reaction.

AbstractFor Abstract see ChemInform Abstract in Full Text.