37087-68-6

Usage

Uses

Used in Pharmaceutical Industry:
2-(4-METHOXYPHENYL)-1-CYCLOHEXANONE is used as a synthetic intermediate for the development of rac-14-epi-Dextromethorphan (D299440), an analog of Dextromethorphan (D299445). Dextromethorphan is a well-known antitussive compound that also exhibits analgesic properties, making it a common ingredient in cough medication formulations. The synthesis of rac-14-epi-Dextromethorphan through the use of 2-(4-METHOXYPHENYL)-1-CYCLOHEXANONE allows for the exploration of new therapeutic options and potential improvements in the treatment of cough and pain.

InChI:InChI=1/C13H16O2/c1-15-11-8-6-10(7-9-11)12-4-2-3-5-13(12)14/h6-9,12H,2-5H2,1H3

Upstream product

• 93-59-4 Perbenzoic acid 
• 20758-60-5 1-(4-methoxyphenyl)cyclohexene 
• 854727-09-6 6-(4-methoxy-phenyl)-cyclohex-3-enone 
• 13139-86-1 4-methoxyphenyl magnesium bromide 
• 822-87-7 2-Chlorocyclohexanone 
• 670-80-4 4-cyclohexen-1-ylmorpholine 
• 18649-43-9 4-methoxyphenyllead(IV) triacetate 
• 2562-37-0 1-nitrocyclohexene 
• 100-66-3 methoxybenzene 
• 937-14-4 3-chloro-benzenecarboperoxoic acid 
• 823-45-0 2-(hydroxymethylene)cyclohexanone 
• 20859-19-2 (+/-)-trans-2-(4-methoxyphenyl)cyclohexanol 
• 104-92-7 1-bromo-4-methoxy-benzene 
• 5720-07-0 4-methoxyphenylboronic acid 

Downstream Products

• 20859-19-2 (+/-)-trans-2-(4-methoxyphenyl)cyclohexanol 
• 79664-42-9 2-(4-Methoxy-phenyl)-1-p-tolyl-cyclohexanol 
• 89008-80-0 2-(4-Methoxy-phenyl)-cyclohexan-1-ol 
• 52839-57-3 (2R,3R,4R)-4-(4-Methoxy-phenyl)-1-oxa-spiro[2.5]octane-2-carbonitrile 
• 52839-58-4 (2S,3R,4R)-4-(4-Methoxy-phenyl)-1-oxa-spiro[2.5]octane-2-carboxylic acid methyl ester 
• 15638-15-0 1,2-bis(p-methoxyphenyl)cyclohexene 
• 190256-71-4 (R)-2-(4-methoxyphenyl)cyclohexan-1-one 
• 152140-46-0 (lR,2S)-trans-2-(p-methoxyphenyl)cyclohexan-1-ol 
• 146744-35-6 (1S,2R)-trans-2-(4-methoxyphenyl)cyclohexanol 

Relevant academic research and scientific papers

The Silicon-Hydrogen Exchange Reaction: Catalytic Kinetic Resolution of 2-Substituted Cyclic Ketones

We have recently reported the strong and confined, chiral acid-catalyzed asymmetric 'silicon-hydrogen exchange reaction'. One aspect of this transformation is that it enables access to enantiopure enol silanes in a tautomerizing σ-bond metathesis, via deprotosilylation of ketones with allyl silanes as the silicon source. However, until today, this reaction has not been applied to racemic, 2-substituted, cyclic ketones. We show here that these important substrates readily undergo a highly enantioselective kinetic resolution furnishing the corresponding kinetically preferred enol silanes. Mechanistic studies suggest the fascinating possibility of advancing the process to a dynamic kinetic resolution.

Selective C-C Bond Cleavage of Cycloalkanones by NaNO2/HCl

A novel selective fragmentation of cycloalkanones by NaNO2/HCl has been established. The C-C bond cleavage reaction proceeds smoothly under mild conditions, selectively affording versatile keto acids or oxime acids. The methodology can streamline the synthesis of valuable chiral molecules and isocoumarins from readily available feedstocks.

I(III)-catalyzed oxidative cyclization - Migration tandem reactions of unactivated anilines

An I(III)-catalyzed oxidative cyclization-migration tandem reaction using Selectfluor as the oxidant was developed that converts unactivated anilines into 3H-indoles is reported herein. The reaction requires as little as 1 mol % of the iodocatalyst and is mild, tolerating pyridine and thiophene functional groups, and the dependence of the diastereoselectivity of the process on the identity of the iodoarene or iodoalkane precatalyst suggests that the catalyst is present for the stereochemical determining C-N bond forming step.

Ylide-Functionalized Phosphine (YPhos)-Palladium Catalysts: Selective Monoarylation of Alkyl Ketones with Aryl Chlorides

Ylide-functionalized phosphine (YPhos) ligands allow the palladium-catalyzed α-arylation of alkyl ketones with aryl chlorides with record setting activity. Using a cyclohexyl-substituted YPhos ligand, a wide range of challenging ketone substrates was efficiently and selectively monoarylated under mild conditions. A newly designed YPhos ligand bearing tert-butyl groups on the coordinating phosphorus atom is already active at room temperature. The synthetic potential was demonstrated by gram-scale reactions and the succinct synthesis of ?-caprolactone derivatives.

Direct Asymmetric α-Hydroxylation of Cyclic α-Branched Ketones through Enol Catalysis

Enantiopure α-hydroxy carbonyl compounds are common scaffolds in natural products and pharmaceuticals. Although indirect approaches towards their synthesis are known, direct asymmetric methodologies are scarce. Herein, we report the first direct asymmetric α-hydroxylation of α-branched ketones through enol catalysis, enabling a facile access to valuable α-keto tertiary alcohols. The transformation, characterized by the use of nitrosobenzene as the oxidant and a new chiral phosphoric acid as the catalyst, delivers a good scope and excellent enantioselectivities.

Enantioselective Protonation of Silyl Enol Ethers Catalyzed by a Chiral Pentacarboxycyclopentadiene-Based Bronsted Acid

The enantioselective protonation of silyl enol ethers was realized in the presence of a pentacarboxycyclopenta-1,3-diene-based chiral Bronsted acid catalyst with water as an achiral proton source to give the corresponding α-aryl ketones in good yields and up to 75percent ee.

Synthesis of α-Arylated Cycloalkanones from Congested Trisubstituted Spiro-epoxides: Application of the House-Meinwald Rearrangement for Ring Expansion

A three-step sequence for the synthesis of α-arylated cyclohexanones and the most challenging cycloheptanones is reported. First, an efficient one-pot synthesis of β,β'-disubstituted benzylidene cycloalkanes (styrenes) using the palladium-catalyzed Barluenga reaction from readily available feedstock chemicals is described. Furthermore, an epoxidation followed by the House-Meinwald rearrangement (HMR) of spiro-epoxides is reported to produce a number of α-arylated cycloalkanones upon ring expansion. Reactions catalyzed by bismuth triflate underwent quasi-exclusively ring expansion for all substrates (electronically poor and rich), with yields ranging from 15% to 95%, thus demonstrating the difficulty of achieving ring enlargement for electron-deficient spiro-epoxides. On the other hand, by means of catalysis with aluminum trichloride, the rearrangement of spiro-epoxides proceeded typically in high yields and with remarkable regioselectivity on a broader substrate scope. In this case, a switch of regioselectivity was achieved for spiro-epoxides with electron-withdrawing substituents which enable the method to be successfully extended to some chemospecific arene shifts and the synthesis of aldehydes bearing a α-quaternary carbon. While the HMR has been extensively studied for smaller ring enlargement, we are pleased to report herein that larger cyclohexanones and cycloheptanones can be obtained efficiently from more sterically demanding trisubstituted spiro-epoxides bearing electron-releasing and electron-neutral arene substituents.

Regioselective 1,2-Diol Rearrangement by Controlling the Loading of BF3·Et2O and Its Application to the Synthesis of Related Nor-Sesquiterene- and Sesquiterene-Type Marine Natural Products

The regiocontrolled rearrangement of 1,2-diols has been achieved by controlling the loading of BF3·Et2O. Its applicability is showcased by the divergent synthesis of austrodoral, austrodoric acid, and 8-epi-11-nordriman-9-one, as well as a formal synthesis of siphonodictyal B and liphagal. A new light is shed on piancol-type rearrangements that will be useful in diversity-oriented synthesis of related natural products.

Promoting reductive tandem reactions of nitrostyrenes with Mo(CO)6 and a palladium catalyst to produce 3 h -indoles

The combination of Mo(CO)6 and 10 mol % of palladium acetate catalyzes the transformation of 2-nitroarenes to 3H-indoles through a tandem cyclization-[1,2] shift reaction of in situ generated nitrosoarenes. Mo(CO)6 appears to have dual roles in this transformation: generate CO and promote C-N bond formation to increase the yield of the N-heterocycle product.

Catalytic asymmetric synthesis of sterically hindered tertiary α-aryl ketones

The catalytic asymmetric synthesis of a series of tertiary α-aryl cyclopentanones and cyclohexanones has been accomplished via a Pd-catalyzed decarboxylative protonation of the corresponding α-aryl-β-keto allyl esters. Enantioselectivities of up to 92% ee and 74% ee were achieved for cyclopentanone and cyclohexanone substrates, respectively. The route described gives access to these important structural motifs in moderate to high levels of enantioselectivity. In particular, this is only the second direct approach for the preparation of tertiary α-aryl cyclopentanones. The synthetic approach allows for simple modification of the aryl group. Significantly, substrates containing sterically hindered aryl groups gave the highest levels of enantioselectivity, and these aryl groups were readily installed by a Pb-mediated arylation of a β-keto allyl ester.