Oxoammonium Salt Research Articles

Organocatalytic Asymmetric Dearomative Oxyalkylation of Indoles Enables Access to C2-Quaternary Indolin-3-ones.

A facile and efficient asymmetric dearomative oxyalkylation of indoles with TEMPO oxoammonium salt and a variety of aldehydes and ketones has been described. This metal-free approach provides a straightforward access to C2 quaternary oxindoles in high yields with excellent diastereo- and enantioselectivities under very mild conditions. The reaction goes smoothly even with only 0.1% equivalent catalyst. Moreover, 2-alkylindoles have proven to be suitable substrates for the first time.

Selective synthesis of β-nitrated N-heterocycles and N-nitroso-2-alkoxyamine aldehydes from inactivated cyclic amines promoted by tBuONO and oxoammonium salt.

A convenient synthesis of β-nitrated tetrahydropyridines has been successfully realized via dehydrogenative β-C-H nitrification of N-arylpiperidines promoted by tBuONO and the oxoammonium salt in THF. In addition, changing the solvent to an acetone/water mixture resulted in selective cleavage and tunable functionalization of the inert C-N bonds in cyclic amines to afford N-nitroso chain 2-alkoxyamine aldehydes. Notably, the application of N-nitroso-2-alkoxyamine aldehydes was showcased by their efficient transformation into 4-substituted 1,2-diazepines featuring a facile construction of a seven-membered ring.

Direct oxidative dearomatization of indoles: access to structurally diverse 2,2-disubstituted indolin-3-ones

Described is an efficient oxidative dearomatization of indoles with TEMPO oxoammonium salt and a broad range of nucleophiles. Under very mild conditions, dearomative oxyalkynylation and oxyalkenylation of indoles to structurally diverse 2,2-disubstituted indolin-3-ones were developed for the first time with high atom-economy. In addition, dearomative oxyarylation, oxyallylation, and oxycyanation of indoles were also demonstrated. Mechanism studies indicated that TEMPO oxoammonium salt served as the sole oxidant source through an electron donor-acceptor (EDA) intermediate.

Metal-Free Synthesis of Pyrrolo[1,2-a]quinoxalines Mediated by TEMPO Oxoammonium Salts

We herein describe a novel TEMPO oxoammonium salt initiated Pictet–Spengler reaction of imines, generated in situ from carbonyl compounds and pyrrole- or indole-containing substrates, to afford 4,5-dihydropyrrolo[1,2-a]quinoxalines or 5,6-dihydroindolo[1,2-a]quin­oxalines in good to excellent yields. Moreover, a one-pot synthesis of a biologically important quinoxaline is achieved via a cyclization–dehydrogenation process using one equivalent of the oxoammonium salt.

Direct oxidative C-H alkynylation of N-carbamoyl tetrahydroisoquinolines and dihydroisoquinolines.

An efficient oxidative C-H alkynylation of N-carbamoyl tetrahydroisoquinolines mediated by a TEMPO oxoammonium salt has been established. A variety of electronically varied N-carbamoyl tetrahydroisoquinolines reacted with a range of alkynyl potassium trifluoroborates smoothly under mild metal-free conditions. Dihydroisoquinolines were also suitable components for the reaction. The synthetic applicability of the method for facile access to structurally diverse bioactive molecules was further demonstrated.

Oxoammonium salt-mediated oxidative nitriles synthesis from aldehydes with ammonium acetate

An efficient and scalable route for the synthesis of nitriles was developed by oxoammonium salt (4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate) mediated oxidative conversion of aldehydes with NH4OAc. A variety of aliphatic aldehydes as well as benzaldehydes were converted into the corresponding nitriles in high yields. The nitroxyl radical which is the reduced species of the used oxoammonium salt was recovered by simple acid-base extraction for the recycling.

Enhancement of the Oxidizing Power of an Oxoammonium Salt by Electronic Modification of a Distal Group.

The multigram preparation and characterization of a novel TEMPO-based oxoammonium salt, 2,2,6,6-tetramethyl-4-(2,2,2-trifluoroacetamido)-1-oxopiperidinium tetrafluoroborate (5), and its corresponding nitroxide (4) are reported. The solubility profile of 5 in solvents commonly used for alcohol oxidations differs substantially from that of Bobbitt's salt, 4-acetamido-2,2,6,6-tetramethyl-1-oxopiperidinium tetrafluoroborate (1). The rates of oxidation of a representative series of primary, secondary, and benzylic alcohols by 1 and 5 in acetonitrile solvent at room temperature have been determined, and oxoammonium salt 5 has been found to oxidize alcohols more rapidly than does 1. The rate of oxidation of meta- and para-substituted benzylic alcohols by either 1 or 5 displays a strong linear correlation to Hammett parameters (r > 0.99) with slopes (ρ) of -2.7 and -2.8, respectively, indicating that the rate-limiting step in the oxidations involves hydride abstraction from the carbinol carbon of the alcohol substrate.

Preparation of Some Homologous TEMPO Nitroxides and Oxoammonium Salts; Notes on the NMR Spectroscopy of Nitroxide Free Radicals; Observed Radical Nature of Oxoammonium Salt Solutions Containing Trace Amounts of Corresponding Nitroxides in an Equilibrium Relationship.

Three new homologous TEMPO oxoammonium salts and three homologous nitroxide radicals have been prepared and characterized. The oxidation properties of the salts have been explored. The direct 13C NMR and EPR spectra of the nitroxide free radicals and the oxoammonium salts, along with TEMPO and its oxoammonium salt, have been successfully measured with little peak broadening of the NMR signals. In the spectra of all ten compounds (nitroxides and corresponding oxoammonium salts), the carbons in the 2,2,6,6-tetramethylpiperidine core do not appear, implying paramagnetic properties. This unpredicted overall paramagnetism in the oxoammonium salt solutions is explained by a redox equilibrium as shown between oxoammonium salts and trace amounts of corresponding nitroxide. This equilibrium is confirmed by electron interchange reactions between nitroxides with an N-acetyl substituent and oxoammonium salts with longer acyl side chains.

Catalytic Oxygenative Allylic Transposition of Alkenes into Enones with an Azaadamantane-Type Oxoammonium Salt Catalyst.

The first catalytic oxygenative allylic transposition of unactivated alkenes into enones has been developed using an oxoammonium salt as the catalyst. This reaction converts various tri- and trans-disubstituted alkenes into their corresponding enones with transposition of their double bonds at ambient temperature in good yields. The use of a less-hindered azaadamantane-type oxoammonium salt as the catalyst and a combination of two distinct stoichiometric oxidants, namely, iodobenzene diacetate and magnesium monoperoxyphthalate hexahydrate (MMPP⋅6 H2 O) are essential to facilitate the enone formation efficiently.

In Situ Generated TEMPO Oxoammonium Salt Mediated Tandem Cyclization of β-Oxoamides with Amine Hydrochlorides for the Synthesis of Pyrrolin-4-ones.

A novel in situ generated TEMPO oxoammonium salt mediated one-pot tandem reaction has been developed for the straightforward construction of pyrrolin-4-ones from readily available β-oxoamides with amine hydrochlorides. The reaction tolerates various functional groups and represents a reliable method for the synthesis of highly substituted pyrrolin-4-ones in good yields under mild conditions. Detailed mechanistic studies disclosed that TEMPO oxoammonium salt generated in situ was crucial for the transformation involving the formation of enaminone precursors in situ by condensation of the β-oxoamides with amines, followed by sequential oxidative coupling with β-oxoamides, intramolecular cyclization, and 1,2-alkyl migration steps.

Accessing N-Acyl Azoles via Oxoammonium Salt-Mediated Oxidative Amidation.

An operationally simple, robust, metal-free approach to the synthesis of N-acyl azoles from both alcohols and aldehydes is described. Oxidative amidation is facilitated by a commercially available organic oxidant (4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate) and proceeds under very mild conditions for an array of structurally diverse substrates. Tandem reactions of these activated amides, such as transamidation and esterification, enable further elaboration. Also, the spent oxidant can be recovered and used to regenerate the oxoammonium salt.

Oxidation of terminal diols using an oxoammonium salt: a systematic study.

A systematic study of the oxidation of a range of terminal diols is reported, employing the oxoammonium salt 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate (4-NHAc-TEMPO+ BF4-) as the oxidant. For substrates bearing a hydrocarbon chain of seven carbon atoms or more, the sole product is the dialdehyde. A series of post-oxidation reactions have been performed showing that the product mixture resulting from the oxidation step can be taken on directly to a subsequent transformation. For diols containing four to six carbon atoms, the lactone product is the major product upon oxidation. In the case of 1,2-ethanediol and 1,3-propanediol, when using a 1 : 0.5 stoichiometric ratio of substrate to oxidant, the corresponding monoaldehyde is formed which reacts rapidly with further diol to yield the acetal product. This is of particular synthetic value given both the difficulty of their preparation using other approaches and also their potential application in further reaction chemistry.

Synthesis of 3‐Benzazepines by Metal‐Free Oxidative C–H Bond Functionalization–Ring Expansion Tandem Reaction

AbstractA metal‐free synthesis of biologically important benzazepines is achieved through a single synthetic operation involving an oxidative C–H bond functionalization and ring expansion with diazomethanes as key reagent. This represents a new, strong methodology for the straightforward construction of the seven‐ring N‐heterocyclic structures under mild conditions using a 2,2,6,6‐tetramethylpiperidine 1‐oxyl (TEMPO) oxoammonium salt as oxidant. Moderate to good yields are achieved from simple, readily available tetrahydroisoquinolines, and this methodology has been further successfully applied for the synthesis of the 3‐benzazepine drug Lorcaserin. A possible mechanistic pathway for the ring expansion step, comprising the extrusion of nitrogen in a concerted asynchronic process, is proposed based on both mechanistic proof and density function theory (DFT) calculations.magnified image

ChemInform Abstract: A Metal‐Free Oxidative Cross‐Dehydrogenative Coupling of N‐Aryl Tetrahydroisoquinolines and 2‐Methylazaarenes Using a Recyclable Oxoammonium Salt as Oxidant in Aqueous Media.

ChemInformVolume 47, Issue 48 Preparative Organic Chemistry ChemInform Abstract: A Metal-Free Oxidative Cross-Dehydrogenative Coupling of N-Aryl Tetrahydroisoquinolines and 2-Methylazaarenes Using a Recyclable Oxoammonium Salt as Oxidant in Aqueous Media. Li Fang, Li Fang Key Lab. Green Pharm. Technol., Zhejiang Univ. Technol., Hangzhou 310014, Peop. Rep. ChinaSearch for more papers by this authorZhenhua Li, Zhenhua Li Key Lab. Green Pharm. Technol., Zhejiang Univ. Technol., Hangzhou 310014, Peop. Rep. ChinaSearch for more papers by this authorZhijiang Jiang, Zhijiang Jiang Key Lab. Green Pharm. Technol., Zhejiang Univ. Technol., Hangzhou 310014, Peop. Rep. ChinaSearch for more papers by this authorZhiyong Tan, Zhiyong Tan Key Lab. Green Pharm. Technol., Zhejiang Univ. Technol., Hangzhou 310014, Peop. Rep. ChinaSearch for more papers by this authorYuanyuan Xie, Yuanyuan Xie Key Lab. Green Pharm. Technol., Zhejiang Univ. Technol., Hangzhou 310014, Peop. Rep. ChinaSearch for more papers by this author Li Fang, Li Fang Key Lab. Green Pharm. Technol., Zhejiang Univ. Technol., Hangzhou 310014, Peop. Rep. ChinaSearch for more papers by this authorZhenhua Li, Zhenhua Li Key Lab. Green Pharm. Technol., Zhejiang Univ. Technol., Hangzhou 310014, Peop. Rep. ChinaSearch for more papers by this authorZhijiang Jiang, Zhijiang Jiang Key Lab. Green Pharm. Technol., Zhejiang Univ. Technol., Hangzhou 310014, Peop. Rep. ChinaSearch for more papers by this authorZhiyong Tan, Zhiyong Tan Key Lab. Green Pharm. Technol., Zhejiang Univ. Technol., Hangzhou 310014, Peop. Rep. ChinaSearch for more papers by this authorYuanyuan Xie, Yuanyuan Xie Key Lab. Green Pharm. Technol., Zhejiang Univ. Technol., Hangzhou 310014, Peop. Rep. ChinaSearch for more papers by this author First published: 10 November 2016 https://doi.org/10.1002/chin.201648052Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume47, Issue48November, 2016 RelatedInformation

Synthesis of 1,3-Cycloalkadienes from Cycloalkenes: Unprecedented Reactivity of Oxoammonium Salts.

Few methods allow for the direct conversion of cycloalkenes into cycloalkadienes with high chemo- and regioselectivity. Herein, we report a convenient one-pot process for this transformation that involves the unprecedented N-preferential group transfer of N-oxoammonium salts to cycloalkenes, followed by Cope elimination, to afford cycloalkadienes at room temperature and pressure.

Synthesis of 1,3‐Cycloalkadienes from Cycloalkenes: Unprecedented Reactivity of Oxoammonium Salts

AbstractFew methods allow for the direct conversion of cycloalkenes into cycloalkadienes with high chemo‐ and regioselectivity. Herein, we report a convenient one‐pot process for this transformation that involves the unprecedented N‐preferential group transfer of N‐oxoammonium salts to cycloalkenes, followed by Cope elimination, to afford cycloalkadienes at room temperature and pressure.

Oxidative Cleavage of Silyl Ethers by an Oxoammonium Salt

A method for the oxidative cleavage of silyl ethers to their corresponding carbonyl species mediated by an oxoammonium salt is described. The resulting aldehydes and ketones are obtained under mild reaction conditions with no observed overoxidation. For robust substrates, heating to reflux temperatures significantly reduces the reaction time.

A Metal‐Free Oxidative Cross‐Dehydrogenative Coupling ofN‐Aryl Tetrahydroisoquinolines and 2‐Methylazaarenes Using a Recyclable Oxoammonium Salt as Oxidant in Aqueous Media

A metal‐free oxidative cross‐dehydrogenative coupling ofN‐aryl tetrahydroisoquinolines and 2‐methylazaarenes in water under mild conditions has been developed. 4‐Acetylamino‐2,2,6,6‐tetramethylpiperidine‐1‐oxoammonium tetrafluoroborate was employed as a mild oxidant that can be recovered and reused directly. The reaction proceeds through formation of an iminium ion in situ followed by condensation with various nucleophiles, providing the desired products in moderate to good yields.

有機ニトロキシルラジカルの酸化還元特性を利用した効率的酸化システムの開発 —第一級アルコールからカルボン酸への酸化反応—

One-pot oxidation from primary alcohols to carboxylic acids is one of the most important methods in organic synthesis. With attention to the mechanistic advantage of Merck’s method (cat.2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO)/cat.NaOCl/NaClO2), we have developed an efficient one-pot oxidation using 1-Me-AZADO+X-(oxoammonium salt of 1-methyl-2-azaadamantane N-oxyl) and NaClO2. After that, our research interest was focused on selective oxidation from diols to hydroxy acids. Herein, we report development of a highly active oxidation catalyst for selective oxidation of primary alcohols, 1,5-dimethyl-Nor-AZADO (DMN-AZADO), and DMN-AZADO-catalyzed selective oxidation of diols to hydroxy acids, and also report the chemoselective oxidation of 1,2-diols to α-hydroxy acids together with the one-pot oxidative cleavage from 1,2-diols to one-carbon-shorter carboxylic acids. A mechanistic study suggests that the formation of charge-transfer complex TEMPO-ClO2 is a key for the observed chemoselectivity.

ChemInform Abstract: Access to Nitriles from Aldehydes Mediated by an Oxoammonium Salt.

AbstractThe spent oxidant can be recovered and regenerated.