Bobbitt's Salt-Mediated Oxidation of Alkynyl-ols and -diols to the Corresponding Aldehydes and Their Application in Tandem Reactions.

Propargyl alcohol derivatives were readily oxidized using Bobbitt's salt to yield the corresponding propynal products. 2-Butyn-1,4-diol may be selectively oxidized to provide either 4-hydroxy-2-butynal or acetylene dicarboxaldehyde, and the resulting stable dichloromethane solutions containing the chemically sensitive acetylene aldehydes were used directly in subsequent Wittig, Grignard, or Diels-Alder reactions. This method provides safe and efficient access to propynals and allows the preparation of polyfunctional acetylene compounds from readily accessible starting material without the use of protecting groups.

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.

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.

Metal-Free Oxidation of Primary Amines to Nitriles through Coupled Catalytic Cycles.

Synergism among several intertwined catalytic cycles allows for selective, room temperature oxidation of primary amines to the corresponding nitriles in 85-98% isolated yield. This metal-free, scalable, operationally simple method employs a catalytic quantity of 4-acetamido-TEMPO (ACT; TEMPO=2,2,6,6-tetramethylpiperidine N-oxide) radical and the inexpensive, environmentally benign triple salt oxone as the terminal oxidant under mild conditions. Simple filtration of the reaction mixture through silica gel affords pure nitrile products.

Facile oxidation of primary amines to nitriles using an oxoammonium salt.

The oxidation of primary amines using a stoichiometric quantity of 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate (1) in CH2Cl2-pyridine solvent at room temperature or at gentle reflux affords nitriles in good yield under mild conditions. The mechanism of the oxidation, which has been investigated computationally, involves a hydride transfer from the amine to the oxygen atom of 1 as the rate-limiting step.

Oxoammonium salt oxidations of alcohols in the presence of pyridine bases.

Oxoammonium salt oxidations (using 4-acetylamino-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate) of alcohols containing a ß-oxygen atom in the presence of pyridine yield dimeric esters, while in the presence of 2,6-lutidine the product is a simple aldehyde. The formation of a betaine between pyridine and an aldehyde is presented to explain this disparity in reactivity. The betaine is oxidized by the oxoammonium salt to give an N-acylpyridinium ion that serves as an acylating agent for ester formation. Steric effects deter the formation of such a betaine with 2,6-disubstituted pyridines. A series of alcohols containing a ß-oxygen substituent were oxidized to aldehydes in the presence of 2,6-lutidine, and a short study of the relative reactivity of various alcohols is given. An overall mechanism for oxoammonium cation oxidations is suggested, premised on nucleophilic additions to the oxygen atom of the positively charged nitrogen-oxygen double bond. Possible mechanisms for both dimeric oxidations and simple oxidations are given.

Synthesis of 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate and 4-acetamido-(2,2,6,6-tetramethyl-piperidin-1-yl)oxyl and their use in oxidative reactions.

We describe the synthesis of the lesser-known stoichiometric oxidation reagent 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate (1, Bobbitt's salt), as well as of 4-acetamido-(2,2,6,6-tetramethyl-piperidin-1-yl)oxyl (2, AcNH-TEMPO). Several representative oxidation reactions are also presented to demonstrate the salt's oxidative capabilities. Bobbitt's salt has a range of applications, from the oxidation of various alcohols to their corresponding carbonyl derivatives to the oxidative cleavage of benzyl ethers, whereas 2 has been shown to serve as a catalytic or stoichiometric oxidant. The oxyl radical can be obtained in 85% yield over two steps on a 1-mole scale from commercially available 4-amino-2,2,6,6-tetramethylpiperidine (5), and is far more cost-effective to prepare in-house than purchase commercially. An additional step converts the oxyl radical into the oxoammonium salt (1, Bobbitt's salt) in 88% yield, with an overall yield of 75%. The synthesis of the salt takes ∼5 d to complete. Oxoammonium salts are metal-free, nontoxic and environmentally friendly oxidants. Preparation of 1 is also inherently 'green', as water can be used as the solvent and the use of environmentally unfriendly materials is minimal. Moreover, after it has been used, the spent oxidant can be recovered and used to regenerate 1, thereby making the process recyclable.

Selective oxoammonium salt oxidations of alcohols to aldehydes and aldehydes to carboxylic acids.

The oxidation of alcohols to aldehydes using stoichiometric 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate (1) in CH(2)Cl(2) at room temperature is a highly selective process favoring reaction at the carbinol center best able to accommodate a positive charge. The oxidation of aldehydes to carboxylic acids by 1 in wet acetonitrile is also selective; the rate of the process correlates with the concentration of aldehyde hydrate. A convenient and high yield method for oxidation of alcohols directly to carboxylic acids has been developed.

Oxidative cleavage of benzylic and related ethers, using an oxoammonium salt.

Benzylic ethers and related ArCH(2)OR substrates are oxidatively cleaved by 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate (1) in wet CH(3)CN at room temperature to give the corresponding aromatic aldehyde and alcohol in high yield. Primary or secondary alcohol products are further oxidized by 1 to give carboxylic acids and ketones, respectively. The oxidation likely involves a formal hydride abstraction from the benzylic carbon as evidenced by slow reaction of substrates bearing electron-withdrawing substituents.

Mechanism of the oxidation of alcohols by oxoammonium cations.

The mechanism of the oxidation of primary and secondary alcohols by the oxoammonium cation derived from 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) has been investigated computationally at the B3LYP/6-31+G* level, along with free energies of solvation, using a reaction field model. In basic solution, the reaction involves formation of a complex between the alkoxide anion and the oxoammonium cation in a pre-oxidation equilibrium wherein methoxide leads to a much larger formation constant than isopropoxide. The differences in free energy of activation for the rate-determining hydrogen transfer within the pre-oxidation complexes were small; the differences in complex formation constants lead to a larger rate of reaction for the primary alcohol, as is observed experimentally. In acidic solution, rate-determining hydrogen atom transfer from the alcohol to the oxoammonium cation had a large unfavorable free energy change and would proceed more slowly than is observed. A more likely path involves a hydride transfer that would be more rapid with a secondary alcohol than primary, as is observed. Transition states for this process were located.

Ene-like addition of an oxoammonium cation to alkenes: highly selective route to allylic alkoxyamines.

The oxoammonium cation of 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate (1) adds rapidly at room temperature in an ene-like fashion to trisubstituted alkenes to afford allylic alkoxyamines in high yield. [reaction: see text]

Influence of microemulsions on enantioselective synthesis of (R)-cyclopent-2-enol catalyzed by vitamin B12.

The influence of microemulsions on the vitamin B12-catalyzed enantioselective isomerization of 1,2-epoxycyclopentane (1) to form (R)-cyclopent-2-enol (2) has been examined. The reaction was initiated by a reduction of vitamin B12 to the Co(I) form by Zn/NH4Cl. The largest enantiomeric excess (e.e.) in the products was 52% for (R)-2 obtained in a bicontinuous sodium dodecyl sulfate (SDS) microemulsion. A water-in-oil SDS microemulsion gave a poorer percent e.e. probably because of limited catalyst utilization in the water droplets. The influence of the pH of the water phase, the amount of water, and the concentration of vitamin B12 on the enantioselectivity and yield of the reaction was also explored. Results suggest that factors such as higher water content and bicontinuous fluid structure facilitated efficient intermixing of catalyst with reactant to form a key organocobalt intermediate, thus improving enantioselectivity.

Oxoammonium salts. 9. Oxidative dimerization of polyfunctional primary alcohols to esters. An interesting beta oxygen effect.

The use of the oxidant 4-acetylamino-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate in combination with pyridine for the oxidative, dimeric esterification of primary alcohols is described. The ester is the predominant product of the reaction with alcohols containing a beta oxygen. In the absence of a beta oxygen, the corresponding aldehyde is found in appreciable amounts, but a concentration effect can be observed. In the absence of pyridine, little ester is formed, and no appreciable reaction takes place with beta-oxygenated compounds. Delta lactones have been prepared from diethylene glycol and 2,2'-thiodiethanol, without sulfur oxidation.

Asymmetric electrochemical lactonization of diols on a chiral 1-azaspiro[5.5]undecane N-oxyl radical mediator-modified graphite felt electrode.

A graphite felt electrode modified with (6S,7R,10R)-4-amino-2,2,7-trimethyl-10-isopropyl-1-azaspiro[5.5]undecane N-oxyl was prepared for electrocatalytic oxidation of diols; electrolysis of diols on the modified electrode yielded optically active lactones (92.0-96.4%), with an enantiopurity of 82-99% ee.