Amides oxidation potential

For synthetic purposes, aldol-rype condensations of aldehydes with esters or amides are potentially of great utility because the carbonyl group is easily transformed either by further additions or by oxidation or reduction. Deprotonation of an ester [7, 19, 20] or amide of fluoroacetic acid [9, 27] has led to aldol condensations in high yields (equation 17) (Table 7)... 

Using esters instead of acids reduces the rate of formation of lactones and gives rise to trapping by solvent as well as the formation of overall diene substitution products. Oxidation of amidomalonic ester 57, for example, yields as major products the acetic acid trapping product 58 and the diene substitution product 59, but only 5% of lactone 60 (equation 26). The oxidation of the initially formed amidomalonic ester radical, of increased importance in this case due to the amide substituent, could be largely reduced through addition of sodium acetate or trifluoroacetic acid, which are known to reduce the oxidation potential of the Mn(III) acetate. 

In addition to using indirect oxidation reactions, electroauxiliaries have been used to circumvent problems with problematic amide oxidations. As mentioned in Sect. 10.2.2, an electroauxiliary is a group that is added to a molecule in order to reduce the oxidation potential of the... 

Scheme 28 Lowering the oxidation potential of amide by an electroauxiliary.

Both anodic oxidation reactions proceeded well. As illustrated in Scheme 44, an anodic methoxylation of menthyl pyroglutamate followed by the trapping of an incipient A-acyliminium ion with allyl-silane in the presence of Lewis acid led to (138) [86]. While the stereoselectivity of this reaction was not high, the major product from the reaction could be fractionally crystallized from hexane and the route used to conveniently prepare (138) on a scale of 10 g. In this case, a platinum wire anode was used in order to keep the current density high. This was required because of the high oxidation potential of the secondary amide relative to the methanol solvent used in the reaction. 

Pentadentate macrocyclic ligands L13-L15 accommodate Ni(II) ion with simultaneous dissociation of the two amide protons to form the square-pyramidal high-spin complex of [NiH 2L]°, 27. These complexes are air-sensitive and show a very low Ni(II)/Ni(III) oxidation potential of +0.24 V vs SCE (72, 73). They form 1 1 dioxygen adducts, 27-02, at room temperature in aqueous solution, which are formulated as Nilu-02 based on the EPR spectral data. The magnetic moment of the 1 1 02 adduct is 2.83 BM, which is interpreted in terms of weak interactions of Ni(III) with the superoxide where the spin coupling is weak. The oxygen uptake reaction is first-order with respect to both [02] and [NiH 2L]° in aqueous solutions and yields a second-order rate constant... 

The electrochemical oxidation of acyl silanes has been investigated, giving rise to esters and amides when carried out in the presence of alcohols and amines. The oxidation potentials of acyl silanes proved to be much lower than those of the corresponding ketones213. 

Perhaps the most useful type of alkene substrates for these reactions are enol ethers, enol esters and vinyl sulfides. Silyl enol ethers have excellent electron-donor properties, with an ionization potential of about 8 eV and an oxidation potential in various solvents of approximately 1.0-1.5 V vs SCE161. These compounds are easily synthesized by reaction of an enolate with a chlorosilane. (A very recent report synthesized a variety of silyl enol ethers with extremely high stereochemical yield, using the electrogenerated amidate of 2-pyrolidinone as the base.)162 An interesting point is that the use of oxidative or reductive cyclization reactions allows carbonyl functionalities to be ambivalent, either oxidizable or reducible (Scheme 65)163. 

Electrochemical studies confirmed the presence of redox-active nanoparticles. Differential pulse and cyclic voltammetry studies were conducted. Cyclic voltammetry showed that the complex displays an electrochemically reversible ferrocene/ ferrocenium couple (Figure 9.6). The oxidation potential for the hybrid CPMV-Fc conjugate and free ferrocenecarboxylic acid in solution was determined E1/2 of CPMV-Fc was 0.23 V, and Elj2 of free ferrocenecarboxylic acid was 0.32 V versus the Ag/AgCl electrode, respectively. This shift is expected for the conversion of the carboxyl group of ferrocenecarboxylic acid to an amide on coupling to the virus capsid, since the amide is less electron-withdrawing. 

During the above study, it became apparent that stannyl amides exhibit lower oxidation potential compared with the original nonstan-nylated amides. These phenomena have also been reported by Yoshida et al. in their measurements of oxidation potentials of a-stannyl derivatives (Table 7). Yoshida and co-workers explained that the decrease in the oxidation potential is attributed to the rise of the HOMO level of the stannyl (or silyl) compound by interaction of the carbon-tin (or carbon-silicon) a bond and the nonbonding p orbital of the oxygen atom. 

J.K. Cha et al. developed a stereocontrolled synthesis of bicyclo[5.3.0]decan-3-ones from readily available acyclic substrates. Acyclic olefin-tethered amides were first subjected to the intramolecular Kulinkovich reaction to prepare bicyclic aminocyclopropanes. This was followed by a tandem ring-expansion-cyclization sequence triggered by aerobic oxidation. The reactive intermediates in this tandem process were aminium radicals (radical cations). The p-anisidine group was chosen to lower the amine oxidation potential. This substituent was crucial for the generation of the aminium radical (if Ar = phenyl, the ring aerobic oxidation is not feasible). 

Acyliminium ions. Oxidative destannylation of A/-(a-stannylalkyl) amides leads to reactive electrophiles, which can react with enol silyl ethers, allylsilanes, allylstannanes, and trimethylsilyl cyanide. The stannyl group lowers the oxidation potential of the amidic nitrogen, without which the acyliminium ions do not form under the oxidation conditions. 

In sum, the course of heteroatom oxidation appears to be sensitive to the oxidation potential of the heteroatom, the acidity of hydrogens on the adjacent carbon, and steric factors. The bulk of the evidence suggests that oxidation of the nitrogen in amines generally involves electron abstraction followed primarily by A-dealkylation if a labile proton is present, or nitrogen oxidation if it is not. As the nitrogen oxidation potential increases, there is a shift toward direct insertion into the C-H bond, as is thought to occur in the A-dealkylation of amides. 

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