Oxidation of enamines

The formation of a-acetoxyketones by oxidation of enamines with thallic acetate has been studied in detail (27) and found to be of preparative value (80 % yields) particularly in five- and six-membered-ring ketone derivatives. Enamines of linear or seven-membered-ring ketones were oxidized also, but at very much slower rates. Enamines of aldehydes with a-hydrogen substituents underwent self-eondensations during the oxidation reactions. Lead tetraacetate was less satisfactory as an oxidizing agent. 

From the oxidation of enamines with aromatic nitro compounds a-keto-enamines were obtained in modest yields (70J). Photooxygenation led to cleavage of the enamine double bond (706,707). 

Scheme 6.36 Oxidation of enamines with alumina-supported potassium permanganate.

Oxidation of enamines.1 Oxidation of enamines of cyclic ketones in the presence of BFj etherate results in a Favorski type rearrangement to esters of contracted cycloalkanoic acids. A related reaction also occurs with enamines of aryl methyl ketones. 

Anodic oxidation of enamine ketones or esters in CH30H-NaC104 at a graphite anode gives substituted pyrroles in 15-45% yield.101 Formation of the symmetrically substituted pyrroles 47 indicated radical dimerization of radical-cations formed as primary products from 46. This process leads to dications from which the pyrroles can be formed by cyclization and elimination of an amine [Eq. (44)]. 

A different route to pyrones is the preparative electrochemical oxidation of enamines in acetonitrile in the presence of tetraethylammonium perchlorate (88MI2) (Scheme 46). The synthesis of 2-pyrone derivatives has been carried out by reaction of /3-dicarbonyl compounds with methyl-a-benzoylamino-/3-dimethylaminoacrylate (96JHC751). Thiapyran derivatives can be obtained by interaction of enamines based on (/3-amino-a-cyanoacryloylmethyl)pyridinium chloride derivatives with carbon disulfide (95M711).The synthesis of pyridine derivatives based on analogous enamines has been described as well (95M711). 

The oxidation of enamines 313) was used for the synthesis of potential drug intermediates ... 

Oxidation of enamines derived from cyclic and acyclic ketones with thallium triacetate in equivalent amount leads to the formation of the corresponding 2-acetoxy ketones75 (Scheme 52). The reactions are stereoselective (the antiparallel attack of the oxidizing agent is preferred over a parallel attack on 3- and 4-/-butylcyclohexanone enamines) and the attack occurs preferentially at the tetrasubstituted enamine double bond, when there is more than one possibility due to isomerism. 

Nitric acid oxidation of enamines produces fission of the C—C double bond in preference over fission of the C—N bond and this preference increases on increasing the concentration of N02, which was shown to be the reactive species89 (Scheme 66). 

Hydroboration-oxidation of enamines has been reported by Borowitz and Williams171 to furnish the corresponding trans amino alcohols (Scheme 119). 

The anodic oxidation of enamines in methanol containing sodium methoxide as the supporting electrolyte shows a reaction pattern different from that of enol ethers or enol acetates. The main products are mixtures of isomeric methoxylated enamines, (18) and (19), with yields in the range 74-76% (equation... 

Oxidation of Enamines. Enamines are rapidly oxidized by (+)-(camphorylsulfonyl)oxaziridine (1). Disubstituted enamines give rise to racemic ot-amino ketones, while trisubstituted enamines afford, after hydrolysis, ot-hydroxy ketones (eq 2). A mechanism involving initial oxidation of the enamine to an a-amino epoxide is suggested to account for these products. 

By electrochemical oxidation of enamines, in situ prepared from an aldehyde and a secondary amine, using KI as mediator system, )6-ketoamines were formed in 30 to... 

Anodic oxidation of enamines in NaCN-MeOH with iodide ion as mediator provides ring-fused cyclopropane aminonitriles with the nitrile group exclusively in exo position [Eq. (29)] [256]. This reaction is possibly an electrocyclic ring closure of an intermediate allyl cation LXXIII. 

A Favorskii-type rearrangement occurs on boron trifluoride promoted lead tetraacetate oxidation of enamines " (Scheme 119). Five-membered rings may also be constructed by a Michael addition-radical cyclization process (Scheme 120). 

Enamines of unsaturated aldehydes can be converted into the corresponding dienes for example, citronellal, a chiral aldehyde, gives the chiral non-conjugated diene, /f-citronellene, in 92% enantiomeric excess - (Scheme 172). The combination of the Lewis hydroboration procedure with the thallium acetate acetoxylation of enamines provides a means of converting enamines into acetoxycycloalkenes (Scheme 173). The hydroboration oxidation of enamines to give -aminoalcohols was first reported by Borowitz and Williams . Cw-l,2-addition of BH3 occurs, to give the trans-ji-ammocy-... 

Scheme 2.2-42 Oxidation of enamines with KMnO. on alumina.

Wang and coworkers achieved p-functionalisation of simple aldehydes. This concept was realised by oxidation of an enamine formed from the catalyst and aldehydes with suitable oxidant, such as IBX. The thus-formed unsaturated iminium ion underwent a Michael addition with various nucleophiles. Similarly, Hayashi s laboratory described oxidation of enamines with 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (DDQ) and then Michael addition using nitromethane as nucleophile. ... 

Pyrroles are very sensitive to the action of singlet oxygen ( O2). Wasserman (1970) has observed a novel type of oxidation in the case of aryl-substituted pyrroles exemplified by the photooxidation of 2,3,4,5-tetraphenylpyrrole in methanol. There is special interest in the reactions of imidazoles with O2 since it has been shown that photooxi-dative inactivation of certain enzymes involves destruction of histidine residues, and more specifically oxidation of the imidazole ring (Wasserman and Lenz). These heterocyclic system behave in many respects like furans and pyrroles, but are more prone to cleavage through reactions resembling the oxidation of enamines by 02 (Wasserman et al. 1968). 

The air oxidation of substituted catechols to the corresponding 0-benzoquinones is catalyzed by a variety of Cu(II)-amine systems. It appears that the mechanism involves the formation of a dicopper(II) catecholate intermediate electron transfer then occurs from the aromatic ring to give the o-benzoquinone and two Cu(I) centers. The latter then react with dioxygen and the catechol to regenerate the dicopper(II) catecho-late. A study of the effect of chloride ions on the kinetics of the copper-catalyzed oxidation of ascorbic acid by dioxygen does not rule out the involvement of Cu(I) intermediates but a mechanism involving Cu(III) is preferred. Kinetic studies on Cu(II)-catalyzed oxidation of enamines [e.g., equation (26)] and 3-phenylpropanal have been reported. 

Scheme 39.1 Formation of SOMO activated chiral intermediate upon preferential oxidation of enamine.

Asymmetric Functionalization via Oxidation of Enamine and Breslow Intermediates... 

Radical cations, generated by single electron oxidation of enamines that are generated in situ by the reaction of aldehydes with a chiral imidazolidinone, serve as a new class of electrophiles for silyl enol ethers (Scheme 3-1and allylsilanes. This novel Umpolung strategy allows the introduction of a chiral center at the a-position of aldehydes with these silicon reagents. The chiral imidazolidinone works as an... 

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