Oxidative Rearrangements of Ketones

Methyl esters of a-arylalkanoic acids 907 can be prepared by oxidative rearrangement of ketones 906 via a 1,2-aryl shift using iodic acid in methanol in the presence of trimethyl orthoformate and sulfuric acid (Scheme 3.364) [1304]. 

Thallium compounds, especially in the form of thallium(i) and thallium(iii) salts, are ahle to mediate a great numbers of reactions, including oxidative rearrangements of ketones and alkenes, cyclisation reactions, a-oxidation of ketones, aromatic thallations, oxidative couplings, oxidations of phenols and nitrogen compounds and disulfide bond formation, thus, constituting a useful tool in synthetic organic chemistry. However, their application as catalysts has been less explored and there are only a few successful examples reported in the literature. 

Clays and celite Inorganic support for oxidative rearrangements of ketones and olefins oxidations of alcohols to ketones by KMn04 and Collins reagent Andersen and Uh, 1973 Kakis et al., 1974 Fetizon and Mourges, 1974 Taylor et al., 1976 Regen and Koteel, 1977... 

This reaction was first reported in 1899 [25] and represents an oxidative rearrangement of ketones to esters of carboxylic acids, with peroxy acids or hydrogen peroxide as oxidants (Scheme 8.22) [26]. 

Oxidative Rearrangements of Ketones 9.3.2.1 Baeyer-Villiger Reactions Introduction and mechanism... 

Examination of the reactions of a wide variety of olefins with TTN in methanol (92) has revealed that in the majority of cases oxidative rearrangement is the predominant reaction course (cf. cyclohexene, Scheme 9). Further examples are shown in Scheme 18, and the scope and limitations of this procedure for the oxidative rearrangement of various classes of simple olefins to aldehydes and ketones have been defined. From the experimental point of view these reactions are extremely simple, and most of them are... 

Oxidative rearrangement of the tertiary-cyclopropylcarbinol 262 using PCC leads to the / ,y-unsaturated ketone 263 and halide 264 [149], (Scheme 104)... 

A simple two-step protocol for the generation of a terminal diene is to add allyl magnesium bromide to an aldehyde or a ketone and subsequent acid or base catalysed dehydration (equation 34)72. Cheng and coworkers used this sequence for the synthesis of some indole natural products (equation 35)72a. Regiospecific dienones can be prepared by 1,2-addition of vinyllithium to a,/l-unsaturated carbonyl compounds and oxidative rearrangement of the resulting dienols with pyridinium dichromate (equation 36)73. 

Addition of isopropyl lithium to the surviving ketone followed by oxidative rearrangement of the resulting tertiary ailylic alcohol and concomitant oxidation of the secondary allylic alcohol gave the diketone 10. Selective addition of methyl lithium to the less hindered of the two ketones, again from the more open face, then gave 3. 

Methyla-arylacetates. These esters have been obtained by oxidative rearrangement of alkyl aryl ketones with thallium(III) nitrate in acidic methanol or trimethyl orthoformate (4,496 5, 656 7, 362). A new method, which avoids the toxic TTN, is based on the Woodward version of the Prevost reaction. Thus, treatment of the ketone with iodine (or bromine) and silver nitrate (2 equiv.) in refluxing methanol containing trimethyl orthoformate results in methyl a-arylacetates in 90% yield from simple substrates. Yields are lowered by electron-withdrawing substituents on the aromatic group and by a-branching in the alkyl group.2... 

Oxidative rearrangement of aryl methyl ketonesThese ketones have been converted into methyl a-methoxyarylacetates on reaction with T1(N03)2 in trimethyl orthoformate (7, 362). This oxidative rearrangement can also be effected with C6H5I(OAc)2 (2 equiv.) in trimethyl orthoformate in equally good yield. 

The Baeyer-Villiger rearrangement often is called Baeyer-Villiger oxidation (see the last subsection of Section 14.3.2, Oxidative Cleavage of Ketones). In the Baeyer-Villiger rearrangement a carbonyl compound (ketones are almost always used) and an... 

The chroniium(VI) oxide-dipyridine complex also has beoi found to cause oxidative rearrangement of tertiary allylic alcohols to a,3-epoxy aldehydes and small amounts of a,3-unsaturated aldehydes (equation 6 and Table 3). This is potentially useful as a homologation sequence since the starting materials are readily available from vinyl metal addition to ketones. Use of pyridinium chlorochromate (PCC) for this transformation gives mosdy a,3 unsaturated aldehydes. 

The oxidative rearrangement of allylic alcohols to a -unsaturated ketones or aldehydes is one of the most widely used synthetic reactions in this group, and forms part of a 1,3-carbonyl transposition sequence. Scheme 7 shows this reaction and the related conversion of the allylic alcohol to an a, -epoxy carbonyl compound. Chromate reagents induce some allylic alcohol substrates to undergo a dirMted epoxidation of the alkene without rearrangement, but this reaction is beyond the scope of the present discussion. 

The oxidative rearrangement of cyclic alkenes and ketones often leads to ring expansion or ring contraction reactions. The reagents generally used for this purpose are hypervalent main group oxidants such as thallium(III), lead(lV), iodine(III) and selenium(IV), alAough palladium(II) has been used as well. 

Oxidative rearrangement of cyclopropylearbinoh to, y-enoues Tertiary cyclopropylcarbinols (1), which can be prepared by addition of cyclopropyl organometallic reagents to ketones, are oxidized by PCC (5 equiv.) mainly to /3,y-enones (2). The related reagent C5H5NHCr03BF4 is equally effective. Traces... 

Sharghi, H., Hosseini, M. Solvent-free and one-step Beckmann rearrangement of ketones and aldehydes by zinc oxide. Synthesis 2002, 1057-1060. 

Syntheses of ( )-akuammigine, (+)-tetrahydroalstonine, ( )-ajmali-cine, (+)-3-iso-19-epiajmalicine, and the oxindoles (+ )-formosanine and ( )-isoformosanine, obtained by oxidative rearrangement of 3-iso-19-epi-ajmalicine, have been carried out starting with the key ketone (59). Scheme 7 illustrates how the product of either kinetic or thermodynamic control of the addition of malonate to this ketone can be used to synthesise d/e cts-alkaloids e.g., akuammigine (60)] or d/e trans-alkaloids [e.g., 3-iso-19-epi-ajmalicine (61)]. 

This racemic synthesis of actinophyllic acid (3) was accomplished in eight steps with an overall 15% yield from the readily available indole di-ferf-butyl malonate 9. The intramolecular oxidative coupling of ketone and malonate enolates and an aza-Cope-Mannich rearrangement for the construction of the unprecedented actinophyllic acid ring skeleton are the key transformations. 

Carbon-Oxygen Bond Formation. CAN is an efficient reagent for the conversion of epoxides into /3-nitrato alcohols. 1,2-cA-Diols can be prepared from alkenes by reaction with CAN/I2 followed by hydrolysis with KOH. Of particular interest is the high-yield synthesis of various a-hydroxy ketones and a-amino ketones from oxiranes and aziridines, respectively. The reactions are operated under mild conditions with the use of NBS and a catalytic amount of CAN as the reagents (eq 25). In another case, N-(silylmethyl)amides can be converted to A-(methoxymethyl)amides by CAN in methanol (eq 26). This chemistry has found application in the removal of electroauxiliaries from peptide substrates. Other CAN-mediated C-0 bondforming reactions include the oxidative rearrangement of aryl cyclobutanes and oxetanes, the conversion of allylic and tertiary benzylic alcohols into their corresponding ethers, and the alkoxylation of cephem sulfoxides at the position a to the ester moiety. 

The chemistry of lead tetrakistrifluoroacetate and aryl-lead tristrifluoroacetates has continued to merit considerable attention. Norman and his co-workers, in a study of the oxidative rearrangement of styrene and related compounds to aldehydes and ketones, have found that the preferred reagent is(CF3 C02)4Pb-CF3 C02H at 20 C. The yields obtained (see Table 4) for the 1-methylstyrenes increase in the order 4-Me < 4-H < 4-NO2, which runs opposite to that expected on the basis of migratory aptitudes 1-methylstyrene also gave the dimer (33) (39%). High yields... 

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