Ketone To methylene

The oxidation of activated methylenes to ketones under GoAggv-type conditions was reported by Kim et al. in 2002 [24] and by Nakanishi and Bolm in 2007 [26]. In the latter case, no acid was needed and, as pyridine was used as a solvent, an additional ligand was unnecessary. Interestingly, p-methoxytoluene was converted to the corresponding carboxylic acid, albeit in moderate yield (53%). The oxidation of... 

Oxidation of benzylic methylenes to ketones with sodium bismuthate general procedure... 

Out first example is 2-hydroxy-2-methyl-3-octanone. 3-Octanone can be purchased, but it would be difficult to differentiate the two activated methylene groups in alkylation and oxidation reactions. Usual syntheses of acyloins are based upon addition of terminal alkynes to ketones (disconnection 1 see p. 52). For syntheses of unsymmetrical 1,2-difunctional compounds it is often advisable to look also for reactive starting materials, which do already contain the right substitution pattern. In the present case it turns out that 3-hydroxy-3-methyl-2-butanone is an inexpensive commercial product. This molecule dictates disconnection 3. Another practical synthesis starts with acetone cyanohydrin and pentylmagnesium bromide (disconnection 2). Many 1,2-difunctional compounds are accessible via oxidation of C—C multiple bonds. In this case the target molecule may be obtained by simple permanganate oxidation of 2-methyl-2-octene, which may be synthesized by Wittig reaction (disconnection 1). 

The unique chemical behavior of KO2 is a result of its dual character as a radical anion and a strong oxidizing agent (68). The reactivity and solubiHty of KO2 is gready enhanced by a crown ether (69). Its usefiilness in furnishing oxygen anions is demonstrated by its appHcations in SN2-type reactions to displace methanesulfonate and bromine groups (70,71), the oxidation of benzyHc methylene compounds to ketones (72), and the syntheses of a-hydroxyketones from ketones (73). 

Condensation between carboxylic esters and aldehydes or ketones Addition of a-metalated esters to ketones Oxidation of methylene to OH, O2CR, or OR... 

The late stages of the synthesis (Scheme 1.17) proceeded with Wittig methylenation of ketone 144 with Ph3P=CH2 at 70 °C to furnish exocyclic alkene 145 in 77 % yield. Finally, the alcohol was installed via a Se02-mediated allylic hydroxylation [57] of the exocyclic alkene 145 to afford ( )-nominine (1) in 66 % and 7 1 dr. The structure of nominine (1) was verified via an X-ray crystal structure determination, thereby completing the racemic total synthesis of ( )-nominine (1). 

Primary and secondary alcohols are oxidized slowly at low temperatures by benzyltriethylammonium permanganate in dichloromethane primary alcohols produce methylene esters (60-70%), resulting from reaction of the initially formed carboxylate anion with the solvent, with minor amounts of the chloromethyl esters and the carboxylic acids. Secondary alcohols are oxidized (75-95%) to ketones [34] the yields compare favourably with those obtained using potassium permanganate on a solid support. 1,5-Diols are oxidized by potassium permanganate under phase-transfer catalytic conditions to yield 8,8-disubstituted-8-valerolactones [35] (Scheme 10.1). 

By indirect oxidation with electrogenerated NO3 radicals in f-butanol/ water/HN03/02, saturated hydrocarbons were oxidized to ketones with a statistical H-abstraction at the methylene... 

The reaction is even more general and applicable to ketones bearing an a-methylene. Yields up to 90% of the corresponding dimethyl esters are obtained in the case of benzylic substrates (Scheme 4.19). 

Eisch and Piotrowski reported the preparation of gem-dizinc compounds from diiodomethane and zinc powder in the titanocene chloride mediated methylenation of ketones in 1983 (equation 5)7. In this case, it was not mentioned that they had used pyrometallurgy zinc. The Tebbe-type reagent 2 was shown as an intermediary species. Before addition of titanocene chloride, the amount of methane was measured after hydrolysis of the reaction mixture to determine the formation of gem-dizinc species7. 

The amount of EGA (the current efficiency of EGA generation) is measured in both acetone and methylene chloride-THF. Both Figs. 1 and 2 show that a sharp increase in the concentration of EGA is observed in the electrolysis of lithium, sodium, and magnesium perchlorate solution, being consistent with the result of the oxirane ring opening reaction to ketones (Table 2). 

Permanganate ion is a strong oxidant and tends to cleave aromatic side chains. However, when used under phase-transfer conditions,109,849 it converts benzylic methine groups into alcohols, and benzylic methylene compounds to ketones. Convenient oxidations can be carried out when KMn04 is applied in Et3N, an organic solvent (CHC13), and traces of water at room temperature.850... 

Epoxides derived from indene,21 1,2- and 1,4-dihydronaphtha lenc 1702 a,4-benzo-1,S cycloheptadicne, 68 and 3,4-benzo-l,3-cycIo-octodlene841 are a)) reported to undergo isomerization to ketones in the presence of magnesium bromide (Eq. 450). That the carbonyl function is separated in every instance from the benzene ring by a methylene group may be taken to indicate probable existence of an open car-bonium ion in these processes. Bing contraction has been noted in one... 

Freshly prepared Mn02 is a useful reagent in organic chemistry and has been used in a large variety of oxidative transformations.311 These reactions involve the allylic oxidation of alkene to a,/3-unsaturated carbonyl compounds, the transformation of methylarenes to benzaldehyde and benzoic acid derivatives, the oxidation of secondary methylene groups to ketones, and the oxidation of alcohols to carbonyl compounds.311 The yields are generally fair to good. 

Methylenation. This phosphonate ester is generally regarded as unsuitable for methylenation of ketones, even though the anion forms the intermediate adduct in satisfactory yield. However, under suitable experimental conditions, this reagent was used for methylenation of 1 to give 2 in 90% yield, higher than that obtained with methylphosphonic acid bis(dimethylamide) (78%).1 The optimum yield is obtained if exactly 2 equiv. of base and 1 equiv. of water are used to quench the adduct before cycloelimination. 

Alkyttdenation. Methylenation of ketones can be effected in 50 99% yield by reaction with the lithium anion (2) of 1 with 0=CR R2 to give a stable adduct (3) that undergoes cycloelimination to alkenes (4) on methylation. When applied to aldehydes, the yield is low except for benzaldehydes or a,/ -unsaturated enals. 

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