Oxidations ketone synthesis

Other methods for a-hydroxy ketone synthesis are addition of O2 to an enolate followed by reduction of the a-hydroperoxy ketone using triethyl phosphite 9 the molybdenum peroxide-pyridine-HMPA oxidation of enolates 10 photooxygenation of enol ethers followed by triphenylphosphine reduction 11 the epoxidation of trimethyl silyl enol ethers by peracid 1 - the oxidation of trimethylsilyl enol ethers by osmium tetroxide in N-methylmorpholine N-... 

Similar to the Dakin-West procedure previously mentioned, the Henry nitro-aldol condensation reaction is most widely used to synthesize trifluoromethyl ketones, although there are many examples of a,a-difluoroalkyl ketones synthesized by this method (Table 6)JU 12271 The method for a,a-difluoroalkyl and trifluoromethyl ketone synthesis is identical except for the final oxidation although fluoroalkyl and a,a-difluoroalkyl ketones are easily oxidized by the Sarett method (Cr03/pyridine),[12 the corresponding trifluoromethyl ketones can only be oxidized under basic conditions (0.3 M NaOH) with KMn04Jul Also, in some of the syntheses of a,a-difluoroalkyl ketones, the nitro alcohol intermediate was protected by si-lylation with /ert-butylchlorodimethylsilane. The silyl group was later removed by TosOH prior to oxidation. The full details of this method are given in Section 15.1.4.3.2. 

This ketone synthesis was developed further by Ipatieff and by Sabatier, Mailhe, and Senderens. Thoria and manganous oxide proved to be more effective catalysts than the carbonates. The method was extended to higher fatty acids and to the production of mixed ketones. 

The oxides of zinc, cadmium, manganese, nickel, cobalt, and chromium and their mixtures are satisfactory catalysts. In a later work Dolgov and Golodnikov (6) developed an activated copper catalyst and produced a mixture of esters and ketones from alcohol. The reactions proceed by ester mechanism, and at lower temperatures (275°-300°) the formation of esters predominates. This ketone synthesis is equally applicable to higher members of the primary alcohol series. 

J. Tsuji, Synthetic Applications of the Palladium-Catalysed Oxidation of Olefins to Ketones, Synthesis 1984, 369. 

Tsuji, J. 1984. Synthetic applications of the palladium-catalyzed oxidation of olefins to ketones. Synthesis 369-383. 

Ganem, B., Boeckman, R. K., Jr. Silver-assisted dimethyl sulfoxide oxidations. Improved synthesis of aldehydes and ketones. Tetrahedron Lett. 1974, 917-920. 

An interesting amine oxide (78) finds utility in the ketone synthesis. Good enantioselectivity for reduction of ketones by A-benzyl-3-p-toluenesulfinyl-1,4-dihydropyridine ° and a 2,5-pyridinophane 79, NADH models, in the presence of Mg(C10 )2 has been observed. 

With loss of insulin action and an excess of catabolic hormones, hydrolysis of triglycerides is markedly increased, glycerol supply rises and triglyceride turnover in plasma increases with a concomitant increase in ketoacid derived from hepatic oxidation of FFA. Fatty acids are partly oxidized to ketonic compounds. Ketone synthesis increases more than threefold in the state of insulin deficiency as the result of a low insulin/glucagon ratio and a high FFA supply to the liver. At low insulin levels, ketone uptake and utilization of peripheral tissue is also significantly reduced. 

Tin hydride-mediated radical cyclizations onto a C-0 double bond, coupled with subsequent oxidation, can be applied to ketone synthesis. Fraiser-Reid and co-workers demonstrated that the radical cyclization onto an aldehyde carbonyl group is particularly useful for the construction of cyclohexanol derivatives [35]. Examples shown in Scheme 4-17 well feature the cyclization. As Beckwith s kinetic work predicts (Scheme 4-18) [36], when this method is applied to a five-membered ring system, the rapid ring opening hinders the formation of cyclopen-tanols. Accordingly, only cyclohexanols can be reliably prepared using this approach. 

Our synthesis of (9S)-dihydroerythronolide A, which constitutes a formal synthesis of erythronolideA (226), depends on a key aldol reaction between the racemic aldehyde 244 and imide auxiliary 245 (Scheme 9-66) [84]. In this reaction, the auxiliary overrides any aldehyde facial bias, thus leading to an equimolar mixture of separable syn adducts 246 and 247. These two compounds were then processed separately and together provide five of the ten necessary stereocenters of erythronolideA (C9 will be oxidized). This synthesis also features the thioalkyla-tion of silyl enol ether 248 giving ketone 249, a process which can be compared with the Mukaiyama addition to aldehydes. Presumably, Felkin selectivity controls the Cii stereocenter while the mixture of C12 epimers was not detrimental as epi-merization could be effected in the subsequent elimination step. 

Corbel. B.. Medinger, L., Haelters, J.P, and Sturtz, G.. An efficient synthesis of dialkyl 2-oxoalka-nephosphonates and diphenyl-2-oxoalkylphosphine oxides from 1-chloroalkyl ketones, Synthesis, 1048. 1985. 

The final step is the usual oxidation with alkaline hydrogen peroxide. Both groups on the boron 232 are now tertiary so an excess of oxidant must be used to drive both across to oxygen. The products are /-hexanol and the hydrate of the ketone 234. This doesn t affect the ketone synthesis, only the by-product. 

---