Benzylic derivative oxidation

Oxidation (Section 11.13) Oxidation of alkylbenzenes occurs at the benzylic position of the alkyl group and gives a benzoic acid derivative. Oxidizing agents include sodium or potassium dichromate in aqueous sulfuric acid. Potassium permanganate (KMn04) is also an effective oxidant. 

Total synthesis of (+)-validamycins A and B starting from a common synthetic intermediate was elaborated by the following sequence. Tetra-(9-benzyl-(-l-)-valienamine (370), derived from 211, and the di-O-benzyl derivative (371) of the epoxide were coupled in 2-propanol to produce the protected dicarba compound (374), the structure of which was confirmed by conversion into (-1-)-validoxylamine B nonaacetate. Concurrently, compound 372 was glycosylated and the product oxidized with a peroxy acid, to afford a mixture of products from which the desired epoxide (373) was obtained in 70% yield. Coupling of 370 with 373 in 2-propanol at 120° afforded two carba-trisaccharides, and the major product (47%) was depro-tected and characterized as the dodecaacetate of validamycin B. The pro-... 

N-benzylation of the sodium salt of 4//-pyrido[2,3-e][l,2,4]triazin-3-one 1-oxide 45 gave (82JHC497) the respective 4-N-benzyl derivative. 

N-Hydroxy-N-nitrosamines with an aliphatic group at O2 produce a compound stable to aqueous acid and base (Fig. 3.4, 29) [158], whereas all other N-hydroxy-N-nitrosamines are susceptible to hydrolysis and appropriate 02-derivatives also render these materials vulnerable. The hydrolysis endpoint is the formation of nitroxyl (HNO) [which dimerizes to form nitrous oxide (N20)] and a C-nitroso compound. These products are formed from aryl [159] and alkyl bound unsubstituted diazenium-diolates as well as Oralkylated derivatives [160]. Studies of the solvolysis of Oi-alkyl derivatives are complicated by their tendency to decompose via competing radical pathways [161], but the Oi-benzyl derivatives are unique in that they hydrolyze back to the original synthetic precursors (Scheme 3.14) [162]. 

The benzyl derivative Cp Ta( j -02)Bn was structurally characterized by X-ray diffraction the 02-ligand is side-on coordinated and lies in the equatorial plane of the bent metallocene fragment. The 0-0 distance of 1.477(8) A and the 0-0 stretching frequency (vo-o = 863cm ) are consistent with a peroxo hgand (02 ) coordinated to tantalum in its highest possible formal oxidation state (+V). Notably, base appears to stabihze these complexes i.e., in the presence of triethylamine Cp Ta( 7 -02)Me did not decompose even when heated to 80 °C. 

Benzyl-2,4,6-triphenyl-4//-thiopyran (2451) reacts with perchloric acid with loss of the 4-benzyl group to afford perchlorate 404.236 A similar elimination of the substituents was found for 4-benzyl derivatives 253.3<8 The reported conversion of 4,4-dichloro-4//-thiopyran (336b) to perchlorate 408, involving the loss of a 4-chlorine,325 is not an oxidation process. Similar transformations are also reported.349... 

Toluene is oxidized to cresols (ortho meta para ratio = 5 1 4) and not to the benzyl derivatives, despite the low dissociation energy of the benzylic C—H bond. p-Xylene undergoes oxidation to 2,5-dimethylphenol. 

Anodic oxidation of 4-silylazetidin-2-ones in the presence of fluoride ions provides 4-fluoroazetidin-2-ones in high yields33. This fluorination is completely regioselective. Even in the case of the TV-benzyl derivative, a fluorine atom is selectively introduced into the C-4 position of the /1-lactam ring (equation 28). In contrast, unsilylated azetidin-2-ones give no fluorinated product. 

Carbonylat ion of 13 4-nitrophenyloxycarbonyl chloride (J 6) in pyridine] gave a good yield of the trityl ether-carbonate 14 which was de-tritylated by hydrogenolysis (2 4) to afford the 7,8-diol-4,5-carbonate 15 in practically quantitative yield. Compound 15.. by way of its 7,8-0 -dibutylstannylidene derivative (25> 26) was regioselectively 8-0-benzylated (dibutyltin oxide, benzene, reflux then benzyl bromide, dimethyl formamide, 95 ), in fair yield (J ). Finally, the aglycon U3 was obtained in high yield by sequential 7-Q-tert.-butyldimethylsilylation (27) (compound 17) and Zemplen saponification. 

Benzyl 4, 6 -0-benzylidene-P-lactoside with five free hydroxyl groups was converted to the dibutylstannylene intermediate by azeotropic removal of water from its mixture with 2.5 molar equiv. dibutyltin oxide in benzene, the reaction with benzyl bromide in the presence of tetrabutylammonium bromide then gave the 2,3 -di-0-benzyl derivative in 52% yield [139]. When the 3, 4 -0-isopropylidene analog was treated with 1.2 molar equiv. only, the 2-O-benzyl derivative was the main product [150]. 

Treatment of benzyl 3, 4 -0-isopropylidene-P-lactoside with 3 molar equiv. of bis(tributyl)tin oxide and subsequent reaction with benzyl bromide gave a complex mixture of products. When benzylation was carried out in the presence of tetrabutylammonium bromide or TV-methylimidazole, 50% of the 2-O-benzyl derivative was obtained after some hours. After 7 days, the 2,6,6 -tri-0-benzyl derivative was the main product (38%) [150]. 

O-Benzylation of 148 with benzyl bromide in the usual manner yielded the tri-0-benzyl derivative (149), [a]p7 —0.8° (chloroform). On hydrolysis with aqueous acetic acid, 149 gave the compound (150), which was further converted to the compound (151) by sodium borohydride reduction. Periodic acid oxidation of 151 and successive sodium borohydride reduction gave 5,6-di-<9-acetyl-2,3,4-tri-0-benzyl-pseudo-a-L-altropyranose (152), [a] 6 —25.7° (chloroform), after conventional acetylation. Reductive cleavage of 152 with sodium in liquid ammonia and subsequent acetylation afforded pseudo-a-L-altropyranose pentaacetate (153), m.p. 84-85 °C, [ ]q6 —13.7° (chloroform). Hydrolysis of 153 gave 154, [ot] —43.6° (methanol) [35] (Scheme 24). 

O-Deacetylation of J58 and successive O-benzylation gave the tri-O-benzyl derivative (159), [a]p +36.7° (chloroform). When 159 was hydrolyzed with aqueous acetic acid and subsequently hydrogenated with sodium borohydride, the compound (160), [a] + 4.4° (chloroform), was obtained. Periodic acid oxidation of 160 and reduction with sodium borohydride afforded 4,6-di-0-acetyl-l,2,3-tri-0-benzyl-pseudo-(3-L-allopyr-anose (161), [a] —40.2° (chloroform), after acetylation. Catalytic hydrogenolysis of 161 and successive acetylation gave pseudo-P-L-allopyranose pentaacetate (162), m.p. 135-136 °C, [a] f +3.7° (chloroform) [36]. (Scheme 25). 

L-Rhodinose (174) was prepared from the readily available L-rhamnose.269 The method required deoxygenation of C-2 and C-3 and inversion of configuration at C-4 (Scheme 56). Oxidation of 187 with ruthenium dioxide-IOj, followed by reduction of the keto groups with lithium aluminum hydride yielded the alcohol 188. After protection as the benzyl derivative, an alkenic linkage was... 

Methylation of the sodium salt of 37/,4//-pyrido[2,3-e]-l,2,4-triazin-3-one 1-oxide (174) using Mel did not occur, even after refluxing the mixture in acetonitrile for 20 hours. iV-Benzylation was possible, delivering 36% of the benzyl derivative (175). The sodium salt of compound (174) was also treated with a solution of acetobromoglucose in DMF producing the /1-glycoside (176) (4%)... 

A second preparation in the same paper using the same method but at 10°C higher temperature gave a 77% yield of the 2-O-benzyl derivative. d Ratio of diol to bis(tributyltin) oxide 1 2.2. e Ratio of diol to bis(tributyltin) oxide 1 1.8. 

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