Homoallyl acetates oxidation

Oxidation of allylic andhomallylic acetates (cf. 10,175-176).1 This system is an efficient catalyst for oxygenation of terminal alkenes to methyl ketones (Wacker process). Similar oxidation of internal olefins is not useful because it is not regioselective. However, this catalyst effects oxygenation of allylic ethers and acetates regioselectively to give the corresponding /i-alkoxy ketones in 40-75% yield. Under the same conditions, homoallylic acetates are oxidized to y-acetoxy ketones as the major products. 

Homoallyl acetates were oxidized to form the corresponding y-acetoxy ketones with high regio-selectivity. The results are shown in Table 4. In this oxidation, small amoimts of B-acetoxy ketones were sometimes formed (<10%). 

P-Alkoxy kettmes and y-acetoxy ketones prepared by the oxidation of allyl ethers and homoallyl acetates, respectively, are synthetically useful intermediates. The reaction of (K) in the presence of excess sodium methoxide with 2-methylcyclohexanone afforded methyloctalone (94) in 42% yield (equation... 

The oxidation of cyclohexene has been the subject of considerable discussion, and it is now apparent that it behaves differently from the straight-chain olefins. Cyclohexene was originally reported to yield both cyclohex-2-en-l-yl acetate, structure (VII), and cyclohex-3-en-l-yl acetate, structure (VIII), in chloride-containing acetic acid (76) and only the allylic isomer with Pd(OAc)a in chloride-free acetic acid (6). However, it has now been demonstrated that if no oxidants are present to regenerate the Pd(0) to Pd(II) in neutral or basic HOAc, the Pd(0) formed will disproportionate the cyclohexene to give benzene (22, 295). In acetic acid containing perchloric acid, cyclohexanone (structure VIII) and cyclohex-1-en-l-yl acetate are formed (22). If Pd(0) is prevented from precipitating by use of oxidants in neutral or basic acetic acid, the allylic and homoallylic acetates are formed. 

Studies of the oxidation of 3,3,6,6-d4-cyclohexene (127, 295) indicated the allylic product arose from a 7r-allyl intermediate, whereas the homoallylic acetate arose from the mechanism suggested for oxidation of straight-chain olefins. Thus the allylic product was a 50 50 mixture of the two deuterium-labeled isomers, structures (IX) and (X), which would be expected from a symmetrical intermediate. An acetoxypallada-tion mechanism would have predicted only X. It has also been demon-... 

The 4-hydroxy-1-alkene (homoallylic alcohol) 81 is oxidized to the hetni-acetal 82 of the aldehyde by the participation of the OH group when there is a substituent at C3. In the absence of the substituent, a ketone is obtained. The hemiacetal is converted into butyrolactone 83[117], When Pd nitro complex is used as a catalyst in /-BuOH under oxygen, acetals are obtained from homoallylic alcohols even in the absence of a substituent at C-3[l 18], /-Allylamine is oxidized to the acetal 84 of the aldehyde selectively by participation of the amino group[l 19],... 

The mechanism of the Zn chloride-assisted, palladium-catalyzed reaction of allyl acetate (456) with carbonyl compounds (457) has been proposed [434]. The reaction involves electroreduction of a Pd(II) complex to a Pd(0) complex, oxidative addition of the allyl acetate to the Pd(0) complex, and Zn(II)/Pd(II) transmetallation leading to an allylzinc reagent, which would react with (457) to give homoallyl alcohols (458) and (459) (Scheme 157). Substituted -lactones are electrosynthesized by the Reformatsky reaction of ketones and ethyl a-bromobutyrate, using a sacrificial Zn anode in 35 92% yield [542]. The effect of cathode materials involving Zn, C, Pt, Ni, and so on, has been investigated for the electrochemical allylation of acetone [543]. 

The addition of trimethyl (2-methylallyl)silane 28 to acetal 27 was chosen as the key step. The reaction proceeded smoothly and generated homoallylic ether 29 with high diastereoselectivity. The desired homoallylic alcohol 30 could subsequently be obtained, in high enantiomeric purity, by oxidative deprotection of the chiral template (Scheme 13.12). 

Acetals result from oxidative coupling of alcohols with electron-poor terminal olefins followed by a second, redox-neutral addition of alcohol [11-13]. Acrylonitrile (41) is converted to 3,3-dimethoxypropionitrile (42), an intermediate in the industrial synthesis of thiamin (vitamin Bl), by use of an alkyl nitrite oxidant [57]. A stereoselective acetalization was performed with methacrylates 43 to yield 44 with variable de [58]. Rare examples of intermolecular acetalization with nonactivated olefins are observed with chelating allyl and homoallyl amines and thioethers (45, give acetals 46) [46]. As opposed to intermolecular acetalizations, the intramolecular variety do not require activated olefins, but a suitable spatial relationship of hydroxy groups and the alkene[13]. Thus, Wacker oxidation of enediol 47 gave bicyclic acetal 48 as a precursor of a fluorinated analogue of the pheromone fron-talin[59]. 

In order to prevent competing homoallylic asymmetric epoxidation (AE, which, it will be recalled, preferentially delivers the opposite enantiomer to that of the allylic alcohol AE), the primary alcohol in 12 was selectively blocked as a thexyldimethylsilyl ether. Conventional Sharpless AE7 with the oxidant derived from (—)-diethyl tartrate, titanium tetraisopropoxide, and f-butyl hydroperoxide next furnished the anticipated a, [3-epoxy alcohol 13 with excellent stereocontrol (for a more detailed discussion of the Sharpless AE see section 8.4). Selective O-desilylation was then effected with HF-triethylamine complex. The resulting diol was protected as a base-stable O-isopropylidene acetal using 2-methoxypropene and a catalytic quantity of p-toluenesulfonic acid in dimethylformamide (DMF). Note how this blocking protocol was fully compatible with the acid-labile epoxide. 

Chiral homoallylic alcohols. The chiral acetals 2 formed from an aldehyde and 1. undergo titanium-catalyzed coupling with allyltrimcthylsilane with marked stereoselectivity. Highest sterco.selectivity is usually obtained with the mixed catalyst TiClj-Ti(0-/-Pr)j (6 5). Cleavage of the chiral auxiliary, effected by oxidation to the ketone followed by -elimination, provides optically active alcohols (4) with —95% ee (equation I). ... 

Oxidative acetoxylation provides a direct access from alkenes to alkenyl esters the alkene molecule undergoes replacement of an H atom by an acetate (or generally OCOR) group in its vinylic (v), allylic (a), or homoallylic (h) position according to Scheme 1, where Ox is an oxidant such as O2, Cu p-benzoquinone, and Red a reduced form of Ox such as H2O, Cu hydroquinone. A typical example is the Pd-catalyzed co-oxidation of ethylene and acetic acid to vinyl acetate (eq. (D). 

Under the conditions of stoichiometric (eq. (4)) or catalytic (Scheme 2) reactions, propylene is oxidized to isopropenyl acetate as the main reaction product, along with allyl and cis- and trans -n-propenyl acetates. Higher acyclic alkenes C4-C10 are converted to mixtures of allyl and vinyl esters [5]. Cyclic alkenes also produce homoallylic esters [6, 7]. 

The synthesis of the C1-C7 fragment, which corresponds to the lactone, starts with the homoallylic alcohol 2 which was prepared from 1. The existing stereocenter and the conjugate addition method of Evans [21] allow the control of the C5 stereocenter. The homoallylic alcohol 2 was oxidatively cleaved and homologated to the trans enoate 3 by a Wittig olefination. Treatment of 3 with benzaldehyde and a catalytic amount of KHMDS provided acetal 4. The internal Michael addition of the hemiacetal intermediate proceeds with complete stereoselectivity [22]. After deprotection and oxidation, the corresponding aldehyde was treated with Amberlyst-15 and then with camphor sulfonic acid (CSA), to yield pyrane 5 as a mixture of (3- and a-anomers (1.8/1). This compound was converted to the thiophenyl acetal 6 (4 steps) as this compound can be hydrolyzed later under mild conditions (Hg +) with subsequent oxidation of the lactol to the desired lactone. Compound 6 represents the C1-C7 fragment of discodermolide (Scheme 1). 

Ozonolysis of unsaturated hydroperoxy acetal 226, readily obtained by trapping carbonyl oxides with primary unsaturated allylic or homoallylic alcohols <1997J(P1)5>, with ozone in methanol/ether at —78°G gave the 6-hydroxy-l,2,4-trioxane derivatives 227 almost quantitatively and as a single isomer (structure confirmed by 1-D NOE spectroscopy see Scheme 64) <1997JOC4949>. In the case of substitution (R R = H, Me or Me, Me), a mixture of two and three isomers, respectively, were obtained, all completely assigned by H NMR spectroscopy <1997JOC4949>. 

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