Allyl ethers regioselective oxidation

O-Deprotection. Free-radical-initiated bromination followed by treatment with water removes a benzyl ester. A similar method is also effective to cleave allyl ethers. Regioselective oxidations. An alkane-1,2-diol can be selectively oxidized to give the ketol (instead of the hydroxy aldehyde) via NBS reaction of the dibutylstan-nylene acetal. ... 

Allyllic ether 53 is oxidized regioselectively to the /3-alkoxy ketone 54, which is converted into the a,/i-unsaturated ketone 55 and used for annulation[99]. The ester of homoallylic alcohol 56 is oxidized mainlv to the 7-acetoxy ketone 57[99]. 

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. 

The conversion of the cycloadduct 546 to ( )-crinamine (376), ( )-6-hy-droxycrinamine (379), (+)-criwelline (398), and (+)-macronine (401) commenced by reduction of 546 with NaBH4 followed by acetylation to produce solely the acetate 554, which arose by hydride attack on the hindered neopentyl ketone exclusively from the convex face syn to the aryl substituent (Scheme 50) (216). The stereo- and regioselective addition of the elements of PhSeOMe to the carbon-carbon double bond of 554 followed by oxidation of the intermediate methoxy selenide and elimination of phenylselenous acid gave the allylic ether... 

The oxidation of various allyl ethers and acetates with internal alkenes using PdCl2/CuG/02 or PdCl2/p-benzoquinone catalyst systems gave the corresponding p-alkoxy ketones regioselectively (equation 19). No a-alkoxy or o-acetoxy ketone was detected. 

In the oxidation of 2-octenyl acetate, in addition to the normal oxidation, palladium-catalyzed allylic rearrangement and subsequent oxidation took place to give a small amount of 3-acetoxy-2-octanone as a byproduct. Ethers of secondary allylic alcohols also underwent the regioselective oxidation to give the corresponding 3-alkoxy ketones in 30-40% yields. But in this case too, by-products derived from the allylic reanangement a subsequent oxidation were also detected. Results of the oxidation of some allyl ethers are shown in Table 3. °... 

Regioselective Oxidation Allyl and Homoallyl Ethers and Esters... 

The intermolecular coupling of allenes 123 and enones 124 selectively afforded dienones 125 in 53-81% yields (Scheme 4.45) [93]. As a catalyst precursor, [CpRuCl(cod)] was employed with CeCl3 7H20 and an alkynol 126 as activators. The proposed reaction mechanism involves the regioselective oxidative cyclization of the two components on a cationic ruthenium center, leading to the ruthenacyclopentane intermediate 127. When allenyl alcohols 128 were employed under otherwise identical conditions, the final products were cyclic ethers 129 (Scheme 4.46) [94]. As a catalyst precursor, the cationic ruthenium complex 68 can be used in the absence of the alkynol 126. The ether ring was considered to be formed directly via the ruthenacyclopentane 130 or alternatively through its Jt-allyl form 131. 

In addition to the regioselectively derivatized CDs, a number of statistically substituted CDs are in use. Highly water-soluble statistic derivatives are obtained by reaction of CDs with methyl halides [68], with epoxides (e.g., ethylene oxide, propylene oxide [69,70], or allyl glycidylether [71]), and with cyclic sulfates (e.g., butane sultone [72]). Statistical allyl ethers were converted to sulfonates by addition of sulfite [71], Monochlorotriazinyl-P-CD is another available reactive CD. Since these synthetic procedures are rather simple compared to the regioselective ones, many of these statistical compounds are available at the technical scale. 

Regiospecific oxidation of internal olefins bearing neighbouring oxygen functions by means of palladium catalysts can be achieved. The method is an effective way of preparing synthetically useful y-keto-esters or 1,4-diketones. Later work showed that the process could also be applied to allylic and homo-allylic ethers and esters (Scheme Similarly, regioselective oxidation of a -unsaturated esters furnishes p-keto-esters, and this has been elegantly applied in the -lactam field (Scheme 8). ... 

In a different vein, the biosynthetic route taking as a model [8,9], one of the most common methods to prepare furocoumarin derivatives, involves the initial O-allylation of a hydroxycoumarin followed by the regioselective Claisen rearrangement of the resulting allyl ether to generate the corresponding hydroxyallylcoumarin which is subsequently cyclized and oxidized (Scheme 19). These two steps can be performed in any order, and several protocols have been developed so far [13]. 

Alteration of regioselectivity of the Wacker oxidation of styrenes (90) in favour of the corresponding aldehydes (92) rather than methylketones has been achieved simply using t-BuOH rather than water. The reaction presumably proceeds via the vinyl ether (91), resulting from the anti-Markovnikov attack of the bulky nucleophile at the sterically less hindered terminal carbon. A similar reversion was observed for other terminal olefins (styrenes, allyl ethers, and 1,5-dienes) when the oxidation was carried out in the presence of pinacol, another bulky nucleophile, which produced acetals of the corresponding aldehydes. Similar effects of bulky alcohols have been reported previously. ... 

All that remains before the final destination is reached is the introduction of the C-l3 oxygen and attachment of the side chain. A simple oxidation of compound 4 with pyridinium chlorochro-mate (PCC) provides the desired A-ring enone in 75 % yield via a regioselective allylic oxidation. Sodium borohydride reduction of the latter compound then leads to the desired 13a-hydroxy compound 2 (83% yield). Sequential treatment of 2 with sodium bis(trimethylsilyl)amide and /(-lactam 3 according to the Ojima-Holton method36 provides taxol bis(triethylsilyl ether) (86 % yield, based on 89% conversion) from which taxol (1) can be liberated, in 80 % yield, by exposure to HF pyridine in THF at room temperature. Thus the total synthesis of (-)-taxol (1) was accomplished. 

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