Ethers, allyl oxidation

Oxidative Heck-Type Reactions (Fujiwara-Moritani Reactions) 373 Table 9.2 The palladium-catalysed oxidative cyclization of aryl allyl ethers oxidant studies. 

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]. 

The 7, i5-unsaturated alcohol 99 is cyclized to 2-vinyl-5-phenyltetrahydro-furan (100) by exo cyclization in aqueous alcohol[124]. On the other hand, the dihydropyran 101 is formed by endo cyclization from a 7, (5-unsaturated alcohol substituted by two methyl groups at the i5-position. The direction of elimination of /3-hydrogen to give either enol ethers or allylic ethers can be controlled by using DMSO as a solvent and utilized in the synthesis of the tetronomycin precursor 102[125], The oxidation of the optically active 3-alkene-l,2-diol 103 affords the 2,5-dihydrofuran 104 in high ee. It should be noted that /3-OH is eliminated rather than /3-H at the end of the reac-tion[126]. 

The a-bromo-7-lactone 901 undergoes smooth coupling with the acetonyltin reagent 902 to afford the o-acetonyl-7-butyrolactone 903[763j. The o-chloro ether 904, which has no possibility of //-elimination after oxidative addition, reacts with vinylstannane to give the allyl ether 905, The o -bromo ether 906 is also used for the intramolecular alkyne insertion and transmetallation with allylstannane to give 907[764],... 

Allyl ethers are oxidized to acrylates with this reagent. 

With the polycyclic framework of the natural product intact, the completion of the total synthesis only requires a short sequence of reactions. At this juncture, the decision was made to address the problem of reconstituting the A-ring lactone. It was hoped that a selective oxidation of the A-ring allylic ether could be achieved. 

Oxidation, allylic, 56,25 of alcohols, 55, 84 58,122 Oxime ( -allyl ethers, 58,10 S y-(2-Oxobut-3-yl)butanethioate, 55, 129 4-Oxocarboxylic acid esters, 58, 81 S-substituted, 58, 82... 

The rearrangements of allylic sulfoxides, selenoxides, and amine oxides are an example of the first type. Allylic sulfonium ylides and ammonium ylides also undergo [2,3]-sigmatropic rearrangements. Rearrangements of carbanions of allylic ethers are the major example of the anionic type. These reactions are considered in the following sections. 

Scheme 44 Oxidative addition reactions of Cp2Zr derivatives with allylic ethers.

Since nucleophilic addition to a metal-coordinated alkene generates a cr-metal species bonded to an -hybridized carbon, facile 3-H elimination may then ensue. An important example of pertinence to this mechanism is the Wacker reaction, in which alkenes are converted into carbonyl compounds by the oxidative addition of water (Equation (108)), typically in the presence of a Pd(n) catalyst and a stoichiometric reoxidant.399 When an alcohol is employed as the nucleophile instead, the reaction produces a vinyl or allylic ether as the product, thus accomplishing an etherification process. 

High oxidation state alkylidene complexes in which a heteroatom is bound to the alkylidene carbon atom are extremely rare [41]. Since the approach shown in Eq. 43 failed, the related approach shown in Eq. 44 was taken to prepare the medium-sized ring subunits [222]. The latter product was formed in good yield when n=2, R H, R2=Et, but only poor yield when n=2, R =Et, R2=H, possibly due to unfavorable interactions between the ethyl substituent and transannular groups in the transition state for cyclization of the allyl ether [222]. Ruthenium catalysts either failed or gave low yields, presumably because of the steric hindrance associated with ring-closing dienes of this type. 

Scheme 1.6. Four-step mechanism for oxidative addition of allyl ethers to Cp2Zr complexes.

The reaction proceeds through ligand exchange and a subsequent P-elimination akin to the oxidative addition of Cp2Zr to allylic ethers [58], In this way, allyltitanium compounds can be obtained from readily available allylic alcohol derivatives and inexpensive Ti(OiPr)4. The method allows the preparation of functionalized allyltitaniums bearing functional groups such as ester or halide (Scheme 13.28). 

Because the reduction potential of ether is usually more negative than that of halides, examples that belong to this category are rather rare. Generally, cathodic reduction of ethers is similar to that of alcohols, and nonactivated ethers are not reducible under the conditions of electroreduction. Activated ethers such as benzylic and allylic ethers are elec-trochemically reduced to a limited extent (Scheme 7) [1, 15, 16]. Reduction of epoxides is usually difficult however, electroreductive cleavage of activated epoxides to the corresponding alcohols is reported [17, 18]. The cleavage of the C—O bond of ethers is more easily accomplished in anodic oxidation than in cathodic reduction, which is stated in Chapter 6. 

The same basic strategy was applied to the synthesis of the smaller fragment benzyl ester 28 as well (Scheme 4). In this case, aldehyde 22 prepared from (S)-2-hydroxypentanoic acid [9] was allylated with ent-10 and tin(IV) chloride, and the resulting alcohol 23 was converted to epimer 24 via Mitsunobu inversion prior to phenylselenenyl-induced tetrahydrofuran formation. Reductive cleavage of the phenylselanyl group, hydrogenolysis of the benzyl ether, oxidation, carboxylate benzylation, and desilylation then furnished ester 28. 

The oxygen atom has also been used to generate other functionalities, such as the aldehyde moiety in Kibayashi s syntheses of (—)-coniine (197) and its enantiomer (Scheme 1.43) (253). Here, reaction of tetrahydropyridine N-oxide 93 with a silylated chiral allyl ether dipolarophile 198 delivered the adduct 199 with the desired bridgehead stereochemistry via the inside alkoxy effect . Desilylation and hydrogenolytic N—O bond rupture with palladium(II) chloride provided the diol 200... 

Type I (fast homodimerization) Terminal olefins, allylsilanes" Terminal olefins, allylsilanes," 1° allylic alcohols, ethers, and esters, " allyl boronate esters, allyl halides, alkyl-substituted allenes Terminal olefms, allyl boronate esters, 1° allylic alcohols, ethers, and esters,styrenes (no large ortho substit.), " " allyl allylsilanes, allyl sulfides, allyl phosphonates, " allyl phosphine oxides, protected allylamines ... 

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