Hydrogenolysis, cleavage ethers

Open-chain aliphatic ethers are completely resistant to hydrogenolysis. Cyclic ethers (for epoxides, see p. 83) may undergo reductive cleavage under strenuous conditions. The tetrahydrofuran ring was cleaved in vigorous hydrogenations over Raney nickel [420] and copper chromite [420] to give, ultimately, alcohols. 

Cbz-protected amines behave like amides—they are no longer nucleophilic, because the nitrogen s lone pair is tied up in conjugation with the carbonyl group. They are resistant to both aqueous acid and aqueous base, but they have, to use the analogy we developed in the last chapter, an Achilles heel or safety catch—the benzyl ester. The same conditions that removed benzyl ethers in Chapter 24 will remove Cbz HBr or hydrogenolysis. cleavage of Cbz (Z) in HBr/AcOH... 

Exposure of benzylic alcohols, ethers, or esters to hydrogen in the presence of metal catalysts results in rupture of the reactive benzylic carbon-oxygen bond. This transformation is an example of hydrogenolysis, cleavage of a o- bond by catalytically activated hydrogen. 

An example of a conventional cascade system with two catalysts comprising a high-valent metal triflate Lewis add and a supported Pd catalyst for the hydrogenolysis of ethers is illustrated in Fig. 8.24. Since primary C—O bonds are resistant to cleavage, in the presence of water, there is formation of the parent primary alcohol that further undergoes acid-catalyzed dehydration to alkene and rapid, irreversible metal-catalyzed hydrogenation to alkane. 

Picolyl ethers are prepared from their chlorides by a Williamson ether synthesis (68-83% yield). Some selectivity for primary versus secondary alcohols can be achieved (ratios = 4.3-4.6 1). They are cleaved electrolytically ( — 1.4 V, 0.5 M HBF4, MeOH, 70% yield). Since picolyl chlorides are unstable as the free base, they must be generated from the hydrochloride prior to use. These derivatives are relatively stable to acid (CF3CO2H, HF/anisole). Cleavage can also be effected by hydrogenolysis in acetic acid. ... 

The 4-(dimethylaminocarbonyl)benzyl ether has been used to protect the phenolic hydroxyl of tyrosine. It is stable to CF3CO2H (120 h), but not to HBr/AcOH (complete cleavage in 16 h). It can also be cleaved by hydrogenolysis (H2/Pd-C). ... 

Hydrogenolysis (Section 26.7) Cleavage of a bond by reaction with hydrogen. Benzylic ethers and esters, for instance, are cleaved by hydrogenolysis. 

The completion of the synthesis of gilvocarcin V (2) only requires a few functional group manipulations. Hydrogenolysis of the four benzyl groups, followed by acetylation of the liberated hydroxyl groups, provides 30 in 68 % overall yield. After cleavage of the MOM ether in 30 with bromotrimethylsilane, application... 

The completion of the synthesis of 1 only requires two deprotection steps. Hydrogenolysis of the four benzyl ethers, followed by cleavage of the triisopropylsilyl ether with hydrofluoric acid in acetonitrile, provides paeoniflorin (1) in an overall yield of 92 %. 

The benzyl group can serve as a hydroxy-protecting group if acidic conditions for ether cleavage cannot be tolerated. The benzyl C—O bond is cleaved by catalytic hydrogenolysis,176 or by electron-transfer reduction using sodium in liquid ammonia or... 

The bonds between an oxygen and an sp3 carbon atom in alcohols, ethers, or esters are quite resistant to hydrogenolysis. Elevated temperatures and pressures are required to induce C-O bond cleavage and the high temperature can cause the cleavage of the C—C bonds, too. 

Desulfoxidation was achieved using Ra-Ni in ether. This was followed by selective hydrogenolysis of the benzyl group on W2 Ra-Ni under a hydrogen atmosphere in EtOH.420-422 Desulfoxidation had to be performed in ether use of ethanol as the solvent in desulfoxidation led to cleavage of a C-7-C-8 bond (Scheme 4.123). 

Model compound studies were also carried out in MeOH/KOH, and the results are shown in Table VI. Phenanthrene and biphenyl were quantitatively recovered unchanged by the reactions, and bibenzyl was recovered in 95% yield, with small amounts of toluene observed. Anthracene and diphenyl ether, on the other hand, were converted respectively to 9,10-dihydroanthracene and a mixture of polymethyl-phenols similar to that observed in the work with coal. The cleavage of diphenyl ether via hydrogenolysis should yield both benzene and phenol as products we saw no benzene in our study, and our... 

The cleavage of the tricyclic structure such as the product presented in Eq. 8.83 leads to a linear aminopolyhydroxylated structure (Scheme 8.25).135 Two-step unfolding (silyl ether hydroxydesilylation/nitroso acetal hydrogenolysis) can be useful in the preparation of hydroxy-lated amino acids (Eq. 8.84). 

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. 

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