Benzyl ethers Subject

You will note that the oxygen atoms attached to carbons 5 and 12 in 43 reside in proximity to the C-9 ketone carbonyl. Under sufficiently acidic conditions, it is conceivable that removal of the triethylsilyl protecting groups would be attended by a thermodynamically controlled spiroketalization reaction.30 Indeed, after hydro-genolysis of the C-26 benzyl ether in 43, subjection of the organic residue to the action of para-toluenesulfonic acid in a mixture of methylene chloride, ether, and water accomplishes the desired processes outlined above and provides monensin methyl ester. Finally, saponification of the methyl ester with aqueous sodium hydroxide in methanol furnishes the sodium salt of (+)-monensin [(+)-1], Still s elegant synthesis of monensin is now complete.13... 

The outcomes of intramolecular cyclizations of hydroxy vinylepoxides in more complicated systems can be difficult to predict. In a study of the synthesis of the JKLM ring fragment of dguatoxin, epoxide 44 was prepared and subjected to acid-mediated cydization conditions (Scheme 9.24) [114]. Somewhat surprisingly, the expected oxepane 45 was not formed, but instead a mixture of tetrahydropyran 46 and tetrahydrofuran 47 was obtained, both compounds products of attack of the C6 and C5 benzyl ether oxygens, respectively, on the allylic oxirane position (C3). Repetition of the reaction with dimsylpotassium gave a low yield of the desired 45 along with considerable amounts of tetrahydropyran 48. 

The reagent most commonly used for oxidation of ethers is RuO. The subject is well summarized in an early review by Gore [75], Primary methyl ethers RCHjOCHj are oxidised to esters RCOOCH, and secondary methyl ethers R R CjHjOCHj to ketones R COR while with benzyl ethers PhCH OR the esters PhCOOR are formed. For cyclic ethers, the carbon atoms adjacent to the O atom are oxidised, and if there are two secondary carbon atoms the main products are lactones, sometimes with partial hydrolysis to carboxylic acids [75], There is a short review on oxidation of ethers by RuO, principally on the mechanisms involved [76],... 

Protodedeuteration reaction has, however, some limitations. It cannot be used to study compounds subject to secondary condensation in acidic medium, such as certain benzyl alcohol and benzyl ether derivatives. Moreover, the partial rate factors depend greatly on the medium used because different acids show different degrees of selectivity. For instance, the reported partial rate factors for the para position of toluene (/PMe) range from 170 (in sulfuric acid at 6S°C.) (13) to 4000 (in hydrogen bromide) 22). 

Thus the alkyl ester end groups of convergently grown poly(benzyl ether) dendrimers can be subjected to post-synthetic modification by hydrolysis [28], reduction [29], transesterification/amidation [28] in a variety of ways. Subsequent modification of poly(benzyl ether) dendrons bearing p-bromobenzyl end groups by palladium-catalysed coupling reactions permitted preparation of dendrons with phenyl, pyridinyl, or thiophenyl end groups [30]. 

Although a number of different reagents have been discovered for the selective oxidation of ethers, e.g. halogens, iodine tris(trifluoroacetate), trichloroisocyanuric acid, UFs, A(,N-dibromobenzenesul-fonamide and lead tetraacetate, few have assumed any synthetic importance. Of these, the most significant are the metallic oxidants chromic acid and ruthenium tetroxide. DDQ has also been widely used for the oxidative d rotection of benzyl ethers. It is the aim of this chapter to review the latest developments in ether oxidation by these, and other reagents, with particular emphasis on chemo- and regio-selectivity. Several reviews on the subject have appeared previously. " The related oxidation of acetals has been reviewed recently" and will not be dealt with here. 

The C23-C26 segment 173 was prepared from 180, which was derived from ribose (O Scheme 20). After 0-benzylation of 180, the resulting benzyl ether was treated with MeMgCl and CuBr Me2S to afford 181. Thiol acetal formation followed by selective silyla-tion provided 182. The dithioacetal was cleaved and the resulting aldehyde was reduced with NaBH4 to afford a diol, which was subjected to direct epoxidation to provide 173. 

Both catalytic and chemical methods are effective for the hydrogenolysis of benzyl ethers. Catalytic methods have found much wider use than the chemical methods, presumably because of the milder conditions that prevail. A general survey of the hydrogenolysis of benzyl compounds (benzyl amines, sulfides, and esters are also subject to hydrogenolysis to varying degrees) has recently been made, and the reader is referred to this discussion for a complete treatment of the scope of the reaction. 

The C-4 acids (183 and 184) have also been subjected to borane reduction conditions to afford alcohol 195 in 23-50% yield or 64% yield as the C-8 epimeric mixture (195 and 196, Scheme 29) [34, 49, 64]. The C-8 alcohol epimers 195 and 196 have been treated separately as a common intermediate for a number of C-4 derivatives including esters, ethers, and amines [34, 49, 64], Alcohols 195 and 196 was subjected to DCC, DMAP, and desired acid chloride or carboxylic acid in CH2CI2 affording ester analogs in 50-92% yield [64], Esters prepared include alkyl, aryl, and fluorenylmethyloxycarbonyl (Fmoc) protected amino acid derivatives (197 and 198) [64]. Ethers were prepared with various alkyl halides and Ag20 in CH3CN at 40 °C. Alkyl, allyl, and benzyl ethers were prepared in 45-80% yield (199 and 200) [34,64]. Alcohols 195 and 196 were then activated to the triflates and displaced by a variety of amines by treatment with trifluoromethanesulfonic anhydride and desired amine in 22% - quantitative yield over two steps (201 and 202)... 

The preparations of dextran, and certain ethers and esters of dextran have been the subjects of about fifteen recent patents. The dextran (of L. mesenteroides or dextraniczim) may be precipitated first from the culture by the addition of ethanol or acetone, or the culture itself may be treated directly with the appropriate halide and sodium hydroxide in either a single stage or a two-stage procedure. The benzyl ether of dextran, formed by the reaction of dextran with benzyl chloride and sodium hydroxide at 75-185° for three to ten hours, is soluble in acetone and other solvents, and may be used in lacquers. Mixed ether and ester derivatives of dextran, e. g., benzyl and phthalate or butyl and benzoate, have been used for forming films, coatings or molded products. A preparation of dextran acetate has also been patented. ... 

Organic Reactions contains a review of the fission of benzyl ethers, including cyclic benzyl ethers, by hydrogenation.43 Ring fission of furans has been reviewed by Jones and Taylor.44 Burwell45 has written an excellent and detailed report on the cleavage of ethers, in which he discusses also the theoretical problems involved he concludes with some indications for the fission of sulfides, a subject that is treated also by Tarbell and Hamish.46... 

Benzyl ethers can be prepared from THP ethers by the Me3SiOTf-catalyzed reaction with PhCHO and EtiSiH." Analogously, amides, carbamates, and ureas are A -alkylated via condensation with aldehydes followed by in situ reduction with Et SiH. The aldehyde may be replaced by a thioester that is subject to reduction in situ. Thus, a mixture of sodium triacetoxyborohydride, triethylsilane, and Pd-C catalyst is employed. ... 

A new synthesis of N-formylnordihydrothebainone, and hence a formal synthesis of codeine and morphine, has been reported. The (+)-(R)-isomerof the tetrahydroisoquinoline (156) was subjected to Birch reduction, iV-formylation, and cyclization (with scission of the benzyl ether groups) to give N-formyl-2-hydroxynordihydrothebainone (157). Selective conversion of this into the 2-(l-... 

The DDQ oxidation technique identifies only the linkage sites of carbohydrates involved in benzyl ether-type LCC bonds (Fig. 5) [18,73-76]. Briefly, an LCC preparation is thoroughly acetylated, then subjected to DDQ oxidation to induce the oxidative cleavage of LCC bonds of the benzyl ether type into the corresponding a-carbonyl in acetylated lignin and terminal hydroxyl groups in acetylated carbohydrate moieties, respectively. The resulting carbohydrate mixture is then methylated by Prehm s procedure and hydrolyzed... 

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