Methoxymethyl ether hydrolysis

Obayashi and Schlosser [43] have briefly described syntheses of erythro-sphingo-sine and threo-sphingosine from D-mannose and D-ribono-1,4-lactone, respectively. For the synthesis of ery/Aro-sphingosine (35) D-mannose was converted into benzyl 2,3 5,6-di-O-isopropylidene-manno-furanosides and hydrolysis of the 5,6-0-iso-propylidene group followed by periodate oxidation and borohydride reduction and protection gave the methoxymethyl ether (28). This was converted into the chloride... 

Show all of the steps in the mechanism for the hydrolysis of this methoxymethyl ether. What other products are formed in this reaction ... 

A synthesis of 2-fluoroshikimic acid 91.2 [Scheme 3.91]169 exposes the robust nature of the methylene acetal Hydrolysis of the methoxymethyl ether and methylene acetal in 91.1 required concentrated hydrochloric add at reflux for 17,5 h to give a 60% yield of the target. 

On a related front, the reactions of carbonyl compounds with metallated derivatives of 2-methylthia-zoline furnish adducts (85). Although the initial nucleophilic addition occurs smoothly with a wide variety of aldehydes and ketones, the intermediate 3-hydroxythiazolines (85) suffer thermal reversion upon attempted purification by distillation. Moreover, attempted cleavage of the corresponding 3-hydroxythia-zolidines, which are readily produced from (85) upon dissolving metal reduction (Al-Hg), leads to the formation of 3-hydroxy aldehydes only in simple systems numerous complications arising from dimerization, dehydration and retroaldol processes of the products usually intervene. Consequently it is necessary to protect the initial 1,2-adducts (85 R2 = H) as the corresponding O-methoxymethyl ether derivatives (86 R2 = MOM), which can then be easily transformed into protected 3-hydroxy aldehydes by sequential reduction and hydrolysis (Scheme 32).55... 

The tricyclic amines (81 R = Me, Ph, COMe) fragmented when refluxed in aqueous base to give N-substituted 3-aminomethyl-7,7-dimethylcyclo-octane-l,5-diones. Treatment of the bisdibromocarbene adduct of cyclohexa-1,4-diene-1,5-diol (prepared by hydrolysis of the bisdibromocarbene adduct of the corresponding bis (methoxymethyl)ether) with pyridine gave the cyclo-octatrienone (82) whereas the isomeric bisdibromocarbene adduct of cyclohexa-1,4-diene-1,4-diol, gave only a low yield of benzocyclobutenone (83). ... 

The corresponding methyl ethers, i.e., alkylated rranj-1-acyl-2,5-bis(methoxymethyl)pyrrolidines 1 (R3 = CH,). are first demethylated by trichloroborane in CH,C12 prior to the acidic hydrolysis (see Tabic l)1. 

Related oxidants that have been exploited to similar ends include l-(tert-butoxy)-l,2-benzoiodoxol-3(l//)-one292 and sodium bromate.293 Oxidation of benzyl ethers by l-(/erf-butoxy)-l,2-benzoiodoxol-3(l/f)-one followed by easy basic hydrolysis of the resultant benzoate ester provides a convenient alternative to the usual reductive deprotection. The reaction is carried out in the presence of alkali metal carbonates and the conditions are mild enough to be compatible with other hydroxyl protecting groups such as methoxymethyl, tetrahydropyranyl, TBS and acetate. 

Petrini and co-workers used the bis(methoxymethyl)-protected nitrone 150, also derived frern L-tartrate, as an electrophile rather tfaiui as a 1,3-dipole (Scheme 21, top line) (89). In their key step, reaction with 4-ben loxybutylmagnesium bromide gave the cyclic hydroxylamine 151 in 82% yield (de 90%). Transfer hydrogenation with ammonium formate and a palladium catalyst cleaved both the hydroxylamine and the benzyl ether, affording the aminoalcohol 152. Cyclization via the corresponding primary chloride created the protected indolizidine 153, acidic hydrolysis of t ch completed this short synthesis of ( + )-132 in 16%... 

If there is a leaving group in the (i-position of the carbonyl starting material 132 during homologation by the methoxymethyl reagents 116 or 117, it is lost during the hydrolysis of the enol ether product 133 to form an enal 134. 

Ether cleavage. The polymer-bound reagent catalyzes hydrolysis of TBS ether and acetals in aqueous acetonitrile. Methoxymethyl and tetrahydropyranyl ethers are stable under such conditions. 

Carbon-Oxygen Bond Formation. CAN is an efficient reagent for the conversion of epoxides into /3-nitrato alcohols. 1,2-cA-Diols can be prepared from alkenes by reaction with CAN/I2 followed by hydrolysis with KOH. Of particular interest is the high-yield synthesis of various a-hydroxy ketones and a-amino ketones from oxiranes and aziridines, respectively. The reactions are operated under mild conditions with the use of NBS and a catalytic amount of CAN as the reagents (eq 25). In another case, N-(silylmethyl)amides can be converted to A-(methoxymethyl)amides by CAN in methanol (eq 26). This chemistry has found application in the removal of electroauxiliaries from peptide substrates. Other CAN-mediated C-0 bondforming reactions include the oxidative rearrangement of aryl cyclobutanes and oxetanes, the conversion of allylic and tertiary benzylic alcohols into their corresponding ethers, and the alkoxylation of cephem sulfoxides at the position a to the ester moiety. 

The initial olefination was accomplished using the Wittig olefination conditions developed by Corey (NaH/DMSO) to afford E/Z mixtures of enol ethers. The enol ethers undergo hydrolysis to the corresponding aldehydes upon treatment with 5% aqueous HF in acetonitrile. Modest degrees of stereoselectivity were observed. The ability of fluoride to mediate the hydrolysis of the (trimethylsilyl)ethoxymethyl moiety may provide opportunities not available when (methoxymethyl)triphenylphosphonium salts are employed. However, it should be noted that Zbiral and Schonauer reported that hydrolysis could not be realized with the use of tetrabutylammonium formate or triethylamine 2HF. 

Different alcohols and protected alcohols (as hemiacetals, silyl, methoxymethyl or phenyl ethers) were lithiated at the d-position to give the corresponding organolithium compounds. In the case of alcohols, a previous deprotonation of the hydroxyl functionality is required. The chiral intermediate 197 was prepared from the phenylsulfanyl derivative 196 first by deprotonation followed by carbon-sulfur bond cleavage with LiDTBB at low temperature. The reaction of the dianionic system 197 with y- and d-lactones in the presence of cerium(III) salts gave, after hydrolysis, spiroketal pheromones 198 (Scheme 2.27) [163]. 

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