Methoxymethyl ethers, formation with

This derivative is stable to TsOH/benzene at reflux and to Cr03/H. It is stable to NBS// . In the formation of this derivative formaldehyde from formalin can react with a C,-hydroxyl group to form a methoxymethyl ether. Paraformaldehyde can be used to avoid formation of the ethers. ... 

The hindered 11 )5-hydroxyl group fails to react with dihydropyran. However, mixed acetals [e.g., methoxymethyl ether (97)] and hemiacetals e.g., hydroxymethyl ether (98)] are obtained as by-products in the formation of the BMD group. ... 

One of the mildest methods for preparing methylene acetals involves reaction of a diol with dimethoxymethane in the presence of a suitable activating agent such as phosphorus pentoxide,176 trimethylsilyl Inflate.177 or lithium bromide and p-toluenesulfonic acid.178 The reaction is also used to make methoxymethyl ethers (see section 4.4,1) from alcohols. Scheme 3,95 illustrates the simultaneous formation of a methoxymethyl ether and a methylene acetal from Shikimic Acid.169 The reaction was adapted to the synthesis of the methylene acetal moiety of the marine antitumour agent Mycalamide B [Scheme 3.96],179... 

The effects of changes in the nature of the aikoxy group (equation 3) are evident in Table 2. High levels of asymmetric induction are achieved by the use of a-substituents such as methoxymethyl ether, benzyl ether, and methylthiomethyl (MTM) ether. The sterically demanding tetrahydropyranyl ether substituent, however, interferes with chelate formation, and its use generates poor selectivities. 

On a related front, the reactions of carbonyl compounds with metaliated 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 P-hydroxythiazolines (85) suffer thermal reversion upon attempted purification by distillation. Moreover, attempted cleavage of the corresponding P-hydroxythia-zolidines, which are readily produced from (85) upon dissolving metal reduction (Al-Hg), leads to the formation of p-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 = H) as the corresponding 0-methoxymethyl ether... 

The formation of the methoxymethyl ether (MOM) is achieved by conventional techniques (chloromcthyl methyl ether/Afi.V-diisopropylethylamine) analogously, the methyl ether is obtained by reaction with NaH/ iodomethanc35. The, V-benzyl group is finally removed with Pd-C H,. Thus. (25.55)-2.5-bis-(inethoxymethoxymethyl)pyrrolidine is obtained yield 3.1 g (66%). 

Reductive cycHzations have been shown to be diastereoselective in the synthesis of bicyclic products as well as various macrocycles. There are also instances of chirahty transfer in intermolecular reductive couphngs. The synthesis of anti-1,2-diols has been demonstrated using a-alkoxyaldehydes with a methoxymethyl ether (MOM) protecting group and mono-aryl internal alkynes (Scheme 8.25) [49]. Dias-tereoselectivities are high for the formation of anfi-l,2-diols in cases where the aldehyde has a branched sp -P-carbon. 

Recently, Aumann et al. reported that rhodium catalysts enhance the reactivity of 3-dialkylamino-substituted Fischer carbene complexes 72 to undergo insertion with enynes 73 and subsequent formation of 4-alkenyl-substituted 5-dialkylamino-2-ethoxycyclopentadienes 75 via the transmetallated carbene intermediate 74 (Scheme 15, Table 2) [73]. It is not obvious whether this transformation is also applicable to complexes of type 72 with substituents other than phenyl in the 3-position. One alkyne 73, with a methoxymethyl group instead of the alkenyl or phenyl, i.e., propargyl methyl ether, was also successfully applied [73]. 

Attempted formation of the benzyl ether of ( f-ethyl lactate with NaH/BnBr results in considerable racemization (50-75 % ee). This racemization is obviated by use of the amide analog noted in eq 2. Diisobutylaluminum Hydride has been used to convert the ester directly to the aldehyde employing the methoxymethyl, benzyl, ... 

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%... 

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. 

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