Benzyloxymethyl ether

Through some conventional functional group manipulations, intermediate 5 could be derived from compound 9. Retrosynthetic disassembly of intermediate 9, in the manner illustrated in Scheme 2, furnishes the benzyloxymethyl ether of (/ )-/ -hydroxyisobutyral-dehyde (10) as a potential precursor and introduces the interesting... 

Benzyloxymethyl ethers are comparable in base stability to MOM, MEM. and SEM ethers. However, like benzyl ethers they can be removed by hydrogenoly-sis or Birch reduction. The advantage BOM ethers have over benzyl ethers is their easier preparation and easier removal. However, unlike benzyl ethers, they decompose in aqueous acid. The BOM group was introduced in 1975 by Stork and Isobe,501 but it has not been as widely applied as MOM or MEM groups though its virtues are gaining in appreciation. 

Benzyloxymethyl ether Methylthiomethyl ether Tetrahydropyranyl ether... 

The reaction of the trimethylsilyl enol ether derived from 2-phenylcyclohexanone with the bis[trimethylsilyl(ethoxy)methyl (SEM)] ether of (/ )-BINOL, (f )-BINOL(SEM)2, was promoted in the presence of SnCU, and the (i )-a-SEM ketone was obtained in 91 % yield and 75 % ee (Table 6). In contrast, the use of the benzyloxymethyl ether gave the corresponding R adduct in 55 % yield and 43 % ee. This unique phenomenon can be explained by the interaction between silicon and a y positive charge as homohyperconjugation. Finally, the highest ee value of 94 % was achieved by performing the reaction in 1 -chloropropane at -125 °C for long periods. 

More recently, Danishefsky reported a fully synthetic route to tunicamin-yluracil (274) derived from tunicamycin (85JA7761) and hikosamine (284) (85JA7762). Cyclocondensation of the ribosederived aldehyde (260) (84JOC1955) (Scheme 35) with diene 259 under catalysis by Eu(fod)3 (83JA3716) afforded an 86% yield of the carbon-linked disaccharide 261. Ozonolysis of 261, followed by oxidative treatment and esterification, furnished the /3-hydroxy ester 262 and its benzyloxymethyl ether 263. 

Alkoxymethyl Ethers The principal members of this set of protecting groups are methoxy-methyl ether (MOM) [188], methoxyethoxymethyl ether (MEM) [189], benzyloxymethyl ether (BOM) [190], /7-methoxybenzyloxymethyl ether (PMBM) [191], and trimethylsi-lylethoxymethyl ether (SEM) [192] (O Fig. 4). Since these protecting units are devoid of chirality, their use introduces no stereochemical complications. 

A transition state similar to 285 also explains the syn-selectivity observed with the DIBAL-H reduction of the benzyloxymethyl ether derivative of 280 (see Table 4.8). It does not explain, however, the anti-selectivity observed with LiAlH4 or when other substituents are present, as seen in Table 4.8. For these cases, a chelation model (286) must be invoked to explain the erythro (anti) selectivity, where path b is less hindered. Chelation... 

In 1999 Holmes and coworkers reported preliminary results on the enantioselective synthesis of the Overman indohzidinone (—)-2369 by a route involving a diastereoselective intramolecular [3 + 2] cycloaddition of nitrones such as 2374. Full experimental details as well as the conversion of 2369 into (+)-aUopumihotoxin 323B (1714) were subsequently published. In this apphcation (Scheme 303), base-induced aldol reaction between 2369 and aldehyde (—)-2375, prepared in eight steps from (S)-3-bromo-2-methylpropanol, produced a mixture of diastereomers (—)-2376. Base-promoted dehydration of the trifluoroacetates gave rise to a single enone (- -)-2377, which was reduced stereoselectively with tetramethyl-ammonium tris(acetoxy)borohydride iyide supra) followed by mild deprotection of the benzyloxymethyl ether with lithium di-tefi-butylbiphenyl (LiDBB) to give the target alkaloid 1714. 

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