Formyl group, selective removal

Benzylic oxidation of alkoxybenzyl ethers is particularly facile, and since some of the more activated derivatives are cleaved under conditions which leave benzyl, various ester, and formyl groups unaffected, they have found application in the protection of primary and secondary alcohols. Deprotection with DDQ in dichloromethane/water follows the order 3,4-dimethoxy > 4-methoxy > 3,5-dimethoxy > benzyl and secondary > primary, thus allowing the selective removal of one function in the presence of another. 2,6-Dimethoxybenzyl esters are readily cleaved to the corresponding acids on treatment with DDQ in wet dichloromethane at rt, whereas 4-methoxybenzyl esters are stable under these conditions. Oxidative cleavage of N-linked 3,4-dimethoxybenzyl derivatives with DDQ has also been demonstrated. ... 

Use of peptide deformylase in aspartame synthesis. The cheap formyl group is used for protection and coupling proceeds chemically. After coupling, the formyl group of the desired product is selectively removed by peptide deformylase. 

The fluorophenol could be converted into 56 in four good steps but the insertion of the vinyl group to give 57 by formylation and a Wittig reaction went in only 18% and the cyclo-propanation with a diazoester and Cu(I) (chapter 30) gave poor selectivity in favour of the cis isomer of 57. Worse still, it was necessary to protect the phenol as a methyl ether and the removal of the methyl group, the last step, went in only 52% yield, wasting nearly half of all the material. 

Dihydroxycoumarin (55) underwent selective methylation (dimethyl sulfate) to the 7-methoxy derivative (56), which upon benzylation and oxidation (selenium dioxide), afforded the 4-formyl coumarin (74). Conversion to the acetal (75) occured upon treatment with triethyl orthoformate, and subsequent catalytic hydrogenation served the dual purpose of removal of the benzyl group and reduction of the coumarin double bond, to give (76). Hydride reduction of the derived acetate (77), followed by acidic workup, gave directly the furobenzofiiran (75) [presumably through the hydroxy aldehyde (75)]. Comparison of the spectra of racemic (75) with those of the naturally derived material showed the compounds to be identical. 

Tricarbonyliron complexes of conjugated trienes react with diazoalkanes at the free (uncom-plexed) double bond. In the synthesis of dimethyl 2-formylcyclopropane-l, 1-dicarboxylate (48), the ceric ion served the double function of catalyzing the deazetization and removing the tricarbonyl iron protecting group. When the optically active iron carbonyl complex was used, the addition of diazomethane gave selectively one diastereomer and this was used to make optically active dimethyl 2-formylcyclopropane-l,1-dicarboxylate (>90% ee). A similar route was employed to make the optically active formyl cyclopropanes 49, precursors to optically active cis- and tran.v-chrysanthemic acids. 

Another technique is to block one of the a-positions by introduction of a removable substituent which prevents formation of the corresponding enolate. Selective alkylation can be performed after acylation with ethyl formate and transformation of the resulting formyl (or hydroxymethylene) substituent into a group that is stable to base, such as an enamine, an enol ether or an enol thioether. An example of this procedixre is shown in Scheme 1.16, in the preparation of 9-methyl-1-decalone from rra 5-1-decalone. Direct alkylation of this compound gives mainly the 2-alkyl derivative, whereas blocking the 2-position allows the formation of the required 9-alkyl-1-decalone (as a mixture of cis and trans isomers). 

The amino alcohol 69 was selectively N-formylated to give the formamide 70, deoxygenation of which was achieved by bromin-ation with PBr followed by hydrogenation to yield 72. Removal of the protective group by acid treatment afforded (t)-dihydro-pinidine (73) (Fig. 12). 

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