Ether, 1-ethoxyethyl, protecting

The most systematically investigated acyl anion equivalents have been the IMS ethers of aromatic and heteroaromatic aldehyde cyanohydrins, TBDMS-protected cyanohydrins, - benzoyl-protected cyanohydrins, alkoxycaibonyl-protected cyanohydrins, THP-protected cyanohydrins, ethoxyethyl-protect cyanohydrins, a-(dialkylamino)nitriles, cyanophosphates, diethyl l-(trimethylsiloxy)-phenyimethyl phosphonate and dithioacetals. Deprotonation di these masked acyl anions under the action of strong basie, usually LDA, followed by treatment with a wide varies of electrophiles is of great synthetic value. If the electrophUe is another aldehyde, a-hydroxy ketones or benzoins are formed. More recently, the acyl caibanion equivalents formed by electroreduction of oxazolium salts were found to be useful for the formation of ketones, aldehydes or a-hydroxy ketones (Scheme 4). a-Methoxyvinyl-lithium also can act as an acyl anion equivalent and can be used for the formation of a-hydroxy ketones, a-diketones, ketones, y-diketones and silyl ketones. - - ... 

More recently, Yamamoto and coworkers [36] have developed a new acyl anion equivalent based upon the ethoxyethyl-protected a-hydroxymalonodini-trile derivative shown in Scheme 13 and have applied it in the area of N-sulfonyl imine chemistry. Thus, the carbanion derived from the dinitrile was added to imine 60 to afford adduct 61 which was rather unstable. However, N-alkylation of 61 with chloromethyl methyl ether yielded the stable product 62. Removal of... 

Stork has demonstrated that the readily available protected cyanohydrins of aldehydes are useful acyl carbanion equivalents, and has now applied these in the preparation of small rings. Treatment of the ethoxyethyl-protected cyanohydrin of 4-chlorobutyraldehyde (17) with sodium hexamethyldisilazide gives the cyclo-butanone cyanohydrin derivative (18) in high yield. The cyanohydrin derivative is easily hydrolysed to the ketone, or may be reduced with lithium aluminium hydride to the P-amino-ether (19), which is also a useful synthetic intermediate. 

Among the tasks remaining is the replacement of the C-16 hydroxyl group in 16 with a saturated butyl side chain. A partial hydrogenation of the alkyne in 16 with 5% Pd-BaS04 in the presence of quinoline, in methanol, followed sequentially by selective tosylation of the primary hydroxyl group and protection of the secondary hydroxyl group as an ethoxyethyl ether, affords intermediate 17 in 79% overall yield from 16. Key intermediate 6 is formed in 67 % yield upon treatment of 17 with lithium di-n-butylcuprate. 

In a reaction sequence202 protected a-hydroxy sulphones were alkylated, after which acid hydrolysis followed by mild basic hydrolysis gave ketones. The protecting group used was the 1-ethoxyethyl ether, and overall yields for the sequence were generally modest (equation 89). 

Ethyl vinyl ether is also useful for hydroxy group protection. The resulting derivative (1-ethoxyethyl ether) is abbreviated as the EE group.156 As with the THP group, the EE group introduces an additional stereogenic center. 

As an alternative to protection as ethers, alcohols can also be protected as acetals, the most common being tetrahydropyranyl ethers (THP-OR) and 1-ethoxyethyl ethers (EE-OR) (Table 7.7). Support-bound secondary aliphatic alcohols have been... 

Trifluoromethyl-P-lactam 63 was prepared in racemic form via a ketene-imine [2 + 2] cycloaddition, following previously published methods81 with modifications.46 The subsequent oxidative cleavage of PMP, acylation of NH with (f-Boc)20, hydrogenolysis over Pd/C, and protection as 1-ethoxyethyl ether gave N-f-Boc-P-lactam 63 in good overall yield (Scheme 13). 

As a similar protecting function the 1-ethoxyethyl ether, formed by reaction of the alcohol with ethyl vinyl ether, was introduced (Scheme 28). It displayed advantageous properties for the construction of oligonucleotides since it could be cleaved with 5% acetic acid without affecting the intemucleotide bond. ... 

The ethoxyethyl cyanohydrin was prepared (NaCN, HCl, THF, 0°C, 75% yield, followed by EtOCH CH2, HCl, 50% yield) to convert an aldehyde ultimately to a protected ketone. It was cleaved by hydrolysis (0.01 N HCl, MeOH, 25°C, followed by NaOH, 0°C, 85% yield). Butyl vinyl ether can be used similarly. 

The 1-ethoxyethyl (EE) protecting group can be introduced by reaction of the appropriate malate ester with ethyl vinyl ether in the presence of an acidic catalyst, such as pyridinium p-toluenesulfonate [14] or trifluoroacetic acid [15,16]. In either case, the (AS)-malate ester EE ether 9 is isolated in quantitative yield. 

Protection of hydroxyl groups as a-ethoxyethyl ethers Removal of the protective group... 

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