Hydroxyl protecting groups, asymmetric

Dihydrooxazoles continue to occupy an important place in organic synthesis and medicinal chemistry as they have found use as versatile synthetic intermediates, protecting groups/pro-drugs for carboxylic acids, and chiral auxiliaries in asymmetric synthesis. There are several protocols in the literature for the transformations of functional groups such as acids, esters, nitriles, hydroxyl amides, aldehydes, and alkenes to 2-oxazolines. Newer additions to these methods feature greater ease of synthesis and milder conditions. 

In general, the level of asymmetric induction achieved with imines derived from achiral aldehydes and chiral amines is lower than that observed when a chiral aldehyde or chiral ketene is used. Nevertheless, threonine-derived imines 52 give the cis-P-lactams 53 with diastereoselectivity which increases as the size of the protecting group on the hydroxyl group increases <00SC3685>. 

A major disadvantage of the tetrahydropyranyl ether as a protecting group is that an asymmetric center is produced at C-2 of the tetrahydropyran ring on reaction with the alcohol. This asymmetry presents no difficulties if the alcohol is achiral, since a racemic mixture results. If the alcohol has an asymmetric center anywhere in the molecule, however, condensation with dihydropyran can afford a mixture of diastereomeric tetrahydropyranyl ethers, which may complicate purification and characterization. One way of surmounting this problem is to use methyl 2-propenyl ether, rather than dihydropyran. No asymmetric center is introduced, and the acetal offers the further advantage of being hydrolyzed under milder conditions than those required for tetrahydropyranyl ethers. Ethyl vinyl ether is also useful as a hydroxyl-... 

The combination of both asymmetric catalysis and differential innate functional group reactivity also allowed preparation of a number of inositol polyphosphates (Scheme 3c) [35]. Key to this last strategy was the site-selective phosphitylation of the 4-hydroxyl over the 6-hydroxyl of intermediate 21 to yield 22 the latter hydroxyl was sterically encumbered by a bulky TBS protecting group on the 1-hydroxyl. This hypothesis regarding steric differentiation was supported by the selective phosphitylation of 23 to yield 24, which, using the smaller BOM... 

Primary and secondary hydroxyl groups can be fluorinated by reaction with di-ethylaminosulfiir trifluoride (DAST) [103]. The reaction of asymmetric secondary alcohols produces inversion of the configuration. Thus, the reaction of the protected diacetone allose with DAST, followed by removal of the protective groups, gives 3-deoxy-3-fluoro-D-glucose [104] (reaction 4.100). 

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