Hydroxyl-protected vinyl ether

Living cationic polymerization has been achieved with the hydroxyl and amino protected vinyl ether monomers (Scheme The bulkier i-butyldimethylsilyl... 

The hydroxyl group was usually protected, because cyanohydrins have tendency to racemization or even decomposition. Vinyl ethers or acetal and acid catalysts furnish acetals [62]. Trialkylsilyl chlorides and imidazole are used to give silyl ethers [63]. Commonly used protective groups are silyl ether, ester, methoxy isopropyl (MIP) ether, and tetrahydro-pyranyl ether. ( -Protected cyanohydrins are tolerant to a wider range of cyanide/nitrile transformations and are utilized widely in the synthesis of compounds of synthetic relevance in organic chemistry. 

Ethyl vinyl ether is also useful for hydroxyl-group protection. The resulting derivative (1-ethoxyethyl ether) is abbreviated as the EE group.5 As with the THP group, the EE group contains a stereogenic center. 

Benzylic ethers (Ph CH2 OR), allylic ethers (R-CH=CH-CH2 OR) and vinylic ethers [R CH=CH(OR)] together with the most commonly encountered tetrahydropyranyl ethers [THP-ethers, (5)] and /J-methoxyethoxymethyl ethers [MEM-ethers, R0CH2 0(CH2)2 0CH3] play an important role in the protection of a hydroxyl group (p. 550). Macrocyclic ethers (the crown ethers) are important phase transfer catalysts [e.g. 18-Crown-6 (6)]. 

Among these, in particular, the acetate [17] and the silyloxyl [31] derivatives are often used as the protecting groups for the hydroxyl (alcohol) function. For example, polymers of 2-acetoxyethyl vinyl ether are readily transformed into a polyalcohol, poly(2-hydroxyethyl vinyl ether), by alkaline hydrolysis [17]. Due to the polar pendant functions, the polymers are of course hydrophilic and often water-soluble, and serve as hydrophilic segments in so-called amphiphilic polymers, as will be discussed later (Sections III.D and VI.B.5). Other important protecting groups include the malonate [23] and the imides [29,30], which lead to polymeric carboxylic acids and amines, respectively (Scheme 1). 

Synthesis of ketones. Stork and Maldonado have disclosed a new synthesis of ketones from aldehydes RCHO- RCOR. The aldehyde is first converted into the cyanohydrin and then the hydroxyl group is protected by reaction with ethyl vinyl ether to give (1). This is then converted into the anion by reaction with lithium diiso-propylamide under carefully controlled conditions. The base is generated from butyl-lithium and diisopropylamine in THF and then (1) in hexamethylphosphorie triamide... 

In model studies of the reaction of 20-ketosteroids with the reagent, Pettit et al.2 found it desirable to protect hydroxyl groups as the tetrahydropyranyl ethers and to carry out the reaction in refluxing diethylene glycol dimethyl ether (7 hrs.). Thus they obtained the vinyl ether (2) from the tetrahydropyranyl ether of pregnenolone in 83% yield. The vinyl ether was converted into the corresponding aldehyde by 70% perchloric acid-diethyl ether (the protective group is also hydrolyzed). 

All of the free hydroxyl groups are protected as acetals by reaction with methyl vinyl ether. The 0-acyl groups are then split off by treatment with alkali, and the resulting material is methylated (see Scheme 20). After hydrolysis of the methylated material, and analysis of the hy-drolyzate as alditol acetates by g.l.c.-m.s., it is possible to determine the positions and proportions of O-methyl groups and, hence, the substitution pattern of the 0-acyl groups. This procedure has been used to locate 0-acetyl groups in bacterial polysaccharides and wood polysaccharides. ... 

Some aspects of these inherent characteristics were addressed a few years later in the early 1980s when the preparation of polyacetals was described using a single (A-B) monomer 7 comprised of a vinyl ether and a hydroxyl moiety that could be polymerized to give a polyacetal [30] (Figure 13.2b). However, the vinyl ether moiety in monomers such as 7 must still be protected from hydrolysis, and as will be seen, the approach in Figure 13.2a is more flexible and has been followed to prepare different polyacetals for potential biomedical use [23,31,34]. 

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-... 

Acetal Protected PHS. Scheme 2 illustrates the possible equilibrium reactions of PHS (IV) with vinyl ethers. Under acidic conditions the phenolic hydroxyl groups of IV are converted into acetal groups (VI). The conversion degree depends on the reaction conditions (temperature, cat yst, time, solvent). 

Ethyl vinyl ether is also useful as a hydroxyl-protecting group although it, like dihydropyran, also gives rise to diastereomers when a chiral alcohol is used. 

It was anticipated all along that the vinylsilane residue could serve as a vinyl iodide surrogate. After protection of the C-14 secondary hydroxyl in 180 in the form of a triisopropylsilyl ether, the vinyltrimethylsilyl function can indeed be converted to the requisite vinyl iodide with AModosuccinimide (NIS) (see 180—>181, Scheme 43). Vinyl iodide 181 is produced stereospecifically with retention of the A17,18 double bond geometry. This transformation is stereospecific since the stereochemistry of the starting vinylsilane and the vinyl iodide product bear a definite relationship to each other.67b 75... 

---