Protection of carbonyl groups

Protection of Carbonyl Groups by Formation of Trimetbylsilyl Enol Ethers 

Carbonyl compounds are easily converted to trimethylsilyl enol ethers (Eq. 4.21)  

An example will be given here for each kind of carbonyl group which may be protected as a trimethylsilyl enol ether. 

For the insertion of some /-alkyl groups into the a-position, the trimethylsilyl enol ether may be allowed to react with a /-alkyl chloride and TiC in dichloromethane at 

Protection of Carbonyl Groups as Trimethylsilyl Cyanohydrin Ethers 

Exercise 16-35 A radical-chain reaction similar to that described for the air oxidation of benzaldehyde occurs in the peroxide-initiated addition of aldehydes to alkenes (see Table 10-3). Write a mechanism for the peroxide-induced addition of ethanal to propene to give 2-pentanone. 

Exercise 16-36 Certain aldehydes decompose to hydrocarbons and carbon monoxide when heated in the presence of peroxides  

Write a reasonable chain mechanism for such reactions that is supported by calculations of the AH° values for the propagation steps. Use needed data from Table 4-3 and Table 4-6. Your answer should reflect the fact that this reaction does not proceed well with most aldehydes unless the reactants are heated (above about 120°). 

There are few reactions of aldehydes and ketones that do not in some way affect the carbonyl function. For this reason, it may be necessary to protect the carbonyl function when it is desirable to avoid reaction at this function. For example, you may plan to synthesize 4-cyclohexylidene-2-butanone by way of a Wittig reaction (Section 16-4A), which would involve the following sequence  

This synthesis would fail in the second step because the phenyllithium would add irreversibly to the carbonyl group. To avoid this, the carbonyl group would have to be protected or blocked, and the most generally useful method of 

The dimethyl ketal function (51) is one of the most suitable base stable protecting groups for saturated 5a- and 5/i-3-ketones. It is formed by reaction of the ketone (50) with methanol in the presence of a suitable catalyst. Good selectivity can also be achieved with this group since 2-, 6-, 11-, 12-, 17- and 20-ketones do not form dimethyl ketals under these conditions. The 2-ketone is converted in part to the dimethyl ketal in the presence of homogeneous rhodium catalyst. y -Toluenesulfonic acid is the catalyst of 

Estr-5(10)-en-3-ones also react with methanol to give dimethyl ketals. Weak acid catalysts such as malonic and oxalic acid or selenium dioxide, which are unable to promote conjugation of the double bond, are conveniently used.  

The saturated 3-ketone can also be protected as the ethylene ketal, which is prepared directly by reaction with ethylene glycol or by exchange dioxo-lanation. Selective formation of 3-ethylenedioxy compounds is also possible, but the former method is not particularly effective in the presence of 6-, 17- or 20-ketones. However, the exchange dioxolanation technique is more sensitive to steric effects and good selectivity at C-3 can be achieved in the presence of a 17-ketone, provided the reagent does not contain glycol.  

Selective ketalization at C-3 in the presence of a 20-ketone is achieved by the selenium dioxide procedure, at room temperature with or without an additional acid catalyst. 

Thioketals are readily prepared by reaction of saturated 3-ketones with thiols or dithiols in the presence of boron trifluoride or hydrogen chloride catalysts. Selective protection of the 3-ketone in the presence of a 6-ketone is possible by carrying out the reaction in diluted medium. Similarly, 3-ketones react selectively with monothiols or with bulky dithiols in the presence of 6-, 7-, 11- and 12-ketones. 

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B. Factors Governing Selectivity in Formation of Protecting Groups 1. Protection of carbonyl groups... 

Protection of carbonyl groups. A number of organosilicon pseudohalides (e.g., Me3SiX X-CH, SR, N3 etc.) have been shown to add to carbonyl groups, especially in the presence of suitable catalysts. 

Open chain and cyclic thioacetals 1,3-Dithiolane and 1,3-dithiane derivatives are versatile intermediates in the synthesis and interconversion of monocarbonyl and 1,2-dicarbonyl compounds. Protection of carbonyl groups as their open-chain and cyclic thioacetals is an important method in the synthesis of organic molecules. Thioacetals are stable... 

Protection of carbonyl groups. The reagent (I) reacts with aldehydes or ketones in refluxing benzene (p-TsOH catalysis) to give bromomethylethylene kctals (2) in... 

The adducts can also be used as a means of protection of carbonyl groups. They are stable in aprotic media, but the carbonyl group is readily regenerated in dilute aqueous acid or base. 

An example is offered by the room temperature cholinium chlorozincate ionic liquid 22, an efficient catalyst for the protection of carbonyl groups with diols under solvent-free conditions (Strategy C). An equimolar mixture of a diol (1,2- to 1,5-diol) and a carbonyl compound is stirred at room temperature for 10-20 h in the presence of 22. Very high yields of acetals are reported and the catalyst is easily recovered and recycled. A typical reaction is reported in Figure 22. 

Protection of carbonyl groups,2 The reagent reacts with ketones under slightly alkaline conditions to form N,N-dimethylhydrazones. They can be cleaved under neutral conditions with methyl iodide in refluxing 95% ethanol. The method is... 

Protection of carbonyl groups. Aldehydes and ketones are converted into acetals and ketals in high yield by reaction with (1) in refluxing benzene (TsOH catalysis) with azeotropic removal of water. Deprotection has been carried out by... 

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