Protective groups ketones

Methyl ethers have been employed, but alkyl glycosides may be unstable following hydrogen abstraction from the anomeric center (see Section 11,9). Benzyl ethers and benzylidene (and other aldehyde-based) acetals, which themselves undergo ready radical bromination,27 can be expected to be entirely unsuitable protecting groups. Ketone-derived acetals, on the other hand, should be stable, at least in the absence of acid, and a few examples of successful brominations in their presence are reported in Section 11,4. 

The ability to convert a protective group to another functional group directly without first performing a deprotection is a potentially valuable transformation. Silyl-protected alcohols have been converted directly to aldehydes, ketones, bro-mides, acetates, and ethers without first liberating the alcohol in a prior deprotection step. 

This protective group was used to direct the selective cyclopropanation of a variety of enones. Hydrolysis (HCl, MeOH, H2O, it, 94% yield) affords optically active cyclopropyl ketones. 

The 1,3-dioxolane group is probably the most widely used carbonyl protective group. For the protection of carbonyls containing other acid-sensitive functionality, one should use acids of low acidity or pyridinium salts. In general, a molecule containing two similar ketones can be selectively protected at the less hindered carbonyl, assuming that neither or both of the carbonyls are conjugated to an al-kene. ... 

Androst-4-ene-3,l 1,17-trionehas been converted into several 3,17-dienamine derivatives which, on reduction with LiAlH4 followed by removal of the protecting groups, give 11 jS-hydroxyandrost-4-ene-3,17-dione. An unsaturated 3-ketone has also been protected as an enamine in the LiAlH4 reduction of a 21-ester group a further example is the conversion of 7-methylene-5a-an-drostane-3,17-dione into the 3-pyrrolidine enamine followed by reduction of the 17-ketone by Li[OC(CH3)3]3 AlH. ... 

Protecting groups are generally formed by nucleophilic attack on the carbonyl group and the rate of this process is determined by steric and electronic factors associated with the ketone. In steroid ketones steric effects are usually more important due to the rigid tetracychc skeleton. 

Steric hindrance due to the presence of other substituents a to the carbonyl group may diminish reactivity during the formation of ketone protecting groups. Thus a marked decrease in reactivity has been observed with 2- or... 

However, treatment of cortisone 3,20-bissemicarbazone with acetic anhydride and pyridine removes the 20-semicarbazone group preferentially. Selective removal of a protecting group can be also achieved by a selective reaction to give a new intermediate which can be converted into the desired product ketone. Thus progesterone 20-monoenol acetate (42) is prepared from the 3,20-bisenol acetate (40) via selective electrophilic attack of iodine at C-6 followed by reductive dehalogenation of (41). ... 

Enol acetates are not very stable compounds and this limits their use as protecting groups. They are readily hydrolyzed to the parent ketones by acids and bases. 

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... 

Enol ethers of saturated 3-ketones are not usually obtained directly from the ketone and therefore are of little importance as protective groups. However, enol ether (52) has been used instead of the bulkier 3-dimethyl ketal to protect the 3-ketone during angular methylation to (53). ... 

A -Dien-3-ol esters e.g., acetates) have greater utility as reaction intermediates than as protecting groups. They are prepared from A" -3-ketones by reaction with the acetic anhydride"" or by exchange with isopropenyl acetate. 

Cross-conjugated dienones are quite inert to nucleophilic reactions at C-3, and the susceptibility of these systems to dienone-phenol rearrangement precludes the use of strong acid conditions. In spite of previous statements, A " -3-ketones do not form ketals, thioketals or enamines, and therefore no convenient protecting groups are available for this chromophore. Enol ethers are not formed by the orthoformate procedure, but preparation of A -trienol ethers from A -3-ketones has been claimed. Another route to A -trien-3-ol ethers involves conjugate addition of alcohol, enol etherification and then alcohol removal from la-alkoxy compounds. 

The 3-methoxime (74) provides a base-stable protecting group for A " -3-ketones. It is removed in low yield by conversion to the corresponding semicarbazone. 

Semicarbazones can be prepared from 17-ketones by the conventional procedure. The formation of 17-cyanohydrins by exchange with acetone cyanohydrin and the use of this protective group has been already discussed (see section II-A-2). ... 

Severe nonbonded interactions with the angular methyl groups at C-10 and C-13 and the 8/ -hydrogen strongly hinder formation of tetrahedral derivatives of the 11-ketone. The formation of protecting groups is therefore difficult to achieve. 

A recent publication describes the protection of a S-keto-A" system via its eniminium salt, permitting enol acetylation of a 20-ketone, epoxidation, hydrolysis and finally removal of the A-ring protecting group. 

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