Factors governing selectivity in formation of protecting groups

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

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. 

20-Ketones are usually more hindered and less reactive than simple cyclohexanones. 

In practice the 3-ketone in both 5a- and 5i -steroids is the least hindered and most reactive carbonyl group, whereas the 11-ketone is the most hindered and least reactive. The 6-ketone is less reactive than the 3-ketone but it can be selectively protected in the presence of a 17- or 20-ketone. The 7-ketone is more reactive than a 12-ketone. 

Similarly, reaction of (3) with methyl orthoformate yields the trimethoxy compound (6) via the intermediate 1,4-adduct (5). 

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Factors governing choice of protecting groups / 375 Factors governing selectivity in formation of protecting groups / 375... 

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