Strategy IV Protecting Groups

Background Needed for this Chapter Reference to Clayden, Organic Chemistry Chapter 24 Chemoselectivity Selective Reactions and Protection. 

Protecting groups have been mentioned occasionally in previous chapters in this chapter the ideas behind their use are systematically presented and a collection of protecting groups suitable for a range of functional groups is tabulated. Protection allows us to overcome simple problems of chemoselectivity. It is easy to reduce the keto-ester I to the alcohol 2 with a nucleophilic reagent such as NaBHU that attacks only the more electrophilic ketone. 

Making alcohol 3 by reducing the less electrophilic ester is not so easy but protection of the ketone as an acetal 4—a functional group that does not react with nucleophiles—allows reduction of the ester with the more nucleophilic L1AIH4. 

Another important function of protecting groups is to prevent a reagent from attacking itself. In the last chapter, when we discussed the synthesis of the bicyclic amine monomorine, we used the protected enone 12 but did not say how it was made. The chloroketone 9 is first made1 in 89-93% yield from the ketolactone 6 simply by reaction with HC1. Chloride displaces the protonated ester group 7 and the product 8 decarboxylates under the conditions of the reaction. 

It must be resistant to reagents that would attack the unprotected functional group. 

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Figure 3. Protective group strategy in DNA-synthesis by the standard phosphoramidite method on solid support. I Protected 5 -hydroxy group by the DMT (dimethoxytrityl) group, 3 -cyanoethyl-phosphora-midite II, III, IV Protection of nucleobases V Thymine remains unprotected.

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