To select a specifi c protective group, the chemist must consider in detail all the reactants,
reaction conditions, and functionalities involved in the proposed synthetic
scheme. First he or she must evaluate all functional groups in the reactant to determine
those that will be unstable to the desired reaction conditions and require protection.
The chemist should then examine reactivities of possible protective groups,
listed in the Reactivity Charts, to determine compatibility of protective group and
reaction conditions. A guide to these considerations is found in Chapter 10. (The
protective groups listed in the Reactivity Charts in that chapter were the most widely
used groups at the time the charts were prepared in 1979 in a collaborative effort with
other members of Professor Corey’s research group.) He or she should consult the
complete list of protective groups in the relevant chapter and consider their properties.
It will frequently be advisable to examine the use of one protective group for several
functional groups (i.e., a 2,2,2-trichloroethyl group to protect a hydroxyl group
as an ether, a carboxylic acid as an ester, and an amino group as a carbamate). When
several protective groups are to be removed simultaneously, it may be advantageous
to use the same protective group to protect different functional groups (e.g., a benzyl
group, removed by hydrogenolysis, to protect an alcohol and a carboxylic acid).
When selective removal is required, different classes of protection must be used (e.g.,
a benzyl ether cleaved by hydrogenolysis but stable to basic hydrolysis, to protect an
alcohol, and an alkyl ester cleaved by basic hydrolysis but stable to hydrogenolysis, to
protect a carboxylic acid). One often overlooked issue in choosing a protective group
is that the electronic and steric environments of a given functional group will greatly
infl uence the rates of formation and cleavage. For an obvious example, a tertiary acetate
is much more diffi cult to form or cleave than a primary acetate.