Protective groups examples

Fig. 5 Hydrosilylation without protective groups example of l-allyloxy-2-3-propanediol...

These systems are based on acid-catalyzed thermolysis of side-chain protecting groups. Examples of polymers that function in this fashion are listed in Chart 3.1. 

We shall describe a specific synthetic example for each protective group given above. Regiosdective proteaion is generally only possible if there are hydroxyl groups of different sterical hindrance (prim < sec < tert equatorial < axial). Acetylation has usually been effected with acetic anhydride. The acetylation of less reactive hydroxyl groups is catalyzed by DMAP (see p.l44f.). Acetates are stable toward oxidation with chromium trioxide in pyridine and have been used, for example, for protection of steroids (H.J.E. Loewenthal, 1959), carbohydrates (M.L. Wolfrom, 1963 J.M. Williams, 1967), and nucleosides (A.M. Micbelson, 1963). The most common deacetylation procedures are ammonolysis with NH in CH OH and methanolysis with KjCO, or sodium methoxide. 

Trichloro- and 2,2,2-tribromoethoxycarbonyl (Tceoc and Tbeoc) protecting groups are introduced with the commercially available 2,2,2-trihaloethyl chloroformates. These derivatives are stable towards CrOj and acids, but can smoothly be cleaved by reduction with zinc in acetic acid at 20 °C to yield 1,1-dihaloethene and CO. Several examples in lipid (F.R. Pfeiffer, 1968, 1970) and nucleotide syntheses (A.F. Cook, 1968) have been described. 

Since (A) does not contain any other functional group in addition to the formyl group, one may predict that suitable reaction conditions could be found for all conversions into (A). Many other alternative target molecules can, of course, be formulated. The reduction of (H), for example, may require introduction of a protecting group, e.g. acetal formation. The industrial synthesis of (A) is based upon the oxidation of (E) since 3-methylbutanol (isoamyl alcohol) is a cheap distillation product from alcoholic fermentation ( fusel oils ). The second step of our simple antithetic analysis — systematic disconnection — will now be exemplified with all target molecules of the scheme above. For the sake of brevity we shall omit the syn-thons and indicate only the reagents and reaction conditions. 

Three selective methods to remove protective groups are receiving much attention assisted, electrolytic, and photolytic removal. Four examples illustrate assisted removal of a protective group. A stable allyl group can be converted to a labile vinyl ether group (eq. 4) a /3-haloethoxy (eq. 5) or a /3-silylethoxy (eq. 6) derivative is cleaved by attack at the /3-substituent and a stable o-nitro-phenyl derivative can be reduced to the o-amino compound, which undergoes cleavage by nucleophilic displacement (eq. 7) ° ... 

Photolytic cleavage reactions (e.g., of o-nitrobenzyl, phenacyl, nitrophenylsul-fenyl derivatives) take place in high yield on irradiation of the protected compound for a few hours at 254-350 nm. For example, the o-nitrobenzyl group, used to protect alcohols, amines, and carboxylic acids,has been removed by irradiation. Protective groups that have been removed by photolysis are described at the appropriate places in this book in addition, the reader may wish to consult five review articles. 

Total Synthesis of Palytoxin Carboxylic Ad An Example of the Selection, Introduction, and Removal of Protective Groups... 

In the following example the acetonide protective group is selectively converted to one of two t-butyl groups. The reaction appears to be general, but the alcohol bearing the t-butyl group varies with structure.Benzyli-dene ketals are also cleaved. 

Protection of the amide — NH is an area of protective group chemistiy that has received little attention, and as a consequence few methods exist for amide — NH protection. Most of the cases found in the literature do not represent protective groups in the true sense, in that the protective group is often incoiporated as a handle to introduce nitrogen into a molecule rather than installed to protect a nitrogen which at some later time is deblocked. For this reason many of the following examples deal primarily with removal rather than with both formation and cleavage. 

M (marginal) indicates that the stability of the protected functionality is marginal, and depends on the exact parameters of the reaction. The protective group may be stable, may be cleaved slowly, or may be unstable to the conditions. Relative rates are always important, as illustrated in the following example (in which a monothioacetal is cleaved in the presence of a dithiane), and may have to be determined experimentally. 

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. ... 

SYNTHESIS OF COMPLEX SUBSTANCES TWO EXAMPLES (AS USED IN THE SYNTHESIS OF HIMASTATIN AND PALYTOXIN) OF THE SELECTION, INTRODUCTION, AND REMOVAL OF PROTECTIVE GROUPS... 

The use of biocatalysts for the selective introduction and cleavage of esters is vast and has been extensively reviewed." Therefore only a few examples of the types of transformations that are encountered in this area of protective group chemistry will be illustrated to show some of the basic transformations that have appeared in the literature. The selective... 

Isothiazolone dioxide rings are readily cleaved in diluted aqueous alkaline solution at r.t. and this feature allows their use, in some cases, as a protecting group (95TL(36)6227). An example is the efficient Fischer indole synthesis of 72. 

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