Protection with pivaloyl ester

Three additional protecting groups in this category are the mesitoate ester (OCOC6H22,4,6-trimethyl, O— Mes), the pivaloyl ester (OCO—f-Bu), and the para-methoxybenzoyl ester (OCO—C6H4-4-Me). The mesitoate ester is formed by reaction of an alcohol with mesitoyl chloride in the presence of pyridine or triethylamine. The main advantage of this ester is its stability to hydrolysis (pH 1-12), nucleophilic attack,... 

Hydrolysis of ester 16 proceeds smoothly. Activation of the resulting acid is achieved via conversion into the mixed anhydride 60. The amino group of (S)-2-amino-l-propanol is more basic than the alcohol function therefore there is no need for protection. It attacks the anhydride at the carbonyl carbon of the former acid because of the steric interaction with the pivaloyl group and gives amide 17 in 71 % yield. 

Imidazole carboxylic esters of secondary or tertiary alcohols, such as 1053 and 1054,, form carbonates exclusively with primary alcohols (Scheme 253). Thus, 1054 is a useful reagent for the BOC-protection of primary hydroxyl groups < 19990L933>. In some cases, 1054 offers better selectivity than pivaloyl chloride in the protection of carbohydrates <1998S1787>. Similarly, l-(methyldithiocarbonyl)imidazole 1055 and its methyl triflate salt convert alcohols to ri -methyldithiocarbonates <1997SL1279> and amines to 6 -methyldithiocarbamates or thioureas <2000T629>. 

The removal of NSEC carbonates is carried out by reaction with TBAF in the presence of esters including acetyl, levulinoyl, benzoyl and pivaloyl, but also allyl and PMB ethers are not affected. However, the NSEC group cannot be selectively removed in the presence of Fmoc protecting groups. 

The use of carboxylic acid esters as protective groups for alcohols is limited since they may undergo acyl substitution, hydrolysis or reduction. Reagents used for the preparation of esters in the presence of EtgN or pyridine are AcjO, AC2O-DMAP (note that DMAP increases the rate of acylation of alcohols with AcjO by a factor of 10" ), PhCOCl, (PhC0)20, and r-BuCOCl (pivaloyl chloride)." Deprotection of esters is usually done under basic conditions. ... 

We reported earlier that the presence in a molecule of phosphodiester units does not interfere with the next 0-phosphoryIation step by means of the H-phosphonate method (i.e., P-protection for phosphodiesters is not required). Indeed, compound 40 (containing a phosphodiester at 0-6" ) was successfully phospholipidated (Scheme 6) by pivaloyl chloride assisted reaction with the acylalkylglyceiyl hydrogenphosphonate 7 followed by oxidation (in situ) with iodine to provide the fully protected oleic ester GPI [Sp = -1.4 and -1.2 (0.5 P each),... 

The pivaloyl (trimethylacetyl) protecting group has been used in nucleoside chemistry [52, 109]. Presumably due to its bulky size, pivaloyl chloride showed appreciable selectivity in its reaction with thymidine in pyridine solution and crystalline 5 -0-pivaloylthymidine could be isolated from the products in 82% yield [109]. In the same way, 2 -0-tetrahydropyranyl-5 -0-pivaloyluridine (52 R = H), a useful intermediate in oligoribonucleotide synthesis, was prepared from 2 -0-tetra-hydropyranyluridine in satisfactory yield [52]. As pivalate esters are comparatively stable to NHs/MeOH [52], deacetylation is possible in the presence of pivaloyl groups thus (52 ... 

R = Ac) was converted into (52 R = H) in good yield [52]. The pivaloyl protecting group may be removed by alkaline hydrolysis [52, 109] or with MeNH2 in aqueous or aqueous alcoholic solution [52]. 1-Adamantoyl chloride (53) shows similar selectivity in its reactions with deoxyribonucleosides, and the esters obtained are again comparatively resistant to alkaline hydrolysis [110]. 

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