Pivaloyl group alcohol protection

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. 

An intermediate in the synthesis of laulimalide by Davidson8 illustrates the differential protection of alcohols. The starting materials 56 and 57 already have an alcohol protected as a TBDMS silyl ether and a diol protected as an acetal. The alcohol in 58 is protected as a p-methoxybenzyl ether and the acetal hydrolysed by acetal exchange to give the free diol 60. Selective protection of the primary alcohol by a bulky acyl group (pivaloyl, i-BuCO ) 61 allows silylation of the secondary alcohol with a TIPS group 62. Finally the pivaloyl group is selectively removed by DIBAL reduction to release just one free alcohol 63. 

Cyclic sulfonamides can also be prepared via intramolecular Mizoroki-Heck reaction starting from pyrrolidine derivatives [124], Evans [125] showed that alcohol 171, under standard Mizoroki-Heck conditions, gave a 50 50 mixture of regioisomers 172 and 173 resulting from an unselective 6-exo-cyclization at both the 3- and 4-positions (Scheme 6.49). If protected alcohol 174 is used, more 4-isomer 175 was obtained, probably due to the sterically demanding pivaloyl group. 

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 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. ... 

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,... 

The first step was an aldol-Iike reaction of the enolate of 437 with 4-(t-butyldiphenylsilyloxy)butanal where a separable mixture of the two diastereomers 438 and 439 was obtained. Diastereomer 438 could be converted through an oxidation-reduction strategy into the other conformer 439, which was achieved in 74% yield (438 13%). hi order to protect the secondary alcohol group with MOM-chloride, it was necessary to deprotect the primary alcohol group and then reprotect it with pivaloyl chloride, with 440 being obtained. The reaction of MOM-chloride with 439 was rather slow and the desired MOM-ether was only sustained in low yields. After having obtained compound 441, Jones oxidation led to a carboxylic acid, which was directly esterified to 442. Dieckmann cyclization followed by protection with TBSOTf afforded a separable diastereomeric mixture of the tricyclic compound, with 443 as the major product (Scheme 8.11). 

When the mixed anhydride between 4-ethyl-4-pentenoic acid and pivalic acid (prepared using pivaloyl chloride on the pentenoic acid) was treated with the lithium salt of (i )-4-benzyl-2-oxazolidinone an imide was formed where one (the bottom as drawn) face is encumbered by the bulky benzyl group. Thus, cyanoeth-ylation occurred with diastereoselectivity, and a single isomer was isolated. Reduction of the imide with sodium borohydride (NaBU,) then resulted in the formation of the primary alcohol, and the latter was protected as the f-butyldiphenylsilyl (TBDPS)... 

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