Pivaloyl group protection with

Pyrrolo[2,3-/ ]pyridinones react with diethyl cyanomethanylphosphonate to give two different products, depending on the substitution pattern of the starting material. For compounds without substituents in the 2-position, pyrrolo[2,3-3]-pyridinyl acetonitriles, 55, are produced. When the nitrogen atom is protected with a pivaloyl group, alkenyl nitriles, 56, are formed (Scheme 2) <2001T1995>. 

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. 

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). 

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 ... 

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