Esters Cleaved by -Elimination Reactions

Esters Cleaved by -Elimination Reactions 437 6.5.3 2-Tosylethyl Esters and Related Base-Labile Groups... 

Hydrolysis. Esters are cleaved (hydroly2ed) into an acid and an alcohol through the action of water. This hydrolysis is cataly2ed by acids or bases. The mechanistic aspects of ester hydrolysis have received considerable attention and have been reviewed (16). For most esters only two reaction pathways are important. Both mechanisms involve a tetrahedral intermediate and addition-elimination reactions i7i7... 

The reaction proceeds by an Ei-mechanism. The /3-hydrogen and the carboxy-late are cleaved synchronously from the substrate molecule, while forming a new bond. This elimination reaction belongs to the class of -eliminations in the case of the ester pyrolysis, the substrate molecule passes through a six-membered cyclic transition state 4 ... 

The use of picolinic and 6-methylpicolinic acids in a Mitsunobu reaction has been advocated because the resultant esters are readily cleaved by copper(II) (Scheme 22.6). The advantage is that ester cleavage occurs under neutral conditions, which minimizes the risk of elimination even with base-sensitive systems.9... 

Winterfeldf s synthesis of brefeldin A (Scheme 1.36) also entailed use of a Michael addition in an anti fashion to a 4-substituted cyclopentenone. Dithiane anion 217 was added in a 1,4 sense to enone 216 to give, after elimination of acetic acid, cyclopentenone 218. Addition of cuprate 219 to 218 in the expected anti manner cleanly afforded the trans cyclopentane 220. Hydride reduction gave the unnatural P-alcohol, which was inverted by a Mitsunobu reaction and the resulting ester cleaved to the desired a-alcohol 221. Protection of the alcohol... 

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