Claisen reaction ring size

In the simple Claisen rearrangement of cyclopentanonc, cyclohexanone and cycloheptanonc, the xyn/anti ratio depends on the ring size and the reaction time. The initially observed diastereoselectivity drops with the progress of the reaction due to enolization of the cycloalka-none product, especially for the cyclopentanone derivative (Table 18, entries 1-3)522. The predominant s-yn-diastereomers arise from the chairlike transition state 3A. 

A computational study of ring size effect on the Bellus-Claisen rearrangement shows the reaction to have a high asynchronous character (Scheme 13)7 ... 

An intramolecular version of this Claisen rearrangement was used for the synthesis of a natural 10-membered lactone, phoracantholide J (8). The synthesis involves preparation of 6 by known reactions. Treatment of 6 with C MsSeBr in the presence of Hiinig s base gives the cyclic acetal 7 as a mixture of diastereoisomers in 71% yield. Decomposition of the selenoxide results in the rearranged y,B-unsaturated lactone 8 as the major product. The ready formation of a 10-membered ring is noteworthy because yields of rings of this size are low on lactonization of 0-hydroxy acids. 

In some cases, there is a competition within a molecule for closure to rings of different sizes. If the closure is an irreversible reaction such as alkylation of an enolate, kinetic control may allow three-membered ring closure to predominate over five-membered as in Equation 8.17 [27]. The electrophilic carbon closer to the nucleophilic site is found first, in spite of the incorporation of ring strain. With reversible reactions, the thermodynamic product predominates. That is, the low strain five- or six-membered rings whl form to the exclusion of three- or four-membered alternatives (Scheme 8.13). In Claisen and aldol cychzations, five- and six-membered rings are not in competition with each other. Seven-membered rings may sometimes be closed readily without high dilution (Eq. 8.18) [28]. 

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