Asymmetric Synthesis with Medium-Sized Rings

4 Asymmetric Synthesis with Medium-Sized Rings 

In contrast to the selectivities observed for the cyclooctanones, alkylation of the nine- or ten-membered ring ketones affords nearly 1 1 mixtures of cis and trans stereoisomers [3]. The alkylation reactions of enolates derived from medium-sized lactones, however, are notable. The series of methyl-substituted lactones from the nine-membered (27) through to the 1.3-membered (30) rings all show a strong preference for cis substitution (Equation 1) [3]. 

Notable diastereoselectivity was observed in the conjugate addition of Me2CuLi to cyclooctenone 35, which afforded the trans product 26 with 99 1 dr (Equation 2) [3]. Thus, enolate alkylation provides cis products (cf. 20— 25) with a stereochemical pattern complementary to that observed in conjugate additions (35— 26). 

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