Abstract
We report detailed studies of the facile synthesis of functionalized 8-, 9-, 10-, 11-, and 15-membered-ring lactones from simple ethyl 1-allyl-2-oxocycloalkanecarboxylates, resulting from a three-atom ring enlargement. Similarly, four-atom ring enlargements of a 5- to 9- and 6- to 10-membered-ring lactones were achieved. Alkoxy radical fragmentation (ARF) with hypervalent iodine was used as the key step for these ring expansions. The ring enlargement proceeds via an unstable hemiketal intermediate, which was isolable in some cases. Where hemiketals were not isolated, molecular modeling calculations are consistent with the relative stability of hydroxy ketones vs. hemiketals. The same substrates can be diverted in an ionic pathway on reaction with iodine or bromine to afford spirolactones. The formation of spirolactones occurs in a highly stereoselective manner, apparently involving participation of the ester carbonyl group.
Keywords
spiro compounds - ring expansion - radical reaction - diastereoselectivity - lactone
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