Cyclopentene and Cyclohexene Annulation via Copper-Catalyzed Conjugate Addition of Acetal-Containing Grignard Reagents

Article abstract of DOI:10.1021/jo00147a001

The Grignard reagents 2 derived from 2-(bromoethyl)- and 2-(3-chloropropyl)-1,3-dioxolane undergo conjugate addition to a number of α,β-unstaurated ketones in the presence of a catalytic amount of a cuprous salt.The resulting keto acetals, upon treatment with hydrochloric acid, undergo sequential hydrolysis, intramolecular aldol condensation, and dehydration to give cyclopentene and cyclohexene annulation products.The entire series of reactions, starting with the conjugate addition, may be performed as a one flask experiment leading to direct formation of thecyclization products.The Grignard reagents may also be alkylated with epoxides or acylated with an acid chloride to give intermediates that may be converted into cyclic products by pathways related to those above.