Intramolecular alkylation of of α,β-unsaturated ketones: a study of the effect of substrate structure and experimental conditions on the site of alkylation

The syntheses of 4a-(3-chloropropyl)- (22), 4a-(3-iodopropyl)- (23), and 4a-mesyloxymethyl-4,4a,5,6,7,8-hexahydro-2(3H)-naphthalenone (24) are described. The results obtained from the intramolecular alkylation of each of these compounds under a variety of experimental conditions are summarized in Tables 1 and 2. It was found that alkylative cyclization of compounds 22 and 23 gave varying amounts of two products, one (34) resulting from α′ alkylation and the other (35) being derived from α alkylation. In contrast, intramolecular alkylation of the enone 24 produced only the γ alkylation product 11, or afforded a mixture of 11 and the α alkylation product 41. The intramolecular alkylation results are discussed in terms of Scheme 5.