Neighboring Group Effects in Intramolecular Aldol Condensations. Rate Enhancement by gamma Substituents(1).
The O-acetyl dieneol 1b, obtained from the Grignard addition of 2-(2-bromoethyl)-1,3-dioxolane to 2,4-hexadienal via 1a, and followed by an acetylation, was treated with maleic anhydride to give the crystalline Diels-Alder adduct 2b with good stereoselectivity. The acetal of 2b was selectively hydrolyzed to the acetoxy aldehyde 3b. This was treated with potassium hydride in tetrahydrofuran. A stereoselective intramolecular Aldol reaction resulted in the formation of the tricyclic lactone 4b. However, attempts to achieve an Aldol condensation under similar reaction conditions with the analogous aldehyde 3c, lacking the acetoxy group, failed, giving back the starting material 3c. On the other hand, the methoxy aldehyde 3d was cyclized to the tricyclic compound 4d.
Eberle
Marcel K.
MK
Preclinical Research, Sandoz Ltd., 4002 Basel, Switzerland.