1994 Merck Frosst Award Lecture New strategies for the stereoselective synthesis of natural and unnatural products via organometallic reagents and catalysts

Samarium in the presence of diiodomethane selectively cyclopropanates an allenic alcohol to yield a methylenecyclopropane with modest to excellent diastereoselectivity. The effect of substituents at the carbinol carbon and the allenic carbon on the diastereoselectivity was investigated. A palladium catalyst was shown to promote the intramolecular cycloaddition of the methylenecyclopropane with an electron-deficient alkyne to yield a methylenecyclopentane. The reaction was stereospecific with retention of stereochemistry as proven by X-ray diffraction. Nickel catalysts accelerate the hydroalumination of oxabicyclo[3.2.1]alkenes, leading to bicyclic trialkylalanes. Upon treatment with a Lewis acid (diisobutylaluminum chloride), the trialkylalanes fragment to provide cycloheptenols. This reaction, followed by an enantioselective enzyme-catalyzed esterification, was used as a key step in a synthesis of the mevinic acid lactone.