Intramolecular Cycloaddition/Rearrangement of Alkylidenecyclopropane Nitrones from Palladium(0)-Catalyzed Alkylation of Amino Acid Derivatives

Abstract

Several alkylidenecyclopropanes have been synthesized in high yields and optical purity by palladium(0)-catalyzed substitution of 1-tosyloxy-1-vinyl cyclopropane using N-tosylamino esters or glycolic ester as nucleophiles. The new alkylidenecyclopropanes were transformed to the corresponding nitrones without loss of optical purity, except in the case of the phenylglycine derivative. The alkylidenecyclopropane nitrones underwent smooth in situ intramolecular cycloaddition with a stereoselectivity that was moderate with most substituted substrates, but complete with phenylglycine and proline derivatives. The spirocyclopropane isoxazolidines were transformed by selective thermal rearrangements in octahydro-2H-pyrrolo[3,4-b]pyridin-7-ones and octahydrofuro[3,4-b]pyridin-7-one, uncommon ring systems resembling biologically active natural and nonnatural products. An example of the extension of the process to an alkylidenecyclopropane nitrile oxide is also reported.