Hypervalent Iodine(III)-Promoted Intermolecular C-C Coupling of Vindoline with β-Ketoesters and Related Substrates

The regioselective intermolecular coupling reaction of vindoline with a wide range of substrates including beta-ketoesters, beta-diketones, beta-ketoaldehydes, beta-ketonitriles, malononitriles, and beta-cyanoesters provides an opportunity for the synthesis of vinblastine analogues containing deep-seated changes in the upper velbanamine subunit The transition-metal-free hypervalent iodine(III)-promoted intermolecular sp(3)/sp(2) coupling, representing a special class of selective C-H activation with direct carbon carbon bond formation, proceeds with generation of a quaternary center capable of incorporation of the vinblastine C16' methyl ester and functionalized for subsequent divergent heterocycle introduction.