Formal total synthesis of (-)-taxol through Pd-catalyzed eight-membered carbocyclic ring formation
Sho Hirai1, Masayuki Utsugi, Mitsuhiro Iwamoto
1Department of Chemistry and Biochemistry, School of Advanced Science and Engineering, Waseda University, 3-4-1 Ohkubo, Shinjuku-ku, Tokyo 169-8555 (Japan), Fax: (+81) 3-5286-3240.
Abstract:
A formal total synthesis of (-)-taxol by a convergent approach utilizing Pd-catalyzed intramolecular alkenylation is described. Formation of the eight-membered carbocyclic ring has been a problem in the convergent total synthesis of taxol but it was solved by the Pd-catalyzed intramolecular alkenylation of a methyl ketone affording the cyclized product in excellent yield (97 %), indicating the high efficiency of the Pd-catalyzed intramolecular alkenylation. Rearrangement of the epoxy benzyl ether through a 1,5-hydride shift, generating the C3 stereogenic center and subsequently forming the C1-C2 benzylidene, was discovered and utilized in the preparation of a substrate for the Pd-catalyzed reaction.
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