This work describes the development of a highly enantioselective asymmetric catalysis on the intramolecular cyclopropanation of alpha-diazo-beta-keto sulfones. We have found that the catalytic asymmetric intramolecular reactions of alpha-diazo-beta-keto sulfones generally proceed with high enantioselectivity when the alpha-diazo-beta-keto mesityl sulfone is used with the newly prepared ligand 2e. The absolute configuration of products has been determined by X-ray crystallographic analysis, and the outcome of the enantioselectivities is explained well by our proposed models A and B. The products possess great potential for natural product synthesis because (1) many different chemistries of cyclopropane, ketone, and sulfone are available, and (2) the products are generally highly crystalline, facilitating the supplies of enantiomerically pure synthetic intermediates.

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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Formal total synthesis of ( ) taxol is described herein. This convergent synthesis was accomplished by utilizing two chiral fragments, both of which were prepared via asymmetric catalysis. A palladium catalyzed reaction was found to afford the eight membered ring effectively, i.e., a B alkyl Suzuki Miyaura coupling reaction and an intramolecular alkenylation of a methyl ketone successfully constructed the B ring of taxol in excellent yield. During the preparation of a substrate for the palladium catalyzed reaction, a unique rearrangement of the epoxy benzyl ether, via a 1,5 hydride shift that generates the C3 stereogenic center and subsequently forms the C1 C2 benzylidene moiety, was observed. Strenuous efforts were required for transformations after the construction of the taxane scaffold to achieve the formal total synthesis of taxol because very few approaches are available for the synthesis of the target compound.

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