Pergamon Tetrahedron: Asymmetry 10 (1999) 193–206 TETRAHEDRON: ASYMMETRY Studies towards the total synthesis of taxoids: a rapid entry into bicyclo[6.4.0]dodecane ring system. Part 2 Siméon Arseniyadis, * Maria del Rosario Rico Ferreira, José Quilez del Moral, José Ignacio Martin Hernando, Nicolas Birlirakis and Pierre Potier Institut de Chimie des Substances Naturelles, CNRS, F-91198 Gif-sur-Yvette, France Received 13 November 1998; accepted 9 December 1998 Abstract We report a synthetic route that allows access into A-seco taxoid frameworks embodying the entire carbon skeleton and a large number of oxygen functionalities. The BC-subunit (-)-4 was constructed in five steps from (+)-3, through a step-efficient and stereocontrolled bond construction. © 1999 Elsevier Science Ltd. All rights reserved. 1. Introduction Recently, we have published a synthetic approach of the taxoid BC-subunit, which served the dual purpose of elucidating the stereochemistry of our aldol–annelation–fragmentation methodology and pro- viding adequate material for further transformations. 1 We thus described the development of a synthetic strategy for advanced taxoid substructures such as (+)-3, establishing the feasibility of incorporating all of the 20 carbons and of essential oxygen functionalities of the taxoid 2 diterpene skeleton I in 12 steps starting from two achiral aldol partners 1 and 2. With the efficient synthesis of the bicyclo[6.4.0]dodecane ring system (+)-3 realized, the stage was now set for the completion of the synthesis. So, we went on to prepare the more advanced intermediates represented by formulas II, III and IV, precursors of taxoid ABC-tricyclic core of type I, which incorporate ring A in its seco form. An elementary retrosynthetic analysis (Scheme 1; P stands for ketal protection) of I would suggest two routes to achieve C11–C12 bond formation: samarium iodide 3 induced reductive coupling for precursors of types II and III, and either samarium iodide coupling or aldol chemistry for precursor IV. Key questions at this stage include the likelihood of obtaining chemoselectivity in epoxide-ring opening and the nature of functional group interconversion to be chosen en route towards one of the targeted A-seco taxoid frameworks of type II, III or IV for final ring closing (C11–C12). * Corresponding author. Fax: +33 169-077-247; e-mail: simeon.arseniyadis@icsn.cnrs-gif.fr 0957-4166/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved. PII: S0957-4166(98)00491-1