Hydroxy-Directed Diastereoselective Installation of a Methyl Group on Indalone Models and Spiroketal Potential Precursors for the Bafilomycin A1 C15−C25 Subunit

• Published in: Journal of organic chemistry 2002-04, Vol.67 (7), p.2118-2124
• Main Authors: Poupon, Jean-Christophe, Lopez, Roman, Prunet, Joëlle, Férézou, Jean-Pierre
• Format: Article
• Language: English
• Subjects: Chemistry; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives; Organic chemistry; Preparations and properties
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo016231l

Current efforts devoted to the synthesis of Bafilomycin A1 led us to investigate a synthetic route through a spiroketal intermediate for the construction of the C15−C25 subunit. Preliminary studies for the diastereoselective installation of the methyl-16 cis with respect to the vicinal OH-15 group through radical opening of either siloxafuran intermediate 7 or cyclopropyl compounds 9 and 13 have been carried out using model compounds derived from commercial Indalone 6. In each case the expected "cis" diastereoisomer was obtained in good to excellent yield. Application of these results to Bafilomycin A1 synthon led to the opposite "trans" stereoselectivity when α-carboxy- or α-keto-substituted spiroketals 4 or 19 were used. However, the expected potential intermediate has been obtained from the α-hydroxymethyl cyclopropanated synthon 21. A Barton−Motherwell xanthate radical deoxygenation−cylopropane opening methodology, followed by a hydroboration−oxidation of the exovinylic intermediate, delivered the expected product 22 cis in high yield and excellent stereoselectivity.