Stereoselective preparation of trisubstituted (Z)-alkenes;: synthesis of the C17-C27 fragment of (-)-laulimalide

A Ni-catalyzed cross-coupling reaction of (Z)-5-(tert-butyldiphenylsilyl)oxy-3-bromo-1-trimethylsilyl-3-penten-1-yne (1) with alkyl Grignard reagent gives (Z)-3-alkyl-5-(tert-butyldiphenylsilyl)oxy-1-trimethylsilyl-3-penten-1-ynes (2) stereospecifically in good yields. The (Z)-enyne 2a is transformed in four steps to (Z)-3-methyl-5-silyloxy-3-pentenaI (3), which is coupled with ketophosphonate 4 to give enone 13. The eta-hydroxyallyl methanesulfonate derived from 13 is cyclized to 3,6-dihydro[2H]pyran by an intramolecular SN2' reaction stereoselectively, furnishing a C17-C27 carbon unit of (-)-laulimalide. (C) 2005 Elsevier Ltd. All rights reserved.