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 () with alkyl Grignard reagent gives (Z)-3-alkyl-5-(tert-butyldiphenylsilyl)oxy-1-trimethylsilyl-3-penten-1-ynes () stereospecifically in good yields. The (Z)-enyne is transformed in four steps to (Z)-3-methyl-5-silyloxy-3-pentenal (), which is coupled with ketophosphonate to give enone . The η-hydroxyallyl methanesulfonate derived from is cyclized to 3,6-dihydro[2H]pyran by an intramolecular SN2′ reaction stereoselectively, furnishing a C17–C27 carbon unit of (−)-laulimalide.