New synthetic applications of organotin compounds: Synthesis of stereodefined 2-iodo-2-alkenones, 2-substituted (E)-2-alkenones and 2-methyl-2-cycloalkenones

Article abstract of DOI:10.1016/S0040-4020(01)81297-7

Stereoisomeric mixtures of 3-iodo-3-nonen-2-one, 8a, 2-iodo-1-phenyl-2-octen-1-one, 8b, 2-iodo-1,3-diphenyl-2-propen-1-one, 8c, as well as (Z)-3-iodo-4-phenyl-3-buten-2-one, 8d, have been efficiently synthesized by a reaction sequence involving a Pd-catalyzed reaction between the corresponding 1-alkynyl ketones, 10, and Bu₃SnH followed by iododestannylation. Stereomutation experiments carried out in the presence of daylight and using catalytic amounts of I₂ showed that the Z stereoisomers of 8a, 8b and 8c, which could be separated by MPLC on silica gel from the corresponding E stereoisomers, as well as compound (Z)-8d were more stable than their E stereoisomers. Compounds 8a-d underwent Pd-catalyzed cross-coupling reactions with C₆H₅SnMe₃, CH₂=CH-SnBu₃ and SnMe₄ providing an efficient route to the corresponding 2-substituted 2-alkenones, 13. However, the Pd-catalyzed reaction between (Z)-8c and PhSnMe₃ afforded a mixture of the expected cross-coupled product, (E)-13f with the compound derived from methyl transfer, (E)-13e. The couplings involving (Z)-8a, (Z)-8b, (Z)-8c and (Z)-8d proceeded with clean retention of stereochemistry, but the Pd-catalyzed reaction between (E)-8c and SnMe₄ afforded a stereoisomeric mixture of 13e. On the contrary, the coupling between (E)/(Z)-8b and SnMe₄ produced stereoisomerically pure (E)-13c. Two 2-iodo-2-cycloalkenones, i.e. compounds 18a and 18b, also reacted with SnMe₄, in the presence of a Pd catalyst, to give the corresponding 2-methyl-2-cycloalkenones, 19a and 19b, respectively, in satisfactory yields. Compound 19b represents a very useful precursor to methylenomycin B, 9.