Stereoselective synthesis of trienoic acids: Synthesis of retinoic acids and analogues

Stereoselective construction of conjugated trienoic acids was achieved through two successive Stille reactions, the first step consisting of the coupling of (E)- 1,2-bis(tributylstannyl)ethene and tributylstannyl (Z)- or (E)-3-iodoalk-2-enoates. Two different routes were used for the second step: (1) cross-coupling of the stannyldienoic acid reagents and vinyl iodides, or (2) cross-coupling of vinylstannane reagents and the tributylstannyl 5-iodopenta-2,4-dienoates generated by iododestannylation of stannyldienes. Vinyl-stannanes synthesized by stannylmetalation of the Negishi dienyne derived from beta- or alpha-ionone and safranal thus provided access to stereodefined retinoic acids. Some retinoid and yne analogues were also prepared by Sonogashira coupling.