Stereoselective synthesis of 9-cis-retinoic acid by Suzuki reaction

The entire polyenic side chain of ethyl 9-cis-retinoate (7) has been stereo selectively synthesized and attached to the hydrophobic ring by a high-yiel ding thallium-accelerated Suzuki cross-coupling reaction. The Suzuki reacti on partners, tetraenyl iodide 18 and alkenyl organoborane 19, are more conv eniently used immediately after generation from their precursors. Alternati ve approaches using either the Stille reaction or a Suzuki reaction with a shorter polyenic component proved less efficient. The highly convergent seq uence can be adapted to the preparation of analogs of 9-cis-retinoic acid ( 2), the natural ligand for the retinoid X (RXR) subfamily of nuclear recept ors. (C) 1999 Published by Elsevier Science Ltd. All rights reserved.