A comprehensive survey of Stille-type Csp2-Csp2 single bond forming processes in the synthesis of retinoic acid and analogs

The synthesis of the retinoid skeleton has been exhaustively explored using the Stille coupling for the formation of the side-chain single bonds. On employing the experimental catalytic conditions developed by Farina [Pd-2(dba)(3), AsPh3, NMP] we have modified the electronic and steric requirement of the coupling partners, alkenyl stannanes and electrophiles (alkenyl iodides and triflates). The comprehensive survey afforded appropriately matched components for every bond formation considered. Moreover, from the comparison of the reactivities of different coupling partners with different degrees of steric hindrance, the sensitivity of the Stille coupling to steric effects was confirmed. Besides providing a variety of building blocks for retinoid synthesis, the study highlights some vends that might be useful for the application of the Stille reaction to the synthesis of unsubstituted conjugated polyenes. (C) 1999 Elsevier Science Ltd. All rights reserved.