Stereoselective synthesis of 9-trans-9-desmethyl-9-fluororetinals based onthe four-components coupling approach

9-trans-9-Desmethyl-9-fluororetinal analogs were synthesized by the four-co mponents coupling approach. Horner-Emmons olefination of 3 afforded the und esired 2E-isomer 5 which was transformed to 6E-triene 8 via the Stille coup ling reaction. Isomerization of 6E-triene 8 with an iodine catalyst proceed ed in a highly regioselective manner to give the 6Z-isomer 9. Wittig reacti on of 13 derived from oxidation of 9 followed by reduction and oxidation pr ovided 13-cis-9-desmethyl-9-fluororetinal 17. The 13-cis-analog 17 was regi oselectively converted to the all-trans-isomer 19 by treatment with trifluo roacetic acid. (C) 1999 Elsevier Science Ltd. All rights reserved.