Stereocontrolled synthesis of 6-s-cis- and 6-s-trans-locked 9Z-retinoids by hydroxyl-accelerated Stille coupling of (Z)-tri-n-butylstannylbut-2-en-1-ol and bicyclic dienyl triflates.
Analogues of 9-cis-retinoic acid with locked 6-s-cis and 6-s-trans conformations have been stereoselectively synthesized using a Stille coupling reaction between bicyclic dienyl triflates (5and 6, respectively) and (Z)-tributylstannylbut-2-en-1-ol (7) to stablish the Z geometry of the polyenic side chain. The mild conditions (25 degrees C, 30 min) of this coupling stand in contrast to the reluctance of the isomeric (E)-tributylstannylbut-2-en-1-ol (18) to react with triflates 5/6. The significant rate differences experimentally observed in Stille reactions between isomeric (Z)- and (E)-tri-n-butylstannylalkenols in favor of the former isomer, even with highly hindered alkenyl triflates, is ascribed to internal coordination of palladium to the heteroatom in the presumably rate-limiting transmetalation step. Dienals and trienals with an E geometry, which are not efficiently available by direct coupling of the corresponding triflates and E-stannanes, can in turn be obtained by isomerization of their Z-isomers.
Domínguez
B
B
Departamento de Química Orgánica, Universidade de Vigo, 36200 Vigo, Spain.
Pazos
Y
Y
de Lera
A R
AR
D000077556:Alitretinoin; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D009682:Magnetic Resonance Spectroscopy; D010165:Palladium; D012176:Retinoids / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D014212:Tretinoin / Q000737:chemistry*
D001643:Bridged Bicyclo Compounds; D012176:Retinoids; D000077556:Alitretinoin; D014212:Tretinoin; D010165:Palladium