Total synthesis of prostaglandin F2alpha using nickel-catalyzed stereoselective cyclization of 1,3-diene and tethered aldehyde via transmetalation of nickelacycle with diisobutylaluminum acetylacetonate.
Total synthesis of prostaglandin F2alpha utilizing a nickel(0)-catalyzed cyclization of 1,3-diene and tethered aldehyde was achieved. The cyclization proceeded via a transmetalation of nickelacycle with diisobutylaluminum acetylacetonate (iBu2-ALAC). Thus, the reaction of 19, having a side chain corresponding to the alpha-chain in PGF2alpha with Ni(cod)2 (10 mol %), PPh3 (20 mol %), and 1,3-cyclohexadiene (25 mol %) in the presence of iBu2-ALAC (1.5 eq) proceeded stereoselectively to give the cyclized product 26 in 54% yield. During the cyclization of 19, the Z-olefin at C-5 in the side chain completely retained its geometry, and the four contiguous chiral carbon centers in PGF2alpha were stereoselectively constructed. Transformation of the key intermediate 19 into PGF2alpha was successfully achieved.
Sato
Y
Y
Graduate School of Pharmaceuitical Sciences, Hokkaido University, Sapporo, Japan.
Taknioto
M
M
Mori
M
M
D000447:Aldehydes / Q000737:chemistry*; D000466:Alkadienes / Q000737:chemistry*; D002384:Catalysis; D003500:Cyclization; D015237:Dinoprost / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D009532:Nickel; D009942:Organometallic Compounds / Q000737:chemistry; D013237:Stereoisomerism
D000447:Aldehydes; D000466:Alkadienes; D007202:Indicators and Reagents; D009942:Organometallic Compounds; C421544:diisobutylaluminum acetylacetonate; D009532:Nickel; D015237:Dinoprost