Fully stereocontrolled syntheses of 3-oxacarbacyclin and carbacyclin by the conjugate addition-azoalkene-asymmetric olefination strategy.
A fully stereocontrolled synthesis of 3-oxacarbacyclin (3) and a formal synthesis of carbacyclin (2) are described. The syntheses are based on the conjugate addition-azoalkene-asymmetric olefination strategy. Its key features are (1) the stereoselective establishment of the complete omega-side chain of 2 and 3 through conjugate addition of the enantiopure C13-C20 alkenylcopper derivative 10 to the enantiopure C6-C12 bicyclic azoalkene 9 and (2) the 5E-stereoselective construction of the alpha-side chain through a Horner-Wadsworth-Emmons olefination of the bicyclic ketone 7 with the chiral lithium phosphonoacetate 26 with formation of ester E-27. The allylic alcohol 6 serves at late stage as the joint intermediate in the synthesis of 2 and 3.
Kim
Mikhail
M
Institut für Organische Chemie der Rheinisch-Westfälischen Technischen Hochschule Aachen, Landoltweg 1, D-52056 Aachen, Germany.
Gais
Hans-Joachim
HJ
D000475:Alkenes; D000478:Alkylation; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D013237:Stereoisomerism
C519732:3-oxacarbacyclin; D000475:Alkenes; C026678:carboprostacyclin; D011464:Epoprostenol