A step-economical synthesis of clinprost is reported that concludes with 3 different transition metal-catalyzed reactions: Pd-catalyzed decarboxylation with allylic rearrangement, Rh-catalyzed diene-ene [2+2+1] reaction, and Ru-catalyzed cross-metathesis reaction. The complexity bestowed to the molecule from these reactions converts a readily accessible ester to clinprost without using protecting groups in only 9 total steps.

Dienoic acids and pentadienyl alcohols are coupled in a decarboxylative and dehydrative manner at ambient temperature using Pd(0) catalysis to generate 1,3,6,8-tetraenes. Contrary to related decarboxylative coupling reactions, an anion-stabilizing group is not required adjacent to the carboxyl group. Of mechanistic importance, it appears that both the diene of the acid and the diene of the alcohol are required for this reaction. To further understand this reaction, substitutions at every unique position of both coupling partners was examined and two potential mechanisms are presented.

Experiments reported in Part III1 of this series have resulted in the elucidation of the structure and configuration of a monotoluenesulfonyl anhy-drohexitol2 which has been shown to represent the 1-p-toluenesulfonyl2,5-anhydro-L-iditol (I). However, we have been unable to prepare the 2,5anhydro-L-iditol from this derivative by hydrolysis, or from the 1,6-diiodo derivative in the usual manner.

Sequential Pd(0)-, Rh(I)-, and Ru(II)-Catalyzed Reactions in a Nine-Step Synthesis of Clinprost (X). -(NAGY, E. E.; HYATT, I. F. D.; GETTYS, K. E.; YEAZELL, S. T.; FREMPONG, S. K. J.; CROATT*, M. P.; Org. Lett. 15 (2013) 3, 586-589, http://dx.