TOTAL SYNTHESES OF (-RICINELAIDIC ACID LACTONE AND OF (-)-GLOEOSPORONE BASED ON TRANSITION-METAL-CATALYZED C-C BOND FORMATIONS())

Total syntheses of the macrolides (R)-(+)-ricinelaidic acid lactone (6 ) and (-)-gloeosporone (7), a fungal germination self-inhibitor, are p resented, which are distinctly shorter and more efficient than any of the previous approaches to these targets reported in the literature. B oth of them benefit from the remarkable ease of macrocyclization of 1, omega-dienes by means of ring-closing olefin metathesis (RCM) using th e ruthenium carbene la as catalyst precursor. The diene substrates are readily formed via the enantioselective addition of dialkylzinc reage nts to aldehydes in the presence of catalytic amounts of Ti(OiPr)(4) a nd bis-triflamide 18 and/or the stereoselective allylation of aldehyde s developed by Keck et al, using allyltributylstannane in combination with a catalyst formed from Ti(OiPr)(4) and (S)-(-)-1,1'-bi-2-naphthol . Comparative studies show this latter procedure to be more practical than the stoichiometric allylation reaction employing the pha',alpha'- tetraaryl-1,3-dioxolane-4,5-dimethanol complex 3b. Finally, a method f or the efficient ring closure of 4-pentenoic acid esters by RCM is pre sented that relies on the joint use of la and Ti(OiPr)(4) as a binary catalyst system. These results not only expand the scope of RCM to pre viously unreactive substrates but also provide additional evidence for the important role of ligation of the evolving ruthenium carbene cent er to a polar relay substituent on the substrate which constitutes the necessary internal bias for the RCM-based macrocyclization process.