Pestalotiopsin A. Side Chain Installation and Exhaustive Probing of Olefin Metathesis as a Possible Tool for Elaborating the Cyclononene Ring

A program directed toward an asymmetric synthesis of pestalotiopsin A is described. The routing begins with the dextrorotatory cyclobutanol 37, which is combined with the enantiomerically defined building blocks ent-15 and 16. These units are incorporated via stereocontrolled 1,2-nucleophilic addition and anti-aldol coupling, respectively. With these straightforward reactions accomplished, the sequel involved the introduction of terminal double bonds in anticipation of the fact that the (E)-cyclononene substructure could be realized by ring-closing metathesis. This central issue was evaluated with several diene substrates and catalysts, all to no avail. Cross-metathesis experiments involving 59 and 65 with the functionalized heptene 60 revealed a marked difference in the inability to engage interaction with the ruthenium catalyst. This awkwardness could not be skirted.