Catalytic Z-selective cross-metathesis in complex molecule synthesis: a convergent stereoselective route to disorazole C1.
- Author(s): Speed, Alexander WH
- Mann, Tyler J
- O'Brien, Robert V
- Schrock, Richard R
- Hoveyda, Amir H
- et al.
Published Web Locationhttps://doi.org/10.1021/ja509973r
A convergent diastereo- and enantioselective total synthesis of anticancer and antifungal macrocyclic natural product disorazole C1 is reported. The central feature of the successful route is the application of catalytic Z-selective cross-metathesis (CM). Specifically, we illustrate that catalyst-controlled stereoselective CM can be performed to afford structurally complex Z-alkenyl-B(pin) as well as Z-alkenyl iodide compounds reliably, efficiently, and with high selectivity (pin = pinacolato). The resulting intermediates are then joined in a single-step operation through catalytic inter- and intramolecular cross-coupling to furnish the desired 30-membered ring macrocycle containing the critical (Z,Z,E)-triene moieties.