Catalytic Z‑Selective Cross-Metathesis in Complex Molecule Synthesis: A Convergent Stereoselective Route to Disorazole C1

ABSTRACT: A convergent diastereo- and enantioselec-tive 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 illus-trate 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. We recently introduced a direct method for preparation ofalkyl- and aryl-substituted Z-(pinacolato)alkenylboron [alkenyl−B(pin)] compounds through catalytic stereoselectiv