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Catalytic Z-selective cross-metathesis in complex molecule synthesis: a convergent stereoselective route to disorazole C1.

Research paper by Alexander W H AW Speed, Tyler J TJ Mann, Robert V RV O'Brien, Richard R RR Schrock, Amir H AH Hoveyda

Indexed on: 08 Nov '14Published on: 08 Nov '14Published in: Journal of the American Chemical Society



Abstract

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.