Catalytic Z-selective cross-metathesis in complex molecule synthesis: a convergent stereoselective route to disorazole C1.
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.
Department of Chemistry, Merkert Chemistry Center, Boston College , Chestnut Hill, Massachusetts 02467, United States.
Alexander W H
AW
Speed
Tyler J
TJ
Mann
Robert V
RV
O'Brien
Richard R
RR
Schrock
Amir H
AH
Hoveyda
D002384:Catalysis; D060326:Chemistry Techniques, Synthetic; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry*; D010080:Oxazoles / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism; D013379:Substrate Specificity
D018942:Macrolides; D010080:Oxazoles; C436383:disorazole C1