188260-10-8Relevant articles and documents
Efficient and selective formation of macrocyclic disubstituted Z alkenes by ring-closing metathesis (RCM) reactions catalyzed by Mo- or W-based monoaryloxide pyrrolide (MAP) complexes: Applications to total syntheses of epilachnene, yuzu lactone, ambrettolide, epothilone C, and nakadomarin A
Wang, Chenbo,Yu, Miao,Kyle, Andrew F.,Jakubec, Pavol,Dixon, Darren J.,Schrock, Richard R.,Hoveyda, Amir H.
, p. 2726 - 2740 (2013/04/10)
The first broadly applicable set of protocols for efficient Z-selective formation of macrocyclic disubstituted alkenes through catalytic ring-closing metathesis (RCM) is described. Cyclizations are performed with 1.2-7.5 mol % of a Mo- or W-based monoaryloxide pyrrolide (MAP) complex at 22 °C and proceed to complete conversion typically within two hours. Utility is demonstrated by synthesis of representative macrocyclic alkenes, such as natural products yuzu lactone (13-membered ring: 73 % Z) epilachnene (15-membered ring: 91 % Z), ambrettolide (17-membered ring: 91 % Z), an advanced precursor to epothilones C and A (16-membered ring: up to 97 % Z), and nakadomarin A (15-membered ring: up to 97 % Z). We show that catalytic Z-selective cyclizations can be performed efficiently on gram-scale with complex molecule starting materials and catalysts that can be handled in air. We elucidate several critical principles of the catalytic protocol: 1) The complementary nature of the Mo catalysts, which deliver high activity but can be more prone towards engendering post-RCM stereoisomerization, versus W variants, which furnish lower activity but are less inclined to cause loss of kinetic Z selectivity. 2) Reaction time is critical to retaining kinetic Z selectivity not only with MAP species but with the widely used Mo bis(hexafluoro-tert-butoxide) complex as well. 3) Polycyclic structures can be accessed without significant isomerization at the existing Z alkenes within the molecule.
Total synthesis of (-)-epothilone A
Schinzer, Dieter,Bauer, Armin,Boehm, Oliver M.,Limberg, Anja,Cordes, Martin
, p. 2483 - 2491 (2007/10/03)
The total synthesis of (-)-epothilone A by a convergent route is reported. The synthesis of the required key intermediates has been improved with respect to stereoselectivity and availability. The access to ethyl ketone 2 has been significantly improved b
