Design and stereoselective preparation of a new class of chiral olefin metathesis catalysts and application to enantioselective synthesis of quebrachamine: catalyst development inspired by natural product synthesis.

摘要: A total synthesis of the Aspidosperma alkaloid quebrachamine in racemic form is first described. key catalytic ring-closing metathesis an achiral triene used to establish all-carbon quaternary stereogenic center and tetracyclic structure natural product; transformation proceeds with reasonable efficiency through use existing Ru or Mo catalysts. Ru- Mo-based chiral olefin catalysts have proven be inefficient entirely nonselective cases where desired product observed. In present study, route thus serves as a platform for discovery new that allow efficient completion enantioselective quebrachamine. Accordingly, on basis mechanistic principles, stereogenic-at-Mo complexes bearing only monodentate ligands been designed. The provide significantly higher levels activity than observed previously reported complexes. Enantiomerically enriched alkylidenes are generated diastereoselective reactions involving bispyrrolides enantiomerically pure silyl-protected binaphthols. Such initiate step efficiently (1 mol % loading, 22 °C, 1 h, >98% conversion, 84% yield) high selectivity (98:2 er, 96% ee).