Enantioselective Synthesis of Cyclic Amides and Amines through Mo-Catalyzed Asymmetric Ring-Closing Metathesis

First, an efficient method for the synthesis of optically enriched N-fused bicyclic structures is
reported. Through Mo-catalyzed desymmetrization of readily available achiral polyene substrates, 5,6-,
5,7-, and 5,8-bicyclic amides can be synthesized in up to >98% ee. The effects of catalyst structure, olefin
substitution, positioning of Lewis basic functional groups and ring size are examined and discussed in
detail. In the second phase of investigations, a catalytic asymmetric method for highly enantioselective (up
to 97% ee) synthesis of small- and medium-ring unsaturated cyclic amines is reported; optically enriched
products bear a secondary amine or a readily removable Cbz or acetamide unit. Regio- and diastereoselective functionalizations of olefins within the optically enriched amine products have been carried out.
Both catalytic asymmetric methods include transformations that lead to the formation of trisubstituted as
well as disubstituted cyclic alkenes. The protocols outlined herein afford various cyclic amines of high
optical purity; such products are not easily accessed by alternative protocols and can be used in
enantioselective total syntheses of biologically active molecules.