Enantioselective Synthesis of Pyrrolidine-, Piperidine-, and Azepane-Type N-Heterocycles with α-Alkenyl Substitution: The CpRu-Catalyzed Dehydrative Intramolecular N-Allylation Approach

A cationic CpRu complex of chiral picolinic acid derivatives [(R)- or (S)-Cl-Naph-PyCOOCH2CH═CH2] catalyzes asymmetric intramolecular dehydrative N-allylation of N-substituted ?-amino- and -aminocarbonyl allylic alcohols with a substrate/catalyst ratio of up to 2000 to give α-alkenyl pyrrolidine-, piperidine-, and azepane-type N-heterocycles with an enantiomer ratio of up to >99:1. The wide range of applicable N-substitutions, including Boc, Cbz, Ac, Bz, acryloyl, crotonoyl, formyl, and Ts, significantly facilitates further manipulation toward natural product synthesis. A cationic CpRu complex of chiral picolinic acid derivatives [(R)- or (S)-Cl-Naph-PyCOOCH2CH═CH2] catalyzes asymmetric intramolecular dehydrative N-allylation of N-substituted ?-amino- and -aminocarbonyl allylic alcohols with a substrate/catalyst ratio of up to 2000 to give α-alkenyl pyrrolidine-, piperidine-, and azepane-type N-heterocycles with an enantiomer ratio of up to >99:1. The wide range of applicable N-substitutions, including Boc, Cbz, Ac, Bz, acryloyl, crotonoyl, formyl, and Ts, significantly facilitates further manipulation toward natural product synthesis.