Concise Total Syntheses of Dipiperidine Alkaloids Virgidivarine and Virgiboidine through Ru‐Mediated Ene‐Ene‐Yne Ring Rearrangement Metathesis (RRM)

Abstract

Abstract Herein, we report on the first enantioselective synthesis of the sparteine‐type alkaloids virgidivarine ( 1 ) and virgiboidine ( 2 ). The stereoselective construction of the challenging dipiperidine core within 1 and 2 was realized by applying an intramolecular ene‐ene‐yne ring‐rearrangement metathesis (RRM) protocol. In combination with this sequence, an unprecedented tandem metathesis/oxidation reaction was established. Subsequent to the RRM event, the Ru‐alkylidene species was converted into the highly potent dihydroxylation catalyst RuO 4 by the addition of NaIO 4 . This transformation rendered five sequential reactions that include an ene‐ene‐yne RRM/dihydroxylation/glycol cleavage in a one‐pot procedure. This approach provides practical and general access to dipiperidines and piperidino‐quinolizidines. Despite their wide use in organic and organometallic chemistry as well as their occurrence in biologically active natural products, methods are still lacking for the stereoselective synthesis of these motifs.