Improved Total Synthesis of Indolizidine and Quinolizidine Alkaloids via Nickel-Catalyzed (4 + 2) Cycloaddition
Jonas Renner1, Sleight R Smith1, Jacob M Cowley1
1Department of Chemistry, University of Utah, 315 South 1400 East, Salt Lake City, Utah 84112-8450, United States.
Abstract:
A Ni-catalyzed (4 + 2) cycloaddition of bicyclic 3-azetidinones and alkynes was developed to access indolizidine and quinolizidine alkaloids. A key element was the development of a diazomethylation procedure that allows the efficient synthesis of bicyclic azetidinones from pyroglutamic and 6-oxopiperidine-2-carboxylic acid. A ligand screening led to improved regioselectivity and enantiopurity during the Ni-catalyzed (4 + 2) cycloaddition. This straightforward methodology was leveraged to synthesize (+)-ipalbidine, (+)-septicine, (+)-seco-antofine, and (+)-7-methoxy-julandine.
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