Cyclic Allene Approach to the Manzamine Alkaloid Keramaphidin B

We report an approach to the core of the manzamine alkaloidkeramaphidinB that relies on the strain-promoted cycloaddition of an azacyclicallene with a pyrone trapping partner. The cycloaddition is tolerantof nitrile and primary amide functional groups and can be complementedwith a subsequent retro-Diels-Alder step. These efforts demonstratethat strained cyclic allenes can be used to build significant structuralcomplexity and should encourage further studies of these fleetingintermediates.

Automated summary

We present a method for constructing the core structure of the manzamine alkaloid keramaphidin B using a strain-promoted cycloaddition reaction. This method tolerates nitrile and primary amide functional groups, and can be followed by a retro-Diels-Alder reaction to increase structural complexity. These findings highlight the potential of strained cyclic allenes in building intricate structures, and provide inspiration for further studies on these transient intermediates.