Stereoselective Synthesis of Tropanes via a 6π-Electrocyclic Ring-Opening/ Huisgen [3+2]-Cycloaddition Cascade of Monocyclopropanated Heterocycles.
Carina M SonnleitnerSaerom ParkRobert EcklThomas ErtlAnd Oliver ReiserPublished in: Angewandte Chemie (International ed. in English) (2020)
The synthesis of tropanes via a microwave-assisted, stereoselective 6π-electrocyclic ring-opening/ Huisgen [3+2]-cycloaddition cascade of cyclopropanated pyrrole and furan derivatives with electron-deficient dipolarophiles is demonstrated. Starting from furans or pyrroles, 8-aza- and 8-oxabicyclo[3.2.1]octanes are accessible in two steps in dia- and enantioselective pure form, being versatile building blocks for the synthesis of pharmaceutically relevant targets, especially for new cocaine analogues bearing various substituents at the C-6/C-7 positions of the tropane ring system. Moreover, the 2-azabicyclo[2.2.2]octane core (isoquinuclidines), being prominently represented in many natural and pharmaceutical products, is accessible via this approach.
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