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A Stereoselective [3+1] Ring Expansion for the Synthesis of Highly Substituted Methylene Azetidines
Author(s) -
Schmid Steven C.,
Guzei Ilia A.,
Schomaker Jennifer M.
Publication year - 2017
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201705202
Subject(s) - aziridine , stereocenter , methylene , chemistry , azetidine , stereoselectivity , stereochemistry , bicyclic molecule , ring (chemistry) , carbene , medicinal chemistry , enantioselective synthesis , organic chemistry , catalysis
The reaction of rhodium‐bound carbenes with strained bicyclic methylene aziridines results in a formal [3+1] ring expansion to yield highly substituted methylene azetidines with excellent regio‐ and stereoselectivity. The reaction appears to proceed through an ylide‐type mechanism, where the unique strain and structure of the methylene aziridine promotes a ring‐opening/ring‐closing cascade that efficiently transfers chirality from substrate to product. The resultant products can be elaborated into new azetidine scaffolds containing vicinal tertiary‐quaternary and even quaternary‐quaternary stereocenters.