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Dearomatization of electron poor six-membered N-heterocycles through [3 + 2] annulation with aminocyclopropanes
Johannes Preindl1, Shyamal Chakrabarty1, Jérôme Waser1
1Laboratory of Catalysis and Organic Synthesis , Institut des Sciences et Ingénierie Chimiques , École Polytechnique Fédérale de Lausanne , CH-1015 Lausanne , Switzerland .
Abstract:
Many abundant and highly bioactive natural alkaloids contain an indolizidine skeleton. A simple, high yielding method to synthesize this scaffold from N-heterocycles was developed. A wide range of pyridines, quinolines and isoquinolines reacted with donor-acceptor (DA)-aminocyclopropanes via an ytterbium(iii) catalyzed [3 + 2] annulation reaction to give tetrahydroindolizine derivatives. The products were obtained with high diastereoselectivities (dr > 20 : 1) as anti-isomers. Additionally, the formed aminals could be easily converted into secondary and tertiary amines through iminium formation followed by reduction or nucleophile addition. This transformation constitutes the first example of dearomatization of electron-poor six-membered heterocycles via [3 + 2] annulation with DA cyclopropanes.
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