Ring-rearrangement metathesis of 7-azanorbornenes as an entry to 1-azabicyclo[n.3.0]alkenones

Resum

Pyrrolizidine, indolizidine, and pyrrolo[1,2-a]azepine substructures are present in a large number of naturally occurring azabicyclic compounds, which are currently of special interest because of their biological activities. To obtain this class of compounds, we envisioned a ring-rearrangement metathesis (RRM) process of 7-azanorbornene systems that incorporates several exocyclic olefin patterns at the nitrogen position. By using this methodology, we have synthesized a set of new 1-azabicyclo[n.3.0]alkenones, which include derivatives of pyrrolam. In all cases, only one regioisomer was obtained. Moreover, new spiro compounds with tricyclic structures have been synthesized by using a domino metathesis process that involves a ring-opening/ring-closing/ring-closing metathesis (ROM/RCM/RCM) sequence. A new synthetic strategy for nitrogen heterocycles was developed that incorporates fused-ring systems and takes advantage of a stereodefined ring-rearrangement metathesis process of substituted 7-azanorbornenes as the stereocontrolled key step. A set of new 1-azabicyclo[n.3.0]alkenones (n = 3, 4, and 5) that include new analogues of pyrrolam were prepared by using this methodology. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.