Synthesis of Bicyclic Guanidines via Cascade Hydroamination/ Michael Additions of Mono‑N‑acryloylpropargylguanidines

ABSTRACT: A cascade silver(I)-catalyzed hydroamination/Michael addition sequence has been developed to deliver highly substituted bicyclic guanidines. This transformation gives rise to geometrically and constitutionally stable ene−guanidines and generates a remote stereocenter with moderate to high diastereoselectivity. Polycyclic guanidinium ion natural products exhibit a broadspectrum of biological activity and embed an important structural unit that is critical for medicinal chemistry and for broader discovery-based applications.1 Unnatural polycyclic guanidines have also been employed as competent organo-catalysts with unique coordination arrangements and an array of donor/acceptors.2,3 Given their broad utility, a variety of synthetic methods have been developed to access this class of compounds. Some of these methods include the cyclization of propargylguanidines,4 intermolecular diamination of alkenes,5 reaction of unsaturatedmolecules with aziridines and diazirenes,