Pd/C-Catalyzed Dehydrogenative [3+2] Cycloaddition For The Synthesis Of Functionalized Tropanes

The tropane skeleton has already been recognized as a “privileged scaffold” in a great many natural bioactive products and pharmaceuticals.Many tropane derivatives play pivotal roles in a myriad of immune,neurological and psychiatric diseases.Benzotropane,containing a phenyl ring in the tropane moiety,also occurs in numerous lead compounds and pharmaceuticals for the treatment of diabetes and antitumor drug candidates.The medicinal relevance of tropane derivatives has stimulated considerable interest among synthetic chemists,and several catalytic methods have been developed for the construction of optically pure tropane frameworks,but in general,there are only a few cases of related reports.Therefore,the development of a novel,green,and simple method for the synthesis of tropane,especially for the optically active tropane,is of great significance.A Pd/C-catalyzed cascade approach for the synthesis of attractive benzo-fused tropanes was developed.The reaction proceeds through a sequential Pd/C-catalyzed dehydrogenative formation of azomethine ylides from amines and 1,3-dipolar cycloaddition.It allows the generation of structurally complex benzo-fused tropanes in good yields with excellent diastereoselectivities under mild reaction conditions.Preliminary results of asymmetric version of the reaction reveal that the copper catalyst and chiral monophosphoramidite ligand can furnish optically active products with moderate ee.