Tandem Addition/Cycloisomerisation reactions catalyzed by [Ag(I)(Pc-L*)] complexes

The tandem emiacetalization/cycloisomerization of ortho-alkynylbenzaldehydes (Scheme 1), originally reported by Yamamoto using Pd(OAc)2 or CuI as a catalysts, gives 1H-isochromene derivatives that can have useful medicinal properties. Although several related tandem processes are known, no enantioselective version of this reaction has appeared until the very recent report by Slaughter and coworkers. Their study, is based on the use of chiral gold(I) acyclic diaminocarbene complexes as catalysts in the presence of LiNTf2 (Tf = trifluoromethanesulfonyl) as a necessary additive to achieve useful activity. Recent studies in our research group demonstrated the efficacy of Cu(I) complexes, derived from novel macrocyclic ligands containing a pyridine ring (Pc-L*), in cyclopropanation reactions.5 The excellent results obtained up to now with copper prompted us to verify the application of silver(I) complexes of these ligands in catalysis. We herein report the synthesis and characterization of the new Ag(I) macrocyclic complexes, 1 (Figure 1) and their catalytic activity in the synthesis of oxygenated heterocycles by addition/cycloisomerization reactions of alcohols and ortho-alkynylbenzaldehydes. Reactions are characterized by mild conditions, complete regioselectivity and 1H-isochromene derivatives are obtained in good to excellent yields starting from both electron rich and electron poor ortho-alkynylbenzaldehydes. When optically pure ligands are used, chiral induction in the reaction products is observed, although, up to now, with modest enantiomeric excesses.