Diastereoselective Synthesis of trans-2,3,6,7-Tetrahydro-4(5H)-benzofuranones and trans-2,3-Dihydrofurocoumarins via Pyridinium Ylide Assisted Tandem Reactions

摘要

An efficient, one-pot tandem reaction of pyridine, an alpha-haloacetate, an aromatic aldehyde and cyclohexane-l,3-dione, dimedone or 4-hydrocoumarin in acetonitrile using 1,4-diazabicyc-lo[2.2.2]octane as a basic catalyst is described. The products, 2,3,6,7-tetrahydro-4(5H)-benzofuranones and 2,3-dihydrofurocou-marins, are obtained in a diastereoselective manner via a mechanism involving in situ formation of a pyridinium ylide. ~1H NMR spectroscopy and single crystal X-ray analysis indicates that the products are formed exclusively as the trans isomers. Tandem reactions have attracted particular attention because of their high efficiency in the construction of complex molecular frameworks. Compared to stepwise reactions, tandem processes minimize waste since the amounts of solvents, reagents, adsorbents and energy are dramatically decreased. Tandem reactions are often accompanied by significant increases in molecular diversity and impressive selectivity. In this regard, the development of new tandem reactions is a very attractive field in organic and medicinal chemistry. Recently, we reported the versatile reactivity and simple in situ formation of pyridinium salts. These salts were used as synthons to develop new tandem reactions, and we obtained very interesting results on the preparation of some cyclic compounds.