Highly enantioselective synthesis of 1-aryl-tetrahydroisoquinolines via an aryl transfer to 3,4-dihydroisoquinoline N-oxide

ORGN 609

Sa Wang, Sa_Wang@Brown.edu, M. Burak Onaran, Mehmet_Onaran@Brown.EDU, and Christopher T. Seto. Department of Chemistry, Brown University, 324 Brook Street, Providence, RI 02912
1-Aryl-tetrahydroisoquinolines are important skeletons of a great number of pharmacologically active compounds related to central nervous diseases. A novel asymmetric synthesis of 1-aryl-tetrahydroisoquinolines was introduced, in which the key step was an aryl transfer from a variety of arylzinc reagents to 3,4-dihydroisoquinoline N-oxide using an amino acid-based N-acylethylenediamine ligand. Excellent yields (up to 97%) and extremely high enantioselectivities (97- 99% ee) have been achieved. The methodology was further applied to the synthesis of a single enantiomer of solifenacin (YM905). The mechanism of the catalyzed asymmetric aryl transfer was investigated by NMR Spectroscopy.
 

Materials, Devices and Switches, Metal-Mediated Reactions, Asymmetric Reactions, Total Synthesis, Biologically-Related Molecules and Processes
7:00 PM-9:00 PM, Wednesday, April 9, 2008 Morial Convention Center -- La Louisiane, Blrm. C, Poster

Division of Organic Chemistry

The 235th ACS National Meeting, New Orleans, LA, April 6-10, 2008