Stereoselective cyclization and pyramidal inversion strategies for P-chirogenic phospholane synthesis.
Preparation of P-chirogenic mono- and bisphospholanes is reported. The demonstrated method employs a stereoselective cyclization of cyclic sulfates with primary phosphines in the presence of base to generate "cis" or "cis/cis" P-chirogenic phospholanes followed by heat-induced pyramidal inversion to provide "trans" or "trans/trans" P-chirogenic phospholanes. A rhodium complex of one "trans/trans" phospholane is applied to the highly enantioselective asymmetric hydrogenation of a substrate precursor to the pharmaceutical candidate pregabalin.
Hoge
Garrett
G
Pfizer Global Research and Development, 2800 Plymouth Road, Ann Arbor, Michigan 48105, USA. garrett.hoge@pfizer.com