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.

本研究报道了P手性（P-chirogenic）单磷杂环戊烷与双磷杂环戊烷的制备方法。所采用的合成方法为：在碱存在下，通过环状硫酸盐与伯膦的立体选择性环化反应，生成“顺式”或“顺式/顺式”构型的P手性磷杂环戊烷；随后经热诱导的锥型反转，得到“反式”或“反式/反式”构型的P手性磷杂环戊烷。将一款“反式/反式”构型的磷杂环戊烷与铑形成的配合物，应用于药物候选化合物普瑞巴林（pregabalin）前体底物的高对映选择性不对称氢化反应。