Enantiomeric separation of biaryl atropisomers using cyclofructan based chiral stationary phases

使用基于环果聚糖的手性固定相对双芳基阻转异构体进行对映体分离

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作者:Ross M Woods, Darshan C Patel, Yeeun Lim, Zachary S Breitbach, Hongyin Gao, Craig Keene, Gongqiang Li, László Kürti, Daniel W Armstrong

Abstract

Normal phase chiral HPLC methods are presented for the enantiomeric separation of 30 biaryl atropisomers including 18 new compounds recently produced via a novel synthetic approach. Three new cyclofructan based chiral stationary phases were evaluated. Separations were achieved for all but six analytes and the LARIHC™ CF6-P alone provided 15 baseline separations. Effects of polar modifiers and temperature effects also were studied. Apparent thermodynamic parameters were determined by van't Hoff plots. Preparative scale methods were developed and employed resulting in the first ever isolation of these novel atropisomers in their pure enantiomeric form. Insights into the mechanism of retention and chiral discrimination are presented.

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