Stereoselective P‐Cyclisation and ­Diastereoisomeric Purification of 5‐Phenyl‐3‐(pyridin‐2‐yl)‐1,3,2‐oxazaphospholidine Formed from a Thermolabile Protecting Group

Abstract

AbstractA one‐pot, two‐step synthesis of 5‐phenyl‐3‐(pyridin‐2‐yl)‐1,3,2‐oxazaphospholidine from linear precursor bis(diisopropylamino){2‐[(pyridin‐2‐yl)amino]‐1‐phenylethoxy}phosphine is achieved using a stereoselective intramolecular cyclisation. Application of a pure enantiomer {1‐phenyl‐2‐[(pyridin‐2‐yl)amino]ethanol} enabled partial diastereopurification by crystallisation. For all four diastereoisomers, the absolute configuration of the P‐centre was determined using X‐ray crystallography and correlative 31P NMR data. Stereochemically pure 5a was then used in nucleoside phosphitylation reactions with partial loss of stereopurity by retention of configuration on the phosphorus centre.