Identifying stereoisomers of the asymmetric hydrogenation catalyst [Me-BPE-Rh(COD)]+BF4 -.
The performance of a catalyst used in asymmetric synthesis is likely to be dependent upon its stereoisomeric purity. An impurity was detectable by (31)P NMR in early development batches of the asymmetric hydrogenation catalyst [(S,S)-Me-BPE-Rh(COD)](+)BF(4) (-) made from the ligand bis((2S,5S)-2,5-dimethylphospholano)ethane [(S,S)-Me-BPE]. Its identity as a stereoisomer with one chiral and one meso-phospholane ring was deduced by comparison of the (31)P NMR spectra and GC traces of the ligand with a deliberately synthesized mixture of isomers. Interestingly, the impurity corresponded to a trans-meso isomer formed by thermal (200 degrees C) pyramidal inversion at phosphorus of the initially synthesized cis-meso-phospholane when the ligand was purified by distillation. Low levels of this trans-meso/chiral impurity do not significantly impair the enantioselectivity of the rhodium complex as an asymmetric hydrogenation catalyst, but high levels of stereochemical impurities resulted in a loss of both enantioselectivity and activity. Therefore it is indeed important to establish that a catalyst used in asymmetric catalysis is sufficiently stereoisomerically pure. Owing to strict control of the stereochemical purity of the key hexane-2,5-diol intermediate, the impurity is not detected in production batches.
Fox
Martin E
ME
Dowpharma, Chirotech Technology Ltd, A Subsidiary of The Dow Chemical Company, Unit 321, Cambridge Science Park, Cambridge CB4 0WG, England, UK. mfox@dow.com
McCague
Raymond
R
D002384:Catalysis; D002849:Chromatography, Gas; D015195:Drug Design; D006859:Hydrogen / Q000737:chemistry; D006865:Hydrogenation; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D013237:Stereoisomerism; D013696:Temperature
C514361:(1,5-cyclooctadiene)bis((2,5-dimethylphospholano)ethane)rhodium(I); D008024:Ligands; D009942:Organometallic Compounds; D006859:Hydrogen