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Identifying stereoisomers of the asymmetric hydrogenation catalyst [Me‐BPE‐Rh(COD)] + BF 4 −
Author(s) -
Fox Martin E.,
McCague Raymond
Publication year - 2005
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.20147
Subject(s) - chemistry , asymmetric hydrogenation , catalysis , impurity , ligand (biochemistry) , rhodium , stereochemistry , enantioselective synthesis , medicinal chemistry , organic chemistry , receptor , biochemistry
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((2 S ,5 S )‐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°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. Chirality 17:177–185, 2005. © 2005 Wiley‐Liss, Inc.