Asymmetric Activation of Conformationally Flexible Monodentate Phosphites for Enantioselective Hydrogenation.

A new method is presented with which achiral, conformationally flexible biphenylphosphites can be activated by easily available chiral alcohols to give monodentate phosphite ligands that are effective in rhodium-catalysed enantioselective hydrogenation. © 2001 Elsevier Science Ltd. All rights reserved. Racemic catalysts can be made enantioselective by the introduction of chiral activators capable of selectively activating one of the enantiomers of the catalyst (Scheme 1). This process has been termed asymmetric activation and has proven its utility with a number of catalysts based on bidentate ligands. For example, by using an enantiomerically pure diamine, Noyori, Mikami and co-workers showed that ketones can be hydrogenated in the presence of the racemic [RuCl2(TolBINAP)(dmf)n ] catalyst to give alcohols with enantiomeric purity close to that attainable with a catalyst containing the enantiomerically pure TolBINAP ligand and the same diamine. Mikami has further extended this concept to Ru(II) complexes containing the conformationally flexible, proatropisomeric biphenylphosphine (BIPHEP) ligands. While the latter cannot be isolated in enantiopure forms, their Ru(II) complexes can be obtained in a diastereomerically enriched form upon complexation with a chiral diamine activator, which controls chirality of BIPHEP through epimerisation and leads to asymmetric activation of the complexes to give enantioselective catalysts for the hydrogenation of ketones. The advantage of such an approach to asymmetric catalysis is that the physical separation of a racemic catalyst is circumvented, provided that a matching chiral activator can be identified. In the examples that have appeared, the asymmetric activation begins with a racemic metal catalyst, where one of the enantiomers combines preferentially with a chiral activating molecule, producing a more catalytically active and enantioselective species. We present herein a method that leads to asymmetric activation of conformationally flexible monodentate phosphite ligands and our preliminary results on the use of these ligands in the rhodium catalysed enantioselective hydrogenation of an unsaturated carboxylic acid derivative. Monodentate phosphonites and phosphites have recently been shown to be excellent ligands in the rhodium catalysed asymmetric hydrogenation of unsaturated carboxylic acids and dehydroamino acids. We have also reported that diastereomerically pure binaphthylphosphites can be obtained from the inexpensive, racemic binaphthol, (L)-menthol and PCl3 and the phosphites so generated are excellent ligands in the enantioselective hydrogenation of some unsaturated carboxylic acid derivatives. In this approach, one may consider L-menthol to be a chiral activator, generating two easily separable chiral ligands out of a racemic chiral building block. Scheme 1. Asymmetric activation of racemic catalysts via chiral molecules.