Hybrid P/N ligands for catalysis

This is the project with which Mimi started her independence career, and so have the longest history within the group. Generally, a project is divided into two stages: (i) ligand synthesis; (ii) preparation and characterisation of transition metal complexes and their applications to catalytic processes.

Ligand Synthesis


(i) Aminophosphine ligands containing chirality on N/P (types I and II)


Early on in this project, we developed a rapid synthesis of amino(di)phosphines of types I or II, achieved in two steps by the addition of nucleophilic amines to vinylphosphine oxides (Scheme 1). The reaction was found to be greatly accelerated by protic solvents. The product can then be reduced by silane to the corresponding phosphine ligands.

Scheme 1. Synthesis of amino(di)phosphines by an aza-Michael reaction.

"Michael Addition of Amines to Vinyldiphenylphosphine oxide: Efficient Synthesis of Aminophosphines R-NH(CH2CH2PPh2) and Aminodiphosphines R-N(CH2CH2PPh2)2", M. S. Rahman, J. W. Steed and K. K. Hii, Synthesis, 2000, 1320-1326.

DOI: 10.1055/s-2000-6422

This paved a way for the facile synthesis of libraries of optically active PN and PNP ligands, by using chiral amines/aminoalcohols or chiral vinylphosphine oxides (containing stereogenic a phosphorus donor), which were examined as ligands in Pd-catalysed C-C and C-N coupling reactions, as well as ruthenium-catalysed (asymmetric) transfer hydrogenation of ketones. In the latter case, as the chirality of the N and P donors can be independently controlled, match/mismatch of chirality in these asymmetric processes can be examined. In these cases, ee’s in excess of 90% can be achieved.


"Coordination Chemistry and Catalytic Activity of Ruthenium Complexes of Terdentate Phosphorus-Nitrogen-Phosphorus (PNP) and Bidentate Phosphorus-Nitrogen (PNH) Ligands", M. S. Rahman, P. D. Prince, J. W. Steed and K. K. Hii, Organometallics, 2002, 21, 4927-4933. DOI: 10.1021/om0201314


"Phosphorus-Nitrogen-Phosphorus Ligands: Cooperative Effects Between Nitrogen and Phosphorus Substituents on Catalytic Activity", S. L. Parisel, N. D. Moorcroft, A. Jutand, D. J. Aldous and K. K. Hii, Org. Biomol. Chem., 2004, 2, 301-306. DOI: 10.1039/b312702h


"Mixed Donor Aminophosphine Oxide Ligands in Ruthenium-catalysed Asymmetric Transfer Hydrogenation Reactions", M. S. Rahman, M. Oliana and K. K. Hii, Tetrahedron Asymmetry, 2004, 15, 1835-1840. DOI: 10.1016/j.tetasy.2004.05.001


"Aminohydroxy Phosphine Oxide Ligands in Ruthenium-catalysed Asymmetric Transfer Hydrogenation Reactions", X. Cheng, P. N. Horton, M. B. Hursthouse and K. K. Hii, Tetrahedron Asymmetry (Special issue on Chiral Phosphorus Chemistry), 2004, 15, 2241-2246. DOI:10.1016/j.tetasy.2004.04.040


"Reversal of Aryl Bromide Reactivity in Palladium-catalysed Aryl Amination Reactions Catalysed by an Aminophosphine Ligand", S. L. Parisel, L. A. Adrio, A. A. Pereira, M. M. Pérez, J. M. Vila and K. K. Hii, Tetrahedron (Symposium-in-Print), 2005, 61, 9822-9826. DOI: 10.1016/j.tet.2005.06.073


"Practical Synthesis of Chiral Vinylphosphine Oxides by Direct Nucleophilic Substitution. Stereodivergent Synthesis of Aminophosphine Ligands", M. Oliana, F. King, P. N. Horton, M. B. Hursthouse and K. K. Hii, J. Org. Chem., 2006, 71, 2472-2479. DOI: 10.1021/jo052575q

(ii) Aminophosphine ligands based on proline (types III and IV)


The other part of the project focussed on the synthesis of proline-derived aminophosphines of type III and IV. Here we examined effects of combining different donor groups (PNN, PNP) within the chiral ligand scaffold, and the introduction of additional stereogenic centres (on carbon or phosphorus). These ligands were tested in Pd-catalysed asymmetric allylic substitution reactions, as well as Ru-catalysed asymmetric reduction of ketones. In all cases, ee’s in excess of 90% can be achieved. More interestingly are the observation of cooperative effects between donor groups.


"Examining the Effect of Hemilabile Donor Groups in Non-C2 Symmetrical Terdentate Ligands", H. Lam, X. Cheng, J. W. Steed, D. J. Aldous and K. K. Hii, Tetrahedron Lett., 2002, 43, 5875-5877. DOI:10.1016/S0040-4039(02)00988-7 


"Unsymmetrical Terdentate Phosphorus-Nitrogen-Nitrogen (PNN) Ligands: Effect of the Pendant Group on Stereoselectivity", X. Cheng and K. K. Hii, Tetrahedron Asymmetry, 2003, 14, 2045-2052. DOI:10.1016/S0957-4166(03)00361-6


"Synthesis of P-Chirogenic Diarylphosphinoacetic Acids and Their Proline Derivatives for Palladium-catalysed Allylic Alkylation Reactions", H. Lam, S. J. Coles, M. B. Hursthouse, D. J. Aldous and K. K. Hii, Tetrahedron Lett., 2005, 46, 8145-8148. DOI:10.1016/j.tetlet.2005.09.136