Phosphinooxazolines (often abbreviated PHOX) are a class of chiral ligands used in asymmetric catalysis. Colorless solids, PHOX ligands feature a tertiary phosphine group, often diphenyl, and an oxazoline ligand in the ortho position. The oxazoline, which carries the stereogenic center, coordinates through nitrogen, the result being that PHOX ligands are P,N-chelating ligands. Most phosphine ligands used in asymmetric catalysis are diphosphines, so the PHOX ligands are distinctive. Some evidence exists that PHOX ligands are hemilabile.[1]
The synthesis of phosphinooxazolines is modular. Methods exist for installing the phosphine ligand before the oxazoline and the reverse.[2] Commonly a phenyloxazoline is combined with a source of diphenylphosphine. Methods for doing this depend on the nature of the substituent in the X position:
Palladium complexes containing chiral phosphinooxazolines are efficient catalysts for the Heck reaction.[14][15] Pd-PHOX catalysts have also been used for intramolecular Heck reactions and examples exist where they have been shown to be superior to more common ligands such as BINAP.[16]
^ abBraunstein, Pierre; Naud, Fre´de´ric; Rettig, Steven J. (2001). "A new class of anionic phosphinooxazoline ligands in palladium and ruthenium complexes: catalytic properties for the transfer hydrogenation of acetophenone". New Journal of Chemistry. 25 (1): 32–39. doi:10.1039/b004786o. ISSN1144-0546.
^Koch, Guido; Lloyd-Jones, Guy C.; Loiseleur, Olivier; Pfaltz, Andreas; Prétôt, Roger; Schaffner, Silvia; Schnider, Patrick; von Matt, Peter (2 September 2010). "Synthesis of chiral (phosphinoaryl)oxazolines, a versatile class of ligands for asymmetric catalysis". Recueil des Travaux Chimiques des Pays-Bas. 114 (4–5): 206–210. doi:10.1002/recl.19951140413.
^Peer, Markus; de Jong, Johannes C.; Kiefer, Matthias; Langer, Thomas; Rieck, Heiko; Schell, Heico; Sennhenn, Peter; Sprinz, Jürgen; Steinhagen, Henning; Wiese, Burkhard; Helmchen, Günter (1996). "Preparation of Chiral Phosphorus, Sulfur and Selenium containing 2-Aryloxazolines". Tetrahedron. 52 (21): 7547–7583. doi:10.1016/0040-4020(96)00267-0. ISSN0040-4020.
^Sprinz, Jürgen; Helmchen, Günter (1993). "Phosphinoaryl- and phosphinoalkyloxazolines as new chiral ligands for enantioselective catalysis: Very high enantioselectivity in palladium catalyzed allylic substitutions". Tetrahedron Letters. 34 (11): 1769–1772. doi:10.1016/S0040-4039(00)60774-8.
^Zhang, Xumu; Liu, D.; Dai, Q. (27 June 2005). "A New Class of Readily Available and Conformationally Rigid Phosphino-Oxazoline Ligands for Asymmetric Catalysis". Tetrahedron. 61 (26): 6460–6471. doi:10.1016/j.tet.2005.03.111.
^Helmchen, Günter; Pfaltz, Andreas (June 2000). "PhosphinooxazolinesA New Class of Versatile, Modular P,N-Ligands for Asymmetric Catalysis". Accounts of Chemical Research. 33 (6): 336–345. doi:10.1021/ar9900865. PMID10891051.
^Armstrong, Paul B.; Dembicer, Elizabeth A.; DesBois, Andrew J.; Fitzgerald, Jay T.; Gehrmann, Janet K.; Nelson, Nathaniel C.; Noble, Amelia L.; Bunt, Richard C. (2012). "Investigation of the Electronic Origin of Asymmetric Induction in Palladium-Catalyzed Allylic Substitutions with Phosphinooxazoline (PHOX) Ligands by Hammett and Swain–Lupton Analysis of the 13C NMR Chemical Shifts of the (π-Allyl)palladium Intermediates". Organometallics. 31 (19): 6933–6946. doi:10.1021/om3007163.
^Wiese, Burkhard; Helmchen, Günter (1998). "Chiral phosphinooxazolines with a bi- or tricyclic oxazoline moiety - applications in Pd-catalyzed allylic alkylations". Tetrahedron Letters. 39 (32): 5727–5730. doi:10.1016/S0040-4039(98)01173-3.
^Loiseleur, Olivier; Hayashi, Masahiko; Keenan, Martine; Schmees, Norbert; Pfaltz, Andreas (1999-03-15). "Enantioselective Heck reactions using chiral P,N-ligands". Journal of Organometallic Chemistry. 576 (1–2): 16–22. doi:10.1016/S0022-328X(98)01049-3.
^Loiseleur, Olivier; Hayashi, Masahiko; Schmees, Norbert; Pfaltz, Andreas (1 November 1997). "Enantioselective Heck Reactions Catalyzed by Chiral Phosphinooxazoline-Palladium Complexes". Synthesis. 1997 (11): 1338–1345. doi:10.1055/s-1997-1341.
^Ripa, Lena; Hallberg, Anders (1997). "Intramolecular Enantioselective Palladium-Catalyzed Heck Arylation of Cyclic Enamides". The Journal of Organic Chemistry. 62 (3): 595–602. doi:10.1021/jo961832b. PMID11671454.
^Roseblade, Stephen J.; Pfaltz, Andreas (December 2007). "Iridium-Catalyzed Asymmetric Hydrogenation of Olefins". Accounts of Chemical Research. 40 (12): 1402–1411. doi:10.1021/ar700113g. PMID17672517.
^Hopmann, Kathrin Helen; Bayer, Annette (2011). "On the Mechanism of Iridium-Catalyzed Asymmetric Hydrogenation of Imines and Alkenes: A Theoretical Study". Organometallics. 30 (9): 2483–2497. doi:10.1021/om1009507.
^Smidt, Sebastian P.; Pfaltz, Andreas; Martínez-Viviente, Eloísa; Pregosin, Paul S.; Albinati, Alberto (2003). "X-ray and NOE Studies on Trinuclear Iridium Hydride Phosphino Oxazoline (PHOX) Complexes". Organometallics. 22 (5): 1000–1009. doi:10.1021/om020805a.
^Smidt, Sebastian P.; Zimmermann, Nicole; Studer, Martin; Pfaltz, Andreas (2004). "Enantioselective Hydrogenation of Alkenes with Iridium–PHOX Catalysts: A Kinetic Study of Anion Effects". Chemistry: A European Journal. 10 (19): 4685–4693. doi:10.1002/chem.200400284. PMID15372652.