Phosphinooxazolines

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Chiral phosphinooxazoline (PHOX) in its free and coordinated forms PHOX2.png
Chiral phosphinooxazoline (PHOX) in its free and coordinated forms

Phosphinooxazolines (often abbreviated PHOX) are a class of chiral ligands used in asymmetric catalysis. Their complexes are particularly effective at generating single enatiomers in reactions involving highly symmetric transition states, such as allylic substitutions, which are typically difficult to perform stereoselectively. The ligands are bidentate and have been shown to be hemilabile [1] with the softer P‑donor being more firmly bound than the harder N‑donor.

Enantiomer 1 of 2 stereoisomers that are mirror images of each other that are non-superposable,not identical,much as ones left&right hands are the same except for being reversed along one axis(the hands cannot be made to appear identical simply by reorientatio

In chemistry, an enantiomer, is one of two stereoisomers that are mirror images of each other that are non-superposable, much as one's left and right hands are mirror images of each other that cannot appear identical simply by reorientation. A single chiral atom or similar structural feature in a compound causes that compound to have two possible structures which are non-superposable, each a mirror image of the other. Each member of the pair is termed an enantiomorph ; the structural property is termed enantiomerism. The presence of multiple chiral features in a given compound increases the number of geometric forms possible, though there may still be some perfect-mirror-image pairs.

Transition state set of states (each characterized by its own geometry, energy) in which an assembly of atoms, when randomly placed there, would have an equal probability of forming the reactants or of forming the products of that elementary reaction

The transition state of a chemical reaction is a particular configuration along the reaction coordinate. It is defined as the state corresponding to the highest potential energy along this reaction coordinate. It is often marked with the double dagger ‡ symbol.

In coordination chemistry and catalysis hemilability refers to a property of many polydentate ligands which contain at least two electronically different coordinating groups, such as hard and soft donors. These hybrid or heteroditopic ligands form complexes where one coordinating group is easily displaced from the metal centre while the other group remains firmly bound; a behaviour which has been found to increase the reactivity of catalysts when compared to the use of more traditional ligands.

Contents

Synthesis

The synthesis of phosphinooxazolines is modular and it is not normally necessary to introduce the phosphine and oxazoline moieties in any particular order. However while examples exist of the phosphine being introduced first, [2] it is more common to see the synthesis of a phenyloxazoline which is subsequently combined with a source of diphenylphosphine. Methods for doing this depend on the nature of the subsituent in the X position:

Phosphine chemical compound

Phosphine (IUPAC name: phosphane) is the compound with the chemical formula PH3. It is a colorless, flammable, toxic gas and is classed as a pnictogen hydride. Pure phosphine is odorless, but technical grade samples have a highly unpleasant odor like garlic or rotting fish, due to the presence of substituted phosphine and diphosphane (P2H4). With traces of P2H4 present, PH3 is spontaneously flammable in air (pyrophoric), burning with a luminous flame. Phosphines are also a group of organophosphorus compounds with the formula R3P (R = organic derivative). Organophosphines are important in catalysts where they complex to various metal ions; complexes derived from a chiral phosphine can catalyze reactions to give chiral, enantioenriched products.

Oxazoline chemical compound

Oxazoline is a five-membered heterocyclic chemical compound containing one atom each of oxygen and nitrogen. It was likely first synthesized in 1884 but it was not until 5 years later that Siegmund Gabriel correctly assigned the structure. It was named in-line with the Hantzsch–Widman nomenclature and is part of a family of heterocyclic compounds, where it exists between oxazole and oxazolidine in terms of saturation.

PHOX ligand synthesis 2.png
Grignard reaction Organometallic coupling reaction

The Grignard reaction is an organometallic chemical reaction in which alkyl, vinyl, or aryl-magnesium halides add to a carbonyl group in an aldehyde or ketone. This reaction is important for the formation of carbon–carbon bonds. The reaction of an organic halide with magnesium is not a Grignard reaction, but provides a Grignard reagent.

Chlorodiphenylphosphine chemical compound

Chlorodiphenylphosphine is an organophosphorus compound with the formula (C6H5)2PCl, abbreviated Ph2PCl. It is a colourless oily liquid with a pungent odor that is often described as being garlic-like and detectable even in the ppb range. It is useful reagent for introducing the Ph2P group into molecules, which includes many ligands. Like other halophosphines, Ph2PCl is reactive with many nucleophiles such as water and easily oxidized even by air.

Diphenylphosphine chemical compound

Diphenylphosphine, also known as diphenylphosphane, is an organophosphorus compound with the formula (C6H5)2PH. This foul-smelling, colorless liquid is easily oxidized in air. It is a precursor to organophosphorus ligands for use as catalysts.

Of these methods the copper iodide catalysed reaction method is by far the simplest to carry out, as it does not require the synthesis of discrete anionic or organometallic species and is able to couple a wide range of materials in good to excellent yields.

In catalysis

Phosphinooxazolines are able to influence both the enantioselectivity and regioselectivity of a range of metal catalysed reactions. [7] In reactions involving symmetric transition states these properties work in concert to induce asymmetry and thus promote the formation of a single product. Enantioselectivity is controlled by the chirality of the ligand which is normally located on the oxazoline ring, however the P-centre may also be stereogenic. [8] Regioselectivity is controlled by variety of steric and electronic factors [9] the most important of which being a form of trans effect, in which atoms complexed trans to the P‑atom become more electrophilic than ones located trans to the N‑atom. This is caused by the P‑atom engaging in back bonding, as it is a π‑electron acceptor.

Regioselectivity

In chemistry, regioselectivity is the preference of one direction of chemical bond making or breaking over all other possible directions. It can often apply to which of many possible positions a reagent will affect, such as which proton a strong base will abstract from an organic molecule, or where on a substituted benzene ring a further substituent will add.

Asymmetric induction

Asymmetric induction in stereochemistry describes the preferential formation in a chemical reaction of one enantiomer or diastereoisomer over the other as a result of the influence of a chiral feature present in the substrate, reagent, catalyst or environment. Asymmetric induction is a key element in asymmetric synthesis.

Chirality property of an object that is distinguishable from its mirror image

Chirality is a property of asymmetry important in several branches of science. The word chirality is derived from the Greek χειρ (kheir), "hand," a familiar chiral object.

Allylic substitutions

Phosphinooxazolines are used as ligands in allylic substitution reactions as both enantio- and regioselectivity is required to give an enantiomerically pure product due to the transition state being highly symmetric. In the example below all additions are enantioselective however the symmetric complex has no regiocontrol, resulting in a racemic product. The asymmetric complex is both regioslective and enantioselective, resulting in a single enantiomer.

Symmetric vs asymmetric.png

The primary application of PHOX ligands is in palladium catalysts used for enantioselective allylic substitutions. They are able to effect a wide range of substitiuations including allylic alkylations (Tsuji-Trost reaction), [10] aminations [11] and sulfonylations. [12]

Heck Reaction

Heck Reaction Scheme.png

Palladium complexes containing chiral phosphinooxazolines have been shown to be efficient catalysts for the Heck reaction. [13] High yields and good to excellent enantioselectivities have been obtained, with the formation of by-products via C=C bond migration being greatly reduced. [14] 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. [15]

Asymmetric Hydrogenation

The high enantio- and regiocontrol afforded by phosphinooxazoline ligands has fuelled research into their use for asymmetric hydrogenation. Iridium complexes incorporating phosphinooxazoline ligands have been shown to be effective for 'classic' hydrogenation using H2, [16] with ruthenium and palladium catalysts having also been investigated for transfer hydrogenation. [1] In addition to theoretical studies, [17] the structural [18] and kinetic properties [19] of Ir-PHOX complexes have been investigated to better understand their behaviour as hydrogenation catalysts.

See also

Other oxazoline based ligands

Structurally related ligands

Related Research Articles

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DuPhos

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Hydrogenation of carbon–nitrogen double bonds

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Josiphos ligands

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(<i>S</i>)-iPr-PHOX chiral, bidentate, ligand

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Trisoxazolines

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In homogeneous catalysis, a C2-symmetric ligands usually describes bidentate ligands that are dissymmetric but not asymmetric by virtue of their C2-symmetry. Such ligands have proven valuable in catalysis. With C2 symmetry, C2-symmetric ligands limit the number of possible reaction pathways and thereby increase enantioselectivity, at least relative to asymmetrical analogues. Chiral ligands combine with metals to form chiral catalyst, which engages in a chemical reaction in which chirality is transfer to the reaction product. C2 symmetric ligands are a subset of chiral ligands.

References

  1. 1 2 Braunstein, 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. ISSN   1144-0546.
  2. ↑ 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.
  3. ↑ 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. ISSN   0040-4020.
  4. ↑ 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.
  5. ↑ Tani, Kousuke; Behenna, Douglas C.; McFadden, Ryan M.; Stoltz, Brian M. (1 June 2007). "A Facile and Modular Synthesis of Phosphinooxazoline Ligands" (PDF). Organic Letters. 9 (13): 2529–2531. doi:10.1021/ol070884s. PMID   17536810.
  6. ↑ 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.
  7. ↑ 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. PMID   10891051.
  8. ↑ Yamagishi, Takamichi; Ohnuki, Masatoshi; Kiyooka, Takahiro; Masui, Dai; Sato, Kiyoshi; Yamaguchi, Motowo (1 October 2003). "Construction of P-stereogenic center by selective ligation of N–P–N type ligands and application to asymmetric allylic substitution reactions". Tetrahedron: Asymmetry. 14 (21): 3275–3279. doi:10.1016/j.tetasy.2003.09.004.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ von Matt, Peter; Loiseleur, Olivier; Koch, Guido; Pfaltz, Andreas; Lefeber, Claudia; Feucht, Thomas; Helmchen, Gunter (1994). "Enantioselective allylic amination with chiral (phosphino-oxazoline)pd catalysts". Tetrahedron: Asymmetry. 5 (4): 573–584. doi:10.1016/0957-4166(94)80021-9.
  12. ↑ Eichelmann, Holger; Gais, Hans-Joachim (1995). "Palladium-catalyzed asymmetric allylic sulfonylation". Tetrahedron: Asymmetry. 6 (3): 643–646. doi:10.1016/0957-4166(95)00049-U.
  13. ↑ 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.
  14. ↑ 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.
  15. ↑ 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. PMID   11671454.
  16. ↑ 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. PMID   17672517.
  17. ↑ 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.
  18. ↑ 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.
  19. ↑ 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. PMID   15372652.
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