Iron bis(oxazoline) complexes in asymmetric catalysis
Asymmetric reactions catalyzed by iron complexes have attracted considerable attention because iron is a ubiquitous, inexpensive, and environmentally benign metal. Various chiral iron complexes can be prepared from bis(oxazoline) ligands and be used in asymmetric reactions. This overview charts the development and application of chiral iron bis(oxazoline) and pyridine-2,6-bis(oxazoline) catalysts through their most prominent and innovative uses in asymmetric catalysis, especially in Lewis acid and oxidation catalysis.
Catal. Sci. Technol., 2015, Advance Article
DOI: 10.1039/C5CY01357G, Minireview
Asymmetric reactions catalyzed by iron complexes have attracted considerable attention because iron is a ubiquitous, inexpensive, and environmentally benign metal. This overview charts the development and application of chiral iron bis(oxazoline) and pyridine-2,6-bis(oxazoline) catalysts through their most prominent and innovative uses in asymmetric catalysis, especially in Lewis acid and oxidation catalysis.
Iron bis(oxazoline) complexes in asymmetric catalysis
aDépartement de chimie, Pavillon Alexandre-Vachon, Université Laval, 1045 avenue de la Médecine, Québec (Qc) G1V 0A6, Canada
Catal. Sci. Technol., 2015, Advance Article
In chemistry, bis(oxazoline) ligands (often abbreviated BOX ligands) are a class of privileged chiral ligands containing two oxazoline rings. They are typically C2‑symmetric and exist in a wide variety of forms; with structures based around CH2 or pyridine linkers being particularly common (often generalised BOX and PyBOX respectively). The coordination complexes of bis(oxazoline) ligands are used extensively in asymmetric catalysis.
The synthesis of oxazoline rings is well established and in general proceeded via the cyclisation of a 2‑amino alcohol with any of a number of suitable functional groups. In the case of bis(oxazoline)s, synthesis is most conveniently achieved by using bi-functional starting materials; as this allows both rings to be produced at once. Of the materials suitable, dicarboxylic or dinitrile compounds are the most commonly available and hence the majority bis(oxazoline) ligands are produced from these materials.
Part of the success of the BOX and PyBOX motifs lies in their convenient one step synthesis from malononitrile and dipicolinic acid, which are commercially available at low expense. Chirality is introduced with the amino alcohols, as these are prepared from amino acids and hence are chiral (e.g. valinol).
The advantages C2-symmetry
The left hand structure has a C2‑rotational axis
whereas the right hand structure is asymmetric. Arrows indicate the theoretical attack trajectories of reagents, identical colours lead to identical transition states (and hence products) with red arrows being disfavoured due to steric
In bis(oxazoline) complexes the metal is held close to the stereogenic centres, which will strongly influence the enantioselectivity of any process taking place there. However the C2‑symmetry of the ligand is also important in controlling this enantioselectivity.
While the presence of any symmetry element within a ligand intended for asymmetric induction might appear counterintuitive, asymmetric induction only requires that the ligand be chiral (i.e. have no improper rotation axis); it does not have to be asymmetric (i.e. devoid of any symmetry element). C2‑symmetry actually improves the enantioselectivity of the complex by reducing the number of transition states with a unique geometry. Steric/kinetic factors then usually favour the formation of a single product. The benefits of C2‑symmetry in bis(oxazoline) ligands have been reviewed in depth
In general, for methylene bridged BOX ligands the stereochemical outcome is consistent with a twisted square planar intermediate that was proposed based on related crystal structures. The substituent at the oxazoline’s 4-position blocks one enantiotopic face of the substrate, leading to enantioselectivity. This is demonstrated in the following aldol-type reaction, but is applicable to a wide variety of reactions such as Mannich-type reactions, ene reaction, Michael addition, Nazarov cyclization, and hetero-Diels-Alder reaction.
On the other hand, two-point binding on a Lewis acid bearing the meridially tridentate PyBOX ligand would result in a square pyramidal complex. A study using (benzyloxy)acetaldehyde as the electrophile showed that the stereochemical outcome is consistent with the carbonyl oxygen binding equatorially and the ether oxygen binding axially.
Metal complexes incorporating bis(oxazoline) ligands are effective for an wide range of asymmetric catalytic transformations and have been the subject of numerous literature reviews. The neutral character of bis(oxazoline)s makes them well suited to use with noble metals, with copper complexes being particularly common. Their most important and commonly used applications are in carbon–carbon bond forming reactions.
Carbon–carbon bond forming reactions
bis(oxazoline) ligands have been found to be effective for a range of asymmetric cycloaddition reactions, this began with the very first application of BOX ligands in carbenoid cyclopropanations and has been expanded to include 1,3-Dipolar cycloaddition and Diels-Alder reactions. Bisoxazoline ligands have also been found to be effective for Aldol, Michael and Ene reactions, amongst many others
BOX assisted Aldol reaction
The success of bis(oxazoline) ligands for carbenoid cyclopropanations led to their application for aziridination. Another common reaction is hydrosilylation, which dates back to the first use of PyBOX ligands. Other niche applications include as fluorination catalysts and for Wacker-type cyclisations.
The development of bis(oxazoline) ligands
Oxazoline ligands were first used for asymmetric catalysis in 1984 when Brunner et al. showed a single example, along with a number of Schiff bases, as being effective for enantioselective carbenoid cyclopropanation. Schiff bases were prominent ligands at the time, having been used by Ryōji Noyori during the discovery of asymmetric catalysis in 1968 (for which he and William S. Knowles would later be awarded the Nobel Prize in Chemistry). Brunner’s work was influenced by that of Tadatoshi Aratani, who had worked with Noyori, before publishing a number of papers on enantioselective cyclopropanation using Schiff bases.
In this first usage the oxazoline ligand performed poorly, giving an ee of 4.9% compared to 65.6% from one of the Schiff base ligands. However Brunner reinvestigated oxazoline ligands during research into the monophenylation of diols, leading to the development of chiral pyridine oxazoline ligands, which achieved ee’s of 30.2% in 1986 and 45% in 1989. In the same year Pfaltz et al. reported the use of C2‑symmetric semicorrin ligands for enantioselective carbenoid cyclopropanations, achieving impressive results with ee’s of between 92-97%. Reference was made to both Brunner’s and Aratani’s work, however the design of the ligands was also largely based on his earlier work with various macrocycles. A disadvantage of these ligands however, was that they required a multi-step synthesis with a low overall yield of approximately 30%.
C2-symmetric bis(oxazoline) ligands with axial chirality
Brunner’s work led to the development of very first bisoxazolines by Nishiyama et al., who synthesised the first PyBox ligands in 1989. These ligands were used in the hydrosilylation of ketones; achieving ee’s of up to 93% The first BOX ligands where reported a year later by Masamune et al. and were first used in copper catalysed carbenoid cyclopropanation reactions; achieving ee’s of up to 99% with 1% molar loadings. This was a remarkable result for the time and generated significant interest in the BOX motif. As the synthesis of 2-oxazoline rings was already well established at this time (literature reviews in 1949 and 1971), research proceeded quickly, with papers from new groups being published within a year. and review articles being published by 1996. Today a considerable number of bis(oxazoline) ligands exist; structurally these are still largely based around the classic BOX and PyBOX motifs, however they also include a number of alternative structures, such as axially chiral compounds.
- Whitesell, James K. (1 November 1989). “C2 symmetry and asymmetric induction”. Chemical Reviews 89 (7): 1581–1590. doi:10.1021/cr00097a012.
- Rasappan, Ramesh; Laventine, Dominic; Reiser, Oliver (2008). “Metal-bis(oxazoline) complexes: From coordination chemistry to asymmetric catalysis”. Coordination Chemistry Reviews 252 (5-7): 702–714. doi:10.1016/j.ccr.2007.11.007.
- Evans, David A.; Miller, Scott J.; Lectka, Thomas; von Matt, Peter (1 August 1999). “Chiral Bis(oxazoline)copper(II) Complexes as Lewis Acid Catalysts for the Enantioselective Diels−Alder Reaction”. Journal of the American Chemical Society 121 (33): 7559–7573. doi:10.1021/ja991190k.
- Thorhauge, Jacob; Roberson, Mark; Hazell, Rita G.; Jørgensen, Karl Anker (15 April 2002). “On the Intermediates in Chiral Bis(oxazoline)copper(II)-Catalyzed Enantioselective Reactions—Experimental and Theoretical Investigations”. Chemistry – A European Journal 8 (8): 1888. doi:10.1002/1521-3765(20020415)8:8<1888::AID-CHEM1888>3.0.CO;2-9.
- Evans, David A.; Burgey, Christopher S.; Kozlowski, Marisa C.; Tregay, Steven W. (1 February 1999). “-Symmetric Copper(II) Complexes as Chiral Lewis Acids. Scope and Mechanism of the Catalytic Enantioselective Aldol Additions of Enolsilanes to Pyruvate Esters”. Journal of the American Chemical Society 121 (4): 686–699. doi:10.1021/ja982983u.
- Marigo, Mauro; Kjærsgaard, Anne; Juhl, Karsten; Gathergood, Nicholas; Jørgensen, Karl Anker (23 May 2003). “Direct Catalytic Asymmetric Mannich Reactions of Malonates and -Keto Esters”. Chemistry – A European Journal 9 (10): 2359–2367. doi:10.1002/chem.200204679.
- Evans, David A.; Burgey, Christopher S.; Paras, Nick A.; Vojkovsky, Tomas; Tregay, Steven W. (1 June 1998). “C2-Symmetric Copper(II) Complexes as Chiral Lewis Acids. Enantioselective Catalysis of the Glyoxylate−Ene Reaction”. Journal of the American Chemical Society 120 (23): 5824–5825. doi:10.1021/ja980549m.
- Evans, David A.; Willis, Michael C.; Johnston, Jeffrey N. (1 September 1999). “Catalytic Enantioselective Michael Additions to Unsaturated Ester Derivatives Using Chiral Copper(II) Lewis Acid Complexes”. Organic Letters 1 (6): 865–868. doi:10.1021/ol9901570. PMID 10823215.
- Aggarwal, Varinder K.; Belfield, Andrew J. (1 December 2003). “Catalytic Asymmetric Nazarov Reactions Promoted by Chiral Lewis Acid Complexes”. Organic Letters 5 (26): 5075–5078. doi:10.1021/ol036133h. PMID 14682768.
- Yao, Sulan; Johannsen, Mogens; Audrain, Hélène; Hazell, Rita G.; Jørgensen, Karl Anker (1 September 1998). “Catalytic Asymmetric Hetero-Diels−Alder Reactions of Ketones: Chemzymatic Reactions”. Journal of the American Chemical Society 120 (34): 8599–8605. doi:10.1021/ja981710w.
- Evans, David A.; Kozlowski, Marisa C.; Murry, Jerry A.; Burgey, Christopher S.; Campos, Kevin R.; Connell, Brian T.; Staples, Richard J. (1 February 1999). “C2-Symmetric Copper(II) Complexes as Chiral Lewis Acids. Scope and Mechanism of Catalytic Enantioselective Aldol Additions of Enolsilanes to (Benzyloxy)acetaldehyde”. Journal of the American Chemical Society 121 (4): 669–685. doi:10.1021/ja9829822.
- Ghosh, Arun K.; Mathivanan, Packiarajan; Cappiello, John (1998). “C2-Symmetric chiral bis(oxazoline)–metal complexes in catalytic asymmetric synthesis”. Tetrahedron: Asymmetry 9 (1): 1–45. doi:10.1016/S0957-4166(97)00593-4.
- Johnson, Jeffrey S.; Evans, David A. (1 June 2000). “Chiral Bis(oxazoline) Copper(II) Complexes: Versatile Catalysts for Enantioselective Cycloaddition, Aldol, Michael, and Carbonyl Ene Reactions”. Accounts of Chemical Research 33 (6): 325–335. doi:10.1021/ar960062n. PMID 10891050.
- Desimoni, Giovanni; Faita, Giuseppe; Jørgensen, Karl Anker (9 November 2011). “Update 1 of: C2-Symmetric Chiral Bis(oxazoline) Ligands in Asymmetric Catalysis”. Chemical Reviews 111 (11): PR284–PR437. doi:10.1021/cr100339a.
- Lowenthal, Richard E; Abiko, Atsushi; Masamune, Satoru (1990). “Asymmetric catalytic cyclopropanation of olefins: bis-oxazoline copper complexes”. Tetrahedron Letters 31 (42): 6005–6008. doi:10.1016/S0040-4039(00)98014-6.
- Evans, David A.; MacMillan, David W. C.; Campos, Kevin R. (1 November 1997). “-Symmetric Tin(II) Complexes as Chiral Lewis Acids. Catalytic Enantioselective Anti Aldol Additions of Enolsilanes to Glyoxylate and Pyruvate Esters”. Journal of the American Chemical Society 119 (44): 10859–10860. doi:10.1021/ja972547s.
- Aggarwal, Varinder K.; Anderson, Emma S.; Elfyn Jones, D.; Obierey, Kerstin B.; Giles, Robert (1 January 1998). “Catalytic asymmetric Diels–Alder reactions of α-thioacrylates for the preparation of norbornenone”. Chemical Communications (18): 1985–1986. doi:10.1039/a805366i.
- Nishiyama, Hisao.; Sakaguchi, Hisao.; Nakamura, Takashi.; Horihata, Mihoko.; Kondo, Manabu.; Itoh, Kenji. (1 March 1989). “Chiral and C2-symmetrical bis(oxazolinylpyridine)rhodium(III) complexes: effective catalysts for asymmetric hydrosilylation of ketones”. Organometallics 8 (3): 846–848. doi:10.1021/om00105a047.
- Ma, Jun-An; Cahard, Dominique (2004). “Copper(II) triflate-bis(oxazoline)-catalysed enantioselective electrophilic fluorination of β-ketoesters”. Tetrahedron: Asymmetry 15 (6): 1007–1011. doi:10.1016/j.tetasy.2004.01.014.
- Uozumi, Yasuhiro; Kyota, Hirokazu; Kato, Kazuhiko; Ogasawara, Masamichi; Hayashi, Tamio (1 March 1999). “Design and Preparation of 3,3‘-Disubstituted 2,2‘-Bis(oxazolyl)-1,1‘-binaphthyls (boxax): New Chiral Bis(oxazoline) Ligands for Catalytic Asymmetric Wacker-Type Cyclization”. The Journal of Organic Chemistry 64 (5): 1620–1625. doi:10.1021/jo982104m.
- Brunner, Henri; Miehling, Wolfgang (1 October 1984). “Enantioselektive Cyclopropanierung von 1,1-Diphenylethylen und Diazoessigester mit Kupfer-Katalysatoren”. Monatshefte für Chemie – Chemical Monthly 115 (10): 1237–1254. doi:10.1007/BF00809355.
- Nozaki, H.; Takaya, H.; Moriuti, S.; Noyori, R. (1968). “Homogeneous catalysis in the decomposition of diazo compounds by copper chelates”. Tetrahedron 24 (9): 3655–3669. doi:10.1016/S0040-4020(01)91998-2.
- Nozaki, H.; Aratani, T.; Toraya, T.; Noyori, R. (1971). “Asymmetric syntheses by means of (−)-sparteine modified organometallic reagents”. Tetrahedron 27 (5): 905–913. doi:10.1016/S0040-4020(01)92490-1.
- Aratani, T.; Yoneyoshi, Y.; Nagase, T. (1975). “Asymmetric synthesis of chrysanthemic acid. An application of copper carbenoid reaction”. Tetrahedron Letters 16 (21): 1707–1710. doi:10.1016/S0040-4039(00)72239-8.
- Aratani, T.; Yoneyoshi, Y.; Nagase, T. (1977). “Asymmetric synthesis of chrysanthemic acid. An application of copper carbenoid reaction”. Tetrahedron Letters 18 (30): 2599–2602. doi:10.1016/S0040-4039(01)83830-2.
- Aratani, Tadatoshi; Yoneyoshi, Yukio; Nagase, Tsuneyuki (1982). “Asymmetric synthesis of permethric acid. stereochemistry of chiral copper carbenoid reaction”. Tetrahedron Letters 23 (6): 685–688. doi:10.1016/S0040-4039(00)86922-1.
- Brunner, Henri; Obermann, Uwe; Wimmer, Peter (1 November 1986). “Asymmetrische katalysen”. Journal of Organometallic Chemistry 316 (1-2): C1–C3. doi:10.1016/0022-328X(86)82093-9.
- Brunner, Henri.; Obermann, Uwe.; Wimmer, Peter. (1 March 1989). “Asymmetric catalysis. 44. Enantioselective monophenylation of diols with cupric acetate/pyridinyloxazoline catalysts”. Organometallics 8 (3): 821–826. doi:10.1021/om00105a039.
- Fritschi, Hugo; Leutenegger, Urs; Pfaltz, Andreas (1 November 1986). “Chiral Copper-Semicorrin Complexes as Enantioselective Catalysts for the Cyclopropanation of Olefins by Diazo Compounds”. Angewandte Chemie International Edition in English 25 (11): 1005–1006. doi:10.1002/anie.198610051.
- Pfaltz, Andreas (1999). “From Corrin Chemistry to Asymmetric Catalysis – A Personal Account”. Synlett (S1): 835–842. doi:10.1055/s-1999-3122.
- Wiley, Richard H.; Bennett, Leonard L. “The Chemistry of the Oxazolines.”. Chemical Reviews 44 (3): 447–476. doi:10.1021/cr60139a002.
- Frump, John A. “Oxazolines. Their preparation, reactions, and applications”. Chemical Reviews 71 (5): 483–505. doi:10.1021/cr60273a003.
- Evans, David A.; Woerpel, Keith A.; Hinman, Mira M.; Faul, Margaret M. (1 January 1991). “Bis(oxazolines) as chiral ligands in metal-catalyzed asymmetric reactions. Catalytic, asymmetric cyclopropanation of olefins”. Journal of the American Chemical Society 113 (2): 726–728. doi:10.1021/ja00002a080.
- Corey, E. J.; Imai, Nobuyuki; Zhang, Hong Yue (1 January 1991). “Designed catalyst for enantioselective Diels-Alder addition from a C2-symmetric chiral bis(oxazoline)-iron(III) complex”. Journal of the American Chemical Society 113 (2): 728–729. doi:10.1021/ja00002a081.
- Pfaltz, Andreas; Adolfsson, Hans; Wärnmark, Kenneth; Aasbø, Kari; Klinga, Martti; Romerosa, Antonio (1 January 1996). “Design of Chiral Ligands for Asymmetric Catalysis: from C2-Symmetric Semicorrins and Bisoxazolines to Non-Symmetric Phosphinooxazolines.” (PDF). Acta Chemica Scandinavica 50: 189–194. doi:10.3891/acta.chem.scand.50-0189.
- Gant, Thomas G.; Noe, Mark C.; Corey, E.J. (1 November 1995). “The first enantioselective synthesis of the chemotactic factor sirenin by an intramolecular [2 + 1] cyclization using a new chiral catalyst”. Tetrahedron Letters 36 (48): 8745–8748. doi:10.1016/0040-4039(95)01924-7.
Aza-bis(oxazolines) – New Chiral Ligands for Asymmetric Catalysis
M. Glos, O. Reiser, Org. Lett. 2000, 2, 2045-2048
Web edition: http://dx.doi.org/10.1021/ol005947k
Aza-bis(oxazolines) are introduced as chiral ligands for asymmetric catalysis combining the advantages of easy availability of bis(oxazolines) and backbone variability of aza-semicorrins. Especially, the title ligands could be attached to a polymeric support, which allowed the development of easily recoverable copper(I)-catalysts for asymmetric cyclopropanation reactions.
Synthesis of Polymer Bound Azabis(oxazoline) Ligands and their Application in Asymmetric Cyclopropanations
H. Werner, C. I. Herrerías, M. Glos, A. Gissibl, J. M. Fraile, I. Pérez, J. A. Mayoral, O. Reiser, Adv. Synth. Catal. 2006, 348, 125-132
Web edition: http://dx.doi.org/10.1002/adsc.200505197
Aza(bisoxazoline) ligands were attached to various polymeric supports and the resulting immobilized ligands were evaluated in copper(I)-catalyzed asymmetric cyclopropanations. The efficiency of these transformations depends greatly on the polymeric support, on the protocol being applied for the immobilization of the ligands, and on the preparation of the catalysts.
Cu(II)-Aza(bisoxazoline)-Catalyzed Asymmetric Benzoylations
A. Gissibl, M. G. Finn, O. Reiser, Org. Lett. 2005, 7, 2325-2328
Web edition: http://dx.doi.org/10.1021/ol0505252
Racemic 1,2-diols and a-hydroxy carbonyl compounds can be asymmetrically benzoylated in a kinetic resolution in the presence of various Cu(II)-azabis(oxazoline) catalysts. A novel bisbenzyl substituted aza(bisoxazoline) ligand proved to be especially effective when immobilized on MeOPEG5000, giving 91 – ≥99% ee in 37 – 49% yield for each of five sequential reactions.
The role of binding constant in the efficiency of chiral catalysts immobilized by electrostatic interactions. The case of azabis(oxazoline)-copper complexes
J. M. Fraile, J. I. García, C. I. Herrerías, A. Mayoral, O. Reiser, A. Socuéllamos, H. Werner, Chem. Eur. J. 2004, 10, 2997-3005
Web edition: http://dx.doi.org/10.1002/chem.200305739
Azabis(oxazoline)-copper complexes are considerably more stable than the analogous bis(oxazoline)-copper complexes, as shown by theoretical calculations. The enhanced stability allows the efficient immobilization by means of electrostatic interactions with different anionic supports, such as clays and nafion-silica nanocomposites, without the loss of ligand observed with bis(oxazolines). In this way, enantioselectivities around 90% ee are obtained in the cyclopropanation reaction
Improved Synthesis of Aza-bis(oxazoline) Ligands
H. Werner, R. Vicha, A. Gissibl, O. Reiser, J. Org. Chem. 2003, 68, 10166-10168
Web edition: http://dx.doi.org/10.1021/jo0350920
A straightforward synthesis of chiral aza-bis(oxazoline) (Azabox) ligands from commercial available aminoalcohols is described. The new protocol allows access to previously reported Azabox ligands in considerably improved yields but also to new derivatives, including non C2-symmetrical ones.
Research Group Prof. Reiser