Solvias® Ligand Portfolio for Enantioselective Hydrogenation

William Sommer, Daniel Weibel

Hans-Ulrich Blaser, Garrett Hoge, Matthias Lotz, Benoît Pugin, Anita Schnyder, Felix Spindler

Solvias AG, P.O. Box, CH-4002 Basel, Switzerland , Contact: Dr. Garrett Hoge, Product Manager Catalysis,

garrett.hoge@solvias.com

Today's Solvias Ligand Portfolio has its roots in the development of the Josiphos ligands and the successful implementation in the (S)-metolachlor process—the largest industrial enantioselective manufacturing process—in the former Ciba-Geigy. Over the last decade, several additional ligand families have been added, either via Solvias' own research or via licensing from other companies.1 The central concept for all Solvias ligands is their modularity, usually via the introduction of different phosphino moieties in the very last stages of their synthesis. This allows the easy tuning of the steric and electronic properties and, thereby, the adaptation to the needs of a specific reaction. All ligands in the Solvias portfolio are available on a research scale with very short lead times; several ligands are being produced regularly in multikilogram quantities. The number of ligands within the different families varies between 10 to >100; therefore, it is not practical to have all of them available in a catalog. For this reason the members offered via Sigma-Aldrich® are a selection representing different steric and electronic properties. Further derivatives for optimization or fine tuning are usually available on request from Solvias.

MeOBIPHEP

In many respects, the catalytic profile of the MeOBIPHEP ligands is rather similar to that of other atropisomeric diphosphines such as BINAP and its many analogs.1–3 The nature of the PR2 group strongly influences the catalytic performance of the metal complexes, and the ligands available have different steric bulk.1 MeOBIPHEP complexes are highly effective for the hydrogenation of α- and β-functionalized ketones (Figure 1), the hydrogenation of allylic alcohols and α,β-unsaturated esters (Figure 2), the hydrogenation of heteroarenes (Figure 3) and a variety of synthetically useful C–C coupling reactions (Figure 4).

MeOBIPHEP complexes are highly effective for the hydrogenation of α- and β-functionalized ketones

Figure 1.


 hydrogenation of allylic alcohols and α,β-unsaturated esters

Figure 2.


hydrogenation of heteroarenes

Figure 3.


variety of synthetically useful C–C coupling reactions

Figure 4.

Josiphos

The Josiphos ligands arguably constitute one of the most versatile and successful ligand families, second probably only to the BINAP ligands. Since the two phosphine groups are introduced in consecutive steps with very high yields,1,2 a variety of ligands are readily available with widely differing steric and electronic properties. Up to now, only the (R,SFc)-family (and its enantiomers) but not the (R,RFc) diastereomers have led to high enantioselectivities. At present, about 150 different Josiphos ligands have been prepared and 40 derivatives are available in a ligand kit (12000) for screening and on a multikilogram scale for production.3

Catalytic applications of the Josiphos ligand family were reviewed up to 2002.3 Until now, Josiphos ligands have been applied in 4 production processes and about 5 or 6 pilot and bench scale processes involving Rh, Ir, and Ru catalyzed hydrogenation reactions of C=C and C=N bonds.4 Selected applications are summarized in Figure 1. The most important application is undoubtedly the Ir/J005‑1 catalyzed hydrogenation of a hindered N-aryl imine of methoxyacetone, the largest known enantioselective process operated for the enantioselective production of the herbicide (S)-metolachlor.2,5 The hydrogenation of tetrasubstituted olefins was the key step for two production processes developed for the synthesis of biotin by Lonza and of methyl dihydrojasmonate by Firmenich.6 Pilot processes were developed by Lonza for a building block of crixivan and for dextromethorphane.6 Recently, Merck & Co. chemists reported the unprecedented hydrogenation of unprotected dehydro β-amino acid derivatives catalyzed by Rh-Josiphos with ee's up to 97%. It was shown that not only simple derivatives but also the complex intermediate for MK-0431 depicted in Figure 1 can be hydrogenated successfully. Regular production on a multiton/year scale with ee's up to 98% has been started in 2006.7

Josiphos ligands

Figure 1.

Rh and Ir complexes with chiral Josiphos ligands are highly selective, active, and productive catalysts for various enantioselective reductions. Very high enantioselectivities were described for the enantioselective hydrogenation of enamides, itaconic acid derivatives, acetoacetates as well as N-aryl imines (in presence of acid and iodide) and phosphinylimines.3 Josiphos J001 is the ligand of choice for the Cu catalyzed reduction of activated C=C bonds with polymethylhydrosiloxane (PMHS) (Figure 2) with very high enantioselectivities for nitro alkenes,8 α,β-unsaturated ketones,9a esters,9b,c and nitriles.10 Very recently, it was disclosed that Ru-Josiphospyridinyl- alkylamines complexes (best ligands J001 and J007) are extraordinarily effective for the enantioselective transfer hydrogenation of aryl ketones with turnover frequencies for full conversion exceeding 20,000 h-1 (Figure 3).11

Cu catalyzed reduction of activated C=C bonds with polymethylhydrosiloxane

Figure 2.


enantioselective transfer hydrogenation of aryl ketones

Figure 3.

Josiphos complexes have been successfully applied to various asymmetric catalytic coupling reactions such as allylic alkylation or hydroformylation.3 Selected recent examples are depicted in Figure 4. Feringa's group reported high ee's for the Cu catalyzed Michael addition of Grignard reagents to α,β-unsaturated esters,12a thioesters,12b,c and for selected cyclic enones.12d The preferred ligands were J001 and J004. The Rh/J001 was very effective for the nucleophilic ring opening of various oxabicyclic substrates leading to interesting new tetrahydronaphthalene and cyclohexene derivatives.13a,b This reaction was scaled up to the kilogram scale.13c The Pd catalyzed opening of various cyclic anhydrides with Ph2Zn was described by Bercot and Rovis to occur with very high ee's in presence of J001.14 Lorman et al.15 reported up to 95% ee for an intermolecular Heck reaction using a Pd/J001 catalyst.

 allylic alkylation or hydroformylation

Figure 4.

Josiphos ligands were not only applied to enantioselective reactions but also were shown to be useful for Pd catalyzed coupling reactions with very high activities. Hartwig's group reported that Pd/J009 (88733 and 88734) complexes were effective catalysts for the amination of aryl halides or sulfonates with ammonia,16a coupling of aryl halides or sulfonates with thiols,16b and Kumada coupling of aryl or vinyl tosylates with Grignard reagents.16c

Walphos

Like Josiphos, Walphos ligands are modular but form 8‑membered metallocycles due to the additional phenyl ring attached to the cyclopentadiene ring.1 There are noticeable electronic effects but the scope of this ligand family is still under investigation; several derivatives are available from Solvias on a research scale. Walphos ligands show promise for various enantioselective hydrogenations and pertinent examples are depicted in Figure 1. Rh/Walphos catalysts gave good results for dehydro amino and itaconic acid derivatives1–3 (ee 92–95%, preferred ligands W001, W002, W004, W006 and W009) and of vinyl boronates4 (see Figure 1). Ru/Walphos complexes were highly selective for β-keto esters (ee 91‑95%, W001, W002, W003 and W005) and acetyl acetone (ee >99.5%, s/c 1000, W001).2,3 Recently, two novel transformations were reported to be catalyzed by Rh/Walphos complexes with high enantioselectivities (Figure 1): the 4+2‑addition of 4‑alkynals with an acryl amide by Tanaka and co-workers5 and the reductive coupling of enynes with α-keto esters by Krische's group.6

 Walphos ligands

Figure 1.

The first industrial application has just been realized in collaboration with Speedel/Novartis for the hydrogenation of SPP100‑SyA, a sterically demanding α,β-unsaturated acid intermediate of the renin inhibitor SPP100.2 The process has already been operated on a multiton scale. Lilly's chemists7 developed a process of a PPAR agonist using the Rh-catalyzed asymmetric hydrogenation of (Z)-cinnamic acid as key step. A screen of over 250 catalysts and conditions revealed Rh-W001 as the most effective ligand, giving the product in 92% ee.

Taniaphos

Compared to Josiphos, the Taniaphos ligands developed by the Knochel group1 have an additional phenyl ring inserted at the side chain of the Ugi amine. Besides the two-phosphine moieties, the substituent at the stereogenic center can also be varied and, up to now, three generations of Taniaphos ligands with different substituents at the α-position have been prepared. Several Taniaphos ligands are being marketed by Solvias in collaboration with Umicore and selected derivatives are being produced on a multikilogram scale.

A variety of Taniaphos ligands are very selective in a number of model hydrogenation reactions.1,2 Both the nature of two phosphine moieties, as well as the substituent and the configuration of the stereogenic center at the α-position, have strong effects on the catalytic performance, sometimes even on the sense of induction. Taniaphos complexes are highly active and stereoselective for the Rh catalyzed hydrogenation of methyl acetamido cinnamate (ee 94–99.5%) and dimethyl itaconate (91–99.5% ee), and in the Ru catalyzed hydrogenation of β-ketoesters (94–98% ee), cyclic β-ketoesters (85–94% ee, 99% de of anti-product, s/c up to 25,000) and 1,3‑diketones (97–99.4% ee, ~99% de of anti-product). Enamides are hydrogenated with 92–97% ee's but low TOFs (Rh/T021) and a β-dehydroacetamido acid with 99.5% (Rh/T003).

Recently, a variety of highly enantioselective transformations were described using Taniaphos complexes.3,4 Selected reactions are depicted in Figure 1. T001 was found to be very selective for the Rh catalyzed nucleophilic ring opening of an azabicycle.3 Cu Taniaphos complexes were also very effective for the reductive addition of aldehydes4a to methyl acrylate and of methyl ketones to methyl acrylate.4b

Taniaphos complexes

Figure 1.

Mandyphos (Ferriphos)

Ferriphos was first prepared by Ito and coworkers1 as a bidentate analog of PPFA. In 1998, Knochel2 developed a general synthesis for a highly modular ligand family which was later called Mandyphos in which not only the PR'2 moieties but also the substituents at the side chain can be used for fine tuning purposes. Selected Mandyphos derivatives are commercialized by Solvias in collaboration with Umicore. Even though the scope of this family is not yet fully explored, screening results3 indicate high enantioselectivities as well as high activity for several Mandyphos derivatives in the Rh catalyzed hydrogenation of dehydroamino acid derivatives (preferred ligand M004, 95 – >99% ee, s/c up to 20,000) and the Ru catalyzed hydrogenation of tiglic acid (M004, 97% ee). M004 was also the ligand of choice for the Rh catalyzed hydrogenation of various methyl 2‑furyl acrylates4 while Rh/Ferriphos was highly selective for Rh catalyzed ring opening of azabicycles with amines5 (see Figure 1). Several Mandyphos derivatives are being produced on a multikilogram scale.

Rh/Ferriphos was highly selective for Rh catalyzed ring opening of azabicycles with amines

Figure 1.

Naud Catalyst

Complexes prepared in situ from RuCl2(PPh3)3 and chiral phosphine-oxazoline ligands (Naud catalysts) are effective catalysts for the hydrogenation of various aryl ketones with up to 99% ee's and substrate to catalyst ratios of 10,000–50,000. The reaction tolerates high substrate concentrations,1 and several derivatives are being produced on a multikilogram scale. A pilot process has been developed for the hydrogenation of 3,5‑bistrifluoromethyl acetophenone.2 The reaction was carried out twice on a 140 kg scale at 20 bar and 25 °C with substrate to catalyst ratios of 20,000 with an enantiomeric excess of >95%. After crystallization, (R)-3,5‑bistrifluoromethyl phenyl ethanol was obtained with an ee between 97.7 and 98.6% in 70% chemical yield (Figure 1). A feasibility study was reported by Merck & Co. for the reduction of a highly functionalized aryl ketone.3

Naud Catalyst

Figure 1.

Butiphane

In many respects the catalytic profile of the Butiphane ligands1 P005‑1 (53361) and P005‑2 (53362) is rather similar to that of other phospholane diphosphines such as DuPhos and its many analogs.2 Up to now, the potential of the ligand has only been demonstrated in the Rh catalyzed hydrogenation of dehydroamino acid derivatives, enamides, and itaconates, achieving ee values of up to 98.7%.1

Materials
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Reference (MeOBIPHEP)

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Tang W, Zhang X. 2003. New Chiral Phosphorus Ligands for Enantioselective Hydrogenation. Chem. Rev.. 103(8):3029-3070. http://dx.doi.org/10.1021/cr020049i
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Blanc D, Ratovelomanana-Vidal V, Gillet J, Genêt J. 2000. Asymmetric synthesis of fluorinated ?-hydroxy esters via ruthenium-mediated hydrogenation. Journal of Organometallic Chemistry. 603(1):128-130. http://dx.doi.org/10.1016/s0022-328x(00)00174-1
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Cederbaum F, Lamberth C, Malan C, Naud F, Spindler F, Studer M, Blaser H. 2004. Synthesis of Substituted Mandelic Acid Derivativesvia Enantioselective Hydrogenation: Homogeneous versus Heterogeneous Catalysis. Advanced Synthesis & Catalysis. 346(7):842-848. http://dx.doi.org/10.1002/adsc.200404022
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Ratovelomanana-Vidal V, Genêt J, Mordant C, Caño de Andrade C, Touati R, Hassine BB. 2003. Stereoselective Synthesis of Diltiazem via Dynamic Kinetic Resolution. Synthesis.(15):2405-2409. http://dx.doi.org/10.1055/s-2003-42397
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Makino K, Iwasaki M, Hamada Y. 2006. Enantio- and Diastereoselective Hydrogenation via Dynamic Kinetic Resolution by a Cationic Iridium Complex in the Synthesis of ?-Hydroxy-?-amino Acid Esters. Org. Lett.. 8(20):4573-4576. http://dx.doi.org/10.1021/ol061796v
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Jacobsen EN, Yamamoto H, Pfaltz A. 1999. Comprehensive Asymmetric Catalysis. p 1439.. Berlin: Springer .
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Crameri Y, Foricher J, Hengartner U, Jenny C, Kienzle F, Ramuz H, Scalone M, Schlageter M, Wang S. 1997. Asymmetric Hydrogenation vs. Resolution in the Synthesis of POSICOR®, a New Type of Calcium Antagonist. CHIMIA International Journal for Chemistry. 51(6)303-5..
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Blaser HU, Schmidt E. 2003. Large Scale Asymmetric Catalysis. Weinheim Wiley-VCH.71.
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Bulliard M, Laboue B, Lastennet J, Roussiasse S. 2001. Large-Scale Candoxatril Asymmetric Hydrogenation. Org. Process Res. Dev.. 5(4):438-441. http://dx.doi.org/10.1021/op010005w
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Wang W, Lu S, Yang P, Han X, Zhou Y. 2003. Highly Enantioselective Iridium-Catalyzed Hydrogenation of Heteroaromatic Compounds, Quinolines. J. Am. Chem. Soc.. 125(35):10536-10537. http://dx.doi.org/10.1021/ja0353762
16.
Kong JR, Krische MJ. 2006. Catalytic CarbonylZ-Dienylation via Multicomponent Reductive Coupling of Acetylene to Aldehydes and ?-Ketoesters Mediated by Hydrogen:  Carbonyl Insertion into Cationic Rhodacyclopentadienes. J. Am. Chem. Soc.. 128(50):16040-16041. http://dx.doi.org/10.1021/ja0664786
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Han X, Widenhoefer RA. 2006. Platinum-Catalyzed Intramolecular Asymmetric Hydroarylation of Unactivated Alkenes with Indoles. Org. Lett.. 8(17):3801-3804. http://dx.doi.org/10.1021/ol061441b
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Koh JH, Larsen AO, Gagné MR. 2001. Asymmetric Pt(II)-Catalyzed Ene Reactions:? Counterion-Dependent Additive and Diphosphine Electronic Effects1. Org. Lett.. 3(8):1233-1236. http://dx.doi.org/10.1021/ol015702n
19.
Tschoerner M, Pregosin PS, Albinati A. 1999. Contributions to the Enantioselective Heck Reaction Using MeO?Biphep Ligands. The Case Against Dibenzylidene Acetone. Organometallics. 18(4):670-678. http://dx.doi.org/10.1021/om980783l

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2.
Blaser HU, Buser HP, Coers K, Hanreich R, Jalett HP, Jelsch E, Pugin B, Schneider HD, Spindler F, Wegmann A. 1999. The chiral switch of metolachlor: The development of a large-scale enantioselective catalytic process.. CHIMIA International Journal for Chemistry. 53(6)275-80..
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Blaser H, Brieden W, Pugin B, Spindler F, Studer M, Togni A. 2002. 19(1):3-16. http://dx.doi.org/10.1023/a:1013832630565
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6.
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Hsiao Y, Rivera NR, Rosner T, Krska SW, Njolito E, Wang F, Sun Y, Armstrong JD, Grabowski EJJ, Tillyer RD, et al. 2004. Highly Efficient Synthesis of ?-Amino Acid Derivatives via Asymmetric Hydrogenation of Unprotected Enamines. J. Am. Chem. Soc.. 126(32):9918-9919. http://dx.doi.org/10.1021/ja047901i
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Kubryk M, Hansen KB. 2006. Application of the asymmetric hydrogenation of enamines to the preparation of a beta-amino acid pharmacophore. Tetrahedron: Asymmetry. 17(2):205-209. http://dx.doi.org/10.1016/j.tetasy.2005.12.016
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Clausen AM, Dziadul B, Cappuccio KL, Kaba M, Starbuck C, Hsiao Y, Dowling TM. 2006. Identification of Ammonium Chloride as an Effective Promoter of the Asymmetric Hydrogenation of a ?-Enamine Amide. Org. Process Res. Dev.. 10(4):723-726. http://dx.doi.org/10.1021/op050232o
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Czekelius C, Carreira EM. 2003. Catalytic Enantioselective Conjugate Reduction of?,?-Disubstituted Nitroalkenes. Angew. Chem. Int. Ed.. 42(39):4793-4795. http://dx.doi.org/10.1002/anie.200352175
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Czekelius C, Carreira EM. 2004. Convenient Catalytic, Enantioselective Conjugate Reduction of Nitroalkenes Using CuF2. Org. Lett.. 6(24):4575-4577. http://dx.doi.org/10.1021/ol048035h
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Lipshutz BH, Servesko JM. 2003. CuH-Catalyzed Asymmetric Conjugate Reductions of Acyclic Enones. Angew. Chem. Int. Ed.. 42(39):4789-4792. http://dx.doi.org/10.1002/anie.200352313
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Lipshutz BH, Servesko JM, Taft BR. 2004. Asymmetric 1,4-Hydrosilylations of ?,?-Unsaturated Esters. J. Am. Chem. Soc.. 126(27):8352-8353. http://dx.doi.org/10.1021/ja049135l
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Lipshutz BH, Tanaka N, Taft BR, Lee C. 2006. Chiral Silanes via Asymmetric Hydrosilylation with Catalytic CuH. Org. Lett.. 8(10):1963-1966. http://dx.doi.org/10.1021/ol0529593
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Lee D, Kim D, Yun J. 2006. Highly Enantioselective Conjugate Reduction of ?,?-Disubstituted ?,?-Unsaturated Nitriles. Angew. Chem. Int. Ed.. 45(17):2785-2787. http://dx.doi.org/10.1002/anie.200600184
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Baratta W, Chelucci G, Herdtweck E, Magnolia S, Siega K, Rigo P. 2007. Highly Diastereoselective Formation of Ruthenium Complexes for Efficient Catalytic Asymmetric Transfer Hydrogenation. Angew. Chem. Int. Ed.. 46(40):7651-7654. http://dx.doi.org/10.1002/anie.200702278
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López F, Harutyunyan SR, Meetsma A, Minnaard AJ, Feringa BL. 2005. Copper-Catalyzed Enantioselective Conjugate Addition of Grignard Reagents to ?,?-Unsaturated Esters. Angewandte Chemie International Edition. 44(18):2752-2756. http://dx.doi.org/10.1002/anie.200500317
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Reference (Walphos)

1.
Sturm T, Xiao L, Weissensteiner W. 2001. Preparation of novel enantiopure ferrocenyl-based ligands for asymmetric catalysis. CHIMIA International Journal for Chemistry.. 55(9):688-93.
2.
Sturm T, Weissensteiner W, Spindler F. 2003. A Novel Class of Ferrocenyl-Aryl-Based Diphosphine Ligands for Rh- and Ru-Catalysed Enantioselective Hydrogenation. Advanced Synthesis & Catalysis. 345(12):160-164. http://dx.doi.org/10.1002/adsc.200390003
3.
Morgan JB, Morken JP. 2004. Catalytic Enantioselective Hydrogenation of Vinyl Bis(boronates). J. Am. Chem. Soc.. 126(47):15338-15339. http://dx.doi.org/10.1021/ja044396g
4.
Moran WJ, Morken JP. 2006. Rh-Catalyzed Enantioselective Hydrogenation of Vinyl Boronates for the Construction of Secondary Boronic Esters. Org. Lett.. 8(11):2413-2415. http://dx.doi.org/10.1021/ol060735u
5.
Tanaka K, Hagiwara Y, Noguchi K. 2005. Rhodium-Catalyzed Regio- and Enantioselective Intermolecular [4+2] Carbocyclization of 4-Alkynals withN,N-Dialkyl Acrylamides. Angew. Chem. Int. Ed.. 44(44):7260-7263. http://dx.doi.org/10.1002/anie.200502380
6.
Kong J, Ngai M, Krische MJ. 2006. Highly Enantioselective Direct Reductive Coupling of Conjugated Alkynes and ?-Ketoesters via Rhodium-Catalyzed Asymmetric Hydrogenation. J. Am. Chem. Soc.. 128(3):718-719. http://dx.doi.org/10.1021/ja056474l
7.
Houpis IN, Patterson LE, Alt CA, Rizzo JR, Zhang TY, Haurez M. 2005. Synthesis of PPAR Agonist via Asymmetric Hydrogenation of a Cinnamic Acid Derivative and Stereospecific Displacement of (S)-2-Chloropropionic Acid. Org. Lett.. 7(10):1947-1950. http://dx.doi.org/10.1021/ol050367e

Reference (Taniaphos)

1.
Ireland T, Grossheimann G, Wieser‐Jeunesse C, Knochel P. 1999. Ferrocenyl ligands with two phosphanyl substituents in the α, ε positions for the transition metal catalyzed asymmetric hydrogenation of functionalized double bonds.. Angewandte Chemie International Edition.. 38(21):3212-5.
2.
Ireland T, Tappe K, Grossheimann G, Knochel P. 2002. Synthesis of a new class of chiral 1, 5‐diphosphanylferrocene ligands and their use in enantioselective hydrogenation Chemistry. A European Journal. 8(4):843-52.
3.
Lotz M, Polborn K, Knochel P. 2002. New Ferrocenyl Ligands with Broad Applications in Asymmetric Catalysis. Angew. Chem. Int. Ed.. 41(24):4708-4711. http://dx.doi.org/10.1002/anie.200290024
4.
Tappe K, Knochel P. 2004. New efficient synthesis of Taniaphos ligands: application in ruthenium- and rhodium-catalyzed enantioselective hydrogenations. Tetrahedron: Asymmetry. 15(1):91-102. http://dx.doi.org/10.1016/j.tetasy.2003.11.004
5.
Spindler F, Malan C, Lotz M, Kesselgruber M, Pittelkow U, Rivas-Nass A, Briel O, Blaser H. 2004. Modular chiral ligands: the profiling of the Mandyphos and Taniaphos ligand families. Tetrahedron: Asymmetry. 15(14):2299-2306. http://dx.doi.org/10.1016/j.tetasy.2004.06.033
6.
Lautens M, Fagnou K, Zunic V. 2002. An Expedient Enantioselective Route to Diaminotetralins:? Application in the Preparation of Analgesic Compounds. Org. Lett.. 4(20):3465-3468. http://dx.doi.org/10.1021/ol026579i
7.
Chuzel O, Deschamp J, Chausteur C, Riant O. 2006. Copper(I)-Catalyzed Enantio- and Diastereoselective Tandem Reductive Aldol Reaction. Org. Lett.. 8(26):5943-5946. http://dx.doi.org/10.1021/ol062398v
8.
Deschamp J, Chuzel O, Hannedouche J, Riant O. 2006. Highly Diastereo- and Enantioselective Copper-Catalyzed Domino Reduction/Aldol Reaction of Ketones with Methyl Acrylate. Angew. Chem.. 118(8):1314-1319. http://dx.doi.org/10.1002/ange.200503791

Reference (Mandyphos (Ferriphos))

1.
Sawamura M, Hamashima H, Ito Y. 1991. A trans-chelating chiral diphosphine ligand: Synthesis of 2,2?-bis[1-(diphenylphosphino)ethyl]-1,1?-biferrocene and its complexes with platinum(II) and palladium(II). Tetrahedron: Asymmetry. 2(7):593-596. http://dx.doi.org/10.1016/s0957-4166(00)86110-8
2.
Lotz M, Ireland T, Almena Perea JJ, Knochel P. 1999. Stereoselective substitution of ?-aminoalkylferrocenes with diorganozincs. A fast synthesis of new chiral FERRIPHOS ligands for asymmetric catalysis. Tetrahedron: Asymmetry. 10(10):1839-1842. http://dx.doi.org/10.1016/s0957-4166(99)00182-2
3.
Lotz M, Ireland T, Almena Perea JJ, Knochel P. 1999. Stereoselective substitution of ?-aminoalkylferrocenes with diorganozincs. A fast synthesis of new chiral FERRIPHOS ligands for asymmetric catalysis. Tetrahedron: Asymmetry. 10(10):1839-1842. http://dx.doi.org/10.1016/s0957-4166(99)00182-2
4.
Almena Perea JJ, Lotz M, Knochel P. 1999. Synthesis and application of C2-symmetric diamino FERRIPHOS as ligands for enantioselective Rh-catalyzed preparation of chiral ?-amino acids. Tetrahedron: Asymmetry. 10(2):375-384. http://dx.doi.org/10.1016/s0957-4166(99)00002-6
5.
Spindler F, Malan C, Lotz M, Kesselgruber M, Pittelkow U, Rivas-Nass A, Briel O, Blaser H. 2004. Modular chiral ligands: the profiling of the Mandyphos and Taniaphos ligand families. Tetrahedron: Asymmetry. 15(14):2299-2306. http://dx.doi.org/10.1016/j.tetasy.2004.06.033
6.
Hashmi ASK, Haufe P, Schmid C, Rivas Nass A, Frey W. 2006. Asymmetric Rhodium-Catalyzed Hydrogenation Meets Gold-Catalyzed Cyclization: Enantioselective Synthesis of 8-Hydroxytetrahydroisoquinolines. Chem. Eur. J.. 12(20):5376-5382. http://dx.doi.org/10.1002/chem.200600192
7.
Cho Y, Zunic V, Senboku H, Olsen M, Lautens M. 2006. Rhodium-Catalyzed Ring-Opening Reactions ofN-Boc-Azabenzonorbornadienes with Amine Nucleophiles. J. Am. Chem. Soc.. 128(21):6837-6846. http://dx.doi.org/10.1021/ja0577701

Reference (Naud Catalyst)

1.
Naud F, Malan C, Spindler F, Rüggeberg C, Schmidt A, Blaser H. 2006. Ru-(Phosphine-Oxazoline) Complexes as Effective, Industrially Viable Catalysts for the Enantioselective Hydrogenation of Aryl Ketones. Adv. Synth. Catal.. 348(1-2):47-50. http://dx.doi.org/10.1002/adsc.200505246
2.
Naud F, Spindler F, Rueggeberg CJ, Schmidt AT, Blaser H. 2007. Enantioselective Ketone Hydrogenation:  From R&D to Pilot Scale with Industrially Viable Ru/Phosphine?Oxazoline Complexes. Org. Process Res. Dev.. 11(3):519-523. http://dx.doi.org/10.1021/op0601619
3.
Tellers DM, Bio M, Song ZJ, McWilliams JC, Sun Y. 2006. Enantioselective hydrogenation of an ?-alkoxy substituted ketone with chiral ruthenium (phosphinoferrocenyl)oxazoline complexes. Tetrahedron: Asymmetry. 17(4):550-553. http://dx.doi.org/10.1016/j.tetasy.2005.12.028

Reference (Butiphane)

1.
Berens U, Englert U, Geyser S, Runsink J, Salzer A. 2006. A Flexible Approach to Different Families of Bidentate P,P Ligands as Highly Efficient Ligands for Asymmetric Catalysis. Eur. J. Org. Chem.. 2006(9):2100-2109. http://dx.doi.org/10.1002/ejoc.200500937
2.
Cornelis J, Elsevier, Johannes GdV. 2007. In Handbook of Homogeneous Hydrogenation p 773. Wiley- VCH.

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