CATIONIC COBALT COMPLEXES FOR ASYMMETRIC HYDROGENATION AND METHODS OF MAKING THE SAME

Abstract

In one aspect, methods for the facile synthesis of cationic cobalt complexes for asymmetric hydrogenation of alkenes are provided. Synthetic methods described herein, in some embodiments, provide Co(I) precatalysts on a time scale and yield permitting catalytic evaluation of a significant number of enantiopure ligands.

Claims

1. A method of making a cationic cobalt(I) complex comprising: providing a precursor complex of the formula: ##STR00012## wherein one or both of the pyridine ligands are optionally substituted with one or more substituents; and substituting ligands of the precursor complex with optically active bis(phosphine) ligand and arene ligand to provide the cationic cobalt(I) complex of formula: ##STR00013## wherein R.sup.1 and R.sup.2 are independently selected from the group consisting of alkyl and heteroalkyl, and X.sup. is a counterion.

2. The method of claim 1, wherein the optically active bis(phosphine) ligand is enantiopure.

3. The method of claim 1, wherein the optically active bis(phosphine) ligand displaces the pyridine ligands of the precursor complex to provide an intermediate complex of the formula: ##STR00014##

4. The method of claim 1 having a yield of the cationic cobalt(I) complex of greater than 90%.

5. The method of claim 1, wherein the cationic cobalt(I) complex is synthesized in a time period less than 10 minutes.

6. The method of claim 1, wherein the cationic cobalt(I) complex is synthesized in a time period of 5 minutes of less.

7. The method of claim 1, wherein the optically active bis(phosphine) ligand is selected from the group consisting of DuPhos, BenzP*, TangPhos, and DuanPhos.

8. The method of claim 1, wherein the precursor complex is of the formula ##STR00015## wherein R.sup.3 and R.sup.4 are independently alkyl.

9. A method of asymmetric alkene hydrogenation comprising: providing an alkene substrate, and hydrogenating the alkene substrate in the presence of a cationic cobalt(I) catalyst to yield a single enantiomer reaction product, wherein the cationic cobalt(I) catalyst is derived from a precatalyst of the formula: ##STR00016## wherein ##STR00017## is optically active bis(phosphine) ligand, and X.sup. is a counterion, the precatalyst being synthesized by providing a precursor complex of the formula: ##STR00018## wherein one or both of the pyridine ligands are optionally substituted with one or more substituents, and substituting ligands of the precursor complex with the optically active bis(phosphine) ligand and arene ligand, wherein R.sup.1 and R.sup.2 are independently selected from the group consisting of alkyl and heteroalkyl.

10. The method of claim 9, wherein the optically active bis(phosphine) ligand is selected from the group consisting of DuPhos, BenzP*, TangPhos, and DuanPhos.

11. The method of claim 9, wherein the alkene substrate is a pharmaceutical compound or a pharmaceutical precursor.

12. The method of claim 11, wherein the alkene substrate is of the formula: ##STR00019## wherein R is selected from the group consisting of hydrogen and alkyl, and R is selected from the group consisting of hydrogen, acetate, and benzyl chloroformate.

13. The method of claim 11, wherein the alkene is of the formula: ##STR00020## is selected from the group consisting of hydrogen and alkyl, and R is selected from the group consisting of hydrogen, acetate, and benzyl chloroformate, and Y is selected from the group consisting of hydrogen and aryl.

14. The method of claim 9, wherein the precursor complex is of the formula ##STR00021## wherein R.sup.3 and R.sup.4 are independently alkyl.

15. A transition metal complex of the formula: ##STR00022## wherein ##STR00023## is optically active bis(phosphine) ligand, and R.sup.1 and R.sup.2 are independently selected from the group consisting of alkyl and heteroalkyl.

16. The transition metal complex of claim 15, wherein the optically active bis(phosphine) ligand is selected from the group consisting of DuPhos, BenzP*, TangPhos, and DuanPhos.

17. A method of making a cationic cobalt (I) complex comprising: providing a cationic cobalt(I) arene sandwich precursor complex, and substituting an arene ligand of the precursor complex with an optically active bis(phosphine) ligand to provide the cationic cobalt(I) complex of formula: ##STR00024## wherein X.sup. is a counterion.

18. The method of claim 17, wherein the cationic cobalt(I) arene sandwich precursor complex is of the formula: ##STR00025##

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0013] FIG. 1 illustrates various cationic Co(I) complexes synthesized according to methods described herein.

[0014] FIG. 2 illustrates various alkene substrates for asymmetric hydrogenation with Co(I) complexes described herein.

[0015] FIG. 3 illustrates a synthetic route for a Co(I) complex according to one embodiment.

[0016] FIG. 4 illustrates a synthetic route for a Co(I) complex according to one embodiment.

[0017] FIG. 5 illustrates a synthetic route for a Co(I) complex according to one embodiment.

[0018] FIG. 6 illustrates a synthetic route for a Co(I) complex according to one embodiment.

[0019] FIG. 7 illustrates a synthetic route for a Co(I) complex according to one embodiment.

DETAILED DESCRIPTION

[0020] Embodiments described herein can be understood more readily by reference to the following detailed description and examples and their previous and following descriptions. Elements, apparatus and methods described herein, however, are not limited to the specific embodiments presented in the detailed description and examples. It should be recognized that these embodiments are merely illustrative of the principles of the present invention. Numerous modifications and adaptations will be readily apparent to those of skill in the art without departing from the spirit and scope of the invention.

Example 1Synthesis of Cationic Co(I) Complex for Asymmetric Hydrogenation

[0021] A Co(I) complex for asymmetric hydrogenation was prepared according to the reaction scheme of FIG. 3 and as follows.

[0022] Preparation of [(S,S)-(.sup.MeDuPhos) Co(.sup.6C.sub.6H.sub.6)][BAr.sup.F.sub.4]. In a nitrogen-filled glovebox, a 20 mL scintillation vial was charged with (py).sub.2Co(CH.sub.2SiMe.sub.3).sub.2 (0.097 g, 0.24 mmol) as a dark green semi-solid and 2 mL of diethyl ether were added. In a separate vial, (S,S)-.sup.MeDuPhos (0.078 g, 0.25 mmol) was weighed out as a crystalline white solid and dissolved in diethyl ether. To the ethereal solution of (S,S)-.sup.MeDuPhos was added (py).sub.2Co(CH.sub.2SiMe.sub.3).sub.2 dropwise. The dark green ethereal solution of (py).sub.2Co(CH.sub.2SiMe.sub.3).sub.2 instantly turned dark red when combined with bis(phosphine) and was stirred for 30 seconds at ambient temperature. Single-crystals of (S,S)-(.sup.MeDuPhos) Co(CH.sub.2SiMe.sub.3).sub.2 deposited on the sides of the scintillation vial could be collected and used in the oxidatively-induced reductive elimination, however, routine precatalyst synthesis was done in one-pot. Finally, [(.sup.5C.sub.5H.sub.5).sub.2Fe][BAr.sup.F.sub.4] (0.251 g, 0.24 mmol) was weighed out as a deep blue solid and dissolved in 3 mL of a mixture of diethyl ether and benzene (2:1). When [(.sup.5C.sub.5H.sub.5).sub.2Fe][BAr.sup.F.sub.4] was added dropwise to the dark red ethereal solution of (S,S)-(.sup.MeDuPhos) Co(CH.sub.2SiMe.sub.3).sub.2 (formed in situ), the deep blue color instantly gave way to bright yellow. The reaction mixture was stirred for 5 minutes at ambient temperature, at which point the solution became cloudy. Volatiles were removed under reduced pressure and the residue was washed with pentane to remove ferrocene and silane byproducts. The residue was taken up in diethyl ether and passed through a pad of Celite where it was then dried under reduced pressure to yield 0.301 g (96% yield) of [(S,S)-(.sup.MeDuPhos)Co(.sup.6C.sub.6H.sub.6)][BAr.sup.F.sub.4] as an orange crystalline powder.

[0023] Anal Calcd for C.sub.52H.sub.46BCoF.sub.24P.sub.2: C, 51.48; H, 3.55. Found: C, 51.5; H, 3.2. .sup.1H NMR (500 MHz, THF-d.sub.8, 23 C.): 7.79 (br m, 8H, o-B[(3,5-(CF.sub.3).sub.2)C.sub.6H.sub.3].sub.4), 7.68 (br m, 2H, .sup.iPrDuPhos ArH), 7.59 (br m, 2H, .sup.iPrDuPhos ArH), 7.57 (br m, 4H, p-B[(3,5-(CF.sub.3).sub.2)C.sub.6H.sub.3].sub.4), 6.38 (s, 6H, .sup.6C.sub.6H.sub.6), 2.65 (br m, 2H, .sup.iPrDuPhos CH), 2.34 (br m, 2H, .sup.iPrDuPhos CH), 2.31 (br m, 2H, .sup.iPrDuPhos CH.sub.2), 2.20 (br m, 2H, .sup.iPrDuPhos CH.sub.2), 1.80 (br m, 2H, .sup.iPrDuPhos CH.sub.2), 1.55 (br m, 2H, .sup.iPrDuPhos CH.sub.2), 1.37 (br m, 6H, .sup.iPrDuPhos CH.sub.3), 0.86 (br m, 6H, .sup.iPrDuPhos CH.sub.3). .sup.13C{.sup.1H} NMR (125.7 MHz, THF-d.sub.8, 23 C.): 162.9 (q, .sup.1J.sub.B-C=50.1 Hz, B[(3,5-(CF.sub.3).sub.2)C.sub.6H.sub.3].sub.4), 143.8 (app t, .sup.iPrDuPhos Ar), 135.8 (br s, B[(3,5-(CF.sub.3).sub.2)C.sub.6H.sub.3].sub.4), 132.5 (s, .sup.iPrDuPhos Ar), 132.0 (app t, .sup.iPrDuPhos Ar), 130.2 (m, B[(3,5-(CF.sub.3).sub.2)C.sub.6H.sub.3].sub.4), 125.7 (q, .sup.1J.sub.C-F=272.5 Hz, B[(3,5-(CF.sub.3).sub.2)C.sub.6H.sub.3].sub.4), 118.4 (br s, B[(3,5-(CF.sub.3).sub.2)C.sub.6H.sub.3].sub.4), 93.6 (s, .sup.6C.sub.6H.sub.6), 45.9 (app t, .sup.iPrDuPhos CH), 42.6 (app t, .sup.iPrDuPhos CH), 37.2 (.sup.iPrDuPhos CH.sub.2), 36.8 (.sup.iPrDuPhos CH.sub.2), 17.9 (.sup.iPrDuPhos CH.sub.3), 13.9 (.sup.iPrDuPhos CH.sub.3). .sup.31P{.sup.1H} NMR (202.4 MHz, THF-d.sub.8, 23 C.): 96.2 (s, 2P). .sup.19F NMR (376.5 MHz, THF-d.sub.8, 23 C.): 63.4 (s, B[(3,5-(CF.sub.3).sub.2)C.sub.6H.sub.3].sub.4).

Example 2Synthesis of Cationic Co(I) Complex for Asymmetric Hydrogenation

[0024] A Co(I) complex for asymmetric hydrogenation was prepared according to the reaction scheme of FIG. 4 and as follows.

[0025] Preparation of [(R,R)-(BenzP*)Co(.sup.6C.sub.6H.sub.6)][BAr.sup.F.sub.4]. In a nitrogen-filled glovebox, a 20 mL scintillation vial was charged with (py).sub.2Co(CH.sub.2SiMe.sub.3).sub.2 (0.051 g, 0.13 mmol) as a dark green semi-solid and 2 mL of diethyl ether were added. In a separate vial, (R,R)-BenzP* (0.037 g, 0.13 mmol) was weighed out as a crystalline white solid and dissolved in diethyl ether. To the diethyl ether solution of (R,R)-BenzP* was added a diethyl ether solution of (py).sub.2Co(CH.sub.2SiMe.sub.3).sub.2 dropwise. A color change to bright orange was observed immediately and the mixture was stirred for an additional 30 seconds at ambient temperature. Finally, [(.sup.5C.sub.5H.sub.5).sub.2Fe][BAr.sup.F.sub.4] (0.136 g, 0.13 mmol) was weighed out as a deep blue solid and dissolved in a mixture of diethyl ether and benzene (2:1). When [(.sup.5C.sub.5H.sub.5).sub.2Fe][BAr.sup.F.sub.4] was added dropwise to the stirring ethereal solution of (R,R)-(BenzP*)Co(CH.sub.2SiMe.sub.3).sub.2 (formed in situ), the deep blue color instantly gave way to bright yellow. The reaction mixture was stirred for 5 minutes at ambient temperature, at which point the solution became cloudy. Volatiles were removed under reduced pressure and the residue was washed with pentane to remove ferrocene and silane byproducts. The residue was extracted into diethyl ether and passed through a pad of Celite where it was then dried under reduced pressure to yield 0.163 g (99% yield) of [(R,R)-(BenzP*)Co(.sup.6C.sub.6H.sub.6)][BAr.sup.F.sub.4] as an orange crystalline powder. Anal Calcd for C.sub.54H.sub.46BCoF.sub.24P.sub.2: C, 50.57; H, 3.62. Found: C, 46.07; H, 2.75. .sup.1H NMR (500 MHz, THF-d.sub.8, 23 C.): .sup.1H NMR (500 MHz, THF-d.sub.8, 23 C.): 7.79 (br m, 8H, o-B[(3,5-(CF.sub.3).sub.2)C.sub.6H.sub.3].sub.4), 7.76 (br m, 2H, BenzP* Ar), 7.64 (br m, 2H, BenzP* Ar), 7.57 (br m, p-B[(3,5-(CF.sub.3).sub.2)C.sub.6H.sub.3].sub.4), 6.38 (s, 6H, .sup.6C.sub.6H.sub.6), 1.89 (m, 6H, BenzP* CH.sub.3), 0.93 (m, 18H, BenzP* CH.sub.3). .sup.13C{.sup.1H} NMR (125.7 MHz, THF-d.sub.8, 23 C.): 162.9 (q, .sup.1J.sub.B-C=51.4 Hz, B[(3,5-(CF.sub.3).sub.2)C.sub.6H.sub.3].sub.4), 135.7 (br s, B[(3,5-(CF.sub.3).sub.2)C.sub.6H.sub.3].sub.4), 131.9 (s, BenzP* Ar), 131.4 (app t, BenzP* Ar), 127.9 (q, .sup.1J.sub.C-F=269.9 Hz, B[(3,5-(CF.sub.3).sub.2)C.sub.6H.sub.3].sub.4), 118.3 (br m, B[(3,5-(CF.sub.3).sub.2)C.sub.6H.sub.3].sub.4), 93.3 (s, .sup.6C.sub.6H.sub.6), 36.8 (m, BenzP* CH.sub.3), 27.4 (s, BenzP* C(CH.sub.3).sub.3), 11.7 (s, BenzP* C(CH.sub.3).sub.2). .sup.31P{.sup.1H} NMR (202.4 MHz, THF-d.sub.8, 23 C.): 77.3 (s, 2P). .sup.19F NMR (376.5 MHz, THF-d.sub.8, 23 C.): 6-63.4 (s, B[(3,5-(CF.sub.3).sub.2)C.sub.6H.sub.3].sub.4).

Example 3Synthesis of Cationic Co(I) Complex for Asymmetric Hydrogenation

[0026] A Co(I) complex for asymmetric hydrogenation was prepared according to the reaction scheme of FIG. 5 and as follows.

[0027] Preparation of [(1S,1S,1R,1R)-(DuanPhos)Co(.sup.6C.sub.6H.sub.6)][BAr.sup.F.sub.4]. In a nitrogen-filled glovebox, a 20 mL scintillation vial was charged with (py).sub.2Co(CH.sub.2SiMe.sub.3).sub.2 (0.070 g, 0.18 mmol) as a dark green semi-solid and 2 mL of diethyl ether were added. In a separate vial, (1S,1S,1R,1R)-DuanPhos (0.075 g, 0.18 mmol) was weighed out as a crystalline orange solid and dissolved in diethyl ether. To the ethereal solution of (1S,1S,R,1R)-DuanPhos was added a diethyl ether solution of (py).sub.2Co(CH.sub.2SiMe.sub.3).sub.2 dropwise. A color change to bright orange was observed and the reaction mixture was stirred an additional 30 seconds at ambient temperature.

[0028] Finally, [(.sup.5C.sub.5H.sub.5).sub.2Fe][BAr.sup.F.sub.4] (0.188 g, 0.18 mmol) was weighed out as a deep blue solid and dissolved in a mixture of diethyl ether and benzene (2:1). The solution containing the [(.sup.5C.sub.5H.sub.5).sub.2Fe][BAr.sup.F.sub.4] was added dropwise to the stirring ethereal solution of (1S,1S,R,1R)-(DuanPhos)Co(CH.sub.2SiMe.sub.3).sub.2 (formed in situ), and a color change from deep blue to dark orange was observed. The reaction mixture was stirred for 5 minutes at ambient temperature, at which point the solution became cloudy. Volatiles were removed under reduced pressure and the residue was washed with pentane to remove ferrocene and silane byproducts. The residue was taken up in diethyl ether and passed through a pad of Celite where it was then dried under reduced pressure to yield 0.253 g (92% yield) of [(1S,1S,1R,1R)-(DuanPhos)Co(.sup.6C.sub.6H.sub.6)][BAr.sup.F.sub.4] as a dark orange crystalline powder. Anal Calcd for C.sub.62H.sub.50BCoF.sub.24P.sub.2: C, 50.41; H, 3.92. Found: C, 50.04; H, 3.51. .sup.1H NMR (500 MHz, THF-d.sub.8, 23 C.): at 23 C., spectra were broad and uninformative. .sup.31P{.sup.1H} NMR (202.4 MHz, THF-d.sub.8, 23 C.): 127.2 (s, 2P). .sup.19F NMR (376.5 MHz, THF-d.sub.8, 23 C.): 63.5 (s, B[(3,5-(CF.sub.3).sub.2)C.sub.6H.sub.3].sub.4).

Example 4Synthesis of Cationic Co(I) Complex for Asymmetric Hydrogenation

[0029] A Co(I) complex for asymmetric hydrogenation was prepared according to the reaction scheme of FIG. 6 and as follows.

[0030] Preparation of [(S,S,R,R)-(TangPhos)Co(.sup.6C.sub.6H.sub.6)][BAr.sup.F.sub.4]. In a nitrogen-filled glovebox, a 20 mL scintillation vial was charged with (py).sub.2Co(CH.sub.2SiMe.sub.3).sub.2 (0.070 g, 0.18 mmol) as a dark green semi-solid and 2 mL of diethyl ether were added. In a separate vial, (S,S,R,R)-TangPhos (0.075 g, 0.18 mmol) was weighed out as a crystalline orange solid and dissolved in diethyl ether. To the ethereal solution of (S,S,R,R)-TangPhos was added (py).sub.2Co(CH.sub.2SiMe.sub.3).sub.2 dropwise. The dark green ethereal solution of (py).sub.2Co(CH.sub.2SiMe.sub.3).sub.2 instantly turned bright orange when combined with bis(phosphine) and was stirred for 30 seconds at ambient temperature.

[0031] Finally, [(-C.sub.5H.sub.5).sub.2Fe][BAr.sup.F.sub.4] (0.188 g, 0.18 mmol) was weighed out as a deep blue solid and dissolved in a mixture of diethyl ether and benzene (2:1). When [(.sup.5C.sub.5H.sub.5).sub.2Fe][BAr.sup.F.sub.4] was added dropwise to the stirring ethereal solution of (S,S,R,R)-(TangPhos)Co(CH.sub.2SiMe.sub.3).sub.2 (formed in situ), the deep blue color instantly gave way to dark orange. The reaction mixture was stirred for 5 minutes at ambient temperature, at which point the solution became cloudy. Volatiles were removed under reduced pressure and the residue was washed with pentane to remove ferrocene and silane byproducts. The residue was taken up in diethyl ether and passed through a pad of Celite where it was then dried under reduced pressure to yield 0.253 g (92% yield) of [(S,S,R,R)-(TangPhos)Co(.sup.6C.sub.6H.sub.6)][BAr.sup.F.sub.4] as a dark orange crystalline powder. Anal Calcd for C.sub.54H.sub.50BCoF.sub.24P.sub.2: C, 50.41; H, 3.92. Found: C, 50.04; H, 3.51. .sup.1H NMR (500 MHz, THF-d.sub.8, 23 C.): 7.78 (br m, 8H, o-B[(3,5-(CF.sub.3).sub.2)C.sub.6H.sub.3].sub.4), 7.57 (br m, p-B[(3,5-(CF.sub.3).sub.2)C.sub.6H.sub.3].sub.4), 6.26 (s, 6H, .sup.6C.sub.6H.sub.6), 2.43-2.31 (ov m, 4H, TangPhos CH+TangPhos CH.sub.2), 2.09-1.94 (ov m, 6H, TangPhos CH.sub.2), 1.63 (m, 2H, TangPhos CH.sub.2), 1.17 (m, 18H, TangPhos C(CH.sub.3).sub.3). .sup.13C{.sup.1H} NMR (125.7 MHz, THF-d.sub.8, 23 C.): 162.9 (q, .sup.1J.sub.B-C=50.1 Hz, B[(3,5-(CF.sub.3).sub.2)C.sub.6H.sub.3].sub.4), 135.7 (br s, B[(3,5-(CF.sub.3).sub.2)C.sub.6H.sub.3].sub.4), 130.1 (br m, B[(3,5-(CF.sub.3).sub.2)C.sub.6H.sub.3].sub.4), 125.7 (q, .sup.1J.sub.C-F=272.2 Hz, B[(3,5-(CF.sub.3).sub.2)C.sub.6H.sub.3].sub.4), 118.3 (br m, B[(3,5-(CF.sub.3).sub.2)C.sub.6H.sub.3].sub.4), 92.8 (s, .sup.6C.sub.6H.sub.6), 46.5 (app t, TangPhos CH), 37.4 (app t, TangPhos CH.sub.2), 35.5 (app t, TangPhos CH.sub.2), 33.6 (app t, TangPhos CH.sub.2), 28.5 (s, TangPhos C(CH.sub.3).sub.3), 28.2 (s, TangPhos C(CH.sub.3).sub.3). .sup.31P{.sup.1H} NMR (202.4 MHz, THF-d.sub.8, 23 C.): 121.7 (s, 2P). .sup.19F NMR (376.5 MHz, THF-d.sub.8, 23 C.): 6-63.4 (s, B[(3,5-(CF.sub.3).sub.2)C.sub.6H.sub.3].sub.4).

Example 5Synthesis of Cationic Co(I) Complex for Asymmetric Hydrogenation

[0032] A Co(I) complex for asymmetric hydrogenation was prepared according to the reaction scheme of FIG. 7 and as follows.

[0033] This method utilizes a 20-electron arene sandwich cation, (e.g. [Co(.sup.6C.sub.6H.sub.6).sub.2][X]) stabilized by either the weakly coordinating anion (WCA), [Al(OR.sup.F).sub.4].sup. (R.sup.FC(CF.sub.3).sub.3) developed by the group of Ingo Krossing, or commonly-used anions including BAr.sup.F.sub.4.sup., SbF.sub.6.sup., PF.sub.6.sup., and BF.sub.4.sup.. We have shown that combinations of [Co(.sup.6C.sub.6H.sub.6).sub.2][Al(OR.sup.F).sub.4] and optically-active bis(phosphines) including (R,R)-.sup.iPrDuPhos, lead to air-stable, 18-electron bis(phosphine) cobalt cations similar to those described above with the key distinction being the composition of the anion. The reaction to generate the 18-electron cations must be carried out in 1,2-difluorobenzene given the poor stability of the 20-electron arene sandwich complex [Co(.sup.6C.sub.6H.sub.6).sub.2][Al(OR.sup.F).sub.4] in coordinating solvents including THF. A representative example is given below: In a nitrogen-filled glovebox, a 20 mL scintillation vial was charged with [Co(.sup.6C.sub.6H.sub.6).sub.2][Al(OR.sup.F).sub.4] (0.010 g, 8.5 mol) and dissolved in 2 mL of 1,2-difluorobenzene to give an amber-colored solution. Separately, (R,R)-.sup.iPrDuPhos (0.004 g, 8.6 mol) was dissolved in 2 mL of benzene and added to [Co(.sup.6C.sub.6H.sub.6).sub.2][Al(OR.sup.F).sub.4] at ambient temperature resulting in an immediate color change from amber to bright yellow. Characterization of the product by multinuclear NMR spectroscopy in THF-d.sub.8 gave nearly-identical shifts to the 18-electron cobalt complex [(R,R)-(.sup.iPrDuPhos)Co(.sup.6C.sub.6H.sub.6)][BAr.sup.F.sub.4] with the exception of the .sup.19F NMR spectrum which contained a single peak corresponding to the CF.sub.3 groups of the aluminate anion. The activity of this complex was surveyed in the asymmetric hydrogenation of dehydro-sitagliptin where it maintained excellent enantioselectivity (96% ee) at 50 C. under 1000 psi of H.sub.2.

Example 6Synthesis of Cationic Co(I) Complex for Asymmetric Hydrogenation

[0034] Preparation of [(RR)-(.sup.iPrDuPhos)Co(.sup.6C.sub.6H.sub.6)][BAr.sup.F.sub.4]. In a nitrogen-filled glovebox, a 20 mL scintillation vial was charged with (3,5-(Me).sub.2-C.sub.5H.sub.3N).sub.2Co(CH.sub.2SiMe.sub.3).sub.2 (0.081 g, 0.18 mmol) as a dark green crystalline solid and dissolved in 2 mL of diethyl ether. In a separate vial, (R,R)-.sup.iPrDuPhos (0.075 g, 0.18 mmol) was weighed out as a crystalline white solid and dissolved in diethyl ether. To the ethereal solution of (R,R)-.sup.iPrDuPhos was added (3,5-(Me).sub.2-C.sub.5H.sub.3N).sub.2Co(CH.sub.2SiMe.sub.3).sub.2 dropwise. The dark green ethereal solution of (3,5-(Me).sub.2-C.sub.5H.sub.3N).sub.2Co(CH.sub.2SiMe.sub.3).sub.2 instantly turned bright orange when combined with bis(phosphine) and was stirred for 30 seconds at ambient temperature. Finally, [(.sup.5C.sub.5H.sub.5).sub.2Fe][BAr.sup.F.sub.4] (0.188 g, 0.18 mmol) was weighed out as a deep blue solid and dissolved in a mixture of diethyl ether and benzene (2:1). When [(.sup.5C.sub.5H.sub.5).sub.2Fe][BAr.sup.F.sub.4] was added dropwise to the stirring ethereal solution of (R,R)-(.sup.iPrDuPhos)Co(CH.sub.2SiMe.sub.3).sub.2 (formed in situ), the deep blue color instantly gave way to bright yellow. The reaction mixture was stirred for 5 minutes at ambient temperature, at which point the solution became cloudy. Volatiles were removed under reduced pressure and the residue was washed with pentane to remove ferrocene and silane byproducts. The residue was taken up in diethyl ether and passed through a pad of Celite where it was then dried under reduced pressure to yield 0.251 g (98% yield) of [(R,R)-(.sup.iPrDuPhos)Co(.sup.6C.sub.6H.sub.6)][BAr.sup.F.sub.4] as an orange-yellow crystalline powder. Characterization data were consistent with our previously-reported method involving chloride abstraction from [(R,R)-(.sup.iPrDuPhos)Co(-Cl)].sub.2 with NaBAr.sup.F.sub.4.

[0035] Various embodiments of the invention have been described in fulfillment of the various objectives of the invention. It should be recognized that these embodiments are merely illustrative of the principles of the present invention. Numerous modifications and adaptations thereof will be readily apparent to those skilled in the art without departing from the spirit and scope of the invention.