Active catalysts for stereoselective ring-opening reactions

Details Active catalysts for stereoselective ring-opening reactions Active catalysts for stereoselective ring-opening reactions

2002-09-17

2004-08-24

Nazario-Gonzalez, Porfirio (Department: 1621)

Organic compounds -- part of the class 532-570 series

Organic compounds

Heavy metal containing

C556S034000, C549S230000, C502S158000, C502S167000

Reexamination Certificate

active

06781006

ABSTRACT:

FIELD OF THE INVENTION
The present invention is directed to catalysts, more particularly, active transition metal-ligand catalyst complexes, for use in catalyzing stereoselective ring opening reactions.
BACKGROUND OF THE INVENTION
The stereoselective reaction of various nucleophiles in the ring-opening of epoxides catalyzed by chiral (salen)Co(III) complexes provides ready access to a large number of enantiomerically enriched chiral products useful to the pharmaceutical, agrochemical and flavor and fragrance industries. These products can be accessed via the kinetic resolution of racemic epoxides using sub-stoichiometric amounts of the nucleophile or via the stereoselective stoichiometric reaction of a nucleophile with a resolved epoxide. For these processes, the generation of the active Co(III) catalyst, either from inactive Co(II) species or from the chiral ligand and a metal salt, requires the use of a suitable solvent (typically a chlorinated hydrocarbon such as methylene chloride), a Brønsted acid (typically acetic acid), and air or oxygen. In the published procedures, the generation of active catalyst is typically performed each time the ring-opening reaction is run, and is subject to variability in quality and performance. U.S. Pat. Nos. 5,665,890, 5,929,232, 5,663,393, 5,637,739, 6,262,278, Tokunaga, M.; Larrow, J. F.; Kakiuchi, F.; Jacobsen, E. N. “Asymmetric Catalysis with Water: Efficient Kinetic Resolution of Terminal Epoxides by Means of Catalytic Hydrolysis,”
Science
1997 277, 936-938. Schaus, S. E.; Brandes, B. D.; Larrow, J. F.; Tokunaga, M.; Hansen, K. B.; Gould, A. E.; Furrow, M. E.; Jacobsen, E. N. “Highly Selective Hydrolytic Kinetic Resolution of Terminal Epoxides Catalyzed by Chiral (salen)Cobalt(III)-Complexes. Practical Synthesis of Enantioenriched Terminal Epoxides and 1,2-Diols,”
J. Am. Chem. Soc
2002, 124, 1307. Furrow, M. E., Schaus, S. E., Jacobsen, E. N. “Practical Access to Highly Enantioenriched C-3 Building Blocks via Hydrolytic Kinetic Resolution”
J. Org. Chem
. 1998, 63, 6776.
Currently, catalyst activation involves the reacting of inactive (salen)Co(II) complex with 2 equivalents of acetic acid in methylene chloride. Air is sparged through the mixture for several hours (depending on scale) to form the active (salen)Co(III)OAc catalyst and water (from the reduction of O
2
). At this point, the solvent is removed by reduced pressure distillation, which deposits the catalyst as a film of an amorphous solid on the walls of the vessel. There are several issues with this process which become magnified on scale. First, the sparging of air requires the use of a non-flammable solvent, or one with a high flashpoint due to the generation of air-solvent vapor mixtures. Since methylene chloride is low boiling and an environmental hazard, its vapor must be removed from the air effluent prior to release to the atmosphere. This requires scrubbing equipment that must be maintained. Second, the solvent removal takes time, which makes the process more costly, and the complete removal of solvent is virtually impossible, especially on larger scale. The residual solvent must then be removed from the product after the ring-opening reaction, which introduces further costs. Next, because the activation reaction is performed each time, there is an undesirable element of variability every time the ring-opening reaction is performed.
SUMMARY OF THE INVENTION
In a first aspect, the present invention is directed to a method for making a chiral catalyst complex, comprising:
contacting an asymmetric tetradentate ligand with a Brønsted acid, a Co(II) or Cr(II) salt, wherein the acidity of the conjugate acid of the salt is the same as or less than the acidity of the Brønsted acid, and an oxidant under conditions effective to allow formation of a chiral catalyst complex of Co(III) or Cr(III) and the ligand,
forming a solution of the complex in a water-miscible, protic solvent from which the complex can be precipitated by the addition of water, and
adding water to the solution to precipitate at least a portion of the complex.
In a second aspect, the present invention is directed to a method for making a chiral catalyst complex in particulate solid form, comprising:
providing a solution of a chiral catalyst complex of Co(III) or Cr(III) with an asymmetric tetradentate ligand in a water-miscible, protic solvent comprising a compound selected from methanol, ethanol, n-propanol and 1-methoxy-2-propanol,
adding water to the solution to precipitate at least a portion of the complex, and
isolating the precipitated complex as a particulate solid.
In a third aspect, the present invention is directed to a catalyst active in catalyzing stereoselective ring opening reactions, comprising a chiral catalyst complex of Co(III) or Cr(III) with an asymmetric tetradentate ligand and a counterion or nucleophile selected from carboxylate, hydroxide, alkoxide thiolate, sulfonate, sulfonamide, isocyanate, isothiocyanate, and halide, wherein the complex is in crystalline solid form.
In a fourth aspect, the present invention is directed to a method for stereoselective ring opening, comprising:
providing, in crystalline solid form, a chiral catalyst complex of Co(III) or Cr(III) with an asymmetric tetradentate ligand and a counterion or nucleophile selected from carboxylate, hydroxide, alkoxide, thiolate, sulfonate, sulfonamide, isocyanate, isothiocyanate, or halide that is active in catalyzing nucleophilic attack by a nucleophile of a chiral or prochiral cyclic substrate, wherein said substrate comprises a carbocycle or a heterocycle having a reactive center susceptible to the nucleophilic attack by the nucleophile,
reacting the nucleophile and the chiral or prochiral cyclic substrate in the presence of a catalytic amount of the catalyst complex under conditions effective to allow production of a stereoisomerically enriched product.
In a fifth aspect, the present invention is directed to a method for providing a chiral catalyst complex having known activity in catalyzing a stereoselective ring opening reaction, comprising:
isolating a chiral catalyst complex of Co(III) or Cr(III) with an asymmetric tetradentate ligand,
using a portion of the isolated complex to catalyze a first stereoselective ring opening reaction, and
characterizing the reaction rate of the first reaction, and
providing the remaining isolated complex for use in catalyzing stereoselective ring opening reactions analogous to the first stereoselective ring opening reaction


REFERENCES:
patent: 4746748 (1988-05-01), Aoki et al.
patent: 5637739 (1997-06-01), Jacobsen et al.
patent: 5663393 (1997-09-01), Jacobsen et al.
patent: 5665890 (1997-09-01), Jacobsen et al.
patent: 5929232 (1999-07-01), Jacobsen et al.
patent: 6262278 (2001-07-01), Jacobsen et al.
Tokunaga, M.; Larrow, J.F.; Kakiuchi, F.; Jacobsen, E.N. “Asymmetric Catalysis with Water: Efficient Kinetic Resolution of Terminal Epoxides by Means of Catalytic Hydrolysis,” Science 1997 277, 936-938.
Furrow, M.E., Schaus, S.E., Jacobsen, E.N. “Practical Access to Highly Enantioenriched C-3 Building Blocks via Hydrolytic Kinetic Resolution,” J. Org. Chem. 1998, 63, 6776.
Schaus, S.E.; Brandes, B.D.; Larrow, J.F.; Tokunaga, M.; Hansen, K.B.; Gould A.E., Furrow, M.E.; Jacobsen, E.N. “Highly Selective Hydrolytic Kinetic Resolution of Terminal Epoxides Catalyzed by Chiral (salen)Cobalt III) Complexes. Practical Synthesis of Enantioenriched Terminal Epoxides and 1,2-Diols,” J. Am. Chem. Soc 2002, 124, 1307.

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