Catalyst for Pauson-Khand reaction

Details Catalyst for Pauson-Khand reaction Catalyst for Pauson-Khand reaction

2002-04-19

2004-10-19

Barts, Samuel (Department: 1621)

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

Organic compounds

Oxygen containing

C568S349000, C568S365000, C502S152000, C502S162000

Reexamination Certificate

active

06806389

ABSTRACT:

The invention relates to the use of an immobilised transition metal carbonyl complex as a catalyst in the Pauson-Khand reaction and to processes using such a catalyst
The reaction between an &pgr;-alkynedicobalt hexacarbonyl complex, an alkene, and carbon monoxide to produce a cyclopentenone is generally referred to as the Pauson-Khand reaction (P. L. Pauson,
Tetrahedron
, 1985, 41, 5860) (Scheme 1).
The products of the Pauson-Khand reaction are in general chiral except in the case of certain symmetrical alkenes (X=X′ and Y=Y′). If the components of the reaction are racemic or prochiral then chiral cyclopentenones produced by the reaction are produced in racemic form.
The reaction succeeds for a wide range of substrates with the exception of tetrasubstituted alkenes, which are normally unreactive. The stereochemisty (e.g. M. E. Kraft,
J Amer. Chem. Soc
., 1988, 110, 968) and regiochemistry (e.g. K. H. Dotz and M. Popall,
Teirahedron
, 1985, 41, 5797) of the reaction have been the subject of investigation, for instance in the case of unsymmetrical alkynes the larger substituent (e.g. R′) generally forms the substituent at the a carbon of the cyclopentenone. In cases where the alkyne and alkene are both part of the same organic molecule the reaction forms two rings and where the olefin is itself cyclic tricyclic products are easily produced so that the reaction can give products of great complexity.
Accordingly the reaction is valuable because it makes complex organic molecules from simple components and these complex molecules are valuable per se or as intermediates for the production of high value-added products such as pharmaceuticals and fine chemicals.
Mixtures of an alkyne, an alkene, and carbon monoxide can also be converted in situ into &pgr;-alkynedicobalt hexacarbonyl complexes using stoichiometric amounts of dicobalt octacarbonyl or its tricobalt or tetracobalt homologues as part of the synthetic route leading to cyclopentenones.
Substoichiometric amounts of dicobalt octacarbonyl or &pgr;-alkynedicobalt hexacarbonyl have also been used to catalyse the formation of cyclopentenones from alkynes, alkenes, and carbon monoxide (e.g. I. U. Khand, G. R. Knox, P. L. Pauson, W. E. Watts, and M. I. Foreman,
J. Chem. Soc., Perkin Trans. I
, 1973, 977; D. B. Belanger, D. J. R O'Mahoney and T. Livinghouse,
Tetrahedron Lett
., 1998, 39, 7637; and D. B. Belanger and T. Livinghouse,
Tetrahedron Lett
., 1998, 39, 7641).).
Derivatives of &pgr;-alknedicobalt hexacarbonyl complexes such as &pgr;-alkynedicobaltcarbonylphosphine complexes have been used in the Pauson-Khand reaction (P. Bladon, P. L. Pauson, H. Brunner and R. Eder,
J. Organometal. Chem
., 1988, 355, 449) and catalysis of the Pauson-Khand reaction using dicobalt octacarbonyl has been performed in the presence of added ligands such as phosphites and phosphines (N. Jeong, S. H. Hwang, Y. Lee and Y. K. Chung,
J. Amer. Chem. Soc
., 1994, 116, 3159). Heterobimetallic analogues in which a cobalt atom has been replaced by molybdenum are also known (D. T. Rutherford and S. D. R. Christie
Tetrahedron Lett
., 1998, 39, 9805).
We use the term “Pauson-Khand” reaction to include all reactions between carbon monoxide, alkenes, and alkynes that are promoted by transition metal complexes and that lead to cyclopentenone formation. Specifically, and preferably, by the use of the term “Pauson-Khand” reaction we refer to Scheme 1, wherein Co is cobalt or any other transition metal as described herein, R and R′, X and X′, Y and Y′ may be the same or different and wherein X and R may be joined together, or X and Y together form a ring system.
Although the Pauson-Khand reaction produces useful products it suffers from a number of drawbacks. Dicobaltoctacarbonyl and its analogues are volatile, toxic, and unstable both to loss of carbon monoxide and to aerial oxidation. Accordingly the cobalt carbonyl reagent poses hazards in storage, use, disposal, and product purification. For best results the commercial reagent often requires rigorous purification immediately before use (e.g. “Impure samples of commercial Co
2
(CO)
8
must be rigorously purified by recrystallisation from degassed HPLC grade hexane or room temperature sublimation at 50 mTorr immediately prior to use”. T. Livinghouse,
Tetrahedron Lett
, 1998, 39, 7637). In addition, generally, the cyciopentenone product may retain metal impurities, especially when used stoicheometrically.
We have recently described the use of immobilised transition metal complexes as traceless linkers for unsaturated organic molecules (WO00/007966). A class of immobilised &pgr;-alkynedicobalt hexacarbonyl complexes used as disclosed, in which an alkyne is immobilised using its &pgr;-alkynedicobalt hexacarbonyl complex as a traceless link, the alkyne or its derivative would can be easily liberated at the end of a sequence of stoichiometric steps.
We have now found that immobilised cobalt carbonyl complexes prepared for use as traceless linkers are members of an advantageous class of catalysts that promote the Pauson-Khand reaction. The invention is illustrated below.
Where the Transition ion Metal Complex is drawn from the group of transition metal-ligand complexes Known to promote the Pauson-Khand reaction and is preferably a cobalt carbonyl or cobalt complex derivative thereof.
For instance, the invention is illustrated below (Catalyst A) where the support is a cross linked polystyrene resin, the linker ligand is a diphenylphosphine, and the transition metal complex is derived from dicobalt octacarbonyl. The representation of Catalyst A is schematic and is not intended to define the chemical constitution or the bonding of the catalytically active species.
The method of the invention offers considerable advantages. It is safe and convenient to use at all stages of the operation. The immobilised catalysts may be prepared in active form from commercially available precursors such as dicobalt octacarbonyl (Strem Chemical Co. Inc.) and they retain their activity for longer than their analogues that are not immobilised. The immobilised catalysts are not volatile and are easier to contain than their analogues that are not immobilised. Accordingly they are safer to use, store, and transport. The immobilised catalyst may also be easily recovered from the reaction, for example, by filtration so that valuable catalysts may be recovered for reuse, potential environmental contaminants may be easily eliminated, and the product may be separated from potentially noxious transition metal carbonyl contaminants. Because the catalyst may be easily recovered for reuse the method of the invention enables the economic use of costly transition metal complexes designed to confer special benefits such as the production of enantiomerically pure or enriched cyclopetenones.
An example of the use of an immobilised catalyst is given in Scheme 2.
Presented as a first feature of the invention is the use of an immobilised cobalt carbonyl complex as a catalyst in a Pauson-Khand reaction.
The immobilised &pgr;-alkynecobaltcarbonyl complex may also be activated as a catalyst for the Pauson-Khand reaction by prior conversion into an alkyne complex. The alkyne may be one which is the same as the alkyne reagent used in the Pauson-Khand reaction or may be one which is readily displaced by the alkyne reagent used in the Pauson-Khand reaction and therefore will exchange with the alkyne reagent to form a complex with the cobalt.
Presented as a further feature of the invention is the use of an immobilised &pgr;-alkynecobalt carbonyl complex as a catalyst for the Pauson-Khand reaction.
A further feature is the use of immobilised analogues and derivatives of cobalt carbonyls and their alkyne complexes as catalysts in a Pauson-Khand reaction.
As discussed above, depending upon the starting alkene starting material, chiral centres may be found in the cyclopentenone product. However, typically, Pauson-Khand reactions produce racemic mires of any product with a chiral centre. In the prior art it

Affiliated with

Also associated with

Rating

Catalyst for Pauson-Khand reaction does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Catalyst for Pauson-Khand reaction, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Catalyst for Pauson-Khand reaction will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3296574