Preparation of arylphosphines

Details Preparation of arylphosphines Preparation of arylphosphines

2000-11-15

2001-11-20

Geist, Gary (Department: 1623)

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

Organic compounds

Carboxylic acid esters

C560S100000, C564S134000

Reexamination Certificate

active

06320068

ABSTRACT:

FIELD OF THE INVENTION
This invention relates to processes suitable for the large scale preparation of arylphosphines. especially those useful as ligand precursors or ligands in asymmetric allylic substitution catalysts.
BACKGROUND OF THE INVENTION
Chiral phosphine ligands such as (1) and (2)
and the opposite enantiomers thereof, have been shown to be effective in palladium(0)-catalysed asymmetric allylic substitution reactions. For a review, see Trost and Van Vranken, Chem Rev. (1996) 96: 395. See also U.S. Pat. No. 5,739,396.
Such catalysts are eminently suitable for industrial applications, especially for the provision of chiral pharmaceutical intermediates such as phthalimidovinyl glycinol, in high enantiomeric purity. For this purpose, and in other industrial applications such as flavour and fragrance fine chemicals, the development of manufacturing processes requires in turn large amounts of a ligand such as (1) or (2), e.g. in kilogram quantity or greater. Thus, there is a requirement for efficient and scaleable methods for synthesis of such ligands.
A key intermediate in the synthesis of these ligands is 2-diphenylphosphino-1-naphthoic acid and derivatives thereof. Several processes for the synthesis of arylphosphines from aryl triflates have been described in the literature.
For example, WO-A-9312260 and U.S. Pat. No. 5,739,396 disclose the reaction of trimethylsilyldiphenylphosphine, an aryl iodide and bis(benzonitrile)palladium dichloride in toluene at reflux. Trimethylsilyldiphenylphosphine is expensive and not readily available. This procedure gives only moderate yields (60%) and requires silica chromatography for purification of the product. Bis(benzonitrile)palladium dichloride is also expensive, and a high catalyst loading is used (5 mol %).
Another known process comprises the reaction of an aryl triflate with chlorodiphenylphosphine, a reductant (zinc) and a nickel catalyst in DMF at 100° C.; see Ager et al, Chem. Commun. (1997) 2359. This procedure typically requires a high catalyst loading (4-10 mol %) and can involve prolonged heating at reflux. The nickel catalyst is highly toxic and, as well as considerations for operator safety and residue disposal, filtration through a plug of silica is typically required to remove the catalyst.
Cai et al, J. Org. Chem. (1994) 59:7180-1, and U.S. Pat. No. 5,399,771 disclose the preparation of BINAP using the appropriate aryl triflate with diphenylphosphine. The preferred catalyst is nickel, palladium catalysis giving no reaction al all. Cai et al reports that DMF is the only satisfactory solvent. A chelating phosphine was also present.
Gilbertson et al, J. Org. Chem. (1996) 61:2922-3, discloses the palladium-catalysed conversion of aryl triflates, specifically tyrosine derivatives, to the corresponding aryl diphenylphosphines, by reaction with diphenylphosphine. The solvent is DMSO. It is reported that the reaction does not take place in DMF, using palladium. The Supplementary Material shows that 5 mol % of each of the catalyst Pd(OAC)
2
and 1,4-bis(diphenylphosphino)butane, i.e. a chelating phosphine, are used. Isolation of pure aryl diphenylphosphine products requires conversion to the corresponding phosphine sulfide, column chromatography and desulfurization with Raney nickel.
Reaction of diphenylphosphine, a base, palladium catalyst and aryl iodide (or bromide) also gives the corresponding triarylphosphine; see Werd et al, J. Organomet. Chem. (1996), 522: 69. For the synthesis of ligand (1) or (2), however, a 2-iodo- or 2-bromo-1-naphthoic acid derivative is not readily accessible.
SUMMARY OF THE INVENTION
The present invention is based on the discovery of an alternative process for preparing aryl phosphines, which allows the limitations of the prior art to be overcome. In particular, it has been discovered that an aryl sulfonyloxy compound can participate in a cross-coupling reaction with diphenylphosphine and palladium catalyst, without many of the restrictions that prejudice the development of an efficient, scaleable and economical synthesis of phosphines. The invention concerns the use of sulfonyloxy derivatives, readily prepared from the parent phenol, with a phosphine (HPR
2
R
3
), a base and palladium catalyst, in the following reaction:
R
1
OC—Ar—OSO
2
R
4
—R
1
OC—Ar—PR
2
R
3
The group R
1
may be an alkoxy or amino group. The groups R
2
and R
3
are any hydrocarbon group including, for example, aryl and alkyl. The group R
4
may be an aryl or alkyl group including those with halogen substitution.
Each of the respective R groups may optionally be substituted with one or more non-interfering group. Each such group may be of, for example, up to 20 C atoms.
One advantage of this invention is that no chelating phosphine is required. Another is that the solvent is not critical, thereby allowing the use of common, easy-to-handle organic solvents such as toluene and acetonitrile. Without wishing to be bound by theory, these two factors may be linked.
A further advantage of the invention is that the catalyst loading need not be especially high. For example, it is typically less than 1%, and often less than 0.5% (mol % relative to sulfonate). In particular, one-to-one stoichiometries of the phosphine and sulfonyloxy compound may be used, and with low catalyst loadings, for example 0.4 mol %, purification of the product is relatively simple.
In summary, this invention allows the aryl phosphine to be manufactured economically on a large scale. Material of reproducible quality can be manufactured in high yields.
DESCRIPTION OF THE INVENTION
Ar may represent any aromatic nucleus, mono or poly-cyclic, with or without hetero atoms such as N, O or S. Although the respective points of substitution of the COR
1
and PR
2
R
3
groups on the nucleus are not thought to be critical, they are typically in 1,2, 1,3 or 1,4-relationship on a benzene ring that is optionally otherwise substituted and/or fused to another ring or ring system. Thus, for example, a starting material for use in the invention may have the formula
wherein R is any non-interfering substituent and/or represents a fused ring.
Ar is most preferably naphthyl. R
1
is preferably alkoxy, more preferably methoxy.
A preferred embodiment of the present invention is a process for the preparation of 2-diphenylphosphino-1-naphthoic acid and derivatives thereof, for example those compounds therein where R
2
and R
3
are both phenyl and R
1
OC—Ar is 1-carboalkoxy-2-naphthyl. See the reaction shown in Example 1.
The preferred catalyst for this invention is a palladium (II) salt, more preferably palladium (II) acetate. The preferred base is a tertiary amine, more preferably triethylamine. The preferred groups for R
4
are perfluoroalkyl groups, including trifluoromethyl and perfluoro-1-butyl.
Typically the reagents are heated together at reflux in an appropriate solvent, for example toluene or acetonitrile, e.g. for approximately 16 hours. The solvent can be much less volatile than DMSO, e.g. boiling below 125° C. Progress of the reaction may be monitored by TLC or taking aliquots for analysis by
1
H NMR or
31
P NMR.


REFERENCES:
patent: 5399771 (1995-03-01), Cai et al.
patent: 9312260 (1993-06-01), None
patent: 9924444 (1999-05-01), None
Gilbertson et al, Journal of Organic Chemistry, 61(9), pp. 2922-2923 and Suplemental material provided by Applicants.*
Ager et al, Chemical Communications, 24 (21) pp. 2359-2360.*
Herd et al, Journal of Organometallic Chemistry, 522, (1)69-76.*
Gilbertson, S. R. et al. (1996) “Palladium-Catalyzed Synthesis of Phosphine-Containing Amino Acids”Journal of Organic Chemistry 61(9):2922-2923.
Herd, O. et al. (1996) “Water Soluble Phosphines VIII. Palladium-Catalyzed P-C Cross Coupling Reactions Between Primary or Secondary Phosphines and Functional Aryliodides—A Novel Synthetic Route to Water Soluble Phosphines”Journal of Organometallic Chemistry 522(1):69-76.
Wilson, S. R. et al. (1990) “Preparation of a New Class of C2-Symmetric Chiral Phosphines: The First Asymmetric Staudinger Reaction”Synlett(4):199-200.
Ager, D. J. et al. (1997) “Co

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