Organic compounds -- part of the class 532-570 series – Organic compounds – Heavy metal containing
Reexamination Certificate
2002-01-22
2003-09-02
Vollano, Jean F. (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heavy metal containing
C558S073000, C564S013000, C568S012000, C562S808000
Reexamination Certificate
active
06613922
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to new bidentate phosphines, phosphonite, phosphonous diamide and phosphonoamidite ligands having a p-cyclophane backbone, precursors thereof, and their use as ligands for transition metal-catalysed asymmetric reactions, notably rhodium, iridium and ruthenium-catalysed hydrogenation of double bonds.
BACKGROUND OF THE INVENTION
At the heart of most asymmetric catalytic synthesis is the use of catalysts based on a transition metal surrounded by appropriate chiral, enantiomerically enriched, organic ligands. Bidentate chiral phosphines (phosphorus III compounds with three C—P bonds) are the most widely used class of ligands, finding applications in a range of asymmetric reactions (R. Noyori,
Asymmetric Catalysis in Organic Synthesis,
John Wiley & Sons, 1994; N. Jacobsen, A. Pfaltz, H. Yamamoto editors,
Comprehensive Asymmetric Catalysis,
Springer, 1999). Asymmetric catalytic hydrogenation has a particular industrial relevance because of its high efficiency and reduced environmental impact.
It has recently been shown that some of the results obtained with phosphines-based catalysts can be matched by the use of complexes where the phosphane ligands have been replaced by phosphonites (two P—O bonds and one P—C bond, Reetz et al,
Chem. Commun.
1998, 2077), phosphine-phosphonites (Reetz et al,
Tetrahedron: Asymmetry
1999, 2129) or phosphoramidites (two P—N and one P—O bond, Feringa et al,
J. Am. Chem. Soc.
2000, 11539). Chiral monodentate phosphonites (Pringle et al,
Chem. Commun.
2000, 961; Reetz et al,
Tetrahedron Lett.
2000, 6333) and mono-phosphites (three P—O bonds, M. T. Reetz et al,
Angew. Chem. Int. Ed.
2000, 3889) were often as effective as the analogous bidentate ligands. The above ligands often have the advantage of being easier and cheaper to prepare than the corresponding diphosphines.
Chiral bidentate phosphonites are disclosed in WO-00/14096 and U.S. Pat. No. 5817850. They are composed of three building blocks, i.e. an achiral carbon backbone (1,1′-disubstituted ferrocene, 1,2-disubstituted ethane) joining the two phosphorus atoms; and two chiral units derived from a chiral diol to form the P-heteroatom bonds. Examples of this class of ligands are described by Reetz et al,
Chem. Commun.
1998, 2077).
Some phosphorus diamide ligands have been reported, and their complexes have been demonstrated to be useful in hydroformilation reactions and allylic substitutions (Wills et al,
J.Org.Chem.
1999, 9735; Spilling et al.
Tetrahedron
1998, 54, 10513
; Tetrahedron: Asymmetry
1998, 927; Knochel et al.
Tetrahedron: Asymmetry
1997, 987).
[2.2]-p-Cyclophane derivatives bearing two identical substituents at so-called pseudo-ortho positions (4- and 12-positions; abbreviated as ps-ortho) possess planar chirality. The successful diphosphine ligand PhanePhos (Pye et al,
J. Am. Chem. Soc.
1997, 6207; WO 97/47632), is based on this skeleton.
SUMMARY OF THE INVENTION
According to one aspect of the present invention, a novel compound is ps-ortho-diphosphino-[2.2]-p-cyclophane (1)
This compound is useful as a general intermediate that allows ready access to a range of cyclic phosphine ligands having application in asymmetric catalysis. Preferably, compound (1) is enriched to at least 80% ee in the enantiomer depicted (S) or in the opposite enantiomer (R). More preferably, it is enriched to 95% ee, or higher. Compound (1) may be prepared using the tetrachloro analogue described below as compound 4d.
Further, it has now been appreciated that by combining the structural features of PhanePhos ligands (the chiral backbone) with either DuPHOS or FerroTANE ligands (phosphine atoms in 4- or 5-membered saturated ring) hybrid ligands represented by general formulae (2) and (3) can be envisaged, wherein R
1
and R
2
represent H or alkyl and n is 1 or 2. To date, no ligand of this type has been described in the literature. Importantly, the presence of a chiral backbone allows a flexible approach to ligand design, since the cyclic phosphine units may either be chiral (e.g. R
1
=methyl, R
2
=H or vice versa), allowing catalyst tuning through a “matched” diastereomeric pairing, or achiral (e.g. R
1
=R
2
=H), allowing construction from inexpensive diols of the type HO—(CH
2
)
n
—OH. It cannot be readily predicted which of ligands (2) and (3) will have industrial utility and, in order for this to be assessed systematically through screening experiments, the availability of a range of such ligands is required. To date, access to these ligands has been limited by the non-availability of suitable precursors. Through the provision of compound (1), this limitation no longer applies.
According to another aspect, this invention is based on investigation of chiral phosphonites and phosphorus diamides, ligands having a chiral backbone. Based on the ps-ortho disubstituted [2.2]-p-cyclophane skeleton, a new class of molecules is of general formula 4
The most convenient synthesis of compounds 4a-c is based on the reaction of ps-ortho-bis(dichlorophosphino)-p-cyclophane 4d with the appropriate conjugate base pre-generated from a diol, diamine, amino-alcohol, alcohol or amine. Alternatively, compound 4d can be reacted with the appropriate diol, diamine, alcohol or amine in the presence of stoichiometric or catalytic amounts of a suitable base, for example a tertiary amine. Compound 4d can be obtained from the easily accessible precursor (S)-ps-ortho-dibromo-p-cyclophane (5) (D. J. Cram et al,
J. Am. Chem. Soc.
1969, 3527) via different synthetic routes.
The ease of preparation of compounds 4a-c and the ready availability of the dioxo and diamido building blocks allows the generation of an unprecedented range of modifications based on the p-cyclophane backbone. In addition, the use of chiral chelating dialkoxo and di-amido substituents can enhance the chirality transfer in the catalytic process by means of a matching effect of the chirality of the backbone and the chirality of the heteroatom units. The use of mono-dentate alkoxo and amido ligands produces more flexible ligands that can complement the more rigid and sterically congested dialkoxo/di-amido ligands. Chiral phosphonites derived from monodentate alcohols or amines are completely unprecedented.
Chiral di-phosphonites and phosphorus diamides based on the ps-ortho disubstituted p-cyclophane skeleton are good ligands for transition metals, notably rhodium, iridium and ruthenium. Compounds 6-8 are specific examples of the above mentioned complexes.
[(4
a-c
)Rh(COD)]BF
4
6
a-c
[(4
a-c
)Ir(COD)]BF
4
7
a-c
(4
a-c
)Ru(diamine)Cl
2
8
a-c
Using the most bulky chiral dialkoxo substituents, a very strong matching/mismatching effect was found in the formation of the metal complexes. Complexes 6-8 act as highly efficient catalysts for asymmetric reactions, notably asymmetric hydrogenation. They may also be used for asymmetric hydroformylation.
In particular, high levels of stereoselection are induced by rhodium complexes 6a of p-cyclophane phosphonites in the hydrogenation of dehydroaminoacids. These results match and in certain applications surpass the results reported for the known rhodium-phosphonites systems. Surprisingly, better results than in the literature are obtained in protic solvents; aprotic solvents give a noticeable increase in selectivity.
Further, the ruthenium complexes 8a of p-cyclophane-phosphonite 4a and a chiral diamine catalyse the reduction of non functionalised ketones and imines. While it is known that the reduction of ketones is catalysed by phosphine-ruthenium-diamine complexes (Noyori and Ohkuma,
Angew.Chem.Int.Ed.,
2001, 40), the results here presented are unprecedented.
DESCRIPTION OF PREFERRED EMBODIMENTS
Compounds 4 of the invention may be prepared from enantiomerically pure ps-ortho-dihalogen-p-cyclophane 5 (X═Br). Phosphonites 4a can be obtained by direct metalation of 5 with a strong organometallic base and reaction with the appropriate chlo
Henschke Julian
Herzberg Daniela
Malan Christophe Guillaume
Zanotti-Gerosa Antonio
Chirotech Technology Limited
Vollano Jean F.
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