DE10337013A1 - New bisarylbisphosphine compounds are used for production of catalysts for asymmetric synthesis - Google Patents

Abstract

Bisarylbisphosphine compounds (I) are new. New bisarylbisphosphine compounds are of formula (I): [Image] B : -(CHR 1>) n-((R 2>)C=C(R 3>))-(CHR 4>) m or -(CHR 1>) n-((R 2>)C=C(R 3>)) m-(CHR 4>) o; R 1>-R 4>H or alkyl; R', R'' : alkyl or aryl; n, m : 0-8; m+n+o : 1-8, preferably 3-4; G : H or Cl Independent claims are included for: (1) compounds of formula (IV); (2) the preparation of compounds of formula (IV) by reaction of a compound of formula (III) with a compound of formula X 3>-(CHR 1>) n - (R 2>C=CHR 3>) (VIa) or X 4> - (CHR 4>) m - (R 3>C=CHR 6>) (VIb) or successively with two different compounds of formula (VIa) and (VIb) to form a compound of formula (VII) followed by transformation of the compounds of formula (VII) to the compounds of formula (IV) in the presence of an olefin metathesis catalyst; (3) transition metal complexes (II) containing the compounds (I); (4) catalysts containing the complexes (II); (5) a process for the production of enantiomer enriched compounds in the presence of said catalysts; (6) compounds of formula (VII). [Image] [Image] X 3>, X 4>Cl, Br, I or sulfonate.

Description

The The present invention relates to biaryl bisphosphines and intermediates from that. Furthermore, the scope of the invention includes the biaryl bisphosphines Preparable catalysts and their use in asymmetric Syntheses.

enantioenriched Biarylbisphosphines, especially those derived from substituted binaphthylene and biphenyls lead as ligands of transition metal complex catalysts often to good to very good enantioselectivity (see, e.g., Helv. Chim. Acta 1988, 71, 897-929; Acc. Chem. Res. 1990, 23, 345-350; Synlett 1994, 501-503; Ang. Chem. 2001, 113, 40-75).

steric and electronic factors caused by the nature and arrangement of substituents be determined on the biaryl system or within the phosphine groups, affect both the enantioselectivity and the activity of catalysts prepared from such ligands.

In individual cases become Rh and Ru catalysts of this type for enantioselective C = C Doppelbindungsisomerisierungen and for enantioselective hydrogenation used industrially. The number of such industrial processes is so far limited because the number of available ligands, the wide for a larger number of substrates can be used successfully, is small. Rather, show the extensive investigations in this area that because of the In principle existing substrate specificity of often for a very specific substrate "tailored" catalyst already minor changes within the same substrate group, the requisite enantiomeric unit for a very similar Product can not be reached.

From J. Org. Chem. 2000, 65, 6223-6226, WO 01/21625, representatives of a new group of biphenyl bisphosphines bridged in the 6,6'-position are known which, by varying the length of the alkylene group within the bridge element, adapt the catalysts made from these ligands, allow for certain substrates (here: β-ketoesters), so that optimized enantioselectivities are achieved. As a result of the study published in J. Org. Chem., An optimized enantioselectivity for a ligand-containing ligand with a - (CH ₂ ) ₄ moiety as a bridging member ("C4TunaPhos") is described.

Independent of The aforementioned publications were a single representative of these Ligand group published in EP-A 1 095 946.

It However, there is still a need a group of ligands or catalysts which can be prepared therefrom providing both a generally high level of enantioselectivity and activity, as well as an adaptation to a particular substrate by variation allow the substituent on the ligand system in a simple manner.

in der B für eine bivalente Gruppierung der Formel -(CHR¹)_n-(R²-C=CR³)-(CHR⁴)_m steht, wobei R¹, R², R³ und R⁴ jeweils unabhängig voneinander für Wasserstoff oder Alkyl, vorzugsweise für C₁-C₆-Alkyl stehen, und n und m jeweils unabhängig voneinander für null oder eine ganze Zahl von 1 bis 8 stehen, wobei jedoch die Summe aus n und m 1 bis 8, vorzugsweise 2 oder 4 und besonders bevorzugt 2 beträgt, und in der weiterhin
G für Chlor oder Wasserstoff und
R' und R'' jeweils unabhängig voneinander für Aryl oder Alkyl stehen.The present invention now relates to compounds of the formula (I)

in which B is a bivalent moiety of the formula - (CHR ¹ ) _n - (R ² -C = CR ³ ) - (CHR ⁴ ) _m wherein R ¹ , R ² , R ³ and R ^{4 are} each independently hydrogen or alkyl, preferably C ₁ -C ₆ -alkyl, and n and m are each independently zero or an integer from 1 to 8, but the sum of n and m is 1 to 8, preferably 2 or 4 and more preferably 2, and in the further
G for chlorine or hydrogen and
R 'and R "each independently represent aryl or alkyl.

From The invention includes both the pure stereoisomers and any Mixtures thereof, in particular including racemic mixtures. Preference is given to the stereoisomerically enriched compounds of Formula (I) which has a stereoisomeric purity of 95% and more, especially preferably 99% or more. For compounds of the formula (I) which may occur in two enantiomeric forms is accordingly a ee of 90% or more preferred, particularly preferably an ee of 99% or more.

in the Within the scope of the invention all of the above and listed below, general or in Preferential ranges mentioned remainder definitions, parameters and explanations among themselves, including between the respective areas and preferred areas be combined in any way.

enantiomerically For the purposes of the invention, enantiomerically pure compounds or mixtures of enantiomers of a compound in which one enantiomer in one Enantiomeric excess, in Hereafter also called ee (enantiomeric excess), in comparison to other enantiomer is present. This enantiomeric excess is preferably 10 to 100% ee, more preferably 80 to 100% ee and especially preferably 95 to 100% ee.

The The terms stereoisomer or stereoisomer are enriched in Analogy for Compounds used in which diastereomers may occur.

Alkyl is, for example, unbranched, branched, cyclic or acyclic C ₁ -C ₁₂ -alkyl radicals which may be either unsubstituted or at least partially substituted by fluorine, chlorine, or unsubstituted or substituted aryl, or C ₁ -C ₆ -alkoxy. Alkyl is particularly preferably branched, cyclic or acyclic C ₁ -C ₁₂ -alkyl radicals which are not further substituted.

Aryl is, for example, carbocyclic aromatic radicals having 6 to 18 skeletal carbon atoms or heteroaromatic radicals having 5 to 18 skeletal carbon atoms in which none, one, two or three skeletal carbon atoms per cycle, throughout the molecule at least one skeleton carbon atom, by heteroatoms selected from the group consisting of nitrogen , Sulfur or oxygen, may be substituted. Furthermore, the carbocyclic aromatic radicals or heteroaromatic radicals may be substituted with up to five identical or different substituents per cycle, selected from the group free or protected hydroxy, iodine, bromine, chlorine, fluorine, cyano, free or protected formyl, C ₁ -C ₁₂ -alkyl such as methyl, ethyl, n-propyl, iso-propyl, n-butyl, tert-butyl, cyclohexyl, n-hexyl, n-octyl or iso-octyl, C ₆ -C ₁₂ aryl, such as for example, phenyl, C ₁ -C ₆ alkoxy, tri (C ₁ -C ₆ alkyl) siloxyl, such as trimethylsiloxyl, triethylsiloxyl and tri-n-butylsiloxyl.

Examples for carbocyclic Aromatic radicals having 6 to 18 skeleton carbon atoms are for Example phenyl, naphthyl, phenanthrenyl, anthracenyl or fluorenyl, heteroaromatic radicals having 5 to 18 skeletal carbon atoms in which none, one, two or three skeletal carbon atoms per cycle, throughout the molecule but at least one skeleton carbon atom, by heteroatoms from the group nitrogen, sulfur or oxygen, substituted could be are, for example, pyridinyl, oxazolyl, thiophen-yl, benzofuranyl, Benzothiophen-yl, dibenzofuran-yl, dibenzothiophen-yl, furanyl, Indolyl, pyridazinyl, pyrazinyl, pyrimidinyl, thiazolyl, triazolyl or quinolinyl.

Protected formyl is within the scope of the invention a formyl residue, which by conversion into a Aminal, acetal or a mixed aminal acetal is protected, wherein the aminals, acetals and mixed aminal acetals are acyclic or cyclic.

Protected hydroxy is within the scope of the invention a hydroxy radical which is converted by conversion into an acetal, carbonate, carbamate or carboxylate is protected. Examples of this are the flyover in a tetrahydropyranyl adduct, into a benzyloxycarbonyl, allyloxycarbonyl or a tert-butyloxycarbonyl derivative.

The preferred ranges for compounds of the formula (I) are defined below.
R ¹ , R ² , R ³ and R ⁴ are each independently of one another hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl and n-pentyl, particularly preferably hydrogen, methyl, ethyl, n- Propyl and iso-propyl, and especially becorzugt in each case identically for hydrogen.
R 'and R "are each preferably independently of one another, more preferably in each case identical to C ₃ -C ₈ -alkyl or C ₅ -C ₁₀ -aryl which is not monosubstituted or polysubstituted by radicals which are selected from the group Chlorine, fluorine, cyano, phenyl, C ₁ -C ₆ -alkoxy and C ₁ -C ₆ -alkyl, particularly preferably cyclopentyl, cyclohexyl, cycloheptenyl, phenyl, o-, m-, p-tolyl, 3,5-dimethylphenyl , 3,5-di-tert-butylphenyl, 3,5-dimethyl-4-methoxyphenyl, 3,5-di-tert-butyl-4-methylphenyl, 4-trifluoromethylphenyl, 4-fluorophenyl, 2, 3 Furyl, 2-, 3-thiophen-yl, 2-N-methyl-pyrrolyl, N-methyl-2-indolyl and 2-thiazolyl.

As particularly preferred compounds of formula (I) may be mentioned:
(R) - and (S) - [5,5'-dichloro-6,6 '- (cis-1,4-but-2-endioxy) -biphenyl-2,2'-diyl] -bis - [( diphenyl) phosphine, (R) - and (S) - [5,5'-dichloro-6,6 '- (cis-1,4-but-2-endioxy) -biphenyl-2,2'-diyl] - bis - [(di-cyclohexyl) phosphine, (R) - and (S) - [5,5'-dichloro-6,6 '- (cis-1,4-but-2-endioxy) -biphenyl-2, 2'-diyl] -bis - [(di-3,5-di-tert-butyl-4-methoxyphenyl) phosphine, (R) - and (S) - [5,5'-dichloro-6,6 ' - (cis-1,4-but-2-endioxy) -biphenyl-2,2'-diyl) -bis - [(di-3,5-dimethyl-phenyl) -phosphine, (R) - and (S) - [5 , 5'-dichloro-6,6 '- (cis-1,4-but-2-endioxy) biphenyl-2,2'-diyl] -bis - [(di-3,5-dimethyl-4-methoxyphenyl ) phosphine, (R) - and (S) - [5,5'-dichloro-6,6 '- (cis-1,4-but-2-endioxy) -biphenyl-2,2'-diyl] -bis - [(di-4-fluorophenyl) phosphine and (R) - and (S) - [5,5'-dichloro-6,6 '- (cis-1,4-but-2-endioxy) -biphenyl-2 ', 2'-diyl] -bis - [(di-3,5-di-tert-butylphenyl) phosphine and the corresponding trans compounds, the said cis compounds being preferred.

The Compounds of the invention of the formula (I) for example, in an analogous manner to known methods be prepared for the synthesis of biphenyl bisphosphines bridged in the 6,6'-position have already been described

Thus, for example, from 5,5'-dichloro-6,6'-dimethoxybiphenyl-2,2'-diyl] bisphosphine or analogous compounds by ether cleavage, the corresponding 6,6'-Dihydroxybisphosphine obtained, which is then treated by treatment with compounds of the formula (II) X ¹ -BX ² (II) in which B has the meaning and preferred ranges given in the legend of formula (I) and in which
X ¹ and X ^{2 are} each independently chlorine, bromine or iodine,
under conditions known per se (see, for example, J. Org. Chem. 2000, 65, 6224) to give the compounds of the formula (I) according to the invention.

durch Etherspaltung in Verbindungen der Formel (III) überführt werden,

in einem Schritt b)
die Verbindungen der Formel (III) durch Umsetzung mit Verbindungen der Formel (II) in Gegenwart von Base zu Verbindungen der Formel (IV) umgesetzt werden,

und in einem Schritt c)
die Verbindungen der Formel (IV) zu Verbindungen der Formel (I) reduziert werden,

wobei B, G, R' und R'' die gleichen Bedeutungen und Vorzugsbereiche besitzen, die oben unter den Formeln (I) und (II) bereits definiert worden sind.For the preparation of compounds of the formula (I), the procedure is preferably such that
in a step a)
Compounds of the formula (V)

be converted by ether cleavage into compounds of formula (III),

in a step b)
the compounds of the formula (III) are reacted by reaction with compounds of the formula (II) in the presence of base to give compounds of the formula (IV),

and in a step c)
the compounds of the formula (IV) are reduced to compounds of the formula (I),

wherein B, G, R 'and R "have the same meanings and preferred ranges already defined above under formulas (I) and (II).

R in formula (V) is C ₁ -C ₆ -alkyl.

The ether cleavage according to step a) can be carried out, for example, in a manner known per se by reaction with BBr ₃ and subsequent treatment with water.

The Reaction of the compounds of the formula (III) with compounds of the Formula (II) according to step b) is preferably in organic solvent in the presence of Bases performed.

When solvent Alcohols, such as methanol, are particularly suitable. Ethanol, propanol, ethylene glycol or ethylene glycol monomethyl ether and amide solvents such as. N, N-dimethylformamide, N, N-dimethylacetamide or N-methylpyrrolidone or mixtures of the solvents mentioned.

When Bases can For example, alkali and alkaline earth compounds such as oxides, hydroxides, Carbonates or alcoholates are used, for example, be called: calcium oxide, sodium hydroxide, potassium carbonate or sodium methoxide. It is also possible, tertiary Amines such as e.g. Use triethylamine or tributylamine as bases.

The molar ratio between inserted compound of formula (III) and compound of the formula (II) is preferably between 1: 1 and 1: 4; I. A. is enough for one full Implement a slight surplus to compound of the formula (II). The base is preferably at least equivalent Amount used for the compound of formula (III). When using from in the solvent insoluble Bases, for example of potassium carbonate in DMF, it is expedient, the to use four to ten times the molar amount and at the same time for an intensive Mixing the suspension to provide.

The Reaction according to step b) can also be carried out in a two-phase system, using as a non-aqueous phase solvent are used, in which the resulting product of formula (IV) at least predominantly soluble is, for that For example, dichloromethane is suitable. It is useful in this Variant of the reaction phase transfer catalysts such. quaternary ammonium or phosphine salts and tetrabutylammonium salts. Prefers are tetrabutylammonium salts.

The Reaction temperature in the reaction of compounds of the formula (III) for the preparation of the compounds of formula (IV), for example in the range of about 20 ° C up to 100 ° C, preferably in the range of 20 ° C up to 80 ° C, lie.

The reduction of the compounds of the formula (IV) to give the compounds of the formula (II) according to step c) is preferably carried out by methods known per se, for example by reaction with trichlorosilane in inert solvents such as toluene or xylene and in the presence of tertiary amines such as Tri-n-butylamine at reflux temperature, (see, for example, EP-A 398 132, EP-A 749 973 and EP-A 926 152).

• – mit einer Verbindung der Formel (VIa) oder (VIb) oder sukzessive mit zwei verschiedenen Verbindungen der Formeln (VIa) und (VIb) X³-(CHR¹)_n-(R²C=CHR⁵) (VIa) X⁴-(CHR⁴)_m-(R³C=CHR⁶) (VIb)in denen X³ und X⁴ jeweils für Chlor, Brom, Iod oder ein Sulfonat, bevorzugt für- Chlor, Brom oder Iod stehen und R¹, R², R³ und R⁴ die oben stehend genannte Bedeutung einschließlich der Vorzugsbereiche besitzen und R⁵ und R⁶ jeweils unabhängig voneinander für Wasserstoff oder C₁-C₄-Alkyl stehen

zu Verbindungen der Formel (VII) umgesetzt werden

und
die Verbindungen der Formel (VII) dann in Gegenwart eines Olefin-Metathesekatalysators in Verbindungen der Formel (IV) überführt werden.Furthermore, the compounds of the formula (IV) according to the invention can also be prepared by initially reacting the compounds of the formula (III) with the abovementioned meaning

• With a compound of the formula (VIa) or (VIb) or successively with two different compounds of the formulas (VIa) and (VIb) X ³ - (CHR ¹ ) _n - (R ² C = CHR ⁵ ) (VIa) X ⁴ - (CHR ⁴ ) _m - (R ³ C = CHR ⁶ ) (VIb) in which X ³ and X ^{4 are} each chlorine, bromine, iodine or a sulfonate, preferably chlorine, bromine or iodine and R ¹ , R ² , R ³ and R ^{4 have} the meaning given above, including the preferred ranges and R Each of R ⁵ and R ⁶ is independently hydrogen or C ₁ -C ₄ alkyl

be converted to compounds of formula (VII)

and
the compounds of formula (VII) are then converted into compounds of formula (IV) in the presence of an olefin metathesis catalyst.

The Compounds of formula (IV) can then in the manner described above to the compounds of formula (I) can be reduced.

For the implementation the compounds of the formula (III) with compounds of the formula (VIa) and or (VIb) apply to Step b) of the first-mentioned process, Temperatures, molar ratios and other reaction parameters in the same way.

wobei in Formel (Xa)
Ar für Aryl, Hal für Chlor, Brom oder Iod und R⁷ jeweils unabhängig für C₁-C₁₂-Alkyl, C₅-C₁₂-Aryl oder C₆-C₁₃-Arylalkyl steht und
wobei in Formel (Xb)
o-Aryldiyl für einen ortho-divalenten C₅-C₂₄-Arylrest steht, der weiterhin bis zu vier Reste tragen kann, wie sie bereits für Aryl obenstehend definiert worden sind, Hal für Chlor, Brom oder Iod, B für gegebenenfalls ein- oder zweifach durch C₁-C₁₂-Alkyl, C₅-C₁₂-Aryl oder C₆-C₁₃-Arylalkyl substituiertes 1,2-Ethandiyl- oder 1,2-Ethendiyl und R⁸ jeweils unabhängig für C₁-C₁₂-Alkyl, C₅-C₁₂-Aryl oder C₆-C₁₃-Arylalkyl steht.Ruthenium-carbene complexes are particularly suitable as olefin metathesis catalysts for the reaction of the compounds of the formula (VII) to give compounds of the formula (IV). Preferred ruthenium-carbene complexes are, for example, those of the formulas (Xa) and (Xb)

where in formula (Xa)
Ar is aryl, Hal is chlorine, bromine or iodine and R ^{7 is} each independently C ₁ -C ₁₂ alkyl, C ₅ -C ₁₂ aryl or C ₆ -C ₁₃ arylalkyl, and
where in formula (Xb)
o-aryldiyl is an ortho-divalent C ₅ -C ₂₄ -aryl radical which may further bear up to four radicals as already defined above for aryl, Hal represents chlorine, bromine or iodine, B optionally represents on or 1,2-ethanediyl or 1,2-ethenediyl which is monosubstituted by C ₁ -C ₁₂ -alkyl, C ₅ -C ₁₂ -aryl or C ₆ -C ₁₃ -arylalkyl and R ^{8 is} each independently C ₁ -C ₁₂ - Alkyl, C ₅ -C ₁₂ aryl or C ₆ -C ₁₃ arylalkyl.

The last-mentioned process for the preparation of compounds of the formula (I) is likewise encompassed by the invention, such as the compounds of the formula For the preparation of compounds of the formula (I) (IV) and (VII), both in the form of their pure stereoisomers and in any mixtures thereof, in particular the racemic mixture.

As compounds of formula (VII) may be mentioned:
(R) - and (S) - [5,5'-dichloro-6,6 '- (bis-allyloxy) -biphenyl-2,2'-diyl] -bis - [(di-cyclohexyl) phosphine oxide, (R.B. ) - and (S) - [5,5'-dichloro-6,6 '- (bis-allyloxy) -biphenyl-2,2'-diyl] -bis - [(di-3,5-di-tert. -butyl-4-methoxyphenyl) phosphine oxide, (R) - and (S) - [5,5'-dichloro-6,6 '- (bis-allyloxy) -biphenyl-2,2'-diyl] -bis [ (di-3,5-dimethylphenyl) phosphine oxide, (R) - and (S) - [5,5'-dichloro-6,6 '- (bis-allyloxy) -biphenyl-2,2'-diyl] -bis - [(di-3,5-dimethyl-4-methoxyphenyl) phosphine oxide, (R) - and (S) - [5,5'-dichloro-6,6 '- (bis-allyloxy) -biphenyl-2,2 '-diyl] -bis - [(di-4-fluorophenyl) phosphine oxide and (R) - and (S) - [5,5'-dichloro-6,6' - (bis-allyloxy) -biphenyl-2,2 'diyl] -bis - [(di-3,5-di-tert-butylphenyl) phosphine oxide.

As compounds of formula (IV) may be mentioned:
(R) - and (S) - [5,5'-dichloro-6,6 '- (cis-1,4-but-2-ene-dioxy) -biphenyl-2,2'-diyl] -bis [(dicyclohexyl) phosphine oxide, (R) - and (S) - [5,5'-dichloro-6,6 '- (cis-1,4-but-2-ene-dioxy) -biphenyl-2,2' -diyl] -bis - [(di-3,5-di-tert-butyl-4-methoxyphenyl) phosphine oxide, (R) - and (S) - [5,5'-dichloro-6,6 '- ( cis-1,4-but-2-ene-dioxy) -biphenyl-2,2'-diyl] -bis - [(di-3,5-dimethylphenyl) phosphine oxide, (R) - and (S) - [5 , 5'-dichloro-6,6 '- (cis-1,4-but-2-endioxy) biphenyl-2,2'-diyl] -bis - [(di-3,5-dimethyl-4-methoxyphenyl ) phosphine oxide, (R) - and (S) - [5,5'-dichloro-6,6 '- (cis-1,4-but-2-ene-dioxy) -biphenyl-2,2'-diyl] -bis - [(di-4-fluorophenyl) phosphine oxide and (R) - and (S) - [5,5'-dichloro-6,6 '- (cis-1,4-but-2-endioxy) -biphenyl -2,2'-diyl] bis - [(di-3,5-di-tert-butylphenyl) phosphine oxide and the respective trans compounds, with the cis compounds being preferred.

The Compounds of formula (I) are particularly suitable as ligands for the Preparation of transition metal complexes, as catalysts for Process for the preparation of enantiomerically enriched compounds can be used.

Therefore Both invention are transition metal complexes comprising compounds of the formula (I), as well as catalysts, the transition metal complexes of the invention contain.

Preferred transition metal complexes are those which, by reacting compounds of the formula (I) in the presence of transition metal compounds available are.

Preferred transition metal compounds are compounds of rhodium, iridium, ruthenium, palladium and Nickel, with those of rhodium, iridium and ruthenium more preferred are.

Preferred transition metal compounds are, for example, those of the formula (VIIIa) M (Y ¹ ) ₃ (VIIIa) in the
M for ruthenium, rhodium, iridium and
Y ¹ for chloride, bromide, acetate, nitrate, methanesulfonate, trifluoromethanesulfonate or acetylacetonate and
or transfer metal compounds of the formula (VIIIb) M (Y ² ) _p B ¹ ₂ (VIIIb) in the
M for ruthenium, rhodium, iridium and
Y ^{2 is} chloride, bromide, acetate, methanesulfonate, trifluoromethanesulfonate, tetrafluoroborate, hexafluorophosphate perchlorate, hexafluoroantimonate, tetra (bis-3,5-trifluoromethylphenyl) borate or tetraphenylborate, and
p for rhodium and iridium for 1 and
Ruthenium stands for 2,
B ¹ is a C ₂ -C ₁₂ alkene such as ethylene or cyclooctene, or a nitrile such as acetonitrile, benzonitrile or benzylnitrile, or
B ¹ ₂ together represents a (C ₄ -C ₁₂ ) -diene such as norbornadiene or 1,5-cyclooctadiene
or transition metal compounds of the formula (VIIIc) [MB ² Y ¹ ₂ ] ₂ (VIIIc) in the
M for ruthenium and
B ^{2 is} aryl radicals such as cymene, mesityl, phenyl or cyclooctadiene, norbornadiene or methylallyl
or transition metal compounds of the formula (VIIId) Me ₃ [M (Y ³ ) ₄ ] (VIIId), in which
M for iridium or rhodium and
Y ^{3 is} chloride or bromide and
Me stands for lithium, sodium, potassium, ammonium or organic ammonium and
or transition metal compounds of the formula (VIIIe) [M (B ³ ) ₂ ] An (VIIIe), in which
M for iridium or rhodium and
B ^{3 is} a (C ₄ -C ₁₂ ) -diene such as norbornadiene or 1,5-cyclooctadiene
An is a non or weakly coordinating anion such as, for example, methanesulfonate, trifluoromethanesulfonate, tetrafluoroborate, hexafluoro-phosphate, perchlorate, hexafluoroantimonate, tetra (bis-3,5-trifluoromethylphenyl) borate or tetraphenylborate.

In addition, as transition metal compounds cyclopentadienyl ₂ Ru, Rh (acac) (CO) ₂ , Ir (pyridine) ₂ (1,5-cyclooctadiene) or polynuclear bridged complexes such as [Rh (1,5-cycloctadiene) Cl] ₂ and [ Rh (1,5-cyclooctadiene) Br] ₂ , [Rh (ethene) ₂ Cl] ₂ , [Rh (cyclooctene) ₂ Cl] ₂ , [Ir (1,5-cyclooctadiene) Cl] ₂ and [Ir (1, 5-cyclooctadiene) Br] ₂ , [Ir (ethene) ₂ Cl] ₂ , and [Ir (cyclooctene) ₂ Cl] ₂ .

Very particular preference is given to using as transition metal metal compounds:
[Rh (cod) Cl] _2, [Rh (cod) ₂ Br], [Rh (cod) _2] ClO _4, [Rh (cod) _2] BF _4, [Rh (cod) _2] PF _6, [Rh (cod) ₂ ] OTf, [Rh (cod) ₂ ] BAr ₄ (Ar = 3,5-bistrifluoromethylphenyl) [Rh (cod) ₂ ] SbF ₆ RuCl ₂ (cod), [(cymene) RuCl ₂ ] ₂ , [ (Benzene) RuCl ₂ ] ₂ , [(mesityl) RuCl ₂ ] ₂ , [(cymene) RuBr ₂ ] ₂ , [(cymene) RuI ₂ ] ₂ , [(cymene) Ru (BF ₄ ) ₂ ] ₂ , [( Cymene) Ru (PF ₆ ) ₂ ] ₂ , [(cymene) Ru (BAr ₄ ) ₂ ] ₂ , (Ar = 3,5-bistrifluoromethylphenyl), [(cymene) Ru (SbF ₆ ) ₂ ] ₂ , [Ir ( cod) ₂ Cl] ₂ , [Ir (cod) ₂ ] PF ₆ , [Ir (cod) ₂ ] ClO ₄ , [Ir (cod) ₂ ] SbF ₆ [Ir (cod) ₂ ] BF ₄ , [Ir (cod ) ₂ ] OTf, [Ir (cod) ₂ ] BAr ₄ (Ar = 3,5-bistrifluoromethylphenyl) RuCl ₃ , RhCl ₃ , [Rh (nbd) Cl] ₂ , [Rh (nbd) ₂ Br], [Rh ( nbd) ₂ ] ClO ₄ , [Rh (nbd) ₂ ] BF ₄ , [Rh (nbd) ₂ ] PF ₆ , [Rh (nbd) ₂ ] OTf, [Rh (nbd) ₂ ] BAr ₄ (Ar = 3, 5-bistrifluoromethylphenyl) [Rh (nbd) ₂ ] SbF ₆ RuCl ₂ (nbd), [Ir (nbd) ₂ ] PF ₆ , [Ir (nbd) ₂ ] ClO ₄ , [Ir (nbd) ₂ ] SbF ₆ [Ir (nbd) ₂ ] BF ₄ , [Ir (nbd) ₂ ] OTf, [Ir (nbd) ₂ ] BAr ₄ (Ar = 3,5-bistrifluoromethylphenyl), Ir (pyridine) ₂ (nbd), RuCl ₃ , [Ru (DMS O) ₄ Cl ₂ ], [Ru (CH ₃ CN) ₄ Cl ₂ ], [Ru (PhCN) ₄ Cl ₂ ], [Ru (cod) Cl ₂ ] _n , [Ru (cod) (methallyl) ₂ ] and [Ru (acetylacetonate) ₃ ].

Particularly preferred transition metal complexes are those of the formulas (VIIIa, b, c) [M (I) Hal] ₂ (VIIIa) [M (cod) (I)] An (VIIIb) [M (nbd) (I)] An (VIIIc) in which
M stands for rhodium or iridium and
Hal for chloride, bromide or iodide and
(I) represents a compound of formula (I) and
An is a non or weakly coordinating anion such as, for example, methanesulfonate, trifluoromethanesulfonate, tetrafluoroborate, hexafluoro-phosphate, perchlorate, hexafluoroantimonate, tetra (bis-3,5-trifluoromethylphenyl) borate or tetraphenylborate, and
Compounds of the formulas (IXa, b, c, d, e, f) [Ru (AcO) ₂ (I)] (IXa) [Ru ₂ Cl ₄ (I) ₂ NEt ₃ ] (IXb) [RuHal (I) (AR)] ₂ (IXc) [Ru (I)] (An) ₂ (IXd) [{RuHal (I)} ₂ (μ-Hal) ₃ ] - [(R ''') ₂ NH ₂ ] ⁺ (IXe) [RuHal ₂ (I) (diamine)] (IXf) in which
Hal for chloride, bromide or iodide and
(I) represents a compound of formula (I) and
An is a non or weakly coordinating anion such as, for example, methanesulfonate, trifluoromethanesulfonate, tetrafluoroborate, hexafluoro-phosphate, perchlorate, hexafluoroantimonate, tetra (bis-3,5-trifluoromethylphenyl) borate or tetraphenylborate, and
Each R '''is independently C ₁ -C ₆ alkyl and
Diamine is chiral 1,2-diamines, which are preferably selected from the group (S, S) and (R, R) -1,2-diphenyl-ethylene-diamine and (R) - or (S) -1, 1-bis (4-methoxyphenyl) -3-methyl-1,2-butanediamine and
AR is an arene ligand which is preferably selected from the group of benzene, p-cymene and mesitylene.

The Production of such types of complex is known in principle and, for example analogous to Chemistry Letters, 1851, 1989; J. Organomet. Chem., 1992, 428, 213 (VIIIa, b, c); J. Chem. Soc., Chem. Commun., 922, 1985 (IXa, b, c, d) EP-A 945 457 (IXe) and Pure Appl. Chem., Vol. 71, 8493-1501, 1999 (IXf) possible.

The transition metal complexes according to the invention and catalysts are particularly suitable for use in a process to the transition metal catalyzed Preparation of enantiomerically enriched compounds and for C = C double bond isomerizations, which is also included in the invention.

there can both isolated transition metal complexes such as those of formulas (VIIIa-c) and (IXa-e) as well in situ prepared transition metal complexes can be used, the latter being preferred.

Prefers become the transition metal complexes and catalysts for asymmetric hydrogenations used. Preferred asymmetric Hydrogenations are, for example, hydrogenations of prochiral C = C bonds such as prochiral enamines, olefins, enol ethers, C = O bonds such as prochiral ketones and C = N bonds such as prochiral imines. Particularly preferred asymmetric Hydrogenations are hydrogenations of prochiral ketones such as especially alpha and beta keto esters such as acetoacetic esters or chloroacetate esters.

The Amount of the transition metal compound used or the transition metal complex used can, for example, 0.001 to 5 mol%, based on the used Substrate amount, preferably 0.01 to 2 mol%.

On this way you can with the aid of the catalysts according to the invention ee and activities achieved so far not with similar catalysts were achievable.

example 1

Preparation of (S) - [5,5'-dichloro-6,6'-dihydroxybiphenyl-2,2'-diyl] -bis (diphenylphosphine oxide)

In a solution of 8 g of (S) - [5,5'-dichloro-6,6'-dimethoxybiphenyl-2,2'-diyl] bis (diphenyl-phosphine oxide) in 160 ml over CaH ₂ dried methylene chloride, which in a Stirred vessel was cooled to -78 ° C with exclusion of moisture, added dropwise 3.4 ml of BBr ₃ (= 8.77 g) with stirring and kept the reaction mixture for 1 hour at this temperature. Then the temperature was allowed to rise to room temperature over 2 hours and stirred at this temperature for a further 24 hours. Under ice-cooling, a total of 50 ml of water were then added dropwise with thorough mixing within 1 hour, then the methylene chloride was distilled off and kept at 80 ° C with stirring for 6 hours after addition of another 110 ml of water. After cooling to RT, the resulting precipitate was filtered off with suction through a glass filter frit, washed with 100 ml of water and then with 200 ml of methylene chloride with thorough mixing. After drying the remaining product, 6.3 g (= 82% of theory) of pure (S) - [5,5'-dichloro-6,6'-dihydroxy biphenyl-2,2'-diyl] bis (diphenyl-phosphine oxide), m.p. 236-237 ° C.

In addition to 38 mg of the intermediate used 123 mg of (S) -cis compound of the formula given above.
Mp 126 ° C-128 ° C, [α] _D = + 57.6 ° (c = 1.0, CHCl ₃ ) and
118 mg of the (S) -trans compound of the formula given above.
Mp 141 ° C-142 ° C, [α] _D = -48.4 ° (c = 1.4, CHCl ₃ ).

Example 2

Production of cis- and trans- (S) - [5,5'-dichloro-6,6 '- (1,4-but-2-en-dioxy) biphenyl-2,2'-diyl] bis (diphenyl-phosphine)

A mixture of 0.50 g (0.76 mmol) of (S) - [5,5'-dichloro-6,6'-dihydroxybiphenyl-2,2'-diyl] bis (diphenylphosphine oxide) and of 0.42 g (3.04 mmol) of potassium carbonate in 10 ml of DMF is stirred vigorously for 30 minutes at room temperature. With further intensive stirring, 0.223 g (3.04 mmol) of allyl chloride are added and this mixture is kept at 40 ° C for 26 hours. Subsequently, the reaction mixture is worked up analogously to the procedure given in Example 1. In addition to 0.136 g of Dichlordihydroxbiphenylphosphinoxids used and 58 mg of a mixed fraction of monoallyloxy and bisallyloxy-dichlorobisphenylbisphosphinoxid 0.395 g of pure (S) - [6,6'-bisallyloxy-5,5'-dichlorobiphenyl-2,2'-diyl] to (diphenyl-phosphine oxide).
Mp 214 ° C-215 ° C (Z), [α] _D = -56.8 ° (c = 1.0, CHCl ₃ ).

To a solution of 18 mg Grubbs catalyst, 1st generation, in 40 ml of dry CH ₂ Cl ₂ are added dropwise with stirring for one hour at room temperature and under an argon atmosphere 295 mg of the above-described intermediate dissolved in 40 ml of CH ₂ Cl ₂ . Thereafter, the mixture is refluxed at 40 ° C. for 5 hours and at room temperature for 24 hours. Then, by stirring under air, (1 hour), the catalyst was destroyed and the resulting product mixture was filtered through silica gel and the crude product was separated by chromatography analogously to the procedure in Example 1.

Example 3

Preparation of (R) - (1,4-but-2-endioxy) biphenyl-2,2'-diyl] -bis (diphenylphosphine oxide)

A Mixture of 4.1 g (6.99 mmol) of (R) - (6,6'-dihydroxybiphenyl-2,2'-diyl) bis (diphenylphosphine oxide) and 3.85 g (27.96 mmol) of potassium carbonate in 50 ml of dimethylformamide becomes 1 Stirred vigorously at room temperature. After that, continue to the intensely stirred Mixture 0.96 g (7.69 mmol) of cis-1,1-dichloro-but-2-ene dissolved in 5.0 ml of DMF was added dropwise and the mixture was stirred at RT for a further 12 hours and at 80 ° C. for 8 hours. To cooling, the reaction mixture is filtered.

Out the filtered precipitate is obtained after acidification with 2N hydrochloric acid 0.71 g of Dihydroxybisphenylbisphosphinoxids used unchanged in pure form back.

The Filtrate is carefully brought to dryness at 0.5 mbar while warming to 60.degree and subsequently dissolved in 60 ml of dry dichloromethane. After 12 hours will be under Addition of silica gel as a filter aid, this solution filtered. From the filtered solid product, a further 0.13 g of the used Recovered bisphosphine oxide.

The filtrate is evaporated, giving 3.41 g of a crude product which is separated by chromatography (silica gel Merck type 9385, eluent: ethyl acetate / methanol / water, 500: 50: 5). This gives 2.76 g of pure products of the formula given above.
Mp 116 ° C-118 ° C, [α] _D = -161.1 ° (c = 1.0, CHCl ₃ ).

Example 4

Analogously to Example 3, (S) -cis- [6,6 '- (1,6-hex-3-endioxy) biphenyl-2,2'-diyl'] - bis (diphenylphosphine oxide)
Mp 234 ° C-235 ° C, [α] _D = -99 ° (c = 0.5, EtOH).

Example 5

Analogously to Example 3, (R) -trans- [6,6 '- (1,4-but-2-endioxy) biphenyl-2,2'-diyl'] - bis (diphenylphosphine oxide)
Mp 192 ° C-194 ° C (Z), [α] _D = + 86.8 ° (c = 0.5, CHCl ₃ ).

Example 6

Preparation of (R) -cis- [6,6 '- (1,4-but-2-endioxy) biphenyl-2,2'-diyl] bis (diphenyl) phosphine

The phosphine oxide from Example 3 (0.686 g, 1 mmol) was initially charged with xylene (18 ml) under argon, the resulting mixture was initially treated with tri (n-butyl) amine (3.5 ml, 15 mmol) and trichlorosilane (1, 5 ml, 15 mmol) and then heated under reflux for 2 hours. It was allowed to cool, briefly stirred with degassed NaOH solution (30%, 15 ml), 25 ml of degassed water added and the phases were separated. The aqueous phase was extracted 3 times with methyl tert-butyl ether (10 ml) and the combined organic phases were washed first with sat. Brine and then dried over MgSO ₄ . The organic solvent was removed in vacuo to give the product as a colorless powder.
Yield: 95% of theory

Example 7

Preparation of (S) -cis- [6,6 '- (1,4-hex-3-endioxy) biphenyl-2,2'-diyl] bis (diphenyl) phosphine

The Phosphine oxide from Example 4 was reduced completely analogously to Example 6 and obtained in a yield of 91%.

Example 8

Preparation of (S) -cis- [5,5'-dichloro-6,6 '- (1,4-but-2-endioxy) biphenyl-2,2'-diyl] bis (diphenyl) phosphine

The Phosphine oxide from Example 2 was reduced completely analogously to Example 6 and obtained in a yield of 94%.

Enantioselective hydrogenation of methyl acetoacetate (S1)

Example 9

(S) -cis [6,6 '- (1,4-hex-3-endioxy) biphenyl-2,2'-diyl] bis (diphenyl) phosphine (4.4 mg, 2 mol%), RuCl ₃ (1.4 mg, 1 mol%) and 75 mg of S1 were initially charged in methanol (1.3 ml) and the mixture was heated to 50 ° C. under a hydrogen pressure of 10 bar for 23 h. After this time, an enantiomeric purity of the product of 97.3% ee was determined.

Example 10

(R) -cis- [6,6 '- (1,4-But-2-endioxy) biphenyl-2,2'-diyl] bis (diphenyl) phosphine (4.4 mg, 2 mol%), RuCl ₃ (1.4 mg, 1 mol%) and 75 mg of S1 were initially charged in methanol (1.3 ml) and the mixture was heated to 50 ° C. under a hydrogen pressure of 10 bar for 23 h. After this time, an enantiomeric purity of the product of 98.6% ee was determined.

Example 11

(S) -cis [5,5'-dichloro-6,6 '- (1,4-but-2-endioxy) biphenyl-2,2'-diyl] bis (diphenyl) phosphine (4,4 mg, 2 mol%), RuCl ₃ (1.4 mg, 1 mol%) and 75 mg of S1 were initially charged in methanol (1.3 ml) and the mixture was heated to 50 ° C. under a hydrogen pressure of 10 bar for 5 h heated. After this time, an enantiomeric purity of the product of 98.3% ee was determined.

Example 12 (for comparison)

(S) - [5,5'-dichloro-6,6'-dimethoxy-biphenyl-2,2'-diyl] -bis (diphenyl) -phosphine (4.4 mg, 2 mol%), RuCl ₃ (1 , 4 mg, 1 mol%) and 75 mg of S1 were initially charged in methanol (1.3 ml) and the mixture was added under a hydrogen pressure of 10 bar heated to 50 ° C for 23 h. After this time, an enantiomeric purity of the product of 96.4% ee was determined.

Claims (13)

Compounds of the formula (I)

in which B is a divalent moiety of the formula - (CHR ¹ ) _n - (R ² C = CR ³ ) - (CHR ⁴ ) _m wherein R ¹ , R ² , R ³ and R ^{4 are} each independently hydrogen or Alkyl, and n and m are each independently zero or an integer from 1 to 8, but wherein the sum of n and m is 1 to 8 and in which further G is chlorine or hydrogen and R 'and R "are each independently represent aryl or alkyl. Compounds according to claim 1, characterized in that R ¹ , R ² , R ³ and R ⁴ each independently represent hydrogen, methyl, ethyl, n-propyl, iso-propyl, n-butyl and n-pentyl. Compounds according to at least one of claims 1 and 2, characterized in that R 'and R''each independently of one another represent C ₃ -C ₈ -alkyl or C ₅ -C ₁₀ -aryl, which are not mono- or polysubstituted by radicals which are selected from the group chlorine, fluorine, cyano, phenyl, C ₁ -C ₆ alkoxy and C ₁ -C ₆ alkyl. Compounds according to at least one of claims 1 and 3, characterized in that they are the following: (R) - and (S) - [5,5'-dichloro-6,6 '- (cis-1,4-but-2-endioxy) biphenyl-2,2'-diyl] -bis - [(di-phenyl) phosphine . (R) - and (S) - [5,5'-dichloro-6,6 '- (cis-1,4-but-2-endioxy) -biphenyl-2,2'-diyl] -bis - [( di-cyclohexyl) phosphine, (R) - and (S) - [5,5'-dichloro-6,6 '- (cis-1,4-but-2-endioxy) -biphenyl-2,2'-diyl] -bis - [( di-3,5-di-tert-butyl-4-methoxyphenyl) phosphine, (R) - and (S) - [5,5'-dichloro-6,6 '- (cis-1,4-but-2-endioxy) -biphenyl-2,2'-diyl] -bis - [( di-3,5-dimethylphenyl) phosphine, (R) - and (S) - [5,5'-dichloro-6,6 '- (cis-1,4-but-2-endioxy) -biphenyl-2,2'-diyl] -bis - [( di-3,5-dimethyl-4-methoxyphenyl) phosphine, (R) - and (S) - [5,5'-dichloro-6,6 '- (cis-1,4-but-2-endioxy) -biphenyl-2,2'-diyl] -bis - [( di-4-fluoro-phenyl) phosphine and (R) - and (S) - [5,5'-dichloro-6,6 '- (cis-1,4-but-2-endioxy) -biphenyl-2,2'-diyl] -bis [ (di-3,5-di-tert-butylphenyl) phosphine as well as the corresponding trans compounds. Process for the preparation of compounds of the formula (IV),

in which B, G, R 'and R "have the meaning given in claim 1, characterized in that compounds of the formula (III)

with a compound of the formula (VIa) or (VIb) or successively with two different compounds of the formulas (VIa) and (VIb) X ³ - (CHR ¹ ) _n - (R ² C = CHR ⁵ ) (VIa) X ⁴ - (CHR ⁴ ) _m - (R ³ C = CHR ⁶ ) (VIb) in which X ³ and X ^{4 are} each chlorine, bromine, iodine or a sulfonate and R ¹ , R ² , R ³ and R ^{4 have} the meaning given in claim 1 and R ⁵ and R ^{6 are} each independently hydrogen or C C ₁ -C ₄ -alkyl are converted into compounds of the formula (VII)

and the compounds of formula (VII) are then converted into compounds of formula (IV) in the presence of an olefin metathesis catalyst. Method according to claim 5, characterized in that that the compounds of the formula (VII) are subsequently converted into compounds of the formula (I) according to claim 1 reduced. Compounds of the formula (VII)

in which R ¹ , R ² , R ³ , R ⁴ , R 'and R "have the meaning given in claim 1 and R ⁵ and R ^{6 are} each independently of one another hydrogen or C ₁ -C ₄ -alkyl. Compounds according to claim 7, characterized in that that are the following: (R) - and (S) - [5,5'-dichloro-6,6 '- (bis-allyloxy) -biphenyl-2,2'-diyl] -bis - [(dicyclohexyl) phosphine oxide, (R) - and (S) - [5,5'-dichloro-6,6 '- (bis-allyloxy) -biphenyl-2,2'-diyl] -bis - [(di-3,5-di-) tert -butyl-4-methoxyphenyl) phosphine oxide, (R) - and (S) - [5,5'-dichloro-6,6 '- (bis-allyloxy) -biphenyl-2,2'-diyl] -bis - [(di-3,5-dimethylphenyl) phosphine oxide. (R) - and (S) - [5,5'-dichloro-6,6 '- (bis-allyloxy) -biphenyl-2,2'-diyl] -bis - [(di-3,5-dimethyl- 4-methoxyphenyl) phosphine, (R) - and (S) - [5,5'-dichloro-6,6 '- (bis-allyloxy) -biphenyl-2,2'-diyl] -bis - [(di-4-fluorophenyl) phosphine oxide and (R) - and (S) - [5,5'-dichloro-6,6 '- (bis-allyloxy) -biphenyl-2,2'-diyl] -bis - [(di-3,5-di tert-butylphenyl) phosphine oxide. Compounds of the formula (IV)

in which B, R 'and R''have the meaning given in claim 1. Compounds according to claim 9, characterized that are the following: (R) - and (S) - [5,5'-dichloro-6,6 '- (cis-1,4-but-2-ene-dioxy) -biphenyl-2,2'-diyl] -bis [(di-cyclohexyl) phosphine, (R) - and (S) - [5,5'-dichloro-6,6 '- (cis-1,4-but-2-ene-dioxy) -biphenyl-2,2'-diyl] -bis [(di-3,5-di-tert-butyl-4-methoxyphenyl) phosphine, (R) - and (S) - [5,5'-dichloro-6,6 '- (cis-1,4-but-2-ene-dioxy) -biphenyl-2,2'-diyl] -bis [(di-3,5-dimethylphenyl) phosphine, (R) - and (S) - [5,5'-dichloro-6,6 '- (cis-1,4-but-2-ene-dioxy) -biphenyl-2,2'-diyl] -bis [(di-3,5-dimethyl-4-methoxyphenyl) phosphine, (R) - and (S) - [5,5'-dichloro-6,6 '- (cis-1,4-but-2-ene-dioxy) -biphenyl-2,2'-diyl] -bis [(di-4-fluorophenyl) phosphine oxide and (R) - and (S) - [5,5'-dichloro-6,6 '- (cis-1,4-but-2-endioxy) -biphenyl-2,2'-diyl] -bis [ (di-3,5-di-tert-butylphenyl) phosphine oxide as well the respective trans compounds, the cis compounds being preferred are. Transition metal complexes containing compounds according to one or more of claims 1 to 4. Catalysts containing transition metal complexes according to Claim 11. Process for transition metal catalyzed Preparation of enantiomerically enriched compounds, by characterized in that it in the presence of catalysts according to claim 13 is performed.