Process for preparing optically active biophosphinylalkanes
The present invention relates to a process for preparing optically active bisphosphinylalkanes from the correspondingly substituted, racemic 1,2-diols. The optically active bisphosphinylalkanes which can be obtained in this way are suitable as ligands for preparing chiral transition metal catalysts.
1. A process for preparing an optically active bisphosphinylalkanes of formula (I)
wherein
R 1 and R 2
identically are a straight-chain, branched, or cyclic alkyl radical which has up to 12 carbon atoms and is optionally substituted with one or more identical or different substituents selected from the group consisting of halogen, C 6 -C 12 -aryl, NR 5 R 6 , NHR 7 , OR 8 , and aryl radicals having from 6 to 12 carbon atoms and optionally substituted with one or more identical or different substituents selected from the group consisting of C 1 -C 6 -alkyl, halogen, C 6 -C 12 -aryl, NR 5′ R 6′ , NHR 7′ , and OR 8′ ; or together define an aliphatic ring or bicycle having from 4 to 12 ring members and is optionally substituted with one or more substituents selected from the group consisting of halogen, oxo, C 6 -C 12 -aryl, C 1 -C 10 -acyl, and C 1 -C 10 -sulfonyl, and optionally comprises one or more heteroatoms O or NR 9 ;
R 3 and R 4
identically or differently are each a straight-chain, branched, or cyclic alkyl radical having up to 12 carbon atoms or an aryl radical having from 6 to 12 carbon atoms, each of which is optionally substituted with one or more identical or different substituents selected from the group consisting of C 1 -C 12 -alkyl, halogen, NR 5″ R 6″ , NHR 7″ , OR 8″ , sulphonyl, C(O)OR 14 , and C(O)NR 14′ R 14″ ;
R 5 , R 6 , R 5′ , R 6′ , R 5″ , and R 6″
are, independently of one another, C 1 -C 12 -alkyl or C 6 -C 12 -aryl;
R 7 to R 7″
are C 1 -C 10 -acyl or C 1 -C 10 -sulfonyl;
R 8 to R 8″
are C 1 -C 12 -alkyl or C 6 -C 12 -aryl;
R 9 is C 1 -C 12 -alkyl, C 6 -C 12 -aryl, C 1 -C 10 -acyl, or C 1 -C 10 -sulfonyl;
R 14 , R 14′ are hydrogen, C 1 -C 12 -alkyl, C 6 -C 12 -aryl, or C 7 -C 17 -aralkyl;
R 14″ is C 1 -C 12 -alkyl, C 6 -C 12 -aryl, or C 7 -C 17 -aralkyl; and
* is an asymmetrically substituted carbon atom;
comprising
a) reacting a diol of formula (II)
wherein R 1 and R 2 are as defined in formula (I),
to form a compound of formula (III)
wherein R 1 and R 2 are as defined in formula (I), and both Z together in formula (III) form a structural fragment selected from group consisting of —O—S(O) 2 —O—, —O—P(O)(OR 15 ) 2 —O—, —O—C(O)—O—, and —O—C(O)—C(O)—O—, wherein R 15 is C 1 -C 12 -alkyl, C 7 -C 17 -aralkyl, or C 6 -C 12 -aryl;
b) reacting the compound of formula (III) obtained in a) with a phosphine oxide of formula (IV)
wherein R 3 and R 4 are as defined in formula (I),
in the presence of a base which is capable of deprotonating said phosphine oxide of formula (IV),
to form a racemic 1,2-trans-configured-bis(phosphine oxide) of formula (V)
wherein R 1 , R 2 , R 3 , and R 4 are as defined in formula (I);
c) resolving the racemic-bis(phosphine oxide) of formula (V) obtained in b) to give an optically active-bis(phosphine oxide) of formula (V*)
wherein R 1 , R 2 , R 3 , and R 4 are as defined in formula (I), and
* is an asymmetrically substituted carbon atom, and
d) reducing the compound of formula (V*) obtained in c) to give the compound of formula (I).
2. The process of claim 1 , wherein
R 1 and R 2
are, identical and are each a straight-chain, branched, or cyclic alkyl radical having up to 12 carbon atoms or together define an aliphatic ring or bicycle which has from 4 to 12 ring members and is optionally substituted with one or more substituents selected from the group consisting of halogen, oxo, C 6 -C 12 -aryl, C 1 -C 10 -acyl, and C 1 -C 10 -sulfonyl, and optionally comprises one or more heteroatoms O or NR 9 ; and
R 3 and R 4
are, identically or differently, an aryl radical having from 6 to 12 carbon atoms and is optionally substituted with one or more identical or different substituents selected from the group consisting of C 1 -C 6 -alkyl, halogen, NR 5″ R 6″ , NHR 7′ , OR 8″ , carboxy, and sulphonyl.
3. The process of claim 1 , wherein
R 1 and R 2
are identical and are each a straight-chain, branched, or cyclic alkyl radical having up to 6 carbon atoms or together form an aliphatic ring or bicycle having from 4 to 12 ring members and is optionally substituted with one or more substituents selected from the group consisting of halogen, oxo, C 6 -C 12 -aryl, C 1 -C 10 -acyl, and C 1 -C 10 -sulfonyl, and optionally comprises one or more heteroatoms O or NR 9 ; and
R 3 and R 4
are identical and are each an aryl radical having from 6 to 12 carbon atoms and is optionally substituted with one or more identical or different substituents selected from the group consisting of C 1 -C 12 -alkyl, halogen, NR 5″ R 6″ , NHR 7′ , OR 8″ , carboxy, and sulphonyl.
4. The process of claim 1 , wherein R 1 and R 2 together define a cyclohexyl ring and R 3 and R 4 are each substituted or unsubstituted phenyl.
5. The process of claim 1 , wherein R 1 and R 2 are each methyl and R 3 and R 4 are each substituted or unsubstituted phenyl.
6. The process of claim 1 , wherein b) is carried out in the presence of a polar aprotic solvent.
7. The process of claim 1 , wherein c) is achieved by carrying out a crystallization in the presence of a chiral auxiliary reagent.
8. The process of claim 7 , wherein said chiral auxiliary reagent is a chiral carboxylic or sulfonic acid in optically active form.
9. A process for preparing an optically active transition metal catalyst comprising preparing an optically active chiral bisphosphinylalkane of formula (I) by the process of claim 1
wherein
R 1 and R 2
identically are a straight-chain, branched, or cyclic alkyl radical which has up to 12 carbon atoms and is optionally substituted with one or more identical or different substituents selected from the group consisting of halogen, C 6 -C 12 -aryl, NR 5 R 6 , NHR 7 , OR 8 , and aryl radicals having from 6 to 12 carbon atoms and optionally substituted with one or more identical or different substituents selected from the group consisting of C 1 -C 6 -alkyl, halogen, C 6 -C 12 -aryl, NR 5′ R 6′ , NHR 7′ , and OR 8′ ; or together define an aliphatic ring or bicycle having from 4 to 12 ring members and is optionally substituted with one or more substituents selected from the group consisting of halogen, oxo, C 6 -C 12 -aryl, C 1 -C 10 -acyl, and C 1 -C 10 -sulfonyl, and optionally comprises one or more heteroatoms O or NR 9 ;
R 3 and R 4
identically or differently are each a straight-chain, branched, or cyclic alkyl radical having up to 12 carbon atoms or an aryl radical having from 6 to 12 carbon atoms, each of which is optionally substituted with one or more identical or different substituents selected from the group consisting of C 1 -C 12 -alkyl, halogen, NR 5″ R 6″ , NHR 7″ , OR 8″ , sulphonyl, C(O)OR 14 , and C(O)NR 14′ R 14″ ;
R 5 , R 6 , R 5 , R 6′ , R 5″ , and R 6″
are, independently of one another, C 1 -C 12 -alkyl or C 6 -C 12 -aryl;
R 7 to R 7″
are C 1 -C 10 -acyl or C 1 -C 10 -sulfonyl;
R 8 to R 8″
are C 1 -C 12 -alkyl or C 6 -C 12 -aryl;
R 9 is C 1 -C 12 -alkyl, C 6 -C 12 -aryl, C 1 -C 10 -acyl, or C 1 -C 10 -sulfonyl;
R 14 , R 14′
are hydrogen, C 1 -C 12 -alkyl, C 6 -C 12 -aryl, or C 7 -C 17 -aralkyl;
R 14″ is C 1 -C 12 -alkyl, C 6 -C 12 -aryl, or C 7 -C 17 -aralkyl; and
* is an asymmetrically substituted carbon atom;
and contacting said chiral bisphosphinyl alkane of formula (I) with a suitable transition metal compound.
10. The process of claim 9 , wherein said transition metal compound is a compound of a metal selected from the group consisting of Fe, Ru, Co, Rh, Ir, Ni, Pd, Pt, Cu, Ag, and Au.
11. The process of claim 9 , wherein said chiral bisphosphinylalkane is (R,R)-chiraphos.
12. A process for preparing an optically active bisphosphinylalkane of formula (I)
wherein
R 1 and R 2
identically are a straight-chain, branched, or cyclic alkyl radical which has up to 12 carbon atoms and is optionally substituted with one or more identical or different substituents selected from the group consisting of halogen, C 6 -C 12 -aryl, NR 5 R 6 , NHR 7 , OR 8 , and aryl radicals having from 6 to 12 carbon atoms and optionally substituted with one or more identical or different substituents selected from the group consisting of C 1 -C 6 -alkyl, halogen, C 6 -C 12 -aryl, NR 5′ R 6′ , NHR 7′ , and OR 8′ ; or together define an aliphatic ring or bicycle having from 4 to 12 ring members and is optionally substituted with one or more substituents selected from the group consisting of halogen, oxo, C 6 -C 12 -aryl, C 1 -C 10 -acyl, and C 1 -C 10 -sulfonyl, and optionally comprises one or more heteroatoms O or NR 9 ;
R 3 and R 4
identically or differently are each a straight-chain, branched, or cyclic alkyl radical having up to 12 carbon atoms or an aryl radical having from 6 to 12 carbon atoms, each of which is optionally substituted with one or more identical or different substituents selected from the group consisting of C 1 -C 12 -alkyl, halogen, NR 5″ R 6″ , NHR 7″ , OR 8″ , sulphonyl, C(O)OR 14 , and C(O)NR 14′ R 14″ ;
R 5 , R 6 , R 5′ , R 6′ , R 5″ , and R 6″
are, independently of one another, C 1 -C 12 -alkyl or C 6 -C 12 -aryl;
R 7 to R 7″
are C 1 -C 10 -acyl or C 1 -C 10 -sulfonyl;
R 8 to R 8″
are C 1 -C 12 -alkyl or C 6 -C 12 -aryl;
R 9 is C 1 -C 12 -alkyl, C 6 -C 12 -aryl, C 1 -C 10 -acyl, or C 1 -C 10 -sulfonyl;
R 14 , R 14′ are hydrogen, C 1 -C 12 -alkyl, C 6 -C 12 -aryl, or C 7 -C 17 -aralkyl;
R 14″ is C 1 -C 12 -alkyl, C 6 -C 12 -aryl, or C 7 -C 17 -aralkyl; and
* is an asymmetrically substituted carbon atom;
comprising
a) reacting a diol of formula (II)
wherein R 1 and R 2 are as defined in formula (I),
to form a compound of formula (III)
wherein R 1 and R 2 are as defined in formula (I), and
both Z together in formula (III) form a structural fragment selected from the group consisting of —O—S(O) 2 —O—, —O—P(O)(OR 15 ) 2 —O—, —O—C(O)—O—, and —O—C(O)—C(O)—O—, wherein R 15 is C 1 -C 12 -alkyl, C 7 -C 17 -aralkyl, or C 6 -C 12 -aryl;
b) reacting the compound of formula (III) obtained in a) with a phosphine oxide of formula (IV)
wherein R 3 and R 4 are as defined in formula (I),
in the presence of a base-selected from the group consisting of alkali metal hydroxides, alkaline earth metal hydroxides, alkali metal alkoxides, and alkaline earth metal alkoxides,
to form a racemic 1,2-trans-configured-bis(phosphine oxide) of formula (V)
wherein R 1 , R 2 , R 3 , and R 4 are as defined in formula (I);
c) resolving the racemic bis(phosphine oxide) of formula (V) obtained in b) to give an optically active bis(phosphine oxide) of formula (V*)
wherein R 1 , R 2 , R 3 , and R 4 are as defined in formula (I), and
* is an asymmetrically substituted carbon atom, and
d) reducing the compound of formula (V*) obtained in c) to give the compound of formula (I).
13. The process of claim 1 , wherein R 3 and R 4
identically or differently are each a straight-chain, branched, or cyclic alkyl radical having up to 12 carbon atoms or an aryl radical having from 6 to 12 carbon atoms, each of which is optionally substituted with one or more identical or different substituents selected from the group consisting of C 1 -C 12 -alkyl, halogen, NR 5″ R 6″ , NHR 7″ , OR 8″ , sulphonyl, and C(O)NR 14′ R 14″ .
14. The process of claim 12 , wherein R 3 and R 4
identically or differently are each a straight-chain, branched, or cyclic alkyl radical having up to 12 carbon atoms or an aryl radical having from 6 to 12 carbon atoms, each of which is optionally substituted with one or more identical or different substituents selected from the group consisting of C 1 -C 12 -alkyl, halogen, NR 5″ R 6″ , OR 8″ , sulphonyl, and C(O)NR 14′ R 14″ .
15. The process of claim 1 , wherein R 3 and R 4
identically or differently are each a straight-chain, branched, or cyclic alkyl radical having up to 12 carbon atoms or an aryl radical having from 6 to 12 carbon atoms, each of which is optionally substituted with one or more identical or different substituents selected from the group consisting of C 1 -C 12 -alkyl, halogen, NR 5″ R 6″ , NHR 7″ , OR 8″ , sulphonyl and C(O)NR 14′ R 14″ .
16. The process of claim 12 , wherein R 3 and R 4
identically or differently are each a straight-chain, branched, or cyclic alkyl radical having up to 12 carbon atoms or an aryl radical having from 6 to 12 carbon atoms, each of which is optionally substituted with one or more identical or different substituents selected from the group consisting of C 1 -C 12 -alkyl, halogen, NR 5″ R 6″ NHR 7″ , OR 8″ , sulphonyl, and C(O)NR 14′ R 14″ .
17. A process for preparing an optically active bisphosphinylalkane of formula (I)
wherein
R 1 and R 2 together define a cyclohexyl ring;
R 3 and R 4
identically or differently are each a straight-chain, branched, or cyclic alkyl radical having up to 12 carbon atoms or an aryl radical having from 6 to 12 carbon atoms, each of which is optionally substituted with one or more identical or different substituents selected from the group consisting of C 1 -C 12 -alkyl, halogen, NR 5″ R 6″ , NHR 7″ , OR 8″ , sulphonyl, C(O)OR 14 , and C(O)NR 14′ R 14″ ;
R 5″ and R 6″
are, independently of one another, C 1 -C 12 -alkyl or C 6 -C 12 -aryl;
R 7″ is C 1 -C 10 -acyl or C 1 -C 10 -sulfonyl;
R 8″ is C 1 -C 12 -alkyl or C 6 -C 12 -aryl;
R 14 and R 14′ are hydrogen, C 1 -C 12 -alkyl, C 6 -C 12 -aryl, or C 7 -C 17 -aralkyl;
R 14″ is C 1 -C 12 -alkyl, C 6 -C 12 -aryl, or C 7 -C 17 -aralkyl; and
* is an asymmetrically substituted carbon atom;
comprising
a) reacting a diol of formula (II)
wherein R 1 and R 2 are as defined in formula (I),
to form a compound of formula (III)
wherein R 1 and R 2 are as defined in formula (I), and each Z is a leaving group or both Z together form a structural fragment selected from the group consisting of —O—S(O) 2 —O—, —O—P(O)(OR 15 ) 2 —O—, —O—C(O)—O—, and —O—C(O)—C(O)—O—, wherein R 15 is C 1 -C 12 -alkyl, C 7 -C 17 -aralkyl, or C 6 -C 12 -aryl;
b) reacting the compound of the formula (III) obtained in a) with a phosphine oxide of formula (IV)
wherein R 3 and R 4 are as defined in formula (I),
in the presence of a base which is capable of deprotonating said phosphine oxide of formula (IV),
to form a racemic 1,2-trans-configured bis(phosphine oxide) of formula (V)
wherein R 1 , R 2 , R 3 , and R 4 are as defined in formula (I);
c) resolving the racemic bis(phosphine oxide) of formula (V) obtained in b) to give an optically active bis(phosphine oxide) of formula (V*)
wherein R 1 , R 2 , R 3 , and R 4 are as defined in formula (I), and
* is an asymmetrically substituted carbon atom, and
d) reducing the compound of the formula (V*) obtained in c) to give the compound of formula (I).
18. The process of claim 17 , wherein R 3 and R 4 are each substituted or unsubstituted phenyl.