Chiral C2-symmetric biphenyls, their preparation and also metal complexes in which these ligands are present and their use as catalysts in chirogenic syntheses
A new class of C 2 -symmetric biaryldiphosphines comprising a fused ring system (dioxacycle) which has at least seven ring atoms and can be varied synthetically. The biaryldiphosphines can be used as ligands for preparing metal complexes useful as catalysts in organic synthesis, and the dioxacycles can be varied to optimize reaction with specific substrates.
1 . A compound of the formula (I)
wherein
R 1 and R 2 are each hydrogen,
R 3 and R 4 are identical or different and are independently selected from the group consisting of hydrogen, fluorine, C 1 -C 10 -alkyl, and CF 3 ,
Y is a divalent radical selected from the group consisting of CR 9 2 , CHR 9 , (cis)-CH═CH, CR 9 2 CR 10 2 , CHR 9 CHR 10 , 1,2-arylene, CHR 9 -O-CHR 10 , and CR 9 2 —O—CR 10 2 ,
where R 9 and R 10 are identical or different and are independently selected from the group consisting of hydrogen; Q; monosubstituted, polysubstituted or unsubstituted C 1 -C 10 -alkyl, C 3 -C 10 -cycloalkyl, C 2 -C 10 -alkenyl, C 4 -C 10 -cycloalkenyl, C 2 -C 10 -alkynyl, C 6 -C 15 -aryl, and C 1 -C 15 -heteroaryl, where the substituents are optionally Q and
Q is selected from the group consisting of —F, —Cl, —Br, —I, —CN, —NO 2 , —NR 7 R 8 , —NR 7 OR 8 , —OR 7 , —C(O)R 7 , SR 7 , —SO 3 R 7 , —C(O)OR 7 , —C(O)NR 7 R 8 , —OC(O)R 7 , and —NR 7 C(O)R 8 ,
R 7 and R 8 are identical or different and are independently selected from R 9 ,
R 5 and R 6 are identical or different and are independently selected from the group consisting of monosubstituted, polysubstituted or unsubstituted C 3 -C 10 -cycloalkyls, C 4 -C 10 -cycloalkenyls, C 5 -C 15 -aryls and C 1 -C 15 -heteroaryls, where the substituents are optionally Q.
2 . The compound of claim 1 in an optical configuration of the formulae (Ia) and (Ib)
3 . A process for preparing a compound of claim 1 , comprising the steps:
A) reacting a compound of the formula (IV)
where X is halogen,
with a phosphinyl chloride R 5 R 6 P(O)Cl, to form a compound of the formula (IIIa)
B) converting the compound of the formula (IIIa) obtained in step A into a compound of the general formula (II)
by oxidative coupling and
C) reducing the compound of the formula (II) obtained in step B.
4 . The process of claim 3 , wherein, in step B, the compound of the general formula (IIIa) obtained from step A is firstly converted by iodination into an intermediate of the formula (IIIb)
and this intermediate is subsequently converted in a metal-catalyzed coupling reaction into a compound of the formula (II).
5 . The process of claim 3 , wherein the compounds of the formula (II) obtained in step B are prepared in enantiomerically pure or enantiomerically enriched form corresponding to the general formulae (IIa) and (IIb)
by fractional crystallization in the presence of complexing chiral compounds.
6 . The process of claim 4 , wherein the compounds of the formula (II) obtained in step B are prepared in enantiomerically pure or enantiomerically enriched form corresponding to the general formulae (IIa) and (IIb)
by fractional crystallization in the presence of complexing chiral compounds.
7 . The process of claim 3 , wherein the compounds of the formula (I) are prepared in enantiomerically pure or enantiomerically enriched form corresponding to the formulae (Ia) and (Ib) by converting to a chiral palladium complex in an additional step D.
8 . The process of claim 4 , wherein the compounds of the formula (I) are prepared in enantiomerically pure or enantiomerically enriched form corresponding to the formulae (Ia) and (Ib) by converting to a chiral palladium complex in an additional step D.
9 . A compound of the formula (II)
wherein
R 1 and R 2 are each hydrogen,
R 3 and R 4 are identical or different and are independently selected from the group consisting of hydrogen, fluorine, C 1 -C 10 -alkyl, and CF 3 ,
Y is a divalent radical selected from the group consisting of CR 9 2 , CHR 9 , (cis)-CH═CH, CR 9 2 CR 10 2 , CHR 9 CHR 10 , 1,2-arylene, CHR 9 —O—CHR 10 , and CR 9 2 —O—CR 10 2 ,
where R 9 and R 10 are identical or different and are independently selected from the group consisting of hydrogen; Q; monosubstituted, polysubstituted or unsubstituted C 1 -C 10 -alkyl, C 3 -C 10 -cycloalkyl, C 2 -C 10 -alkenyl, C 4 -C 10 -cycloalkenyl, C 2 -C 10 -alkynyl, C 6 -C 15 -aryl, and C 1 -C 15 -heteroaryl, where the substituents are optionally Q and
Q is selected from the group consisting of —F, —Cl, —Br, —I, —CN, —NO 2 , —NR 7 R 8 , —NR 7 OR 8 , —OR 7 , —C(O)R 7 , SR 7 , —SO 3 R 7 , —C(O)OR 7 , —C(O)NR 7 R 8 , —OC(O)R 7 , and —NR 7 C(O)R 8 ,
R 7 and R 8 are identical or different and are independently selected from R 9 ,
R 5 and R 6 are identical or different and are independently selected from the group consisting of monosubstituted, polysubstituted or unsubstituted C 3 -C 10 -cycloalkyls, C 4 -C 10 -cycloalkenyls, C 5 -C 15 -aryls and C 1 -C 15 -heteroaryls, where the substituents are optionally Q.
10 . A compound of claim 9 in an optical configuration of the formulae (IIa) and (IIb)
11 . A process for preparing enantiomerically pure or enantiomerically enriched compounds of claim 10 by fractional crystallization of compounds of the formula II in the presence of at least one complexing chiral compound.
12 . A process for preparing enantiomerically pure or enantiomerically enriched compounds of claim 2 by converting compounds of the formula I into chiral palladium complexes.
13 . A compound of the formula (IIIa) or (IIIb)
wherein
R 1 and R 2 are each hydrogen,
R 3 and R 4 are identical or different and are independently selected from the group consisting of hydrogen, fluorine, C 1 -C 10 -alkyl, and CF 3 ,
Y is a divalent radical selected from the group consisting of CR 9 2 , CHR 9 , (cis)-CH═CH, CR 9 2 CR 10 2 , CHR 9 CHR 10 , 1,2-arylene, CHR 9 —O—CHR 10 , and CR 9 2 —O—CR 10 2,
where R 9 and R 10 are identical or different and are independently selected from the group consisting of hydrogen; Q; monosubstituted, polysubstituted or unsubstituted C 1 -C 10 -alkyl, C 3 -C 10 -cycloalkyl, C 2 -C 10 -alkenyl, C 4 -C 10 -cycloalkenyl, C 2 -C 10 -alkynyl, C6-C 15 -aryl, and C 1 -C 15 -heteroaryl, where the substituents are optionally Q and
Q is selected from the group consisting of —F, —Cl, —Br, —I, —CN, —NO 2 , —NR 7 R 8 , —NR 7 OR 8 , —OR 7 , —C(O)R 7 , SR 7 , —SO 3 R 7 , —C(O)OR 7 , —C(O)NR 7 R 8 , —OC(O)R 7 , and —NR 7 C(O)R 8 ,
R 7 and R 8 are identical or different and are independently selected from R 9 ,
R 5 and R 6 are identical or different and are independently selected from the group consisting of monosubstituted, polysubstituted or unsubstituted C 3 -C 10 -cycloalkyls, C 4 -C 10 -cycloalkenyls, C 5 -C 15 -aryls and C 1 -C 15 -heteroaryls, where the substituents are optionally Q.
14 . A compound of the formula (IV)
where
R 1 and R 2 are each hydrogen,
R 3 and R 4 are identical or different and are independently selected from the group consisting of hydrogen, fluorine, C 1 -C 10 -alkyl, and CF 3 ,
R 7 and R 8 are identical or different and are independently selected from R 9 ,
Y is a divalent radical selected from the group consisting of CR 9 2 , CHR 9 , (cis)-CH═CH, CR 9 2 CR 10 2 , CHR 9 CHR 10 , 1,2-arylene, CHR 9 —O—CHR 10 , and CR 9 2 —O—CR 10 2 ,
where R 9 and R 10 are identical or different and are independently selected from the group consisting of hydrogen; Q; monosubstituted, polysubstituted or unsubstituted C 1 -C 10 -alkyl, C 3 -C 10 -cycloalkyl, C 2 -C 10 -alkenyl, C 4 -C 10 -cycloalkenyl, C 2 -C 10 -alkynyl, C 6 -C 15 -aryl, and C 1 -C 15 -heteroaryl, where the substituents are optionally Q,
Q is selected from the group consisting of —F, —Cl, —Br, —I, —CN, —NO 2 , —NR 7 R 8 , —NR 7 OR 8 , —OR 7 , —C(O)R 7 , SR 7 , —SO 3 R 7 , —C(O)OR 7 , —C(O)NR 7 R 8 , —OC(O)R 7 , and —NR 7 C(O)R 8 ,
with the proviso that CR 3 2 —Y—CR 4 2 cannot be (CH 2 ) 3 when X is Br.
15 . A complex comprising at least one ligand of formula (I) of claim 1 , and at least one metallic center.
16 . The complex of claim 15 , wherein at least one ligand of formula (I) is present in enantiomerically pure or enantiomerically enriched form.
17 . The complex of claim 15 , wherein, when a ligand of the general formula (I) which is not enantiomerically pure is present, another chiral ligand is additionally present.
18 . The complex of claim 15 , wherein the metallic center is selected from the group consisting of rhodium, ruthenium, iridium, palladium, copper and nickel.
19 . The complex of claim 17 , wherein the metallic center is selected from the group consisting of rhodium, ruthenium, iridium, palladium, copper and nickel.
20 . A process for preparing a complex of claim 15 , comprising reacting a compound of the formula (I) with a precursor containing the metallic center, in the presence of an organic solvent.
21 . In an orgnic synthesis wherein a metal complex catalyst is employed, the improvement comprising selecting as a catalyst, a complex of claim 15 .
22 . The synthesis of claim 21 , wherein a chiral complex is used as the catalyst in an asymmetric organic synthesis.
23 . The synthesis of claim 21 wherein the catalyst is a homogeneous catalyst or is present in immobilized form as a heterogeneous catalyst.
24 . The synthesis of claim 21 which is a hydrogenation, isomerization, or C—C bond formation reaction.
25 . A process for hydrogenating C═O, C═C or C═N groups in a substrate, comprising hydrogenating in the presence of a complex of claim 15 .
26 . The process claim 25 , wherein said process is an asymmetric hydrogenation carried out in the presence of a chiral complex of Formula I.
27 . The process of claim 26 , wherein hydrogenation is carried out in the presence of a complex containing (S)-(−)-[6,6′-bis(3,4-dihydro-2H-1,5-benzodioxepin)-7,7′-diyl]bis(diphenylphosphine) (VIIa)
or (R)-(+)-[6,6′-bis(3,4-dihydro-2H-1,5-benzodioxepin)-7,7′-diyl]bis(diphenylphosphine) (VIIb)
as a ligand.