Ligands and complexes for enantioselective hydrogenation

Details Ligands and complexes for enantioselective hydrogenation Ligands and complexes for enantioselective hydrogenation

1999-12-20

2001-02-20

Nazario-Gonzalez, Porfirio (Department: 1621)

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

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

C556S014000, C556S028000, C556S136000, C556S143000, C502S154000, C502S155000, C585S275000

Reexamination Certificate

active

06191284

ABSTRACT:

BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention is related to ligands and complexes for homogeneous catalytic enantioselective hydrogenation. More particularly, the invention relates to ligands of formula (I)
Another aspect of the invention is related to complexes of formula (II), and to
a method for their preparation and use.
Enantioselective introduction of stereogenic centers into organic molecules by homogeneously catalyzed hydrogenation is established industrially for special applications. The enantioselective products are valuable starting substances for the production of biologically active agents.
2. Discussion of the Background
The use of catalysts containing bisphosphine ligands for enantioselective homogeneous catalytic hydrogenation for the above purposes is known (Burk et al., Tetrahedron, 1994, 4399).
Knochel et al. (Chem. Eur. J. 1988, 4, 950-968), Hayashi et al. (J. Chem. Soc., Chem. Commun. 1989, 495-496) and Ikeda et al. (Tetrahedron Lett. 1996, 4545-4448) describe Pd complexes with C
2
symmetric ferrocenyl (bis-tert-phosphine) ligands. However, these complexes were used only in asymmetric allylations.
In contrast, Yamamoto et al. (Bull. Chem. Soc. Jpn. 1980, 53, 1132-1137) reported the use of non-C
2
-symmetric ferrocenyl(bis-tert-phosphine) ligands in enantioselective homogeneous catalytic hydrogenation reactions. However, only very sporadically good enantiomer excesses are obtained with these ligands.
The basic suitability of non C
2
symmetric ferrocenyl ligands for enantioselective hydrogenation is taught in WO 96/32400 and WO 95/21151.
SUMMARY OF THE INVENTION
Accordingly, one object of the present invention is to provide an enantiomer-enriched bisphosphine ligand system and catalysts derived therefrom which are consistently of good effectiveness for the homogeneous enantioselective catalytic hydrogenation of multiple bonds.
Multiple bonds within the scope of the invention are understood to mean double bonds between a carbon atom and another carbon atom or oxygen atom or nitrogen atom.
Briefly, this object and other objects of the present invention as hereinafter will become more readily apparent can be attained by an enantiomer-enriched ligand and salts thereof of formula (I)
wherein
R
1
and R
2
, independent of one another, are R
8
, NR
6
R
7
, SR
6
, (C
1
-C
18
)-alkyl, (C
1
-C
18
,)-alkoxy, (C
2
-C
18
)-alkoxyalkyl, (C
1
-C
18
)-acyloxy, (C
6
-C
18
)-aryl, (C
7
-C
19
)-aralkyl, (C
3
-C
18
)-heteroaryl, (C
4
-C
19
)-heteroaralkyl, (C
1
-C
8
)-alkyl-(C
6
-C
18
)-aryl, (C
1
-C
19
)-alkyl-(C
3
-C
19
)-heteroalkyl, (C
3
-C
8
)-cycloalkyl, (C
1
-C
8
)-alkyl-(C
3
-C
8
)-cycloalkyl, (C
3
-C
8
)-cycloalkyl-(C
1
-C
8
)-alkyl;
or R
1
and R
2
are bonded via a (C
3
-C
7
)-carbocycle, which is optionally substituted at least once by linear or branched (C
1
-C
8
)-alkyl, (C
1
-C
8
)-acyl, (C
1
-C
8
)-alkoxy, (C
2
-C
8
)-alkoxyalkyl and/or optionally contains at least one heteroatom selected from the group consisting of N, O, P and S, in the ring;
R
3
and R
4
, independent of one another, are H, (C
1
-C
18
)-alkyl, (C
1
-C
18
)-alkoxy, (C
2
-C
18
)-alkoxyalkyl, (C
1
-C
18
)-acyloxy, (C
6
-C
18
)-aryl, (C
7
-C
19
)-aralkyl, (C
3
-C
18
)-heteroaryl, (C
4
-C
19
)-heteroaralkyl, (C
1
-C
8
)-alkyl-(C
6
-C
18
) aryl, (C
1
-C
8
)-alkyl-(C
3
-C
19
)-heteroalkyl, (C
3
-C
8
)-cycloalkyl, (C
1
-C
8
)-alkyl-(C
3
-C
8
) cycloalkyl and (C
3
-C
8
)-cycloalkyl-(C
1
-C
8
)-alkyl;
or R
3
and R
4
arc bonded via a (C
3
-C
5
)-bridge, which optionally contains at least one double bond and/or is optionally substituted at least once by linear or branched (C
1
-C
8
)-alkyl, (C
1
-C
8
)-acyl, (C
1
-C
8
)-alkoxy, (C
2
-C
8
)-alkoxyalkyl or optionally contains at least one heteroatom selected from the group consisting of N, O, P and S in the ring;
R
5
is (C
1
-C
18
)-alkyl, (C
6
-C
18
)-aryl, (C
3
-C
8
)-heteroaryl, (C
1
-C
8
)-alkyl-(C
6
-C
18
)-aryl, (C
1
-C
8
)-alkyl-(C
3
-C
19
)-heteroalkyl, (C
3
-C
8
)-cycloalkyl, (C
1
-C
8
)-alkyl-(C
3
-C
8
)-cycloalkyl, where the radical R
5
on the same phosphorus atom and/or the two phosphorus atoms can be different;
R
6
and R
7
, independent of one another, are H, (C
1
-C
18
)-alkyl, (C
1
-C
18
)-alkoxy, (C
2
-C
18
)-alkoxyalkyl, (C
1
-C
18
)-acyl, (C
6
-C
18
)-aryl, (C
7
-C
19
)-aralkyl, (C
3
-C
18
)-heteroaryl, (C
4
-C
19
)-heteroaralkyl, (C
1
-C
8
)-alkyl-(C
6
-C
18
)-aryl, (C
1
-C
18
)-alkyl-(C
3
-C
19
)-heteroalkyl, (C
3
-C
8
)-cycloalkyl, (C
1
-C
8
)-alkyl-(C
3
-C
8
)-cycloalkyl and (C
3
-C
8
)-cycloalkyl-(C
1
-C
8
)-alkyl,
or R
6
and R
7
are bonded via a (C
3
-C
7
)-carbocycle, which is optionally substituted at least once by linear or branched (C
1
-C
8
) alkyl, (C
1
-C
8
) acyl, (C
1
-C
8
) alkoxy, (C
2
-C
8
)-alkoxyalkyl and/or optionally contains at least one heteroatom selected from the group consisting of N, O, P and S in the ring;
R
8
is H or a moiety B-X-Z, where B is a radical selected from the group consisting of CR
9
2
, NR
9
, O, S and SiR
9
2
, X is a spacer selected from the group consisting of 1,4′-biphenyl, 1-,2-ethylene, 1-,3-propylene, PEG-(2-10) and Z is a radical bonded to a polymer via a functional group selected from the group consisting of —O—, —NH—, —CONH, -ethenyl-, —NHCONH—, —OCONH— or —NHCOO—, or the radical R
8
of the two cyclopentadienyl rings is bonded via an &agr;,&ohgr;-(C
2
-C
4
)-alkylene bridge to each other;
R
9
is H or (C
1
-C
18
)-alkyl.
Especially preferred are ligands in which R
1
, R
2
, independent of one another, are H, NR
6
R
7
, (C
1
-C
8
)-alkyl, (C
1
-C
8
)-acyloxy, (C
6
-C
18
)-aryl and (C
3
-C
8
)-cycloalkyl;
or R
1
and R
2
are bonded via a (C
3
-C
7
)-carbocycle;
R
3
and R
4
, independent of one another, are (C
1
-C
8
)-alkyl, (C
6
-C
18
)-aryl, (C
3
-C
8
)-cycloalkyl;
or R
3
and R
4
arc bonded via a (C
3
-C
5
)-bridge, which optionally contains at least one double bond;
R
5
is (C
6
-C
18
)-aryl or (C
3
-C
8
)-cycloalkyl,
R
6
and R
7
, independent of one another, are (C
1
-C
18
)-alkyl, (C
1
-C
18
)-acyl, (C
6
-C
18
)-aryl and (C
3
-C
8
)-cycloalkyl;
or R
6
and R
7
are bonded via a (C
3
-C
7
)-carbocycle; and
R
8
is H.
Another aspect of the invention is an enantiomer-enriched complex of formula (II) and salts thereof;
wherein R
1
and R
9
have the meanings given above and M is a metal atom or ion of subgroup 7 or 8 including Co, Ni, Rh, Ru, Ir, Pd, Re and Pt.
Especially preferred are complexes of formula (II), in which R
1
and R
2
, independent of one another, are H, NR
6
R
7
(C
1
-C
8
)-alkyl, (C
1
-C
8
)-acyloxy, (C
6
-C
8
)-aryl and (C
3
-C
8
)-cycloalkyl;
or R
1
and R
2
are bonded together as a (C
3
-C
7
)-carbocycle;
R
3
and R
4
, independent of one another, are (C
1
-C
8
)-alkyl, (C
6
-C
18
)-aryl and (C
3
-C,)-cycloalkyl;
or R
3
and R
4
are bonded via a (C
3
-C
5
)-bridge, which optionally contains at least one double bond;
R
5
is (C
6
-C
18
)-aryl or (C
3
-C
18
)-cycloalkyl;
R
6
and R
7
, independent of one another, are (C
1
-C
18
)-alkyl, (C
1
-C
18
)-acyl, (C
6
-C
18
)-aryl and (C
3
-C
8
)-cycloalkyl;
or R
6
and R
7
are bonded via a (C
3
-C
7
)-carbocycle; and
R
8
is H;
and M is a metal atom or ion of Group 8 such as Rh, Ru or Pd.
A still another aspect of the invention is directed to a method for preparation of the ligands of the invention.
Compounds of formula (III):
where R
3
, R
4
and R
8
are as defined above and R
10
=Hal, can be converted enantioselectively to compounds of formula (IV):
where R
1
and R
2
are H or OH, where R
1
and R
2
must not be the same, R
3
, R
4
and R
8
have the meanings stated above and R
10
is Hal.
Then compounds of formula (IV), where R
1
and R
2
are H or OH, where R
1
and R
2
must not be the same, R
3
, R
4
and R
8
have the meanings stated above and R
10
=H, are converted to compounds of formula (V)
where R
1
and R
2
are H or N(C
1
-C
8
)-alkyl
2
, where R
1
and R
2
must not be the same, R
3
, R
4
and R
8
have the meanings stated above and R
10
=Hal.
In the next step compounds of formula (V), where R
1
and R
2
are H or N(C
1
-C
8
)

Affiliated with

Also associated with

Rating

Ligands and complexes for enantioselective hydrogenation does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Ligands and complexes for enantioselective hydrogenation, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Ligands and complexes for enantioselective hydrogenation will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2597600