Bicyclic 1,3-aminoalcohols, d8-metal complexes and...

Details Bicyclic 1,3-aminoalcohols, d8-metal complexes and... Bicyclic 1,3-aminoalcohols, d8-metal complexes and...

2001-03-06

2003-10-21

Shah, Mukund J. (Department: 1624)

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

Organic compounds

Carboxylic acid esters

C564S012000, C564S057000, C564S080000, C564S090000, C564S095000, C564S222000, C564S307000, C564S414000, C564S460000

Reexamination Certificate

active

06635783

ABSTRACT:

The present invention relates to bicyclic aminoalcohols; metal complexes with d8-metals and bicyclic aminoalcohols as ligands; a process for the asymmetric transfer hydrogenation of prochiral carbon double bonds or hetero atom carbon bonds with alkanols as a source of hydrogen; the use of bicyclic aminoalcohols as ligands in d8-metal complexes; and the use of metal complexes with d8-metals and bicyclic aminoalcohols as ligands for the asymmetric transfer hydrogenation of prochiral carbon/carbon double bonds and hetero atom/carbon double bonds.
In CA-A-2.239.970, a process is described for the asymmetric hydrogenation of carbon-hetero atom double bonds in for example prochiral ketones or imines using inorganic or organic hydrogen donors, for example secondary alkanols, in which process transition metal complexes are used as enantioselective catalysts, which contain chiral nitrogen-containing compounds as ligands. In the entire description, only ligands having a 1,2-aminoethanol basic structure are mentioned. WO 98/42643 describes the same process, using the same or similar ligands, in which Ru, Rh and iridium complexes with cyclopentadienyl ligands are used as catalysts. In addition, open-chained 1,3-aminopropanols are mentioned as ligands, but only moderate optical yields can be attained with these.
In J. Org. Chem. (1998), 63, pages 2749 to 2751, D. A. Alonso et al also describe the said process, whereby 2-aza-1-hydroxymethylnorbomane is used as the bicyclic asymmetric ligand. This likewise has a 1,2-aminoethanol basic structure and the NH-group is additionally bonded in the norbornane ring. Using this ligand, high conversions and optical yields are obtained.
It has now surprisingly been found that, during the asymmetric transfer hydrogenation with asymmetric ligands of a 1,3-aminopropanol basic structure in metal complexes as catalysts, high conversions and optical yields may be attained when the optionally substituted OH and NH groups are bound in the vicinity of the bridge of an at least bicyclic ring system, and together with the metal atom, form a six-membered ring.
A first object of the invention is compounds of formula I in the form of the racemates thereof, mixtures of diastereoisomers or predominantly pure diastereoisomers,
wherein
W signifies a direct bond or C
1
-C
4
-alkylene, X is a direct bond or C
1
-C
4
-alkylene, Y is C
1
-C
4
-alkylene, —O—, —S—, —NR
3
—, —NR
3
—CHR
4
—, —NR
3
—CR
4
R
5
, —SiR
4
R
5
—, —CHR
4
O— or —CR
4
R
5
O—,
R
1
signifies hydrogen, C
1
-C
6
-alkyl, C
2
-C
6
-alkenyl, C
3
-C
8
-cycloalkyl, C
3
-C
8
-cycloalkenyl, C
6
-C
10
-aryl, or C
7
-C
12
-aralkyl,
R
2
is hydrogen, C
1
-C
6
-alkyl, C
3
-C
8
-cycloalkyl, C
6
-C
10
-aryl, or C
7
-C
12
-aralkyl, C
1
-C
8
-acyl, C
1
-C
6
-alkoxycarbonyl, C
1
-C
6
-alkylaminocarbonyl, di(C
1
-C
6
-alkyl)aminocarbonyl, (R
6
)
2
P(O)—, or R
6
SO
2
—,
R
3
signifies C
1
-C
6
-alkyl, cyclohexyl, phenyl or benzyl,
R
4
and R
5
, independently of one another, are C
1
-C
6
-alkyl, cyclohexyl, phenyl or benzyl, and
R
6
is C
1
-C
6
-alkyl, C
1
-C
6
-halogenalkyl; or cyclohexyl, phenyl or benzyl either unsubstituted or substituted by C
1
-C
4
-alkyl, C
1
-C
4
-halogenalkyl, or C
1
-C
4
-alkoxy;
whereby aliphatic, saturated or ethylenically unsaturated and/or aromatic hydrocarbon rings are optionally condensed onto the rings of the bicyclic ring system; and
the optionally condensed bicyclic ring system is unsubstituted or is substituted by C
1
-C
6
-alkyl, C
1
-C
6
-alkoxy, cyclohexyl, C
6
-C
10
-aryl, C
7
-C
12
-aralkyl, C
1
-C
4
-alkyl-C
6
-C
10
-aryl, C
1
-C
4
-alkoxy-C
6
-C
10
-aryl, C
1
-C
4
-alkyl-C
7
-C
12
-aralkyl, C
1
-C
4
-alkoxy-C
7
-C
12
-aralky;
as well as the acid addition salts thereof.
In formula I, W preferably signifies C
1
-C
3
-alkylene, and most preferably C
1
- or C
2
-alkylene. In formula I, X preferably signifies a direct bond or C
1
-C
3
-alkylene, most preferably C
1
- or C
2
-alkylene. In formula I, Y preferably signifies C
1
- or C
2
-alkylene. In an especially preferred embodiment, W, X and Y are selected so that in the bicyclic ring system of formula I they each form a 4- to 8-membered, preferably 5- to 7-membered, most preferably 5- or 6-membered hydrocarbon ring.
R
1
as alkyl preferably contains 1 to 4 C-atoms. Examples of alkyl are methyl, ethyl, n- and isopropyl, n—, iso- and tert.-butyl, as well as the isomers of pentyl and hexyl.
R
1
as alkenyl preferably contains 2 to 4 C-atoms. Examples of alkenyl are vinyl, allyl and crotonyl.
R
1
as cycloalkyl preferably contains 4 to 7 C-atoms. Examples of cycloalkyl are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl. Cyclopentyl and cyclohexyl are preferred.
R
1
as cycloalkenyl preferably contains 4 to 7 C-atoms. Examples of cycloalkyl are cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl and cyclooctenyl. Cyclopentenyl and cyclohexenyl are preferred.
R
1
as aryl may be for example phenyl or naphthyl.
R
1
as aralkyl may be for example phenyl-C
1
-C
4
-alkyl or naphthyl-C
1
-C
4
-alkyl. Benzyl and phenylethyl are preferred.
In a preferred embodiment, R
1
is hydrogen, C
1
-C
4
-alkyl, allyl, cyclopentyl, cyclohexyl, phenyl or benzyl. R
1
is most preferably hydrogen.
R
2
as alkyl preferably contains 1 to 4 C-atoms. Examples of alkyl are methyl, ethyl, n- and isopropyl, n-, iso- and tert.-butyl, as well as the isomers of pentyl and hexyl.
R
2
as cycloalkyl preferably contains 4 to 7 C-atoms. Examples of cycloalkyl are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl. Cyclopentyl and cyclohexyl are preferred.
R
2
as aryl may be for example phenyl or naphthyl.
R
2
as aralkyl may be for example phenyl-C
1
-C
4
-alkyl or naphthyl-C
1
-C
4
-alkyl Benzyl and phenylethyl are preferred.
R
2
as alkoxycarbonyl is preferably C
1
-C
4
-alkoxycarbonyl. Examples of alkoxy are methoxy, ethoxy, n- and isopropyloxy, n-, iso- and tert.-butyloxy, as well as the isomers of pentyloxy and hexyloxy. R
2
is preferably tert.-butyloxycarbonyl.
When R
2
is the radical (R
2
)
2
P(O)— or R
6
—SO
2
—, R
6
is preferably C
1
-C
4
-alkyl, C
1
-C
4
-halogen-alkyl, or phenyl or benzyl either unsubstituted or substituted by methyl, ethyl, trifluoromethyl, methoxy or ethoxy. Halogen in the halogen moiety is preferably chlorine, and more preferably fluorine. Examples of the radical R
6
—SO
2
— are methyl-, ethyl-, n- and iso-propyl-, n- and iso-butyl-, phenyl-, benzyl-, methylphenyl-, ethylphenyl-, dimethylphenyl-, methylbenzyl-, dimethylbenzyl-, trifluoromethylphenyl- and bis(trifluormethyl)phenylsulfonyl. Examples of the radical (R
6
)
2
P(O)— are dimethyl-, diethyl-, diphenyl- and di-p-toluyloxyphosphinyl.
If R
2
signifies acyl, it preferably contains 1 to 6, most preferably 1 to 4 C-atoms. A few examples are formyl, acetyl, propionyl, butyroyl and benzoyl.
If R
2
signifies alkylaminocarbonyl or di(alkyl)aminocarbonyl, the alkyl group preferably contains 1 to 4, most preferably 1 or 2 C-atoms. A few examples are methylamino-, dimethylamino-, ethylamino-, diethylamino-, methyl-ethylamino-, n- or iso-propylamino- and di-n- or -iso-propylaminocarbonyl
If R
3
is alkyl, it preferably contains 1 to 4 C-atoms. R
3
is preferably ethyl and most preferably methyl.
If R
4
and R
5
are alkyl, it preferably contains 1 to 4 C-atoms. R
4
and R
5
are preferably methyl.
In a preferred embodiment, R
2
is C
1
-C
4
-alkyl, cyclopentyl, cyclohexyl, phenyl, benzyl, C
1
-C
4
-alkoxycarbonyl or the radical R
6
—SO
2
—, wherein R
6
is C
1
-C
4
-alkyl, C
1
-C
4
-fluoroalkyl, or phenyl either unsubstituted or substituted by one or two methyl or trifluoromethyl.
If hydrocarbon rings are condensed onto the bicyclic ring system, then these are preferably C
6
-C
10
-aryl (for example benzene or naphthaline), C
3
-C
8
-cycloalkyl, preferably C
5
-C
7
-cycloalkyl, or C
4
-C
8
-cycloalkenyl, preferably C
5
-C
7
-cycloalkenyl.
Preferred substituents for the optionally condensed bicyclic ring system are C
1
-C
4
-alkyl (for example methyl, ethyl, n- and iso-propyl and the isomers of butyl, and C
1
-C
4
-Alko

Affiliated with

Also associated with

Rating

Bicyclic 1,3-aminoalcohols, d8-metal complexes and... does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Bicyclic 1,3-aminoalcohols, d8-metal complexes and..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Bicyclic 1,3-aminoalcohols, d8-metal complexes and... will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3161550