Catalyst – solid sorbent – or support therefor: product or process – Catalyst or precursor therefor
Reexamination Certificate
2000-02-15
2001-01-30
Shah, Mukund J. (Department: 1624)
Catalyst, solid sorbent, or support therefor: product or process
Catalyst or precursor therefor
C544S236000
Reexamination Certificate
active
06180551
ABSTRACT:
FIELD OF THE INVENTION
Process for preparing meo-peg-protected dihydroquinine or dihydroquinidine derivatives
DISCUSSION OF RELATED ART
In
Chem. Rev
. 1994, 94, 2483 (Sharpless, et al), there are described monomeric catalyst systems for enantioselective dihydroxylation based on dihydroquinine and dihydroquinidine derivatives. Although the inantio-selectivity of the charged catalysts is very high, the charged ligands are disadvantageous in the respect that it is difficult or not possible to recycle them and where this is possible, only with poor yield (liquid-liquid extraction yield clearly under 80%).
In
J. Am. Chem. Soc
. 1996, 118, 7632-3 (Janda, et al), there is mentioned the formation of MeO-Peg-protected dihydroquinine, as well as its application in the enantioselective dihydroxylation of double bond containing compounds. The catalyst system mentioned therein achieves the enantioselective dihydroxylation of standard compounds at a level up to 30% worse ee levels as the original system found in Sharpless, et al.
TABLE 1
ee-Value
ee-Value
Nr.
Olefin Charged
Janda et al.
Sharpless et al.
1
88%
99%
2
60%
99%
3
85%
98%
4
43%
98%
In Table 1 there are set forth the best enantioselectivities achieved by Janda, et al and Sharpless, et al, in the dihydroxylation of standard compounds with their catalyst or ligand systems. Clearly, the polymer binding of the ligand system under the reaction conditions optimized for a single system, leads to drastically worse ee values.
SUMMARY OF THE INVENTION
The invention refers to new dihydroquinine or dihydroquinidine derivatives of Formulas (I) and (IV), obtainable by the procedures of the present invention, as well as their use for the enantioselective dihydroxylation of double bonds.
The task of the invention was therefore to develop a procedure for the formation of a catalyst system, which gives rise to good ee values such as in the original Sharpless procedure during dihydroxylation and which can be readily separated from the reaction mixture and so becomes available for a new reaction cycle. The task of the invention was further the provision of new catalyst systems that can serve for the asymmetric dihydroxylation of double bonds, as well as the manner and use of their application.
The invention involves a procedure for the manufacture of dihydroquinine derivatives of Formula (I)
wherein m is a whole number in the range of 50 to 150, n is a whole number in the range of 1 to 5 and z is a whole number in the range of 0 to 4,
R
1
, R
2
, and R
3
independently of each other are the same or different, R
2
and R
3
depend upon a variable n, and these have value H, (C
1
-C
5
)-alkyl, being linear or branched, (C
3
-C
8
)-cycloalkyl, aryl, aralkyl, alkylaryl or (C
1
-C
8
)-alkylalkoxy (sic) which may be linear or branched, and
R is a residue of Formula (II) or (III)
wherein R′ is hydrogen, (C
1
-C
5
) alkyl being linear or branched, (C
3
-C
8
) cycloalkyl, aryl, aralkyl or alkylaryl,
as well as for the formation of dihydroquinidine derivatives of Formula (IV)
wherein m and p independently of each other are the same or different whole numbers in the range of 50-150, n and o independently of each other are whole numbers in the range of 1-5 and z and y independently of each other are the same or different whole numbers in the range of 0 through 4, and R, R
1
, R
2
, and R
3
have the same meaning as in Formula (I) wherein R
2
and R
3
are thereby additionally dependent upon variable o.
When one esterifies compounds of Formula (I) or (VI) with compounds of general Formula (VIII) (see scheme 1), one can obtain compounds of Formulas (II) and (IV) respectively with considerable advantage which can be employed in the enantioselective dihydroxylation with unforeseen success.
The compounds of Formula (V) and (VI) can furthermore be obtained when one reacts compounds of Formulas (VIII) and (IX) with the aromatic compound (X) in the presence of catalytic amounts of a palladium
±0
compound (see scheme 2) and subsequently removes the silyl protecting group with a fluoride containing agent. It is particularly preferred herein to charge tetrabutyl ammonium fluoride.
The charged palladium compound comprises advantageously of the elemental metal and a complexing ligand from the series of triphenylphosphine or triphenylphosphite. Particularly preferred is the compound [Pd(PPh
3
)
4
].
DESCRIPTION OF THE PREFERRED EMBODIMENTS
The compounds of Formulas (VIII) and (IX) can be obtained in different ways.
In a first preferred embodiment, the procedure is characterized thereby that the compound of Formula (VIII)
is obtained by reaction of a substance of Formula (XII)
with DHQ (II) or DHQD (III).
In a second preferred embodiment, the process of the present invention is characterized thereby that a compound of Formula (IX)
is obtained by reaction of a substance of Formula (XIII)
with a DHQ (II) or DHQD (III).
The substances of Formulas (XIII) and (XII) can be prepared in a manner analogous to the procedures known in the literature (
J. Org. Chem
. 1993, 58, 3785), starting from 4-bromo benzonitrile or pyrazine-2,3-dicarboxylic acid in accordance with, for example,
J. Org. Chem
. 1995, 60, 3940.
The new ligand systems of Formulas (I) and (V) are furthermore the subject of the present invention.
The object of the present invention is also the use of the new ligand systems (I) and (IV) which advantageously permit, in the presence of oxidizing agents such as N-methylmorpholine-N-oxide, potassium hexacyanoferrate and/or potassium osmate in a solvent mixture to the dihydroxylation of a double bond in very high enantiomeric excess. A preferred use in accordance with this invention provides that the dihydroxylation is carried out in a solvent mixture containing one or more of the solvents of the group: water, alcohols such as methanol, ethanol, isopropanol, N-propanol, N-butanol, secondary butanol, tert.-butanol, isobutanol, N-pentanol; ethers such as diethylether, tetrahydrofuran, dimethoxy ethane, dioxane; ketones such as acetone, methyl isobutyl ketone, ethyl ketone (sic), diisopropyl ketone; or esters such as acetyl acetic esters or acetic esters, as well as halogenated alkanes such as methylene chloride, chloroform, and trichlorethylene. Preferred solvent mixtures are among others, water tert.butanol, or water acetone. It is particularly advantageous to provide the solvent mixture from at least two of the above-named solvents. Furthermore, the catalysts (I) and (IV) can be readily precipitated after the dihydroxylation by the addition of non-polar organic solvents to the reaction mixture. To the hereto preferred addable solvent materials, there may be counted for example, alkane, such as hexane, cyclohexane, methylcyclohexane; petroleum ethers or ether (sic). Preferred are MTBE, tetrahydrofuran or diethylether as well as DME; ketone, such as acetone, MIBK or ethylmethyl ketone, as well as diisopropyl ketone; esters such as acetic ester or acetyl acetic ester. The temperature of the dihydroxylation lies between −20° C. to +20° C., preferred at temperatures between −10° to +10° C., particularly preferred are temperatures from +2° to −2° C. The recycling occurs as shown in Scheme (III).
TABLE 2
R,R′,R″
Cat.
% ee*
% ee
+
Ph,H,Ph
(IV)
99%
99%
Ph,H,H
(IV)
98%
99%
Ph,Me,H
(IV)
95%
96%
C
8
H
17
,H,H
(I)
87%
89%
Me
3
C,H,H
(I)
90%
92%
*Present Invention
+
Sharpless
Table 2 shows the enantioselectivity obtained in the dihydroxylation of standard compounds in accordance with Example 1 in comparison to those obtainable in the catalyst system of Sharpless, et al. The ee values in accordance with the present invention lie minimally lower. After removal of the ligands from the reaction mixture by precipitation with non-polar solvents in over 80% yield, these can be introduced into a new dihydroxylation which is particularly advantageous and quite unexpected.
Table 3 shows the results obtained in a dihydroxylation of styrene, in a manner analogous to Example I in a 6 times sequential int
Bolm Carsten
Bommarius Andreas
Drauz Karlheinz
Gerlach Arne
Behr Omri M.
Degussa - AG
Liu Hong
Shah Mukund J.
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