Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2000-09-18
2004-05-04
Rotman, Alan L. (Department: 1625)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
active
06730788
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to ligands for metal catalysts. In particular, it relates to 1,10-phenanthroline ligands and to a process for preparing such ligands in chiral or achiral form.
1,10-Phenanthroline binds with almost all metals to form metal complexes and has been the subject of extensive efforts to prepare substituted derivatives for use as metal catalyst ligands especially in chiral form for use in asymmetric metal catalyzed processes. However, the development of such ligands has been hampered in part by the limited number of methods available for the preparation of derivatives suitable as ligands.
SUMMARY OF THE INVENTION
The process of this invention comprises coupling a ketone with a 1,10-phenanthroline and a metal coupling reagent to provide a 2-[(1-hydroxy-substituted-alkyl)]-1,10-phenanthroline represented by the following Formula
wherein
R is hydrogen, alkyl, alkyl substituted by one or two cycloalkyl or cycloalkenyl groups, cycloalkyl, cycloalkenyl, aryl, heterocyclic, bicycloalkyl or bicycloalkenyl;
R
1
and R
2
when taken separately, independently are alkyl, alkyl substituted by one or two cycloalkyl or cycloalkenyl groups, cycloalkyl, cycloalkenyl, bicycloalkyl or bicycloalkenyl, and when taken together with the carbon to which they are bonded are cycloalkyl, cycloalkenyl, bicycloalkyl or bicycloalkenyl; and wherein said R, R
1
and R
2
alkyl, cycloalkyl, cycloalkenyl, bicycloalkyl and bicycloalkenyl groups optionally bear substituents such as hydroxy, sulfhydryl, lower alkoxy, carboxy, phosphono, amino and like coordinating groups.
The term, “1-hydroxy-substituted-alkyl”, refers to the 1-hydroxy group attached to the carbon bearing the R
1
and R
2
radicals as defined above and whether they are taken together or separately.
According to the process a 1,10-phenanthroline represented by the Formula 2
wherein R has the same meanings as defined for Formula 1 is mixed in an inert moderately polar solvent at a temperature between about 0° C. and about 75° C. with the ketone R
1
C(O)R
2
wherein R
1
and R
2
have the above defined meanings, and a metal reagent to provide the compound represented by the Formula 1.
The products of the process represented by Formula 1 can be converted to a variety of other ligands by forming derivatives such as ethers and esters of the 1-hydroxy-substituted-alkyl substituent. The ligands obtained can form complexes with transition metals and the complexes can serve as catalysts in many processes, for example, in substitution and addition reactions and in the polymerization of monomers. In particular, the ligands provided by the process of the invention can be obtained in chiral form or converted to a chiral derivative for use in preparing chiral metal complexes. Such chiral complexes are useful in processes for the preparation of products in desired asymmetric forms.
In a further aspect the invention provides a 1,10-phenanthroline ligand represented by the following structural Formula 3.
wherein R, R
1
, and R
2
have the same meanings as defined herein above and R
3
is hydrogen, hydroxy, or a derivative of hydroxy such as an ether, ester, or a sulfhydryl, thioether, amino or amide group.
DETAILED DESCRIPTION
The coupling of a ketone with 1,10-phenanthroline according to the process of this invention can be regarded as a pinacol-like reaction. Although without being bound to any particular reaction mechanism, it appears that the process proceeds initially via a bimolecular reduction of the ketone mediated by a metal coupling reagent. It is also possible that a free radical mechanism may be involved.
Metal coupling reagents include, for example, magnesium, titanium, vanadium, manganese, copper, nickel, zinc, tin, lanthanides, and actinides and amalgams such as manganese and zinc amalgams. A preferred metal reagent for use in the process is a lanthanide II such as samarium. Samarium diiodide, diacetate or the triflate are useful coupling agents.
Solvents useful in the process are inert, moderately polar solvents which do not react with the metal reagent or the ketone employed. Such solvents include the ethers, for example, dialkyl ethers such as diethyl ether, methyl ethyl ether and the like, cyclic ethers such as tetrahydrofuran, dioxane, tetrahydropyran and the like, and diethers such as 1,2-dimethoxyethane and like ethers; esters such as methyl or ethyl acetate; and amides such as dimethylacetamide or phosphoramides. The choice of solvent will mainly be determined by the ease with which the product can be isolated from the reaction product mixture. Preferably the more volatile solvents are used.
The process can be carried out at a temperature between about 0° C. and about 75° C. and in many cases proceeds readily at or about 25° C. The rate at which the process proceeds varies with reagents and reactants and in general is complete in between about 4 and about 12 hours. The course of the reaction can be followed conveniently by thin layer chromatography. The ketone and metal reagent are used in amounts corresponding up to about 2.5 equivalent of the amount of 1,10-phenanthroline used. The reverse order of addition may be used and the reaction mixture is agitated during the process by stirring, shaking, or sonication.
The starting material, represented by the Formula 2, is obtained by known methods. For example, R substituents can be prepared by alkylation of the 1,10-phenanthroline with an alkyl, cycloalkyl or bicycloalkyl lithium compound. Many R alkyl, substituted alkyl, cycloalkyl and bicycloalkyl substituents also can be obtained, as described hereinafter, by first preparing a 1-hydroxy-substituted coupling product (Formula 1 wherein R is hydrogen) by the process of the invention and then forming a reducible derivative of the 1-hydroxy group. The derivative is subjected to reducing conditions to effect replacement of the reducible group with a hydrogen atom.
The group R (Formula 2) can be hydrogen or a straight or branched chained hydrocarbon group having from 1 to 12 carbon atoms, a cycloalkyl or cycloalkenyl group having from 4 to 10 ring carbon atoms, a mono- or dicycloalkyl substituted alkyl, a mono- or dicycloalkenyl substituted alkyl group wherein said cycloalkyl and cycloalkenyl have from 4 to 10 ring carbon atoms, an aryl or heterocyclic group, or a bicycloalkyl or bicycloalkenyl group having from 6 to 12 carbon atoms in the bicyclo ring. Examples of such R groups include methyl, ethyl, pentyl, iso-pentyl, iso-propyl, n-heptyl, cyclohexyl, cyclopentyl, cyclooctyl, cyclohexenyl, cyclopentenyl, cycloheptenyl, 4-cyclohexylbut-2-yl, 1-cyclohexenylethyl, or 1,3-dicyclopentylprop-2-yl; a dicycloalkylmethyl such as dicyclohexylmethyl, dicycloheptylmethyl, 1,3-dicyclopentylpropyl cyclohexylcyclohexenylmethyl, or cyclopentylcyclohexenylmethyl, an aryl or heterocyclic group such as phenyl, naphthyl or pyridyl, or a bicycloalkyl or bicycloalkenyl group which can be substituted by one or more alkyl groups, for example, a bicyclohexyl or bicycloheptyl group such as the 1-isopropyl-4-methylbicyclo[3.1.0]hex-3-yl group, the 1,7,7-trimethylbicyclo[2.2.1]hept-2-yl group, the 1,7,7-trimethylbicyclo[2.2.1]hept-2-ene-2-yl group and the 6,6-dimethylbicyclo[3.1.1]hept-2-ene-2-yl group. The R groups can be substituted with coordinating groups such as the hydroxy, sulfhydryl, amino, acyl, acetal and carboxy groups.
The ketone employed in the process is represented by the formula R
1
C(O)R
2
wherein R
1
and R
1
and R
2
when taken separately are independently a straight or branched hydrocarbon radical having from 1 to 12 carbon atoms, a mono- or dicycloalkyl or a mono- or dicycloalkenyl-substituted alkyl group, a cycloalkyl or cycloalkenyl group, a bicycloalkyl or bicycloalkenyl group wherein said cycloalkyl and cycloalkenyl groups have from 4 to 10 carbon atoms and wherein said bicycloalkyl and bicycloalkenyl groups have from 6 to 12 carbon atoms. Examples or ketones which can be used in the process include acetone, methyl ethyl ketone, ethyl 2-carboxyethyl ketone
Jagtiani + Guttag
Robinson Binta
University of Notre Dame
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