One-pot synthesis of group 8 transition metal carbene...

Details One-pot synthesis of group 8 transition metal carbene... One-pot synthesis of group 8 transition metal carbene...

2002-04-02

2003-09-02

Nazario-Gonzalez, Porfirio (Department: 1621)

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

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

C556S021000, C556S023000, C556S136000, C502S152000, C548S300100

Reexamination Certificate

active

06613910

ABSTRACT:

TECHNICAL FIELD
This invention relates generally to a method for synthesizing Group 8 transition metal carbene complexes useful as olefin metathesis catalysts, and more particularly relates to a novel one-pot synthesis of mixed ligand transition metal carbene catalysts that contain a heteroatom-stabilized carbene ligand, e.g., an imidazolylidene ligand. The invention also pertains to a method for synthesizing a precursor to heteroatom-stabilized carbene ligands, particularly 1,3-disubstituted-2-trichloromethyl-5-dihydroimidazolidene.
BACKGROUND OF THE INVENTION
To the synthetic organic or polymer chemist, simple methods for forming carbon-carbon bonds are extremely important and valuable tools. One method of C—C bond formation that has proved particularly useful is transition-metal catalyzed olefin metathesis. “Olefin metathesis,” as is understood in the art, refers to the metal-catalyzed redistribution of carbon-carbon bonds. See Trnka and Grubbs (2001)
Acc. Chem. Res.
34:18-29. Over two decades of intensive research effort has culminated in the discovery of well-defined ruthenium and osmium carbenes that are highly active olefin metathesis catalysts and stable in the presence of a variety of functional groups.
These ruthenium and osmium carbene complexes have been described in U.S. Pat. Nos. 5,312,940, 5,342,909, 5,831,108, 5,969,170, 6,111,121, and 6,211,391 to Grubbs et al., assigned to the California Institute of Technology. The ruthenium and osmium carbene complexes disclosed in these patents all possess metal centers that are formally in the +2 oxidation state, have an electron count of 16, and are penta-coordinated. These catalysts are of the general formula (I):
where M is a Group 8 transition metal such as ruthenium or osmium, X and X′ are anionic ligands, L and L′ are neutral electron donors, and R and R′ are specific substituents, e.g., one may be H and the other may be a substituted or unsubstituted hydrocarbyl group such as phenyl or C═C(CH
3
)
2
. Such complexes have been disclosed as useful in catalyzing a variety of olefin metathesis reactions, including ring opening metathesis polymerization (“ROMP”), ring closing metathesis (“RCM”), acyclic diene metathesis polymerization (“ADMET”), ring-opening metathesis (“ROM”), and cross-metathesis (“CM” or “XMET”) reactions.
For the most part, such metathesis catalysts have been prepared with phosphine ligands, e.g., triphenylphosphine or dimethylphenylphospine, exemplified by the well-defined, metathesis-active ruthenium alkylidene complexes (II) and (III):
wherein “Cy” is a cycloalkyl group such as cyclohexyl or cyclopentyl. See U.S. Pat. No. 5,917,071 to Grubbs et al. and Trnka and Grubbs, cited supra. These compounds are highly reactive catalysts useful for catalyzing a variety of olefin metathesis reactions, and are tolerant of many different functional groups. However, as has been recognized by those in the field, the compounds display low thermal stability, decomposing at relatively low temperatures. Jafarpour and Nolan (2000)
Organometallics
19(11):2055-2057.
Recently, however, significant interest has focused on the use of N-heterocyclic carbene ligands as superior alternatives to phosphines. See, e.g., Trnka and Grubbs, supra; Bourissou et al. (2000)
Chem. Rev.
100:39-91; Scholl et al. (1999)
Tetraheron Lett.
40:2247-2250; Scholl et al. (1999)
Organic Lett.
1(6):953-956; and Huang et al. (1999)
J. Am. Chem. Soc.
121:2674-2678. N-heterocyclic carbene ligands offer many advantages, including readily tunable steric bulk, vastly increased electron donor character, and compatibility with a variety of metal species. In addition, replacement of one of the phosphine ligands in these complexes significantly improves thermal stability. The vast majority of research on these carbene ligands has focused on their generation and isolation, a feat finally accomplished by Arduengo and coworkers within the last ten years (see, e.g., Arduengo et al. (1999)
Acc. Chem. Res.
32:913-921). Representative of these second generation catalysts are the four ruthenium complexes (IVA), (IVB), (VA) and (VB):
In the above structures, Cy is as defined previously, “IMes” represents 1,3-dimesityl-imidazol-2-ylidene
and “IMesH
2
” represents 1,3-dimesityl-4,5-dihydroimidazol-2-ylidene
These transition metal carbene complexes, particularly those containing a ligand having the 4,5-dihydroimidazol-2-ylidene structure, such as in IMesH
2
, have been found to address a number of previously unsolved problems in olefin metathesis reactions, particularly cross-metathesis reactions. These problems span a variety of reactions and starting materials.
Previously, synthetic routes to such complexes have involved multiple steps and have required air- and moisture-sensitive carbene precursors as starting materials. Such methods are described, for example, by Scholl et al. (1999)
Tet. Lett.
40:2247-2250, Kingsbury et al. (1999)
J. Am. Chem. Soc.
121:791-799, and Huang et al. (1999), cited supra. There is, accordingly, a need in the art for a practical, convenient synthesis of catalysts such as (IVA), (IVB), (V), and (VB), possessing an N-heterocyclic carbene ligand, which provides the desired complexes in high yield using air- and moisture-stable precursors. It would also be desirable if such a synthesis were broadly applicable in the manufacture of other mixed ligand metal alkylidenes as well as related complexes, e.g., mixed ligand metal vinylidenes. The present invention is, in part, directed to such a synthesis.
The invention additionally addresses the problems those working in the field have encountered with synthesis of N-heterocyclic carbene reactants used to prepare catalysts such as (VA) and (VB). Early efforts sought to generate free N-heterocyclic carbenes from electron-rich olefins known as enetetraamines (Scheme 1, reaction (a)). Unfortunately, these olefins are typically only slightly more air- and light-stable than their constituent carbenes; they often undergo rapid oxidation in solution. Even when these olefins are oxidatively stable, their thermal cleavage remains debatable, thereby preventing these olefins from serving as protected carbenes. As an additional drawback, these olefins cleave only at extremely high temperatures that are often incompatible with sensitive metal species. The electron-rich nature of enetetramines also led to the investigation of their cleavage by reaction with electrophiles (Scheme 1(b)). Unfortunately, such reactions are generally unsuitable for use in organometallic synthesis, given the possibility of diverse problems. For example, many nucleophilic metal species will not tolerate strong electrophiles (such as CO
2
and SO
2
) that are required in the cleavage reactions. More importantly, the mechanisms of these electrophilic reactions remain poorly understood; the choice of optimal electrophile remains unclear. With these observations, the “electrophilic” route appears ill-suited for a general synthesis of N-heterocyclic carbene-coordinated metal species.
An improved method involves the formation of carbene “adducts” by thermal ejection of a leaving group, as illustrated in Scheme 1, reaction (c). In this scheme, the R groups will typically be aryl substituents (e.g., mesitylene) and an optimal “A” group is CCl
3
. Such a synthesis is described by Wanzlick et al. (1961)
Chemiche Berichte
94:2389-2393, and involves direct condensation of N,N′-diaryl-1,2-diamines with chloral (trichloroacetaldehyde), an impractical route since chloral is subject to distribution regulations, preventing its widespread availability.
An improved method for preparing N-heterocyclic carbene reactants useful, inter alia, in the synthesis of metal carbene complexes, would involve readily available reagents, straightforward reaction conditions (e.g., involving non-dry, non-degassed solvents), with generation of any toxic and/or reactive by-products minimized.
SUMMARY OF THE INVENTION
The present invention is addressed to the aforementioned needs in the art, and provides new synthe

Affiliated with

Also associated with

Rating

One-pot synthesis of group 8 transition metal carbene... does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with One-pot synthesis of group 8 transition metal carbene..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and One-pot synthesis of group 8 transition metal carbene... will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3029132