W ORLD INTELLECTU.1
`Intern
`PCT
`INTERNATIONAL APPLICATION PUBLISHED l
`
`W0
`
`9604289A1
`
`(51) International Patent Classification 6 :
`
`(11) International Publication Number:
`
`WO 96/04289
`
`C07F 15/00, C08F 4/80, 32/04, 32/08
`
`(43) International Publication Date:
`
`15 February 1996 (15.02.96)
`
`(21) International Application Number:
`
`PCT/US95/09655
`
`(22) International Filing Date:
`
`28 July 1995 (28.07.95)
`
`(30) Priority Data:
`08/282,826
`08/282,827
`
`29 July 1994 (29.07.94)
`29 July 1994 (29.07.94)
`
`US
`US
`
`(81) Designated States: AM, AT, AU, BB, BG, BR, BY, CA, CH,
`CN, CZ, DE, DK, EE, ES, FI, GB, GE, HU. IS, JP, KE,
`KG, KP, KR, KZ, LK, LR, LT, LU, LV, MD, MG, MN,
`MW, MX, NO, NZ, PL, PT, RO, RU, SD, SE, 80, SI, SK,
`TJ, TM, TT, UA, U0, U2, VN, European patent (AT, BE,
`CH, DE, DK, ES, FR, GB, GR, IE, IT, LU, MC, NL, PT,
`SE), OAPI patent (BF, BJ, CF, CG, CI, CM, GA, GN, ML,
`MR, NE, SN, TD, TG), ARIPO patent (KE, MW, SD, 82,
`UG).
`
`(71) Applicant: CALIFORNIA INSTITUTE OF TECHNOLOGY
`[US/US]; 1201 East California Boulevard, Pasadena, CA
`91125 (US).
`
`Published
`With international search report.
`
`(72) Inventors: GRUBBS, Robert, H.; 1700 Spruce Street, South
`Pasadena, CA 91030 (US).
`NGUYEN, SonBinh, T.;
`Mosher-Jorgensen House #103, Pasadena, CA 91125 (US).
`JOHNSON, Lynda, K.; Apartment A3, 601 Jones Ferry
`Road, Carrboro, NC 27510 (US). HILLMYER, Marc, A.;
`703 East California Boulevard #1, Pasadena, CA 91106
`(US).
`FU, Gregory, C.;
`100 Memorial Drive #218C,
`Cambridge, MA 02142 (US).
`
`(74) Agents: COLEMAN, James, Patricia et al.; Limbach 8:
`Limbach, 2001 Ferry Building, San Francisco, CA 94111-
`4262 (US).
`
`either isopropyl, isobutyl, sec-butyl, neopentyl, neophenyl, cyclopentyl or cyclohexyl.
`
`(54) Title: HIGH ACTIVITY RUIHENIUM OR OSMIUM METAL CARBENE COMPLEXES FOR OLEFIN METATHESIS REAC-
`TIONS AND SYNTHESIS THEREOF
`
`(57) Abstract
`
`Ruthenium and osmium carbene compounds
`which are stable in the presence of a variety of
`functional groups and which can be used to catalyze
`olefin metathesis reactions are discussed. Methods
`for synthesizing these carbene compounds are also
`disclosed. Specifically, the present invention relates
`to carbene compounds of formula (I) wherein: M
`is Os or Ru; R and R1 are independently selected from hydrogen; C2—C20 alkenyl, C2-C20 alkynyl, C1-Czo alkyl, aryl, C1-C20 carboxylate,
`C2-Czo alkoxy, C2-Czo alkenyloxy, C2-Czo alkynyloxy, aryloxy, C2-Czo alkoxycarbonyl, C1-Czo alkylthio, C1-C20 alkylsulfonyl or C1-Czo
`alkylsulfinyl; each optionally substituted with C1-C5 alkyl. halogen. C1-C5 alkoxy or with a phenyl group optionally substituted with halogen,
`C1-C5 alkyl or C1-C5 alkoxy; X and X1 are independently selected from any anionic ligand; and L and Ll are each triallcyl phosphine
`ligands where at least one of the alkyl groups on the phosphine is a secondary alkyl or a cycloalkyl. In a preferred embodiment, all of the
`alkyl groups of the trialkyl phosphine are either a secondary alkyl or a cycloalkyl. In a more preferred embodiment, the alkyl groups are
`
`(I)
`
`

`

`FOR THE PURPOSES OF INFORMATION ONLY
`
`Codes used to identify States party to the PCI‘ on the front pages of pamphlets publishing international
`applications under the PCI‘.
`
`Viet Nam
`
`United Kingdom
`Georgia
`Guinea
`Greece
`Hans-Iv
`Ireland
`Italy
`Japan
`Kenya
`Kyrgyatan
`Democratic People's Republic
`of Korea
`Republic of Korea
`Kazakhstan
`Liechtenstein
`Sri Lanka
`Luxembourg
`Latvia
`Monaco
`Republic of Moldova
`
`AT
`AU
`BB
`BE
`BF
`BG
`3.]
`BR
`BY
`CA
`CF
`CG
`CH
`CI
`CM
`CN
`CS
`CZ
`DE
`
`Austria
`Auau‘alia
`Barbados
`Belgium
`Burkina Faso
`Bulgaria
`Benin
`Brazil
`Belarus
`Canada
`Central African Republic
`Congo
`Switzerland
`COte d'Ivoire
`Cameroon
`China
`Czechoslovakia
`Czech Republic
`Germany
`
`Mauritania
`Malawi
`Niger
`Netherlands
`Norway
`New Zealand
`Poland
`Portugal
`Romania
`Russian Federation
`Sudan
`Sweden
`Slovenia
`Slovakia
`Senegal
`Chad
`Togo
`Tajikistan
`Trinidad and Tobago
`Ukraine
`United Statea of America
`Uzbekistan
`
`

`

`WO 96/04289
`
`PCT/US95/09655
`
`HIGH ACTIVITY RUTHENIUM OR OSMIUM METAL CARBENE
`COMPLEXES FOR OLEFIN METATHESIS REACTIONS
`AND SYNTHESIS THEREOF
`
`The US. Government has certain rights in this invention pursuant to Grant No. CHE-8922072
`awarded by the National Science Foundation.
`
`W
`
`IO
`
`15
`
`20
`
`W
`
`This invention relates to highly active and stable ruthenium or osmium metal carbene complex
`compounds, synthesis methods thereof and their use as catalysts in olefin metathesis reactions.
`
`During the past two decades, research efforts have enabled an in-depth understanding of the olefin
`metathesis reaction as catalyzed by early transition metal complexes.
`In contrast, the nature of the
`intermediates and the reaction mechanism for Group VIII transition metal catalysts has remained elusive.
`In particular, the oxidation states and ligation of the ruthenium and osmium metathesis intermediates are
`not known.
`
`Many ruthenium and osmium metal carbenes have been reported in the literature (for example, see
`Burrell, A.K., Clark, G.R., Rickard, C.E.F., Roper, W.R., Wright, A.H., J. Chem. Soc., Dalton Trans.,
`
`1991, Issue 1, pp. 609-614). However, the discrete ruthenium and osmium carbene complexes isolated to
`
`date do not exhibit metathesis activity to unstrained olefins.
`Academic Press: London, 1983).
`
`(Ivin, Olefin Metathesis pp. 34-36,
`
`SUMMARY OF THE INVENTION
`
`The present invention relates to ruthenium or osmium carbene compounds which are stable in the
`
`presence of a variety of functional groups and which can be used to catalyze olefin metathesis reactions
`on unstrained cyclic and acyclic olefins.
`
`Specifically, the present invention relates to carbene compounds of the formula
`
`1
`
`'
`X\| _ a
`x‘/T— \FI
`
`L1
`
`25
`
`wherein:
`
`M is Os or Ru;
`R and R1 are independently selected from hydrogen or a hydrocarbon selected from the group
`consisting of C2-C20 alkenyl, C2-C20 alkynyl, C1-C20 alkyl, aryl, C1-C20 carboxylate, C2-C20
`alkoxy, CZ'CZO alkenyloxy, C2-C20 alkynyloxy, aryloxy, C2-C20 alkoxycarbonyl, C1-C20
`alkylthio, CI'CZO alkylsulfonyl and C1-C20 alkylsulfinyl;
`X and X1 are independently selected from any anionic ligand; and
`L and L] are independently selected from any neutral electron donor, preferably phosphine,
`sulfonated phosphine, phosphite, phosphinite, phosphonite, arsine, stibine, ether, amine, amide,
`
`sulfoxide, carboxyl, nitrosyl, pyridine and thioether, most preferably trialkylphosphine ligands
`where at least one of the alkyl groups is a secondary alkyl or a cycloalkyl.
`
`In a preferred embodiment, the hydrocarbon is selected from the group consisting of C1-C5 alkyl,
`halogen, C1-C5 alkoxy and a phenyl group. The hydrocarbon also may be substituted with a C1-C5
`alkyl halogen, CI'CS alkoxy, or a phenyl group.
`In an alternative embodiment, the phenyl group is optionally substituted with halogen, Cl-C5 alkyl
`or C1-C5 alkoxy.
`
`30
`
`35
`
`40
`
`SUBSTITUTE SHEET (RULE 26)
`
`

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`WO 96104289
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`PCT/U895109655
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`In a preferred embodiment, all of the alkyl groups of the trialkyl phosphine are either a secondary
`
`In a more preferred embodiment, the alkyl groups are either isopropyl, isobutyl,
`alkyl or a cycloalkyl.
`sec-butyl, neopentyl, neophenyl, cyclopentyl or cyclohexyl.
`Carbene compounds where L and L1 ligands are alkyl phosphines where the carbon backbone of at
`least one alkyl group of the alkyl phosphine is a secondary alkyl or cycloalkyl have been found to
`
`possess higher metathesis activity, enabling these compounds to coordinate to and catalyze metathesis
`reactions between all types of olefins. By contrast, previous metathesis catalysts were only able to
`
`catalyze metathesis reactions involving highly strained olefins. As a result, a broad array of metathesis
`
`10
`
`reactions are enabled using the carbene compounds of the present invention that cannot be performed
`using less reactive catalysts.
`
`15
`
`20
`
`The present invention also relates to the synthesis of ruthenium or osmium carbene compounds
`which can be used to catalyze olefin metathesis reactions.
`
`Certain of the carbene compounds of the present invention are the only Ru and Cs carbene
`complexes known to date in which the metal is formally in the +2 oxidation state, have an electron count
`
`of 16, and are pentacoordinate. Unlike most metathesis catalysts presently known which are poisoned by
`functional groups, the carbene compounds of the present invention are stable in the presence of alcohol,
`
`thiol, ketone, aldehyde, ester, ether, amine, amide, nitro acid, carboxylic acid, disulfide, carbonate,
`
`carboalkoxy and halogen functional groups and may therefore be used in protic or aqueous solvent
`systems.
`
`In another embodiment of the present invention, the carbene compounds can be in the form
`wherein 2, 3 or 4 of the moieties X, X], L, and L] can be taken together to form a chelating
`multidentate ligand.
`In one aspect of this embodiment, X, L, and L1 can be taken together to form a
`cyclopentadienyl, indenyl, or fluorenyl moiety.
`
`25
`
`The ruthenium or osmium carbene compounds may be prepared by reacting a compound of the
`formula (XXIMLnLIm)p,
`in the presence of solvent, with a cyclopropene of the formula
`
`R2
`
`R3
`
`wherein:
`
`M, X, X1, L, and LI have the same meaning as
`indicated above;
`
`it and m are independently 0-4, provided n+m= 2, 3 or 4;
`
`30
`
`35
`
`40
`
`p is an integer equal to or greater than I; and
`R2 and R3 are independently selected from hydrogen or a hydrocarbon selected from the group
`consisting of CZ‘CIS alkyl, C2-C18 alkenyl, C2-C18 alkynyl, C2-C18 alkoxycarbonyl, aryl, C1-
`C18 carboxylate, C1-C18 alkenyloxy, C2-C18 alkynyloxy, C1-C18 alkoxy, aryloxy, C1-C1 8
`alkylthio, CI'CIS alkylsulfonyl or C1-C18 alkylsulfmyl;
`in a preferred embodiment the hydrocarbon is substituted with CI'CS alkyl, halogen, C1-C5
`alkoxy or with a phenyl group.
`
`In a preferred embodiment the phenyl group is substituted with halogen, C1-C5 alkyl or Cl’
`C5 alkoxy.
`
`In one embodiment of the process, X, L, and L1 are taken together to form a moiety
`selected from the group consisting of cyclopentadienyl, indenyl or fluorenyl, each optionally
`substituted with hydrogen; C2-C20 alkenyl, C2-C20 alkynyl, C1-C20 alkyl, aryl, C1-C20
`carboxylate, C1-C20 alkoxy, C2-C20 alkenyloxy, C2-C20 alkynyloxy, aryloxy, C2-C20
`-2-
`
`SUBSTITUTE SHEET (RULE 26)
`
`

`

`
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`WO 96/04289
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`PCTIU 895/09655
`
`alkoxycarbonyl, C1-C20 alkylthio, C1-C20 alkylsulfonyl, C1-C20 alkylsulfinyl; each optionally
`substituted with C1—C5 alkyl, halogen, C1-C5 alkoxy or with a phenyl group optionally substituted
`with halogen, C1-C5 alkyl or C1-C5 alkoxy.
`A further method of preparing the compounds of this invention comprises reacting
`compound of the formula (XXIMLnle)
`formula
`
`p in the presence of solvent with a phosphorane of the
`
`R‘\—/R
`“5 /
`\R.
`R6
`
`“I" P_C
`
`wherein:
`
`M, X, X‘, L, L'. n, m, p, R, and RI have the same meaning as indicated above; and
`R4, R5 and R6 are independently selected from aryl, Cl-C6 alkyl, C1-C6 alkoxy or phenoxy, each
`optionally substituted with halogen, C1-C3 alkyl, C1-C3 alkoxy, or with a phenyl group
`optionally substituted with halogen, C1-C5 alkyl or C1-C5 alkoxy.
`The present invention also pertains to a preferred method of preparing the aforementioned
`ruthenium and osmium compounds comprising reacting [(Ar) MX Xllz dimer complex with two
`equivalents of a phosphine ligand and a cyclopropene of the formula
`
`R2
`
`R3
`
`in a one step synthesis wherein:
`M, X and X1 have the same meaning as indicated above;
`Ar is an aromatic compound, preferably a di-, tri-, tetra- or hexa- substituted benzene, most
`preferably selected from benzene, toluene, xylene, cymene, tetramethylbenzene or
`hexamethylbenzene; and phosphine ligand is represented by the formula PR7R8R9 wherein
`R7, R8 and R9 are independently selected from substituted and unsubstituted C1-C10 alkyl,
`secondary alkyl, cycloalkyl and aryl.
`
`Another embodiment of the present invenLtion comprises preparing compounds of Formula ll
`
`5
`
`10
`
`15
`
`20
`
`L | M
`
`:
`
`lL
`
`‘
`
`Y\
`x/
`
`.3-
`
`SUBSTITUTE SHEET (RULE 25)
`
`and Formula 11]
`
`

`

`WO 96/04289
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`PCT/US95I09655
`
`from compound of Formula I
`
`1
`
`X\I\|»=c’R
`x
`|1
`R
`
`1/
`
`\
`
`L
`
`5
`
`comprising reacting said compound of Formula 1, in the presence of solvent, with compound of the
`formula MIY wherein:
`M, R, R1 X, X], L, and L1 have the same meaning as indicated above, and wherein:
`(l) M1 is Li, Na or K, and Y is Cl'clo alkoxide, arylalkoxide, amide or arylamide each
`optionally substituted with C1-Clo alkyl or halogen, diaryloxide; or
`(2) MI is Na or Ag, and Y is Cl04, PF6, BF4, SbF6, halogen. B(a.ryl)4, C1-Clo alkyl sulfonate
`or aryl sulfonate.
`
`Another embodiment of the present invention is a method of preparing compounds of structures of
`Formula IV
`
`10
`
`and Formula V
`
`from a compound of Formula I
`
`-4-
`
`SUBSTITUTE SHEET (RULE 26)
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`

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`WO 96/04289
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`PCT/US95/09655
`
`comprising reacting a compound of
`
`5
`
`10
`
`Formula I, in the presence of
`solvent, with L2 wherein:
`M, R, R1, X, and XI have the same meaning as indicated above; and
`L, L1, and L2 are independently selected from any neutral electron donor, preferably secondary
`alkyl or cycloalkyl phosphine ligands.
`
`The compounds of Formulae II, Ill, IV, and V are species of, i.e., fall within, the scope of
`compounds of Formula I.
`In other words, certain compounds of Formula I are used to form other
`compounds of Formula I by ligand exchange.
`In this case, X and X1 in Formula I are other than the Y
`in Formulae II and III that replaces X. Similarly, L and L] in Formula I are other than the L2 in
`Formulae IV and V.
`If any 2 or 3 of X, X', L, and L1 form a multidentate ligand of Formula I, only
`the remaining ligand moieties would be available for ligand replacement.
`The reference above to X, X], L, and L1 having the same meaning as indicated above refers to
`these moieties individually and taken together to form a multidentate ligand as described above.
`
`l5
`
`The present invention also relates to metathesis coupling of olefins catalyzed by the carbene
`compounds of the present invention. The high level metathesis activity of the ruthenium and osmium
`
`carbene compounds of the present invention enable these compounds to coordinate with and catalyze
`metathesis reactions between all types of olefins. By contrast, previous non-carbene ruthenium and
`
`osmium metathesis catalysts are only able to catalyze metathesis reactions involving highly strained
`
`20
`
`olefins. As a result, a broad array of metathesis reactions are enabled using the carbene compounds of
`the present invention that cannot be performed using less reactive catalysts.
`Examples of metathesis olefin coupling reactions enabled by the ruthenium and osmium carbene
`
`compounds of the present invention include, but are not limited to, ring-opening metathesis
`
`polymerization of strained and unstrained cyclic olefins, ring closing metathesis of acyclic dienes, cross
`
`25
`
`metathesis reactions involving at least one acyclic or unstrained cyclic olefin and depolymerization of
`olefinic polymers.
`
`The present invention relates to new highly active and stable ruthenium or osmium carbene
`
`compounds which can be used to catalyze olefin metathesis reactions.
`
`30
`
`Specifically, the present invention relates to carbene compounds of the formula
`
`DETAILED DESCRIPTION
`
`L
`x\ l _ R‘
`‘/M c\
`l
`L1
`
`R
`
`x
`
`wherein:
`
`M is Os or Ru;
`R and R1 are independently selected from hydrogen; C2-C20 alkenyl, C2-C20 alkynyl, Cl'CZO
`alkyl, aryl, C1-C20 carboxylate, C2-C20 alkoxy, C2-C20 alkenyloxy, C2-C20 alkynyloxy, aryloxy,
`C2-C20 alkoxycarbonyl, CI’CZO alkylthio, C1-C20 alkylsulfonyl or C1-C20 alkylsulfinyl; each
`
`35
`
`-5-
`
`SUBSTITUTE SHEET (RULE 26)
`
`

`

`WO 96104289
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`PCT/US95/09655
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`optionally substituted with C1-C5 alkyl, halogen, C1-C5 alkoxy or with a phenyl group optionally
`substituted with halogen, C1-C5 alkyl or C1-C5 alkoxy;
`X and X1 are independently selected from any anionic ligand; and
`L and L1 are independently selected from any neutral electron donor, preferably phosphine,
`sulfonated phosphine, phosphite, phosphinite, phosphonite, arsine, stibine, ether, amine, amide,
`
`sulfoxide, carboxyl, nitrosyl, pyridine and thioether, most preferably trialkylphosphine ligands
`where at least one of the alkyl groups is a secondary alkyl or a cycloalkyl.
`In a preferred embodiment, all of the alkyl groups of the trialkyl phosphine are either a secondary
`alkyl or a cycloalkyl.
`In a more preferred embodiment, the alkyl groups are either isopropyl, isobutyl,
`sec-butyl, neopentyl, neophenyl, cyclopentyl or cyclohexyl.
`
`The high level metathesis activity of the carbene compounds of the present invention is observed
`when L and L1 are alkyl phosphines where the carbon backbone of at least one alkyl group of the alkyl
`phosphine is a secondary alkyl or cycloalkyl. Substitution of the secondary alkyl and cycloalkyl with
`additional carbon moieties and/or other functional groups are intended to be included with the terms
`secondary alkyl and cycloalkyl.
`
`10
`
`15
`
`The ruthenium or osmium carbene complexes of the invention are useful for catalyzing olefin
`metathesis reactions. The propagating carbene moiety has been found to be stable and continues to
`
`polymerize additional aliquots of monomer for a period after the original amount of monomer has been
`
`20
`
`consumed. The propagating carbene moiety ha also been found to be stable in the presence of alcohol,
`thiol, ketone, aldehyde, ester. ether, amine, amide, nitro acid, carboxylic acid, disulfide, carbonate,
`
`carboalkoxy and halogen functional groups. Aspects of this invention include the metal carbene
`
`compounds, methods for their synthesis, as well as their use as catalysts in a wide variety of olefin
`metathesis reactions.
`
`25
`
`The intermediate compounds (X)(1MLnLl
`prepared by standard known methods.
`
`m)p are either available commercially or can be
`
`30
`
`35
`
`40
`
`The phosphorane and cyclopropene reactants used in the present invention may be prepared in
`
`accordance with the following respective references. Schmidbaur, H., et al., Phosphorus and Sulfur, Vol.
`
`18, pp. 167-170 (1983); Carter, F.L., Frampton, V.L., Chemical Reviews Vol. 64, No. 5 (1964), which
`are incorporated herein by reference.
`
`The present invention also relates to metathesis coupling of olefins catalyzed by the carbene
`
`compounds of the present invention. The high level metathesis activity of the ruthenium or osmium
`
`carbene compounds of the present invention cause these compounds to coordinate with and catalyze
`metathesis reactions between all types of olefins. By contrast, previous non-carbene ruthenium or
`
`osmium metathesis catalysts are only able to catalyze metathesis reactions involving strained olefins. As
`
`a result, a broad array of metathesis reactions are enabled using the carbene compounds of the present
`invention that cannot be performed using less reactive catalysts.
`
`Examples of reactions enabled by the ruthenium and osmium carbene compounds of the present
`invention include, but are not limited to, ring-opening metathesis polymerization of strained and
`
`unstrained cyclic olefins, ring closing metathesis of acyclic dienes, cross metathesis reactions involving at
`least one acyclic or unstrained cyclic olefin and depolymerization of olefinic polymers.
`The carbene compounds disclosed in the present invention, as well as those disclosed in US. Serial
`
`No. 863,606, filed April 3, 1992, are the only Ru and Os carbene complexes known to date in which the
`
`metal is formally in the +2 oxidation state (the carbene fragment is considered to be neutral), have an
`
`45
`
`electron count of 16, and are pentacoordinate. Unlike most metathesis catalysts presently known which
`are poisoned by functional groups, the carbene compounds of the present invention are stable in the
`
`presence of a wide variety of functional groups including alcohol, thiol, ketone, aldehyde, ester, ether,
`
`amine, amide, nitro acid, carboxylic acid, disulfide, carbonate, carboalkoxy acid, carboxylic acid,
`
`disulfide. carbonate. isocyanate, carbodiimide carboalkoxy and halogen functional groups. As a result of
`
`-6-
`
`SUBSTITUTE SHEET (RULE 26)
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`

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`WO 96/04289
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`PCT/US95/09655
`
`their stability in the presence of functional groups. these catalysts may be employed in protic and aqueous
`solvents as well as mixtures of protic, aqueous. and/or organic solvents.
`
`With regard to compounds of Formula I:
`
`alkenyl can include vinyl, 1-propenyl, 2-propenyl; 3-propenyl and the different butenyl, pentenyl
`
`and hexenyl isomers, 1.3-hexadienyl and 2,4,6-heptatrienyl, and cycloalkcnyl;
`
`alkenyloxy can include H2C=CHCH20. (CH3)2C=CHCH20, (CH3)CH=CHCH20,
`CH3CH=CHCH20, (CH3)CH=C(CH3)CH20 and CH2=CHCH2CH20;
`alkoxide can include methoxide. t-butoxide and phenoxide;
`
`10
`
`alkoxy can include methoxy, ethoxy, n-propyloxy, isopropyloxy and the different butoxy, pentoxy
`and hexyloxy isomers;
`
`cycloalkoxy can include cyclopentyloxy and cyclohexyloxy;
`
`15
`
`20
`
`alkoxyalkyl can include CH3OCH2, CH3OCH2CH2, CH3CH20CH2, CH3CH2CH2CH20CH2 and
`CH3CH20CH2CH2; and
`alkoxycarbonyl can include CH30C(=O); CH3CH20C(=O), CH3CH2CH20C(=O),
`(CH3)2CHOC(=O) and the different butoxy-, pentoxy- or hexyloxycarbonyl isomers;
`alkyl can include methyl, ethyl, n-propyl, i-propyl, or the several butyl, pentyl or hexyl isomers
`and primary, secondary and cycloalkyl isomers;
`
`alkylsulfinyl can include CH3SO, CH3CH2SO, CH3CH2CH2SO, (CH3)2CHSO and the different
`butylsulfinyl, pentylsulflnyl and hexylsulfinyl isomers;
`
`alkylsulfonyl can include CH3SOZ, CH3CH2802, CH3CH2CHZSOZ, (CH3)2CH802 and the
`different butylsulfonyl, pentylsulfonyl and hexylsulfonyl isomers;
`alkylthio can include, methylthio, ethylthio, and the several propylthio, butylthio, pentylthio and
`hexylthio isomers;
`
`25
`
`alkynyl can include ethynyl, l-propynyl, 3-propynyl and the several butynyl, pentynyl and hexynyl
`isomers, 2,7-octadiynyl and 2,5,8-decatriynyl;
`
`30
`
`35
`
`40
`
`45
`
`alkynyloxy can include HC=CCH20, CH3C=CCH20 and CH3C=CCH20CH20;
`amide can include HC(=O)N(CH3)2 and (CH3)C(=O)N(CH3)2;
`amine can include tricyclohexylamine, triisopropylamine and trineopentylamine;
`
`arsine can include triphenylarsine,tricyclohexylarsine and triisopropylarsine;
`
`aryl can include phenyl, p-tolyl and p-fluorophenyl;
`
`carboxylate can include CH3C02CH3CH2C02, C6H5C02, (C6H5)CH2COZ;
`cycloalkenyl can include cyclopentenyl and cyclohexenyl.
`
`cycloalkyl can include cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl;
`diketonates can include acetylacetonate and 2,4-hexanedionatc;
`
`ether can include (CH3)3CCH20CH2CH3, THF, (CH3)3COC(CH3)3, CH30CH2CH20CH3, and
`CH3OC6H5;
`'
`phosphine can include triphenylphosphine, tricyclohexylphosphine, triisopropylphosphine,
`trineopentylphosphine and methyldiphenylphosphine;
`
`phosphinite can include triphenylphosphinite, tricyclohexylphosphinite, triisopropylphosphinite, and
`
`methyldiphenylphosphinite;
`
`phosphite can include triphenylphosphite, tricyclohexylphosphite, tri-t—butylphosphite,
`
`triisopropylphosphite and methyldiphenylphosphite;
`secondary alkyl includes ligands of the general formula -CHRRl where R and R1 are carbon
`moieties;
`
`stibinc can include triphenylstibine, tricyclohexylstibine and trimethylstibine;
`sulfonate can include trifluoromethanesulfonate, tosylate, and mesylate;
`
`sulfoxide can include CH3S(=O)CH3, (C6H5)280; and
`thioether can include CH3SCH3, C6HSSCH3, CH3OCH2CHZSCH3, and tetrahydrothiophene.
`-7-
`
`SUBSTITUTE SHEET (RULE 26)
`
`

`

`WO 96/04289
`
`PCT/US95I09655
`
`A neutral electron donor is any ligand which, when removed from a metal center in its closed shell
`
`electron configuration, has a neutral charge, i.e.,
`
`is a Lewis base.
`
`"halogen" or "halide", either alone or in compound words such as "haloalkyl", denotes fluorine,
`chlorine, bromine or iodine.
`
`An anionic ligand is any ligand which when removed from a metal center in its closed shell
`
`electron configuration has a negative charge. An important feature of the carbene compounds of this
`invention is the presence of the ruthenium or osmium in the formal +2 oxidation state (the carbene
`
`fragment is considered to be neutral), an electron count of l6 and pentacoordination. A wide variety of
`ligand moieties X, Xi, L, and L1 can be present and the carbene compound will still exhibit its catalytic
`activity.
`
`A preferred embodiment of the carbene compounds of the present invention is a compound of the
`invention of Formula I wherein:
`
`R and R1 are independently selected from hydrogen, vinyl, C1-C10 alkyl, aryl, Cl-Clo
`carboxylate, CZ'CIO alkoxycarbonyl, C1-C10 alkoxy, aryloxy, each optionally substituted
`with C1-C5 alkyl, halogen, C1-C5 alkoxy or with a phenyl group optionally substituted with
`halogen, C1-C5 alkyl or C1-C5 alkoxy; and
`X and XI are independently selected from halogen, hydrogen, diketonates, or Cl'CZO alkyl, aryl,
`C1-C20 alkoxide, aryloxide, C2-C20 alkoxycarbonyl, arylcarboxylate, Cl'c20 carboxylate,
`aryl or C1-C20 alkylsulfonate, C1-C20 alkylthio, C1-C20 alkylsulfonyl, C1-C20
`alkylsulfinyl, each optionally substituted with CI'CS alkyl, halogen, C1-C5 alkoxy or with a
`phenyl group optionally substituted with halogen, C1-C5 alkyl or CI'CS alkoxy; and
`L and L1 are independently selected from phosphine, sulfonated phosphine, phosphite, phosphinite,
`phosphonite, arsine, stibine, ether, amine, amide, sulfoxide, carbonyl, nitrosyl, pyridine or
`thioether.
`
`7
`
`A more preferred embodiment of the carbene compounds of the present invention is a compound of
`Formula I wherein:
`
`R and R1 are independently selected from hydrogen; vinyl, C1-C5 alkyl, phenyl, C2-C5
`alkoxycarbonyl, CI'CS carboxylate, CI'CS alkoxy, phenoxy; each optionally
`substituted with CI'CS alkyl, halogen, C1-C5 alkoxy or a phenyl group optionally
`substituted with halogen, C1-C5 alkyl or C1-C5 alkoxy;
`X and X1 are independently selected from Cl, Br, I, or benzoate, acetylacetonate, C1-C5
`carboxylate, C1-C5 alkyl, phenoxy, C1-C5 alkoxy, C1-C5 alkylthio, aryl, and C1-C5
`alkyl sulfonate; each optionally substituted with C1-C5 alkyl or a phenyl group
`optionally substituted with halogen, CI'CS alkyl or C1-C5 alkoxy; and
`L and L1 are independently selected from aryl, C1-C5 alkyl, secondary alkyl or
`cycloalkylphosphine, aryl- or CFC") alkylsulfonated phosphine, aryl or C1-C10
`alkylphosphinite, aryl- or C1-C10 alkylphosphonite, aryl- or CFC") alkylphosphite,
`aryl— or C1-C10 alkylarsine, aryl- or CFC”) alkylamine, pyridine, aryl- or C1-C10
`alkyl sulfoxide, aryl- or C1-Clo alkylether, or aryl- or C1-Clo alkylamide, each
`optionally substituted with a phenyl group optionally substituted with halogen, Cl-C5
`alkyl or C1-C5 alkoxy.
`A further preferred embodiment of the present invention is carbene compounds of Formula I wherein:
`R and R1 are independently vinyl, H, Me, Ph;
`X and X1 are independently Cl, CF3C02, CH3C02, CFHZCOZ, (CH3)3CO,
`(CF3)2(CH3)CO, (CF3) (CH3)2CO, PhO, MeO, EtO, tosylate, mesylate, or
`trifluoromethanesulfonate; and
`L and L1 are independently PPh3, P(p-Tol)3, P(o-Tol)3, PPh(Cl-l3)2, P(CF3)3, P(p-
`FC6H4)3, pyridine, P(p-CF3C6H4)3, (p-F)pyridine, (p-CF3)pyridine, P(C6H4-
`-3-
`
`10
`
`15
`
`20
`
`25
`
`30
`
`35
`
`40
`
`45
`
`SUBSTITUTE SHEET (RULE 26)
`
`

`

`WO 96/04289
`
`PCT/US95/09655
`
`SO3Na)3, P(CH2C6H4-SO3Na)3, P(iPr)3, P(CHCH3(CH2CH3))3, P(cyclopentyl)3,
`P(cyclohexyl)3, P(neopentyl)3 and P(neophenyl)3.
`For any of the foregoing described preferred groups of compounds, any 2, 3, or 4 of X, X], L, L1
`can be taken together to form a chelating multidentate ligand. Examples of bidentate ligands include, but
`
`are not limited to, bisphosphines, dialkoxides, alkyldiketonates, and aryldiketonates. Specific examples
`
`include Ph2PCH2CH2PPh2, thAsCH2CH2AsPh2, thPCHZCH2C(CF3)20‘, binaphtholate dianions,
`pinacolate dianions, Me2P(CH2)2PMe2 and 0C(CH3)2(CH3)2CO. Tridentate ligands include, but are
`not limited to, (CH )ZNCHZCHZP(Ph)Cl-12CH2N(CH3)2. Other preferred tridentate ligands are those in
`which X, L, and L are taken together to be cyclopentadienyl, indenyl or fluorenyl, each optionally
`
`substituted with C2-C20 alkenyl, C2-C20 alkynyl, C1-C20 alkyl, aryl, C1-C20 carboxylate, C1-C20
`alkoxy, C2-C20 alkenyloxy, C2-C20 alkynyloxy, aryloxy, C2-C20 alkoxycarbonyl, C1-C20 alkylthio, Cl'
`C20 alkylsulfonyl, C1-C20 alkylsulfinyl, each optionally substituted with C1-C5 alkyl, halogen, C1-C5
`alkoxy or with a phenyl group optionally substituted with halogen, C1-C5 alkyl or C1—C5 alkoxy. More
`preferably in compounds of this type, X, L, and L1 are taken together to be cyclopentadienyl or indenyl,
`
`each optionally substituted with hydrogen; vinyl, Cl’clo alkyl, aryl, C1-C10 carboxylate, CZ'CIO
`alkoxycarbonyl, C1-Clo alkoxy, aryloxy, each optionally substituted with C1-C5 alkyl, halogen, C1-C5
`alkoxy or with a phenyl group optionally substituted with halogen, C1-C5 alkyl or C1-C5 alkoxy. Most
`preferably, X, L, and L1 are taken together to be cyclopentadienyl, optionally substituted with vinyl,
`hydrogen, Me or Ph. Tetradentate ligands include, but are not limited to
`
`02C(CH2)2P(Ph)(CH2)2P(Ph)(CH2)2C02, phthalocyanines, and porphyrins.
`Carbene compounds of Formula 1 wherein L and L1 are alkyl phosphines where at least one alkyl
`group is either a secondary alkyl or a cycloalkyl. These carbene compounds have been found to be more
`stable, more reactive to nonsterically strained cyclic alkenes and unreactive to a wider variety of
`
`(Nguyen, S., et al., J. Am. Chem. Soc., 1993, m:9858-9859; Fu, 0., et 31., J. Am. Chem.
`substituents.
`m 1993, £29856-9557.)
`Specifically, carbene compounds wherein L and 1..1 are triisopropyl phosphine or tricyclohexyl
`phosphine have been found to be stable in the presence of oxygen, moisture, adventitious impurities
`
`thereby enabling reactions to be conducted in reagent grade solvents in air (Fu, 6., et al., J. Am. Chem.
`
`IO
`
`15
`
`20
`
`25
`
`30
`
`&, 1993, m:9856-9857). Further these carbenes are stable in the presence of alcohol, thiol, ketone,
`aldehyde, ester, ether, amine, amide, nitro acid, carboxylic acid, disulfide, carbonate, carboalkoxy and
`
`In addition, these carbene can catalyze olefin metathesis reactions on acyclic
`halogen functional groups.
`oleinfs and strained cyclic olefins.
`
`The most preferred carbene compounds of the present invention include:
`
`PC H
`c1\|
`ya
`nu—
`Cl/l
`PCya
`
`H
`
`Ph
`
`Ph
`
`P'PraH
`Cl\|
`__
`/Ftu
`c:
`II
`PPr3
`
`H
`
`Ph
`
`Ph
`
`wherein
`
`35
`
`iPr = isopropyl
`Cy = cyclohexyl
`
`The compounds of the present invention can be prepared in several different ways, each of which
`is described below.
`
`-9-
`
`SUBSTITUTE SHEET (RULE 26)
`
`

`

`WO 96/04289
`
`PCT/US95/09655
`
`The most general method for preparing the compounds of this invention comprises reacting
`(XXIMLnle)p with a cyclopropene or phosphoranc in the presence of a solvent to produce a carbene
`complex, as shown in the equations below:
`REACTION E UATIONS
`
`(xx'ML,,I.‘,.,)P
`
`i
`
`(xx ML..L m),
`
`1
`
`+
`
`+
`
`Ra
`
`R3
`
`__
`
`L
`x\ I = x
`
`1R
`
`,1st C\ 1
`
`R6
`
`Fl
`
`_ = —_> M:
`
`x‘/|
`
`1
`
`L
`
`\R
`
`5
`
`wherein:
`
`M, x, x‘, L, L‘, n, m, p, R2, R3, R4, R5, and R6 are as defined above. Preferably, R2, R3, R4,
`R5, and R6 are independently selected from the group consisting of C1-C6 alkyl or phenyl.
`Examples of solvents that may be used in this reaction include organic, protic, or aqueous solvents
`which are inert under the reaction conditions, such as: aromatic hydrocarbons, chlorinated hydrocarbons,
`
`10
`
`ethers, aliphatic hydrocarbons, alcohols, water, or mixtures thereof. Preferred solvents include benzene,
`
`toluene, p-xylene, methylene chloride, dichloroethane, dichlorobenzene, chlorobenzene, tetrahydrofuran,
`diethylether, pentane, methanol, ethanol, water, or mixtures thereof. More preferably, the solvent is
`benzene, toluene, p-xylene, methylene chloride, dichloroethane, dichlorobenzene, chlorobenzene,
`
`tetrahydrofuran, diethylether, pentane, methanol, ethanol, or mixtures thereof. Most preferably, the
`solvent is toluene or a mixture of benzene and methylene chloride.
`
`15
`
`A suitable temperature range for the reaction is from about -20°C to about l25°C, preferably 35°C
`to 90°C, and more preferably 50°C to 65°C. Pressure is not critical but may depend on the boiling point
`of the solvent used, i.e., sufficient pressure is needed to maintain a solvent liquid phase. Reaction times
`
`are not critical, and can be from several minutes to 48 hours. The reactions are generally carried out in
`an inert atmosphere, most preferably nitrogen or argon.
`The reaction is usually carried out by dissolving the compound (XXIMLnle)p, in a suitable
`solvent, adding the cyclopropene (preferably in a solvent) to a stirred solution of the compound, and
`optionally heating the mixture until the reaction is complete. The progress of the reaction can be
`
`monitored by any of several standard analytical techniques, such as infrared or nuclear magnetic
`resonance.
`Isolation of the product can be accomplished by standard procedures, such as evaporating the
`solvent, washing the solids (e.g., with alcohol or pentane), and then recrystallizing the desired carbene
`complex. Whether the moieties X, X], L, or L1 are (unidentate) ligands or