Cross-metathesis reaction of functionalized and substituted olefins using group 8 transition metal carbene complexes as metathesis catalysts

Abstract

The invention pertains to the use of Group 8 transition metal carbene complexes as catalysts for olefin cross-metathesis reactions. In particular, ruthenium and osmium alkylidene complexes substituted with an N-heterocyclic carbene ligand are used to catalyze cross-metathesis reactions to provide a variety of substituted and functionalized olefins, including phosphonate-substituted olefins, directly halogenated olefins, 1,1,2-trisubstituted olefins, and quaternary allylic olefins. The invention further provides a method for creating functional diversity using the aforementioned complexes to catalyze cross-metathesis reactions of a first olefinic reactant, which may or may not be substituted with a functional group, with each of a plurality of different olefinic reactants, which may or may not be substituted with functional groups, to give a plurality of structurally distinct olefinic products. The methodology of the invention is also useful in facilitating the stereoselective synthesis of 1,2-disubstituted olefins in the cis configuration.

1 . A method for synthesizing a plurality of structurally diverse functionalized olefins from a common olefinic reactant via a cross-metathesis reaction, comprising: 
 (a) contacting an olefinic substrate with a first olefinic reactant in the presence of a catalyst composed of a Group 8 transition metal alkylidene complex containing an N-heterocyclic carbene ligand, under conditions and for a time period effective to allow cross-metathesis to occur, wherein the olefinic substrate is substituted with at least one -(Z) n -Fn moiety in which n is zero or 1, Z is a hydrocarbylene or a substituted and/or heteroatom-containing hydrocarbylene linking group, and Fn is selected from phosphonato, phosphoryl, phosphanyl, phosphino, sulfonato, C 1 -C 20  alkylsulfanyl, C 5 -C 20  arylsulfanyl, C 1 -C 20  alkylsulfonyl, C 5 -C 20  arylsulfonyl, C 1 -C 20  alkylsulfinyl, C 5 -C 20  arylsulfinyl, sulfonamido, amino, amido, imino, nitro, nitroso, hydroxyl, C 1 -C 20  alkoxy, C 5 -C 20  aryloxy, C 2 -C 20  alkoxycarbonyl, C 5 -C 20  aryloxycarbonyl, carboxyl, carboxylato, mercapto, formyl, C 1 -C 20  thioester, cyano, cyanato, carbamoyl, epoxy, styrenyl, silyl, silyloxy, silanyl, siloxazanyl, boronato, boryl, stannyl, and germyl;    (b) in a separate reaction, contacting the first olefinic reactant with a second olefinic reactant having a molecular structure that is different from that of the first olefinic reactant, in the presence of the Group 8 transition metal alkylidene complex, under conditions and for a time period effective to allow cross-metathesis to occur; and    (c) optionally repeating step (b) with a plurality of olefinic reactants each having a different molecular structure.    
     
     
         2 . The method of  claim 1 , wherein the second olefinic reactant is also substituted with at least one -(Z) n -Fn moiety.  
     
     
         3 . A method for synthesizing a directly halogenated olefin via an olefin metathesis reaction, comprising: 
 contacting a directly halogenated olefinic reactant with a second olefinic species in the presence of a catalyst composed of a Group 8 transition metal alkylidene complex, under conditions and for a time period effective to allow metathesis to occur.    
     
     
         4 . The method of  claim 3 , wherein the olefin cross metathesis reaction is a cross metathesis reaction.  
     
     
         5 . The method of  claim 4 , wherein the catalyst has the structure of formula (VIA)  
       
         
           
           
               
               
           
         
       
       wherein: 
 M is a Group 8 transition metal;  
 X 1  and X 2  may be the same or different, and are anionic ligands or polymers;  
 R 1  is selected from the group consisting of hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, substituted heteroatom-containing hydrocarbyl, and carboxyl;  
 R 2  is selected from the group consisting of hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, and substituted heteroatom-containing hydrocarbyl;  
 L is a neutral electron donor ligand;  
 X and Y are heteroatoms selected from N, O, S, and P;  
 p is zero when X is O or S, and is 1 when X is N or P;  
 q is zero when Y is O or S, and is 1 when Y is N or P;  
 Q 1 , Q 2 , Q 3 , and Q 4  are selected from hydrocarbylene, substituted hydrocarbylene, heteroatom-containing hydrocarbylene, substituted heteroatom-containing hydrocarbylene, and —(CO)—;  
 w, x, y and z are independently zero or 1; and  
 R 3 , R 3A , R 4 , and R 4A  are independently selected from the group consisting of hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, and substituted heteroatom-containing hydrocarbyl,  
 wherein any two or more of X 1 , X 2 , L, R 1 , R 2 , R 3 , R 3A , R 4 , and R 4A  can be taken together to form a chelating multidentate ligand.  
 
     
     
         6 . The method of  claim 5 , wherein: 
 X 1  and X 2  are anionic ligands, and are optionally linked to form a cyclic group;    L is a neutral electron donor ligand that is optionally linked to R 2 , X 1 , and/or X 2  through a spacer moiety; and    R 3A  and R 4A  are optionally linked to form a cyclic group.    
     
     
         7 . The method of  claim 6 , wherein w, x, y and z are zero, X and Y are N, and R 3A  and R 4A  are linked to form -Q-, such that the catalyst has the structure of formula (VIB)  
       
         
           
           
               
               
           
         
       
       wherein Q is a hydrocarbylene, substituted hydrocarbylene, heteroatom-containing hydrocarbylene, or substituted heteroatom-containing hydrocarbylene linker, and further wherein two or more substituents on adjacent atoms within Q may be linked to form an additional cyclic group.  
     
     
         8 . The method of  claim 7 , wherein Q has the structure —CR 22 R 22A —CR 23 R 23A — or —CR 22 ═CR 23 —, wherein R 22 , R 22A , R 23 , and R 23A  are independently selected from the group consisting of hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, substituted heteroatom-containing hydrocarbyl, and functional groups, and or wherein any two of R 22 , R 22A , R 23 , and R 23A  may be linked together to form a substituted or unsubstituted, saturated or unsaturated ring.  
     
     
         9 . The method of  claim 8 , wherein Q has the structure —CR 22 R 22A —CR 23 R 23A —, such that the catalyst has the structure of formula (VIC)  
       
         
           
           
               
               
           
         
       
     
     
         10 . The method of  claim 9 , wherein: 
 M is Ru;    X 1  and X 2  may be the same or different, and are selected from the group consisting of hydrogen, halide, C 1 -C 20  alkyl, C 5 -C 20  aryl, C 1 -C 20  alkoxy, C 5 -C 20  aryloxy, C 3 -C 20  alkyldiketonate, C 5 -C 20  aryldiketonate, C 2 -C 20  alkoxycarbonyl, C 5 -C 20  aryloxycarbonyl, C 2 -C 20  acyl, C 1 -C 20  alkylsulfonato, C 5 -C 20  arylsulfonato, C 1 -C 20  alkylsulfanyl, C 5 -C 20  arylsulfanyl, C 1 -C 20  alkylsulfinyl, or C 5 -C 20  arylsulfinyl, any of which, with the exception of halide, are optionally further substituted with one or more groups selected from halide, C 1 -C 6  alkyl, C 1 -C 6  alkoxy, and phenyl;    R 1  is hydrogen and R 2  is selected from the group consisting of C 1 -C 20  alkyl, C 2 -C 20  alkenyl, and aryl;    L is a neutral electron donor ligand selected from the group consisting of phosphine, sulfonated phosphine, phosphite, phosphinite, phosphonite, arsine, stibine, ether, amine, amide, imine, sulfoxide, carboxyl, nitrosyl, pyridine, substituted pyridine, imidazole, substituted imidazole, pyrazine, and thioether;    R 3  and R 4  are aromatic, substituted aromatic, heteroaromatic, substituted heteroaromatic, alicyclic, substituted alicyclic, heteroatom-containing alicyclic, or substituted heteroatom-containing alicyclic, composed of from one to about five rings; and    R 8  and R 9  are hydrogen, and R 8A  and R 9A  are selected from hydrogen, lower alkyl and phenyl, or are linked to form a cyclic group.    
     
     
         11 . The method of  claim 10 , wherein: 
 R 1  is hydrogen, and R 2  is phenyl, vinyl, methyl, isopropyl, or t-butyl, optionally substituted with one or more moieties selected from the group consisting of C 1 -C 6 alkyl, C 1 -C 6 alkoxy, phenyl, and a functional group Fn, wherein Fn is phosphonato, phosphoryl, phosphanyl, phosphino, sulfonato, C 1 -C 20  alkylsulfanyl, C 5 -C 20  arylsulfanyl, C 1 -C 20  alkylsulfonyl, C 5 -C 20  arylsulfonyl, C 1 -C 20  alkylsulfinyl, C 5 -C 20  arylsulfinyl, sulfonamido, amino, amido, imino, nitro, nitroso, hydroxyl, C 1 -C 20  alkoxy, C 5 -C 20  aryloxy, C 2 -C 20  alkoxycarbonyl, C 5 -C 20  aryloxycarbonyl, carboxyl, carboxylato, mercapto, formyl, C 1 -C 20  thioester, cyano, cyanato, carbamoyl, epoxy, styrenyl, silyl, silyloxy, silanyl, siloxazanyl, boronato, boryl, halogen, stannyl, or germyl; and    L is a phosphine of the formula L is a phosphine of the formula PR 27 R 28 R 29 , where R 27 , R 28 , and R 29  are each independently aryl or C 1 -C 10  alkyl.    
     
     
         12 . The method of  claim 11 , wherein: 
 X 1  and X 2  are independently selected from the group consisting of halide, CF 3 CO 2 , CH 3 CO 2 , CFH 2 CO 2 , (CH 3 ) 3 CO, (CF 3 ) 2 (CH 3 )CO, (CF 3 )(CH 3 ) 2 CO, PhO, MeO, EtO, tosylate, mesylate, and trifluoromethanesulfonate;    L is selected from the group consisting of —P(cyclohexyl) 3 , —P(cyclopentyl) 3 , —P(isopropyl) 3 , —P(phenyl) 3 , P(phenyl) 3 , —P(phenyl) 2 (R 7 ) and —P(phenyl)(R 7 ) 2 , in which R 7  is tower alkyl; and    R 3  and R 4  are the same and are either aromatic or C 7 -C 12  alicyclic, if aromatic, each having the structure of formula (XI)                          in which R 24 , R 25 , and R 26  are each independently hydrogen, C 1 -C 10  alkyl, C 1 -C 10  alkoxy, aryl, substituted aryl, halogen, or a functional group.    
     
     
         13 . The method of  claim 12 , wherein: 
 X 1  and X 2  are halide;    R 2  is hydrogen or 2,2-dimethylvinyl;    R 3  and R 4  are mesityl;    L is selected from the group consisting of —P(cyclohexyl) 3  and —P(cyclopentyl) 3 ; and    R 22  and R 23  are hydrogen.    
     
     
         14 . The method of  claim 4 , wherein the directly halogenated olefinic reactant has the structure of formula (IX)  
       
         
           
           
               
               
           
         
       
       wherein X 3  is halo, and R 8 , R 9 , and R 10  are independently selected from the group consisting of hydrogen, halide, hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, substituted heteroatom-containing hydrocarbyl, -(Z) n -Fn where n is zero or 1, Z is a hydrocarbylene or a substituted and/or heteroatom-containing hydrocarbylene linking group, and Fn is a functional group selected from the group consisting of phosphonato, phosphoryl, phosphanyl, phosphino, sulfonato, C 1 -C 20  alkylsulfanyl, C 5 -C 20  arylsulfanyl, C 1 -C 20  alkylsulfonyl, C 5 -C 20  arylsulfonyl, C 1 -C 20  alkylsulfinyl, C 5 -C 20  arylsulfinyl, sulfonamido, amino, amido, imino, nitro, nitroso, hydroxyl, C 1 -C 20  alkoxy, C 5 -C 20  aryloxy, C 2 -C 20  alkoxycarbonyl, C 5 -C 20  aryloxycarbonyl, carboxyl, carboxylato, mercapto, formyl, C 1 -C 20  thioester, cyano, cyanato, carbamoyl, epoxy, styrenyl, silyl, silyloxy, silanyl, siloxazanyl, boronato, boryl, stannyl, and germyl.  
     
     
         15 . The method of  claim 14 , wherein at least one of R 8 , R 9 , and R 10  is a halogen atom.  
     
     
         16 . The method of  claim 15 , where X 3  and at least one of R 8 , R 9 , and R 10  is chloro or fluoro.  
     
     
         17 . The method of  claim 14 , where X 3  is chloro or fluoro, R 8  and R 9  are hydrogen or lower alkyl, and R 10  is hydrogen, lower alkyl, chloro, or fluoro.  
     
     
         18 . The method of  claim 14 , wherein the second olefinic reactant has the molecular structure R 18 R 19 C═CR 20 R 21  wherein R 18 , R 19 , R 20 , and R 21  are independently selected from the group consisting of hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, and substituted heteroatom-containing hydrocarbyl.  
     
     
         19 . A method for synthesizing a substituted olefin via a cross-metathesis reaction, comprising: 
 contacting a substituted olefin selected from the group consisting of geminal disubstituted olefins and quaternary allylic olefins with an olefinic reactant in the presence of a catalyst composed of a Group 8 transition metal alkylidene complex containing an N-heterocyclic carbene ligand, under conditions and for a time period effective to allow cross-metathesis to occur.    
     
     
         20 . The method of  claim 19 , wherein the catalyst has the structure of formula (VIA)  
       
         
           
           
               
               
           
         
       
       wherein: 
 wherein:  
 M is a Group 8 transition metal;  
 X 1  and X 2  may be the same or different, and are anionic ligands or polymers;  
 R 1  is selected from the group consisting of hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, substituted heteroatom-containing hydrocarbyl, and carboxyl;  
 R 2  is selected from the group consisting of hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, and substituted heteroatom-containing hydrocarbyl;  
 L is a neutral electron donor ligand;  
 X and Y are heteroatoms selected from N, O, S, and P;  
 p is zero when X is O or S, and is 1 when X is N or P;  
 q is zero when Y is O or S, and is 1 when Y is N or P;  
 Q 1 , Q 2 , Q 3 , and Q 4  are selected from hydrocarbylene, substituted hydrocarbylene, heteroatom-containing hydrocarbylene, substituted heteroatom-containing hydrocarbylene, and —(CO)—;  
 w, x, y and z are independently zero or 1; and  
 R 3 , R 3A , R 4 , and R 4A  are independently selected from the group consisting of hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, and substituted heteroatom-containing hydrocarbyl,  
 wherein any two or more of X 1 , X 2 , L, R 1 , R 2 , R 3 , R 3A , R 4 , and R 4A  can be taken together to form a chelating multidentate ligand.