Highly active metathesis catalysts selective for romp and rcm reactions

Abstract

The present invention relates to a kind of novel carbene ligands and ruthenium catalysts, which is highly active and selective for ROMP and RCM reactions, respectively. It discloses the significant electronic and steric effect of different substituted carbene ligands on the catalytic activity and stability of corresponding carbene ruthenium complexes; some of novel ruthenium complexes in the invention can be broadly used as catalysts highly effectively and selective for ROMP and RCM reactions. The invention also relates to preparation of new ruthenium catalysts and the uses in metathesis. Moreover, the invention also provides effective methods of making various functional polymers by ROMP reaction in the presence of new ruthenium catalysts.

1 - 20 . (canceled) 
     
     
         21 . A cycloolefin substrate having the following structure VIa-VIc; 
       
         
           
           
               
               
           
         
       
       wherein:
 r=1, 2, 3 or 4; s=1, 2, 3 or 4; 
 A is oxygen (O), sulfur (S), alkyl, alkoxy, aryloxy, alkylthio, alkoxycarbonyl, alkylamino, arylamino, alkylaminocarbonyl, arylaminocarbonyl, alkylamido, arylamido or heterocyclic amido group; 
 G is a group of compounds with specific properties and uses; each is optionally selected from commercial drugs or liquid crystal monomers; 
 R 10  and R 11  are each H, halogen, alkyl, alkoxy, alkylthio, alkylsilyoxy, aryloxy, aryl, heterocyclic, heterocyclic aryl, alkylcarbonyl, alkyloxycarbonyl, aryloxycarbonyl, alkylaminocarbonyl, arylaminocarbonyl, alkylamido, alkylsulfonyl, alkylsulfonamido, liquid crystal monomer or modified prodrug; 
 “Linker” is alkyl, alkoxy, alkylthio, alkylsilyoxy, aryloxy, aryl, alkoxycarbonyl, aryloxycarbonyl, alkylaminocarbonyl, arylaminocarbonyl, alkylamido, arylamido, alkylsulfonamido, arylsulfonamido, heteroaryl or heterocyclic group. 
 
     
     
         22 . The cycloolefin substrate according to  claim 21 , wherein A is oxygen (O), CH 2  or C 1 -C 5  alkylamino group. 
     
     
         23 . The cycloolefin substrate according to  claim 21 , wherein R 10  and R 11  each is H, C 1 -C 12  alkoxycarbonyl, C 6 -C 12  aryloxycarbonyl, C 1 -C 12  alkylaminocarbonyl, C 6 -C 12  arylaminocarbonyl, liquid crystal monomer or modified prodrug of Lipitor. 
     
     
         24 . The cycloolefin substrate according to  claim 21 , wherein “Linker” is C 1 -C 12  alkyl, C 1 -C 12  alkoxy, C 1 -C 12  alkoxycarbonyl, C 1 -C 12  alkylaminocarbonyl or C 1 -C 12  alkylamido group. 
     
     
         25 . The cycloolefin substrate according to  claim 21 , wherein G is a kind of optionally modified prodrug of commercial drug Lipitor having the following structure VIIa-VIId: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         wherein R 12  and R 13  each is cyclopropyl, C 1 -C 12  alkyl, C 3 -C 12  cycloalkyl, C 6 -C 12  aryl, C 1 -C 12  alkylamino, C 6 -C 12  arylamino, C 1 -C 12  alkylsulfonamido, C 6 -C 12  arylsulfonamido, C 3 -C 12  heteroaryl or C 2 -C 12  heterocyclic group. 
       
     
     
         26 . A functional polymer, comprising a modified prodrug or functional group G having the following structure VIIIa-VIIIc: 
       
         
           
           
               
               
           
         
       
       wherein:
 r=1, 2, 3 or 4; s=1, 2, 3 or 4; 
 A, G, “Linker”, R 10  and R 11  each is defined as in  claim 21 ; R 12  and R 13  each is defined as in  claim 25 . 
 
     
     
         27 . A process for preparing Ru complexes Va-Vb, wherein a compound of formula IV (e.g., 4-SM) forms a substituted benzylidene carbene in the presence of NaOEt when Z is TsNHN, followed by reacting with a reagent RuCl 2 (PPh 3 ) 3  directly to produce the Ru complex intermediate Va or Vb: 
       
         
           
           
               
               
           
         
         wherein: 
         p=0; L is P(Ph) 3 ; 
         m, n, E, E 1 , E 2 , E 3 , E 4 , E 5 , E 6 , E 7 , L, L 1 , L 2 , L 3 , R 1 , R 2 , X, Y, X 1  and Y 1  each is as defined in claim  1 . 
       
     
     
         28 . A process for preparing the Ru complexes Ia-Ib, wherein a compound of formula Va or Vb as defined in  claim 29  is reacted with another complex ligand IIa or IId (PCy 3 ) as defined in claim  8  to produce the Ru complex/catalyst Ia or Ib: 
       
         
           
           
               
               
           
         
       
       wherein:
 p=0; L is as defined in claim  9 ; 
 m, n, E, E 1 , E 2 , E 3 , E 4 , E 5 , E 6 , E 7 , L 1 , L 2 , R 1 , R 2 , X, Y, X 1  and Y 1  each is as defined in claim  1 . 
 
     
     
         29 . A method of making a prodrug-linked polymer VIIIa-VIIIc in the presence of one or two more mixed catalysts of claim  1  with a cycloolefin substrate VIa-VIc as defined in  claim 21 . 
     
     
         30 . A method of making a quality-modified polymer having the following structure IXa or IXb in the presence of one or two more mixed catalysts of claim  1  with a cycloolefin substrate cyclooctene or dicyclopentadiene as defined in  claim 22 . 
       
         
           
           
               
               
           
         
       
     
     
         31 . (canceled)