Methods for the synthesis of dicarba bridges in organic compounds

Abstract

The present invention related to methods for forming dicarba bridges in organic compounds. This involves the use of a pair of complementary metathesisable groups on the organic compound, and subjecting the compound to cross-metathesis under microwave radiation conditions. In an alternative, the compounds containing a turn-induced group between the pair of cross metathesisable groups to facilitate the cross-metathesis.

1 . A method for the synthesis of an organic compound with a dicarba bridge, comprising:
 providing a reactable organic compound having a pair of unblocked complementary metathesisable groups, or two or more reactable organic compounds having between them a pair of unblocked complementary metathesisable groups, and   subjecting the reactable organic compound or compounds to cross-metathesis using a cross-metathesis catalyst to form an organic compound with an unsaturated dicarba bridge,   
       wherein the reactable organic compound, or one of the reactable organic compounds, is attached to a solid support during the cross-metathesis of the complementary metathesisable groups and the cross-metathesis is performed in a solvent combination of a resin-swelling solvent with a co-ordinating solvent for the catalyst. 
     
     
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         5 . The method of  claim 1 , wherein the loading of the reactable organic compound on the solid support is at least 0.2 mmol/g. 
     
     
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         7 . The method of  claim 1 , wherein the co-ordinating solvent is an alcohol. 
     
     
         8 . The method of  claim 1 , wherein the co-ordinating solvent is used in an amount of about 1-30% by volume, with respect to the total solvent combination. 
     
     
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         37 . The method of  claim 1 , wherein the resin-swelling solvent is a polar solvent. 
     
     
         38 . The method of  claim 37 , wherein the polar solvent is dichloromethane. 
     
     
         39 . The method of  claim 1 , wherein the solid support is a polystyrene-based resin. 
     
     
         40 . The method of  claim 39 , wherein the polystyrene-based resin is a cross-linked polystyrene containing divinylbenzene functionalised with linkers to provide a reversible linkage between the reactable organic compound and the resin. 
     
     
         41 . The method of  claim 39 , wherein the polystyrene-based resin is selected from the group consisting of Wang resin, Rink amide resin, BHA-Gly-Gly-HMBA resin and 2-chlorotrityl chloride resin.