Synthesis of CC-1065/duocarmycin analogs

Abstract

The dihydroindole C-ring found in CC-1065/duocarmycin analogs is formed by the 5-exo-trig radical cyclization of an aryl halide onto a tethered vinyl chloride forming with chlorine installed as a suitable leaving group for subsequent cyclopropane spirocyclization. The versatility of this approach is disclosed in the context of six CC-1065/duocarmycin analogs previously synthesized in this laboratory.

What is claimed:  
     
         1 . A method for the synthesis of a dihydroindole C-ring of a CC-1065/duocarmycin analog wherein the method comprises the steps of: 
 Step A: alkylating an aryl halide with 1,3-dichloropropene and a catalytic amount of n-tetrabutylammonium iodide for forming a vinyl chloride; then    Step B: cyclizing the vinyl chloride of said step A under conditions using tribuytyl tin hydride, catalytic AIBN and toluene as the solvent for forming the dihydroindole C-ring of the CC-1065/duocarmycin analog.    
     
     
         2 . A compound represented by the following structure:  
       
         
           
           
               
               
           
         
       
     
     
         3 . A compound represented by the following structure:  
       
         
           
           
               
               
           
         
       
     
     
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         5 . A compound represented by the following structure:  
       
         
           
           
               
               
           
         
       
     
     
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         12 . A compound represented by the following structure:  
       
         
           
           
               
               
           
         
       
     
     
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         18 . A compound represented by the following structure: