butt_1
butt_2
butt_3
butt_4
butt_5
butt_6
                           
     

The effect of the presence of electron withdrawing group     -  Cyanide

    
                           
 

When electron withdrawing group such as cynate present, they stabilize both intermediate lithiated cubanes very well. As a result, only a small amount of LiTMP is need to achieve fairly complete deprotonation even at -78°C.

The inductive effect of the cyano group clearly enhances the reaction. However, the adding of cyano groups results in competitive lithiation and a mixture of products. However, this problem can be well trackled by adding MgBr2.The product ratio was improved to 9:1 favoring carboxyliation ortho to the amide function.

 

  

A mixture of product formed.

     
                     
       
         

Increased selectivity by adding MgBr2

  
 
 
 
    Since the reactivity of cubane metalation is enhanced greatly with presence of cyano groups, it is possible to substitute all three positions ortho to the amide in a simple reaction. For instance, 4-cyanocubanamide can be converted directly into the tri(tert-butylcarbonyl)derivative as shown below.
                             
             
                             
    Through Baeyer-Villiger oxidation, ter-butyl cuybl ketones can be converted easily to the polycarboxyliated cubane.