Enantioselective nickel catalysis : exploiting activated C-H bonds

Abstract

A method for the nickel-catalyzed cross-coupling between benzoxazole and secondary halides was explored. This method was to make use of the activated C-H bond found in benzoxazole at the 2-position to generate the nucleophilic species in situ. After an extensive survey of parameters no such method could be found. However, it was found that copper(I) salts promoted the coupling of benzoxazole and benzylic bromides in high yield, albeit in a racemic fashion. Additionally a method to cross-couple terminal alkynes with secondary halides employing nickel-catalysis was explored. After surveying a number of alkynylmetal species, generated in situ, alkynyl borates were found to cross-couple with allylic chlorides to furnish product with the best enantioselectivity (enantiomeric excess ca. 70%), however in low yield.