C2, C5, and C4 Azole <i>N</i>-Oxide Direct Arylation Including Room-Temperature Reactions

Abstract

The N-oxide group imparts a dramatic increase in reactivity at all positions of the azole ring of thiazoles and imidazoles and changes the weak bias for C5 > C2 arylation to a reliable C2 > C5 > C4 reactivity profile. Use of this cross-coupling strategy enables high yielding and room-temperature C2 arylations, mild reactions at C5, and the first examples of C4 arylationproviding a unique opportunity for exhaustive functionalization of the azole core with complete control of regioselectivity. A correlation of reactivity with the relative contributions of each carbon atom to the HOMO is observed and discussed.