Targeted activation of alcoholic sp3 Cα-H by H-bonding protection of O–H for the hydroxyalkylation of N-heterocycles

Abstract

The direct sp3 C–H functionalization of alcohol with N-heterocycles is the most atom-economical pathway to produce hydroxyalkylated N-heterocycles. However, the targeted C–H activation to enable the direct C–C coupling still remains of great challenge due to the concomitant activation of alcoholic O–H. This work puts forward a H-bonding protection for alcoholic O–H for the targeted activation of alcoholic Cα-H bonds. Atomic Fe-N sites anchored in graphitic carbon nitride with uncoordinated nitrogen sites has thus been proposed for this strategy, in which atomic Fe(II)-N sites are supposed to be responsible for the targeted activation of alcoholic Cα-H and the surface uncoordinated nitrogen to for the H-bonding with alcoholic O–H. To demonstrate the strategy, the precise modulation on the atomic Fe-N coordination in the 6-fold cavity from three heptazines have been elaborated. Atomic Fe with four N atoms from two heptazines assisted with the uncoordinated N from the free one heptazine has presented a synergistic H-bonding protection of alcoholic O–H bonds. As a result, the targeted generation and excellent stabilization of hydroxyethyl radicals have been achieved under ambient temperature. The strategy has been successfully applied for 1-propanol, 2-propanol, 1-butanol, and 1-pentanol, thus achieving efficient C–C formation in the hydroxyalkylation of varied N-heterocycles.