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

[Display omitted] • A novel strategy on targeted activation of alcoholic sp 3 C α -H bonds by synergistic H-bonding protection of O–H bonds is put forward. • Atomic Fe-N sites with the uncoordinated N species presents a synergistic adsorption of ethanol O–H bonds, providing the O–H protection by H bonding. • Targeted generation and excellent stabilization of •CH(OH)R radicals under ambient temperature are achieved. • Direct C–C construction of generated •CH(OH)R radicals with a variety of N -heterocycles contributes to an efficient Minisci hydroxyalkylation in a yield of 64 ∼ 98 %. The direct sp 3 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 C α -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 C α -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. [ABSTRACT FROM AUTHOR]