Temperature-modulated selective C(sp3)−H or C(sp2)−H arylation through palladium catalysis

Transition metal-catalysed C−H bond functionalisations have been extensively developed in organic and medicinal chemistry. Among these catalytic approaches, the selective activation of C(sp3)−H and C(sp2)−H bonds is particularly appealing for its remarkable synthetic versatility, yet remains highly challenging. Herein, we demonstrate the first example of temperature-dependent selective C−H functionalisation of the unactivated C(sp3)−H or C(sp2)−H bonds at remote positions through palladium catalysis using 7-pyridyl-pyrazolo[1,5-a]pyrimidine as a new directing group. At 120 oC, C(sp3)−H arylation was triggered by the chelation of rare [6, 5]-fused palladacycle, whereas at 140 oC, C(sp2)−H arylation proceeded instead through the formation of a 16-membered tetramer containing four 7-pyridyl-pyrazolo[1,5-a]pyrimidine-palladium chelation units. The subsequent mechanistic study revealed that both C−H activations shared the common 6-membered palladacycle intermediate which was then directly transformed to either the [6,5]-fused palladacycle for C(sp3)−H activation at 120 oC or the tetramer for C(sp2)−H arylation at 140 oC with catalytic amount of Pd(OAc)2 and AcOH. Raising the temperature from 120 oC to 140 oC can also convert the [6,5]-fused palladacycle to the tetramer with above-mentioned catalysts, hence completing the C(sp2)−H arylation ultimately.