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 it remains highly challenging. Herein, we demonstrate the first example of temperature-dependent selective C-H functionalisation of 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 °C, C(sp3)-H arylation was triggered by the chelation of a rare [6,5]-fused palladacycle, whereas at 140 °C, 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 a common 6-membered palladacycle intermediate, which was then directly transformed to either the [6,5]-fused palladacycle for C(sp3)-H activation at 120 °C or the tetramer for C(sp2)-H arylation at 140 °C with catalytic amounts of Pd(OAc)2 and AcOH. Raising the temperature from 120 °C to 140 °C can also convert the [6,5]-fused palladacycle to the tetramer with the above-mentioned catalysts, hence completing the C(sp2)-H arylation ultimately.