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

ABSTRACT: 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.

SUBMITTER: Gogula T

PROVIDER: S-EPMC8162910 | biostudies-literature |

REPOSITORIES: biostudies-literature

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