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...

HFIP in Organic Synthesis

“…A temperature-dependent Pd­(II)-catalyzed C­(sp 2 )–H and C­(sp 3 )–H arylation of pyrazolo­[1,5- a ]­pyrimidines employed a 7-pyridyl DG (Scheme ). Initial screening for this transformation revealed HFIP as the most suitable solvent in comparison to DCE and TFE. HFIP/AcOH solvent mixtures were also screened but delivered product in 18–46% yields compared to HFIP alone (74%).…”

Remote ortho-C–H functionalization via medium-sized cyclopalladation

“…44 A wide variety of substituted g-arylpropylamine derivatives were used, noting that substrates bearing electron-rich aryl substituents provided higher reactivity (46)(47)(48)(49)(50)(51)(52)(53)(54). The applicability of this method to the derivatization of heteroarenes was showcased by the synthesis of a chiral analogue of rucaparib, a recently approved drug for ovarian cancer (55). Applications to late-stage modification of di-and tripeptides were also demonstrated (56,57).…”

“…45 This achievement is remarkable given the high selectivity for arene C-H activation over aliphatic C-H activation typically displayed by Pd. [46][47][48][49][50][51][52][53][54][55] 2. Formation of C-X bonds…”

Functional Pyrazolo[1,5-a]pyrimidines: Current Approaches in Synthetic Transformations and Uses As an Antitumor Scaffold

“…The authors optimized the solvent, base, ligand, and palladium source; once the optimal conditions were founded, the authors proved various aryls bromines ( Scheme 31 ) [ 72 ]. Furthermore, Gogula et al provided a method to modulate the C–H activation of (sp 2 ) or (sp 3 ) carbon based on the temperature over the fused pyrazole 113 and analogs [ 73 ]. In addition, the added palladium generates a stable coordination complex 114 which the authors obtained, this species is responsible for the activation of the methyl C–H leading to a palladation (not shown) and subsequent formation of the C–C bond with the aryl iodine, delivering 115 a–f .…”