Synthesis of Active Hexafluoroisopropyl Benzoates through a Hydrogen‐Bond‐Enabled Palladium(II)‐Catalyzed C−H Alkoxycarbonylation Reaction

Abstract

A Pd -catalyzed ortho C-H alkoxycarbonylation reaction of aryl silanes toward active hexafluoroisopropyl (HFIP) benzoate esters has been developed. This efficient reaction features high selectivity and good functional-group tolerance. Notably, given the general nature of the silyl-tethered directing group, this method delivers products bearing two independently modifiable sites. NMR studies reveal the presence of hydrogen bonding between HFIP and a pyrimidine nitrogen atom of the directing group, and it is thought to be crucial for the success of this alkoxycarbonylation reaction.

Diverse meta‐C−H Functionalization of Arenes across Different Linker Lengths

“…Theb iphenyl pyrimidine-based template T5 provided better yield and excellent meta selectivity compared to T4.T he observed high yield and regioselectivity can be explained by the hydrogen-bonding interactions of the solvent, 1,1,1,3,3,3hexafluoroisopropanol (HFIP), with the pyrimidine-directing group (DG), interactions which decrease the basicity of DG and concurrently increase the p-acidity towards the palladium center. [11] NMR studies show the existence of strong hydrogen bonding between the pyrimidine DG and HFIP (see the Supporting Information). [7b] Ac ontrol experiment without the directing template did not produce any of the alkylated product (Table 1).…”

Diverse meta‐C−H Functionalization of Arenes across Different Linker Lengths

“…Nitrile-and heterocycle-based directing templates were tethered to phenylpropyl alcohol (T1-T5)f or meta-CÀH alkylation using 3-buten-2-ol as the coupling partner (Table 1). [11] NMR studies show the existence of strong hydrogen bonding between the pyrimidine DG and HFIP (see the Supporting Information). Theb iphenyl pyrimidine-based template T5 provided better yield and excellent meta selectivity compared to T4.T he observed high yield and regioselectivity can be explained by the hydrogen-bonding interactions of the solvent, 1,1,1,3,3,3hexafluoroisopropanol (HFIP), with the pyrimidine-directing group (DG), interactions which decrease the basicity of DG and concurrently increase the p-acidity towards the palladium center.…”

Decoding Directing Groups and Their Pivotal Role in C−H Activation

“…[282] Gevorgyan group also described a palladium-catalyzed ortho-CÀ H-alkoxycarbony-lation of arylsilanes for the synthesis of active hexafluoropropanol (HFIP) esters. [283] This method enables access to products bearing two modifiable sites for further transformations, including transesterification of the HFIP ester and many transformations in the silane center. [282,283] The pyrimidyldiisopropylsilyl-arene synthesis starts from the preparation of an aryl-Grignard reagent through the iodine-magnesium exchange in 2-iodopyrimidine using i PrMgCl•LiCl.…”