Facile Benzylic Alkylation of Arenes with Alcohols by Catalysis with Spirocyclic NHC Ir^III Pincer Complex

Abstract

A facile benzylic alkylation of indenes and other arenes was developed from readily available primary and secondary alcohols using our newly investigated CCC pincer IrIII catalyst (SNIr−H). Excellent regioselectivity and yield (89 %) of the C3‐alkylated indenes were obtained. Additionally, the challenging sp2C‐alkylation was readily accomplished. This method could be utilized for the synthesis of the analogs of a histamine H1 receptor antagonist and the functional material template molecule, indeno[2,1‐a]indene. A hemilabile IrIII‐dihydride intermediate was proposed based on control experiments and previous density functional theory (DFT) calculations for the borrowing hydrogen mechanism and is key to the success of this IrIII catalyst in the reduction of unactivated multi‐substituted olefin intermediates.

Alcohols as Substrates in Transition-Metal-Catalyzed Arylation, Alkylation, and Related Reactions

“…An iridium-NHC pincer catalyst was employed by Tu in 2022 in the benzylic alkylation of activated arenes such as fluorene, xanthene, and methyl heteroarenes with primary and secondary alcohols (Scheme 54c). 342 The authors demonstrated the synthetic utility of this method in the synthesis of a histamine H1 receptor agonist. Finally, Zhao and colleagues demonstrated the redox-enabled direct enantioconvergent heteroarylation of simple alcohols in the presence of an achiral iridium catalyst and chiral phosphoric acid (Scheme 54d).…”

“…Obora and colleagues extended this transformation to include the alkylation of methyl quinolines in subsequent years . Iridium catalysis has steadily remained the most utilized metal catalysis for the functionalization of alcohols through in situ carbonyl generation, proving useful in the functionalization of ketones, − nitriles, , and C–H bonds. , …”

“…An iridium-NHC catalyst was used, and the absence of a strong stoichiometric base permitted the authors to achieve a broad functional group tolerance. An iridium-NHC pincer catalyst was employed by Tu in 2022 in the benzylic alkylation of activated arenes such as fluorene, xanthene, and methyl heteroarenes with primary and secondary alcohols (Scheme c) . The authors demonstrated the synthetic utility of this method in the synthesis of a histamine H1 receptor agonist.…”

“…331 Iridium catalysis has steadily remained the most utilized metal catalysis for the functionalization of alcohols through in situ carbonyl generation, proving useful in the functionalization of ketones, 332−338 nitriles, 339,340 and C−H bonds. 341,342 Donohoe and colleagues have developed many methods for the deoxygenative functionalization of alcohols through iridium-catalyzed borrowing hydrogen and related transformations. In 2015, they reported the development of an αmethylation reaction to generate branched ketones (Scheme 53a).…”

Regioselective 1,n-Diborylation of Alkylidenecyclopropanes Enabled by Catalysis with a Spirocyclic NHC IrIII Pincer Complex

“…Recently, we developed a novel spirocyclic N -heterocyclic carbene (SNHC)-based Ir­(III) CCC pincer complexes (SNIr-Cl), which showed excellent activities in C–H silylation, olefin isomerization, and borrowing hydrogen reactions. In these reactions, one of the Ph–Ir bonds cleaved and formed an Ir I species, which showed high reactivities in C–H bond activation and hydrogen borrowing hydrogen reactions.…”