Switchable reactivity of homopropargylic alcohols towards γ-arylated ketones and α-arylated tetrahydrofurans in HFIP
Abstract
A divergent synthetic strategy to access γ-arylated ketones and α-arylated tetrahydrofurans from readily available homopropargylic alcohols and arene nucleophiles is reported. This method expands the accessible chemical space of γ-arylated ketones via a unique triflic acid-catalyzed hydroalkoxylation/ring-opening arylation sequence proceeding through a 2,3-dihydrofuran intermediate, enabled by the properties of 1,1,1,3,3,3-hexafluoroisopropan-2-ol (HFIP) as solvent. This protocol provides a solution for preparing γ-arylated ketones incorporating sterically hindered arenes, while displaying compatibility with synthetically relevant functionalities to deliver linear and branched γ-arylated ketones, including both aliphatic and aromatic variants. Switching the reaction pathway by employing p-cymene as a hydride donor promotes a reductive hydroalkoxylation, affording α-arylated tetrahydrofurans with high efficiency. Mechanistic studies supported by DFT computations reveal a complex catalytic reaction network in which multiple pathways converge to the observed products.
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BibTeX
@article{miesch2026switchable,
title = {{Switchable reactivity of homopropargylic alcohols towards γ-arylated ketones and α-arylated tetrahydrofurans in HFIP}},
author = {Claire Miesch and Ewelina Krolicka and Robert J Mayer and David Leboeuf},
journal = {Chemical Science},
year = {2026},
month = jun,
doi = {10.1039/d6sc03645g},
url = {https://hal.science/hal-05743915v1},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Switchable reactivity of homopropargylic alcohols towards γ-arylated ketones and α-arylated tetrahydrofurans in HFIP
AU - Claire Miesch
AU - Ewelina Krolicka
AU - Robert J Mayer
AU - David Leboeuf
PY - 2026
DA - 2026/06/09
JO - Chemical Science
DO - 10.1039/d6sc03645g
UR - https://hal.science/hal-05743915v1
AB - A divergent synthetic strategy to access γ-arylated ketones and α-arylated tetrahydrofurans from readily available homopropargylic alcohols and arene nucleophiles is reported. This method expands the accessible chemical space of γ-arylated ketones via a unique triflic acid-catalyzed hydroalkoxylation/ring-opening arylation sequence proceeding through a 2,3-dihydrofuran intermediate, enabled by the properties of 1,1,1,3,3,3-hexafluoroisopropan-2-ol (HFIP) as solvent. This protocol provides a solution for preparing γ-arylated ketones incorporating sterically hindered arenes, while displaying compatibility with synthetically relevant functionalities to deliver linear and branched γ-arylated ketones, including both aliphatic and aromatic variants. Switching the reaction pathway by employing p-cymene as a hydride donor promotes a reductive hydroalkoxylation, affording α-arylated tetrahydrofurans with high efficiency. Mechanistic studies supported by DFT computations reveal a complex catalytic reaction network in which multiple pathways converge to the observed products.
SN - 2041-6520
SN - 2041-6539
ER -