Categories: C-O Bond Formation >
Synthesis of aryl ethers
Two types of ligands promote Cu-catalyzed alkoxylations of (hetero)aryl halides to provide alkyl aryl ethers. In case of coupling with aryl chlorides and bromides, two oxalic diamides serve as the powerful ligands. In addition, tert-butoxide enables a Cu-catalyzed alkoxylation of aryl iodides at room temperature.
Z. Chen, Y. Jiang, L. Zhang, Y. Guo, D. Ma, J. Am. Chem. Soc., 2019, 141, 3541-3549.
Self-assembled octanuclear copper clusters catalyzed the coupling of aryl iodides with alcohols under mild conditions. Reactions involving low catalyst loadings (0.4%) and tetrahydrofurfuryl alcohol were typically complete in 4-8 h at 110°C using an oil bath or 1-3 h with microwave heating.
G. F. Manbeck, A. J. Lipman, R. A. Stockland, A. L. Freidl, A. F. Hasler, J. J. Stone, I. A. Guzei, J. Org. Chem., 2005, 70, 244-250.
The use of 3,4,7,8-tetramethyl-1,10-phenanthroline (Me4Phen) as a ligand improves the Cu-catalyzed cross-coupling reactions of aryl iodides and bromides with primary and secondary aliphatic, benzylic, allylic, and propargylic alcohols. The relatively mild conditions, tolerate a wide array of functional groups on both the electrophilic and nucleophilic coupling partners.
R. A. Altman, A. Shafir, P. A. Lichtor, S. L. Buchwald, J. Org. Chem., 2008, 73, 284-286.
In an efficient and mild copper-catalyzed ether formation from aryl halides and aliphatic alcohols, the key to a successful coupling is the use of lithium alkoxide, directly or in situ generated by lithium tert-butoxide, and the corresponding alcohol as solvent.
J. Huang, Y. Chen, J. Chan, M. L. Ronk, R. D. Larsen, M. M. Faul, Synlett, 2011, 1419-1422.
Ullmann-type coupling reactions of aryl iodides and aliphatic alcohols occur at 110 °C with N,N-dimethylglycine as the ligand, giving aryl alkyl ethers in high yields.
H. Zhang, D. Ma, W. Cao, Synlett, 2007, 243-246.
A simple and mild coupling method of aryl iodides and aliphatic alcohols, which does not require alkoxide bases, can be performed in neat alcohol or toluene as solvent. An optically active benzylic alcohol underwent the reaction with complete retention of configuration.
M. Wolter, G. Nordmann, G. E. Job, S. L. Buchwald, Org. Lett., 2002, 4, 973-976.
A Cu-catalyzed cross-coupling reaction between aryl bromides and 9-BBN-OMe provide aryl methyl ethers under mild conditions. The oxalamide ligand BHMPO plays a key role in the transformation. Various functional groups on bromobenzenes are well tolerated.
J.-R. Wang, Z.-Q. Song, C. Li, D.-H. Wang, Org. Lett., 2021, 23, 8450-8454.
The use of a biaryl phosphine ligand was key to achieving efficient cross-coupling of (hetero)aryl chlorides with near-equimolar amounts of secondary alcohols. An unusual reactivity difference between an electron-rich aryl bromide and the analogous aryl chloride was observed.
H. Zhang, P. Ruiz-Castillo, A. W. Schuppe, S. L. Buchwald, Org. Lett., 2020, 22, 5369-5374.
Palladium-catalyzed reactions of aryl halides including activated, nonactivated, and (hetero)aryl bromides as well as aryl chlorides with primary alcohols gave the corresponding alkyl aryl ethers in high yield in the presence of a bulky di-1-adamantyl-substituted bipyrazolylphosphine ligand. Functionalizations of primary alcohols in the presence of secondary and tertiary alcohols proceed with excellent selectivity.
S. Gowrisankar, A. G. Sergeev, P. Anbarasan, A. Spannenberg, H. Neumann, M. Beller, J. Am. Chem. Soc., 2010, 132, 11592-11598.
A general Pd-catalyzed coupling of methanol with (hetero)aryl halides proceeds under mild conditions with a wide range of aryl and heteroaryl halides to give methyl aryl ethers in high yield.
C. W. Cheung, S. L. Buchwald, Org. Lett., 2013, 15, 3966-3969.
A one-pot method for the preparation of alkyl aryl ethers from aryl halides and the preparation of substituted benzofurans via a Pd-catalyzed phenol formation/cyclization protocol starting from 2-chloroaryl alkynes are described.
K. W. Anderson, T. Ikawa, R. E. Tundel, S. L. Buchwald, J. Am. Chem. Soc., 2006, 128, 10694-10695.
KHMDS mediates a defluoroetherification of aryl and heteroaryl fluorides with alkoxyboronic acid pinacol esters under transition-metal-free conditions to efficiently and safely provide a wide variety of aryl ethers in high yields. This method can be applied to the late-stage etherification of structurally complex bioactive compounds.
J. Zhou, B. Jiang, Z. Zhao, N. Shibata, Org. Lett., 2022, 24, 5084-5089.
The use of S-arylphenothiaziniums, which can be easily synthesized from boronic acids, enables a transition-metal-free O-arylation of alcohols and phenols to provide a variety of aryl ethers. The selective introduction of the aryl substituent into the hydroxy groups in alcohols and phenols is supported by theoretical calculations.
T. Yoshida, Y. Honda, T. Morofuji, N. Kano, J. Org. Chem., 2022, 87, 7565-7573.
An oxa-Matteson reaction enables sequential oxygen and carbenoid insertions into diverse alkyl- and arylboronates to provide a wide range of boron-substituted ethers. The utilities of this method are demonstrated in the the asymmetric synthesis of an acetyl-CoA-carboxylase inhibitor, and the programmable construction of polyethers.
Q. Xi, G. Dong, J. Am. Chem. Soc., 2022, 144, 8498-8503.
Transition-metal-free arylation of tertiary alcohols with ortho-substituted diaryliodonium salts enables the synthesis of tertiary alkyl aryl ethers of previously unprecedented steric congestion. Cyclic and acyclic aliphatic, benzylic, allylic, and propargylic tertiary alcohols as well as primary and secondary fluorinated alcohols can be converted.
E. Lindstedt, E. Stridfeldt, B. Olofsson, Org. Lett., 2016, 18, 4234-4237.
An arylation of allylic and benzylic alcohols with diaryliodonium salts yields alkyl aryl ethers under mild and metal-free conditions. Phenols are arylated to diaryl ethers in good to excellent yields. The reaction employs diaryliodonium salts and sodium hydroxide in water at low temperature, and avoids the use of excess amounts of the coupling partners.
E. Lindstedt, R. Ghosh, B. Olofsson, Org. Lett., 2013, 15, 6070-6073.
A formal cross-coupling of aryl methyl sulfones and alcohols affords alkyl aryl ethers via an SRN1 pathway. A dimsyl-anion initiated radical chain process was revealed as the major pathway.
J. Bai, T. Wang, B. Dai, Q. Liu, P. Yu, T. Jia, Org. Lett., 2021, 23, 5761-5765.
A palladium-catalyzed synthesis of aryl tert-butyl ethers from a variety of unactivated aryl bromides or chlorides is described. The ether products, which are precursors to phenols, are obtained in very good yield in the presence of air-stable dialkylphosphinobiphenyl ligands.
C. A. Parrish, S. L. Buchwald, J. Org. Chem., 2001, 66, 2498-2500.
A mechanochemical protocol enables a selectively substitution of an aromatic amino group with a trifluoromethoxy group in the presence of pyrylium tetrafluoroborate and 1-methyl-1,4-diazabicyclo[2.2.2]octan1-ium trifluoromethanolate. The presented concise method opens a pathway to new chemical spaces for organic synthesis and medicinal chemistry.
M. Jakubczyk, S. Mkrtchyan, M. Shkoor, S. Lanka, Š. Budzák, M. Iliaš, M. Skoršepa, V. O. Iaroshenko, J. Am. Chem. Soc., 2022, 144, 10438-10445.