Categories: C-O Bond Formation >
Synthesis of ethers
Nucleophilic fluorination using CsF or alkali metal fluorides was completed in short reaction time in the presence of [bmim][BF4] affording the desired products without any byproducts. Facile nucleophilic substitutions such as halogenations, acetoxylation, nitrilation, and alkoxylations in the presence of ionic liquids provided the desired products in good yields.
D. W. Kim, C. E. Song, D. Y. Chi, J. Org. Chem., 2003, 68, 4281-4285.
A novel electrolytic system for non-Kolbe electrolysis based on the acid-base reaction between carboxylic acids and solid-supported bases in MeOH provide the corresponding methoxylated products in excellent yields. The acid-base reaction between carboxylic acids and solid-supported bases preferentially takes place to reduce the cell voltage in MeOH.
T. Tajima, H. Kurihara, T. Fuchigami, J. Am. Chem. Soc., 2007, 129, 6680-6681.
An efficient method chemoselectively converts benzyl alcohols into their methyl or ethyl ethers in the presence of aliphatic or phenolic hydroxyl groups using 2,4,6-trichloro-1,3,5-triazine (TCT) and dimethyl sulfoxide in methanol or ethanol.
L. Sun, Y. Guo, G. Peng, C. Li, Synthesis, 2008, 3487-3488.
A Zn(OTf)2-catalyzed coupling of alcohols/phenols with unactivated tertiary alkyl bromides and a Cu(OTf)2-catalyzed thiolation of unactivated tertiary alkyl oxalates with thiols provide sterically hindered tertiary alkyl ethers and thioethers.
Y. Gong, Z. Zhu, Q. Qian, W. Zong, H. Gong, Org. Lett., 2021, 23, 1005-1010.
A sulfoxonium metathesis reaction between TMSOI and cost-effective DMSO-d6 provides deuterated trimethylsulfoxonium iodide (TDMSOI). Subsequent "one-pot" trideuteromethylation installs the -CD3 moiety into broad functionalities including phenols, thiophenols, acidic amines, and enolizable methylene units in high yield and at a useful level of deuteration.
Z. Shen, S. Zhang, H. Geng, J. Wang, X. Zhang, A. Zhou, C. Yao, X. Chen, W. Wang, Org. Lett., 2019, 21, 448-452.
A new synthetic method for the preparation of potassium organotrifluoroborates through nucleophilic substitution of potassium bromo- and iodomethyltrifluoroborates is described. Potassium halomethyltrifluoroborates have been prepared via in situ reaction of n-BuLi with dibromo- and diiodomethane, respectively, in the presence of trialkyl borates, followed by treatment with KHF2.
G. A. Molander, J. Ham, Org. Lett., 2006, 8, 2031-2034.
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.
A gold-catalyzed, microwave protocol activates alcohols through an intermolecular, SN1-type reaction to directly form unsymmetrical ethers and Cbz-protected amines in good yields. This reaction is highly reproducible and tolerates moisture.
A. R. S. Vinson, V. K. Davis, A. Arunasalam, K. A. Jesse, R. E. Hamilton, M. A. Shattuck, A. C. Hu, R. G. Iafe, A. G. Wenzel, Synlett, 2015, 26, 765-770.
An efficient intermolecular conjugate addition of various primary and secondary alcohols to unsaturated ketones and esters is catalyzed by the free carbene derived from IMes·HCl. No oligomerization is observed under these mild conditions. In addition to reactions with activated alkenes, IMes catalyzes the formation of vinyl ethers through the 1,4-addition of alcohols to ynones.
E. M. Phillips, M. Riedrich, K. A. Scheidt, J. Am. Chem. Soc., 2010, 132, 13179-13181.
The combination of a copper-catalyzed C-O coupling reaction with a subsequent Claisen rearrangement allowed the generation of two adjacent quarternary stereocenters in a one-pot domino process. Furthermore, an experimentally simple stereoselective synthesis of of vinyl ethers is delineated using the same catalyst system.
G. Nordmann, S. L. Buchwald, J. Am. Chem. Soc., 2003, 125, 4978-4979.
The use of a (P,N) ligand enables a highly regioselective Ni-catalyzed hydroalkoxylation of 1,3-dienes. The optimized protocol operates under particularly mild conditions, provides access to a broad range of structurally diverse allylic ethers, and tolerates a number of sensitive functional groups.
G. Tran, C. Mazet, Org. Lett., 2019, 21, 9060-9065.
A Pd[BiPhePhos] catalyst enables the use nonactivated phenols as nucleophiles in the allylation of nonderivatized allylic alcohols to generate allylated phenolic ethers in very good yields with water as the only byproduct. The kinetically favored O-allylated products are formed exclusively over the thermodynamically favored C-allylated products.
T. Rukkijakan, S. Akkarasamiyo, S. Sawadjoon, J. S. M. Samec, J. Org. Chem., 2018, 83, 4099-4104.
A stereospecific and stereoselective, copper-promoted coupling of vinyl pinacol boronate esters and alcohols allows the synthesis of enol ethers in very good yields, is compatible with various functional groups, and occurs at room temperature. Cupric acetate is the copper source, and triethylamine buffer is used to prevent protodeboration.
R. E. Shade, A. M. Hyde, J.-C. Olsen, C. A. Merlic, J. Am. Chem. Soc., 2010, 132, 1202-1203.
Using commercially available Ph3PAuCl and readily prepared, benign arylsilanes, a gold-catalyzed oxyarylation of alkenes proceeds smoothly in air. The oxidant, Selectfluor, not only facilitates entry to the Au(I/III) manifold but also provides a fluoride anion for silane activation, thereby avoiding the need for addition of a stoichiometric base.
L. T. Ball, M. Green G. C. Lloyd-Jones, C. A. Russel, Org. Lett., 2010, 12, 4724-4727.
A microwave-assisted, chemoselective and efficient method for the cleavage of silyl ethers is catalyzed by Selectfluor. A wide range of TBDMS-, TIPS-, and TBDPS-protected alkyl silyl ethers can be chemoselectively cleaved in high yield in the presence of aryl silyl ethers. In addition, the transetherification and etherification of benzylic hydroxy groups in alcoholic solvents is observed.
S. T. A. Shah, S. Singh, P. J. Guiry, J. Org. Chem., 2009, 74, 2179-2182.
A nickel(0) triethyl phosphite complex promotes the reaction of allylic acetates with thiols to produce allylic sulfides with retention of configuration without allylic rearrangement. A similar reaction of allylic acetates with alcohols and phenols also proceeds with retention of regio- and stereochemistry.
Y. Yatusmonji, Y. Ishida, A. Tsubouchi, T. Takeda, Org. Lett., 2007, 9, 4603-4606.
A wide range of ynol ethers can be prepared via displacement at an sp center. The same protocol can be applied to the synthesis of synthetically useful thioynol ethers. This reaction, which generates highly functionalized, heteroatom-substituted alkynes, involves radical intermediates.
V. J. Gray, J. Cuthbertson, J. D. Wilden, J. Org. Chem., 2014, 79, 5869-5874.
The hydroalkoxylation of allenes with alcohols proceeds smoothly in the presence of a catalytic amount of Ph3PAuNO3 and H2SO4 to give allylic ethers in good yields and high regio- and stereoselectivity.
D.-M. Cui, K.-R. Yu, C. Zhang, Synlett, 2009, 1103-1106.
A mild method for the trimethylsilyl trifluoromethanesulfonate (TMSOTf) catalyzed one-pot synthesis of homoallyl ethers from aldehydes has been developed in the ionic liquid 1-butyl-3-methylimidazolium trifluoromethanesulfonate ([bmim] [OTf]). The advantages of this method include the use of a recyclable ionic liquid, facile product isolation without employing excess organic solvent and elimination of an aqueous waste stream.
P. W. Anzalone, R. S. Mohan, Synthesis, 2005, 2661-2663.
A general, Ir(I)-catalyzed enantioselective decarboxylative allylic etherification of aryl allyl carbonates provides aryl allyl ethers with high stereoselection.
D. Kim, S. Reddy, O. V. Singh, J. S. Lee, S. B. Kong, H. Han, Org. Lett., 2013, 15, 512-515.
Chiral phosphine-catalyzed coupling of two readily available partners, γ-aryl-substituted alkynoates and alcohols, under mild conditions enables the enantioselective synthesis of benzylic ethers via internal redox reaction of the alkynoate partner.
D. T. Ziegler, G. C. Fu, J. Am. Chem. Soc., 2016, 138, 12069-12072.
A Pd-catalysed termolecular allenylation cascade followed by a Ru catalysed RCM process affords a diverse range of Δ3-aryl/heteroaryl substituted five-seven membered nitrogen and oxygen heterocycles.
H. A. Dondas, B. Clique, B. Cetinkaya, R. Grigg, C. Kilner, J. Morris, V. Sridharan, Tetrahedron, 2005, 61, 10652-10666.
p-Toluenesulfonic acid efficiently catalyzes direct nucleophilic substitutions of the hydroxy groups of propargylic alcohols with a large variety of carbon- and heteroatom-centered nucleophiles. Reactions can be conducted under mild conditions and in air without the need for dried solvents.
R. Sanz, A. Martinez, J. M. Alvarez-Gutierrez, F. Rodriquez, Eur. J. Org. Chem., 2006, 1383-1386.
A general and efficient FeCl3-catalyzed substitution reaction of propargylic alcohols with carbon- and heteroatom-centered nucleophiles such as allyl trimethylsilane, alcohols, aromatic compounds, thiols, and amides, forms new C-C, C-O, C-S and C-N bonds.
Z.-P. Zhan, J.-L. Yu, Y.-Y. Cui, R.-F. Yang, W.-Z. Yang, J.-P. Li, J. Org. Chem., 2006, 71, 8298-8301.
An economic and practical transformation from secondary alkyl-substituted propargyl acetates to a variety of nucleophilic substitution products is catalyzed by inexpensive InCl3. High yields and excellent chemoselectivity were obtained. Five-, six-, and seven-membered propargyl cycloethers were also successfully constructed.
M. Lin, L. Hao, X.-t. Liu, Q.-z. Chen, F. Wu, P. Yan, S.-x. Xu, X.-l. Chen, J.-j. Wen, Z.-p. Zhan, Synlett, 2011, 665-670.
The preparation of diverse β-chloroethers, β-chloroacetates, and chlorohydrins is efficiently achieved under mild conditions by reaction of alkenes with trichloroisocyanuric acid in alcohols, acetic acid or aqueous acetone, respectively.
G. Fonseca Mendonça, A. Manzolillo Sanseverino, M. C. S. de Mattos, Synthesis, 2003, 45-48.
Electrochemical technology enables alkene alkoxyhalogenation and organohalide dehalogenation in one pot. Anodic conversion of the C=C bond to radical cation intermediates and cathodic transformations of organohalides run in parallel.
T.-T. Zhang, M.-J. Luo, Y. Li, R.-J. Song, J.-H. Li, Org. Lett., 2020, 22, 7230-7233.
A constant current electrolysis synergizing with a Lewis-acid catalysis protocol enables an external oxidant-free oxytrifluoromethylation and aminotrifluoromethylation of styrene derivatives using sodium trifluoromethanesulfinate as the trifluoromethyl source.
L. Zhang, G. Zhang, P. Wang, Y. Li, A. Lei, Org. Lett., 2018, 20, 7396-7399.
A cobalt-catalyzed α-methoxymethylation of ketones with methanol as a sustainable C1 source, cheap CoCl2·6H2O as catalyst and TBHP as oxidant provides the methoxymethylated products within a short reaction time in very good yield. α-Aminomethylated ketones can be produced by a one-pot methylenation/aza-Michael addition sequence or by a base-mediated conversion of the α-methoxymethyl ketones.
J. Yang, S. Chen, H. Zhou, C. Wu, B. Ma, J. Xiao, Org. Lett., 2018, 20, 6774-6779.
Despite the high reactivity of alkoxyl (RO·) radicals and their propensity to easily undergo β-scission or Hydrogen Atom Transfer (HAT) reactions, an efficient photoredox-mediated intermolecular trapping of alkoxyl radicals by silyl enol ethers enables the introduction of both structurally simple and more complex alkoxy groups into a wide range of ketones and amides.
C. Banoun, F. Bourdreux, E. Magnier, G. Dagousset, Org. Lett., 2021, 23, 8921-8925.
The reaction between ethynylbenziodoxol(on)es (EBXs) and phenols driven by visible light provides (Z)-2-iodovinyl phenyl ethers with excellent regio- and stereoselectivity. The (Z)-2-iodovinyl phenyl ether products can be further stereospecifically functionalized to form trisubstituted alkenes, demonstrating the potential of these products en route to chemical complexity.
B. Liu, C.-H. Lim, G. M. Miyake, J. Am. Chem. Soc., 2018, 140, 12829-12835.