Synthesis of Furans
A mild oxidation of alkyl enol ethers to enals employs low loadings of a palladium catalyst and tolerates a diverse array of functional groups, while allowing the formation of di-, tri-, and tetrasubtituted olefins. The application of this methodology to intramolecular reactions of alkyl enol ethers containing pendant alcohols provides furan and 2,5-dihydrofuran products.
M. G. Lauer, W. H. Henderson, A. Awad, J. P. Sambuli, Org. Lett., 2012, 14, 6000-6003.
Gold-catalyzed cyclizations of diols and triols to the corresponding hetero- or spirocycles take place in an aqueous medium within nanomicelles, where the hydrophobic effect is operating, thereby driving the dehydrations, notwithstanding the surrounding water. By the addition of simple salts such as sodium chloride, reaction times and catalyst loadings can be significantly decreased.
S. R. K. Minkler, N. A. Isley, D. J. Lippincott, N. Krause, B. H. Lipshutz, Org. Lett., 2014, 16, 724-726.
A Au(I)-catalyzed hydroamination or hydration of 1,3-diynes allows access to 2,5-diamidopyrroles and 2,5-diamidofurans. This method can also be expanded to 2,5-disubstituted furans and 1,2,5-trisubstituted pyrroles.
S. Kramer, J. L. H. Madsen, M. Rottländer, T. Skrydstrup, Org. Lett., 2010, 12, 2758-2761.
The elimination pathway of stereochemically defined β-halovinyl ketones has been investigated using a mild base, NEt3, leading to the formation of allenyl ketones and propargyl ketones. In the presence of CuCl as a catalyst, the elimination reaction of β-chlorovinyl ketones enables a one-pot synthesis of 2,5-disubstituted furans.
H. Y. Kim, J.-Y. Li, K. Oh, J. Org. Chem., 2012, 77, 11132-11145.
Palladium catalysis enables a highly efficient synthesis of a wide range of 2,5-disubstituted furans in very good yields from enyne acetates in the presence of a Lewis acid.
Z.-W. Chen, M.-T. Luo, Y.-L. Wen, M. Ye, Z.-G. Zhou, L.-X. Liu, Synlett, 2014, 25, 2341-2344.
2,5-Disubstituted 3-iodofurans are readily prepared under very mild reaction conditions by a palladium/copper-catalyzed cross-coupling of (Z)-β-bromoenol acetates and terminal alkynes leading to conjugated enyne acetates as intermediates in high yields, followed by iodocyclization in good yields. The resulting iodine-containing furans can be readily elaborated to 2,3,5-trisubstituted furans.
Z. Chen. G. Huang, H. Jiang, H. Huang, X. Pan, J. Org. Chem., 2011, 76, 1134-1139.
An efficient FeCl3-catalyzed substitution reaction of propargylic acetates with enoxysilanes under mild conditions affords corresponding γ-alkynyl ketones. A subsequent TsOH-catalyzed cyclization without purification of the γ-alkynyl ketone intermediates, offers a straightforward synthetic route to tri- or tetrasubstituted furans.
Z.-P. Zhang, X.-B. Cai, S.-P. Wang, J.-L. Yu, H.-J. Liu, Y.-Y. Cui, J. Org. Chem., 2007, 72, 9838-9841.
Under different conditions, the reaction of propargyl alcohols and terminal alkynes leads to the selective formation of 1,4-diynes and polysubstituted furans/pyrroles. Water is the only byproduct in the atom economic, selective synthesis of 1,4-diynes and pyrroles, whereas the synthesis of furans is fully atom economic.
T. Wang, X.-l. Chen, L. Chen, Z.-p. Zhan, Org. Lett., 2011, 13, 3324-3327.
A 5-Endo-dig electrophilic cyclization of 1,4-diaryl but-3-yn-1-ones with NBS or NIS/acetone and ICl/CH2Cl2 provides 3-halo-2,5-diarylfurans with high yields.
A. Sniady, K. A. Wheeler, R. Dembinski, Org. Lett., 2005, 7, 1769-1772.
Zinc chloride-catalyzed 5-endo-dig cycloisomerization of 1,4-di- and 1,2,4-trisubstituted but-3-yn-1-ones in dichloromethane at room temperature provides 2,5-di- and 2,3,5-trisubstituted furans in high yields.
A. Sniady, A. Durham, M. S. Morreale, K. A. Wheeler, R. Dembinski, Org. Lett., 2007, 9, 1175-1178.
Intramolecular cyclizations of 3-alkyne-1,2-diols and 1-amino-3-alkyn-2-ols with very low catalyst loading of (Ph3P)AuCl-AgNTf2 or (Ph3P)AuCl-AgOTf proceeded at room temperature to provide various substituted furans and pyrroles in excellent yields. This method was also fully applicable to the conversion of 26 g of a substrate using only 0.05 mol % each of the Au and Ag catalysts.
M. Egi, K. Azechi, S. Akai, Org. Lett., 2009, 11, 5002-5005.
Furans, pyrroles, and thiophenes are efficiently and conveniently prepared by gold-catalyzed dehydrative cyclizations of readily available, heteroatom-substituted propargylic alcohols. The reactions provide essentially pure aromatic heterocycles in high yields in minutes under open-flask conditions with low catalyst loadings.
A. Aponick, C.-Y. Li, J. Malinge, E. F. Marques, Org. Lett., 2009, 11, 4624-4627.
A convenient, silver(I)-catalyzed reaction of alk-1-ynyl oxiranes in the presence of p-toluenesulfonic acid and methanol gives functionalized furans. Evidence supported a cascade mechanism.
A. Blanc, K. Tenbrink, J.-M. Weibel, P. Pale, J. Org. Chem., 2009, 74, 4360-4363.
Acetylenic epoxides are directly prepared by nucleophilic ring closure of propargylic alkoxides generated by lithium acetylide addition to α-haloketones. A subsequent, mild and efficient cycloisomerization in the presence of InCl3 as catalyst delivers 2,3,5-trisubstituted furans.
J. Y. Kang, B. T. Connell, J. Org. Chem., 2011, 76, 2379-2383.
Highly substituted furans were conveniently synthesized by the platinum-catalyzed reaction of propargylic oxiranes. Propargylic aziridines were also reacted with the platinum catalyst to produce the corresponding substituted pyrroles in good yields.
M. Yoshida, M. Al-Amin, K. Shishido, Synthesis, 2009, 2454-2466.
Co(III)-carbene radicals generated from activation of α-diazocarbonyls by Co(II)-porphyrin complexes undergo a new type of tandem radical addition reaction with alkynes that affords five-membered furans. The Co(II) complex of 3,5-DitBu-IbuPhyrin is effective in catalyzing the metalloradical cyclization reaction under neutral and mild conditions and tolerates a wide range of α-diazocarbonyls and terminal alkynes.
X. Cui, X. Xu, L. Wojtas, M. M. Kim, X. P. Zhang, J. Am. Chem. Soc., 2012, 134, 19981-19984.
A highly efficient palladium-catalyzed cascade reaction of aryloxy-enynes with aryl halides under mild reaction conditions offers rapid access to 2,3,4-trisubstituted furans in very good yields in a regioselective manner.
E. Li, X. Cheng, C. Wang, Y. Shao, Y. Li, J. Org. Chem., 2012, 77, 7744-7748.
A Cu(I)-catalyzed highly regioselective domino reaction of 2,3-dibromo-1-propenes with β-ketoesters and 1,3-diketones, respectively, in DMF at 120 °C using Cs2CO3 as a base and hydroquinone as an additive delivers 2,3,5-trisubstituted furans and related compounds with good yields via an intermolecular C-allylation followed by an intramolecular Ullmann type O-vinylation and a double bond isomerization.
D. Schmidt, C. C. Malakar, U. Beifuss, Org. Lett., 2014, 16, 4862-4865.
A mild, oxidative cycloisomerization of cis-enynols using a combination of a hypervalent iodine(III) reagent, molecular iodine, and a base offers an efficient synthesis of 2-acyl furans with diverse substitution patterns in a regioselective manner. A mechanistic proposal for these transformations involving alkyne activation by trifluoroacetylhypoiodite generated in situ is presented.
X. Du, H. Chen, Y. Chen, J. Chen, Y. Liu, Synlett, 2011, 1010-1014.
An efficient FeCl3-catalyzed tandem propargylation-cycloisomerization reaction of propargylic alcohols or acetates with 1,3-dicarbonyl compounds leads to highly substituted furans.
W.-h. Ji, Y.-m. Pan, S.-y. Zhao, Z.-p. Zhan, Synlett, 2008, 3046-3052.
The FeCl3-catalyzed addition and cyclization of enamino esters with nitroolefins provides a rapid, straightforward, and general method for the synthesis of tetrasubstituted NH pyrroles in good yields and tolerates a wide range of functionality. Further, an efficient KOAc-promoted addition and cyclization protocol provides substituted furans as well.
L. Li, M.-N. Zhao, Z.-H. Ren, J. Li, Z.-H. Guan, Synthesis, 2012, 44, 532-540.
Different gold catalysts effect either selective bromine migration or hydrogen shift in haloallenyl ketones, leading to the formation of 3- or 2-bromofurans, respectively. AuCl3-catalyzed transformations include 1,2-halogen migrations via proposed halirenium intermediates and allow for mild and efficient synthesis of various types of 3-halofurans.
A. W. Sromek, M. Rubina, V. Gevorgyan, J. Am. Chem. Soc., 2005, 127, 10500-10501.
Gold(III) porphyrin-catalyzed cycloisomerization of allenones gave the corresponding furans in good to excellent yields (up to 98%) and with quantitative substrate conversions. The Au(III) catalyst is recycable.
C.-Y. Zhou, P. W. H. Chang. C.-M. Che, Org. Lett., 2006, 8, 325-328.
An efficient synthesis of structurally diverse fused furans in good yields from 2-alkynylcycloalk-2-enols via gold(III) bromide catalyzed cycloisomerization was achieved under moderate reaction conditions.
C. Praveen, P. Kiruthiga, P. T. Perumal, Synlett, 2009, 1990-1996.
A mild, gold-catalyzed cascade reaction provides efficient access to highly substituted furans. The substrates can be readily prepared from the corresponding enones through cyclopropanation.
J. Zhang, H.-G. Schmalz, Angew. Chem. Int. Ed., 2006, 45, 6704-6707.
A simple and highly efficient protodecarboxylation of various heteroaromatic carboxylic acids is catalyzed by Ag2CO3 and AcOH in DMSO. This methodology enables also a selective monoprotodecarboxylation of several aromatic dicarboxylic acids.
P. Lu, C. Sanchez, J. Cornella, I. Larrosa, Org. Lett., 2009, 11, 5710-5713.
In(OTf)3 or In(NTf2)3 effectively catalyze the cycloisomerization reaction of α-propargyl-β-keto esters and their imine analogues to afford trisubstituted furans and pyrroles, respectively. Both terminal and internal alkynes take part in the reaction with good functional-group compatibility in the presence of only a small catalyst loading.
H. Tsuhi, K.-i. Yamagata, Y. Ueda, E. Nakamura, Synlett, 2011, 1015-1017.
A broad range of highly functional furans can be efficiently generated from Michael acceptors, tributylphosphine, and acyl chlorides in one step at room temperature in good yields. The reaction was proposed to proceed via intramolecular Wittig-type reactions, using phosphorus ylides as intermediates.
T.-T. Kao, S.-e. Syu, Y.-W. Jhang, W. Li, Org. Lett., 2010, 12, 3066-3069.
A convenient one-pot Cu(I)-catalyzed strategy gives trisubstituted α-carbonyl furans derivatives in good yields via (2-furyl) carbene complexes using air as the oxidant.
H. Cao, H. Zhan, J. Cen, J. Lin, Y. Lin, Q. Zhu, M. Fu, H. Jiang, Org. Lett., 2013, 15, 1080-1083.
A reliable method for the direct construction of polysubstituted furans involves Sn(II)- and Cu(I)-promoted addition/oxidative cyclization of alkynoates and 1,3-dicarbonyl compounds in the presence of 2,3-dichloro-5,6-dicyanobenzoquinone.
W. Liu, H. Jiang, M. Zhang, C. Qi, J. Org. Chem., 2010, 75, 966-968.
Easily accessible propargyl vinyl ethers react in a cascade reaction of propargyl-Claisen rearrangement and heterocyclization catalyzed by cationic triphenylphosphinegold(I) to give tri- and tetrasubstituted furans.
M. H. Suhre, M. Reif, S. F. Kirsch, Org. Lett., 2005, 7, 3873-3876.
A new three-component cyclization catalyzed by palladium produces polysubstituted furans in good yields from readily available substrates. A mechanism is proposed.
X.-H. Duan, X.-Y. Liu, L.-N. Guo, M.-C. Liao, W.-M. Liu, Y.-M. Liang, J. Org. Chem., 2005, 70, 6980-6983.
DABCO-catalyzed reactions of α-halo carbonyl compounds with dimethyl acetylenedicarboxylate (DMAD) at room temperature gave polysubstituted furans and highly functionalized 2H-pyrans in good yields.
M. Fan, Z. Yan, W. Liu, Y. Liang, J. Org. Chem., 2005, 70, 8204-8207.
A mild and efficient domino reaction allows a regiospecific synthesis of polysubstituted furans in moderate yields via a copper(I)-catalyzed rearrangement/dehydrogenation oxidation/carbene oxidation sequence of 1,5-enynes in situ formed from alkynols and diethyl but-2-ynedioate.
H. Cao, H. Jiang, W. Yao, X. Liu, Org. Lett., 2009, 11, 1931-1933.
A highly efficient amidation reaction of heterocycles with N-fluorobenzenesulfonimide (NFSI) presumably proceedes via C-H bond activation in the presence of cuprous iodide as catalyst. Various α-amidated heterocycle derivatives have been generated in good to excellent yields.
S. Wang, Z. Ni, X. Huang, J. Wang, Y. Pan, Org. Lett., 2014, 16, 5648-5651.
A facile oxidative coupling of α-carbonyl radicals to 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) enables the synthesis of 2,3-dicyanofurans and thiophenes from readily available β-diketones, simple ketones, and β-keto thioamides in very good yield. Mechanistic investigations revealed that a radical process and a water-promoted C-C bond cleavage could be involved in this transformation.
Z.-L. Wang, H.-L. Li, L.-S. Ge, X.-L. An, Z.-G. Zhang, X. Luo, J. S. Fossey, W.-P. Deng, J. Org. Chem., 2014, 79, 1156-1165.
The three-component coupling of aldehyde, dimethyl acetylenedicarboxylate (DMAD) and cyclohexyl isocyanide proceeds efficiently in [bmim]BF4 ionic medium under extremely mild conditions to afford 2-aminofurans in high yields. The recovered ionic liquid was reused for five to six times with consistent activity.
J. S. Yadav, B. V. S. Reddy, S. Shubashree, K. Sadashiv, J. J. Naidu, Synthesis, 2004, 2376-2380.
An efficient and highly versatile microwave-assisted Paal-Knorr condensation of various 1,4-diketones gave furans, pyrroles and thiophenes in good yields. In addition, transformations of the methoxycarbonyl moiety, such as Curtius rearrangement, hydrolysis to carboxylic acid, or the conversion into amine by reaction with a primary amine in the presence of Me3Al, are described.
G. Minetto, L. F. Raveglia, A. Sega, M. Taddei, Eur. J. Org. Chem., 2005, 5277-5288.
Substituted 2-hydroxy-3-acetylfurans are synthesized by alkylation of tert-butyl acetoacetate with an α-haloketone followed by treatment of the obtained intermediate with trifluoroacetic acid (TFA). A second alkylation of the intermediate followed by treatment with trifluoroacetic acid provides access to disubstituted 2-methylfurans.
F. Stauffer, R. Neier, Org. Lett., 2000, 2, 3535-3537.
Coupling of acetylene, nitrile, and a titanium reagent generated new azatitanacyclopentadienes in a highly regioselective manner. The subsequent reaction with sulfonylacetylene and electrophiles gave substituted pyridines virtually as a single isomer. Alternatively, the reaction of azatitanacyclopentadienes with an aldehyde or another nitrile gave furans or pyrroles having four different substituents again in a regioselective manner.
D. Suzuki, Y. Nobe, R. Tanaka, Y. Takayama, F. Sato, H. Urabe, J. Am. Chem. Soc., 2005, 127, 7474-7479.
Various di- and triarylfurans were prepared in high yields from but-2-ene-1,4-diones and but-2-yne-1,4-diones using formic acid in the presence of a catalytic amount of palladium on carbon in poly(ethylene glycol)-200 as solvent under microwave irradiation.
H. S. P. Rao, S. Jothilingam, J. Org. Chem., 2003, 68, 5392-5394.
An efficient three-component coupling reaction toward a variety of furan derivatives proceeds via a gold-catalyzed coupling reaction of phenylglyoxal derivatives, secondary amines, and terminal alkynes.
J. Li. L. Liu, D. Ding, J. Sun, Y. Ji, J. Dong, Org. Lett., 2013, 15, 2858-2861.
All isomers of (aminomethyl)furancarboxylic acids were prepared by the Delepine reaction from alkyl (halomethyl)furancarboxylates. Treatment of the initially formed quaternary salt with an ethanolic HCl solution gave the salts of the corresponding unstable amino acid esters. Hydrolysis of the crude esters yielded stable amino acid salts.
I. M. Lapina, L. M. Pevzner, A. A. Potekhin, Russ. J. Gen. Chem., 2006, 1304-1309.