Synthesis of tetrahydrofurans
The synergy between nickel catalysts and simple, cheap and modular diaryl ketones enables a photochemical C-C bond-formation via sp3 C-H functionalization of alkane feedstocks.
Y. Shen, Y. Gu, R. Martin, J. Am. Chem. Soc., 2018, 140, 12200-12209.
In a Ni-catalyzed photoredox reaction, aryl chlorides serve as both cross-coupling partners and the chlorine radical source for the α-oxy C(sp3)-H arylation of cyclic and acyclic ethers. Photolysis of a Ni(III) aryl chloride intermediate, generated by photoredox-mediated single-electron oxidation, leads to elimination of a chlorine radical.
B. J. Shields, A. G. Doyle, J. Am. Chem. Soc., 2016, 138, 12719-12722.
The use of Et3SiH and a catalytic amount of I2 enables transition-metal-free, intramolecular hydroalkoxylation/reduction and hydroamination/reduction of unactivated alkynes at room temperature to provide 2,4- and 2,5-disubstituted pyrrolidines as well as a 2,3-disubstituted tetrahydrofurans with high diastereoselectivity.
S. Fujita, M. Shibuya, Y. Yamamoto, Synthesis, 2017, 49, 4199-4204.
The regioselectivity of the intramolecular cyclization of bifunctional α-phenyl alkenes can be controlled simply by the choice of the organic chromophore as the photocatalyst. Whereas N,N-(4-diisobutylaminophenyl)phenothiazine catalyzes exo-trig cyclizations, 1,7-dicyanoperylene-3,4,9,10-tetracarboxylic acid bisimides catalyze endo-trig additions.
. Weick, D. Steuernagel, A. Belov, H.-A. Wagenknecht, Synlett, 2022, 33, 1199-1203.
(terpy)NiBr2 catalyzes a regioselectively difunctionalisation of unactivated olefins with tethered alkyl halides and arylzinc reagents to provide (arylmethyl)carbo- and heterocyclic scaffolds. The reaction shows an excellent functional group tolerance (such as ketones, esters, nitriles, halides, and base-sensitive racemizable stereocenters).
S. KC, P. Basnet, S. Thapa, B. Shrestha, R. Giri, J. Org. Chem., 2018, 83, 2920-2936.
The platinum-catalyzed hydroalkoxylation of γ- and δ-hydroxy olefins tolerated various substitution patterns and a number of functional groups including pivaloate and acetate esters, amides, silyl and benzyl ethers, and pendant hydroxyl and olefinic groups.
H. Qian, X. Han, R. A. Widenhoefer, J. Am. Chem. Soc., 2004, 126, 9536-9537.
The reaction of tertiary 1,4- and 1,5-diols with cerium ammonium nitrate at room temperature gives tetrahydrofuran and tetrahydropyran derivatives in high yield and stereoselectivity. Various fragrant compounds have been synthesized using this method.
E. J. Alvarez-Manzaneda, R. Chabouna, E. Alvarez, E. Cabrera, R. Alvarez-Manzaneda, A. Haidour, J. M. Ramos, Synlett, 2006, 1756-1758.
A mild, general, and functional group tolerant intramolecular hydroalkoxylation and hydroacyloxylation of unactivated olefins using a Co(salen) complex, an N-fluoropyridinium salt, and a disiloxane reagent at room temperature provides five- and six-membered cyclic ethers and lactones. The powerful Co catalyst system also enables the deprotective hydroalkoxylation of O-protected alkenyl alcohol and hydroacyloxylation of alkenyl esters.
H. Shigehisa, M. Hayashi, H. Ohkawa, T. Suzuki, H. Okayasu, M. Mukai, A. Yamazaki, R. Kawai, H. Kikuchi, Y. Satoh, A. Fukuyama, K. Hiroya, J. Am. Chem. Soc., 2016, 138, 10084-10087.
Silver(I) triflate catalyzes intramolecular additions of hydroxyl or carboxyl groups to olefins in good to excellent yields for a range of substrates under relatively mild conditions. This reaction is one of the simplest methods to construct cyclic ethers or lactones.
C.-G. Yang, N. W. Reich, Z. Shi, C. He, Org. Lett., 2005, 7, 4553-4556.
Lanthanide triflates are efficient catalysts for the intramolecular Markovnikov-type hydroalkoxylation/cyclization of primary/secondary and aliphatic/aromatic hydroxyalkenes in room temperature ionic liquids (RTILs) to give five- and six-membered oxygen heterocycles in very good yields.
A. Dzudza, T. J. Marks, Org. Lett., 2009, 11, 1523-1526.
A Cu(I)-Xantphos system catalyzed the intramolecular hydroalkoxylation of unactivated terminal alkenes, providing five- and six-membered cyclic ethers. A possible reaction pathway involves an addition of a Cu-O bond across the C-C double bond. The use of (R)-DTBM-SEGPHOS as ligand enabled an enantioselective reaction with moderate enantioselectivity.
H. Murayama, K. Nagao, H. Ohmiya, M. Sawamura, Org. Lett., 2015, 17, 2039-2041.
A new, stereoselective, palladium-catalyzed method for the synthesis of substituted tetrahydrofurans from γ-hydroxy alkenes and aryl bromides forms both a C-C and a C-O bond with diastereoselectivities of up to >20:1. The reactions probably proceed via the intramolecular insertion of an olefin into a Pd(Ar)(OR) intermediate.
J. P. Wolfe, M. A. Rossi, J. Am. Chem. Soc., 2004, 126, 1620-1621.
Homogeneous carboamination, carboalkoxylation and carbolactonization of terminal alkenes are realized via oxidative gold catalysis, providing expedient access to various substituted N- or O-heterocycles. Deuterium-labeling studies established the nature of the alkene functionalization and the indispensible role of Au(I)/Au(III) catalysis.
G. Zhang, L. Cui, Y. Wang, L. Zhang, J. Am. Chem. Soc., 2010, 132, 1474-1475.
Nucleophilic ring expansions of enantiomeric 2-mono- and 2,2-disubstituted epoxides and oxetanes with dimethylsulfoxonium methylide is a convenient general approach for a high-yielding preparation of optically active four- and five-membered cyclic ethers from oxiranes.
E. D. Butova, A. V. Barabash, A. A. Petrova, C. M. Kleiner, P. R. Schreiner, A. A. Fokin, J. Org. Chem., 2010, 75, 6229-6235.
The S0 → Tn transition of benzophenone promotes C(sp3)-H alkynylations of ethers and amides with hypervalent iodine reagents under mild conditions. The selective benzophenone excitation prevents the decomposition of the alkynylating reagent.
K. Matsumoto, M. Nakajima, T. Nemoto, J. Org. Chem., 2020, 85, 11802-11811.
Electrophilic bromination or fluorination of homoallylic alcohol O-Bn ethers triggers a diastereoselective hydride transfer to provide diastereomerically enriched haloalkyl alcohols. A subsequent intramolecular nucleophilic substitution affords tetrahydrofurans.
B. Wang, D. A. Gandamana, D. F. L. Rayo, F. Gagosz, S. Chiba, Org. Lett., 2019, 21, 9179-9182.
The synergistic merger of photoredox and nickel catalysis enables a decarboxylative cross-coupling of alkyl carboxylic acids with vinyl halides. Various α-oxy and α-amino acids, as well as simple hydrocarbon-substituted acids and a broad range of vinyl iodides and bromides can be converted to vinylation products in high efficiency under mild, operationally simple reaction conditions.
A. Noble, S. J. McCarver, D. W. C. MacMillan, J. Am. Chem. Soc., 2015, 137, 624-627.
Organoselenium catalysis enables an efficient synthesis of oxygen and nitrogen heterocycles via exo-cyclization under mild conditions in the presence of 1-fluoropyridinium triflate. The reaction offers good functional group tolerance and excellent regioselectivity.
R. Guo, J. Huang, H. Huang, X. Zhao, Org. Lett., 2016, 18, 504-507.
The steric and electronic drivers of 5-exo and 6-endo regioselectivity in platinum-catalyzed intramolecular hydroalkoxylation are elucidated. The main influence arises from an electronic effect, where the alkyne substituent induces a polarization of the alkyne that leads to preferential heteroatom attack at the more electron-deficient carbon.
J. P. Costello, E. M. Ferreira, Org. Lett., 2019, 21, 9934-9939.
A second-generation, water-soluble cobalt catalyst for the formation of trans-THF products via the Mukaiyama aerobic oxidative cyclization gives superior yields and enables greatly simplified purification compared to the previous catalysts. Quarternization of the amino group of the ligand with MeI allows a simple, neutral water extraction.
C. Palmer, N. A. Morra, A. C. Stevens, B. Bajtos, B. P. Machin, B. L. Pagenkopf, Org. Lett., 2009, 11, 5614-5617.
A mild and convenient free-radical cyclization of organohalides in the presence of a NiCl2 • DME/Pybox complex as the catalyst and zinc powder in methanol efficiently gives carbo-, oxa-, and azacycles as products in high yields from unsaturated alkyl halides.
H. Kim, C. Lee, Org. Lett., 2011, 13, 2050-2053.
A nitrite-catalyzed ring contraction reaction of substituted tetrahydropyrans provides 2-acyltetrahydrofurans in good yields via a dehydrogenative dual functionalization under aerobic conditions. On the other hand, the oxidation reaction of 1-substituted isochromans occurred via a bromohydroxylation to give 1-(dibromoalkyl)-1-hydroxyisochromans in high yields.
K. Watanabe, T. Hamada, K. Moriyama, Org. Lett., 2018, 20, 5803-5807.
Cinchona-alkaloid-thiourea-based bifunctional organocatalysts enable a straightforward asymmetric cycloetherification of ε-hydroxy-α,β-unsaturated ketones for the synthesis of tetrahydrofuran rings. This catalytic process represents a highly practical cycloetherification method that provides excellent enantioselectivities, even with low catalyst loadings at ambient temperature.
K. Asano, S. Matsubara, J. Am. Chem. Soc., 2011, 133, 16711-16713.
The use of a cation-binding oligoEG catalyst and KF as the base enables a highly enantioselective cycloetherification for the straightforward synthesis of enantioenriched tetrahydrofurans, tetrahydropyrans, and oxepanes from ε-, ζ-, and η-hydroxy-α,β-unsaturated ketones.
A. P. Jadhav, J.-A Oh, I.-S. Hwang, H. Yan, C. E. Song, Org. Lett., 2018, 20, 5319-5322.
Substituted carbocycles, tetrahydrofurans, and tetrahydropyrans can be efficiently obtained from unsaturated carboxylic acids. The methodology involves a Kolbe decarboxylation followed by an intramolecular radical cyclization and a radicalradical cross-coupling process.
F. Lebreux, F. Buzzo, I. E. Markó, Synlett, 2008, 2815-2820.
C(sp3)-H dehydrogenative cross-couplings of ethers, tetrahydrothiophenes, and pyrrolidines with alcohols were achieved under visible light irradiation by using iodobenzene and an in situ-formed gold complex. This method offers broad functional group compatibility and was successfully applied in late-stage modifications of bioactive molecules.
X. Si, L. Zhang, Z. Wu, M. Rudolph, A. M. Asiri, A. S. K. Hashmi, Org. Lett., 2020, 22, 5844-5849.
An iron-catalyzed α-C(sp3)-H activation of cyclic and acyclic ethers provides an efficient and green method for the synthesis of mixed acetals in very good yields. The robustness of this protocol is demonstrated by the late-stage oxidation of a structurally complex natural product.
W. Han, L. Cheng, H. Zhao, Synlett, 2020, 31, 1400-1403.
The Au(I)-catalyzed intramolecular hydroamination of N-allenyl carbamates was effective for the formation of various cyclic amines. γ-Hydroxy and δ-hydroxy allenes underwent Au-catalyzed intramolecular hydroalkoxylation to form the corresponding oxygen heterocycles in good yield. 2-Allenyl indoles underwent Au-catalyzed intramolecular hydroarylation to form 4-vinyl tetrahydrocarbazoles in good yield.
Z. Zhang, C. Liu, R. E. Kinder, X. Han, H. Qian, R. A. Widenhoefer, J. Am. Chem. Soc., 2006, 128, 9066-9073.
A new methodology for the cycloisomerization of dienes using a Grubbs carbene complex and trimethylsilyl vinyl ether has been established. The utility of this reaction was demonstrated by in the synthesis of exo-methylene heterocyclic compounds, which could act as key intermediates for pharmacologically active compounds.
Y. Terada, M. Arisawa, A. Nishida, Angew. Chem. Int. Ed., 2004, 43, 4063-4067.
A Rh-catalyzed enyne cycloisomerization provides 1,4-dienes with unique reactivity and selectivity compared to other late transition metal- and Ti-catalyzed processes.
P. Cao, B. Wang, X. Zhang, J. Am. Chem. Soc., 2000, 122, 6490-6491.
FeCl2 and an iminopyridine ligand form in the presence of diethylzinc and magnesium bromide etherate an active catalyst for the reductive cyclization of N- and O-tethered 1,6-enynes to give pyrrolidine and tetrahydrofuran derivatives.
A. Lin, Z.-W. Zhang, J. Yang, Org. Lett., 2014, 16, 386-389.
Tuning the reactivity of arylpalladium intermediates enables 5-exo and 6-endo cyclizations of alkynols. These palladium-catalyzed reactions offer a divergent synthesis of oxygen-containing heterocycles, which are of synthetic use for further derivatization. Formal synthesis of an hNK-1 receptor antagonist also showcases the utility this arylative cyclization.
D. Fujino, H. Yorimitsu, A. Osuka, J. Am. Chem. Soc., 2014, 136, 6255-6258.
Several Pd-catalyzed oxidative cyclizations proceed in excellent yield under simple aerobic conditions. Importantly, this system provided entry into enatioselective catalysis with a readily available Pd-sparteine complex.
R. M. Trend, Y. K. Ramtohul, E. M. Ferreira, B. Stoltz, Angew. Chem. Int. Ed., 2003, 42, 2892-2895.
The use of a two-step coupling-elimination procedure allows successful Julia olefination of sugar-derived lactones to provide exomethylene sugars.
D. Gueyrard, R. Haddoub, A. Salem, N. S. Bacar, P. G. Goekjian, Synlett, 2006, 17, 520-522.
Sulfuryl chloride as chlorinating agent enables an efficient, mild and catalyst-free synthesis of β-chlorotetrahydrofuran derivatives by 5-endo chlorocycloetherification of homoallylic alcohols. A variety of homoallylic alcohols with aryl or alkyl substituents were smoothly converted into β-chlorotetrahydrofurans in very good yields.
X. Zeng, C. Miao, S. Wang, C. Xia, W. Sun, Synthesis, 2013, 45, 2391-2396.
Oxidative bromination of different types of olefins using Selectfluor/KBr afforded addition, monobromo-substituted, or Hunsdiecker-Borodin reaction products in good yields.
C. Ye, J. M. Shreeve, J. Org. Chem., 2004, 69, 8561-8563.
Palladium-catalyzed inter- and intramolecular enyne coupling reactions were developed. The reaction involves the acetoxypalladation of the alkyne, followed by the insertion of the alkene and the protonolysis of the carbon-palladium bond. The coupling allows the construction of synthetically important carbo- and heterocycles.
L. Zhao, X. Lu, W. Xu, J. Org. Chem., 2005, 70, 4059-4063.
Exo-3-furanylidenes and 3-pyranylidenes products having cis-2,5 and cis-2,6 substitution were synthesized from terminally substituted alkynyl alcohols with various aldehydes via Prins-type cyclization and trapping of the resulting vinyl cations as vinyl triflates in good yields. Vinyl triflates underwent a subsequent stereoselective hydrolysis to give the corresponding 3-acyl-substituted products.
S. N. Chavre, H. Choo, J. K. Lee, A. N. Pae, Y. Kim, Y. S. Cho, J. Org. Chem., 2008, 73, 7467-7471.
A concise, stereoselective synthesis of functionalized tetrahydrofuranols involves heating of readily available chloropolyols in water. These reactions are operationally straightforward and chemoselective for the formation of tetrahydrofurans, obviating the need for complicated protecting group strategies. A short asymmetric synthesis of the natural product (+)-goniothalesdiol is demonstrated.
B. Kang, S. Chang, S. Decker, R. Britton, Org. Lett., 2010, 12, 1716-1719.
A diastereoselective synthesis of pentasubstituted tetrahydrofurans via a (3 + 2)-annulation of quaternary donor site cyclopropanes and aldehydes is catalyzed by Sn(OTf)2, SnCl4, or Hf(OTf)4 in yields up to 95% and diastereomeric ratios as high as 99:1.
A. G. Smith, M. C. Slade, J. S. Johnson, Org. Lett., 2011, 13, 1996-1999.
An intramolecular iodo-aldol cyclization of prochiral α-substituted enoate aldehydes and ketones produces hetero- and carbocycles containing quaternary centers adjacent to secondary or tertiary centers. The reactions occur in good yields and are highly trans-selective with hydroxyl and iodomethyl groups on opposite faces of the ring system.
F. Douelle, A. S. Capes, M. F. Greaney, Org. Lett., 2007, 9, 1931-1934.
Treatment of 1,2-O-isopropylidenefuranose derivatives with triethylsilane/boron trifluoride etherate provides tetrahydrofurans. The removal of the 1,2-O-isopropylidene group is accompanied by deoxygenation at the anomeric position. This process is compatible with several hydroxyl protecting groups.
G. J. Ewing, M. J. Robins, Org. Lett., 1999, 1, 635-636.
A mild organophotoredox protocol enables the formation of Csp3-S/Se bonds by reacting redox-active esters with thio/selenosulfonates. The reaction offers an unprecedented broad substrate scope and wide functional group tolerance.
Y. Dong, P. Ji, Y. Zhang, C. Wang, X. Meng, W. Wang, Org. Lett., 2020, 22, 9562-9567.
A nucleophilic substitution of alkyl fluorides was achieved in intramolecular reactions with O- and N-nucleophiles. The reaction is influenced by the nature of nucleophiles, the size of the ring to be formed, and the comformational rigidity of the precursors.
L. Zhang, W. Zhang, J. Liu, J. Hu, J. Org. Chem., 2009, 74, 2850-2853.
Catalytic hydrogenation of acetylenic aldehydes using a chirally modified cationic rhodium catalysts enables highly enantioselective reductive cyclization to afford cyclic allylic alcohols. Using an achiral hydrogenation catalyst, some chiral racemic acetylenic aldehydes engage in highly syn-diastereoselective reductive cyclizations.
J. U. Rhee, M. J. Krische, J. Am. Chem. Soc., 2006, 128, 10674-10675.
Treatment of 3-[(alkoxycarbonyl)alkyl]-substituted conjugated cycloalkenones with diisobutylaluminum hydride at -78 °C followed by acid quenching furnishes spiro ethers, whereas the corresponding 3-(carboxyalkyl)-substituted cycloalkenones generate spiro lactones upon reaction with sodium borohydride at 30 °C followed by acid quenching.
M.-C. P. Yeh, Y.-C. Lee, T.-C. Young, Synthesis, 2006, 3621-3624.
Allenylidene-ruthenium complexes on protonation with HOTf are rearranged to indenylidene-ruthenium complexes, which are efficient catalyst precursors for ring-opening metathesis polymerization, ring-closing metathesis and enyne metathesis of a variety of substrates.
R. Castarlenas, C. Vovard, C. Fischmeister, P. H. Dixneuf, J. Am. Chem. Soc., 2006, 128, 4079-4089.
A chiral iridium diphosphine complex catalyzes an enantioselective intramolecular Pauson-Khand-type reaction to give various chiral bicyclic cyclopentenones. A low partial pressure of carbon monoxide is important to achieve excellent enantioselectivity.
T. Shibata, N. Toshida, M. Yamasaki, S. Maekawa, K. Takagi, Tetrahedron, 2005, 61, 9974-9979.
An entrapped Rh catalyst derived by a sol-gel process (see article for method), has been used in a Pauson-Khand reaction under mild conditions. The catalyst can be reused at least 10 times without losing activity. This catalytic system is not effective for intermolecular reactions.
K. H. Park, S. U. Song, Y. K. Chung, Tetrahedron Lett., 2003, 44, 2827-2830.
A new Pd-catalyzed oxidation reaction for the stereospecific conversion of enynes into cyclopropyl ketones proceeds with net inversion of geometry with respect to the starting olefin. This result is consistent with a mechanism in which the key cyclopropane-forming step involves nucleophilic attack of a tethered olefin onto the PdIV-C bond.
L. L. Welbes, T. W. Lyons, K. A. Cychosz, M. S. Sanford, J. Am. Chem. Soc., 2007, 129, 5836-5837.
The reaction of various 1,6-enynes with N2CHSiMe3 in the presence of RuCl(COD)Cp* as catalyst precursor leads to the general formation of alkenylbicyclo[3.1.0]hexanes at room temperature in good yield with high stereoselectivity. The catalytic formation of alkenylbicyclo[3.1.0]hexanes also takes place in the presence of N2CHCO2Et or N2CHPh.
F. Monnier, C. Vovard-Le Bray, D. Castillo, V. Aubert, S. Dérien, P. H. Dixneuf, L. Toupet, A. Ienco, C. Mealli, J. Am. Chem. Soc., 2007, 129, 6037-6049.
A mild, complete hydrogenation of aromatic rings catalyzed by heterogeneous 10% Rh/C proceeds at 80 °C in water under 5 atm of H2 pressure and is applicable to the hydrogenation of various carbon and heteroaromatic compounds such as alkylbenzenes, biphenyls, pyridines and furans.
Maegawa, A. Akashi, H. Sajiki, Synlett, 2006, 1440-1442.
Diastereoselective and Enantioselective Construction of Cyclic Ethers
Stereocontrolled Construction of Cyclic Ethers
Enantioselective Construction of Naturally-Occurring Cyclic Ethers