Categories: Synthesis of O-Heterocycles, C-O Bond Formation, Synthesis of cyclic ethers >
Synthesis of tetrahydrofurans
Recent Literature
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.
An enantioselective C(sp3)-H functionalization of undirected
oxacycles via photo-HAT/nickel dual catalysis enables the rapid construction of
enantiomerically enriched oxacycles directly from simple and abundant
hydrocarbon feedstocks. The synthetic utility is demonstrated in the late-stage
functionalization of natural products and the synthesis of pharmaceutically
relevant molecules.
S. Xu, Y. Ping, W. Li, H. Guo, Y. Su, Z. Li, M. Wang, W. Kong, J. Am. Chem. Soc.,
2023, 145, 5231-5241.
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.
An operationally simple and efficient strategy for the synthesis of
substituted tetrahydrofurans from readily available cis-butene-1,4-diol
is based on a redox-relay Heck reaction, that generates cyclic hemiacetals. A
subsequent reduction provides the corresponding 3-aryl tetrahydrofurans.
Furthermore, the hemiacetals can also serve as precursors to a range of
disubstituted tetrahydrofurans.
T. J. M. Byrne, M. E. Mylrea, J. D. Cuthbertson, Org. Lett., 2023, 25,
2361-2365.
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.
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 |