Categories: C-H Bond Formation >
Dehalogenations and other reductive cleavages
Recent Literature
(Bis(dimethylamino)carbazole) was used as photocatalyst in the reduction of
unactivated aryl chlorides and alkyl chlorides in the presence of CHD as
hydrogen atom donor at room temperature. The catalytic system can also be
applied to the coupling of aryl chlorides with electron-rich arene and
heteroarenes to affect C-C bond-forming reactions.
R. Matsubara, T. Yabuta, U. M. Idros, M. Hayashi, F. Ema, Y. Kobori, K. Sakata, J. Org. Chem., 2018, 83,
9381-9390.
A combined visible light and base system initiates a radical-mediated
hydrogenation of aryl fluorides, chlorides, bromides, and iodides to the
corresponding (hetero)arenes with excellent yields under mild conditions. This
simple and efficient transition-metal-free hydrogenation tolerates various
functional groups.
T.-H. Ding, J.-P. Qu, Y.-B. Kang,
Org. Lett., 2020, 22, 3084-3088.
Visible-light irradiation enables a Ni-catalyzed photodehalogenation of a
broad scope of aryl bromides that utilizes tetrahydrofuran as hydrogen source.
The protocol obviates the need for exogeneous amine reductants or photocatalysts
and is characterized by its simplicity.
B. Higginson, J. Sanjosé-Orduna, Y. Gu, R. Martin, Synlett, 2021,
32,
1633-1636.
Nanoparticles formed from PdCl2 in the presence of
tetramethyldisiloxane (TMDS) on water enable a mild and environmentally
attractive dehalogenation of functionalized aryl halides. The reaction medium
with the catalyst can be recycled.
A. Bhattacharjya, P. Klumphu, B. H. Lipshutz, Org. Lett.,
2015,
17, 1122-1125.
A transition-metal- and catalyst-free hydrogenation of a wide range of aryl
halides is promoted by bases using either aldehydes or alcohols as hydrogen
source. One equivalent of benzaldehyde affords an equal yield as that of 0.5
equiv of benzyl alcohol. The kinetic study reveals that the initial rate of
PhCHO is nearly 4 times faster than that of BnOH. Radical trapping experiments
indicate the radical nature of this reaction.
H.-X. Zheng, X.-H. Shan, J.-P. Qu, Y.-B. Kang, Org. Lett.,
2017, 19, 5114-5117.
Exposure of (functionalized) aryl chlorides to catalytic quantities of
nickel-on-charcoal in the presence of stoichiometric amounts of Me2NH
· BH3/K2CO3 in refluxing acetonitrile leads
to high yields of the dehalogenated arenes.
B. H. Lipshutz, T. Tomioka, K. Sato, Synlett, 2001, 970-973.
Air- and moisture-stable (NHC)Pd(allyl)Cl complexes have been used in Suzuki-Miyaura cross-coupling, catalytic
dehalogenation of aryl halides, and aryl amination. A general system involving (IPr)Pd(allyl)Cl as catalyst and NaOtBu as base has
proven to be highly active for all reactions.
Microwave-assisted
processes have afforded yields similar to those of the conventionally heated
analogous reactions.
O. Navarro, H. Kaur, P. Mahjoor, S. P. Nolan, J. Org. Chem., 2004,
69, 3173-3180.
Bromo and chloro substituents serve as excellent blocking groups on aromatic
rings. The halo group can be removed by catalytic hydrogenation under neutral
conditions. As expected, bromides are reduced more quickly than chlorides and
the reaction requires the use of less catalyst. Bromides can be selectively
reduced in the presence of nitro, chloro, cyano, keto, or carboxylic acid groups.
A. Ramanathan, L. S. Jimenez, Synthesis, 2010,
217-220.
Aryl halides are reduced into the corresponding arenes in high yields, using
2-propanol as reductant and solvent, cesium carbonate as base, and di-tert-butyl
peroxide (or di-tert-butyl hyponitrite) as radical initiator. This simple
system reduces various aryl bromides and iodides through a SET mechanism with
high functional-group tolerance.
R. Ueno, T. Shimizu, E. Shirakawa,
Synlett, 2016, 27, 747-744.
A simple and efficient Ru(II)-catalyzed transfer hydro-dehalogenation using
2-propanol as the hydride source is applicable for various aromatic halides and
α-haloesters and amides. The potential synthetic application of this method was
demonstrated by efficient gram-scale transformation with catalyst loading as low
as 0.5 mol %.
T. You, Z. Wang, J. Chen, Y. Xia, J. Org. Chem.,
2017, 82, 1340-1346.
A silicon nanoarray palladium catalyst mediates a hydrogenolysis of
iodoarenes under microwave irradiation in the presence of triethanolamine as the
sacrificial reductant. The reductive deiodination proceeded under an aerobic
atmosphere affording the corresponding hydrogen-substituted arenes in high
yields. No reaction occurred in the absence of microwaves.
Y. Matsukawa, Y. M. A. Yamada, Synlett, 2022,
33,
777-780.
Nickel-on-graphite is a very inexpensive, heterogeneous catalyst for the
chemoselective reduction of aryl tosylates and mesylates. The catalyst can
be used under conventional heating conditions or microwave irradiation and
is recyclable without loss of activity.
B. H. Lipshutz, B. A. Frieman, T. Butler, V. Kogan, Angew. Chem. Int. Ed.,
2006,
45, 800-803.
An [IrCl(cod)]2/2,6-bis(benzimidazol-2'-yl)pyridine complex catalyzes
a reduction of alkyl chlorides using triethylsilane. Primary, secondary,
tertiary, and benzylic C-Cl bonds are effectively dehalogenated. The tridentate
N-ligand can be easily prepared in one step from commercially available
reagents.
T. Fukuyama, Y. Hamada, I. Ryu, Synthesis, 2021, 53,
3404-3408.
The aqueous stability of deuterated calcium/sodium hypophosphites as
nontoxic, cost-effective, and environmentally benign deuteration reagents
enables deuteration of a broad range alkyl and aryl iodides with ample isotopic
incorporation in aqueous (H2O) solution using
2,2′-azobis(2-methylpropionamidine) dihydrochloride as radical initiator.
Z. Song, J. Zeng, T. Li, X. Zhao, J. Fang, L. Meng, Q. Wan,
Org. Lett., 2020, 22, 1736-1741.
An operationally simple, tin-free reductive dehalogenation system allows the
reduction of activated C-X bonds in good yields with excellent functional-group
tolerance and chemoselectivity over aryl and vinyl C-X bonds in the presence of
the well-known visible-light-activated photoredox catalyst Ru(bpy)3Cl2
in combination with iPr2NEt and HCO2H or Hantzsch
ester as the hydrogen atom donor.
J. M. R. Narayanam, J. W. Tucker, C. R. J. Stephenson, J. Am. Chem. Soc., 2009,
131, 8756-8757.
(Me3Si)3SiH was successfully used in various radical-based
transformations in water. The system comprising substrate, silane, and initiator
(ACCN) mixed in aqueous medium at 100°C worked well for both hydrophilic and
hydrophobic substrates. In case of water-soluble water-soluble substrates, an
amphiphilic thiol was also needed.
A. Postigo, S. Kopsov, C. Ferreri, C. Chatgilialoglu, Org. Lett., 2007,
9, 5159-5162.
The In(OAc)3-catalyzed reaction of bromo- and iodoalkanes with PhSiH3
in THF at 70 C gave dehalogenated alkanes in good to high yields in the presence
of Et3B and air. 2,6-lutidine as additive enabled an efficient
reduction of simple and functionalized iodoalkanes in EtOH. GaCl3 was
found to be an effective catalyst for the reduction of haloalkanes with
poly(methylhydrosiloxane).
K. Miura, M. Tomita, Y. Yamada, A. Hosomi, J. Org. Chem., 2007,
72, 787-792.
Nanopalladium particles supported on a amphiphilic polystyrene-poly(ethylene
glycol) resin catalyzed hydrogenation of olefins and hydrodechlorination of
chloroarenes under aqueous conditions.
R. Nakao, H. Rhee, Y. Uozumi, Org. Lett., 2005,
7, 163-165.
Several ureates formed by treatment of the corresponding ureas with n-BuLi activate SmI2 to a substantial extent toward
dehalogenations of alkyl and aryl halides including substrates of low reactivity such as aryl fluorides.
C. E. McDonald, J. D. Ramsey, C. C. McAtee, J. R. Mauck, E. M. Hale, J. A.
Cumens, J. Org. Chem.,
2016, 81, 5903-5914.
The combination of HMPA and SmBr2 in THF is a powerful reductant
that is capable of reducing ketimines and alkyl chlorides at room
temperature. The structure of this reductant has not been established.
B. W. Knettle, R. A. Flowers, II, Org. Lett., 2001, 3,
2321-2324.
A highly efficient and catalytic organotin reagent on soluble support has
been developed for free radical reactions. A variety of alkyl
halides (1°, 2°, 3°, aryl) underwent radical reductions in good isolated yields using only 0.01-0.2 equiv of the polymer catalyst.
E. J. Enholm, J. P. Schulte,
Org. Lett., 1999, 1, 1275-1277.
A stannane, which is simple to prepare, was successfully used in standard
radical reactions as replacement of Bu3SnH and Ph3SnH. The
tin-containing byproducts are removed by mild hydrolysis and extraction with
aqueous NaHCO3. The performance of this new reagent was tested for
reactions involving halides, selenides, Barton-McCombie deoxygenation and enyne
cyclization.
D. L. J. Clive, J. Wang, J. Org. Chem., 2002, 67, 1192-1198.
Trifluoromethyl arenes were reduced with lithium aluminum hydride to give
toluene derivatives in good yields in the presence of 5 mol % of niobium(V)
chloride. Stepwise, partial reduction of a bis(trifluoromethyl) arene was
also demonstrated.
K. Fuchibe, Y. Ohshima, K. Mitomi, T. Akiyama, Org. Lett., 2007,
9, 1497-1499.
Indium hydride generated from readily available Et3SiH and InCl3
offers mild conditions and low toxicity, and is therefore a promising
alternative to Bu3SnH.
N. Hayashi, I. Shibata, A. Baba, Org. Lett., 2004, 6,
4981-4983.
N. Hayashi, I. Shibata, A. Baba, Org. Lett., 2004, 6,
4981-4983.
A mild, convenient, fast, and nonreductive deiodination is reported for
ortho-iodo-hydroxylated arenes using pyridine, triethylamine, and N-methylmorpholine
in the presence of water. The regioselectivity is discussed.
R. S. Talekar, G. S. Chen, S.-Y. Lai, J.-W. Chern, J. Org. Chem.,
2005,
70, 8590-8593.
An easily accessible copper(I)/N-heterocyclic carbene (NHC) complex enables a
regioselective allylic reduction of allylic bromides with (TMSO)2Si(Me)H
as hydride source. The reaction provides aryl- and alkyl-substituted branched
α-olefins in good yields, which are valuable building blocks for synthesis.
T. N. T. Nguyen, N. O. Thiel, F. Pape, J. F. Teichert, Org. Lett.,
2016, 18, 2455-2458.
Zinc-promoted reduction of 2-(bromomethyl)alkenoates derived from
Baylis-Hillman adducts gave (E)-2-methylacrylates in good yield and
high stereoselectivity. Synthesis of the male ant pheromone (E)-2,4-dimethyl-2-hexenoic
acid was performed using this simple methodology.
L. Fernandes, A. J. Bortoluzzi, M. M. Sa, Tetrahedron, 2004,
60, 9983-9989.
The use of SmI2 in the reductive elimination of 1,2-acetoxy
sulfones (Julia-Lythgoe olefination) and the reductive cleavage of vinyl
sulfones is reported.
G. E. Keck, K. A. Savin, M. Weglarz, J. Org. Chem., 1995,
60, 3194-3204.
Catalyst-free debrominations and dechlorinations of aromatic α-haloketones
under visible light irradiation in the presence of Hantzsch ester provide
products in excellent yield and tolerate a broad spectrum of substrates.
Z. Lu, Y.-Q. Yang, Synthesis, 2019, 51,
508-515.
NaBH4-TMEDA as hydride source and catalytic PdCl2(dppf) in
THF is an efficient system for the hydrodehalogenation of
bromo(chloro)-heteropentalenes with one or two heteroatoms, while Pd(OAc)2/PPh3
is able to reduce reactive haloheteropentalenes, and PdCl2(tbpf)
allows the removal of the 2-chlorine from a thiophene ring. The reaction
conditions tolerate various functional groups and allow highly chemo- and
regioselective reactions.
G. Chelucci, S. Baldino, A. Ruiu, J. Org. Chem., 2012,
77, 9921-9925.
Treatment of o-bromonitrobenzenes with various vinyl Grignard reagents
gives 7-bromoindoles in good yields, using the o-bromine atom to direct
the cyclization. A subsequent reduction using a heteroaryl radical methodology
gives 7-unsubstituted indoles in nearly quantitative yields.
A. Dobbs, J. Org. Chem., 2001, 66, 638-641.