Zinc
Name Reactions
Recent Literature
A reductive coupling of a vinyl-substituted aromatic or heteroaromatic and an
alkyl bromide or iodide occurs in an aqueous micellar medium in the presence of
Zn and a catalytic amount of an Fe(II) salt at rt. The new C-C bond is
regiospecifically formed at rt at the β-site of the alkene via a radical process.
H. Pang, Y. Wang, F. Gallou, B. H. Lipshutz, J. Am. Chem. Soc.,
2019, 141, 17117-17124.
A nonionic amphiphile (PTS) enables a simple approach to Pd-catalyzed stereoselective sp3-sp2
cross-couplings between alkyl and alkenyl bromides in the presence of zinc
powder in water to give coupled products in good yields without prior formation
of the organozinc reagents. The reaction is conducted at room temperature and
tolerates various functional groups.
A. Krasovskiy, C. Duplais, B. H. Lipshutz, Org. Lett., 2010,
12, 4742-4744.
A direct dehydroxylative radical alkylation reaction of tertiary alcohols with
activated alkenes enables a facile and precise construction of all-carbon
quaternary centers. The reaction tolerates a wide range of electrophilic
coupling partners, including allylic carboxylates, aryl and vinyl electrophiles,
and primary alkyl chlorides/bromides and leaves secondary/primary alcohols and
phenols intact.
H. Xie, J. Guo, Y.-G. Wang, K. Wang, P. Guo, P.-F. Su, X. Wang, X.-Z. Shu, J. Am. Chem. Soc.,
2020, 142, 16787-16794.
Zn-Mediated, Pd-Catalyzed Cross-Couplings in Water at Room Temperature
Without Prior Formation of Organozinc Reagents
A. Krasovskiy, C. Duplais, B. H. Lipshutz, J. Am. Chem. Soc., 2009,
131, 15592-15593.
Ball-milling enables a nickel-catalyzed cross-electrophile coupling of aryl
halides and alkyl halides. Under a mechanochemical manifold, the reductive C-C
bond formation was achieved in the absence of bulk solvent and air/moisture
sensitive setups, in reaction times of 2 h. The mechanical action provided by
ball milling permits the use of a range of zinc sources to turnover the nickel
catalytic cycle.
A. C. Jones, W. I. Nicholson, J. A. Leitch, D. L. Browne, Org. Lett., 2021, 23, 6337-6341.
In the presence of a Ni catalyst and Zn, various aryl and vinyl bromides are
reductively coupled with alkyl bromides in high yields. Under similar conditions,
activated aryl chlorides can also be coupled with bromoalkanes. The protocols
are highly functional-group tolerant, and the reactions are assembled on the
benchtop with no special precautions to exclude air or moisture.
D. A. Everson, B. A. Jones, D. J. Weix, J. Am. Chem. Soc., 2012,
134, 6146-6159.
5-Cyanoimidazole was identified as an inexpensive ligand for nickel-catalyzed
cross-electrophile couplings for the preparation of various alkylated arene
products with good yields. Furthermore, the scope of reductive couplings could
be expanded to challenging substrates, such as sterically hindered neopentyl
halides.
S. Biswas, B. Qu, J.-N. Desrosiers, Y. Choi, N. Haddad, N. K. Yee, J. J.
Song, C. H. Senanayake, J. Org. Chem., 2020, 85,
8214-8220.
A room-temperature Ni-catalyzed reductive coupling of aryl bromides with
secondary alkyl bromides provides products in good to excellent yields. Slight
modification of this protocol allows efficient coupling of activated aryl
chlorides with cyclohexyl bromide and aryl bromides with allylic acetate.
S. Wang, Q. Qian, H. Gong, Org. Lett., 2012,
14, 3352-3355.
Electroreduction of aryl halides in an electrochemical cell fitted with a
sacrificial zinc anode in the presence of cobalt halide and pyridine as ligand
in DMF or acetonitrile as solvent provides the corresponding organozinc species
in good yields. The reaction solution can be used directly in a subsequent
Pd-catalyzed Negishi coupling with aryl iodides at 60°C.
C. Gosmini, Y. Rollin, J. Y. Nédélec, J. Périchon, J. Org. Chem., 2000,
65, 6024-6026.
In a decarboxylative coupling of alkyl N-hydroxyphthalimide esters with
aryl iodides in the presence of a nickel catalyst and Zn as reducing agent, no
photocatalyst, light, or arylmetal reagent is needed to form alkyl radicals from
the carboxylic acid derivative. Methyl, primary, and secondary alkyl groups can
all be coupled in good yield.
K. M. M. Huihui, J. A. Caputo, Z. Melchor, A. M. Olivares, A. M. Spiewak, K. A.
Johnson, T. A. DiBenedetto, S. Kim, L. K. G. Ackerman, D. J. Weix, J. Am. Chem. Soc., 2016,
138, 5016-5019.
A nickel-catalyzed reductive cross-coupling between industrial chemical CF3CH2Cl
and (hetero)aryl bromides and chlorides is synthetically simple, avoids the
preparation of arylmetals, and exhibits high functional group tolerance.
X. Li, X. Gao, C.-Y. He, X. Zhang, Org. Lett., 2021, 23,
1400-1405.
The selectivity challenge associated with cross-coupling of aryl chlorides as
inert electrophiles with aryl triflates as reactive ones is overcome using a
multimetallic strategy with the appropriate choice of additive. LiCl is
essential for effective cross-coupling by accelerating the reduction of Ni(II)
to Ni(0) and counteracting autoinhibition of reduction at Zn(0) by Zn(II) salts.
L. Huang, L. K. G. Ackerman, K. Kang, A. M. Parsons, D. J. Weix, J. Am. Chem. Soc.,
2019,
141, 10978-10983.
The combination of a Ni and Pd complex with Zn as reductant and LiBr as an
additive catalyzed a direct cross-coupling of two different sulfonate esters.
Whereas Pd strongly prefers the aryl triflate, the Ni catalyst has a small
preference for the aryl tosylate, aryl transfer between catalysts is mediated by
Zn, and Pd improves yields by consuming arylzinc intermediates.
K. Kang, L. Huang, D. J. Weix, J. Am. Chem. Soc.,
2020, 142, 10634-10640.
Nickel catalysis accomplishes a decarboxylative cross-coupling of aliphatic
acid anhydrides with vinyl triflates or halides. This methodology works well
with a broad array of substrates and features abundant functional group
tolerance.
H. Chen, S. Sun, X. Liao,
Org. Lett., 2019, 21, 3625-3630.
An efficient Fe-catalyzed cross-electrophile coupling of
vinyl halides with tertiary alkyl methyl oxalates provides vinylated carbon quaternary centers
with
excellent functional group tolerance and broad substrate scope. A
cascade radical cyclization and vinylation affords complex bicyclic and spiral
structural motifs.
Y. Ye, H. Chen, K. Yao, H. Gong,
Org. Lett., 2020, 22, 2070-2075.
Iron catalyzes a cross-coupling of 1-bromoalkynes with terminal alkynes to
generate unsymmetrical 1,3-butadiynes in water under air. Reactions of
1-bromoalkynes derived from less acidic terminal alkynes with more acidic
counterparts offer greatly enhanced yields and selectivity. A coupling of
1-bromoalkynes and trimethylsilyl-protected 1,3-butadiynes provides
1,3,5-hexatriynes.
Y.-A. Liao, W.-S. Peng, L.-J. Liu, T.-Y. Ye, J.-H. Fu, Y.-T. Chan, F.-Y. Tsai, J. Org. Chem., 2022, 87,
13698-13707.
A nickel-catalyzed reductive coupling of redox-active esters with aliphatic
aldehydes using zinc metal as the reducing agent provides silyl-protected
secondary alcohols. This protocol is operationally simple, proceeds under mild
conditions, and tolerates a variety of functional groups.
J. Xiao, Z. Li, J. Montgomery, J. Am. Chem. Soc.,
2021, 143, 21234-21240.
A ball-milling-enabled zinc-mediated Barbier-type allylation of a broad range
of carbonyl compounds is operationally simple and does not require inert
atmospheres or dry solvents. The reaction is applicable across a range of
different zinc metal morphologies.
J. Yin, R. T. Stark, I. A. Fallis, D. L. Browne, J. Org. Chem., 2020, 85,
2347-2354.
A Ti-catalyzed direct dehydroxylation of tertiary aliphatic alcohols under
mild reaction conditions tolerates a wide range of functional groups, including
primary alkyl chloride and carbonyl groups. It allows for selective
dehydroxylation of tertiary alcohols in diols and the formation of deuterated
products with moderate deuterium incorporation.
Q. Lin, W. Tong, X.-Z. Shu, Y. Chen, Org. Lett., 2022, 24,
8459-8464
A nickel-catalyzed reductive cross-coupling reaction of aryl cyclopropyl
ketones with easily accessible unactivated alkyl bromides provides
γ-alkyl-substituted ketones. Initial mechanistic studies revealed that the
reaction proceeds via radical cleavage of the alkyl bromide.
N. Cui, T. Lin, Y.-E. Wang, J. Wu, Y. Han, X. Xu, F. Xue, D. Xiong, P. J.
Walsh, J. Mao, Org. Lett.,
2022, 24, 3987-3992.
Sulfonimines derived from nonenolizable aldehydes can be effectively allylated to the corresponding homoallylic
sulfonamides with allylic bromides promoted by indium or zinc. The
stereoselectivity and regioselectivity of the reactions were examined.
W. Lu, T. H. Chan, J. Org. Chem., 2000,
65, 8589-8594.
A Ni-catalyzed reductive allylation of α-chloroboronates with allyl sulfones
efficiently provides the corresponding homoallylic boronates, which could be
readily converted into valuable homoallylic alcohols or amines or
1,4-diboronates. This reaction features a broad substrate scope with good
functional group compatibility.
Y. Lou, J. Qiu, K. Yang, F. Zhang, C. Wang, Q. Song, Org. Lett., 2021, 23,
4564-4569.
A nickel-catalyzed three-component reductive alkylacylation of
electron-deficient activated alkenes with acid anhydrides and tertiary alkyl
bromides enables the efficient preparation of a variety of ketones with
broad substrate scope and high functionality tolerance starting from simple
precursors.
L. Wang, C. Wang,
Org. Lett., 2020, 22, 8829-8835.
A mild nickel-catalyzed reductive cross-coupling between (hetero)aryl
bromides and vinyl acetate provides a variety of vinyl arenes, heteroarenes, and
benzoheterocycles. Importantly, dimethyl isosorbide as solvent makes this
protocol more sustainable.
M. Su, X. Huang, C. Lei, J. Jin, Org. Lett., 2022, 24,
354-358.
A mild and efficient zinc-mediated decarboxylative alkylation of gem-difluoroalkenes
with N-hydroxyphthalimide (NHP) esters provides Z-monofluoroalkenes
in good yields. The reaction tolerates a broad range of functional groups and
can be easily scaled up.
L. Yu, M.-L. Tang, C.-M. Si, Z. Meng, Y. Liang, J. Han, X. Sun, Org. Lett.,
2018, 20, 4579-4583.
A room-temperature Ni-catalyzed reductive coupling of aryl bromides with
secondary alkyl bromides provides products in good to excellent yields. Slight
modification of this protocol allows efficient coupling of activated aryl
chlorides with cyclohexyl bromide and aryl bromides with allylic acetate.
S. Wang, Q. Qian, H. Gong, Org. Lett., 2012,
14, 3352-3355.
The reaction of styrylsulfonium salts with zinc powder provides zinc
reagents. Transition metals and other additives are not required for promoting
zincation. The reaction tolerates a variety of sensitive functional groups,
including esters, bromides, and boronic esters, and proceeds with complete
retention of stereochemistry.
K. Yamada, M. B. Kintzel, G. J. P. Perry, H. Saito, H. Yorimitsu, Org. Lett.,
2022, 24, 7446-7449.
The efficient olefination from organozinc reagents with aldehydes is
exploited in a new synthesis of aryl and alkyl olefins.
J.-X. Wang, Y. Fu, Y. Hu, K. Wang, Synthesis, 2003, 1506-1510.
In the presence of Co(PPh3)2I2, PPh3,
water, and zinc powder, the reductive coupling of alkynes with alkenes
having an electron-withdrawing substituent proceeded smoothly in
acetonitrile to give the corresponding reductive coupling products in fair
to excellent yields. Possible mechanisms for this highly regio- and
stereoselective ene-yne reaction are proposed.
C.-C. Wang, P.-S. Lin, C.-H. Cheng, J. Am. Chem. Soc., 2002, 124, 9696-9697.
(Ph3P)3RuCl2 is an inexpensive catalyst, that
enables a chemoselective reduction of alkyne, ketones, or nitro groups in the
presence of Zn/water as a stoichiometric reductant. Depending on the nature of
the additive and the temperature, chemoselective reduction of a nitro group in
the presence of a ketone or an alkyne was possible.
T. Schabel, C. Belger, B. Plietker, Org. Lett., 2013,
15, 2858-2861.
Ni catalysis enables a transfer hydrogenative alkyne semireduction protocol that
can be applied to both internal and terminal alkynes in the presence of formic
acid and Zn as the terminal reductants. Both (E)- and (Z)-isomers
can be accessed selectively under similar reaction conditions.
E. Richmond, J. Moran, J. Org. Chem.,
2015,
80, 6922-6929.
Ni catalysis enables a transfer hydrogenative alkyne semireduction protocol that
can be applied to both internal and terminal alkynes in the presence of formic
acid and Zn as the terminal reductants. Both (E)- and (Z)-isomers
can be accessed selectively under similar reaction conditions.
E. Richmond, J. Moran, J. Org. Chem.,
2015,
80, 6922-6929.
A method to produce 1,2-disubstituted olefins in high Z selectivity via
reductive cross-coupling of alkyl halides with terminal arylalkynes employs
inexpensive and nontoxic catalyst (iron(II) bromide) and reductant (zinc). The
substrate scope encompasses primary, secondary, and tertiary alkyl halides, and
the reaction tolerates a large number of functional groups.
C. W. Cheung, F. E. Zhurkin, X. Hu, J. Am. Chem. Soc., 2015,
137, 4932-4935.
TiIII catalysis enables a radical addition of unactivated 2° and 3°
alkyl chlorides to electron-deficient alkenes, while primary alkyl chlorides or
aryl bromides remain untouched. This method offers a new route to C-C bond
formation that is complementary to existing protocols.
X. Wu, W. Hao, K.-Y. Ye, B. Jiang, G. Pombar, Z. Song, Song Lin, J. Am. Chem. Soc.,
2018,
140, 14836-14843.
A Rh/Cu co-catalytic system enables an asymmetric reduction of aromatic
α-dehydroamino acid esters with water as the hydrogen source to provide chiral
α-amino acid esters. The reaction tolerates various functional groups and
provides access to chiral deuterated α-amino esters by using D2O.
Y. Dai, J. Chen, Z. Wang, T. Wang, L. Wang, Y. Yang, X. Qiao, B. Fan, J. Org. Chem., 2021, 86,
7141-7147.
The Zn-AcOH reductive system enables a regioselective and rapid ring-opening of
donor-acceptor cyclopropanes. 2-(Het)Arylcyclopropane-1,1-diesters as well as donor-acceptor
cyclopropanes with other types of electron-withdrawing activating groups
provides γ-substituted propyl-1,1-diesters, ketoesters,
cyanoesters, cyanoamides, dinitriles, etc., which are not readily
accessible with alternative methods.
K. L. Ivanov, E. V. Villemson, G. V. Latyshev, S. I. Bezzubov, A. G. Majouga, M.
Ya. Melnikov, E. M. Budynina, J. Org. Chem.,
2017, 82, 9537-9549.
Simple and mild indium- and zinc-mediated dehalogenation reactions of vicinal
dihalides in an aqueous solvent enable the synthesis of various allenylmethyl
aryl ethers and monosubstituted allenes in very good yields.
M.-H. Lin, W.-S. Tsai, L.-Z. Lin, S.-F. Hung, T.-H. Chuang, Y.-J. Su, J. Org. Chem., 2011,
76, 8518-8523.
A Ni-catalyzed carboxylation of benzyl halides with CO2 proceeds
under mild conditions at room temperature under atmospheric pressure. The method
does not require well-defined and sensitive organometallic reagents and thus is
user-friendly and operationally simple.
T. León, A. Correa, R. Martin, J. Am. Chem. Soc., 2013,
135, 1221-1224.
A mild Ni-catalyzed reductive coupling enables the synthesis of alkyl esters
from readily available alkyl halides and chloroformates. Unactivated primary and
secondary alkyl iodides as well as glycosyl, benzyl, and aminomethyl halides
provide products in good yields with high functional group tolerance.
M. Zheng, W. Xue, T. Xue, H. Gong, Org. Lett.,
2016, 18, 6152-6155.
A Ni-catalyzed regiodivergent reductive carboxylation of allyl esters with CO2
is mild, user-friendly, and operationally simple. The reaction is characterized
by an exquisite selectivity profile that is dictated by the ligand backbone.
T. Moragas, J. Cornella, R. Martin,
J. Am. Chem. Soc., 2014,
136, 17702-17705.
A NiCl2(DME)/dppp/Zn system catalyzed an intermolecular insertion of
aryl iodides to nitriles to provide variously substituted arylketone
derivatives in good yields with tolerance of a wide variety of functional groups.
J.-C. Hsieh, Y.-C. Chen, A.-Y. Cheng, H.-C. Tseng, Org. Lett., 2012,
14, 1282-1285.
A nickel-catalyzed reductive coupling of aryl triflates with O-tBu
S-alkyl thiocarbonates provides thioesters in good yields via a
chemoselective cleavage of the C-O bond of the thiocarbonate. This work broadens
the scope of nickel-catalyzed reductive cross-electrophile coupling reactions.
Z. Zhu, Y. Gong, W. Tong, W. Xue, H. Gong, Org. Lett., 2021, 23,
2158-2163.
A nickel-catalyzed C-C bond cleavage of thioesters with sp2-hybridized
electrophiles enables an efficient thioacylation transfer. The reaction of aryl
bromides, iodides, and alkenyl triflates with 4-(trifluoromethyl)benzothioates
provides a wide range of structurally diverse thioesters in very good yields
under mild reaction conditions.
X. Wu, J. Li, S. Xia, C. Zhu, J. Xie, J. Org. Chem., 2022, 87,
10003-10017.
Simple nickel complexes of bipyridine and PyBox catalyze the addition of aryl
halides to both aromatic and aliphatic aldehydes using zinc metal as the
reducing agent. This convenient approach tolerates acidic functional groups that
are not compatible with Grignard reactions, yet sterically hindered substrates
still couple in high yield.
K. J. Garcia, M. M. Gilbert, D. J. Weix, J. Am. Chem. Soc.,
2019,
141, 1823-1827.
A bipyridine-ligated nickel mediates the addition of functionalized aryl halides,
a vinyl halide, and a vinyl triflate to epoxides under reducing conditions. For
terminal epoxides, the regioselectivity of the reaction depends upon the
cocatalyst employed. Iodide cocatalysis results in opening at the less hindered
position via an iodohydrin intermediate. Titanocene cocatalysis results in
opening at the more hindered position.
Y. Zhao, D. J. Weix, J. Am. Chem. Soc., 2014,
136, 48-51.
Mixing an enone, zinc powder, TMEDA, and an alkyl halide in an aqueous micellar
environement containing catalytic amounts of Cu(I) and Au(III) enables conjugate
additions in water at room temperature via in situ generated organocopper
reagents in good yields. In the presence of Ag(I), the amounts of alkyl halide,
Zn, and AuCl3 can be reduced dramatically.
B. H. Lipshutz, S. Huang, W. W. Y. Leong, G. Zhong, N. A. Isley, J. Am. Chem. Soc., 2012,
134, 19985-19988.
The Reformatsky reaction enables the synthesis of medium-chain-length β-hydroxy
esters in good yield.
M. Sailer, K. I. Dumichi, J. L. Sorensen, Synthesis, 2015, 47,
79-82.
A Mannich-like zinc-mediated three-component reaction of aromatic halides,
amines, and paraformaldehyde allows the straightforward synthesis of a range of
functionalized tertiary benzylamines. This procedure involves the in situ
formation of arylzinc reagents.
E. Le Gall, A. Decompte, T. Martens, M. Troupel, Synthesis, 2010,
249-254.
A nickel-catalyzed reductive cross-coupling of cyclopropylamine NHP esters
with (hetero)aryl halides provides direct access to 1-arylcyclopropylamines, a
bioisosteric motif commonly used in small molecule drug discovery. The reaction
proceeds rapidly (<2 h) with excellent functional group tolerance. The method
can also be extended to the arylation of four-membered strained rings.
M. S. West, A. L. Gabbey, M. P. Huestis, S. A. L. Rousseaux, Org. Lett., 2022, 24,
8441-8446.
A Zn/Cu(OTf)2-mediated addition of alkyl bromides to
dehydroalanine (Dha) derivatives including dipeptides and tripeptides provides
selective and biocompatible access to various amino acid units in good to high
yields in an aqueous medium.
J.-A. Shin, J. Kim, H. Lee, S. Ha, H.-Y. Lee, J. Org. Chem., 2019, 84,
4558-4565.
A straightforward three-component reaction of preformed aromatic or in situ
generated benzylic organozinc reagents with amines and ethyl glyoxylate allows
the synthesis of a range of α-amino esters in very good yields. The procedure,
which is characterized by its simplicity, allows the concise synthesis of esters
bearing a phenylglycine or a phenylalanine scaffold.
C. Haurena, E. Le Gall, S. Sengmany, T. Martens, M. Troupel, J. Org. Chem., 2010,
75, 2645-2650.
A three-component, Ni-catalyzed reductive coupling enables a convergent
synthesis of tertiary benzhydryl amines, which are challenging to access by
traditional reductive amination methodologies. The condensation of secondary
N-trimethylsilyl amines with benzaldehydes provides iminium ions in situ,
which react with several distinct classes of organic electrophiles.
C. Heinz, J. P. Lutz, E. M. Simmons, M. M. Miller, W. R. Ewing, A. G. Doyle, J. Am. Chem. Soc., 2018,
140, 2292-2300.
A reductive cyanation of tertiary alkyl bromides using an electrophilic
cyanating reagent and zinc reductant provides various α-cyano ketones, esters,
and carboxamides containing a nitrile-bearing all-carbon quaternary center in
very good yields under mild reaction conditions.
X. Shen, G. Whang, Z. Shi, X. Tian, K. Dong, Org. Lett., 2021, 23,
2527-2532.
Indium-Catalyzed Henry-Type Reaction of Aldehydes with Bromonitroalkanes
R. G. Soengas, A. M. S. Silva, Synlett, 2012, 23,
873-876.
In acetonitrile as solvent and in the presence of a simple cobalt halide as
catalyst, the reduction by zinc dust of a mixture of aldehydes or ketones
and allylic acetates affords the corresponding homoallylic alcohols in good
yields.
P. Gomes, C. Gosmini, J. Périchon, Synthesis, 2003, 1909-1915.
A rapid and efficient procedure for the solvent-free synthesis of
homoallylic and homopropargyl alcohols has been achieved by zinc-mediated
Barbier-type reaction of carbonyl compounds at room temperature.
J.-X. Wang, X. Jia, T. Meng, L. Xin, Synthesis, 2005, 2669-2672.
J.-X. Wang, X. Jia, T. Meng, L. Xin, Synthesis, 2005, 2669-2672.
A highly α-regioselective prenylation of imines enables the conversion a wide
range of substrates including N- and C-aryl aldimines, N-alkyl
aldimines, C-alkyl aldimines, and N- and C-aryl ketimines.
The approach uses prenyl bromide as prenyl source and inexpensive zinc as
mediator as well as environmentally benign 1,3-dimethyl-2-imidazolidinone (DMI)
as solvent.
L.-M. Zhao, S.-Q. Zhang, H.-S. Jin, L.-J. Wan, F. Dou, Org. Lett., 2012,
14, 886-889.
Titanocene dichloride catalyzes the formation of an organozinc species via
catalytic activation of allyl halides. Nucleophilic addition to carbonyl
derivatives provides the desired homoallylic alcohols in very good yields in
short reaction times. This discovery will have wide ranging applicability in the
generation of highly reactive organometallic reagents.
L. M. Fleury, B. L. Ashfeld, Org. Lett., 2009,
11, 5670-5673.
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.
An efficient cobalt-catalyzed reductive coupling reaction of alkyl halides
with alkenes bearing electron-withdrawing groups in the presence of water
and zinc powder in acetonitrile gave the corresponding Michael-type addition
products in high yields. The mechanism is discussed.
P. Shukla, Y.-C. Hsu, C.-H. Cheng, J. Org. Chem., 2006, 71, 655-658.
Cobalt complex/Zn systems effectively catalyze the reductive coupling of
activated alkenes with alkynes in the presence of water to give substituted
alkenes with very high regio- and stereoselectivity in excellent yields.
H.-T. Chang, T. T. Jayanth, C.-C. Wang, C.-H. Cheng, J. Am. Chem. Soc.,
2007,
129, 12032-12041.
A Fe-catalyzed addition of alkyl radicals, formed from the corresponding alkyl
halides, to ethynyl ethynylboronic acid pinacol ester provides Z-vinyl
boronates in high stereoselectivity. The method works best for tertiary and
secondary alkyl iodides.
G. Barzanò, A. Cheseaux, X. Hu, Org. Lett., 2019, 21,
490-493.
A range of polysubstituted allylic zinc chlorides were obtained in good yield
using a LiCl-mediated zinc dust insertion in polysubstituted allylic chlorides.
A highly diastereoselective synthesis of homoallylic alcohols bearing up to two
adjacent quaternary centers by the addition of polysubstituted allylic zinc
reagents to carbonyl compounds.
H. Ren, G. Dunet, P. Mayer, P. Knochel, J. Am. Chem. Soc., 2007,
129, 5376-5377.
A dizinc reagent, which acts as an effective bidentate Lewis acid, is easily
prepared from diiodomethane and zinc powder.
K. Nomura, K. Oshima, S. Matsubara, Angew. Chem. Int. Ed., 2005,
44, 5860-5863.
Electrochemistry enables smooth Zn-mediated allylic alkylations in aqueous media
under air in the presence of a Pd catalyst between a full range of alkyl halides
(primary, secondary, and tertiary) and substituted allylic halides.
Y.-L. Lai, J.-M. Huang, Org. Lett.,
2017, 19, 2022-2025.
Efficient, simple, cheap, and environmentally benign preparations of
cyclopropanes were achieved. One method is based on a 3-exo-trig cyclisation of
various electron-deficient 2-iodoethyl-substituted olefins with zinc powder in a
mixture of t-butyl alcohol and water, and the other on a 3-exo-tet
cyclisation of various 1,3-dihalopropanes with zinc powder in ethanol.
D. Sakuma, H. Togo, Tetrahedron, 2005,
61, 10138-10145.
D. Sakuma, H. Togo, Tetrahedron, 2005,
61, 10138-10145.
A catalytic reductive cocyclooligomerization of enones and three carbene
equivalents provides cyclopentanes via a formal [2 + 1 + 1 + 1]-cycloaddition.
The reaction is promoted by a (quinox)Ni catalyst and uses CH2Cl2/Zn
as the C1 component.
C. M. Farley, Y.-Y. Zhou, N. Banka, C. Uyeda, J. Am. Chem. Soc.,
2018,
140, 12710-12714.
The CoI2(dppe)-catalyzed diastereoselective reductive [3 + 2]
cycloaddition of allenes and enones gives cyclopentanols in very good yields in
the presence of zinc, zinc iodide, and water.
H.-T. Chang, T. T. Jayanth, C.-H. Cheng, J. Am. Chem. Soc., 2007,
129, 4166-4167.
A zinc/indium chloride-mediated pinacol cross-coupling reaction between aldehyde
and α,β-unsaturated ketone in aqueous media gives 1,2-diols in good yields with
up to 93:7 diastereoselectivity.
Y.-S. Yang, Z.-L. Shen, T.-P. Loh, Org. Lett., 2009,
11, 2213-2215.
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 catalytic synthesis of cycloalkanols in the presence of N2O as
an oxygen transfer agent onto sp3-hybridized carbons of simple
precursors offers mild conditions and wide substrate scope. The reaction even
enables to access carbocyclic compounds in an enantioselective manner.
S. Ni, F. Le Vaillant, A. Mateos-Calbet, R. Martin, J. Cornella, J. Am. Chem. Soc.,
2022, 144, 18223-18228.
The use of 2-pyridyl sulfides as sulfide donors enables a synthesis of aryl
sulfides without using odorous and toxic thiols in the presence of a Ni/dcypt
catalyst capable of cleaving and forming aryl-S bonds. This aryl exchange
reaction works between 2-pyridyl sulfides and a broad range of aryl electrophiles, which include
aromatic esters, arenol derivatives, and aryl halides.
R. Isshiki, M. B. Kurosawa, K. Muto, J. Yamaguchi, J. Am. Chem. Soc.,
2021, 143, 10333-10340.
CuI-nanoparticles catalyze a selective synthesis of phenols, anilines, and
thiophenols from aryl halides in the absence of both ligands and organic
solvents. Anilines were formed selectively with ammonia competing with
hydroxylation and thiophenols were generated selectively with sulfur powder
after subsequent reduction competing with hydroxylation and amination.
H.-J. Xu, Y.-F. Liang, Z.-Y. Cai, H.-X. Qi, C.-Y. Yang, Y.-S. Feng, J. Org. Chem., 2011,
76, 2296-2300.
(Ph3P)3RuCl2 is an inexpensive catalyst, that
enables a chemoselective reduction of alkyne, ketones, or nitro groups in the
presence of Zn/water as a stoichiometric reductant. Depending on the nature of
the additive and the temperature, chemoselective reduction of a nitro group in
the presence of a ketone or an alkyne was possible.
T. Schabel, C. Belger, B. Plietker, Org. Lett., 2013,
15, 2858-2861.
A robust and green protocol for the reduction of functionalized nitroarenes to
the corresponding primary amines relies on inexpensive zinc dust in water
containing nanomicelles derived from the commercially available designer
surfactant TPGS-750-M. This mild process takes place at room temperature and
tolerates a wide range of functionalities including common protecting groups.
S. M. Kelly, B. H. Lipshutz, Org. Lett., 2014,
16, 98-101.
An efficient one-pot procedure for the zinc-mediated reduction of nitroarenes
in the presence of chloroformates leads to the corresponding N,O-bisprotected
hydroxylamines in good yield under ambient conditions in THF-water mixtures.
Solvolysis of the bisprotected hydroxylamines with sodium methoxide at room
temperature provides access to synthetically versatile N-aryl-N-hydroxy
carbamates in excellent yields.
A. Porzelle, M. D. Woodrow, N. C. O. Tomkinson, Synlett, 2009,
798-802.
The combination of zinc powder as reductant and sodium chlorate as oxidant was
used to provide an environmentally friendly, effective, and convenient method
for the synthesis of aromatic amides in good yields from nitroarenes and
aldehydes in a green solvent under atmospheric conditions. Reductants and
oxidants with opposing properties can be used together without any adverse
effects. In addition, a cooperation seems to improve the yield.
G. Sheng, X. Wu, X. Cai, W. Zhang, Synthesis, 2015, 47,
949-954.
Nickel catalyzes a highly chemoselective cleavage of sp2-hybridized
carbon-sulfur bonds of readily available aryldimethylsulfonium triflates to
produce salt-free arylzinc triflates under mild conditions. The generated
arylzinc reagents show both high reactivity and chemoselectivity in
palladium-catalyzed and copper-mediated cross-coupling reactions.
K. Yamada, T. Yanagi, H. Yorimitsu, Org. Lett., 2020, 22,
9712-9718.
A Ni-catalyzed reductive coupling enables the synthesis of
benzonitriles in good yields from aryl (pseudo)halides and 2-methyl-2-phenyl malononitrile (MPMN). MPMN is a bench-stable, carbon-bound
electrophilic CN reagent that does not release cyanide under the reaction
conditions.
L. R. Mills, J. M. Graham, P. Patel, S. A. L. Rousseaux, J. Am. Chem. Soc.,
2019, 141, 19257-19262.
Zn mediates a decarboxylative/defluorinative alkylation of α-trifluoromethyl
alkenes with N-hydroxyphthalimide esters as radical precursors. Several
α-trifluoromethyl alkenes were readily coupled to a wide range of primary,
secondary, and tertiary radicals, affording the desired gem-difluoroethylenes
in good yields.
H.-W. Du, Y. Chen, J. Sun, Q.-S. Gao, H. Wang, M.-D. Zhou, Org. Lett., 2020, 22, 9342-9345.
An asymmetric Ni-catalyzed intramolecular reductive Heck reaction of
unactivated alkenes tethered to aryl bromides provides various benzene-fused
cyclic compounds bearing a quaternary stereogenic center in good to excellent
yields and high enantioselectivities. A mechanism involves an enantiodetermining
migratory insertion and a subsequent protonation with water or alcoholic
solvents.
F. Yang, Y. Jin, C. Wang,
Org. Lett., 2019, 21, 6909-6913.
Upon treatment with aqueous sodium hydroxide in DMF, a range of chalcones
underwent Michael addition reactions with nitroalkanes. The resulting
adducts were reduced in situ with Zn/HCl (aq) to afford substituted Δ1-pyrrolines
in high yields after a cyclization.
Y. Liang, D. Dong, Y. Lu, Y. Wang, W. Pan, Y. Chai, Q. Liu, Synthesis, 2006, 3301-3304.
Asymmetric cross-electrophile difunctionalization of tethered alkenes is a
powerful tool for the production of chiral cyclic scaffolds. An enantioselective
aza-Heck cyclization/cross-coupling sequence proceeds with primary, secondary,
and a few tertiary alkyl iodides, to provide highly enantioenriched pyrrolines
with improved molecular diversity under mild conditions.
X.-G. Jia, Q.-W. Yao, X.-Z. Shu, J. Am. Chem. Soc.,
2022, 144, 13461-13467.
An enantioselective cross-electrophile divinylation reaction of
2-bromo-1,6-dienes offers a mild route to chiral cyclic architectures, which are
key structural motifs found in various biologically active compounds. The use of
chiral t-Bu-pmrox and 3,5-difluoro-pyrox ligands resulted in the
formation of divinylated products with high chemo-, regio-, and
enantioselectivity.
J.-B. Qiao, Y.-Q. Zhang, Q.-W. Yao, Z.-Z. Zhao, X. Peng, X.-Z. Shu, J. Am. Chem. Soc.,
2021, 143, 12961-12967.
A convenient and highly regioselective method allows the synthesis of
5-methylenepyrrolidinone derivatives from various nitriles and acrylamides via a
cobalt-catalyzed reductive coupling reaction. A possible mechanism involves the
formation of a cobaltaazacyclopentene intermediate from nitrile and acrylamide,
protonation, keto-amide cyclization, and dehydration.
Y.-C. Wong, K. Parthsarathy, C.-H. Cheng, J. Am. Chem. Soc., 2009,
131, 18252-18253.
Conjugate reduction of dihydropyridones have generally been carried out using
expensive L or K-Selectrides, as catalytic hydrogenation often leads to over
reduction. The use of zinc/acetic acid enables a simple, inexpensive, and mild
reduction of N-acyl-2,3-dihydro-4-pyridones to various racemic or
enantiopure 4-piperidones or indolizidinones.
D. L. Comins, C. A. Brooks, C. L. Ingalls, J. Org. Chem., 2001,
66, 2181-2182.
A nickel-catalyzed reductive cross-coupling between aryl iodides and
difluoromethyl 2-pyridyl sulfone provides facile access to biaryls under mild
reaction conditions without pregeneration of arylmetal reagents. The new
reactivity of the 2-PySO2CF2H reagent enables C(sp2)-C(sp2)
bond formation through selective C(sp2)-S bond cleavage.
W. Miao, C. Ni, P. Xiao, R. Jia, W. Zhang, J. Hu, Org. Lett., 2021, 23,
711-715.
An efficient and convenient nickel-catalyzed cyclization of 2-iodoanilines
with alkynyl aryl ketones gives 2,4-disubstituted quinolines. Naturally
occurring quinoline derivatives have been prepared in good yields. The
mechanism is discussed.
R. P. Korivi, C.-H. Cheng, J. Org. Chem., 2006, 71, 7079-7082.
Azobenzenes were readily acylated at the 2-position with aldehydes in good
yields through a Pd-catalyzed C-H functionalization in the presence of TBHP. The
obtained acylated azobenzenes could be efficiently converted into the
corresponding indazole derivatives in nearly quantitative yields.
H. Li, P. Li, L. Wang, Org. Lett., 2013,
15, 620-623.
A nickel-catalyzed intramolecular nucleophilic addition reaction of aryl
halides to aryl ketones provides benzofuran derivatives in moderate yields. A number
of substrates bearing electron-donating or electron-withdrawing groups can be
converted.
X.-R. Zhu, C.-L. Deng, Synthesis, 2021, 53,
1842-1848.
A nickel-catalyzed reductive dicarbofunctionalization of
1,1-disubstituted enamides with unactivated alkyl iodides provides
3,3-dialkyl-substituted isoindolinones. This tandem cyclization/reductive
tolerates a broad range of functional groups. The use of a chiral Bn-Biox ligand
induces excellent enantioselectivities.
K. Fang, W. Huang, C. Shan, J. Qu, Y. Chen, Org. Lett., 2021, 23,
5523-5527.
A nickel-catalyzed reductive dicarbofunctionalization of
1,1-disubstituted enamides with unactivated alkyl iodides provides
3,3-dialkyl-substituted isoindolinones. This tandem cyclization/reductive
tolerates a broad range of functional groups. The use of a chiral Bn-Biox ligand
induces excellent enantioselectivities.
K. Fang, W. Huang, C. Shan, J. Qu, Y. Chen, Org. Lett., 2021, 23,
5523-5527.
The highly active mixed-ligand catalytic system NiCl2(dppp)/dppf
combined with the reducing effect of zerovalent Zn enables a dramatic
acceleration of the rate of the neopentylglycolborylation of aryl halides. A
diversity of electron-rich and electron-deficient aryl iodides, bromides, and
chlorides were efficiently neopentylglycolborylated in very good yields,
typically in 1 h or less.
P. Leowanawat, A.-M. Resmerita, C. Moldoveanu, C. Liu, N. Zhang, D. A. Wilson,
L. M. Hoang, B. M. Rosen, V. Persec, J. Org. Chem., 2010,
75, 7822-7828.
The mixed-ligand system NiCl2(dppp)/dppf is an effective catalyst for
the neopentylglycolborylation of ortho-, meta-, and para-substituted
electron-rich and electron-deficient aryl mesylates and tosylates. The addition
of Zn powder as a reductant dramatically increases the reaction yield and
reduces the reaction time, providing complete conversion in 1-3 h.
D. A. Wilson, C. J. Wilson, C. Moldoveanu, A.-M. Resmerita, P. Corcoran, L. M.
Hoang, B. M. Rosen, V. Percec, J. Am. Chem. Soc., 2010,
132, 1800-1801.