Zinc
Name Reactions
Recent Literature

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.

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.

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.

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.

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.

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.

S. Wang, Q. Qian, H. Gong, Org. Lett., 2012,
14, 3352-3355.

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.

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 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 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.

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 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.

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.

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.

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.

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.

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.

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.

