N-Iodosuccinimide (NIS)
N-Iodosuccinimide (NIS) is an iodinating agent that is used for various electrophilic iodinations and as source for iodine in radical reactions.
Recent Literature
Various methoxy- or methyl-substituted aromatic compounds were regioselectively
iodinated with N-iodosuccinimide and a catalytic amount of
trifluoroacetic acid with excellent yields under mild conditions and short
reaction times.
A.-S. Castanet, F. Colobert, P.-E. Broutin, Tetrahedron Lett., 2002,
43, 5047-5048.
N-Halosuccinimides are efficiently activated in
trifluoromethanesulfonic acid and BF3-H2O, allowing
the halogenations of deactivated aromatics. BF3-H2O is
more economic, easy to prepare, nonoxidizing, and offers sufficiently high
acidity.
G. K. S. Prakash, T. Mathew, D. Hoole, P. M. Esteves, Q. Wang, G. Rasul, G.
A. Olah, J. Am. Chem. Soc.,
2004,
126, 15770-15776.
Use of the powerful Lewis acid, iron(III) triflimide, generated in situ from
iron(III) chloride and a readily available triflimide-based ionic liquid allowed
activation of N-iodosuccinimide (NIS) and efficient iodination of a wide
range of arenes under mild conditions.
D. T. Racys, C. E. Warrilow, S. L. Pimlott, A. Sutherland, Org. Lett.,
2015,
17, 4782-4785.
In a mild and rapid method for the iodination of arenes, silver(I) triflimide is
used as a catalyst for activation of N-iodosuccinimide. The is suitable
for a wide range of anisoles, anilines, acetanilides, and phenol derivatives and
allowed the late-stage iodination of biologically active compounds.
D. T. Racys, S. A. I. Sharif, S. L. Pimlott, A. Sutherland, J. Org. Chem.,
2016,
81, 772-780.
The use of a hexafluoroisopropanol as solvent enables a mild and regioselective
halogenation of a broad range of arenes and heterocycles with N-halosuccinimides
in good yields. In addition, the versatility of the method is demonstrated by
the development of one-pot sequential dihalogenation and halogenation-Suzuki
cross-coupling reactions.
R.-J. Tang, T. Milcent, B. Crousse, J. Org. Chem.,
2018, 83, 930-938.
A highly para-selective halogenation of arenes bearing electron-donating
coordinating groups in the presence of a dimidazolium salt rpovides p-haloarenes
in good yields. A plausible mechanism for the catalytic reaction is proposed.
J. Chen, X. Xiong, Z. Chen, J. Huang,
Synlett, 2015, 26, 2831-2834.
Gold(I) catalysis enables an efficient iodination of a various electron-rich
arenes in the presence of N-Iodosuccinimide (NIS) under mild conditions.
D. Leboeuf, J. Ciesielsk, A. J. Frontier, Synlett, 2014, 25,
399-402.
A convenient and efficient visible-light-induced decarboxylative iodination of
aromatic carboxylic acids provides the corresponding aryl iodides in good yields.
The method offers simple and mild conditions, high efficiency, wide substrate
scope and tolerates various functional groups.
M. Jiang, H. Yang, Y. Jin, L. Ou, H. Fu,
Synlett, 2018, 29, 1572-1577.
Aryl and heteroaryl boronic acids react with N-iodosuccinimide and
N-bromosuccinimide to give the corresponding iodo- and bromo-arenes in good
to excellent yields. The reaction is usually highly regioselective and yields
only the ipso-substituted product.
C. Thiebes, G. K. Surya Prakash, N. A. Petasis, G. A. Olah, Synlett,
1998, 141-142.
Cu-catalyzed aryl boronic acid
halodeboronation takes place via a boronate-driven ipso-substitution
pathway. Cu is not required for these processes to operate: general
Lewis base catalysis is operational. This in turn allows the rational
development of a general, simple, and effective base-catalyzed halodeboronation.
J. J. Molloy, K. M. O'Rourke, C. P. Frias, N. L. Sloan, M. J. West, S. L.
Pimlott, A. Sutherland, A. J. B. Watson,
Org. Lett., 2019, 21, 2488-2492.
Using cyano as the directing group, a palladium-catalyzed ortho-halogenation
(I, Br, Cl) reaction gave good to excellent yields. The method is compatible to
arylnitriles with either electron-withdrawing or electron-donating groups. The
present method was successfully applied to the synthesis of the precursors of
paucifloral F and isopaucifloral F.
B. Du, X. Jiang, P. Sun, J. Org. Chem., 2013,
78, 2786-2791.
Silver carbonate or nickel(II) chloride catalyzes an ortho-C-H bond halogenation of anilides and
N-aryl carbamates with N-halosuccinimides to provide 2-haloanilides and carbamates, which may serve as starting
materials for the synthesis of pharmaceutically and biologically active
compounds.
E. Kianmehr, H. Afaridoun, Synthesis, 2021, 53,
1513-1523.
A catalyst- and metal-free visible-light-mediated protocol enables the
iodoamination of miscellaneous olefins in high yields under environmentally
benign reaction conditions using DMC as green and biodegradable solvent.
Furthermore, the protocol allows for late-stage functionalization of bioactive
molecules and can be scaled to gram quantities of product.
S. Engl, O. Reiser, Org. Lett., 2021, 23,
5581-5586.
A β-boron effect accounts for high regioselectivity in electrophilic addition
reactions to allylic MIDA (N-methyliminodiacetic acid) boronates. The
boryl moiety is retained in the product when B(MIDA) is used as the nucleophilic
stabilizer.
Y. Li, W.-X. Fan, S. Luo, A. Tofimova, Y. Liu, J.-H. Xue, L. Yang, Q. Li, H.
Wang, A. K. Yudin, J. Am. Chem. Soc.,
2023, 145, 7548-7558.
Reliable, operationally simple, catalytic α-selective
hydroalumination reactions proceed in the presence of diisobutylaluminum
hydride and (Ni(dppp)Cl2), and, unlike
uncatalyzed transformations, generate little or no alkynylaluminum
byproducts. The derived α-vinyl halides and boronates can be synthesized
through direct treatment with the appropriate electrophiles.
F. Gao, A. H. Hoveyda, J. Am. Chem. Soc., 2010,
132, 10961-10963.
Trapping of a diazo species in an intermolecular fashion by two independent ion
species in tandem at the carbene center installs an electrophile and a
nucleophile on the same carbon. This metal-free concept enables regioselective
syntheses of various vinyl halides, vinyl sulfones, and alkyne derivatives.
D. P. Ojha, K. R. Prabhu, Org. Lett.,
2015,
17, 18-21.
Acetic acid activates N-iodosuccinimide for an efficient and highly
chemoselective direct iodination of terminal alkynes under metal-free conditions.
This convenient process tolerates a variety of terminal alkynes and provides the
desired products in very good yields.
M. Yao, J. Zhang, S. Yang, E. Liu, H. Xiong, Synlett, 2020,
31,
1102-1106.
Using triethylamine as catalyst in Hunsdiecker reactions with N-halosuccinimides
as Br+ or I+ source, cinnamic acids, and propiolic acids are
converted to the corresponding α-halostyrenes and 1-halo-1-alkynes in good isolated yields within 1-5 min.
J. Prakash, S. Roy, J. Org. Chem.,
2002, 67, 7861-7864.
NIS mediates a transition-metal-free arylation of terminal alkynes with a tetracoordinate boron intermediate.
The reaction offers high
efficiency, wide substrate range, and good functional group tolerance.
M. Ye, M. Hou, Y. Wang, X. Ma, K. Yang, Q. Song, Org. Lett., 2023, 25,
1787-1792.
An efficient protocol for a highly stereoselective one-pot synthesis of (E)-β-aryl
vinyl iodides and (E)-β-aryl vinyl bromides from styrenes is based on a
ruthenium-catalyzed silylative coupling followed by a N-halosuccinimide-mediated
halodesilylation reaction.
P. Pawluć, G. Hreczycho, J. Szudkowska, M. Kubicki, B. Marciniec, Org. Lett., 2009,
11, 3390-3393.
Unprecedented decompositions of unprotected alkynyl hydrazones provide
allenoates via DABCO-promoted Wolff-Kishner reduction, tetrasubstituted
α,γ-dihaloallenoates in the presence of N-halosuccinimides, and
functionalized tricyclic azepines in the presence of DBU.
P. Jamwal, A. Sharma, R. Gurubrahamam, Org. Lett., 2023, 25,
6607-6612.
A direct asymmetric iodination reaction of aldehydes with NIS catalyzed by a
novel axially chiral bifunctional amino alcohol represents a rare example of a
highly enantioselective synthesis of optically active α-iodoaldehydes.
T. Kano, M. Ueda, K. Maruoka, J. Am. Chem. Soc., 2008,
130, 3728-3729.
The reaction of alkynes with N-iodosuccinimides and water at 70˚C allows
a convenient and practical approach to α-diketones.
M. Niu, H. Fu, Y. Jiang, Y. Zhao, Synthesis, 2008,
2879-2882.
An efficient synthesis of α-iodo/bromo-α,β-unsaturated aldehydes/ketones
directly from propargylic alcohols is catalyzed collaboratively by Ph3PAuNTf2
and MoO2(acac)2, and Ph3PO as an additive helps
suppress undesired enone/enal formation. Notable features of this method include
low catalyst loadings, mild reaction conditions, and mostly good
diastereoselectivity.
L. Ye, L. Zhang, Org. Lett., 2009,
11, 3646-3649.
A catalytic amount of Au(PPh3)NTf2 converts readily
accessible propargylic acetates into versatile linear α-iodoenones in good to
excellent yields. Very good Z-selectivities are observed for aliphatic
propargylic acetates.
M. Yu, G. Zhang, L. Zhang, Org. Lett., 2007,
9, 2087-2090.
A regio- and stereoselective iodination, along with some examples for
bromination, of readily available acrylamides proceeds under mild conditions via
a Rh(III)-catalyzed C-H-activation/halogenation mechanism. The reaction
represents a rare example of a direct halogenation of electron-poor acrylic acid
derivatives to access a variety of differently substituted Z-haloacrylic
acid derivatives.
N. Kuhl, N. Schröder, F. Glorius, Org. Lett., 2013,
15, 3860-3863.
N-Iodosuccinimide (NIS) mediates a convenient and mild oxidation of
propargyl alcohols for the construction of ynones in good yields.
H. Qi, S. Xu, R. Zhao, S. Chen, J. Org. Chem., 2022, 87,
13726-13733.
A new silver-catalyzed highly regio- and stereoselective difunctionalization
reaction of simple terminal alkynes gives (Z)-β-haloenol acetate
derivatives in good yields. The resulting products are versatile intermediates
in organic synthesis.
Z. Chen, J. Li, H. Jiang, S. Zhu, Y. Li, C. Qi, Org. Lett., 2010,
12, 3262-3265.
Halogen bonding induces an intermolecular Csp3-H amination and
even enables a hydrogen atom transfer relay strategy to access privileged
pyrrolidine structures directly from alkanes. Mechanistic studies support the
presence of multiple halogen bond interactions.
F. Wu, J. P. Ariyarathna, N. Kaur, N.-E. Alom, M. L. Kennell, O. H. Bassiouni,
W. Li,
Org. Lett., 2020, 22, 2135-2140.
Dimethyl sulfoxide (DMSO) and N-iodosuccinimide mediate a metal-free
regioselective 5-exo-dig oxidative cyclization of propargyl-substituted
ynamides via in situ generated enol equivalents. The reaction allows easy access
to functionalized pyrrolidone skeletons. The role of DMSO as oxidant in the
transformation is clarified, and a tentative reaction pathway is proposed.
B. Prabagar, S. Nayak, R. Prasad, A. K. Sahoo, Org. Lett.,
2016, 18, 3066-3069.
A sequence consisting of an electrophilic cyclization in the presence of N-iodosuccinimide
(NIS) and an 1,2-migration allows the construction of 4-iodo-3-furanones from
2-alkynyl-2-silyloxy carbonyl compounds. In a more versatile variant, AuCl3
catalyzes the tandem reaction in the presence of NIS to provide highly
substituted heterocycles in good yields.
B. Crone, S. F. Kirsch, J. Org. Chem., 2007,
72, 5435-5438.
Various tert-butyldimethylsilyl ethers are easily removed in excellent
yields by treatment with a catalytic amount of N-iodosuccinimide in
methanol. This method allows a selective deprotection of TBDMS ethers of
alcohols in the presence of TBDMS ethers of phenols.
B. Karimi, A. Zamani, D. Zarayee, Tetrahedron Lett., 2004,
45, 9139-9141.
N-Iodosuccinimide promotes an attractive and productive protocol for the
position-selective intramolecular C-H amination of aliphatic groups
(Hofmann-Löffler reaction) employing sulfonimides as nitrogen sources initiated
by visible light. The overall transformation provides pyrrolidines under mild
and selective conditions as demonstrated for 17 different substrates.
C. Q. O'Broin, P. Fernández, C. Martínez, Kilian Muñiz, Org. Lett., 2016, 18,
436-439.
Use of La(OTf)3 as a Lewis acid promoter for N-iodosuccinimide-mediated
activation of thioglycosides enables a smooth glycosylation reaction with good
to excellent yields and stereoselectivity.
S. Mukherjee, B. Mukhopadhyay, Synlett, 2010,
2853-2856.
A sequential intermolecular hydroamination reaction of
2-trifluoromethyl-1,3-enynes with aliphatic primary amines under mild reaction
conditions followed by a NXS mediated oxidative cyclization of the
hydroamination product provides halogenated trifluoromethylated pyrroles. This
method offers mild conditions, high efficiency, readily available starting
materials, general substrate scope, and synthetic utility of the products.
C. Huang, Y. Zeng, H. Cheng, A. Hu, L. Liu, Y. Xiao, J. Zhang, Org. Lett.,
2017, 19, 4968-4971.
A [1,2]-phospha-Brook rearrangement under Brønsted base catalysis enables an
efficient synthesis of 2,4,5-trisubstituted-3-iodofurans via a
formal [3 + 2] cycloaddition of an in situ generated α-oxygenated propargyl
anion to an aldehyde and a subsequent intramolecular
cyclization mediated by N-iodosuccinimide. The method provides access to
a wide range of tetrasubstituted furans.
A. Kondoh, K. Aita, S. Ishikawa, M. Terada,
Org. Lett., 2020, 22, 2105-2110.
An efficient copper-catalyzed aerobic oxidative dehydrogenative annulation of
amines, alkynes, and O2 provides trisubstituted oxazoles via dioxygen
activation and oxidative C-H bond functionalization.
J. Pan, X. Li, X. Qiu, X. Luo, N. Jiao, Org. Lett.,
2018, 20, 2762-2765.
Highly substituted oxazoles can be synthesized from readily accessible ynamides
in the presence of ytterbium(III) trifluoromethanesulfonate, N-iodosuccinimide,
and acetonitrile. Hydroamidation and iodo-imidation of ynamides to ketene
aminals are also demonstrated. The reactions are scalable to the gram scale,
testifying the robustness of the transformations.
A gold-catalyzed cyclization of β-amino-ynone intermediates and halodeauration
process enables a rapid and efficient one-step halopyridone synthesis.
K. H. Nguyen, S. Tomasi, M. Le Roch, L. Toupet, J. Renault, P. Uriac, N. Gouault, J. Org. Chem., 2013,
78, 7809-7815.
A facile switchable regioselective 7-endo or 6-exo
iodocyclization of O-homoallyl benzimidates provides various
iodo-substituted 1,3-oxazines and tetrahydro-1,3-oxazepines in a controllable
manner under mild conditions and with excellent functional group compatibility.
The products can further undergo substitution reactions to afford a series of
functionalized heterocyclic molecules.
T.-Y. Cao, L. Qi, L.-J. Wang, J. Org. Chem., 2023, 88,
3035-3045.
A facile switchable regioselective 7-endo or 6-exo
iodocyclization of O-homoallyl benzimidates provides various
iodo-substituted 1,3-oxazines and tetrahydro-1,3-oxazepines in a controllable
manner under mild conditions and with excellent functional group compatibility.
The products can further undergo substitution reactions to afford a series of
functionalized heterocyclic molecules.
T.-Y. Cao, L. Qi, L.-J. Wang, J. Org. Chem., 2023, 88,
3035-3045.
A rapid synthesis of indoles from N-Ts-2-alkenylanilines involves a
NIS-mediated cascade C-N bond formation/aromatization. A series of indoles with
various functional groups have been synthesized in very good yields under mild
conditions without any other additives or catalysts.
Y.-L. Li, J. Li, A.-L. Ma, Y.-N. Huang, J. Deng, J. Org. Chem.,
2015,
80, 3841-3851.
Gold(I)-catalyzed cycloisomerization of 1-(2-(tosylamino)phenyl)prop-2-yn-1-ols
enables the preparation of 1H-indole-2-carbaldehydes and (E)-2-(iodomethylene)indolin-3-ols
in the presence of N-iodosuccinimide (NIS). The reactions were shown to
be operationally simplistic and proceed efficiently for a wide variety of
substrates, affording the corresponding products in very good yields.
P. Kothandaraman, S. R. Mothe, S. S. M. Toh, P. W. H. Chan, J. Org. Chem., 2011,
76, 7633-7640.
A metal-free sequential dual oxidative amination of C(sp3)-H bonds
under ambient conditions affords imidazo[1,5-a]pyridines in very good yields.
The reaction involves two oxidative C-N couplings and one oxidative
dehydrogenation process with six hydrogen atoms removed.
Y. Yan, Y. Zhang, Z. Zha, Z. Wang, Org. Lett., 2013,
15, 2274-2277.
Treatment of 2-arylethylmagnesium bromides, prepared from 2-arylethyl bromides
and magnesium, with aromatic nitriles, followed by reaction with water and then
with N-iodosuccinimide under irradiation with a tungsten lamp, provides
2-arylquinolines in good yields under transition-metal-free conditions.
2-Alkylquinolines could be also obtained in moderate yields.
H. Naruto, H. Togo, Synthesis, 2020, 52,
1122-1130.
Treatment of N-tosyl-2-propynylamines with diphenyliodonium triflate in
the presence of K3PO4 and a catalytic amount of CuCl at
room temperature followed by N-iodosuccinimide and BF3·OEt2
at 0°C, and then NaOH in methanol solution provided 3-iodo-4-arylquinolines.
Products underwent various cross-coupling reactions and were smoothly
dehalogenated with zinc.
T. Sasaki, K. Moriyama, H. Togo, J. Org. Chem.,
2017, 82, 11727-11734.
The intramolecular cyclization of 1-azido-2-(2-propynyl)benzene proceeds
smoothly in the presence of electrophilic reagents in CH3NO2
at room temperature or in the presence of catalytic amounts of AuCl3/AgNTf2
in THF at 100°C to afford the corresponding quinolines 2 in good to high yields.
Z. Huo, I. D. Gridnev, Y. Yamamoto, J. Org. Chem., 2010,
75, 1266-1270.
A convenient radical oxidative cyclization mediated by N-iodosuccinimide
(NIS) enables the synthesis of a series of dibenzopyranones from a wide scope of
2-arylbenzoic acids. The methodology offers good functional group tolerance and
mild reaction conditions without the use of transition metals.
P. Gao, Y. Wei, Synthesis, 2014, 46,
343-347.
