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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.

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.