Categories: C-I Bond Formation >
Synthesis of iodoarenes
DMSO as a mild and inexpensive oxidant enables an efficient and practical bromination and iodination of arenes with HX (X = Br, I) reagents. This oxidative system is amenable to late-stage bromination of natural products and kilogram-scale conversions.
S. Song, X. Sun, X. Li, Y. Yuan, N. Jiao, Org. Lett., 2015, 17, 2886-2889.
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.
In a disulfide-catalyzed electrophilic iodination of electron-rich aromatic compounds using 1,3-diiodo-5,5-dimethylhydantoin (DIH), the disulfide activates DIH as a Lewis base to promote the iodination reaction in acetonitrile under mild conditions. This system is applicable to a wide range of substrates, including anisoles, acetanilides, imidazoles, and pyrazoles.
K. Iida, S. Ishida, T. Watanabe, T. Arai, J. Org. Chem., 2019, 84, 7411-7417.
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.
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.
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.
Deactivated arenes were mono- or diiodinated with strong electrophilic I+ reagents, which were prepared from NaIO4 and either I2 or KI in concentrated sulfuric acid, using either a ‘direct’ or an ‘inverse’ method of aromatic iodination to give mono- or diiodinated pure products in good yields.
L. Kraszkiewicz, M. Sosnowski, L. Skulski, Synthesis, 2006, 1195-1199.
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.
Cu(I) as promoter enables simple strategies for decarboxylative functionalizations of electron-deficient benzoic acids under aerobic conditions. For the conversion of electron-rich benzoic acids, Pd(II) must be used as catalyst. The method provides aryl halides (-I, Br, and Cl) in the presence of readily available halogen sources CuX (X = I, Br, Cl) and benzonitriles in the presence of nontoxic and low-cost K4Fe(CN)6.
Z. Fu, Z. Li, Y. Song, R. Yang, Y. Liu, H. Cai, J. Org. Chem., 2016, 81, 2794-2803.
The regioselectivity of a mild method to prepare aryl and heteroaryl iodides by sequential C-H borylation and iodination is controlled by steric effects on the C-H borylation step and is complementary to existing methods to form aryl iodides.
B. M. Partridge, J. F. Hartwig, Org. Lett., 2013, 15, 140-143.
An environmentally benign protocol for the iodination of activated aromatics, such as phenols, anilines, and hydroxycoumarins, using inexpensive commercially available potassium iodide and ammonium peroxodisulfate in aqueous methanol at room temperature provides predominantly ortho-monoiodinated products. This acid-free method is compatible with various oxidizable functional groups.
N. C. Ganguly, S. K. Barik, S. Dutta, Synthesis, 2010, 1467-1472.
A selective and efficient oxidative iodination of electron rich arenes was carried out with one equivalent of KI and two equivalents of 30% hydrogen peroxide in MeOH in the presence of strong acid.
J. Iskra, S. Stavber, M. Zupan, Synthesis, 2004, 1869-1873.
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.
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.
An organocatalytic iodination of activated aromatic compounds using 1,3-diiodo-5,5-dimethylhydantoin (DIH) as the iodine source with thiourea catalysts in acetonitrile is applicable to a number of aromatic substrates with significantly different steric and electronic properties. The iodination is generally highly regioselective and provides high yields of isolated products.
G. Jakab, A. Hosseini, H. Hausmann, P. R. Schreiner, Synthesis, 2013, 45, 1635-1640.
Eco-friendly laboratory procedures allow the oxidative iodination of various activated and deactivated arenes with molecular iodine, in the presence of UHP (percarbamide), a stable, strongly H-bonded, solid urea-hydrogen peroxide adduct as the oxidant.
P. Lulinski, A. Kryska, M. Sosnowski, L. Skulski, Synthesis, 2004, 441-445.
A simple, general and efficient method enables a metal-free iodination of arylboronic acids with molecular iodine as the halide source and potassium carbonate as the base. The method tolerates various functional groups and can also be applied very effectively in a one-pot, two-step synthesis of biaryl derivatives.
L. Niu, H. Zhang, H. Yang, H. Fu, Synlett, 2014, 25, 995-1000.
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.
AuCl3-catalyzed halogenations of aryl borononates with N-halosuccinimides enables a convenient synthesis of aromatic boronates bearing halogen substituents in the aromatic ring.
D. Qiu, F. Mo, Z. Zheng, Y. Zhang, J. Wang, Org. Lett., 2010, 12, 5474-5477.
Benzene derivatives bearing at least one bulky alkyl group (i-Pr or t-Bu) were selectively and effectively iodinated using elemental iodine activated by Selectfluor. Up to three iodine atoms were progressively introduced at the most electron-rich and sterically less hindered position on the benzene ring.
S. Stavber, P. Kralj, M. Zupan, Synthesis, 2002, 1513-1518.
Halogen abstraction from bromotrichloromethane and diiodomethane enables a metal-free synthesis of aryl bromides and iodides from anilines without isolation of diazonium salts. The transformation offers short reaction times, a simple workup, and insensitivity to moisture and air and avoids excess halogenation. This method represents a convenient alternative to the classic Sandmeyer reaction.
D. A. Leas, Y. Dong, J. L. Vennerstrom, D. E. Stack, Org. Lett., 2017, 19, 2518-2521.
Convenient and simple, sequential diazotization-iodination of aromatic amines with NaNO2/KI in the presence of a sulfonic acid based cation-exchange resin in water is an inexpensive, noncorrosive and eco-friendly synthetic route, that allows the preparation of various electron-rich and deficient iodoarenes in good yields.
V. D. Filimonov, N. I. Semenischeva, E. A. Krasnokutskaya, A. N. Tretyakov, H. Y. Hwang, K.-W. Chi, Synthesis, 2008, 185-187.
A convenient and general one-step preparation of aromatic and some heterocyclic iodides in good yields includes a sequential diazotization-iodination of aromatic amines with KI, NaNO2, and p-TsOH in acetonitrile at room temperature.
E. A. Krasnokutskaya, N. I. Semenischeva, V. D. Filimonov, P. Knochel, Synthesis, 2007, 81-84.
Reaction of [ArN2][BF4] salts immobilized in [BMIM][PF6] ionic liquid (IL) with TMSI and TMSN3 represents an efficient method for the preparation of iodo- and azido-derivatives via dediazoniation. Using TMSBr, competing fluorodediazoniation (ArF formation) and hydrodediazoniation (ArH formation) were observed depending on the substituents on the benzenediazonium cation.
A. Hubbard, T. Okazaki, K. K. Laali, J. Org. Chem., 2008, 73, 316-319.
A photo-induced halogen exchange in aryl or vinyl halides enables the synthesis of a broad scope of aryl iodides at room temperature under exceptionally mild conditions without any metal or photo-redox catalysts. The presence of a catalytic amount of elemental iodine could promote the reaction significantly.
L. Li, W. Liu, H. Zeng, X. Mu, G. Cosa, Z. Mi, C.-J. Li, J. Am. Chem. Soc., 2015, 137, 8206-8218.
A mild and general copper(I)-catalyzed conversion of aryl, heteroaryl, and vinyl bromides into the corresponding iodides was developed. Various functional groups and even N-H containing substrates such as sulfonamides, amides, and indoles are compatible with the reaction conditions.
A. Klapars, S. L. Buchwald, J. Am. Chem. Soc., 2002, 124, 14844-14845.
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.
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.
An efficient diiodination process, that involves the formal insertion of arynes into the I-I σ-bond, allows the synthesis of substituted and polycyclic o-diiodoarenes, which are difficult to obtain by classical methods.
D. Rodríguez-Lojo, A. Cobas, D. Peña, D. Pérez, E. Guitián, Org. Lett., 2012, 14, 1363-1365.
CuX catalyzes an efficient asymmetric halogenation of cyclic diaryliodonium salts to provide a wide range of axially chiral 2,2'-dihalobiaryls in very good yields and with excellent enantioselectivities in the presence of a chiral bisoxazoline ligand, tetrabutylammonium halides, and hexafluoroisopropanol. The products can be transformed into a number of enantiopure chiral ligands.
J. Ke, B. Zu, Y. Guo, Y. Li, C. He, Org. Lett., 2021, 23, 329-333.
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.
Kinetic vs thermodynamic deprotonation studies on secondary and tertiary sulfonamides using n-BuLi have been carried out. Application of the developed conditions allows the synthesis of diverse sulfonamide products (E=I). Subsequent Suzuki cross-coupling reactions of iodo derivatives furnish various biaryl sulfonamides.
S. L. MacNeil, O. B. Familoni, V. Snieckus, J. Org. Chem, 2001, 66, 3662-3670.
A mild palladium-catalyzed, regioselective chlorination, bromination, and iodination of arene C-H bonds using N-halosuccinimides as oxidants is described. These transformations can provide products that are complementary to those obtained via conventional electrophilic aromatic substitution reactions.
D. Kalyani, A. R. Dick, W. Q. Anani, M. S. Sanford, Org. Lett., 2006, 8, 2523-2526.
J. Sedelmeier, C. Bolm, J. Org. Chem., 2005, 70, 6904-6906.
(Hetero)aryl-, alkenyl-, and selected alkyl-substituted acid chlorides can be efficiently coupled with N-Boc-protected propargylamine to produce ynones which are converted to 2-substituted N-Boc-4-iodopyrroles in a one-pot reaction. Upon addition of a further alkyne, another Sonogashira coupling can be carried out in a one-pot fashion.
E. Merkul, C. Boersch, W. Frank, T. J. J. Müller, Org. Lett., 2009, 11, 2269-2272.
A method for the regiospecific synthesis of 1,4,5-trisubstituted-1,2,3-triazole catalyzed by copper(I) iodide was developed. This is the first example of a regiospecific synthesis of 5-iodo-1,4-disubstituted-1,2,3-triazole, which can be further elaborated to a range of 1,4,5-trisubstituted-1,2,3-triazole derivatives
Y.-M. Wu, J. Deng, Y. L. Li, Q.-Y. Chen, Synthesis, 2005, 1314-1318.