A new, green, mild and inexpensive system, I2-KI-K2CO3-H2O, selectively oxidized alcohols to aldehydes and ketones under anaerobic condition in water at 90 °C with excellent yields.
P. Gogoi, D. Konwar, Org. Biomol. Chem., 2005, 3, 3473-3475.
Iodine was compared to other positive halogens as terminal oxidant in chemoselective oxidations of alcohols using catalytic TEMPO and was shown to be superior in cases of electron-rich and heteroaromatic benzylic alcohols.
R. A. Miller, R. S. Hoerrner, Org. Lett., 2003, 5, 285-287.
A simple, efficient, and high-yield procedure for the oxidative conversion of alcohols to various types of esters and ketones was successfully carried out with molecular iodine as the oxidant and potassium carbonate.
N. Mori, H. Togo, Tetrahedron, 2005, 61, 5915-5925.
The use of aqueous hydrogen peroxide as oxidizing agent and molecular iodine as catalyst enables a mild and efficient methodology for the ipso-hydroxylation of arylboronic acids to phenols. The reactions were performed at room temperature in short reaction time under metal-, ligand- and base-free conditions.
A. Gogoi, U. Bora, Synlett, 2012, 23, 1079-1081.
An unprecedented α-hydroxylation strategy using inexpensive N,N-dimethylformamide (DMF) as an oxygen source enables the synthesis of α-hydroxy arones. This reaction provides an alternative strategy for the α-hydroxylation of arones.
W. Liu, C. Chen, P. Zhou, J. Org. Chem., 2017, 82, 2219-2222.
An iodine-NH3 • H2O system enables a direct transformation of aryl, heteroaryl, vinyl, or ethynyl methyl ketones or carbinols to the corresponding primary amides in good yields in aqueous media. A tandem Lieben-Haller-Bauer reaction mechanism is proposed.
L. Cao, J. Ding, M. Gao, Z. Wang, J. Li, A. Wu, Org. Lett., 2009, 11, 3810-3813.
An efficient, metal-free domino protocol for the synthesis of benzamides from ethylarenes proceeds through the formation of triiodomethyl ketone intermediate in the presence of iodine as the promoter and TBHP as an oxidant followed by nucleophilic substitution with aqueous ammonia. This operationally simple, functional-group-tolerant tandem approach provides an easy access to the broad range of biologically important benzamides.
K. S. Vadagaonkar, H. P. Kalmode, S. Prakash, A. C. Chaskar, Synlett, 2015, 26, 1677-1682.
In a metal-free, selective oxidation of cyclic secondary and tertiary amines for the formation of lactams, molecular iodine facilitates both chemoselective and regioselective oxidation of C-H bonds directly adjacent to a cyclic amine. The reaction offers mild conditions, functional group tolerance, and a broad substrate scope.
R. J. Griffiths, G. A. Burley, E. P. A. Talbot, Org. Lett., 2017, 19, 870-873.
A catalytic oxidative cleavage of 1,3-diketones enables the synthesis of the corresponding carboxylic acids by aerobic photooxidation with iodine under irradiation with a high-pressure mercury lamp.
N. Tada, M. Shomura, L. Cui, T. Nobuta, T. Miura, A. Itoh, Synlett, 2011, 2896-2900.
An I2-promoted direct conversion of arylacetic acids into aryl carboxylic acids under metal-free conditions involves decarboxylation followed by an oxidation reaction enabled just by using DMSO as the solvent as well as an oxidant. Notably, aryl carboxylic acids are isolated by simple filtration technique and obtained in good to excellent yields, which makes this protocol applicable for large-scale synthesis.
H. P. Kalmode, K. S. Vadagaonkar, S. L. Shinde, A. C. Chaskar, J. Org. Chem., 2017, 82, 3781-3786.
Formation of unstable but reactive acyl nitroso intermediates from Nα-protected hydroxamic acids in the presence of iodine and DMSO enables an efficient and straightforward coupling with an amino component to yield dipeptide esters.
M. Krishnamurthy, T. M. Vishwanatha, N. R. Panguluri, V. Panduranga, V. V. Sureshbabu, Synlett, 2015, 26, 2565-2569.
A zinc carbenoid-mediated chain extension of β-dicarbonyl compounds provides access to α,β-unsaturated-γ-keto esters and amides with complete E selectivity via an intermediate zinc enolate, which is treated sequentially with iodine and DBU.
M. D. Ronsheim, C. K Zercher, J. Org. Chem., 2003, 68, 4535-4538.
1,3-dicarbonyl compounds and methyl ketones or terminal aryl alkenes as simple and readily available starting materials can be efficiently converted to unsymmetrical 1,4-enediones under mild reaction conditions using a focusing domino strategy. The reaction allows an operationally simple, straightforward synthesis of various unsymmetrical 1,4-enediones.
M. Gao, Y. Yang, Y.-D. Wu, C. Deng, L.-P. Cao, X.-G. Meng, A.-X. Wu, Org. Lett., 2010, 12, 1856-1859.
The Zweifel reaction is a powerful transition-metal-free alternative to the Suzuki-Miyaura reaction for the synthesis of alkenes. This transition-metal-free coupling process enables the coupling of Grignard reagents or organolithiums for an enantiospecific synthesis of a wide variety of functionalized acyclic and cyclic olefin products.
R. J. Armstrong, W. Niwetmarin, V. K. Aggarwal, Org. Lett., 2017, 19, 2762-2765.
A direct conversion of various benzylic alkyl halides and primary alkyl halides into corresponding nitriles was efficiently and simply carried out in aqueous ammonia in the presence of molecular iodine as oxidant.
S. Iida, H. Togo, Synlett, 2008, 1639-1642.
Various alcohols were efficiently converted into the corresponding nitriles at room temperature by treatment with tert-butyl hypochlorite, diiodine, or 1,3-diiodo-5,5-dimethylhydantoin (DIH) in the presence of TEMPO, followed by treatment with diiodine and aqueous ammonia. The nitriles were obtained in good yields and high purities by a simple extraction of the reaction mixture with chloroform and subsequent removal of the solvent.
H. Shimojo, K. Moriyama, H. Togo, Synthesis, 2013, 45, 2155-2156.
Various electron-rich aromatics could be smoothly converted into the corresponding aromatic nitriles in good yields by treatment with POCl3 and DMF, followed by molecular iodine in aqueous ammonia. The present reaction is a novel metal-free one-pot method for the preparation of aromatic nitriles from electron-rich aromatics.
S. Ushijima, H. Togo, Synlett, 2010, 1067-1070.
An I2/CHP-mediated cross-coupling reaction of isocyanides with readily accessible amines gives carbodiimides in good yields. This metal-free strategy for coupling of isocyanides with amines provides an efficient approach for symmetric and unsymmetric functionalized carbodiimide derivative synthesis under mild conditions.
T.-H. Zhu, S.-Y. Wang, Y.-Q. Tao, S.-J. Ji, Org. Lett., 2015, 17, 1974-1977.
An iodine-catalyzed oxidative C-H/N-H cross-coupling enables an efficient construction of α-ketoimides in good to excellent yields from methyl ketones and benzamidines hydrochloride under metal-free and peroxide-free conditions.
X. Wu, Q. Gao, S. Liu, A. Wu, Org. Lett., 2014, 16, 2888-2891.
2-Imidazolines were easily prepared in good yields from the reaction of aldehydes and ethylenediamine with iodine in the presence of potassium carbonate. The 2-imidazolines were smoothly oxidized to the corresponding imidazoles in good yields using (diacetoxyiodo)benzene at room temperature.
M. Ishihara, H. Togo, Synlett, 2006, 227-230.
A series of primary alcohols and aldehydes were treated with iodine in ammonia water under microwave irradiation to give the intermediate nitriles, which wItohut isolation underwent [2 + 3] cycloadditions with dicyandiamide and sodium azide to afford the corresponding triazines and tetrazoles in high yields.
J.-J. Shie, J.-M. Fang, J. Org. Chem., 2007, 72, 3141-3144.
In a direct annulation of hydrazides with methyl ketones for the synthesis of 1,3,4-oxadiazoles, the use of K2CO3 as a base achieves an unexpected and highly efficient C-C bond cleavage. This reaction is proposed to go through oxidative cleavage of Csp3-H bonds, followed by cyclization and deacylation.
Q. Gao, S. Liu, X. Wu, J. Zhang, A. Wu, Org. Lett., 2015, 17, 2960-2963.
An efficient I2/TBPB mediated oxidative formal [4 + 1] cycloaddition of N-tosylhydrazones with anilines represents a simple, general, and efficient approach for the construction of 1,2,3-triazoles under metal-free and azide-free conditions.
Z.-J. Cai, X.-M. Lu, Y. Zi, C. Yang, L.-J. Shen, J. Li, S.-Y. Wang, S.-J. Ji, Org. Lett., 2014, 16, 5108-5111.
A series of primary alcohols and aldehydes were treated with iodine in ammonia water under microwave irradiation to give the intermediate nitriles, which without isolation underwent [2 + 3] cycloadditions with dicyandiamide and sodium azide to afford the corresponding triazines and tetrazoles in high yields.
J.-J. Shie, J.-M. Fang, J. Org. Chem., 2007, 72, 3141-3144.
A novel copper/I2-mediated oxidative cross-coupling/cyclization of 2-(pyridin-2-yl)acetate derivatives and simple olefins provides a straightforward and efficient access to 1,3-di- and 1,2,3-trisubstituted indolizines in good yields.
R.-R. Liu, J. J. Hong, C.-J. Lu, M. Xu, J.-R. Gao, Y.-X. Jia, Org. Lett., 2015, 17, 3050-3053.
A copper/iodine cocatalyzed decarboxylative cyclization of α-amino acids with either 2-benzoylpyridines or 2-benzoylquinolines provides 1,3-disubstituted imidazo[1,5-a]pyridines and 1,3-disubstituted imidazo[1,5-a]quinolines in excellent yields.
H. Wang, W. Xu, L. Xin, W. Liu, Z. Wang, K. Xu, J. Org. Chem., 2016, 81, 3681-3687.
An I2/KI-mediated oxidative N-N bond formation reaction enables an environmentally benign synthesis of various 1,2,4-triazolo[1,5-a]pyridines and other 1,5-fused 1,2,4-triazoles from readily available N-aryl amidines in an efficient and scalable fashion.
L. Song, X. Tian, Z. Lv, E. Li, J. Wu, Y. Liu, W. Yu, J. Chang, J. Org. Chem., 2015, 80, 7219-7225.
An I2/KI-promoted oxidative C-C bond formation reaction from C(sp3)-H and C(sp2)-H bonds enables the constructions of quinazolines in good yields from N,N'-disubstituted amidines, which are readily prepared. This practical and environmentally benign approach works well with crude amidine intermediates and can also be carried out on a gram scale.
Z. Lv, B. Wang, Z. Hu, Y. Zhou, W. Yu, J. Chang, J. Org. Chem., 2016, 81, 9924-9930.
A highly efficient I2-promoted formal [4 + 2] cycloaddition enables the synthesis of 2-acylquinolines from methyl ketones and arylamines using 1,4-dithane-2,5-diol as an ethylene surrogate. This reaction occurred via an iodination/Kornblum oxidation/Povarov/aromatization sequence with an important role of the arylamine substrate in promoting the reaction.
X. Wu, X. Geng, P. Zhao, J. Zhang, X. Gong, Y.-d. Wu, A.-x. Wu, Org. Lett., 2017, 19, 1550-1553.
A metal-free room temperature decarboxylative cross-coupling between cinnamic acids and arylsulfonyl hydrazides provides (E)-vinyl sulfones. A regio- and stereoselective synthesis of 22 derivatives with diverse structural features has been achieved.
R. Singh, B. K. Allam, N. Singh, K. Kumari, S. K. Singh, K. N. Singh, Org. Lett., 2015, 17, 2656-2659.
A combination of o-iodoxybenzoic acid and iodine mediates a direct synthesis of β-keto sulfones from alkenes and arenesulfinates in good yields in a one-pot reaction.
N. Samakkanad, P. Katrun, T. Techajaroonjit, S. Hlekhlai, M. Pohmakotr, V. Reutrakul, T. Jaipetch, D. Soorukram, C. Kuhakarn, Synthesis, 2012, 44, 1693-1699.
A highly efficient, metal-free, and generally applicable iodine-catalyzed reaction of arylacetylenic acids and arylacetylenes with sodium sulfinates provides arylacetylenic sulfones.
J. Meesin, P. Katrun, C. Pareseecharoen, M. Pohmakotr, V. Reutrakul, D. Soorukram, C. Kuhakarn, J. Org. Chem., 2016, 81, 2744-2752.
A highly efficient copper-catalyzed tandem oxidative cyclization gives polysubstituted oxazoles from readily available starting materials under mild conditions. This is an attractive alternative method for the synthesis of oxazole derivatives.
C. Wang, J. Zhang, S. Wang, J. Fan, Z. Wang, Org. Lett., 2010, 12, 2338-2341.
Ring expansion of keto aziridines provides the corresponding 2,5-diaryl oxazoles in the presence of dicyclohexyl carbodiimide and iodine in refluxing acetonitrile. A plausible mechanism is proposed.
H. A. Samimi, S. Mohammadi, Synlett, 2013, 24, 223-225.
The reaction of terminal alkynes with n-BuLi, and then with aldehydes, followed by the treatment with molecular iodine, and subsequently hydrazines or hydroxylamine provided the corresponding 3,5-disubstituted pyrazoles or isoxazoles in good yields and with high regioselectivity.
R. Harigae, K. Moriyama, H. Togo, J. Org. Chem., 2014, 79, 2049-2058.
A direct iodocyclization of 1-mercapto-3-yn-2-ols derivatives enables the synthesis of 3-iodothiophenes. Various substrates were smoothly converted into the corresponding 3-iodothiophene derivatives in good yields by reaction with molecular iodine in the presence of NaHCO3 at room temperature in MeCN as the solvent.
B. Gabriele, R. Mancuso, G. Salerno, R. C. Larock, J. Org. Chem., 2012, 77, 7640-7645.
Stoichiometric molecular iodine mediates a practical and transition-metal-free oxidative cyclization of acylhydrazones into 1,3,4-oxadiazoles in the presence of potassium carbonate. Even crude acylhydrazone substrates obtained from the condensation of aldehydes and hydrazides can be converted. A series of symmetrical and asymmetrical 2,5-disubstituted 1,3,4-oxadiazoles can be conveniently generated in an efficient and scalable fashion.
W. Yu, G. Huang, Y. Zhang, H. Liu, L. Dong, X. Yu, Y. Li, J. Chang, J. Org. Chem., 2013, 78, 10337-10343.
I2 promotes a metal-free domino protocol for the one-pot synthesis of 1,3,4-oxadiazoles in good yields via oxidative cleavage of C(sp2)-H or C(sp)-H bonds, followed by cyclization and deacylation. The use of K2CO3 is an essential factor in the cyclization and the C-C bond cleavage. This procedure offers good functional group compatibility.
Y. Fan, Y. He, X. Liu, T. Hu, H. Ma, X. Yang, X. Luo, G. Huang, J. Org. Chem., 2016, 81, 6820-6825.
A transition-metal-free condensation of semicarbazide/thiosemicarbazide with aldehydes followed by I2-mediated oxidative C-O/C-S bond formation provides 2-amino-substituted 1,3,4-oxadiazoles and 1,3,4-thiadiazoles in an efficient and scalable fashion.
P. Niu, J. Kang, X. Tian, L. Song, H. Liu, J. Wu, W. Yu, J. Chang, J. Org. Chem., 2015, 80, 1018-1024.
A transition-metal-free, iodine-mediated oxidative intramolecular amination of anilines provides indolines via cleavage of unactivated (sp3)C-H and N-H bonds. The reaction could be performed on a gram scale for the synthesis of functionalized indolines.
J. Long, X. Cao, L. Zhu, R. Qiu, C.-T. Au, S.-F. Yin, T. Iwasaki, N. Kambe, Org. Lett., 2017, 19, 2793-2796.
A practical intramolecular C-H amidation methodology using molecular iodine under basic conditions enables a transition-metal-free cyclization of crude imines for the sequential synthesis of N-protected benzimidazoles without purification of less stable condensation intermediates. The required imine substrates were readily obtained by condensation of simple o-phenylenediamine derivatives and a broad range of aldehydes.
Z. Hu, T. Zhao, M. Wang, J. Wu, W. Yu, J. Chang, J. Org. Chem., 2017, 82, 3152-3158.
A novel metal-free iodine-mediated intramolecular oxidative cyclization protocol allows the preparation of various 2-substituted benzothiazoles.
D.-Y. Zhao, X.-K. Guo, J.-H. Li, R.-Y. Zang, Synthesis, 2012, 44, 927-933.
A multipathway coupled oxidation/heterocyclization domino strategy enables an efficient synthesis of 2-acylbenzothiazoles from various substrates including arylethenes, arylacetylenes, 2-hydroxy-aromatic ketones and carbinols via four distinct pathways free of metal in one pot.
Y.-p. Zhu, F.-c. Jia, M.-c. Liu, A.-x. Wu, Org. Lett., 2012, 14, 4414-4417.
Simple azole substrates can be converted into N-substituted 2-aminoazole derivatives in the presence of nitrogen nucleophiles, lithium tert-butoxide as the base, and iodine to mediate carbon-nitrogen bond formation. This method proceeds at room temperature under an air atmosphere using a normal benchtop set-up, or can be performed conveniently using microwave irradiation.
S. Yotphan, D. Beukeaw, V. Reutrakul, Synthesis, 2013, 45, 936-942.
A catalytic amount of iodine enables a metal-free synthesis of 2-aminobenzothiazoles from cyclohexanones and thioureas in the presence of molecular oxygen as the oxidant under mild conditions. Various 2-aminobenzothiazoles, 2-aminonaphtho[2,1-d]thiazoles, and 2-aminonaphtho[1,2-d]thiazoles were prepared in satisfactory yields.
J. Zhao, H. Huang, W. Wu, H. Chen, H. Jiang, Org. Lett., 2013, 15, 2604-2607.
Iodine-mediated intramolecular cyclization of enamines leads to a various 3H-indole derivatives bearing multifunctional groups in good to high yields under transition metal-free reaction conditions.
Z. He, H. Li, Z. Li, J. Org. Chem., 2010, 75, 4296-4299.
A highly efficient molecular iodine mediated formal [3 + 2 + 1] cycloaddition reaction enables the direct synthesis of substituted quinolines from methyl ketones, arylamines, and styrenes. A self-sequenced iodination/Kornblum oxidation/Povarov/aromatization mechanism has been proposed.
Q. Gao, S. Liu, X. Wu, A. Wu, Org. Lett., 2014, 16, 4582-4585.
Iodine efficiently catalyzes the three-component coupling of aromatic aldehydes, enolizable ketones or keto esters, and acetonitrile in the presence of acetyl chloride at room temperature to afford β-acetamido ketones in good yields.
B. Das, K. Ravinder Reddy, R. Ramu, P. Thirupathi, B. Ravikanth, Synlett, 2006, 1756-1758.
A highly effective indium(III)-catalyzed reductive bromination or iodination of various carboxylic acids with 1,1,3,3-tetramethyldisiloxane (TMDS) and a halogen source tolerates many functional groups. This indium catalytic system is also applicable to the reductive iodination of aldehyded, acyl chlorides, and esters. Furthermore, this reducing system can be applied to the one-pot synthesis of alkyl halides and amine derivatives.
T. Moriya, S. Yoneda, K. Kawana, R. Ikeda, T. Konakahara, N. Sakai, J. Org. Chem., 2013, 78, 10642-10650.
A hydroiodation of alkynes using an iodine/hydrophosphine binary system takes place regioselectively to provide the corresponding Markovnikov-type adducts in good yield. This hydroiodation offers mild conditions, convenient operation, and tolerates various functional groups.
S.-i. Kawaguchi, A. Ogawa, Org. Lett., 2010, 12, 1893-1895.
The reduction of IBX to IBA in the presence of molecular iodine in DMSO generates hypoiodous acid (IOH), which reacts with various olefins as well as α,β-unsaturated ketones leading to their respective iodohydrins with anti stereochemistry. The same redox chemistry in acetonitrile containing TFA produces iodonium ions for facile iodination of aromatic compounds.
J. N. Moorthy, K. Senapati, S. Kumar, J. Org. Chem., 2009, 74, 6287-6290.
An efficient and mild thiophenol-promoted ring-opening of aziridines or epoxides with iodine afforded β-iodo amines or β-iodo alcohols in very good yields.
J. Wu, X. Sun, W. Sun, S. Ye, Synlett, 2006, 2489-2491.
Under neutral reaction conditions, aromatic ketones were transformed into the corresponding α-iodo ketones in high yields by the combination of copper(II) oxide and iodine. Copper(II) oxide acts as catalyst to convert iodine into the reactive iodonium ion and as a base to neutralize hydrogen iodide, and reoxidizes iodide into molecular iodine.
G. Yin, M. Gao, N. She, S. Hu, A. Wu, Y. Pan, Synthesis, 2007, 3113-3116.
Selective introduction of an iodine atom at the α-carbonyl position in various aryl alkyl ketones was effectively achieved by reaction of target molecules with elemental iodine in the presence of N-F reagents such as F-TEDA-BF4 (Selectfluor) as iodination mediators and methanol as the solvent.
M. Jereb, S. Stavber, M. Zupan, Synthesis, 2003, 853-858.
Chalcone epoxides form α,α-dimethoxyacetophenones on heating with iodine in methanol through C-C bond cleavage followed by acetalization of the formyl group. The process occurs through ring opening of the chalcone epoxide by methanol to form β-methoxy alcohol, cleavage of the C-C bond in the latter to form α-ketoaldehyde, and acetalization of the formyl group to give the product.
B. G. Jadhav, S. D. Samant, Synlett, 2014, 25, 1591-1595.
An I2-catalyzed hydroxylation of β-dicarbonyl moieties using air as the oxidant under photoirradiation gives α-hydroxy-β-dicarbonyl compounds. With α-unsubstituted malonates, the hydroxylated dimerization product was afforded as the predominant product along with a minor product, α,α-dihydroxyl malonate.
C.-B. Miao, Y.-H. Wang, M.-L. Xing, X.-W. Lu, X.-Q. Sun, H.-T. Yang, J. Org. Chem., 2013, 78, 11584-11589.
The reaction of 1,3-dicarbonyl compounds with molecular iodine and sodium azide in aqueous DMSO provides a general access to a broad range of geminal diazides with various structural motifs including sterically demanding substituents and ordinary functional groups. The diazidation of 1,3-dicarbonyls can be selectively achieved even in the presence of other 1,3-dicarbonyls with substituents at 2-position.
H. Erhardt, A. P. Häring, A. Kotthaus, M. Roggel, M. L. Tong, P. Biallas, M. Jübermann, F. Mohr, S. F. Kirsch, J. Org. Chem., 2015, 80, 12462-12469.
An iodo Meyer-Schuster rearrangement of 3-alkoxypropargyl alcohols using iodine or NIS in dichloromethane at ambient temperature produces α-iodo-α,β-unsaturated esters in good yields. Secondary alcohols gave Z-isomers exclusively.
S. Puri, N. Thirupathi, M. S. Reddy, Org. Lett., 2014, 16, 5246-5249.
Sm(OTf)3 is an effective catalysts for a versatile and efficient halogen-promoted highly regio- and stereoselective Friedel-Crafts (F-C) alkylation of electron-rich arenes with alkenes and α,β-unsaturated carbonyl compounds in the presence of NBS or I2 as halogen sources.
S. Haira, B. Maji, S. Bar, Org. Lett., 2007, 9, 2783-2786.
Phosphorylation of amines, alcohols, and sulfoximines provides various phosphoramidates, phosphorus triesters and sulfoximine-derived phosphoramidates using molecular iodine as a catalyst and H2O2 as the sole oxidant under mild reaction conditions.
J. Dhineshkumar, K. R. Prabhu, Org. Lett., 2013, 15, 6062-6065.
One-pot tandem Meyer-Schuster rearrangement of arylpropynols and successive radical cyclization with disulfides enables the synthesis of 2-sulfenylindenone derivatives in good yields. The reaction tolerates a number of functional groups.
X.-S. Zhang, J.-Y. Jiao, X.-H. Zhang, B.-L. Hu, X.-G. Zhang, J. Org. Chem., 2016, 81, 5710-5716.