Iodine
Name ReactionsRecent Literature
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.
N. Mori, H. Togo, Tetrahedron, 2005,
61, 5915-5925.
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.
Methyl ketones can undergo dichlorination to afford α,α-dichloroketones in
good yields with precise control of the chemoselectivity. Enabled by the I2-dimethyl
sulfoxide catalytic system, in which hydrochloric acid only acts as a
nucleophilic Cl- donor, this straightforward dichlorination reaction is safe and
operator-friendly and has high atomic economy and good functional-group
tolerance.
J.-C. Xiang, J.-W. Wang, P. Yuan, J.-T. Ma, A.-X. Wu, Z.-X. Liao, J. Org. Chem., 2022, 87,
15101-15113.
An efficient iodine-mediated oxidative esterification of acetophenones provides
various α-ketoesters and esters in high yields in the presence of potassium
xanthates. The potassium xanthate not only promotes oxidative esterification but
also provides an alkoxy moiety for the reaction.
X. Luo, R. He, Q. Liu, Y. Gao, J. Li, X. Chen, Z. Zhu, Y. Huang, Y. Li, J. Org. Chem., 2020, 85,
5220-5230.
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.
Direct Transformation of Ethylarenes into Primary Aromatic Amides with N-Bromosuccinimide
and I2-Aqueous NH3
S. Shimokawa, Y. Kawagoe, K. Moriyama, H. Togo, Org. Lett., 2016, 18,
784-787.
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.
A conjugate addition of ethyl cyanoacetates to chalcones and subsequent
iodine-promoted aerobic oxidation provides various α,δ-dicarbonyl esters. The
present protocol features mild reaction conditions, high efficiency, easily
available starting materials, and broad substrate scope.
H. Xu, M.-Y. Weng, H. Chen, Z. Zhang, Synthesis, 2020, 52,
1841-1846.
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.
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.
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.
A facile and practical oxidative cyclization reaction of enamines to
2H-azirines is mediated by molecular iodine under mild conditions. This
transition metal-free approach provides 2H-azirine derivatives in an efficient and scalable fashion.
M. Wang, J. Hou, W. Yu, J. Chang, J. Org. Chem., 2018, 83,
14954-14961.
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.
The combination of I2/PhI(OAc)2 promotes an
efficient and practical one-pot reaction of amines with alkyne esters and
chalcones under solvent-free ball-milling conditions to afford a variety of
polysubstituted trans-2,3-dihydropyrroles in good yields. This protocol
furnishes the corresponding pyrroles with the addition of DDQ as oxidant in a
subsequent step.
H. Xu, H.-W. Liu, K. Chen, G.-W. Wang, J. Org. Chem., 2018, 83,
6035-6049.
Pyrrole-2-carbaldehydes can efficiently be prepared from aryl methyl ketones,
arylamines, and acetoacetate esters via oxidative annulation and Csp3-H
to C=O oxidation in the presence of a copper catalyst, iodine, and oxygen.
Mechanistic investigations indicate that the aldehyde oxygen atom originates
from oxygen. The reaction avoids the use of stoichiometric quantities of
hazardous oxidants.
X. Wu, P. Zhao, X. Geng, C. Wang, Y.-d. Wu, A.-x. Wu, Org. Lett.,
2018, 20, 688-691.
Treatment of N-propargyl-N'-tosylhydrazines with molecular
iodine in the presence of NaHCO3 provided 5-substituted
4-iodo-1-tosylpyrazoles in good yields. In the presence of acetic acid, the
corresponding 5-aryl-4-iodopyrazoles can be obtained in moderate yields. The
reactions are simple and efficient transition-metal-free methods for the
preparation of 5-substituted 4-iodopyrazoles.
A. Saito, K. Yoshida, H. Togo, Synthesis, 2022, 54,
153-160.
An iodine-mediated oxidative [4+1] cyclization of enamines with TMSN3
provides 2,5-disubstituted imidazole-4-carboxylic derivatives. Mechanistic
studies revealed that the reaction proceeds through a sequential removal of two
nitrogen atoms from TMSN3. The synthetic utility was demonstrated
with a gram-scale reaction and various derivatization transformations of the
products.
P. Gao, H. Chen, Z.-J. Bai, S. Zhang, M.-N. Zhao, D. Yang, Y. Li, J. Zhang,
X. Wang, J. Org. Chem., 2021, 86,
10492-10500.
An iodine-mediated formal [2 + 2 + 1] cyclization of methyl ketones, p-toluenesulfonyl
hydrazines, and 1-aminopyridinium iodide provides 4-aryl-NH-1,2,3-triazoles
under metal- and azide-free conditions. This is achieved using p-toluenesulfonyl
hydrazines and 1-aminopyridinium iodide as azide surrogates.
C. Huang, X. Geng, P. Zhao, Y. Zhou, X.-X. Yu, L.-S. Wang, Y.-D. Wu, A.-X.
Wu, J. Org. Chem., 2021, 86,
13664-13672.
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.
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.
An operationally simple direct δ-amination reaction of sp3
C-H bonds, employing molecular iodine (I2) as the sole oxidant under
transition-metal-free conditions, provides facile, efficient access to
pyrrolidines and related heterocyclic derivatives from readily accessible
substrates.
W. Ye, H. Xiong, M. Wang, J. Chang, W. Yu, J. Org. Chem., 2024, 89,
3481-3490.
2,5-disubstituted oxazoles can be synthesized from easily available
arylacetylenes and α-amino acids in the presence of Cu(NO3)2•3H2O
and iodine. This reaction involves an I2/Cu(NO3)2•3H2O-assisted
generation of α-iodo acetophenones, a Kornblum oxidation to phenylglyoxals, a
condensation to imines, and a decarboxylation/annulation/oxidation reaction
sequence.
J. Wang, Y. Cheng, J. Xiang, A. Wu, Synlett, 2019,
30,
743-747.
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.
R. Harigae, K. Moriyama, H. Togo, J. Org. Chem., 2014,
79, 2049-2058.
A molecular iodine-mediated coupling cyclization reaction of N-tosylhydrazones
with sodium azide provides valuable 4-aryl-NH-1,2,3-triazoles via
sequential C-N and N-N bond formation. Mechanistic studies suggest that the
nitrogen atoms of the 1,2,3-triazoles are not entirely from sodium azide.
W.-M. Shu, X.-F. Zhang, X.-X. Zhang, M. Li, A.-J. Wang, A.-X. Wu, J. Org. Chem., 2019, 84,
14919-14925.
I2-mediated oxidative C-N and N-S bond formations in water enable a
metal-free, environmentally benign and convenient strategy for the synthesis of
4,5-disubstituted/N-fused 3-amino-1,2,4-triazoles and 3-substituted
5-amino-1,2,4-thiadiazoles from isothiocyanates. The scalable protocols
exhibited excellent substrate tolerance.
N. Jatangi, N. Tumula, R. K. Palakodety, M. Nakka, J. Org. Chem., 2018, 83,
5715-5723.
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.
The combination of I2 with dimethyl sulfoxide mediates a
cross-coupling cyclization of enaminones, tosylhydrazine, and elemental sulfur
for the synthesis of 5-acyl-1,2,3-thiadiazoles in very good yields under
transition-metal-free conditions. This strategy is operationally simple and
compatible with a wide range of functional groups.
Z. Yang, Y. Liang, A. Li, K. Liu, L. Li, T. Yang, C. Zhou, J. Org. Chem., 2019, 84,
16262-16267
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.
I2-mediated oxidative C-N and N-S bond formations in water enable a
metal-free, environmentally benign and convenient strategy for the synthesis of
4,5-disubstituted/N-fused 3-amino-1,2,4-triazoles and 3-substituted
5-amino-1,2,4-thiadiazoles from isothiocyanates. The scalable protocols
exhibited excellent substrate tolerance.
N. Jatangi, N. Tumula, R. K. Palakodety, M. Nakka, J. Org. Chem., 2018, 83,
5715-5723.
Iodine catalyzes a highly efficient and chemoselective oxidative annulation of
β,γ-unsaturated hydrazones to produce 1,6-dihydropyridazines under mild
conditions. When active β,γ-unsaturated hydrazone compounds containing
electron-donating groups, such as furyl, thienyl, and cycloalkyl, were used,
pyrroles were obtained.
Q. Liu, J. Jiang, X. Ye, J. Sun, Y. Wu, Y. Shao, C. Deng, F. Zhang, J. Org.
Chem., 2023, 88, 10632-10646.
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.
An operationally simple direct δ-amination reaction of sp3
C-H bonds, employing molecular iodine (I2) as the sole oxidant under
transition-metal-free conditions, provides facile, efficient access to
pyrrolidines and related heterocyclic derivatives from readily accessible
substrates.
W. Ye, H. Xiong, M. Wang, J. Chang, W. Yu, J. Org. Chem., 2024, 89,
3481-3490.
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.
An ionic cascade insertion/cyclization reaction of thia-/selena-functionalized
arylisocyanides enables an efficient and practical synthesis of
2-halobenzothiazole/benzoselenazole derivatives. Additionally, a facile access
to 2-aminobenzothiazoles is also achieved by the one-pot cascade reaction of
2-isocyanoaryl thioethers, iodine, and amines.
J. Dong, J. Hu, X. Liu, S. Sun, L. Bao, M. Jia, X. Xu, J. Org. Chem., 2022, 87,
2845-2852.
A highly efficient reaction of readily available aromatic amines,
benzaldehydes, and NH4SCN as a sulfur source provides
2-arylbenzothiazoles with wide functional group compatibility in good yields via
an iodine-mediated oxidative annulation.
A. Dey, A. Hajra,
Org. Lett., 2019, 21, 1686-1689.
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.
I2 and TBHP mediate a convenient synthesis of 2-acylbenzothiazoles in
very good yields from acetophenones and benzothiazoles.
The formal acylation of the benzothiazoles is achieved through a sequence involving
formation of an aryl glyoxal, ring-opening of the
benzothiazole followed by condensation of the amino group with the aryl glyoxal,
cyclization and oxidation.
B. Wang, Q. Zhang, Z. Guo, K. Ablajan, Synthesis, 2020, 52,
3058-3064.
An ionic cascade insertion/cyclization reaction of thia-/selena-functionalized
arylisocyanides enables an efficient and practical synthesis of
2-halobenzothiazole/benzoselenazole derivatives. Additionally, a facile access
to 2-aminobenzothiazoles is also achieved by the one-pot cascade reaction of
2-isocyanoaryl thioethers, iodine, and amines.
J. Dong, J. Hu, X. Liu, S. Sun, L. Bao, M. Jia, X. Xu, J. Org. Chem., 2022, 87,
2845-2852.
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.
A palladium-catalyzed iodine-assisted carbonylation reaction of indoles with
readily available ClCF2CO2Na and alcohols
provides
indole-3-carboxylates via a preiodination strategy of indoles. Different from
classic carbonylation using toxic and difficult-to-handle carbon monoxide, this
operationally simple and scalable reaction employed difluorocarbene as the
carbonyl surrogate.
M. Cao, D. Zuo, D. Wang, Y. Li, J. Zhao, J. Tan, P. Li, J. Org. Chem., 2024, 89,
5871-5877.
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 cross-dehydrogenative coupling enable a low-temperature procedure for the
synthesis of 3,3-disubstituted 2-oxindoles. The use of a strong, nonreversible
base effects a dramatic drop in reaction temperature. With iodine as an "oxidant",
new evidence suggests that this transformation may occur via a transiently
stable iodinated intermediate rather than by direct single-electron oxidation.
J. R. Donald, R. J. K. Taylor, W. F. Petersn, J. Org. Chem.,
2017, 82, 11288-11294.
The combination of Ph3P and I2 promotes a synthesis of
benzimidazolones from readily accessible hydroxamic acids. Upon Lossen-type
rearrangement of the O-activated hydroxamic acids, the in situ generated
isocyanates undergo an intramolecular attack by ortho N-nucleophiles
producing the cyclized products in good yields under mild conditions.
N. Wiriya, D. Yamano, S. Hongsibsong, M. Pattarawarapan, W. Phakhodee, Synlett, 2022,
33,
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An I2/TBHP-mediated oxidation of commercially available indoles
affords isatins in moderate to good yields.
Y. Zi, Z.-J. Cai, S.-Y. Wang, S.-J. Ji, Org. Lett., 2014,
16, 3094-3097.
I2-mediated oxidative C-N and N-S bond formations in water enable a
metal-free, environmentally benign and convenient strategy for the synthesis of
4,5-disubstituted/N-fused 3-amino-1,2,4-triazoles and 3-substituted
5-amino-1,2,4-thiadiazoles from isothiocyanates. The scalable protocols
exhibited excellent substrate tolerance.
N. Jatangi, N. Tumula, R. K. Palakodety, M. Nakka, J. Org. Chem., 2018, 83,
5715-5723.
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.
An efficient copper-catalyzed intermolecular decarboxylative cascade cyclization
of aryl aldehydes, anilines, and acrylic acid permits the direct synthesis of
2-substituted quinolines. This method features promising chemo- and
regioselectivity and also tolerates a wide variety of substrates with excellent
functional-group tolerance, high yields, a radical reaction pathway, and aerobic
reaction conditions.
R. Chatterjee, M. Pothireddy, R. Dandela, Synlett, 2023,
34,
1058-1062.
A practicable quinoline synthesis from aniline and two amino acids provides a
wide range of quinolines with high efficiency and diversity including
pharmaceutical derivatives, photochemical active compounds, and challenging
scaffolds. Mechanistic studies revealed that I2 promotes
decarboxylation, oxidative deamination, and selective formation of new C-N and
C-C bonds.
J.-C. Xiang, Z.-X. Wang, Y. Cheng, S.-Q. Xia, M. Wang, B.-C. Tang, Y.-D. Wu,
A.-X. Wu, J. Org. Chem.,
2017, 82, 9210-9216.
A [5+1]-cyclization of 2-vinylanilines with tetraalkylthiuram disulfides in
the presence of iodine and copper(II) triflate provides a variety of
2-aminoquinolines in very good yields. This facile one-step synthesis directly
employs readily available and low-cost thiurams as both a C1 synthon and a
nitrogen source.
J. Jiao, P. Wang, F. Xiao, Z. Zhang, Synlett, 2022,
33,
569-574.
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.,
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16, 4582-4585.
A synergistic I2/amine promoted formal [4 + 2] cycloaddition of
methyl ketones, arylamines, and aryl(alkyl)acetaldehydes provides various
2-acyl-3-aryl(alkyl)quinolines via an iodination/Kornblum oxidation/Povarov/aromatization
sequence. Notably, the arylamine reactants also acted as indispensable catalysts
to promote enamine formation.
X. Geng, X. Wu, P. Zhao, J. Zhang, Y.-D. Wu, A.-X. Wu, Org. Lett.,
2017, 19, 4179-4182.
An efficient [2 + 1 + 3] cyclization reaction of aryl methyl ketones, arylamines, and
1,3-dicarbonyl compounds provides 2-aryl-4-quinolinecarboxylates in good yields
under mild conditions. This metal-free process achieved a C-C bond cleavage of 1,3-dicarbonyl compounds
for use as a C1
synthon.
Y. Zhou, P. Zhao, L.-S. Wang, X.-X. Yu, C. Huang, Y. D. Wu, A.-X. Wu, Org. Lett., 2021, 23, 6461-6465.
Iodine promotes an oxidative decarboxylation of α-amino acids, followed by an
oxidative cyclization reactio with inexpensive 2-aminobenzamides to provide a
wide range of quinazolinones. The reaction offers operational simplicity,
consistent yield, functional group tolerance and sustainability. Under the same
reaction conditions, benzoxazoles and benzothiazoles can be synthesized too.
S. K. Samanta, M. K. Bera, Synthesis, 2023,
55, 2561-2569.
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.