Synthesis of alkyl iodides

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Recent Literature

Ionic liquids [bmim][X] (X = Cl, Br, I, OAc, SCN) are highly efficient reagents for nucleophilic substitution reactions of sulfonate esters derived from primary and secondary alcohols. The newly developed protocol is very environmentally attractive because the reactions use stoichiometric amounts of ionic liquids as sole reagents without additional solvents and activating reagents. Moreover, these ionic liquids can be readily recycled.
Y. Liu, Y. Xu, S. H. Jung, J. Chae, Synlett, 2012, 23, 2663-2666.

Alcohols were efficiently converted to alkyl halides using 1-n-butyl-3-methylylimidazolium halide ioniq liquids in the presence of Brønsted acids at room temperature. The alkyl halide products were easily isolated from the reaction mixture via simple decantation or extraction.
R. X. Ren, J. X. Wu, Org. Lett., 2001, 3, 3727-3728.

The use of a CeCl₃·7H₂O/NaI system in acetonitrile enables an exceedingly mild preparation of iodides from alcohols. The simplicity of this approach, the low cost of reagents, and the ease of use display the attractiveness of the present method for a wide variety of alcohols.
M. Di Deo, E. Marcantoni, E. Torregiani, G. Bartoli, M. C. Bellucci, M. Bosco, L. Sambri, J. Org. Chem., 2000, 65, 2830-2833.

Grignard reagents can act as halide nucleophiles to form alkyl iodides and bromides from alkyl mesylates. Grignard reagents can also be employed in a one-pot halogenation reaction starting from alcohols, which proceeds through mesylate intermediates. The halogenation reaction is confirmed to occur by an S_N2 pathway with inversion of configuration and also runs on multi-gram scale.
N. Hirbawi, P. C. Lin, E. R. Jarvo, J. Org. Chem., 2022, 87, 12352-12369.

Nucleophilic fluorination using CsF or alkali metal fluorides was completed in short reaction time in the presence of [bmim][BF₄] affording the desired products without any byproducts. Facile nucleophilic substitutions such as halogenations, acetoxylation, nitrilation, and alkoxylations in the presence of ionic liquids provided the desired products in good yields.
D. W. Kim, C. E. Song, D. Y. Chi, J. Org. Chem., 2003, 68, 4281-4285.

Silicaphosphine (Silphos), [P(Cl)₃−n(SiO₂)n] is a new heterogeneous reagent that converts alcohols and thiols to their corresponding bromides and iodides in the presence of molecular halogen in refluxing CH₃CN in high to quantitative yields. Separation of the Silphos oxide byproduct can be achieved by a simple filtration.
N. Iranpoor, H. Firouzabadi, A. Jamalian, F. Kazemi, Tetrahedron, 2005, 61, 5699-5704.

The combination of Ph₃P and easily available 1,2-dihaloethanes (XCH₂CH₂X; X = Cl, Br, or I), was very effective for a mild deoxygenative halogenation of alcohols and aldehydes. The use of (EtO)₃P instead of Ph₃P enables a convenient purification process, as the byproduct (EtO)₃P═O could be removed by aqueous washing. A dehydroxy-fluorination proceeds well in the presence of ICH₂CH₂I and CsF as fluoride source in DMF.
J. Chen, J.-H. Lin, J.-C. Xiao, Org. Lett., 2018, 20, 3061-3064.

Treatment of a range of primary and secondary alcohols with MeSCH═NMe₂⁺ I⁻ affords the corresponding alkyl iodides in excellent yield. Selective formation of a primary iodide in the presence of a secondary alcohol can be achieved.
A. R. Ellwood, M. J. Porter, J. Org. Chem., 2009, 74, 7982-7985.

Primary, secondary, tertiary, benzylic, propargylic and α-functionalized alkyl fluorides react in chlorinated or aromatic solvents at room temperature or upon heating with inexpensive lithium iodide to give the corresponding iodides in very good yields. The reaction is selective for aliphatic monofluorides and can be coupled with in situ nucleophilic iodide replacements.
K. Balaraman, S. Kyriazakos, R. Palmer, F. Y. Thanzeel, C. Wolf, Synthesis, 2022, 54, 4320-4328.

Treatment of primary, secondary, or tertiary alkyl fluorides with a catalytic amount of titanocene dihalides, trialkyl aluminum, and polyhalomethanes as the halogen source achieves a halogen exchange reaction in excellent yields under mild conditions. In the case of a fluorine/iodine exchange, no titanocene catalyst is needed. Only C-F bonds are activated under these conditions, whereas alkyl chlorides, bromides, and iodides remained intact.
Y. Mizukami, Z. Song, T. Takahashi, Org. Lett., 2015, 17, 5942-5945.

An efficient and robust method enables a general conversion of aliphatic and aromatic carboxylic acids to organic iodides without the use of heavy metals or strong oxidizing agents. Commercially available N-iodoamides were used for both initiation and halogen donation under irradiative conditions. Isolation of the product is extremely simple and the major co-product is water-soluble.
K. Kulbitski, G. Nisnevich, M. Gandelman, Adv. Synth. Catal., 2011, 353, 1438-1442.

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.

PPh₃ catalyzes the iododecarboxylation of aliphatic carboxylic acid derived N-(acyloxy)phthalimide with lithium iodide as an iodine source under irradiation of 456 nm blue light-emitting diodes to provide primary, secondary, and bridgehead tertiary alkyl iodides.
M.-C. Fu, J.-X. Wang, R. Shang, Org. Lett., 2020, 22, 8572-8577.

The preparation of alkenyl halides of any length from inexpensive starting reagents is reported. Standard organic transformations were used to prepare straight-chain α-olefin halides in excellent overall yields with no detectable olefin isomerization and full recovery of any unreacted starting material.
T. W. Baughman, J. C. Sworen, K. B. Wagener, Tetrahedron, 2004, 60, 10943-10948.

Anhydrous hydrogen iodide preparated directly from molecular hydrogen and iodine using a rhodium catalyst is highly active in the transformations of alkenes, phenyl aldehydes, alcohols, and cyclic ethers to the corresponding iodoalkanes. Therefore, the present methodology offers a practical method for the preparation of various iodoalkanes in excellent atom economy.
C. Zeng, G. Shen, F. Yang, J. Chen, X. Zhang, C. Gu, Y. Zhou, B. Fan, Org. Lett., 2018, 20, 6859-6862.

The combination of methanesulfonic acid and inorganic halide salts (CaCl₂, LiBr, LiI) mediates hydrochlorinations, hydrobrominations, and hydroiodinations of unactivated alkenes in acetic acid. This approach uses readily available and inexpensive reagents to provide alkyl halides in very good yields. An example of deuteriochlorination using deuterated acetic acid as solvent is also demonstrated.
X. Bertrand, P. Paquin, L. Chabaud, J.-F. Paquin, Synthesis, 2022, 54, 1413-1421.

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.

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.

Peri-xanthenoxanthene mediates a reaction of an iododifluoromethylphosphonium salt with unactivated alkenes under blue-light irradiation. This iododifluoromethylation proceeds via activation of the carbon-iodine bond to generate a (phosphonio)difluoromethyl radical cation, which attacks the double bond with subsequent quenching by the iodine.
A. L. Trifonov, L. I. Panferova, V. V. Levin, V. A. Kokorekin, A. D. Dilman, Org. Lett., 2020, 22, 2409-2413.

The use of catalytic amounts of phosphines and blue light irradiation enables an efficient metal-free, iodo perfluoroalkylation of olefins under mild conditions within short reaction times. The reaction presumably proceeds upon generation of perfluoroalkyl radicals, which are formed by catalyst-induced absorption enhancement.
L. Helmecke, M. Spittler, K. Baumgarten, C. Czekelius, Org. Lett., 2019, 21, 7804-7808.

A metal-free ring opening/halogenation of cycloalkanols, which combines both PPO/TBAX oxidant system and blue LEDs irradiation, provides diverse γ, δ, and even more remotely halogenated ketones in good yields under mild conditions.
R. Zhao, Y. Yao, D. Zhu, D. Chang, Y. Liu, L. Shi, Org. Lett., 2018, 20, 1228-1231.

A highly regioselective iodosulfonylation of allenes in the presence of CuI and 1,10-phenanthroline provides useful (E)-α-iodomethyl vinylsulfones in good yields under very mild conditions. This practical reaction is fast and operationally simple.
N. Lu, Z. Zhang, N. Ma, C. Wu, G. Zhang, Q. Liu, T. Liu, Org. Lett., 2018, 20, 4318-4322.

Two methods are described for the regioselective displacement of the primary hydroxy group in methyl glycosides with iodide. Products of the first method employing triphenylphosphine and iodine need purification on a reverse phase column. A one-pot procedure via sulfonates and subsequent substitution with iodide and methods for the protection of the iodoglycosides are also described.
P. R. Skaanderup, C. S. Poulsen, L. Hyldtoft, M. R. Jørgensen, R. Madsen, Synthesis, 2002, 1721-1727.

A convenient, safe, and green protocol, that uses oxone/halide and Fenton bromide, achieves a halogenative semipinacol rearrangement at room temperature. The key feature of this method is the green in situ generation of reactive halogenating species from oxidation of halide with oxone or H₂O₂, which produces a nontoxic byproduct (potassium sulfate or water).
L. Song, Y. Zhou, H. Liang, H. Li, Y. Lai, H. Yao, R. Lin, R. Tong, J. Org. Chem., 2023, 88, 504-512.

Iodofluorination of aliphatic and aromatic alkenes with iodine and HF·pyridine complex (pyr·9HF) was performed under mild conditions in the presence of K₂S₂O₈ or Na₂S₂O₈ as oxidants. Substitution reactions of the iodofluorinated products by nitrogen, sulfur, and oxygen nucleophiles enable further applications as a building blocks for synthesis of 2-fluoroalkyl-substituted compounds.
T. Kitamura, R. Komoto, J. Oyamada, M. Higashi, Y. Kishikawa, J. Org. Chem., 2021, 86, 18300-18303.

Halofluorination of alkenes in the presence of trihaloisocyanuric acids and HF•pyridine results in the formation of vicinal halofluoroalkanes in good yields. The reaction is regioselective leading to Markovnikov-oriented products and the halofluorinated adducts follow anti-addition in the case of cyclohexene and 1-methylcyclohexene.
L. T. C. Crespo, R. da S. Ribeiro, M. S. S. de Mattos, P. M. Esteves, Synthesis, 2010, 2379-2382.

Sodium trifluoromethanesulfinate and iodine pentoxide as safe solid reagents enable a scalable, selective, and convenient iodotrifluoromethylation of a wide range of alkenes and alkynes in aqueous medium. Mechanistic studies confirm a free-radical processes, in which key radical intermediates such as CF₃ and β-CF₃ alkyl radicals have been detected by spin trapping and electron spin resonance.
Z. Hang, Z. Li, Z.-Q. Liu, Org. Lett., 2014, 16, 3648-3651.

β-Functionalized sulfonamides were produced in good yields by the regioselective ring opening of N-tosylaziridines with trimethylsilylated nucleophiles, catalyzed by N,N,N',N'-tetramethylethylenediamine (TMEDA).
S. Minakata, Y. Okada, Y. Oderaotoshi, M. Komatsu, Org. Lett., 2005, 7, 3509-3512.

A highly efficient deoxygenative haloboration of aldehydes provides secondary α-haloboronates. Even tertiary α-haloboronates can be readily prepared via the same strategy with ketones. Furthermore, enantioselective chloroboration of carbonyls was successfully achieved to give chiral secondary or tertiary α-chloroboronates.
D. Wang, J. Zhou, Z. Hu, T. Xu, J. Am. Chem. Soc., 2022, 144, 22870-22876.

Related

A sequential installation of a carbenoid and a hydride into a carbonyl provides halomethyl alkyl derivatives with uniformly high yields and chemocontrol. The tactic is flexible and is not limited to carbenoids. Also, diverse carbanion-like species can act as nucleophiles.
M. Miele, A. Citarella, T. Langer, E. Urban, M. Zehl, W. Holzer, L. Ielo, V. Pace, Org. Lett., 2020, 22, 7629-7634.