Iodonium salts in organic synthesis

This review summarizes the chemistry of iodonium salts with emphasis of their synthetic applications. The preparation and reactions of diaryliodonium, alkenyl(aryl)iodonium, alkynyl(aryl)iodonium, and alkyl(aryl)iodonium salts are overviewed. Application of these reagents allows mild and highly selective arylations, alkenylations, alkynylations, and alkylations of various organic and inorganic substrates in a facile and environmentally friendly manner.


Introduction
Since the beginning of the 21st century, the organic chemistry of hypervalent iodine compounds has experienced an unprecedented, explosive development.Now hypervalent iodine compounds are widely used in organic synthesis as efficient reagents whose chemical properties are similar to transition metals derivatives, like mercury(II), thallium(III), lead(IV), osmium(VIII) and chromium(VI), but without the toxicity and environmental problems associated with these heavy metals.Many reviews, some comprehensive, but most dealing with specific aspects of hypervalent organoiodine chemistry, have been published just in the last ten years. 1 Particularly noteworthy was the publication of commemorative issue of Arkivoc honoring Prof. Anastasios Varvoglis, in which 22 research articles and accounts covered all key areas of hypervalent iodine chemistry. 2More recently, a Symposium-in-Print Tetrahedron issue dedicated to recent advances and applications of hypervalent iodine chemistry in concert with the third International Conference on Hypervalent Iodine Chemistry (ICHCI2010) has been compiled by Quideau and Wirth. 3Previously we have published two review in Arkivoc summarizing synthetic applications of hypervalent iodine(V) 4a and hypervalent iodine(III) 4b compounds.The purpose of the present review is to summarize the chemistry of iodonium salts, R2I + X -, with emphasis on recent synthetic applications, the literature coverage is through May 2011.To our knowledge, this is the first comprehensive review covering the chemistry of all classes of iodonium salts.Several earlier reviews have discussed more specific aspects of the chemistry of alkynyliodoniun salts, 5a alkenyliodonium salts, 5b-d diaryliodonium salts, 5e,f and fluoroalkyliodonium salts.5g

Classification and General Features of Iodonium Salts
Hypervalent iodine organic compounds belong to two general structural types: (1) iodine(III) compounds 1 and 2, also named  3 -iodanes according to IUPAC recommendations, and (2) iodine(V) compounds 3, or  5 -iodanes (Scheme 1).The iodine atom in  3 -iodanes 1 has a total 10 electrons and the overall geometry of a distorted trigonal bipyramid with two heteroatom ligands L occupying the axial positions, and the least electronegative aryl group and both electron pairs residing in equatorial positions.Iodonium salts 2, with consideration of the closely associated anionic part of the molecule, have similar pseudo trigonal bipyramidal geometry and are generally classified as hypervalent  3 -iodanes with two carbon ligands (R2IX, 2).In the hypervalent model, bonding in RIX2 uses the non-hybridized 5p orbital of iodine in the linear X-I-X bond.Such a linear three-center, four-electron (3c-4e) bond is highly polarized and is longer modification of this procedure involves using aryltrifluoroborates, ArBF3 -K + , instead of tetraarylborates under mild conditions.11a Likewise, fluoroorganoiodonium tetrafluoroborates (C6F5)2I + BF4 -, (4-C5F4N)2I + BF4 -and [C6F5(4-C5F4N)I + BF4 -can be prepared by interaction of the appropriate (difluoroiodo)arenes with fluorinated organodifluoroboranes, ArfBF2, in dichloromethane at 0 to 20 o C. 11b

Scheme 2
Another protocol uses a similar tin-iodine(III) and silicon-iodine(III) exchange reaction of (diacetoxyiodo)arenes or iodosylbenzene with tetraphenylstannane or trimethylsilylbenzene in the presence of boron trifluoride etherate. 12rohn and co-workers reported the preparation of a perfluoroaryliodonium salt, (C6F5)2I + AsF6 -, by the electrophilic arylation of C6F5I with a stable pentafluorophenylxenonium hexafluoroarsenate, C6F5Xe + AsF6 -. 13 Numerous methods for the preparation of symmetrical and unsymmetrical diaryl-and hetaryliodonium sulfates and organosulfonates have been reported.Usually unsymmetrical diaryl-and hetaryl(aryl)iodonium tosylates are obtained by reactions of [hydroxy(tosyloxy)iodo]arenes with arenes, 14a aryl-or hetaryltrimethylsilanes, 14b,c aryltributylstannanes, 14d-f or arylboronic acids.14g The reaction of [hydroxy(tosyloxy)iodo]benzene with arylstannanes proceeds under milder conditions compared to arylsilanes and is applicable to a wide range of arenes with electron-withdrawing substituents.Arylboronic acids in general have some advantage over arylstannanes in the case of the electron-rich heterocyclic precursors.14g A common procedure for obtaining unsymmetrically functionalized diaryliodonium triflates 10 from iodosylbenzene 15a or (diacetoxyiodo)arenes 8 15b in reaction with arenes 9 in trifluoromethanesulfonic acid is shown in Scheme 3.This procedure is simple and provides diaryliodonium triflates in relatively high yields, but it is limited to aromatic substrates that are not sensitive to strong acids.Moreover, the formation of the p-phenylene type oligomeric iodonium salts as side products may occur upon the reaction of (diacetoxyiodo)benzene with trifluoromethanesulfonic acid.15c This procedure was improved to carry out the reaction more selective and under milder conditions, obtaining desired aryl(phenyl)iodonium triflates from (diacetoxyiodo)benzene and arylboronic acids in the presence of triflic acid at -30 o C in 74-97% yields.14g

Scheme 3
Several modified procedures for the preparation of diaryliodonium triflates have recently been reported. 16Kitamura and Hossain have developed a one-pot reaction to obtain symmetrical diaryliodonium triflates in good yields directly from iodoarenes and aromatic substrates using K2S2O8 as an oxidant.16a Additional improvements of this procedure consist of the reaction of arenes with elemental iodine and K2S2O8 in trifluoroacetic acid, followed by treatment with sodium triflate (Scheme 4).16b,c

Scheme 4
Olofsson and co-workers have developed several efficient one-pot syntheses of diaryliodonium salts.16d-i A general and universal procedure provides both symmetrical and unsymmetrical diaryliodonium triflates 13 from both electron-deficient and electron-rich arenes 12 and aryl iodides 11 using mCPBA as the oxidant and triflic acid (Scheme 5).16d-f The electronrich diaryliodonium tosylates are prepared similarly using toluenesulfonic acid instead of triflic acid as the additive.16f Symmetrical diaryliodonium triflates can be synthesized by a modified one-pot procedure from iodine, arenes, mCPBA and triflic acid under similar conditions.16d,e A similar procedure based on a one-pot reaction of arylboronic acids, aryl iodides, mCPBA and BF3•Et2O has recently been used for regioselective synthesis of unsymmetrical diaryliodonium tetrafluoroborates.16g,h In a further improvement of this approach, a range of symmetrical and unsymmetrical diaryliodonium triflates were prepared employing urea-H2O2 as the environmentally benign oxidizing agent.16i Kita and co-workers have recently demonstrated that hexafluoroisopropanol (HFIP) can be used as a highly efficient solvent for the synthesis of various diaryliodonium salts.16j,k Skulski and Kraszkiewicz have also reported a new direct method for the preparation of various symmetrical diaryliodonium bromides (in 15-88% crude yields) from arenes by the reaction of ArH with NaIO4 in sulfuric acid followed by the addition of KBr. 17 A very mild and general method for the preparation of diaryl-and heteroaryliodonium triflates is based on iodonium transfer reactions of iodine(III) cyanides with the respective arylor heteroarylstannanes. 18 Specifically, (dicyano)iodonium triflate 14, generated in situ from iodosyl triflate and TMSCN, reacts with tributyltin derivatives of aromatic and heteroaromatic compounds affording the corresponding symmetrical iodonium salts under very mild conditions (Scheme 6).18c,d

Scheme 6
Similar iodonium exchange reaction involves aryl(cyano)iodonium triflates 15 and stannylated aromatic precursors providing many kinds of diaryl or aryl(heteroaryl) iodonium salts.18a,b,e Tykwinski, Hinkle and co-workers have reported an application of such iodonium transfer reaction for obtaining of a series of mono-and bithienyl(aryl)iodonium triflates 16 with increasingly electron-withdrawing substituents on the aryl moiety (Scheme 7).18e

Scheme 7
The preparation of several macrocyclic iodonium triflates, such as rhomboids 19, a square 22, and a pentagon 23 has been reported (Scheme 8). 19The rhomboid shaped molecules 19 were prepared by the treatment of compounds 17 and 18 with trimethylsilyl triflate.19a The reaction of dication 20 with compound 21 in the presence of Me3SiOTf gave an iodonium containing molecular square 22 in 70% yield. 19In addition, a pentagon-shaped macrocycle 23 was prepared in 60% yield from precursors 20 and 17.The structures of these iodonium-containing charged macrocycles were established using elemental analysis, multinuclear NMR and mass spectrometry.These iodonium-containing macromolecules may find potential application in nanotechnology.19a A very mild and selective approach to aryl-and hetaryliodonium chlorides 26 is based on the reaction of the appropriate aryllithium 24 (generated in situ from bromoarenes and butyllithium) with trans-(chlorovinyl)iodonium dichloride 25 (Scheme 9). 20The iodonium transfer reagent 25 is prepared by the reaction of iodine trichloride with acetylene in concentrated hydrochloric acid; 20c this compound is extremely unstable and should be handled and stored with proper safety precautions.20b The iodonium transfer procedure with reagent 25 is particularly useful for the preparation of bis(hetaryl)iodonium chlorides 28 from the appropriate nitrogen heterocycles 27 (Scheme 9).20b Scheme 9

Alkenyl(aryl)iodonium salts
Boron trifluoride-catalyzed silicon-iodine(III) exchange reaction of organosilanes 29 with iodosylarenes followed by treatment with aqueous NaBF4 constitutes the most general method for synthesis of alkenyl(aryl)iodonium tetrafluoroborates 30 (Scheme 10).10b,21 This reaction proceeds under mild conditions and in a stereospecific manner with retention of geometry of organosilanes.

Scheme 10
A similar borane-iodine(III) exchange of organoboronic acids 31 with iodosylbenzene or (diacetoxyiodo)benzene in the presence of boron trifluoride etherate is an efficient alternative method for a selective preparation of alkenyl(phenyl)iodonium tetrafluoroborates 32 in excellent yields (Scheme 11). 22

Scheme 11
(E)-β-Fluoroalkenyl(tolyl)iodonium tetrafluoroborates 33 are conveniently synthesized by the treatment of terminal alkynes with 4-iodotoluene difluoride in the presence of boron trifluoride etherate (Scheme 12).23a This reaction occurred instantaneously at -78 o C to give fluoroalkenyliodonium salts 33 in good yields with high stereoselectivity.Likewise, various alkenyliodonium organosulfonates can be synthesized via electrophilic addition of the appropriate hypervalent iodine reagents to alkynes.23b-d

Scheme 12
(E)-β-Fluoroalkenyl(phenyl)iodonium tetrafluoroborates 35 can be stereoselectively prepared by the reaction of alkynyl(phenyl)iodonium salts 34 with aqueous HF in good yields (Scheme 13). 24The method is applicable to the synthesis of fluoroalkenyliodonium salts having functional groups such as ketone, ester, and chloride.

Scheme 13
A very general and mild procedure for the stereospecific synthesis of alkenyliodonium organosulfonates 38 involves the reaction of aryl(cyano)iodonium triflates and tosylates 37 with stannylated alkenes 36 (Scheme 14). 25

Alkynyl(aryl)iodonium salts
A widely used method for obtaining the alkynyl(phenyl)iodonium tetrafluoroborates involves the reaction of iodosylbenzene with alkynylsilanes and boron trifluoride etherate followed by treatment with aqueous NaBF4.27a,b Varvoglis, Koumbis and co-workers have used this procedure for the preparation of several ortho-substituted arylethynyl(phenyl)iodonium tetrafluoroborates 43 from alkynylsilanes 42 (Scheme 16).27c

Scheme 16
A modified procedure for the synthesis of alkynyl(phenyl)iodonium tetrafluoroborates 45 reported by Hara and co-workers consists of the direct reaction of terminal alkynes 44 with iodosylbenzene, 42% aqueous solution of tetrafluoroboric acid, and a catalytic amount of mercury oxide (Scheme 17).27d

Scheme 17
Yoshida and coauthors have reported a facile preparation of iodonium salts 47 by the reaction of potassium organotrifluoroborates 46 with (difluoroiodo)arenes under mild conditions (Scheme 18).11a A similar approach to alkynyliodonium salts by the reaction of alkynyldifluoroboranes; polyfluoroorganyliodine difluorides was developed by Frohn and Bardin.11c

Scheme 18
Alkynyl(phenyl)iodonium tosylates are commonly prepared by gentle heating of [hydroxy(tosyloxy)iodo]benzene with terminal alkynes in chloroform or dichloromethane.27b,28 This method is also applicable to the synthesis of alkynyliodonium mesylates and 4nitrobenzenesulfonates by the reaction of the appropriate [hydroxy(organosulfonyloxy)iodo]benzenes with terminal alkynes under similar conditions.28a The most versatile method of preparation of alkynyl(phenyl)iodonium triflates 50 employs the iodonium transfer reaction between cyano(phenyl)iodonium triflate 49 and alkynylstannanes 48 under very mild conditions (Scheme 19).29a This procedure is particularly useful for the preparation of various complex, functionalized alkynyliodonium derivatives, such as compounds 51, 52, 29b 53, 29c 54, 29d and 55. 29e Compounds 51-55 are formed under these very mild conditions in high yields (80-90%) and can be used in subsequent transformations without additional purification.

Scheme 19
An alternative general procedure for the selective preparation of alkynyl(phenyl)iodonium triflates in moderate yields employs the reaction of alkynylsilanes or alkynylstannanes with Zefirov's reagent, 2PhIO•Tf2O.27c,30a This method is also applicable to the synthesis of the parent ethynyl(phenyl)iodonium triflate.30b

Alkyl(aryl)iodonium salts
Iodonium salts with one or two aliphatic groups generally lack stability.The presence of electron-withdrawing groups in the alkyl group of iodonium salts has a pronounced stabilizing effect.The most stable derivatives of this type are fluoroalkyl(aryl)iodonium salts 56, 57 and (arylsulfonylmethyl)iodonium triflates 58.Iodonium salts 56-58 are usually prepared by the reaction of the appropriate bis(trifluoroacetate) like 59 with benzene in the presence of trifluoromethanesulfonic or other strong acid.The structure of iodonium triflate 58 (Ar = Tol) was unambiguously established by a single-crystal X-ray analysis.31a

Scheme 20
The preparation of fluoroalkyliodonium salts 60 by the reaction of bis(trifluoroacetates) 59 with benzene and triflimide acid was reported (Scheme 21).31b-d The structure of trifluoroethyl(phenyl) iodonium salt 60 (n = 1) was established by a single-crystal X-ray analysis.31b In contrast to fluoroalkyliodonium triflates 57, compounds 60 are stable to water and can be used for fluoroalkylations in aqueous media.

Arylations
The most important and synthetically useful reactions of aryliodonium salts include the direct electrophilic arylations of various nucleophiles, the transition metal mediated cross-coupling reactions, and the reactions involving the generation and trapping of the benzyne intermediates.
Numerous examples of the rections of aryliodonium salts with such nucleophiles as thiosulfonate anions, fluoride anion, malonates, and silyl enol ethers under polar, non-catalytic conditions are provided in our previous reviews.1j,u In more recent papers, the electrophilic arylations of sodium arenesulfinates, 32a potassium carbonotrithioates, 32b and benzazoles 32c using diaryliodonium salts in ionic liquids, and the arylations of anilines, 32d sodium tetraphenylborate 32e and vinylindiums 32f have been reported.
The mechanism of solvolysis of methoxy-substituted diaryliodonium tetrafluoroborates, ArI + Ph -BF4, in methanol and 2,2,2-trifluoroethanol has been investigated.32g The solvolysis products include alkoxide substitution products (ArOR and PhOR) as well as iodoarenes (PhI and ArI).The ratios of products, ArOR/PhOR, range from 8/2 to 4/6.The results of this study provide experimental evidence against the formation of aryl cation under these conditions and support the pathways via ligand coupling or SNAr2 mechanisms involving a solvent molecule as a nucleophile in the transition state.32g If the reaction is performed in inert (not nucleophilic) solvent, various nucleophiles may be involved in the reaction with iodonium salt.When diaryliodonium salt reacts with F -anion as nucleophile there is arylfluoride among products.This reaction is widely applied for introduction 18 F isotope into different organic substrates to obtain labeled agents for the positron emission tomography.This topic is separately covered in Section 4.5 hereinafter due to its importance and wide usage.
Arylations of carbon nucleophiles using aryliodonium salts are particularly important.Compounds containing an active methylene group, such as malonates, or the respective carbanions formed in situ, react smoothly with diaryliodonium salts to yield -arylated products.20b,33 Aggarwal and Olofsson have developed a direct asymmetric -arylation of prochiral ketones using chiral lithium amide bases and diaryliodonium salts.20b In a specific example, the deprotonation of cyclohexanone derivative 61 using chiral Simpkins' (R,R)-base followed by the reaction with pyridyl iodonium salt gave the arylated product 62 in 94% enantiomeric excess (Scheme 22).This reaction (Scheme 22) has been employed in a short total synthesis of the alkaloid (-)-epibatidine.20b

Scheme 22
Quideau and co-workers reported a regioselective dearomatizing phenylation of phenols and naphthols using diaryliodonium salts.34a,b For example, the treatment of naphthols 63 substituted at the ortho position by a small electron-donating group with diphenyliodonium chloride leads to their regioselective ortho-phenylation to give products 64 (Scheme 23).The mechanism of this reaction involves a nonradical direct coupling of the ligands on the hypervalent iodine center.34a The formation of phenol ethers due to the O-phenylation can also occur when the reaction of phenolate anion with diphenyliodonium chloride is carried out in a polar aprotic solvent such as dimethylformamide.34a

Scheme 23
Indoles and pyrroles can be efficiently arylated by aryliodonium salts in position 3 in the absence of metal catalysts (Scheme 24).34c The reaction of unsymmetrically substituted diaryliodonium salts results in the preferential transfer of the less sterically hindered aromatic moiety.

Scheme 24
Thienyl(phenyl)iodonium salts and other heteroaryl(phenyl)iodonium salts can be used as the selective heteroaryl transfer agents in reactions with phenol ethers.These heteroarylations occur at room temperature in the hexafluoroisopropanol (HFIP) solution in the presence of TMSOTf via SET-mechanism.34d The O-arylation of the appropriate phenols using symmetrical iodonium salts has been utilized in the synthesis of hydroxylated and methoxylated polybrominated diphenyl ethers, some of which are related to natural products.35a,b In particular, several polybrominated diphenyl ethers 67 were prepared by the reaction of iodonium salt 65 with phenols 66 in N,N-dimethylacetamide solution under basic conditions (Scheme 25).35a

Scheme 25
Very recently, Olofsson and co-workers have reported a general and high-yielding synthesis of various diaryl ethers using the reaction of diaryliodonium salts with phenols under similar conditions (Scheme 26).The scope of products includes bulky ortho-substituted diaryl ethers, which are difficult to obtain by metal-catalyzed protocols.35c

Scheme 26
Several examples of S-arylation of sulfides and P-arylation of phosphines using diaryliodonium salts were reported in the older literature.35d,e These reactions generally follow a radical chain mechanism.The arylation of phosphines has been used to effect the photoinitiation of cationic polymerization.35f Aryliodonium salts have been found applicable for arylation of carbon surface. 36Various iodonium salts can be used as functional groups carriers that allow covering carbon surface by wide range of functional groups, from electron-withdrawing to electron-donating.Properties of modified material are also varied widely.

Scheme 27
Kitamura and co-workers reported the preparation and uses of several efficient benzyne precursors based on aryliodonium salts. 38n particular, phenyl[2-(trimethylsilyl)phenyl]iodonium triflate (70) is readily prepared by the reaction of 1,2bis(trimethylsilyl)benzene with the PhI(OAc)2/TfOH reagent system.38a The treatment of reagent 70 with tetrabutylammonium fluoride in dichloromethane at room temperature generates benzyne, which can be trapped with a diene to afford the respective benzyne adducts in high yields.38a Examples of synthetic application of reagent 70 as benzyne precursor include Oarylation of carboxylic acids leading to aryl esters 71, 39a preparation of 2-aryl-substituted nitriles 73 by arylation of nitriles 72 via a benzyne reaction, 39b and cycloaddition/elimination reaction of thiophene S-oxide 74 with benzyne leading to product 75 (Scheme 28).39c Reagent 70 was also used in the synthesis of spiro(imidazolidine-2,3'-benzo[b]thiophene) by a one-pot reaction of benzyne, aryl isothiocyanates and N-heterocyclic carbenes, 39d and for the preparation of benzo[b]seleno[2,3-b]pyridines by the reaction of acetic acid 2-selenoxo-2H-pyridin-1-yl esters with benzyne.39e

Scheme 28
The efficient acylbenzyne precursors, [5-acyl-2-(trimethylsilyl)phenyl]iodonium triflates 76 have been prepared by the reaction of the appropriate 1,2-bis(trimethylsilyl)benzenes with PhI(OAc)2 in the presence of trifluoromethanesulfonic acid in dichloromethane at room temperature.Treatment of these reagents with Bu4NF in dichloromethane generates acylbenzynes 77, which can be trapped by furan to give adducts 78 in high yield (Scheme 29).38d

Scheme 29
Lee and co-workers reported the preparation of oxadisilole-substituted benzyne precursors, such as iodonium triflate 80, from benzobisoxadisilole 79 and the PhI(OAc)2/TfOH reagent system.39f The treatment of reagent 80 with Bu4NF in THF and diisopropylamine at room temperature generates oxadisilole-substituted benzyne 81, which can be trapped with furan to afford adduct 82 in good yield (Scheme 30).

Scheme 30
Ko, Kang and co-workers have reported the generation and trapping of 1,2dehydrocarborane, the carborane analog of benzyne.39g The 1,2-dehydrocarborane precursor, phenyl[o-(trimethylsilyl)carboranyl]iodonium acetate, was readily prepared by the reaction of [o-(trimethylsilyl)carboranyl]lithium and PhI(OAc)2.1,2-Dehydrocarborane was efficiently generated from phenyl[o-(trimethylsilyl)carboranyl]iodonium acetate by treatment with CsF in ether and trapped with dienes such as anthracene, naphthalene, norbornadiene and 2,5dimethylfuran to give the respective 1,2-dehydrocarborane adducts in high yield.39g Very recently, McMillan and Allen have accomplished the enantioselective -arylation of aldehydes using diaryliodonium salts and a combination of copper and organic amine catalysts.In a specific example, this new asymmetric protocol has been applied to the rapid synthesis of (S)-ketoprofen, a commercially successful oral and topical analgesic. 40

Alkenylations
Alkenyl(phenyl)iodonium salts are very reactive compounds because of the excellent leaving group ability of the phenyliodonium moiety (10 12 times greater than for iodine itself) combined with its high electron-withdrawing properties (the Hammett substituent constant m for the PhI + group is 1.35).41a Several research groups have been involved in the mechanistic studies of nucleophilic substitution in alkenyliodonium salts.41b-i Various mechanisms, including SN1, SN2, ligand coupling, and Michael addition-elimination have been observed in these reactions.The mechanistic aspects of the reactions of vinylic iodonium salts with nucleophiles have been reviewed by Okuyama 5d and by Ochiai. 5b Particularly interesting is the observation of cyclohexyne intermediates 84 as products of elimination in the reactions of 1-cyclohexenyl(phenyl)iodonium salts 83 with mild bases such as tetrabutylammonium acetate, fluoride ion, alkoxides, and amines in aprotic solvents.41a,f,h Cyclohexynes 84 could be effectively trapped with tetraphenylcyclopentadienone to give products of [4+2] cycloaddition 85 in high yields (Scheme 31).Cycloheptyne intermediates can be generated under similar conditions from the appropriate iodonium precursors.41a,f,i

Scheme 31
Alkenyl(phenyl)iodonium salts have found synthetic application as alkenylating reagents in the reactions with various nucleophilic substrates.In most cases these reactions proceed with predominant retention of geometry via the addition-elimination mechanism or ligand coupling on the iodine.Recent examples of alkenylations of nucleophiles under non-catalytic conditions include the stereoselective reactions of alkenyliodonium salts with sodium selenide, sodium sulfide, sodium azide, potassium thiocyanate, 42a and benzotriazole.42b In a specific example, functionalized beta-enamines 86 have been prepared by the reaction of polymer-supported alkenyliodonium tosylates 41 with various nucleophiles at room temperature (Scheme 32).26a

Scheme 33
Only a few examples of non-catalytic alkenylation of carbon nucleophiles are known.In particular, enolate anions derived from various 1,3-dicarbonyl compounds can be vinylated with cyclohexenyl (91) and cyclopentenyl iodonium salts to afford products 92 (Scheme 34). 44

Scheme 34
The selectivity of the alkenylation reactions and the yields of products can be dramatically improved by carrying out the reaction of alkenyliodonium salts with carbon nucleophiles in the presence of transition metal compounds in stoichiometric or catalytic amounts.In the presence of a copper(I) catalyst iodonium salts selectively react with iodide anion, 24 organoborates, 45a Grignard reagents, 45b and terminal alkynes 45c to afford the respective cross-coupling products in high yields with complete retention of geometry.An example of such a reaction is represented by the copper-mediated cross-coupling of H-phosphonates 94 with vinyliodonium salts 93 leading to 2-arylvinylphosphonates 95 under mild conditions (Scheme 35).45d

Scheme 35
Alkenyliodonium salts can be used as highly reactive reagents for Heck-type olefination, 46a,b Sonogashira-type coupling with alkynes, 24a,46c and similar palladium-catalyzed cross-coupling reactions.23a,24b,46d In a specific example, (Z)--fluoro-α,β-unsaturated esters 97 were stereoselectively synthesized from salts 96 by the Pd-catalyzed methoxycarbonylation reaction (Scheme 36).46d The reaction proceeded at room temperature and various functional groups on the substrate can tolerate the reaction conditions.

Scheme 36
Reactions of alkenyliodonium salts with strong bases may lead to the generation of an alkylidenecarbene via a base-induced -elimination.Alkylidenecarbenes generated by this method can undergo a 1,5-carbon-hydrogen insertion, providing a useful route for the construction of substituted cyclopentenes. 47In a recent example, an efficient synthesis of fluorocyclopentenes 99 by the reaction of (Z)-(2-fluoroalkenyl)iodonium salts 98 with potassium tert-butoxide has been developed (Scheme 37).The mechanism of this reaction involves the initial generation of (-fluoroalkylidene)carbenes which give fluorocyclopentenes via 1,5-C-H insertion.47a Scheme 37

Reactions of alkynyl(aryl)iodonium salts
Reactions of alkynyliodonium salts with nucleophiles proceed via an addition-elimination mechanism involving alkylidene carbenes as key intermediates.Depending on the structure of the alkynyliodonium salt, specific reaction conditions, and the nucleophile employed, this process can lead to a substituted alkyne due to the carbene rearrangement, or to a cyclic product via intramolecular 1,5-carbene insertion.5a Both of these reaction pathways have been widely utilized in organic synthesis.

Scheme 38
Scheme 39 Scheme 40 Alkynyl(phenyl)iodonium salts can be efficiently coupled with organocopper reagents, 49a or with organoboronic acids or organostannanes in the presence of Cu(I) catalysts.49b,c Specifically, the copper iodide-catalyzed cross-and carbonylative coupling reactions of alkynyliodonium salts 108 with arylboronic acids 107 or organostannanes 110 under mild conditions afford arylacetylenes 109 and aryl alkynyl ketones 111 in high yields (Scheme 41).49c Interestingly, alkynyliodonium tetrafluoroborates 108 are more efficient in these coupling reactions than the corresponding iodonium triflates and tosylates.

Scheme 42
Ochiai and co-workers have investigated the mechanism for the one-pot synthesis of 2,4disubstituted thiazoles 117 by cyclocondensation of alkynyliodonium salts 115 with thioureas or thioamides 116 (Scheme 43).51a This reaction was originally reported by Wipf and Venkatraman in 1996.51b Ochiai and co-workers have isolated and identified by X-ray analysis intermediate products 120 (as mesylate or tetrafluoroborate salts), which suggests the mechanism involving Michael addition of sulfur nucleophile 116 to alkynyliodonium salt 115 giving intermediate ylide 118 followed by the 1,2-rearrangement of sulfenyl groups in the resulting alkylidene carbene 119 (Scheme 43).51a

Scheme 43
The intramolecular variant of the alkylidene carbene cyclization is achieved by the treatment of functionalized alkynyliodonium salts with the appropriate nucleophile.Recent examples are represented by the preparation of various functionalized 2,5-dihydrofurans by treatment of 3alkoxy-1-alkynyl(phenyl)iodonium triflates with sodium benzenesulfinate, 29e by the utilization of the alkylidene carbene cyclization in the total syntheses of natural products agelastatin A and agelastatin B, 29c and by the preparation of the tricyclic core of (±)-halichlorine through the use of an alkynyliodonium salt/alkylidenecarbene/1,5 C-H insertion sequence.29d In particular, Wardrop and Fritz have utilized the sodium benzenesulfinate induced cyclization of the generated in situ alkynyliodonium triflate 121 leading to dihydrofuran 122 (Scheme 44), which is a key intermediate product in the total synthesis of (±)-magnofargesin.29e

Scheme 44
Feldman and co-workers have applied the sodium p-toluenesulfinate induced cyclizations of alkynyliodonium salts 123 and 54 for the preparation of compounds 124 and 125 (Scheme 45), the key intermediates in the total syntheses of agelastatins 29c and (±)-halichlorine, respectively.29d Scheme 45

Scheme 46
Likewise, compounds 60 (Section 3.4, Scheme 21) are useful reagents for fluoroalkylation of amino acids and peptides.31c,d,52b-e For example, the reaction of iodonium salt 60 (n = 7) with the tert-butyl carboxyl ester of tyrosine 126 in the presence of collidine results in quantitative formation of the monoalkylation product 127 (Scheme 47).31d,52d Due to this reactivity, iodonium salts 60 can be used as fluorous capping reagents for facile purification of peptides synthesized on the solid phase.31d,52d It was recently demonstrated that iodonium salts 60 are also useful for the regioselective N-or C-fluoroalkylation of imidazoles.52f

Scheme 47
Similar to fluoroalkyl(aryl)iodonium salts, iodonium salts 58 are efficient electrophilic alkylating reagents towards a variety of organic nucleophiles (thiophenolate anion, amines, pyridine, triphenyl phosphine, and silyl enol ethers).All these reactions proceed under mild conditions and selectively afforded the appropriate product of alkylation along with iodobenzene as the by-product (Scheme 48). 53

Scheme 48
The unstable -oxoalkyl(phenyl)iodonium salts 129 can be generated by a low temperature reaction of silyl enol ethers with reagent 128.These species have been proposed as the reactive intermediates in synthetically useful carbon-carbon bond forming reactions with various silyl enol ethers 130 (Scheme 49) and other C-nucleophiles to afford the respective products of C-C bond formation. 54Scheme 49 18 F-labeled imaging agents for positron emission tomography have a short lifetime (due to the short half-life of radioactive decay of 18 F) and require fast and convenient methods for introduction of 18 F into organic substrate molecules.Reactions of diaryliodonium salts provide such methods (Scheme 46).15b,55

Scheme 50
In the case of reactions of symmetrical diaryliodonium salts there is no problem with selectivity, however, only half of a molecule of substrate is converted to the target product and the second half gives aryliodide as a byproduct, which results in a low atom economy.Moreover, in this case the problem of separation of aryliodide and arylfluoride may take place due to their similar structure.
One way to eliminate this problem is by appropriate choice of R 1 and R 2 groups in nonsymmetrical diaryliodonium salts to make the aromatic ring with R 2 more electron-rich than the other aryl (Scheme 50).Zhang and coauthors reported a successful synthesis of [ 18 F]DAA1106 (compound 132) from diaryliodonium salt 131 with the radioactive 18 F anion (Scheme 51).55e Compound 132 is used as a positron emission tomography (PET) ligand for imaging a peripheral-type benzodiazepine receptor.

Scheme 51
Another way uses same idea to make leaving aromatic ring more electron-rich, but it is based changing the aromatic ring nature instead of R 1 and R 2 substituents in the phenyl ring.Coenen and coauthors have developed highly efficient fluorination method using aryl-(2thienyl)iodonium salts.55f The 2-thienyl group is very electron-rich group that allows 18 F to be introduced directly into electron-rich arenes like anisoles (Scheme 52).55f

Scheme 52
DiMagno and co-workers have recently shown that exceptionally electron-rich arene rings can be fluorinated exclusively during the reductive elimination reactions of 5methoxy[2.2]paracyclophan-4-yldiaryliodonium salt 133 (Scheme 53).55g,h Use of the sterically hindered cyclophane directing group permits a high degree of control in fluorination reactions of diaryliodonium salts.