Hypervalent iodine (V) catalyzed reactions

The chemistry of hypervalent iodine compounds has been widely recognized in the synthetic community. The utilization of hypervalent iodine compounds as stoichiometric reagents as well as catalysts has tremendously been studied in recent decades. Hypervalent iodine (V)-catalyzed reactions are proven to be versatile catalytic systems to access various oxidative transformations. In this review, the versatility of hypervalent iodine (V)- catalyzed reactions have been discussed in detail. This review highlights the oxidation of various substrates using catalytic amounts of o -iodoxybenzoic acid (IBX), modified IBX derivatives, o -iodoxybenzenesulfonic acid (IBS), recyclable iodine (V)


Introduction
Hypervalent iodine compounds have been extensively studied in organic synthetic chemistry over the last decades. It is well-documented in the literature that these compounds have similar reactivity patterns as that of transition metal-organic complexes, however, their excellent oxidizing ability, low cost, mild reaction conditions, low toxicity over heavy-metal reagents, and easy handling make them superior alternatives to heavymetal reagents. [1][2][3][4][5][6][7][8][9] Hypervalent iodine reagents can be effectively utilized for various transformations such as for oxidation of alcohols, 10,11 sulfides, 12 arylations, 13,14 C-H functionalization, [15][16][17] and oxidative coupling reactions 18 among others. The practical interest of these reagents is increasing day by day due to their widespread applicability as powerful oxidizing agents. However, catalytic reactions using hypervalent iodine compounds were not explored until the beginning of the 21 st century. Groundbreaking reports on the catalytic use of hypervalent iodine (III) species were independently published by Kita 19 and Ochiai 20 groups in 2005. The groups reported the catalytic utilization of these compounds in presence of stoichiometric amounts of co-oxidant, mchloroperbenzoic acid (m-CPBA). These catalytic oxidative transformations include the selective in-situ generation of hypervalent iodine (III) species. In this series, Vinod 21 and Giannis 22 reported the first examples of the catalytic application of hypervalent iodine (V) species for the oxidation of alcohols using aryl iodide and Oxone ® (2KHSO5.KHSO4.K2SO4) as the terminal oxidant. These preliminary reports became the basis of the discovery of numerous other catalytic reactions involving hypervalent iodine (III) and hypervalent iodine (V) species. Many articles on different aspects of hypervalent iodine (V) reagents/catalysts have been published previously which include their preparations and diverse applications. 6,[23][24][25][26][27] We herein elaborate on the hypervalent iodine (V)-mediated catalytic reactions. This review is divided into five sections based on the type of hypervalent iodine catalysts.

Oxidation of alcohols.
Vinod and co-workers generated IBX (1) in-situ by oxidizing 2-iodobenzoic acid (2IBAcid, 2) using eco-friendly oxone as co-oxidant. Oxidation of primary and secondary alcohols using catalytic 2IBAcid (20-40 mol %) (2) and oxone as co-oxidant in water-acetonitrile biphasic solvent system afforded the corresponding carboxylic acids and ketones, respectively (Scheme 1). 21 In another report by Vinod and coworkers, selective oxidation of benzylic C-H using catalytic 2IBAcid (2) and oxone as co-oxidant was elaborated leading to the formation of corresponding carbonyl functionalities. 37 A single electron transfer (SET) mechanism was proposed by the group as depicted in Scheme 2.
Salient features of the proposed mechanism involve initiation via a benzylic H-atom abstraction by the I=O bond, similar to the first step in C-H oxidation by reagents that possess a metal=O bond, followed by a singleelectron transfer (SET) from the resonance stabilized benzylic radical 6 to the odd electron iodine center in 4 that produces the crucial diphenyl carbocation 7 and the peroxy-IBX anion 5. The collapse of peroxy-IBX anion 5 regenerates IBX (1) which can re-enter the catalytic cycle through further activation by KHSO5. Finally, three plausible routes (Reaction 1-3) for the transformation of 7 to 8 are shown in Scheme 2.

Scheme 2.
Proposed free radical mechanism of oxidation of diphenylmethane.
In a similar report, Giannis and Schulze utilized 10 mol % of 2-iodobenzoic acid (2IBAcid, 2) (or 10 mol % of IBX (1)) in ethyl acetate-water biphasic solvent system, in which benzylic alcohols were transformed to their corresponding aldehydes while secondary alcohols were converted to ketones (Scheme 3). 22 However, primary aliphatic alcohols afforded corresponding carboxylic acids. Moreover, in case of allylic and homoallylic alcohols, reaction with IBX (1) gave a complex reaction mixture. The proposed mechanism for the catalytic cycle for the oxidation of alcohols is depicted in Scheme 4. Tetra-n-butylammonium oxone oxidizes the 2-iodobenzoic acid (2) to IBX (1) which oxidizes the alcohols and, resulted in to reduced IBX 9. This reduced IBX 9 gets converted back to IBX (1) using tetra-n-butylammonium oxone.  Page and coworkers developed an efficient catalytic system for the oxidation of primary and secondary alcohols by using catalytic amount of 2-iodobenzoic acid (2-IBAcid) 2 in presence of oxidant, tetraphenylphosphonium monoperoxysulfate (TPPP) in acetonitrile or dichloroethane (DCE) or 4-methylpentan-2-one (Scheme 5). 38 However, the reaction did not proceed in some of the substrates in case of 4-methylpentan-2-one. One of the salient features of the developed protocol is the oxidation of primary alcohols into corresponding aldehydes avoiding the formation of over-oxidized carboxylic acids. Oxidation of alcohols with TPPP in the absence of 2-iodobenzoic acid afforded the corresponding carbonyl product, however, the reaction time was roughly double. Further, the oxidant, TPPP can be easily prepared by simple counterion exchange between oxone ® and tetraphenylphosphonium chloride.

Oxidation of alkenes.
Donohoe and coworkers reported IBX (1) catalysed stereoselective, metal-free syndihydroxylation of electron-rich alkenes using TEMPO in fluorinated solvents i.e. hexafluoroisopropanol (HFIP) or trifluoroethanol (TFE). Alkenes on treatment with IBX/TEMPO afforded orthogonally protected syn 1,2-diols 10 up to 95% yield with high stereocontrol that can be deprotected using K2CO3/MeOH or Zn/AcOH (Scheme 6). 39 The proposed mechanism involves disproportionation of TEMPO 12 in acidic medium that resulted into the generation of hydroxylamine 13 and oxoamonium cation 14. Reaction of the electron-rich olefin 10 with oxoamonium cation (12) may form benzylic cation intermediate 15, which can then be trapped by external nucleophile. The syn-stereochemistry of the product may be attributed to the cation trapping in which the external nucleophile approaches antiperiplanar to R group, that minimizes the allylic strain and gives net syn dihydroxylation 11 (Scheme 7).

o-Iodoxybenzenesulfonic acid (IBS)-catalyzed reactions 2.2.1. Oxidation of alcohols.
Ishihara and coworkers demonstrated the catalytic efficiency of various modified IBX-derivatives and, 2-iodoxybenzenesulfonic acid (IBS, 16) (Scheme 8). 40 2-iodoxybenzenesulfonic acid (IBS, 16) was prepared by Zhdankin and Tykwinski et al from 2-iodobenzenesulfonic acid (17) and Oxone in water, 41 however, its oxidative ability was not investigated due to its low stability 42 . Ishihara's group reported that IBS (16) is more active catalyst than modified IBX-derivatives for the selective oxidation of alcohols to aldehydes, ketones, carboxylic acids and enones using oxone as terminal oxidant. Moroever, electron-donating groupsubstituted derivatives, such as, 5-Me-IBS, 5-OMe-IBS and, 4,5-Me2-IBS showed superior catalytic properties towards alcohol oxidation. In-situ generation of IBX (1) or IBS (16) and catalytic cycle of alcohol oxidation is shown in Scheme 9. The developed protocol was extended towards the large scale oxidation of 4-bromobenzyl alcohol using 1 mol % of the pre-catalyst, potassium 2-iodo-5-methylbenzenesulfonate (18), which gave either the formation of 4-bromobenzaldehyde or 4-bromobenzoic acid depending on the amount of oxone used in the reaction. 43 Further, Ishihara group reported the oxidative rearrangement of cyclic and acyclic tertiary allylic alcohols, 19 and 20, to their corresponding enones 21 and 22, respectively, using pre-catalysts 17 (or 18) and powdered oxone that generates IBS (16) (or 5-MeIBS, 23) in presence of tetrabutylammonium hydrogensulfate (Bu4NHSO4) as phase transfer-catalyst (Scheme 10). 44 This method is extremely effective as it avoids the use of hazardous and expensive reagents and, afforded desired products in good yield (i.e. up to 85%). 5-Me-IBS 23 gets regenerated faster than IBS thus giving much better catalytic activity. The plausible oxidative rearrangement mechanism of tertiary allylic alcohols 20 to enones 22 is depicted in Scheme 11. Selective substrates are also shown in Scheme 10 with the yield of the rearranged products. Konno and coworkers oxidized various fluoroalkyl-substituted methanol derivatives 24 using catalytic amount of sodium 2-iodobenzenesulfonate (17) (5 mol % or 10 mol %) and oxone in acetonitrile or nitromethane as solvent. 45 Oxidation afforded corresponding ketones 25 in 47-99% yield, however, hydrates 26 were found in some cases in low yields, except for 2,2,2-trifluoro-1-(4-nitrophenyl)ethane-1,1-diol and 2,2,2-trifluoro-1-(4-(trifluoro methyl)phenyl)ethane-1,1-diol, in which hydrates were obtained in 49% and 40% yields. The catalytic efficiency was compared to other oxidants, such as Dess-Martin reagent, pyridinium dichromate (PDC) and Swern oxidation and, it was observed that this oxidative protocol showed comparable reactivity to Dess-Martin reagents for almost all substrates. Moreover, pyridinium dichromate (PDC) and Swern oxidation could not be used for allylic, propargylic alcohols as well as for alcohols with aliphatic side chain (Scheme 12).
Micellar catalysis has gained much importance as it uses water as solvent instead of organic solvents. As a commercially available surfactant, cetyltrimethylammonium bromide (CTAB) can form aqueous micelles and has been used in diverse reactions. Wang and coworkers reported the oxidation of primary and secondary alcohols using IBS (16) in catalytic amount (0.02 mmol) with oxone in cetyl trimethylammonium bromide (CTAB) in water (Scheme 13). 46 Secondary benzyl alcohols on oxidation afforded corresponding ketones while primary benzyl alcohols gave corresponding aldehydes in 63-99% yield. However, harsher conditions led to the overoxidation. Scheme 13. IBS (16)-catalyzed oxidation of alcohols in CTAB micelles.

Oxidation of benzylic and alkane C-H bonds.
Zhang and coworkers efficiently utilized the IBS (16)catalyzed oxidation of benzylic and alkane C-H bonds using oxone as terminal oxidant and tetrabutylammonium hydrogensulfate (Bu4NHSO4) as phase transfer-catalyst in anhydrous acetonitrile at 60 0 C (Scheme 14). 47 Various alkylbenzenes, including toluene and ethylbenzene, several oxygen-containing functionalities substituted alkylbenzenes, cyclic benzylether could be efficiently oxidized in good yields. This catalytic system can also be used to the oxidation of alkanes. Moreover, in order to get insight into the mechanistic pathway, catalytic oxidation of adamantane 27 under N2 was investigated, which afforded 1-acetamidoadamantane 28, indicating the intermediacy of carbocation in the adamantane oxidation.
Ishihara and co-workers reported the 5-Me-IBS (23)-catalyzed regioselective oxidation of phenols, naphthols and phenanthrols using stoichiometric amounts of oxone as co-oxidant (Scheme 16). 49 Compounds 34 were oxidized by catalytic amount of pre-catalyst 18, with oxone in the presence of K2CO3 and phase catalyst n-Bu4NHSO4 into their corresponding o-quinones 35 in 2-5 hours up to 84% yield. Interestingly, 2-methoxy-1naphthol 36a and 4-methoxy-1-naphthol 36b afforded corresponding o-quinone derivatives 37a or 37b, while, 3-methoxy-1-naphthol 36c on oxidation gave corresponding 1,4-quinone 37c in 81% yield and, only trace amounts of 1,2-quinone 37d was obtained. The mechanism of IBS-catalyzed oxidation of various phenols to corresponding o-quinones is shown in Scheme 17.  50 The DFT calculations revealed that the methyl groups present in the iodine (V) reagent, Tet-Me IBX 39 lowers the activation energy corresponding to the hypervalent twisting. It is pertinent to mention that Su and Goddard III earlier demonstrated the effect of hypervalent twist on the enhancement of IBX reactivity. 51 Further, the steric relay between successive methyl groups twists the structure, which enhances its solubility in organic solvents. Primary and secondary alcohols are converted to carboxylic acids and ketones, respectively in MeCN : H2O solvent system, while primary alcohols selectively afforded aldehydes in case of nitromethane as solvent.
In 2016, the same research group published another report for the synthesis of lactones through domino oxidation of diols through in-situ generation of TetME-IBX 39 using DIDA (5 mol %) and oxone. 52 Moorthy and co-workers demonstared the catalytic oxidations using pre-catalyst, 3,5-di-tert-butyl-2iodobenzoic acid (DTB-IA) 40 and oxone as terminal oxidant in solid state under mechanochemical ball-milling conditions (Scheme 20). 53 Oxidation of alcohols, vicinal diols and non-vicinal diols using in-situ generated, iodine (V) reagent, 3,5-di-tert-butyl-2-iodoxybenzoic acid (DTB-IBX) 41 from the sterically crowded catalyst DTB-IA (40) gave corresponding carbonyl compounds, oxidatively cleaved products and lactones respectively. Primary aliphatic alcohols under similar conditions afforded corresponding carboxylic acid, while benzylic alcohols afforded carboxylic acid as well as aldehydes. The mechanism of catalytic oxidation in solid state is also presented, in which exchange of alcohols is rapid process while hypervalent twist of alkoxyperiodinane is the rate-determining step (Scheme 19).

Scheme 19.
Mechanism of oxidation of alcohols using pre catalyst 40.

Oxidative cleavage of alkenes.
Moorthy and coworkers further explored the catalytic efficiency of the pre-catalyst, 3,4,5,6,-tetramethyl-2-iodobenzoic acid (TetMe-IA, 38) towards the oxidative cleavage of olefins at room temperature. 55 TetMe-IA 38 catalayzed oxidation of olefins using oxone as co-oxidant afforded corresponding ketones/carboxylic acids. The oxidation starts with dihydroxylation of double bond with oxone, followed by oxidative cleavage by in-situ generated 3,4,5,6-tetramethyl-2-iodoxybenzoic acid (TetMe-IBX, 39), which resulted into the formation of corresponding aldehydes or ketones. In case of aldehydes, further oxidation by oxone gave corresponding carboxylic acids as final product. It is worthwhile to mention that for substrates bearing both electron-rich and electron-deficient double bonds, oxidation takes place in chemoselective manner (Scheme 22).

Dimerization of alkenes.
Donohoe group also reported the dimerization/heterodimerization of electronrich alkenes to access cyclobutanes (symmetrical/unsymmetrical) using catalytic amounts of Dess-Martin periodinane (DMP) 44 in fluorinated solvent, HFIPA (Scheme 23). 56 The protocol was highly diastereoselctive, giving all trans, by a head to head coupling process. Moreover, the group explored the synthetic utility of this developed protocol for the synthesis of natural product, Nigramide R in 24% yield. Scheme 23. Dimerization/heterodimerization of electron-rich alkenes into cyclobutanes by catalyst DMP 44.

Recyclable hypervalent iodine (V) reagents-catalyzed reactions 2.4.1. Oxidation of alcohols.
With the objectives to recover and reuse IBA 9 in IBX 1-mediated/catalyzed reactions, Miura and coworkers developed hypervalent iodine catalyst with a fluorous tag, fluorous IBX 45 (Scheme 24). 57 Oxidation of secondary alcohols using reusuable fluorous IBX 45 in the presence of co-oxidant oxone and Bu4NHSO4 afforded corresponding ketones in 70-88%. Primary alcohols under similar reaction conditions afforded corresponding carboxylic acids in MeNO2-H2O, while in nitromethane as a solvent, afforded corresponding aldehydes. Fluorous hypervalent iodine (V) can be regenerated from fluorous IBA 46, which can be easily recovered by simple filtration. The recovered reagent 46, works very well for atleast five catalytic cycles. The mechanism highlighting the generation of fluorous-IBX 45 and its use for the oxidation of alcohols is depicted in Scheme 25. Selective oxidation of primary and secondary Morita Baylis-Hillman (MBH) alcohols 48 to their corresponding carbonyl compounds 49 was successfullly developed by Rao and coworkers. 58 Catalytic IBA 9 in presence of 1.0 equiv of oxone was utilized for the oxidation of MBH alcohols to their corresponding carbonyl compounds in 84-96% yield (Scheme 26). Furthermore, the developed protocol was extended towards oxidation of MBH alcohols having an ester functionality. The alcoholic group was oxidized to corresponding aldehyde product in these MBH alcohols. Similar contolled oxidation was reported in case of MBH alcohols bearing cyano group. Catalyst 9 could be regenerated by filtration followed by oxidation with oxone and can be reused up to 4 times without any significant loss in activity.
In 2019, Kirsch and Ballaschk synthesized solid-supported hypervalent iodine (V) catalysts (50, 51) derived from IBX and IBS derivatives for the oxidation of secondary alcohols (Figure 2). 59 Treatment of secondary alcohols with hypervalent iodine (V) (5 mol %) and oxone as co-oxidant resulted in the formation of ketones upto 98% yield. IBS-derived catalyst 51 showed superior reactivity over 50 and requires less reaction time as compared to 50. Catalyst 50 and 51 can be seperated by simple filtration and reuse for multiple times (Scheme 27).

Synthesis of heterocycles.
Chaskar and coworkers performed the multicomponent one-pot Biginelli reaction between aldehydes, β-ketoesters 52 and urea/thiourea 53 using catalytic IBX 1 (5 mol %) in aqueous media to synthesize dihydropyrimidinones (DHPMs) 54 in 71-93% yield (Scheme 28). 60 It was revealed that IBX 1 activates the carbonyl group of ketones and aldehydes which accelerates the iminium formation followed by nucleophilic addition of enolised β-keto ester. One of the salient features of this developed protocol is that after the completion reaction, about 60% of catalyst can be easily recovered by filtration and reused for few reaction cycles without any significant loss of activity. Scheme 28. Synthesis of dihydropyrimidinones using catalyst IBX (1).

Oxidation of benzylic and aromatic C-H.
In another report, Rao group reported the selective oxidation of active methylenes, indoles and styrene C-H bonds in to their corresponding carbonyl compounds by using catalytic IBA 9 in DMSO (Scheme 29). 61 Oxygen/DMSO act as oxidants for activation of organocatalytic C-H bond under mild and metal-free conditions. After each cycle, IBA (9) can be simply filtered out and reused up to four cycles without any loss of activity. Scheme 29. IBA (9)-catalyzed oxidation of benzylic and aromatic C-H.

Non-Cyclic and pseudocyclic hypervalent iodine (V)-catalyzed reactions. 2.5.1. Oxidation of alcohols and alkanes.
Liu and co-workers developed an efficient tendem catalytic aerobic oxidation of alcohols in water using catalytic amounts of iodoxybenzene 55, bromine, and sodium nitrite (Scheme 30). 62 Benzylic alcohols on oxidation gave corresponding benzaldehydes without over-oxidation while primary alcohols produced the corresponding aldehydes albeit in low yield. Moreover, aromatic and aliphatic secondary alcohols afforded the corresponding ketones while benzoin and meso-hydrobenzoin gave the C-C bond cleavage products. The proposed mechanism of this oxidative transformation includes three redox cycles. The first redox cycle involves the oxidation of alcohol to the corresponding carbonyl product by PhIO2 55, which is reduced to (dihydroxy)iodobenzene (PhI(OH)2) 56. This cycle is followed by cycle 2 which involves the reoxidation of PhI(OH)2 56 to iodoxybenzene 55 with Br2, which is reduced to HBr. Finally, in the third cycle, the oxidation of NO with O2 produces NO2, which converts HBr back to Br2 (Scheme 31). Notably, Ishihara's group suggested that the actual oxidant, in this case, is Br2 rather than PhIO2 55. 63  Yakura and coworkers synthesized and screened various 2-iodobenzamides as catalysts using oxone as cooxidant towards the oxidation of benzhydrols to corresponding benzophenones. 67 The catalyst 62, bearing 5-OMe group in the benzene ring was found to be most reactive amongst others. The high reactivity of this catalyst was attributed to the rapid generation of iodine (V) reagent. Various benzylic and aliphatic alcohols were subjected to oxidation using catalytic amount of 62 using 2.5 equiv of oxone in a mixture of nitromethane and water mixture (Scheme 36).
In 2018, Wei group reported the inorganic-ligand supported iodine catalyst 63, (NH4)5[IMo6O24] for oxidation of primary and secondary alcohols. 68 This catalyst 63, showed high stability and efficiently oxidizes various aromatic as well as aliphatic alcohols with high selectivity (Scheme 37). It avoids the use of toxic and sensitive organic ligands and can be easily recoverd. The catalyst could be recycled up to six times without any further purification and can be isolated by simple filtration. Scheme 37. Aerobic oxidation of alcohols using catalyst inorganic-ligand supported iodine 63.

Conclusion
In recent years, the area of hypervalent iodine (V) catalysts has shown tremendous growth. Numerous hypervalent iodine (V) catalysts have been developed, and diverse oxidative transformations have been achieved using these catalytic systems. The discovery of safer and efficient methods for the in-situ utilization of iodine (V) has intitiated a major surge of research activity and, added a new dimension to the field of organocatalytic systems. Taking into account the environmental aspects and efficient catalytic systems, it is expected that the utilization of these catalytic systems and the development of new hypervalent iodine (V) catalysts will continue in the future. We hope that this review article will provide a stimulus for further investigations in hypervalent iodine (V) chemistry.