Palladium-Catalyzed Organic Reactions Involving Hypervalent Iodine Reagents

The chemistry of polyvalent iodine compounds has piqued the interest of researchers due to their role as important and flexible reagents in synthetic organic chemistry, resulting in a broad variety of useful organic molecules. These chemicals have potential uses in various functionalization procedures due to their non-toxic and environmentally friendly properties. As they are also strong electrophiles and potent oxidizing agents, the use of hypervalent iodine reagents in palladium-catalyzed transformations has received a lot of attention in recent years. Extensive research has been conducted on the subject of C—H bond functionalization by Pd catalysis with hypervalent iodine reagents as oxidants. Furthermore, the iodine(III) reagent is now often used as an arylating agent in Pd-catalyzed C—H arylation or Heck-type cross-coupling processes. In this article, the recent advances in palladium-catalyzed oxidative cross-coupling reactions employing hypervalent iodine reagents are reviewed in detail.

Palladium, on the other hand, has emerged as a versatile catalyst. It is an essential component of several coupling reactions, such as Stille coupling and the Suzuki-Miyaura, Heck, Buchwald-Hartwig, Sonogashira, and Negishi, resulting in a broad variety of useful compounds [35]. The effect of hypervalent iodine in palladium-catalyzed reactions has received a great deal of attention over the years. In 2007, Sanford and colleagues published the first review paper addressing the unusual reactivity of hypervalent iodine reagents in Pd-catalyzed reactions [36]. Wengryniuk's group later published a piece of a review in 2017 that outlines the critical significance of polyvalent iodine reagents in high-valent palladium chemistry [37]. Polyvalent iodine compounds react efficiently with palladium complexes due to their electrophilic nature and oxidizing property, promoting reactions through Pd(0/II) and Pd(II/IV) catalytic cycles [38]. Furthermore, a handful of these se compounds are used as aryl, alkynyl, and heteroatom ligand sources in several Pd-catalyzed ligand transfer processes. The commonly used hypervalent iodine(III)/(V) reagents in palladium-catalyzed reactions are listed in Figure 1. Hypervalent iodine(III)/(V) reagents, such as phenyliodine(III) diacetate 1 (PIDA), phenyliodine(III) bis(trifluoroacetate) 2 (PIFA), phenyliodine(III) dipivaloate 3 (PIDP), and Dess-Martin periodinane 4 (DMP), are frequently employed oxidants in palladium-catalyzed reactions. Apart from this, cyclic hypervalent iodine(III) reagents 5 and 6 are also used as oxidants, whereas 1-[(triisopropylsilyl)ethynyl]-1,2-benziodoxol-3(1H)-one 7 (TIPS-EBX) is widely explored as an alkylating reagent. Owing to their highly electrophilic nature, diaryliodonium salts 8 are excellent arylating reagents in palladium-catalyzed reactions. In comparison to the Pd(0/II) redox cycle, substantial progress has been achieved in the chemistry of Pd(II/IV)-catalyzed reactions over the last several decades. In this context, the current review focuses on recent progress in palladium-catalyzed transformations utilizing hypervalent iodine reagents, emphasizing possible synthetic applications and mechanistic features. The article is categorized based on the bonds generated, which include C-O, C-N, C-C, C-Si, C-B, and C-halogen bonds, as well as alkene difunctionalization.

C-O Bond Formation
Palladium-catalyzed, ligand-mediated C-H functionalization has been known to be one of the most effectual, atom-efficient, and cost-effective methods for introducing different functional groups to unactivated arene and alkane C-H bonds in organic synthesis. Several research groups have conducted extensive studies on the formation of the C-O bond, using palladium catalysis involving hypervalent iodine reagents as the oxidant or heteroatom ligand. Pd-catalyzed C-H oxidative cyclization, C-H acyloxylation, C-H alkoxylation, and allylic oxidation are significant methods in C-O bond formation that are guided by directing functional groups such as oxime ether, oxazoline, amide, pyridine, pyrimidine, and so on.

C-H Cyclization
Significant progress has been made in the field of palladium-catalyzed oxidative cyclization processes employing hypervalent iodine reagents, which allow access to a variety of oxygen-containing heterocycles. For instance, Yu and co-authors developed a novel method for the construction of dihydrobenzofurans 10 via the palladium-catalyzed C-H activation/C-O cyclization reaction [39]. In the presence of (diacetoxyiodo)benzene 1 as the terminal oxidant and Pd(OAc) 2 as the catalyst, a series of tertiary alcohols 9 were efficiently converted into targeted cyclized products 10 in moderate to good yields (Scheme 1).
Moreover, the scope of the reaction was extended for the preparation of important scaffolds such as spirocyclic dihydrobenzofurans. Scheme 1. Pd-catalyzed synthesis of dihydrobenzofurans 10 via hydroxyl-group directed C-H activation/C-O cyclization reaction of 9 using PhI(OAc) 2 1 as terminal oxidant.
The catalytic cycle for the preparation of dihydrobenzofurans 10 was initiated by the palladium-catalyzed C-H activation of substrate 9 to give intermediate 11, followed by subsequent oxidation using PhI(OAc) 2 1 to give Pd(IV) intermediate 12. Finally, the reductive elimination of 12 gives cyclized product 10 along with the regeneration of the Pd(II) catalytic species to continue the catalytic cycle (Scheme 2). Later, Gevorgyan and coworkers achieved the intramolecular silanol group-directed C-H oxygenation of arenes 13 using PIDA 1 as an oxidant in the presence of a palladium catalyst [40]. These reactions begin with the production of cyclic silicon-protected catechols 14, which are then desilylated with TBAF/THF to yield substituted catechols 15 (Scheme 3). The reaction featured excellent site selectivity and broad substrate scope, particularly as electron-rich substrates react much faster and provide high yields.  Another interesting work published by Gevorgyan's research group is a convenient method for the synthesis of oxasilacycles 23 and 25 from benzyl-silanol 22 and 24, respectively, using a combination of Pd(OAc) 2 and PhI(OAc) 2 1 via C-H oxygenation strategy [41]. Under the optimized conditions, a variety of silanol-directed aromatic substrates 22 and 24 bearing alkyl and aryl substituents were transformed into the corresponding cyclic products in significant yields (Scheme 5). Gratifyingly, the oxasilacycles were found to be valuable intermediates as they contained an easily removable or modifiable Si-O bond and thus could be converted into useful functionality. The reactions include the wellknown Tamao oxidation, Hiyama-Denmark cross-coupling, and nucleophilic addition, as well as the novel Meerwein salt-mediated oxasilacycle ring-opening and nitrone synthesis from the benzylsilane and nitroso compound. The desilylation of the cyclic product in the presence of CsF in DMF to give phenol in good yield is an example of the synthetic usefulness of oxasilacycles. Furthermore, Dong and colleagues reported the production of cyclic ethers 27 by palladium-catalyzed oxime-masked-alcohol-directed dehydrogenative annulation of the substrates 26 sp 3 C-H bonds using (diacetoxyiodo)benzene 1 as an oxidant [42]. Under normal circumstances, the reaction proceeds preferentially at the β position, and the substrates 26 with the primary, secondary, and tertiary hydroxyl groups perform extremely well (Scheme 6). The process might continue through C-H palladation, followed by Pd oxidation, to a higher oxidation state and an intramolecular S N 2 reaction to generate oxonium intermediate 29. Finally, cyclic ethers 27 were synthesized through deprotonation or debenzylation and used to renew the Pd catalyst.
Shi and colleagues demonstrated the Pd-catalyzed intramolecular lactonization of, α, α-disubstituted arylacetic acids 30 in the presence of PhI(OAc) 2 1 and Ac-Gly-OH as the required ligand to obtain a variety of, α,α-disubstituted benzofuran-2-ones 31 in varying yields [43]. The catalytic system is made up of Pd(OAc) 2 and a mixture of NaOAc, CsOAc, and AgOAc as the most efficacious bases (Scheme 7). Wang et al., in 2013, proposed a similar C-H activation/C-O production technique for constructing functionalized benzofuranones [44].
The proposed mechanistic approach for the lactonization of acids 30 is outlined in Scheme 8. Subsequently, a novel route to construct biaryl lactones 38 from biaryl carboxylic acids 37 via palladium-catalyzed C-H activation/C-O cyclization, using PhI(OAc) 2 1 as an effective oxidant, was developed [45]. The presence of acetyl-protected glycine (15 mol% Ac-Gly-OH) as a ligand, along with base KOAc and solvent t-BuOH, provided the best results for the desired products 38 (Scheme 9). Both the electron-rich and the electrondeficient substituents were well tolerated on the aryl rings. Furthermore, the present protocol was successfully utilized for the total synthesis of the natural product cannabinol in a 72% yield. Scheme 8. The catalytic cycle for the intramolecular lactonization of acids 30 to synthesize benzofuranones 31 using PhI(OAc) 2 1 as an oxidant. Scheme 9. Pd(II)-catalyzed C-H activation/C-H cyclization of biaryl carboxylic acids 37 to afford biaryl lactones 38 using PhI(OAc) 2 1.
Shi's group, in 2016, revealed a straightforward method for the synthesis of γ-lactones 40 via the Pd(II)-catalyzed 2-pyridinylisopropyl (PIP) auxiliary-directed intramolecular cyclization of unactivated C(sp 3 )-H bonds, utilizing the oxidant PIDA 1 [46]. The lactonization of aliphatic acids 39 with different substituents on the alkyl chain went exceptionally well, yielding γ-lactones 40 in 32-77% yields (Scheme 10). The formation of a five-membered palladacycle 41 via Pd-catalyzed C-H activation facilitated by bidentate auxiliary is the most plausible pathway for the lactonization of aliphatic acids 39. In the presence of PhI(OAc) 2 1, palladacycle 41 was oxidized to provide Pd(IV) intermediate 42, which was then ligand exchanged to generate 43 and was further reductively eliminated to liberate target product 40 and a Pd(II) catalyst to sustain the catalytic cycle (Scheme 11). Another route to lactone 40 is by a direct S N 2-type attack by the carboxylate group on the Pd(IV)-C bond of 42. Scheme 11. Plausible catalytic cycle for the synthesis of γ-lactones 40.

C(sp 2 /sp 3 )-H Acyloxylation
Over the years, C-H acyloxylation has gained considerable attention because it introduces ester functionality on the aromatic and aliphatic substrates. Using palladium catalysts and iodine(III) reagents as oxidants, notable progress has been achieved in transmuting sp 2 and sp 3 hybridized C-H bonds into useful C-O bonds. In the next section, we will discuss the recent developments made in C-H acyloxylation reactions employing different directing groups.

C(sp 2 )-H Acyloxylation
Several ligand-directed C(sp 2 )-H acyloxylation reactions have been developed, giving facile access to valuable oxygenated arenes. In 2009, Chen and co-authors published the Pd(II)-catalyzed pyrimidine-directed ortho-acetoxylation of phenol derivatives 44 in the presence of PhI(OAc) 2 1 as an efficient oxidant in combination with the Ac 2 O/AcOH solvent system [47]. The reaction proceeded through the Pd-catalyzed ortho C-H activation of pyrimidyl ethers 44, resulting in the formation of six-membered palladacyles which, upon functionalization, furnished acetoxylated products 45 in variable yields (Scheme 12). However, the substrates 44 with electron-withdrawing groups or with ortho-/meta-substituents reacted slowly and gave the desired products in moderate yields. Later, Liang and his co-workers employed the bidentate ligand system for the Pd(II)catalyzed C-H activation/C-H acetoxylation of amide substrates 46 and 48 [48]. Under the optimized conditions, various pyridines 46 and 8-aminoquinoline 48 derivatives were converted to the desired acetoxylated products 47 and 49, respectively, in the presence of PhI(OAc) 2 1 as an oxidant as well as an acetate source (Scheme 13). In 2010, Sanford and co-author employed in situ-generated O-acetyl oxime as an efficient directing group for the sp 2 C-H acetoxylation of 52 [49]. The reaction involves the O-acetylation of oximes 52, occurring upon treatment with AcOH/Ac 2 O for 2 h at 25 • C, to form O-acetylated products 53, which further direct C-H acetoxylation in the presence of Pd(OAc) 2 and PhI(OAc) 2 1 to afford mono-ortho-oxygenation products 54 (Scheme 15). Furthermore, the synthesized compounds were readily transformed into valuable compounds such as ketones, amines, alcohols, and heterocycles using different reaction conditions. Later, Gevorgyan and co-workers described the pyridyldiisopropylsilyl (PyDipSi)directed C-H acetoxylation/pivaloxylation of arenes through palladium catalysis [50]. Arylsilanes 55 reacts in the presence of hypervalent iodine(III) reagents PhI(OAc) 2 1 or PhI(OPiv) 2 56 in 1,2-dichloroethane (DCE) to yield monoacetoxylated or pivaloxylated products 57 in a good yield (Scheme 16). Both of the hypervalent iodine(III) reagents act as oxidants as well as the source of the acyloxyl group. The reaction possessed an easily removable directing group, and it possessed remarkable functional group tolerance and excellent site selectivity. Furthermore, the same group performed double C-H pivaloxylation of the 2-pyrimidyldiisopropylsily (PyrDipSi)-directed arenes 58 to afford bispivaloxylated products 59, using the Pd(OAc) 2 /PhI(OPiv) 2 56 catalytic system [51]. Additionally, the ortho-substituted arenes 60 smoothly transformed into monopivaloxylated products 61 in good yields under similar conditions (Scheme 17). Finally, the PyrDipSi group was easily removed to yield protected resorcinols or was converted into useful synthetic products.
In 2013, Shi and co-workers employed 1,2,3-triazoles-pyridine (TA-Py) as a directing group in the Pd(II)-catalyzed selective ortho-C-H activation of arenes 62 for the first time, using oxidant PhI(OAc) 2 1 and co-oxidant AgOAc [52]. The reaction scope was examined with various TA-Py amides 62 to furnish the desired oxidized products 63 in useful yields (Scheme 18). In the case of the meta-substituted arenes, excellent regioselectivity (dr > 20:1) was achieved with acetoxylation, taking selectively at less sterically hindered carbon. A further TA-Py group also promoted the acetoxylation of unactivated sp 3 C-H substrates under identical conditions.  In 2015, Dong's team published the Pd-catalyzed dimethoxybenzaldoxime-directed orthoacetoxylation of arenes 64, using oxidant PIDA 1 [53]. Both the primary and the secondary masked alcohol-derived substrates 64 smoothly underwent ortho-acetoxylation to yield acetoxylated products 65 in good to excellent yields (Scheme 19). The substrates 64 with orthoor meta-substituents gave mono-oxidation products, while the symmetrical substrates formed bis-oxidation products. In addition, a regioselective approach, including the Pd(II)-catalyzed C-H benzoxylation of 2-arylpyridines 66, yielded mono-benzoxylation products 68 in moderate to good yields [54]. They used the easily accessible iodobenzene dibenzoate derivatives 67 as an oxidant and benzoxyl group source (Scheme 20). Furthermore, the current benzoxylation process was effectively employed for the benzoxylation of 2-thienyl pyridines 69 to obtain 3-benzoxylated thiophenes 70 in a high yield. Scheme 21 depicts a probable mechanism for the ortho C-H benzoxylation process. Initially, the substrates 66 are activated using a palladium catalyst to generate complex 71, which is then oxidatively added to 67 to form complex 72 in a high oxidation state Pd(IV) or a Pd(III)-Pd(III) intermediate [55]. Finally, the reductive elimination of 72 yields the desired product 68 and regenerates the palladium catalyst, bringing the catalytic cycle to a close.
The Pd-catalyzed C-H oxygenation of simple arenes devoid of directing groups remains a challenge as it leads to the formation of mixtures of isomers. Sanford and colleagues discovered the nonchelated-aided Pd-catalyzed C-H acetoxylation of simple arenes, utilizing pyridine as a ligand [56]. Later, the same research group studied the use of the oxidant and ligand in controlling the site selectivity in the Pd-catalyzed C-H acetoxylation of multi-substituted arenes 73 [57] (Scheme 22). Under ligand-free conditions and in the presence of PhI(OAc) 2 1, the C-H acetoxylation of arenes 73 gave a modest yield of products 75 with the selectivity dominated by electronic effects, resulting in preferential acetoxylation at the electron-rich sites (Conditions A). On the other hand, the use of acridine (1.5 mol%) as an ancillary ligand in combination with that of Pd(OAc) 2 and MesI(OAc) 2 74 showed sterically controlled selectivity (Conditions B).
Furthermore, the regioselective C-H functionalization of indoles has been discovered to be a simple approach for obtaining physiologically relevant 3-acetoxyindoles. Suna's and Kwong's groups both separately reported the synthesis of 3-acetoxyindoles 77 by the Pd(II)-catalyzed direct C3-oxidation of indole derivatives, employing PhI(OAc) 2 1 as an efficient terminal oxidant [58,59]. In addition, Lei and colleagues used PhI(OAc) 2 1 and KOH as bases to establish a comparable Pd-catalyzed method for the selective C3-acetoxylation of substituted indoles 76 [60]. Mechanistic studies indicated that electrophilic palladation occurs at the C3 position of indole to form a Pd(II) species, which is oxidized to a Pd(IV) intermediate and then reductively eliminated to provide matching C3-acetoxylated indoles 77. (Scheme 23). Szabó and co-workers presented an excellent example for the preparation of allylic acetates or benzoates 80 via the Pd-catalyzed allylic C-H acetoxylation/benzoyloxylation of alkenes 78, using hypervalent iodine reagent as an oxidant [61]. The reactions were carried out in AcOH or MeCN solvent in the presence of bases KOAc and LiOBz. The catalytic process involved the formation of (η 3 -allyl)palladium intermediate 79, which was confirmed through deuterium-labelling studies. Moreover, the reaction worked perfectly well for both the internal and the terminal alkenes to provide an exclusively trans product. (Scheme 24). Scheme 24. Pd(II)-catalyzed C-H acetoxylation/benzoyloxylation of alkenes 78 to furnish allylic acetates or benzoates 80 using iodonium salts as oxidants.
Later, the same group described the conversion of functionalized cyclic 81 or acyclic alkenes 84 into allylic trifluoroacetates 83 or 85 via Pd-catalyzed C-H trifluoroacetoxylation, employing PhI(OCOCF 3 ) 2 82 as the oxidant and trifluoroacetoxy source [62]. Excellent regioselectivity (d.r: > 95:5) and diastereoselectivity were observed in the case of the monosubstituted cycloalkanes. Furthermore, the cyclic alkenes reacted much faster than the acyclic ones, and therefore, the addition of LiOCOCF 3 was necessary in the case of substrates 84 (Scheme 25).

C(sp 3 )-H Acyloxylation
Another major approach in regioselective C-O bond formation is the acyloxylation of aliphatic C(sp 3 )-H bonds. Simple methods for activating a suitable C-H bond have been designed, utilizing various directing groups. In 2010, a new chelation-assisted Pd(OAc) 2 -catalyzed C(sp 3 )-H acyloxylation of 8-methylquinoline 86 was established in the presence of a stoichiometric amount of the oxidant PhI(OAc) 2 1 [63]. The reaction scope was investigated using a wide variety of carboxylic acids 87 to obtain mono-acyloxylation products 88 in moderate to good yields (Scheme 26). In 2010, Neufeldt and Sanford also reported the Pd-catalyzed in situ-generated Oacetyl oxime-directed sp 3 C-H acetoxylation of dialkyl oximes 92 to afford acetoxylated products 94 in useful yields [49]. The acetoxylation reaction was compatible with different functional groups, such as alkyl chlorides, protected amines, and benzylic C-H bonds (Scheme 28). Moreover, the acetoxylation occurs selectively at primary β sp 3 C-H bonds, in comparison to the analogous secondary sites. Using oxime as the directing group, the acetoxylation of β C-H bond of substrates 95 was performed, employing Pd(OAc) 2 and PhI(OAc) 2 1 [64]. The catalytic reaction was expected to generate a five-membered exo-palladacycle 96, which on oxidation gives masked 1,2diols 97 (Scheme 29). Moreover, the selective functionalization of the β-methylene (CH 2 ) and β-methine (CH) groups in cyclic substrates was also carried out under the same reaction conditions. Furthermore, the deprotection of the DG and acetyl groups was conducted by using Zn/AcOH and K 2 CO 3 /MeOH, respectively, to yield diols in excellent yields. An elegant protocol employing S-methyl-S-2-pyridyl-sulfoximine (MPyS) as the directing group for the selective catalytic oxidation of the unactivated primary β-C(sp 3 )-H bond of the amide substrates 98 at room temperature was developed [65]. In the presence of Pd(OAc) 2 and PhI(OAc) 2 1, the preparation of β C-H acetoxylated products 100 was achieved using carboxylic acids 87 as the solvent and acetate source (Scheme 30). Furthermore, the diacetoxylation of the β, β ' -C(sp 3 )-H bonds of amides 99 was also investigated under the modified conditions to afford diacteoxylated products 101.
Later, the benzylic C(sp 3 )-H bonds of 102 were subjected to Pd-catalyzed acetoxylation, using picolinamide and quinoline-2-carboxamide as efficient directing groups in the presence of PhI(OAc) 2 1 as the oxidant and acetate source [66]. This oxidative transformation furnishes acetoxylated products 103 with excellent functional group compatibility and broad substrate scope (Scheme 31). Furthermore, the amide auxiliary was removed through base hydrolysis to give 2-aminobenzyl alcohols in a high yield.  In 2014, Chen and colleagues accomplished the Pd(OAc) 2 -catalyzed acetoxylation of the C(sp 3 )-H bond of simple alkylamines 106 guided by picolinamide (PA), utilizing PhI(OAc) 2 1 as an oxidant and under an argon atmosphere [67]. The procedure makes it simple to obtain acetoxylated compounds 107 in a high yield. Furthermore, under these conditions, the C-H acetoxylation of the methyl group of arylamines 108 progressed easily, yielding acetoxylated compounds 109. The addition of Li 2 CO 3 was crucial as it suppressed the formation of cyclic azetidine through intramolecular C-H amination (Scheme 33). Stambuli and co-workers reported a Pd-catalyzed PhI(OAc) 2 -mediated allylic oxidation of cis-vinylsilanes 110, using PIDA 1 to give the corresponding cis-silyl allylic acetate 111 as the major product [68]. This ligand-free approach required lower catalyst loading and exhibited good substrate scope, and the oxidation products were isolated in moderate to good yields (Scheme 34). Recently, in 2021, Punji and coworkers reported the palladium-catalyzed chemoselective C(sp 2 )-H and C(sp 3 )-H acetoxylation of tertiary amides through coordinated O-chelation under mild conditions [69]. On screening the reaction parameters, the best results were found on reacting substituted tertiary amide 112 with diacetoxyiodobenzene 1 (3.0 equiv.) in the presence of 1 mol% Pd(OAc) 2 as a catalyst, dissolved in hexafluoroisopropanol (HFIP)/Ac 2 O at 80 • C for 20 h (Scheme 35). On performing the reaction in acetic acid at 120 • C, the mono-acetoxylated product 113, along with the diacetoxylated product, was obtained, but on reducing the temperature to 80 • C and performing the reaction in HFIP/Ac 2 O, a high selectivity of monoacetoxylation was observed. The mild inorganic oxidants, such as Na 2 S 2 O 8 , K 2 S 2 O 8 , and AgOAc, were found to be less effective in comparison to the PhI(OAc) 2 . The amides with cyclic substituents, as well as simple dialkyl amides with different steric properties, were found to be well-tolerated and yielded the desired acetoxylated compounds in good to excellent yields. Under the optimized conditions, the acetoxylation of the methylene C(sp 3 )-H bond on the tertiary and cyclic amides failed to occur. Similarly, simple carboxylic acid and ester could not afford the acetoxylated products.  Ariafard and co-workers recently described the mechanism of the Pd(OAc) 2 -catalyzed alkoxylation of butyramide derivatives facilitated by hypervalent iodine(III) reagents, with the help of density functional theory (DFT) calculations. The calculations led to the result that the process consists of four basic steps: (i) C(sp 3 )-H bond activation, (ii) oxidative addition, (iii) reductive elimination, and (iv) active catalyst regeneration. The first step completes through a concerted metalation-deprotonation (CMD) mechanism. Furthermore, the oxidative addition begins with the transfer of an X ligand from a hypervalent iodine reagent (ArIX2) to Pd(II) to create a square pyramidal complex with an iodonium at the apical position. The Pd(II) oxidation is triggered by a straightforward isomerization of the consequent five-coordinate complex. As a result, moving the ligand trans to the Pd-C(sp 3 ) bond to the apical position enhances the electron transfer from Pd(II) to iodine(III). This leads to the iodine(III) reduction accompanied by the release of the second ligand as a free anion. The C-O reductive elimination of the generated Pd(IV) complex is accomplished by the nucleophilic attack of the solvent (alcohol) on the sp 3 carbon through an outersphere S N 2 mechanism aided by the X anion. The oxidative addition and reductive elimination activities occur with a relatively low activation barrier (DG ‡ 0-6 kcal mol −1 ). Due to the coordination between the alkoxylated product and the Pd(II) center, the regeneration of the active catalyst is endergonic. Thus, the subsequent catalytic cycles proceed with a substantially greater activation barrier in comparison to the initial catalytic cycle [70].

C(sp 2 /sp 3 )-H Alkoxylation
Another intriguing Pd-catalyzed reaction that allows the synthesis of C-O bonds is the -CH alkoxylation of sp 2 and sp 3 bonds, utilizing hypervalent iodine reagents as an oxidant. In 2012, Chen's group reported a Pd(OAc) 2 /PhI(OAc) 2 catalytic method featuring the alkoxylation of the C(sp 3 )-H bonds of picolinamide-coupled amines 116 at γ or δ positions, employing alcohols 118 as a source of the alkoxy group [71]. A series of alkyl ether products 119 were isolated in 42-95% yields with excellent functional group tolerance (Scheme 37). In addition, the C(sp 2 )-H alkoxylation of arenes 117 was also investigated to yield mono-or bisalkoxylated products 120 in variable yields. Finally, the picolinamide auxiliary could be easily removed by treatment with an aqueous HCl/MeOH solution. Additionally, the directing group can be removed via nitrosylation and hydrolysis to yield β-methoxycarboxylic acid, which can be used for further transformation to various functional groups.  [73]. Using this method, the synthesis of ortho-alkoxy aromatic azo scaffolds 126 was prepared with moderate to good yields, using both primary and secondary alcohol 118 as the alkoxylation reagents (Scheme 39). However, alkoxylation occurred only with meta-substituted azobenzenes, while the ortho-and para-substituted azobenzenes gave the desired products in traces. Subsequently, Rao and his co-workers reported the first example of employing cyclic hypervalent iodine(III) reagents 130 as efficient oxidants in the Pd-catalyzed C(sp 3 )-H bond alkoxylation of unactivated methylene and methyl groups [74]. A series of 8-aminoquinolinederived carboxylic acid substrates 129 and 132 were converted into the β-alkoxylated products 131 or 133, respectively, by utilizing a variety of alcohols 118 as an alkoxy source (Scheme 41). Furthermore, the synthetic application of the current approach for the alkoxylation of several Ibuprofen analogues, such as Naproxen, Ketoprofen, and Flurbiprofen, to obtain alkoxylated compounds in varying yields, was proven. Later, the same research group established a similar approach for producing symmetrical acetals 137 through the Pd-catalyzed regioselective double C(sp 3 )-H bond alkoxylation of 8-aminoquinoline-derived substrates 125 with the alcohols 118, using cyclic iodine(III) reagent 130 as an oxidant [75]. However, in the case of unsymmetrical acetals, as per the previous condition, the premixture of both alcohols 118 and 136 would give symmetric acetal as the major product (Scheme 42). Therefore, a modified two-step protocol was developed wherein, initially, the monoalkoxylation of 134 with ROH 118 was carried out at 80 • C for 2-6 h, followed by the addition of R 2 OH 136 and the oxidant 130 to yield unsymmetric acetals 138 in good yields.  [76]. The reaction employed 2-pyridyloxyl as an easily transformable directing group and alcohols 118 as a source of the alkoxy group (Scheme 43). Electron-rich substrate-bearing groups, such as alkoxy and methyl, gave the best results, whereas the electron-deficient substrates led to the lowering in yields.

C(sp 2 )-H Oxidation
Bigi and White transformed terminal olefins 141 into α,β-unsaturated ketones 142 via the Wacker oxidation-dehydrogenation process, employing the Pd(II)/PhI(OAc) 2 cocatalytic system in the presence of 1,4-benzoquinone as an oxidant [77]. Interestingly, PhI(OAc) 2 1 played a crucial role as a dehydrogenation catalyst and not as a terminal oxidant. The reaction occurred under mild conditions (35 • C), tolerating a wide range of functional groups, and α, β-unsaturated ketones 142 were obtained in good yields (Scheme 44). Later, similar to Wacker-type oxidation, Fernandes's research group developed a procedure to convert different aliphatic and aromatic terminal alkenes 143 into functionally diverse methyl ketones 145 using Dess-Martin Periodinane (DMP) 144 as an oxidant under a nitrogen atmosphere [78]. Furthermore, a variety of allylic or homoallylic compounds 146 were examined under similar olefin oxidation conditions to produce substantial quantities of methyl ketones 147. This approach has several benefits, including excellent functional group compatibility with a wide range of substrates and high yields with complete Markovnikov selectivity (Scheme 45).

C-H Phosphorylation/Sulfonation
Huang and colleagues recently demonstrated the Pd(II)-catalyzed sulfonation and phosphorylation of the unactivated benzyl C(sp 3 )-H bonds of 8-methylquinolines 148, using sulfonate or organophosphorus hypervalent iodine(III) reagents 149 as an oxidant as well as a functional group source [79]. Using this technique, the desirable products 150 or 151 were produced in moderate to high yields over a wide range of substrates (Scheme 46). Additionally, the same approach was applicable for the pyridyl-directed C(sp 2 )-H hydroxylation and arylation of arenes.

Miscellenous
In 2015, Kitamura and his research group disclosed a novel route to accessing acyloxyarenes 153 from trimethylsilyl-arenes 152 via a Pd(OAc) 2 -catalyzed desilylative acyloxylation strategy, using the easily available terminal oxidant PhI(OCOCF 3 ) 2 (PIFA) 82 in AcOH [80]. The reaction scope was explored by varying the substituents on arenes as well as by using different carboxylic acids 87 as a source of the acyl group (Scheme 47). Additionally, the hydrolysis of acetoxylated products gave access to phenol derivatives, which further extended the synthetic utility of this method.

C-C Bond Formation
C-H functionalization using a palladium catalyst is an essential technique in C-C bond-forming reactions. A variety of catalytic reactions involving hypervalent iodine(III) reagents as oxidants have been discussed in this section.

Via Oxidative Cyclization
Li and his colleagues developed an intriguing domino process showcasing the Pdcatalyzed C-H functionalization of N-arylpropiolamides 160, utilizing iodine(III) reagent 161 as an aryl source [83]. This ingenious procedure resulted in 3-(1-arylmethylene)oxindoles 162 (Scheme 50). Furthermore, the study was conducted to find the effect of several electron-rich and electron-deficient substituents on the aryl ring and the terminal triple bond. It was also reported by the group that substrates 160 with the N-acetyl or N-H group were unsuitable for the present reaction. Later, the synthesis of (E)-(2-oxindolin-3ylidene)phthalimides and (E)-(2-oxoindolin-3-ylidene)methyl acetates by the palladiumcatalyzed C-H functionalization of N-arylpropiolamides with phthalimide and carboxylic acids as nucleophiles was also reported by Tang et al. [84,85]. In 2012, the palladium-catalyzed PhI(OAc) 2 -mediated intramolecular trifluoromethylation of alkenes 165 was achieved using TMSCF 3 166 as an efficient trifluoromethyl source [91]. This method provided easy-to-access CF 3 -substituted oxindoles 168 at room temperature (Scheme 52). The presence of nitrogen-containing ligand 167 and Lewis acid Yb(OTf) 3 was necessary to obtain the best results for the cyclization reaction. This reaction probably occurs via the arylpalladation of olefins, followed by the nucleophilic attack of arene to generate Pd(II) intermediate 169, which, upon oxidation and reductive elimination, forms Csp 3-CF 3 bond.
Tong and co-authors in 2019 developed an outstanding example of a Pd(II/IV)catalyzed intramolecular cycloaddition of propargylic alcohol or amine and alkene of substrates 170 through an acetoxylative (3 + 2) annulation approach to afford bicyclic heterocycles 171 in a good yield [92].

Via C-H Bond Arylation
In 2011, Mao and colleagues reported an in-situ Heck-type coupling reaction between olefins 143 and iodobenzene, using hypervalent iodine reagents 180 [93]. The reaction was carried out in an open environment at 40-60 • C using Pd(OAc) 2 (4 mol%), K 2 CO 3 as a base, and PEG-400 solvent media. The expected coupling products 181 were obtained in an excellent yield (Scheme 55). The catalytic system was devoid of any ligands and had good catalyst recyclability. Magedov and colleagues discovered a comparable Pd-catalyzed Heck-type arylation of terminal alkenes with aryliodine(III) diacetates [94]. Under the optimized reaction conditions, a number of iodobenzene diacetates 183 bearing various functional groups were coupled with benzoxazoles derivatives 182 to efficiently furnish the corresponding arylation products 184 in modest to excellent yields (Scheme 56) [95]. A further reaction with iodobenzene instead of PIDA 1 gave a trace amount of the arylation products monitored by GC-MS, which indicates that ArI is not the possible intermediate in the present reaction. Cai and colleagues used aryliodine(III) diacetates 183 as a coupling partner in the Pd-catalyzed C-H arylation of polyfluoroarenes 185 [96]. The described protocol exhibits excellent substrate scope and tolerates a wide range of functional groups. The reaction mechanism indicates the in situ formation of aryliodides from ArI(OAc) 2 183 under basic conditions, resulting in moderate to excellent yields of desirable polyfluorobiaryls 186 (Scheme 57).  Furthermore, in the same year, Novák and coworkers developed Pd-catalyzed ortho C-H activation of the aromatic and heteroaromatic system (Scheme 61). Various directing groups (DG), such as the secondary and tertiary amides of anilides, ureas, benzamide derivatives, or ketones, resulted in stereoselective fluorovinylation under mild reaction conditions [99]. The tetrafluoropropenylation reaction of substituted acetanilide 197 with mesityl-(tetrafluoropropenyl) iodonium triflate 198 at 25 • C in the presence of 7.5 mol% palladium(II) acetate catalyst and 2 equiv. trifluoroacetic acid (TFA) dissolved in DCM completed in 4 h to obtain the 2,3,3,3-tetrafluoropropenylated 199 with Z selectively in a high yield. The reaction was observed to be tolerant towards various types of substituents.  [100]. The mesityl(trifluoroethyl)iodonium triflate 192, a hypervalent iodine reagent developed by the Novák group, was used as the coupling partner. The products obtained 201 had a moderate to good yield with stereoselectivity towards the formation of Z-isomers. Under the given reaction conditions, it was observed that the aromatic substitution pattern did not affect the reaction yield. The reaction was well tolerated by a wide range of functional groups, including ester and halogens (Cl, Br, and even I). On changing the directing group, a drastic change in the yield of the products was observed. On using 5-methoxy-8-aminoquinoline as a directing group, the yield of the corresponding product dropped to 18%, while the styrene-directing group resulted in no reaction. Thus, it was concluded that that the directing group played an important role in the transformation.

Via C-H Alkynylation
Waser and colleagues, in 2013, reported the regioselective C2-alkynylation of Nalkylated indoles 202 in the presence of a palladium catalyst and TIPS-EBX 203, an alkynylating reagent [101], for the first time. The process provided a good yield of 2-alkynylated indoles 204 at room temperature (Scheme 63). A variety of substituents, including Cl, Br, F, and I, remained an integral part of the end products, allowing for additional synthetic modifications.

Via Coupling
In 2015, Cai and co-workers reported the first example of the Pd-catalyzed homocoupling of aryliodine(III) diacetates 208 towards the synthesis of synthetically useful symmetrical biaryls 209 [102]. The reaction worked remarkably well under aerobic conditions, required a shorter reaction time, and tolerated a reasonable range of functional groups with good chemoselectivity (Scheme 65). Preliminary mechanistic studies revealed in situ generations of aryl iodide through the base-mediated thermal degradation of 208, accompanied by an Ullmann-type homocoupling to give the desired products 209. In 2016, Huang and co-workers illustrated the use of easily available hypervalent iodine(III) compounds 211 as efficient arylating reagents in the preparation of arylated Nheteroaromatic compounds 212 using palladium catalysis [103]. A variety of N-heteroaromatic bromides 210 were successfully coupled to afford aromatic-substituted pyridines and quinolones in moderate to good yields (Scheme 66). Furthermore, the substrates with electron-donating groups showed higher reactivity as compared to their counterparts.  Recently, in 2020, Song and co-workers reported a C-H arylation reaction of heterocycle compound 216 in the presence of 5 mol% Pd nanoparticle catalyst 217 and 1.3 equv. hypervalent iodine reagent, [Ph 2 I]BF 4 218, as an oxidant at 60 • C (Scheme 68) [104]. The arylation specifically occurred at the C2 position of the heterocyclic compounds, such as indole and furanes, with a high yield of arylated product 119; only sulphur-containing heterocycles benzothiophene and the substituted thiophene provided C3-arylated products. It was also observed that the yield of the arylated product increased by adding water to the reaction. The Pd nanoparticles used as the catalyst were easily recovered after the reaction and were reutilized five more times. The recycled catalyst provided the arylated product in an 80-86% conversion for up to six cycles.

C-N Bond Formation
In recent times chemists have shown a lot of interest in catalytic C-H activation/C-N bond formation as it is a robust method for making N-containing aliphatic/aromatic heterocycles. Many methodologies are reported for the C-H aminations of unactivated sp 3 and sp 2 C-H bonds employing palladium species as the catalyst and hypervalent iodine reagents as oxidants. In the next section, we will discuss various intra-and intermolecular C(sp 2 /sp 3 )-H bond functionalization reactions reported in the last decade using this strategy.

Via Intramolecular C(sp 2 /sp 3 )-H Bond Functionalization
In 2008, Gaunt and co-workers reported an elegant approach for the synthesis of carbazoles 221 at room temperature [105]. The reaction involves the intramolecular C-H amination of N-substituted biphenyls 220 using Pd(OAc) 2 and PhI(OAc) 2 1 as a catalyst and oxidant, respectively (Scheme 69). The possible strategy designed for this reaction involves the coordination of Pd to the amine 220, cyclopalladation, oxidation, and reductive elimination to afford cyclic products 221. Further preparation and isolation of the trinuclear carbopalladation complex confirm that the reaction follows the Pd(II)/Pd(IV) catalytic cycle. Furthermore, the potential scope of this method was extended for the synthesis of N-glycosyl carbazoles, a basic skeleton found in many natural products. Yu and colleagues exhibited that the intramolecular C-H activation/C-H cyclization of phenethylamine derivatives 222 with 2-pyridinesulfonyl as an efficient directing group in the presence of oxidant PhI(OAc) 2 1 affords a variety of functional diverse indoline derivatives 223 in moderate to high yields (Scheme 70) [106]. Furthermore, 2pyridinesulfonyl moiety was removed easily under mild conditions by treating with magnesium in MeOH at 0 • C. Similar intramolecular C-H amination reactions to prepare indolines were previously reported by Daugulis and Chen's research groups independently, using a Pd(OAc) 2 /PhI(OAc) 2 1 catalytic system [107,108].   Chen's research group reported the synthesis of heterocyclic amines 232 and 234 by intramolecular C-H amination reactions in toluene, using Pd(OAc) 2 as catalysts and PhI(OAc) 2 1 as an oxidant, under an inert environment [109]. A series of picolinamide (PA)directed amine substrates 231 and 233 bearing γand δ-C(sp 3 )-H bonds were cyclized smoothly to afford azetidines 232 and pyrrolidines 234, respectively, in significant yields with high diastereoselectivity (Scheme 73). Gratifyingly, PA can be removed easily under acidic conditions at room temperature.

Via Intermolecular C(sp 2 )-H Bond Functionalization
Liu and co-workers disclosed the Pd-catalyzed intermolecular oxidative C-H amination of unactivated terminal olefins 235, using O-alkyl N-sulfonylcarbamates 236 as nitrogen nucleophiles and employing PhI(OPiv) 2 56 as a terminal oxidant and 1,4-naphthoquinone as an additive [110]. This oxidative amination protocol leads to the efficient synthesis of valuable allylic amines 237 in useful yields (Scheme 74). In addition, the present catalytic system provides products in improved yields as compared to previously reported aerobic oxidative protocols. Hartwig and colleagues discovered another intriguing approach using the Pd-catalyzed regioselective intermolecular C-H amination of multi-substituted arenes 238 utilizing phthalimide 239 as the source of nitrogen supply [111]. The reactions require the sequential addition of oxidant PhI(OAc) 2 1 at 9 and 24 h as it reverts Pd black formed into soluble palladium species, thereby increasing product yields. A series of N-aryl phthalimides 240 were synthesized in moderate to good yields with sterically controlled regioselectivity (Scheme 75).

C-B, C-Si, and C-Halogen Bond Formation
For the first time, Szabó and coworkers reported the selective C-H borylation of simple alkenes, using a palladium pincer complex as an efficient catalyst and PhI(OCOCF 3 ) 2 82 as an essential oxidant [112]. A series of cyclic 241 and acyclic alkenes 245 were reacted with bis(pinacolato)diboron (B 2 pin 2 ) 243 as a boronate source to provide valuable organoboronates 244 and 246, respectively, in moderate to good yields (Scheme 76). Furthermore, the reaction was examined with Pd(OAc) 2 as a catalyst; however, the products were obtained with lower yields. Except for cycloheptane, which gave allylic compounds preferentially, the subsequent borylation process proceeded with great vinylic selectivity.  Szabó and colleagues pioneered the first oxidative allylic C-H silylation of terminal olefins 235 with hexamethyldisilane 251 as the silyl source, yielding allylsilanes 254 [113]. This catalytic process employed hypervalent iodine(III) reagent 253 as an oxidant and a Pd(OAc) 2 or a nitrogen-and selenium-based palladium catalyst 252 (Scheme 78). More-over, the functional groups, such as ester, benzyl, and amide were well tolerated under the oxidizing conditions, and the anticipated products were obtained with high regioand stereoselectivity.  The conversion of a C-H bond into a C-Halogen bond, catalyzed by palladium, is an appealing approach for obtaining valuable aryl halides. However, only a few experiments have been conducted in C-H halogenation reactions using high-valent palladium catalysis in the past. Sanford and colleagues presented the very first study on Pd-catalyzed C-H fluorination using AgF as the fluoride source and PhI(OPiv) 2 56 as the oxidant [114]. A variety of 8-methylquinoline analogues 259 with variable substituents were transformed successfully into fluorination products 260 in moderate to good yields (Scheme 80). Further substrates 259 bearing electron-withdrawing groups produced better results than those with electron-donating groups. Rao's research group demonstrated the ortho C-H iodination of phenol carbamates 261 in DCE/TfOH at room temperature using palladium catalysis and cyclic hypervalent reagent 262 as an iodine source and oxidant [115].

Alkene Difunctionalization
The palladium-catalyzed difunctionalization of simple alkenes using hypervalent iodine reagents has emerged as a powerful method in organic synthesis. Various 1,1and 1,2-difunctionalization protocols have been developed by several researchers for preparing a diverse array of useful molecules from alkenes. A general mechanism for the Pd- Later, Sanford and co-workers disclosed the similar 1,1-aryloxygenation protocol, wherein arylstannanes 273 were successfully coupled with terminal olefins 143 in the presence of hypervalent iodine reagents (PhI(OCOR') 2 ) 180 as an oxidant [117]. This catalytic approach enabled a simultaneous generation of C-C and C-O bonds in a single step, furnishing 1,1-arylacetoxylated products 275 in significant yields (Scheme 84). However, the formation of Heck and 1,1-arylchlorinated products was observed under these conditions.

Intramolecular 1,2-Difunctionalization of Alkenes
One of the most potent methods for constructing aromatic and aliphatic cyclic compounds containing heteroatom is the catalytic intramolecular difunctionalization of alkenes. The Pd-catalyzed intramolecular oxidative amination for the production of tetrahydrofurans utilizing the PIDA 1 as an oxidant was reported by Sanford and colleagues [118]. Muñiz's research group then used a palladium catalyst for intramolecular catalytic alkene diamination for the synthesis of bisindoline and cyclic urea scaffolds [119][120][121]. Furthermore, Oshima and co-workers disclosed a novel intramolecular carboacetoxylation protocol for the oxidative cyclization of 4-pentenyl-substituted malonate esters 276, employing oxidant PhI(OAc) 2 1 to afford acetoxymethyl-substituted cyclopentane derivatives 277, along with bicyclic lactones 278 (Scheme 85) [122]. Additionally, the carboacetoxylation products 277 could be easily converted into bicyclic lactones 278 by treating with sulfuric acid under a reflux condition in isopropyl alcohol.  2 and PhI(OAc) 2 1 as an oxidant [123]. Interestingly, when substrate 279 (R 2 = H) was subjected to domino carboacetoxylation, the expected oxindole was isolated along with spirooxindole 282. Thus, the authors re-evaluated the present condition and synthesized spirooxindoles 282 from alkenes 281 via a carboamination process under modified conditions, employing the PdCl 2 catalyst in acetonitrile at 80 • C (Scheme 86). The intramolecular oxyalkynylation of nonactivated terminal alkenes employing hypervalent iodine reagent was reported by Waser and co-workers in 2010 for the first time [124]. Phenol 283 and aliphatic or aromatic acid derivatives 285 in the presence of Pd(hfacac) 2 as a Pd catalyst and hypervalent iodine(III) reagent derived from benziodoxolone 192 as an acetylene transfer reagent in DCM resulted in a good yield of cyclic ethers 284 and γ-lactones 286, respectively (Scheme 87). Later, in 2011, the same research group synthesized 4-propargyl lactams 288 by the intramolecular aminoalkynylation of activated olefins 287, using TIPS-EBX 192 as an alkynylating agent. The catalyst used for the reaction was lithium palladate, Li 2 [PdCl 4 ], which was generated in situ [125]. Additionally, the present protocol was successfully utilized for the synthesis of 4-propargyl oxazolidinone and imidazolidinones 290 through the cyclization of allyl carbamates or allyl urea 289 (Scheme 88). Furthermore, the synthetic utility of this reaction was extended towards the synthesis of the bicyclic heterocycles pyrrolizidine and indolizidine and also in the total synthesis of the natural product (±)-trachelanthamidine. Liu and co-workers achieved the Pd-catalyzed intramolecular aminofluorination of unactivated alkenes 291 to fluorine-containing cyclic amines 292 in moderate to high yields [126]. The reaction employed AgF as a fluorinating agent and PhI(OCO t Bu) 2 56 as a terminal oxidant (Scheme 89). These transformations proceeded via a Pd(II/IV) catalytic cycle involving the trans-aminopalladation of olefins mediated by Pd, oxidation by PhI(OPiv) 2 , and a final reductive elimination, giving aminofluorination products.

Intermolecular 1,2-Difunctionalization of Alkenes
Muñiz and colleagues pioneered intermolecular diamination of terminal alkenes in the presence of a Pd catalyst, using saccharin and bissulfonimides as nitrogen donors and iodosobenzene dipivalate 56 as an oxidant [127]. Later, Martinez and Muñiz used a Pd/PhI(OPiv) 2 catalytic system to effectively perform an intermolecular vicinal diamination of internal alkenes 293 with phthalimide 239 and bissulfonimides 294 as nitrogen sources [128]. The limiting reagent in this reaction was alkene, and the anticipated diamination products 295 were obtained in a variable yield with perfect regio-and diastereoselectivity (Scheme 90). The mechanistic approach towards the intermolecular diamination of alkenes is shown in Scheme 91. Initially, alkene 293 coordinates with the Pd catalyst followed by the subsequent aminopalladation involving the nucleophilic addition of 239 trans stereochemistry to form δ-alkylpalladium complex 296. The rapid oxidation of complex 296 gives Pd(IV) intermediate 297, which is attacked by bissulfonimides 294 to provide desired products 295 with a net inversion of configuration at the benzylic position. Similarly, the allylic ethers 298 underwent a catalytic intermolecular 1,2-diamination reaction in the presence of phthalimide 239 and N-fluoro-bis(phenylsulfonyl)imide 299 as nitrogen sources [129]. In the presence of oxidant iodosobenzene dipivalate 56, the diamination proceeded smoothly with complete regio-and chemoselectivity to furnish the 1,2,3-trisubstituted amination products 300 in good yields (Scheme 92). In continuation, Muñiz and co-workers reported the synthesis of new palladiumphthalimidato complexes 302 and demonstrated their broad applicability as catalysts in the vicinal diamination of allyl ethers 301 and alkenes 235, using phthalimide 239 and tetrafluorophthalimide as nitrogen sources [130]. The treatment of phthalimide 239 with Pd(OAc) 2 in nitrile solution at room temperature resulted in the formation of palladiumphthalimidato complexes 302. The air-stable preformed phthalimidato complexes, which proved to be versatile catalysts for the present diamination reaction, providing the desired products 303 and 304 in useful yields (Scheme 93). Furthermore, the same research group synthesized other bissaccharido palladium(II) complexes and investigated their applications in the catalytic regioselective diamination and aminooxygenation of alkenes [131]. The dioxygenation of vicinal alkene is a critical step in the preparation of valuable 1,2dioxygenated scaffolds. Dong et al. and Shi's research group simultaneously reported Pdcatalyzed vicinal dioxygenation of olefins using hypervalent iodine reagent as the terminal oxidant through a unique Pd(II)/Pd(IV) mechanism [132,133]. Later, Sanford's group developed the chiral oxime-directed asymmetric 1,2-dioxygenation of alkenes 305 in the presence of Pd(II) catalysts, using PhI(OBz) 2 67 as an oxidant and benzoyloxy source [134]. Various chiral allyl oxime ethers were tested, and the results showed that menthonederived substrates had the highest reactivity and diastereoselectivity. This method allows the efficient preparation of dibenzoylated compounds 306 with a disterioisomeric ratio up to 90:10. (Scheme 94). Sorensen and Stahl's groups concurrently reported the Pd-catalyzed aminoacetoxylation of alkenes, using 1 equiv. of nitrogen nucleophiles and 2 equiv. of olefin [135,136]. Muñiz and colleagues later disclosed a modified approach for the intermolecular aminoacetoxylation of internal/terminal alkenes 242 that allowed the alkene substrate to be used as a limiting reagent [137]. Using phthalimide 239 as a nitrogen source, a variety of alkenes, such as allyl ethers, allyl benzenes, (Z)-methylstyrene, etc., were oxidized and transformed into an aminoacetoxylated product 307. (Scheme 95). Based on the results of the experiments, it was shown that PhI(OAc) 2 1 alters the stereochemical aspect of the aminoacetoxylation process, favoring the trans-aminopalladation route. Szabó and colleagues, in 2016, reported the Pd-catalyzed iodofluorination of alkenes 308 using fluoroiodane reagent 309 as an iodine and fluorine source [138]. Pd(BF 4 ) 2 (MeCN) 4 or PdCl 2 (MeCN) 2 or Pd(OAc) 2 in CDCl 3 were used in the reaction. The reaction was planned to proceed to intermediate 311, which, following C(sp 2 )-I bond breakage, would produce iodofluorinated compounds 310 in moderate to excellent yields (Scheme 96). Some alkenes, on the other hand, underwent allylic rearrangement, followed by iodofluorination, to produce internally iodofluorinated compounds. Simple cycloalkenes also produced an iodofluorinated product, but at low yields.
In 2015, Liu and co-workers demonstrated an efficient and simple palladium-catalyzed protocol for the synthesis of β-amino acid derivatives 313 and 315 from alkenes 143 via an intermolecular aminocarbonylation reaction [139]. An array of aliphatic or aromatic terminal alkenes 143 were reacted with either 2-oxazolidone 314 or with phthalimide 239 under a carbon monoxide atmosphere in the presence of a hypervalent iodine(III) reagent as an oxidant (Scheme 97). The reaction possessed excellent regioselectivity, broad substrates scope, and remarkable functional group tolerance. Further experimental evidence revealed that the iodine(III) reagent plays a crucial role in accelerating the intermolecular aminopalladation process. Using PIDA 2 as an oxidant, the same research group devised a new Pd-catalyzed intermolecular oxycarbonylation of terminal 316 or internal alkenes under a CO atmosphere [140]. This difunctionalization procedure allows for the simple synthesis of different oxycarboxylic acids 317 and 319 with high functional group compatibility, regioselectivity, and diastereoselectivity (Scheme 98). This method's potential was expanded to the synthesis of a natural product, (+)-honaucin C, in a 48% yield, up to 99% ee.

Miscellaneous
Das et al., in 2020, introduced an interesting Pd-catalyzed ortho-C(sp 2 )-H variation of (NH)-free 2-substituted benzimidazole, quinazoline, imidazopyridine core as the directing group 320 in the presence of PIDA 1 as a key reagent under mild conditions [141]. Four different functional groups, acetoxy, aryl, iodide, and nitro groups, were installed concurrently on the single substrate by changing the inorganic additives in the presence of PIDA under aerobic conditions. PIDA, a hypervalent iodine catalyst, serves as an oxidant and a source of functional groups in all of the four reactions. In absence of any additive, the acetoxy group becomes attached to the ortho position of the phenyl to give 321, whereas, in the presence of Cs 2 CO 3 , I 2 , and NaNO 2 , the additives in acetonitrile solvent aryl, iodide, and the nitro group attach at the ortho position to give products 322, 323, 324, respectively (Scheme 99). The reactions complete in 3-6 h and are found to be functional-group tolerant. Scheme 99. Pd-catalyzed C(sp 2 )-H functionalization of benzothiazole/benzoxazole/benzimidazole 320 using PIDA 1 as an oxidant.

Conclusions
This review explored the various palladium-catalyzed reactions mediated by hypervalent iodine compounds. Hypervalent iodine compounds have emerged as versatile oxidants, with a wide range of reactivity under mild conditions, and at the same time are non-toxic, environmentally friendly, inexpensive, and easy-to-handle reagents in organic synthesis. In recent years, the use of hypervalent iodine reagents in palladium-catalyzed transformations has received a lot of attention as they are strong electrophiles and powerful oxidizing agents. Together, they act as a powerful tool for the diversification of C-H bonds. The intrinsic oxidizing character and specific reactivity with palladium catalysts have successfully synthesized various useful scaffolds through C-O, C-N, C-C, C-Si, C-B, and C-halogen bond formation reactions. In addition, a variety of Pd-catalyzed alkene difunctionalization processes utilizing hypervalent iodine reagents have recently been established. In future, an intriguing area of investigation would be the use of recyclable polymer-supported hypervalent iodine reagents in palladium-catalyzed processes.