Hypervalent Iodine Reagents in Palladium-Catalyzed Oxidative Cross-Coupling Reactions

Hypervalent iodine compounds are valuable and versatile reagents in synthetic organic chemistry, generating a diverse array of useful organic molecules. Owing to their non-toxic and environmentally friendly features, these reagents find potential applications in various oxidative functionalization reactions. In recent years, the use of hypervalent iodine reagents in palladium-catalyzed transformations has been widely studied as they are strong electrophiles and powerful oxidizing agents. For instance, extensive work has been carried out in the field of C–H bond functionalization via Pd-catalysis using hypervalent iodine reagents as oxidants. In addition, nowadays, iodine(III) reagents have been frequently employed as arylating agents in Pd-catalyzed C–H arylation or Heck-type cross-coupling reactions. In this review, recent advancements in the area of palladium-catalyzed oxidative cross-coupling reactions using hypervalent iodine reagents are summarized in detail.


INTRODUCTION
Hypervalent iodine compounds are ubiquitous in organic synthesis since they have emerged as efficient and environmentally benign reagents for academic and industrial research (Zhdankin, 2014;Yoshimura and Zhdankin, 2016;Singh and Wirth, 2018). They are non-toxic, easily prepared, stable and alternative to metal-derived oxidants/catalysts in various oxidative transformations (Yusubov and Zhdankin, 2012;Wirth, 2014a,b, 2017;Mangaonkar et al., 2018;Singh et al., 2018a;Mangaonkar and Singh, 2019). Several research papers, book chapters and review articles have been published covering various aspects of hypervalent iodine compounds as reagents or as catalysts in α-functionalization of carbonyl compounds (Merritt and Olofsson, 2011;Dong et al., 2014), cyclizations Wirth, 2011, 2012;Singh and Mangaonkar, 2018;Singh et al., 2018b), oxidative rearrangements Singh and Wirth, 2013;Maertens and Canesi, 2015), alkene difunctionalizations (Li et al., 2018;Lee et al., 2019) and atom-transfer reactions (Li Y. et al., 2016). The inherent ability of hypervalent iodine reagents to act as oxidants as well as ligand transfer reagents is the key to the significant progress achieved in this area.
However, these reagents do have limitations such as stoichiometric generation of aryliodides as a byproduct, limited solubility in common organic solvents, and requirement of an excess amount of reagents thus lowering atom economy dramatically. For instance, IBA 6 is less explored due to its lower reactivity while DMP 8 is expensive and moisture sensitive. IBX 9 is associated with drawbacks such as an explosive nature, poor solubility in common organic solvents, and requirement of high reaction temperature which limits its synthetic applications to some extent (Singh and Wirth, 2014b). Also, IBS 11 is thermally unstable and highly reactive toward organic solvents, like acetonitrile, dimethyl sulfoxide, and methanol and readily decomposed into stable thia-analog of IBA 7 (Koposov et al., 2006). Although there are some drawbacks associated with these reagents, there is still great scope for these compounds as potential alternate candidates for toxic heavy-metal oxidants such as mercury, thallium, and lead based reagents (Silva L. F, 2002;Wirth et al., 2002).
On the other hand, palladium as a catalyst has become a fundamental part of various coupling reactions such as Suzuki-Miyaura, Heck, Buchwald-Hartwig, Sonagashira, and Negishi generating diverse array of useful molecules (Biffis et al., 2018). Hypervalent iodine reagents in palladium-catalyzed reactions constitute an interesting area of research in organic synthesis. Deprez and Sanford published the first review article explaining the unique reactivity of hypervalent iodine reagents in Pdcatalyzed reactions in 2007 (Deprez and Sanford, 2007). Later, the 2015 section of the review that describes the key role of polyvalent iodine reagents in high valent palladium chemistry was published by Wengryniuk's group (Silva et al., 2017). Owing to their excellent oxidizing and electrophilic nature, hypervalent iodine reagents reacts with palladium complexes and promotes reactions via Pd(0/II) or Pd(II/IV) redox cycles. For instance, iodine(III) reagents have been employed as a substitute for aryl halides in various Pd(0)/(II)-catalyzed cross-coupling reactions (Deprez and Sanford, 2007). Also, various Pd-catalyzed ligand transfer reactions employ few of these reagents as a source of aryl, alkynyl, and heteroatom ligands. Although substantial work has been carried out in Pd(0)/(II)-catalysis in the past, catalytic reactions via Pd(II)/(IV) pathway were less explored. However, with the aid of hypervalent iodine oxidants, Pd(II)/(IV)catalysis have seen tremendous development in the last couple of decades enabling various synthetic transformations earlier inaccessible via traditional catalytic manifolds. For example, C-H functionalizations have become a powerful tool to construct new C-C and C-heteroatom bonds using Pd(II)/(IV)-catalysis.
Within this context, the present review focuses on the recent advancement accomplished in palladium-catalyzed transformations using hypervalent iodine reagents, highlighting its potential synthetic applications and mechanistic aspects. The article is classified on the basis of bonds formed such as C-O, C-N, C-C, C-Si, C-B, and C-halogen bonds and finally alkene difunctionalization reactions.

C-O BOND FORMATION
Palladium-catalyzed ligand assisted C-H functionalization has been proven to be one of the best, most atom economical, and effective tools in organic synthesis for the introduction of variable functional groups at the unactivated arene/alkane C-H bonds. Extensive research has been carried out by several groups in the field of C-O bond formation via palladium catalysis using hypervalent iodine reagents as oxidant or heteroatom ligand. Among them, Pd-catalyzed C-H oxidative cyclization, C-H acyloxylation, C-H alkoxylation and allylic oxidation constitutes important pathways in C-O bond formation reactions directed by directing functional groups such as oxime ether, oxazoline, amide, pyridine and pyrimidine, etc.

C-H Cyclization
Significant progress has been made in the field of Pd-catalyzed oxidative cyclization reactions using hypervalent iodine reagents, giving access to several oxygen-containing heterocycles. In 2010, Wang et al. developed a novel method for the construction of dihydrobenzofurans via Pd(OAc) 2 -catalyzed hydroxyl groupdirected C-H activation/C-O cyclization reaction in the presence of (diacetoxyiodo)benzene 1 as a terminal oxidant and promoted by base Li 2 CO 3 . Moreover, the scope of the reaction was extended to the preparation of important scaffolds such as spirocyclic dihydrobenzofurans .
Later, Gevorgyan's group demonstrated intramolecular silanol group-directed C-H oxygenation of phenoxy silanols 17 employing Pd(OPiv) 2 as catalyst and PhI(OAc) 2 1 as an oxidant (Huang et al., 2011). This reaction involves the initial formation of cyclic silicon-protected catechols 18 which upon desilylation with TBAF/THF provides substituted catechols 19 (Scheme 1A). The plausible catalytic cycle involves initial coordination of Pd with silanols 17 to form palladacycle 20 accompanied by PIDA-mediated oxidation to forge Pd(IV)-intermediate 21. Next, intermediate 21 is transformed into acetoxylated intermediate 23 via reductive acetoxylation and regenerates back palladium catalyst. Finally, acid-catalyzed transesterification of 24 gives 25 which subsequently loose acetic acid to form cyclic silyl SCHEME 1 | (A) Pd(II)-catalyzed synthesis of substituted catechols 19 using PhI(OAc) 2 1 as an oxidant and (B) Pd(II)-catalyzed synthesis of cyclic ethers 27 using PhI(OAc) 2 1 as an oxidant. protected catechols 18 followed by subsequent desilylation with TBAF furnishes catechols 19. Further formation of products 22 through direct C-O reductive cyclization was eliminated based on 18 O-labeling studies. Further reactions featured excellent site selectivity and broad substrates scope, particularly, electronrich substrates reacted much faster and provided high yields. Another interesting work published by Gevorgyan's research group employing C-H oxygenation strategy is the convenient synthesis of oxasilacycles from substituted benzyl-silanols using combination of Pd(OAc) 2 and PhI(OAc) 2 1 in PhCF 3 at 100 • C (Huang et al., 2012). Furthermore, Thompson et al. reported the preparation of cyclic ethers 27 via Pd-catalyzed oxime masked-alcohol directed dehydrogenative annulation of sp 3 C-H bonds of substrates 26 using PhI(OAc) 2 1 as an oxidant (Thompson et al., 2015). The reaction occurs selectively at the βposition and substrates 26 having primary, secondary, and tertiary hydroxyl group worked smoothly under the standard conditions (Scheme 1B). The reaction could proceed via C-H palladation, followed by oxidation of Pd to higher oxidation state species 28 and a subsequent intramolecular S N 2 reaction to form oxonium intermediate 29. Finally, cyclic ethers 27 SCHEME 2 | (A) Pd(II)-catalyzed α,α-disubstituted benzofuran-2-ones 31 using PhI(OAc) 2 1 and (B) Pd(II)-catalyzed synthesis of γ -lactones 34 using oxidant PhI(OAc) 2 1. were obtained through deprotonation or debenzylation and regenerate Pd-catalyst.
Yang et al. reported Pd-catalyzed intramolecular lactonization of α, α-disubstituted arylacetic acids 30 in the presence of PhI(OAc) 2 1 to furnish a series of α, α-disubstituted benzofuran-2-ones 31 in variable yields ). The catalytic system composed of Pd(OAc) 2 and the combination of NaOAc and CsOAc along with AgOAc as most effective bases (Scheme 2A). The authors proposed that C-H cleavage occurs via concerted metalation deprotonation to form sixmembered palladacycle 32 which further undergoes oxidation and subsequent reductive elimination to afford 31. Similar catalytic C-H activation/C-O formation methods to construct functionalized benzofuranones (Cheng et al., 2013) and biaryl lactones  were also developed employing acetylprotected glycine (Ac-Gly-OH) as requisite ligand along with base KOAc in t-BuOH.
In 2016, Shi's group described a concise route to access γ-lactones 34 featuring Pd(II)-catalyzed PIP auxiliary-directed lactonization of unactivated methylene C(sp 3 )-H bonds using oxidant PIDA 1 (Liu and Shi, 2016). The lactonization of aliphatic acids 33 bearing various substituents on the alkyl chain proceeded remarkably well to furnish anticipated γ-lactones 34 in 32-77% yields (Scheme 2B). The probable mechanism for the lactonization of aliphatic acids 32 involves formation of five-membered palladacycle 35 through Pd-catalyzed C-H activation assisted by bidentate auxiliary. In the presence of PhI(OAc) 2 1, palladacycle 35 underwent oxidation to give Pd(IV) intermediate 36 followed by ligand exchange to form 37 which finally undergoes reductive elimination to release target product 34 along with Pd(II) catalyst to complete the catalytic cycle (Scheme 11). Another path to generate lactone 34 is via direct S N 2-type attack by carboxylate group onto the Pd(IV)-C bond of 36 (Scheme 2B). SCHEME 3 | Pd(II)-catalyzed ortho C-H benzoxylation of 2-arylpyridines 38 using substituted iodobenzene dibenzoates derivatives 39 as oxidant and source of benzoxyl group.
Furthermore, a regioselective protocol featuring Pd(II)catalyzed C-H benzoxylation of 2-arylpyridines 38 was performed by Zhang et al. affording mono-benzoxylation products 40 in moderate to excellent yields . They employed easily accessible iodobenzene dibenzoate derivatives 39 as oxidants and sources of the benzoxyl group (Scheme 3). Furthermore, the present method was successfully applied for the benzoxylation of 2-thienyl pyridines to yield 3benzoxylated thiophenes in high yields. The plausible mechanism proceeds via pyridyl-assisted C-H activation of substrates 38 with a palladium catalyst to form complex 41 which undergoes further oxidative addition with 39 to form high oxidation state complex 42. Finally, the reductive elimination of 42 gives desired product 40 and regenerates the palladium catalyst to complete the catalytic cycle.
Although substantial development has been accomplished in the Pd-catalyzed ligand-directed C-H oxygenation reactions, the non-chelate assisted transformations are rarely explored. For instance, Pd-catalyzed C-H acetoxylation of arenes devoid of directing groups remains a challenge as it leads to the formation of mixtures of isomers. In this context, Emmert et al. developed non-chelate assisted palladium-catalyzed C-H acetoxylation of simple arenes using pyridine (Emmert et al., 2011) and acridine (Cook et al., 2013) as ancillary ligands in combination with hypervalent iodine reagents as oxidants.
Regioselective C-H functionalization of indoles has been found to be a straight forward route to access biologically important 3-acetoxyindoles. In this regard, Suna's and Kwong's groups independently reported the synthesis of 3-acetoxyindoles via direct C3-oxidation of indole derivatives catalyzed by Pd(OAc) 2 (2-5 mol%) in the presence of terminal oxidant PhI(OAc) 2 1 (Mutule et al., 2009;Choy et al., 2011). In continuation, Liu et al. developed a similar Pd-catalyzed approach for the selective C3-acetoxylation of substituted indoles 43 with reduced catalyst loading (1.5 mol%) using PhI(OAc) 2 1 and KOH as a base (Scheme 4; Liu et al., 2011). Mechanistic insights revealed that the electrophilic palladation occurs at the C3 position of indole to generate Pd(II) species 45 which is oxidized to Pd(IV) intermediate 46 and subsequent reductive elimination affords corresponding C3-acetoxylated indoles 44.
Acyloxylation of aliphatic sp 3 C-H bond is another important method for regioselective C-O bond formation. Elegant protocols have been developed employing various nitrogenbased directing groups for the selective oxygenation of unactivated C(sp 3 )-H bond. In 2010, a novel chelation-assisted Pd-catalyzed C(sp 3 )-H acyloxylation of 8-methylquinolines in the presence of a stoichiometric amount of oxidant PhI(OAc) 2 1 was developed employing inexpensive arene carboxylic acids as acyloxy source (Zhang et al., 2010). A similar method for the catalytic acetoxylation of unactivated primary β-C(sp 3 )-H bond of S-methyl-S-2-pyridylsulfoximine-N-amides at room temperature was described by Sahoo's group (Rit et al., 2012). This method employs S-methyl-S-2-pyridylsulfoximine (MPyS) as a bidentate directing group and β-C-H acetoxylated products were synthesized using different carboxylic acids as solvent and acetate sources.
Furthermore, a Pd-catalyzed oxime-directed β-C(sp 3 )-H acetoxylation of substrates 47 was performed employing PhI(OAc) 2 1 as a terminal oxidant (Ren et al., 2012). The catalytic reaction was expected to generate five-membered exo-palladacycle 49 which on oxidation gives masked 1,2diols 48 (Scheme 5A). Also, the selective acetoxylation of βmethylene (CH 2 ) and β-methine (CH) groups in cyclopentanol and norbornyl-derived alcohols were also carried out under the same reaction conditions. Furthermore, the deprotection of DG and acetyl group was carried out by using Zn/AcOH & K 2 CO 3 /MeOH, respectively, to yield diols in excellent yield. Later, Zhang's group described an elegant work on Pd(II)-catalyzed benzylic C(sp 3 )-H acetoxylation of picolinoylor quinoline-2-carbonyl-protected toluidine derivatives using PhI(OAc) 2 1 as an oxidant and acetate source (Ju et al., 2013).  (Li et al., 2014). The process provides an easy access to γ-acetoxylated product 51 in good yields (Scheme 5B). Additionally, C-H acetoxylation of γmethyl group of arylamines proceeded smoothly under this condition. Authors speculated that reaction likely to procced via C, N, N-pincer type Pd(IV) intermediate 52, in which Li 2 CO 3 plays a crucial role as it interacts with O-imidate thereby suppressing the formation of cyclic azetidine through intramolecular C-H amination.

C(sp 2 /sp 3 )-H Alkoxylation
Another interesting Pd-catalyzed transformation enabling C-O bond formation is the C-H alkoxylation of sp 2 and sp 3 bonds using hypervalent iodine reagents as oxidant. Chen and Shi's group independently reported two methods for the palladium-catalyzed PhI(OAc) 2 -mediated alkoxylation of methylene and methyl C(sp 3 )-H bonds with a range of aliphatic alcohols as alkoxylation reagents, using picolinamide  and pyridine (Chen et al., 2013) as easily removable directing groups. Later, azo group-directed selective C(sp 2 )-H alkoxylation of azobenzene compounds with alcohols as the alkoxylation reagents was reported by Yin et al. using palladium catalysis in the presence of oxidant PhI(OAc) 2 1 . Additionally, Zhang and Sun demonstrated the regioselective alkoxylation of ortho-C(sp 2 )-H bond of 2-aryloxypyridines to provide ortho-alkoxylation products in the presence of catalytic amounts of Pd(OAc) 2 and oxidant PhI(OAc) 2 1 (Zhang and Sun, 2014).
Shan et al. for the first time employed cyclic hypervalent iodine(III) reagent 12 as an efficient oxidant in the Pd-catalyzed C(sp 3 )-H alkoxylation of unactivated methylene and methyl groups of 8-aminoquinoline-derived carboxylic acids 53 (Shan et al., 2013) (Scheme 6). The reaction worked perfectly well with DMP 8 (1.1 equivalents) at 110 • C. Gratifyingly, C(sp 3 )-H alkoxylation of cyclic substrates such as cyclopentyl, cyclohexyl, and cycloheptyl were also perfomed under identical conditions. Furthermore, the synthetic applicability of present method was demonstrated for the alkoxylation of various analogs of Ibuprofen such as, Naproxen, Ketoprofen, and Flurbiprofen to afford alkoxylated products in variable yields. Based on preliminary mechanistic studies, authors proposed that either DMP 8 or 1-acetoxy-1,2-benziodoxole-3(1H)-one 12a serve as key precursors for the in situ generation of cyclic iodine(III) oxidant 56 which oxidizes cyclopalladium(II) intermediate 57 to Pd(IV) intermediate 58. Next, ArCO 2 ligand of intermediate 58 could be easily displaced by alcohol 54 to give Pd(IV) intermediate 59 which finally undergoes C-O bond-forming reductive elimination to yield alkoxylated products 55 and regenerates palladium catalyst. Later, the same research group developed a similar method to prepare symmetrical and unsymmetric acetals via Pd-catalyzed regioselective double C(sp 3 )-H bond alkoxylation of 8-aminoquinolinederived substrates using cyclic iodine(III) reagent 12 as an oxidant (Zong and Rao, 2014). SCHEME 6 | Pd-catalyzed C(sp 3 )-H bond alkoxylation of aminoquinoline-derived substrates 53 to provide β-alkoxylated products 55 using cyclic hypervalent iodine(III) reagent 12.

C-H Oxidation and C-H Phosphorylation/Sulfonation
Chaudhari and Fernandes developed a Wacker-type oxidation protocol to convert various aliphatic and aromatic terminal alkenes 61 into functionally diversified methyl ketones 62 employing Dess-Martin Periodinane (DMP) 8 as an oxidant under nitrogen atmosphere (Chaudhari and Fernandes, 2016). Furthermore, the oxidation of a number of allylic or homoallylic compounds were also investigated under identical conditions to deliver methyl ketones in high yields. Excellent functional group compatibility, wide substrates scope and high isolated yields with complete Markovnikov selectivity are the key features associated with this methodology (Scheme 7A). A similar method for the conversion of terminal olefins into α,β-unsaturated ketones was developed by Bigi and White via a Wacker oxidationdehydrogenation process employing Pd(CH 3 CN) 4 (BF 4 ) 2 (10 mol%) and PhI(OAc) 2 1 (25 mol%) co-catalytic system in the presence of 1,4-benzoquinone as oxidant (Bigi and White, 2013). Interestingly, PhI(OAc) 2 1 acts as a dehydrogenation catalyst and not as a terminal oxidant in this reaction.
Very recently, He et al. reported Pd(II)-catalyzed phosphorylation and sulfonation of unactivated benzyl C(sp 3 )-H bond of 8-methylquinolines 63 employing organophosphorus or sulfonate hypervalent iodine(III) reagents 64 as an oxidant and as a functional group source (He et al., 2019). Using this protocol, desired products 65 or 66 were obtained in moderate to high yields with broad substrates scope (Scheme 7B). Additionally, the scope of reaction was extended for the C(sp 2 )-H hydroxylation and arylation of 2-phenylpyridines.

via C-H Bond Arylation
In 2011, Qu et al. demonstrated a Heck-type coupling reaction between olefins 61 and iodobenzene generated in situ from hypervalent iodine reagents 84 (Qu et al., 2011). The coupling reaction was performed using Pd(OAc) 2 (4 mol%), base K 2 CO 3, and PEG-400 as solvent media under an open atmosphere at 40-60 • C to afford coupling products 85 in 91-99% yields (Scheme 10). The catalytic system was free from any ligand or additive and possesses an excellent recyclability of catalyst (Scheme 10). A similar Pd-catalyzed Heck-type arylation of terminal alkenes with aryliodine(III) diacetates was developed by Evdokimov et al. (2011).
Later, Cheng's research group performed Pd(II)-catalyzed C-H functionalization of benzoxazoles 86 to furnish arylation products 88 using iodobenzene diacetates 84 as arylating reagent in the presence of ligand 1,10-phenanthroline 87 and base  . Detailed mechanistic studies revealed in situ generation of aryliodides by the reduction of ArI(OAc) 2 84 under basic conditions to furnish desired polyfluorobiaryls products 90 in moderate to good yields (Scheme 10).
Another interesting strategy to establish C-C bond formation is Pd-catalyzed oxidative coupling reactions of aromatic halides with different arylation reagents. Considering this, Xiong et al. illustrated the synthesis of useful symmetrical biaryls employing aryliodine(III) diacetates 68 as aryl precursor via Pd-catalyzed homocoupling reaction . The reaction was carried out in DMF at 110 • C in the presence of Pd(OAc) 2 (10 mol %), K 2 CO 3 (4 equiv.) under an air atmosphere. In 2016, Wang et al. reported ligand-free arylation of pyridines and quinolines via direct coupling of bromo-substituted pyridines or quinolines with hypervalent iodine(III) compounds as efficient arylating reagents in the presence of catalyst PdCl 2 and base Cs 2 CO 3 in DMF at 110 • C (Wang et al., 2016).

C-N BOND FORMATION
Catalytic C-H activation/C-N bond formation has gained considerable attention in recent times as it represents the versatile approach for the construction of N-containing aliphatic/aromatic heterocycles. Several intra-and intermolecular protocols for the palladium-catalyzed amination of sp 3 and sp 2 C-H bonds have been developed using hypervalent iodine reagents as oxidant. Gaunt has disclosed an elegant work on intramolecular C-H amination of N-substituted biphenyls for the synthesis of carbazoles at room temperature using catalyst Pd(OAc) 2 and oxidant PhI(OAc) 2 1 in the presence of acetic acid in toluene (Jordan-Hore et al., 2008). Furthemore, Chen's research group synthesized azetidines 92 via intramolecular C-H amination of picolinamide-directed amine substrates 91 employing Pd(OAc) 2 and PhI(OAc) 2 1 in toluene under argon atmosphere (Scheme 11A; He et al., 2012a). Additionally, the synthesis of pyrrolidines was also accomplished under identical reaction conditions. Mei et al. demonstrated the synthesis of indolines 94 via Pd(OAc) 2 -catalyzed intramolecular C-H activation/C-N cyclization of phenethylamine derivatives 93 using 2pyridinesulfonyl as efficient directing group in the presence of oxidant PhI(OAc) 2 1 (Mei et al., 2013). The intramolecular amination proposed to proceed via Pd-catalyzed C-H activation to generate organopalladium(II) complex 95, followed by oxidation to form palladium(IV) intermediate 96 and final C-N reductive elimination to provide anticipated products 94. Furthermore, the 2-pyridinesulfonyl moiety was easily removed under mild reaction conditions by treating with magnesium in MeOH at 0 o C (Scheme 11B). Similar protocols to prepare indolines were independently reported by Daugulis, Chen, and Shi's research groups employing Pd(OAc) 2 /PhI(OAc) 2 1 catalytic system (He et al., 2012b;Nadres and Daugulis, 2012;Ye et al., 2013).

C-B AND C-SI BOND FORMATION
Sazabo and his research group demonstrated the first example of selective C-H borylation of simple alkenes 97 employing a palladium pincer complex 98 as an effective catalyst and PhI(TFA) 2 2 as an essential oxidant (Selander et al., 2010). Reaction was performed in neat alkenes (Condition A) or diluted alkenes (Condition B) at ambient temperature (Scheme 12A).
Simple cycloalkenes 97 such as cyclopentene and cyclohexene (R 1 : CH 2 ; n = 1, 2) were readily borylated with B 2 pin 2 99 to provide valuable organoboronates 100 with excellent vinylic selectivity. However, in the case that cycloheptane selectivity was reversed, the formation of allylic product was favored. Further borylation reaction of acyclic alkenes such as allylsilane and vinylboronate 98 (R 1 : CH 2 SiMe 3 , Bpin; n = 0) were also carried out under similar reaction conditions. Additionally, the course of reaction was also studied with Pd(OAc) 2 as a catalyst, but products were obtained in albeit lower yields.
The key step involves formation of Pd(IV) intermediate 101 via oxidation of catalyst using PhI(TFA) 2 2, which further undergoes transmetalation with B 2 pin 2 and subsequent reaction with alkenes to deliver desired products 100. Furthermore, the borylation reaction proceeded with excellent vinylic selectivity, except in the case of cycloheptane which yielded allylic products preferentially.
Later, the same research group developed the first Pdcatalyzed oxidative allylic C-H silylation of terminal olefins 102 using hexamethyldisilane 104 as the silyl source (Larsson et al., 2011). This catalytic process employs hypervalent iodine(III) reagent PhI(OCO(4-NO 2 C 6 H 4 )) 2 105 as an oxidant and Pd(OAc) 2 or nitrogen and selenium-based palladium catalyst 103 (Scheme 12B). The reaction follows Pd(II)/Pd(IV) pathway involving formation of allylpalladium complex 107 which presumably undergoes reductive elimination to furnish allylsilanes 106. Moreover, the functional groups such as ester, benzyl, and amide were well-tolerated under the oxidizing conditions and anticipated products 106 were obtained with high regio-and stereoselectivity.

C-HALOGEN BOND FORMATION
Palladium-catalyzed conversion of C-H bond into C-Halogen bond is an attractive method to access valuable aryl halides.
However, in the past limited studies have been carried out in C-H halogenation reactions via high valent palladium catalysis. McMurtrey et al. published the first report on Pdcatalyzed C-H fluorination employing AgF as a fluoride source in combination with iodosobenzene dipivalate, PhI(OPiv) 2 3 as oxidant (McMurtrey et al., 2012). Although the detailed mechanism is not given, high valent Pd-alkyl fluoride complex 110 was hypothesized as the key intermediate in this process that would further undergo C-F bond-forming reductive elimination to yield fluorination products 109 in moderate to good yields (Scheme 13A). Furthermore, the substrates 108 bearing electronwithdrawing groups produced better results than those with electron-donating groups.
In 2015, Rao's research group achieved ortho C-H iodination of phenol carbamates 111 through palladium catalysis employing Togni's reagent 12b as an iodine source and as oxidant in DCE/TfOH at room temperature (Sun et al., 2015). Both electron-rich and -deficient substituents were well-tolerated, leading to the preparation of o-iodinated phenol derivatives in fair to good yields (Scheme 13B). NMR studies revealed that SCHEME 16 | Pd-catalyzed intramolecular oxyalkynylation of phenols 132 and aminoalkynylation of activated amides 135 by using TIPS-EBX 15 as acetylene transfer reagent. some part of cyclic iodine(III)reagent on treatment with TfOH gets converted into 113 and probably both oxidants participates in this reaction.

ALKENE DIFUNCTIONALIZATION
Palladium-catalyzed difunctionalization of simple alkenes using hypervalent iodine reagents has emerged as a powerful method in organic synthesis. Various 1,1-and 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-catalyzed oxidative functionalization of alkenes 61 is shown in Scheme 14. Later, Satterfield et al. disclosed 1,1-aryloxygenation protocol wherein arylstannanes 129 were successfully coupled with terminal olefins 61 in the presence of hypervalent iodine reagents (PhI(O 2 CR 1 ) 2 ) 130 as an oxidant and palladium catalyst, PdCl 2 (PhCN) 2 (Satterfield et al., 2011). This catalytic approach enabled simultaneous generation of C-C and C-O bond in a single step furnishing 1,1-arylacetoxylated products 131 in significant yields (Scheme 15B).

1,2-Difunctionalization of Alkenes
Over the years, great progress has been achieved in the field of Pd-catalyzed 1,2-difunctionalization of olefins using various hypervalent iodine reagents. Based on this strategy, a number intra-and intermolecular synthetic transformations such as diamination, dioxygenation, aminoacetoxylation, fluoroamination, and oxidative amination have been developed.
containing aromatic and aliphatic cyclic compounds. Sanford and co-workers reported Pd-catalyzed intramolecular oxidative amination strategy for the synthesis of tetrahydrofurans using oxidant PIDA 2 (Desai and Sanford, 2007). Subsequently, Muniz's research group developed an intramolecular alkene diamination protocol for the preparation of bisindoline and cyclic urea scaffolds using palladium catalysis (Streuff et al., 2005;Muniz, 2007;Muniz et al., 2008). Furthermore, Wu et al. performed Pd-catalyzed intramolecular aminofluorination of unactivated N-tosylamine alkenes with AgF as fluorinating reagent in the presence of PhI(OCOtBu) 2 as terminal oxidant and MgSO 4 as additive in acetonitrile at room temperature (Wu et al., 2009).
Zhu's research group reported domino carboacetoxylation of N-aryl acrylamides to synthesize 3,3 ′ -disubstituted oxindoles and spiropyrrolidinyloxindoles using catalytic amount of Pd(OAc) 2 or PdCl 2 and oxidant PhI(OAc) 2 1 in AcOH at 100 • C (Jaegli et al., 2010). Furthermore, another Additionally, the scope of the reaction was examined with both aromatic and aliphatic carboxylic acids leading to the synthesis of γ -lactones under the same optimized reaction condition.
In continuation with the difunctionalization reaction, the Waser's group described an intramolecular aminoalkynylation of activated olefins 135 to afford 4-propargyl lactams 136 employing TIPS-EBX 15 as alkynylating agent (Nicolai et al., 2011). In the presence of PdCl 2 and LiCl, the active catalyst lithium palladate, Li 2 [PdCl 4 ] generates in situ which catalyzes the carboamination reaction (Scheme 16). Furthermore, the present protocol was successfully utilized for the synthesis of 4-propargyl oxazolidinone and imidazolidinones through the cyclization of allyl carbamates and allyl ureas, respectively. Additionally, the synthesized γ-and δ-lactams were employed as precursors for the synthesis of bicyclic heterocycles pyrrolizidine and indolizidine and also in the total synthesis of natural product (±)-trachelanthamidine (Nicolai et al., 2011).

Intermolecular 1,2-Difunctionalization of Alkenes
Iglesias et al. developed the first example of Pd-catalyzed intermolecular diamination of terminal alkenes employing saccharin and bissulfonimides as the nitrogen sources in the presence of PhI(OPiv) 2 3 as an oxidant (Iglesias et al., 2010). Further allylic ethers were subjected to similar catalytic intermolecular 1,2-diamination reaction using nitrogen sources, phthalimide, and N-fluoro-bis(phenylsulfonyl)imide (Muniz et al., 2011). Later, Martinez and Muniz successfully employed Pd/PhI(OPiv) 2 -catalytic system for the intermolecular vicinal diamination of internal alkenes 137 with phthalimide 138 and bissulfonimides 139 as the two nitrogen sources (Martinez and Muniz, 2012). This method employs alkene as the limiting reagent and desired diamination products 140 were isolated in moderate to high yields with complete regio-and diastereoselectivity (Scheme 17A). The mechanistic approach involves initial alkene 137 co-ordination with the Pd catalyst followed by subsequent aminopalladation involving nucleophilic addition of 138 via trans stereochemistry to form δ-alkylpalladium complex 141. Rapid oxidation of complex 141 gives Pd(IV) intermediate 142 which is attacked by bissulfonimide 139 to provide desired product 140 with net inversion of configuration at benzylic position.
In continuation, Martinez and Muniz reported the synthesis of new palladium-phthalimidato complexes 144 and demonstrated its broad applicability as catalysts in the vicinal diamination of alkenes 61 with phthalimide 143 and bissulfonimides 144 as nitrogen sources . The treatment of phthalimide 143 with Pd(OAc) 2 in nitrile solution at room temperature resulted in the formation of palladium-phthalimidato complexes 144. The air-stable preformed phthalimidato complexes proved to be versatile catalysts for the present diamination reaction providing desired products 145 in useful yields (Scheme 17B). Moreover, the same research group synthesized other bissaccharido palladium(II) complexes and investigated their application in catalytic regioselective diaminations and aminooxygenation of alkenes .
In 2015, Cheng et al. have demonstrated an efficient and simple palladium-catalyzed protocol for the synthesis of β − amino acid derivatives 147 and 149 from alkenes 61 via intermolecular aminocarbonylation reaction (Cheng J. et al., 2015). An array of aliphatic or aromatic terminal alkenes 61 were reacted with either phthalimide 138 or with 2oxazolidone 148 under a carbon monoxide atmosphere in the presence of PhI(O 2 CR 1 ) 2 130 as an oxidant (Scheme 18B). The reaction possessed excellent regioselectivity, broad substrates scope, and remarkable functional group tolerance. Reaction mechanism and stereochemistry was studied by taking deuterium labeled alkene 61 and substituted 2-oxazolidone 149 as an example. The reaction initiates with cis-aminopalladation of alkene 61 to form alkyl-Pd complex 151 and subsequent CO insertion gives intermediate 152. Next, nucleophilic attack of carboxylate on to the acyl-Pd species 152 afforded anhydride product 153 which upon alcoholysis yields carboxylic ester 154. Further the experimental evindence revealed that the iodine(III) reagent plays a crucial role in accelerating the intermolecular aminopalladation process.
The same research group developed a novel Pd-catalyzed intermolecular oxycarbonylation of terminal 155 and internal alkenes 157 under CO atmosphere using PIDA 1 as oxidant . This difunctionalization reaction leads to the facile synthesis of various βoxycarboxylic acids 156 and 158 in useful yields with excellent functional group compatibility, regioselectivity, and diastereoselectivity (Scheme 19). The potential scope of this method was extended toward the synthesis of natural product, (+)-honaucin C in 48% yield with ee up to 99% .
Vicinal alkene dioxygenation is an important method for the preparation of valuble 1,2-dioxygenated scaffolds. In this regard, Dong and Shi's research groups independently reported Pd-catalyzed vicinal dioxygenation of olefins employing hypervalent iodine reagent as terminal oxidant following distinct Pd (II) /Pd (IV) mechanism (Li et al., 2008;Wang W. et al., 2010). Subsequently, Sanford's group developed Pd(II)-catalyzed chiral oxime-directed asymmetric 1,2-dioxygenation of alkenes 159 using PhI(OBz) 2 160 as an oxidant and benzoyloxy source (Neufeldt and Sanford, 2013). Various chiral allyl oxime ethers were screened and it was observed that menthone-derived substrates provided best reactivity and diastereoselectivity. This approach enabled efficient preparation of dibenzoylated products 161 with diasteriomeric ratio up to 9:1 (Scheme 20A). The proposed mechanism initiates with the coordination of oxime ether 159 with Pd catalyst to give intermediate 162 followed by subsequent oxypalladation and oxidation proceeding via either trans or cis geometry to deliver intermediate 163 or 164. Final, reductive elimination could occur by direct (path "a" and "c") or by S N 2-type mechanisms (path b and d) that would lead to the formation of syn or anti products. Further, based on the experimental data authors suggested that reaction proceeds via syn addition and primary operative mechanism could be either "b" or "c".
Furthermore, the Pd-catalyzed iodofluorination of alkenes 165 was reported by Ilchenko et al. employing fluoroiodane reagent 166 as iodine and fluorine sources (Ilchenko et al., 2016). The reaction was carried out using either Pd(BF 4 ) 2 (MeCN) 4 or PdCl 2 (MeCN) 2 or Pd(OAc) 2 as palladium catalysts in CDCl 3 (Scheme 20B). The reaction proceeds via threemembered iodonium intermediate 168 which upon ring opening and subsequent C(sp 2 )-I bond cleavage delivers the desired iodofluorinated products 167. Simple cycloalkenes such as cyclohexene and cycloheptene also undergoes iodofluorination reaction to give iodofluorinated products in modest yields.

CONCLUSION
In conclusion, this review described various achievements made in palladium-catalyzed reactions mediated by hypervalent iodine compounds. Hypervalent iodine reagents are versatile, nontoxic, environment friendly, and easy to handle reagents in organic synthesis. In recent years, the use of hypervalent iodine reagents in palladium-catalyzed transformations has been widely studied as they are strong electrophiles and powerful oxidizing agents. Most of the reactions proceed via Pd(II/IV) redox cycles involving hypervalent iodine reagentsinduced oxidation to generate Pd(IV) center as the key step. The inherent oxidizing nature and unique reactivity of these reagents with palladium catalysts enabled efficient preparation of synthetically useful molecules through C-O, C-N, C-C, C-Si, C-B, and C-halogen bond formation reactions. In addition, a number of Pd-catalyzed alkene difunctionalization reactions have been developed in recent times employing hypervalent iodine reagents. More importantly, oxidation of an unactivated C(sp 3 )-H bond has been successfully accomplished using a palladium and hypervalent iodine catalytic system which is a challenging problem. From future perspectives, palladium catalysis is well-established with respect to achiral synthesis, however reactions concerning to asymmetric synthesis are limited. Thus, development of enantioselective Pd-catalyzed reaction with hypervalent iodine reagents would be a muchanticipated area of research in the near future. Apart from this, use of recyclable polymer-supported hypervalent iodine reagents in palladium catalyzed reactions would be another interesting field of research.