Iodonium imides in organic synthesis

Iodonium imides (ArINR) represent an important class of hypervalent iodine(III) compounds recently emerging as versatile, efficient and environmentally friendly synthetic reagents with numerous applications in academic and industrial research. Iodonium imides, which are also known as iminoiodanes, are widely used in organic synthesis as common nitrene precursors in the aziridination of alkenes and the amidation reactions of various organic substrates. In the present review, the preparation and structural features of iminoiodanes are discussed, and recent developments in their synthetic applications are summarized.


Introduction
][3][4][5][6][7][8][9][10] The reactivity pattern of hypervalent iodine reagents in many aspects is similar to that of the heavy metal derivatives, but without the toxicity and environmental problems associated with these metals.Previously we have published several reviews in Arkivoc summarizing synthetic applications of hypervalent iodine reagents, [11][12][13] aryliodonium salts, 14 and aryliodonium ylides. 15odonium imides (ArINR) are considered as the I-N analogues of iodonium ylides (ArICR 2 ) and are also known under the name of iminoiodanes.Iodonium imides represent an important class of iodonium compounds with numerous applications in organic synthesis.In general literature, iodonium imides are commonly shown as compounds with a double bond (ArI=NR); however in fact the iodine-nitrogen bond in these compounds is of a dative 2c-2e nature (ArI + --NR) as demonstrated by adaptive natural density partitioning (AdNDP) computational studies. 16The most important iodonium imide is N-tosyliminophenyliodane (PhINTs) which is widely used as a nitrene precursor in the aziridination of alkenes and the amidation reactions of various organic substrates.0][21] In the present review, the preparation and structural features of iminoiodanes are discussed, and recent developments in their synthetic applications are presented.The literature coverage is through Spring 2019.

Preparation of Iodonium Imides
Iodonium imides 3 are generally synthesized by the interaction of (diacetoxyiodo)arenes 1 with the respective amides 2 under basic conditions (Scheme 1).Some iodonium imides are relatively unstable at room temperature, and low temperature storage is recommended.Exothermic decomposition frequently occurs at the melting point of imides, and some of them are considered to be explosive. 17][24][25][26][27]
Protasiewicz and co-workers reported the preparation and X-ray crystallographic analysis of a highly soluble nitrene precursor 8, in which the intramolecular secondary I---O bond replaces intermolecular interactions that are typical for iodonium imides. 38Iodonium imide 8 is highly soluble in organic solvents (up to 0.14 M in chloroform, which is a 50-fold increase over PhINTs), and it can be analyzed by NMR in solution.
Solubilization of various imides ArINTs in organic solvents can also be achieved by the addition of organic Noxides, such as Me 3 NO. 39he highly soluble iodonium imides 11, which are derived from ortho-alkoxyiodobenzenes, were synthesized in two simple steps starting from readily available 2-iodophenol ethers 9 (Scheme 3). 40In the first step, iodides 9 were oxidized by peracetic acid to form diacetoxyiodo derivatives 10; the structures of two products 10 (R = Me and Bu) were established by X-ray analysis.In the second step, diacetates 10 were converted to iminoiodanes 11 by treatment with tosylamide under basic conditions in methanol.Compounds 11 are relatively stable at room temperature and can be stored for several weeks in a refrigerator.Products 11 have good solubility in dichloromethane, chloroform, and acetonitrile (e.g., the solubility of 10, R = Bu in dichloromethane is 0.25 g/mL).Scheme 3

Structural Studies
Single crystal X-ray structural data have been reported for the following iodonium imides presented in Figure 1: phenyl(N-tosylimino)iodane 12, 28 mesityl(N-tosylimino)iodane 13, 28 o-tolyl(N-tosylimino)iodane 14, 41 orthosulfonyl substituted phenyliodonium imide 8, 39 ortho-methoxy substituted phenyliodonium imide 15, 40 orthomethoxymethyl substituted iodonium imides 16, 42 17, 33 and 18, 33 nitro substituted phenyliodonium imides 19 and 20, 35 and (N-triflylimino)iodane 21. 30 Aryl(N-tosylimino)iodanes in general have a linear polymeric, asymmetrically bridged structure with the Tshaped geometry around the iodine centers.In the case of PhINTs 12, the monomeric units are bridged by I-N interactions, while in the more sterically hindered MesINTs 13 the bridging atom is the oxygen of the tosyl group (Figure 2). 28The structure of 2-TolINTs 14 is intermediate between the structures 12 and 13: it can form two different polymorphic modifications, one with nitrogen and the second with oxygen as the bridging atom in the polymeric chain. 41A polymeric, nitrogen-bridged structure was determined for 4-MeC 6 H 4 INTs by X-ray powder diffraction and EXAFS analyses. 43The intramolecular I-N distance of 2.01-2.04Å in Ntosyliminoiodanes is consistent with a single bond and the positive charge at iodine and the negative charge delocalized at the nitrogen and oxygen atoms of the tosylimino group.A single crystal X-ray analysis of ortho-sulfonyl substituted phenyliodonium imide 8 showed a structure of loosely associated centrosymmetric dimers with a long-range intramolecular I-N and I-O distance of more than 3.0 Å, quite unlike the infinite polymeric chains adopted in the solid state for PhINTs. 44One of the sulfonyl oxygen atoms forms a short intramolecular I-O secondary bond to the iodine atom with a bond length of 2.667 Å.Because of the non-polymeric structure, imide 8 has excellent solubility in common organic solvents.
Similar to the structure of PhINTs 12 (Figure 2), molecules of ortho-methoxy substituted phenyliodonium imide 15, 40 have a polymeric, asymmetrically bridged structure with a T-shaped geometry around the iodine centers formed by two iodine-nitrogen bonds and one iodine-carbon bond.However, in contrast to PhINTs, compound 15 has two additional weak intra-and intermolecular I•••O contacts between the iodine center and the oxygen atoms of the alkoxy and sulfonyl groups.These weak interactions lead to an elongation of the I•••N intermolecular bond in 15 (2.735 Å) compared with that observed in PhINTs (2.482 Å).As a result, the polymeric structure of 15 is weakened and the solubility is significantly increased. 40

Transition metal catalyzed aziridinations and amidations
Iminoiodanes, and especially N-tosyliminoiodanes, ArINTs, have found wide synthetic application as nitrene precursors in transion metal-catalyzed aziridination of alkenes and amidation of various organic substrates. 17,18,45Aziridination of alkenes with tosyliminoiodane PhINTs in the presence of iron-or manganese porphyrins was first reported in 1984. 32This reaction involves a metal-nitrene complex as the initial reactive species and has a mechanism similar to the metal-catalyzed oxygenation reactions with iodosylbenzene.A detailed investigation of copper-or silver-catalyzed alkene aziridination reactions was recently published by Pérez and coauthors. 46,47urrent interest in the transition metal-catalyzed reactions of iminoiodanes was initiated in the 1990s by the groundbreaking works of Evans 48,49 and Jacobsen 50,51 on the asymmetric aziridination of alkenes using PhINTs as the nitrene precursor in the presence of copper catalysts and chiral N,N-ligands.In the following works, the copper-catalyzed aziridination of alkenes was utilized in numerous syntheses.For example, Dodd and co-workers applied the Evans aziridination procedure to the aziridination of 2-substituted acrylates and cinnamates 22 52 and to steroid 23 (Scheme 4). 53

Scheme 4 Scheme 5
A similar catalytic aziridination was used for the functionalization of the optically active azoninones 25, 57 in the preparation of a key intermediate 26 in the total synthesis of kalihinane diterpenoids, 58 in the synthesis of -methylserinal derivatives 27 (Scheme 6), 59 in the preparation of 2,4-disubstituted N-tosylpyrrolidines, 60 in the synthesis of nosylaziridines, 61 and in the synthesis of β-alkoxy-N-protected phenethylamines via one-pot copper-catalyzed aziridination and ring opening. 62

Scheme 6
Alkenes can be efficiently aziridinated using highly soluble iminoiodanes 11 in the presence of copper catalysts under continuous flow conditions. 63This approach can be used to synthesize and use in subsequent reactions aziridines that are difficult to isolate and purify because of their high reactivity.

Scheme 12
Additional examples of C-H amidations using PhINTs as the nitrene precursor are represented by the following publications: highly efficient Ru(II) porphyrin catalyzed C-H bond amidation of aldehydes, 105,106 chemoselective copper-catalyzed -amidation of acylpyrazoles, 107 aromatic C-H amidation mediated by a diiron complex, 108 gold-catalyzed nitrene insertion into aromatic and benzylic C-H bonds, 109,110 silver-catalyzed intermolecular and intramolecular amidation of C-H bond in saturated hydrocarbons, 111,112 -amidation of cyclic ethers catalyzed by Cu(OTf) 2 , 113 mechanistic study of catalytic intermolecular amination of C-H bonds, 114 nitrene insertion into the sp 3 C-H bonds of alkylarenes and cyclic ethers or the sp 2 C-H bonds of benzene using a copper-homoscorpionate complex, 115 Co(II)-catalyzed allylic amidation reactions, 116 the Ru(II) porphyrin-catalyzed amidation of aromatic heterocycles, 117 non-heme iron-catalyzed amidation of aromatic substrates, 118 and by the efficient stereoselective allylic C−H amination of terpenes and enol ethers involving the combination of a chiral aminating agent with a chiral rhodium catalyst. 119anford and co-workers have investigated the carbon-nitrogen bond-forming reactions of palladacycles with aryliodonium imides. 120In particular, palladium(II) complexes (e.g., 36) containing bidentate cyclometalated chelating ligands react with PhINTs at room temperature to give products of insertion of the tosylimino group into the Pd-C bond (Scheme 13).This tosylimino insertion reaction has been applied to palladacyclic complexes of azobenzene, benzo[h]quinoline, and 8-ethylquinoline.The newly aminated organic ligands can be liberated from the metal center by protonolysis with a strong acid. 120

Scheme 14
Similarly, the reaction of PhINTs with sulfoxides 39 in the presence of catalytic amounts of copper(I) triflate affords the corresponding N-tosylsulfoximides 40 in high yield (Scheme 15). 125The imidation of enantiomerically pure sulfoxides 39 allows stereoselective access to N-tosylsulfoximides 40 with complete retention of configuration at sulfur.A similar imidation procedure has been used for the preparation of the chiral ferrocenylsulfoximides. 130,131

Scheme 15
Enantioselective imidation of alkyl aryl sulfides 41 can be achieved by using the chiral manganese(salen) complex as a catalyst (Scheme 16). 132,133Bolm and coworkers reported a similar enantioselective imidation of sulfides catalyzed by a chiral iron complex. 134

Scheme 17
The reaction of PhINTs with complexes of ruthenium(II), 87 osmium(II), 143,144 and cobalt(III) 145 results in the imidation at the metal center with the formation of the respective tosylimidometal complexes.X-Ray crystal structures were determined for several bis(tosylimido)ruthenium(VI) and bis(tosylimido)osmium(VI) porphyrin complexes. 87,143,144The reactivity of a cobalt(II) iminoiodane complex in hydrogen atom abstraction reactions has been investigated by Kundu and coauthors. 146he in situ generated aziridine products can be easily transformed to heterocyclic compounds.Dodd's group has developed the synthesis of 5,5-disubstituted butyrolactones 49 from corresponding alkenes 47 and the in situ generated nosyliminoiodane in the presence of a copper source and ligand 48 (Scheme 18).This reaction presumably involves initial formation of aziridine intermediates followed by aminolactonization to give the final products.The obtained products 47 can be further transformed into novel highly functionalized spiro-heterocyclic compounds. 147

Scheme 18
Amidation of the allylic C-H bond of enolic form of dicarbonyl compound 50 affords the corresponding αacyl-β-amino derivatives in good yields.This reaction can give amination products 51, or the same reaction with increased amounts of iminoiodane 34 can selectively afford 2,2-diacyl aziridine derivatives 52 (Scheme 19). 148A similar aziridination can be also achieved under Brønsted base conditions (DBU or potassium carbonate) in the absence of copper catalyst. 149

Scheme 19
Schomaker's group utilized intramolecular aziridination reactions of appropriate amide precursors and PhIO in the presence of transition metal catalysts in numerous syntheses of stereochemically complex products. 150,151For example, intramolecular aziridination of homoallenic sulfamates 53 (Scheme 20) using a dinuclear Rh(II) catalyst, such as Rh 2 (TPA) 4 (TPA = triphenylacetate), yielded exocyclic methyleneaziridines 54 with excellent chemo-, regio-, and stereoselectivity. 150,152This aziridination was followed by immediate ringopening of the initially formed labile intermediate 54 to afford enesulfamates 55 in good yield and excellent stereoselectivity in favor of the E isomer. 152Most likely, the mechanism of these reactions involves intermediate formation of iodonium imides in situ.

Metal-free reactions of aminoiodanes
Iminoiodanes ArINTs can be used for various amidations under metal-free conditions.In particular, o-alkoxyphenyliminoiodane 57 readily reacts with silyl enol ethers 56 in the presence of BF 3 -etherate giving products of -tosylamination 58 in good yields (Scheme 21). 40Furthermore, reagent 57 in the presence of catalytic amounts of iodine readily reacts with adamantane to give product of tosylamination 59 in excellent yield under very mild conditions.By comparison, PhINTs reacts with adamantane and iodine (0.2 equiv) in dichloromethane at room temperature in 2 h to afford 1-tosylaminoadamantane 59 in only 63% yield. 153

Scheme 23
Saito and co-workers have developed a metal-free [2+2+1] annulation reaction of alkynes 63 with PhINTs in nitrile solvents to give the highly substituted N-tosylimidazoles 64 with high regioselectivities (Scheme 24). 168The N-tosyl group in products 64 can be deprotected by treatment with trifluoroacetic anhydride and pyridine to afford the N-unsubstituted imidazole.This reaction has been used in the synthesis of catharsitoxin E, a natural product isolated from the Chinese remedy qiung laug.

Scheme 24
A very mild procedure for the Hofmann reaction of aromatic and aliphatic carboxamides 65 is based on the use of PhINTs as the oxidant (Scheme 25). 169Due to the mild reaction conditions, this method is particularly useful for the Hofmann reaction of substituted benzamides 65 (R = aryl), which usually afford complex reaction mixtures with other hypervalent iodine oxidants.The mild reaction conditions and high selectivity in the reaction of carboxamides with PhINTs allow the isolation of the initially formed labile isocyanates 66, or their subsequent conversion to stable carbamates 67 by treatment with alcohols.Based on the previously reported mechanistic studies of Hofmann rearrangements using other hypervalent iodine reagents, [170][171][172] it is assumed that this reaction starts from the formation of amidoiodane 68 (Scheme 25).Subsequently, the reductive elimination of iodobenzene and the 1,2-alkyl or -aryl shift to the electrondeficient nitrenium nitrogen atom in the intermediate 67 afford isocyanate 64.Subsequent addition of an alcohol to isocyanate 66 gives the final carbamate 67. 169

Scheme 25
Baeten and Maes have reported the preparation of various guanidines 72 via oxidative rearrangement of amidines 70 with reagent 57 into carbodiimides 671, followed by in situ reaction with amines (Scheme 26). 173he conditions for this reaction are mild and involve the use of a "green" solvent (dimethyl carbonate) and a recyclable oxidant (the reduced form of reagent 57, 2-PrOC 6 H 4 I, can be isolated and recycled).The amine scope is broad, including sterically hindered, oxidation-sensitive and chiral amines.This method was used to prepare the antihypertensive drug Pinacidil in increased yield relative to the previous route.

Scheme 26
A practical metal-free procedure for the imidation of sulfides with aryliodonium imides was recently reported. 174In particular, the reaction of various sulfides 73 with ArINTs 74 in the presence of a catalytic amount of iodine under mild conditions affords the corresponding N-tosylsulfilimines 75 in moderate to good yields (Scheme 27).This facile transfer procedure of sulfonylimino group can also be applied to triphenylphosphine to produce the respective iminotriphenylphosphoranes in high yields.According to the reaction mechanism studies, the process of the sulfonylimino group transfer from PhINTs to sulfide involves radical steps.

Scheme 27
Additional recent examples of metal-free amidation reactions with aryliodonium imides include the following: preparation of N-sulfonylimines 78 from a range of aryl aldehydes 76 by reaction with iminoiodinanes 77 and iodine (Scheme 28), 175 amidation of cyclic ethers 79 followed by substitution with 1,3dicarbonyl compounds (Scheme 29), 176 and organocatalytic C-H amidation reaction using a trifluoromethyl iminium salt 80 as the catalyst (Scheme 30). 177

Figure 1 .
Figure 1.Iminoiodanes analyzed by a single crystal X-ray diffraction.

Figure 2 .
Figure 2. Primary and secondary bonding pattern in single crystal X-ray structures of iminoiodanes 12 and 13.