Iodonium salts alkynyliodonium

Besides iodonium ylides, alkynyliodonium salts are also useful in heterocyclic synthesis. These salts are obtained from the reaction of the alkynes with an appropriate organohypervalent iodine reagent (Scheme... 

Intramolecularity was the next issue to be probed within the context of alkynyliodonium salt/nucleophile addition reactions.53 1 No prior history was available to guide us, and so the prospects for success remained uncertain. Of primary concern was the potential for iodonium salt/base destructive interactions in competition with the desired N-H deprotonation reaction. A substrate that bore some resemblance to key portions of the agelastatin precursor 33 was prepared (Scheme 6), compound 39. This species duplicated the alkynyliodonium/"amide" pairing of the real system, but it lacked the complex piperazine carbene trap of 33. The tosylimide (pre)nucleophile was proposed as a compromise between what we really wanted (an N-methyl amide) and what would likely work (a tosylamide). Simple treatment of 39 with mild base effected the desired bicyclization to afford the tosylimide product 41 in decent yield. A transition state model 40 for C-H insertion that features an equatorial phenyl unit might rationalize the observed sense of diastereoselectivity. So, at least for 39, no evidence for possible interference by iodonium/base reactions was detected. 

The pareitropone project began quite by accident after an unexpected observation expanded our thinking about potentially accessible targets for alkynyliodonium salt/alkylidenecarbene chemistry (Scheme 18). Treatment of the tosylamide iodonium salt 125 with base under standard conditions was designed to provide no more than routine confirmation of the aryl C-H insertion capabilities, which were first exposed in indoleforming reactions using tosylanilide anion nucleophiles and propynyl(phenyl)iodonium triflate,5b of the intermediate carbene 126. However, this substrate did not perform as expected, since only trace amounts of the 1,5 C-H insertion product 127 was detected. One major product was formed, and analysis of its spectral data provided yet another surprising lesson in alkynyliodonium salt chemistry for us. The data was only consistent with the unusual cycloheptatriene structure 129. 

The use of hypervalent iodine reagents in carbon-carbon bond forming reactions is summarized with particular emphasis on applications in organic synthesis. The most important recent methods involve the radical decarboxylative alkylation of organic substrates with [bis(acyloxy)iodo]arenes, spirocyclization of para- and ortho-substituted phenols, the intramolecular oxidative coupling of phenol ethers, and the reactions of iodonium salts and ylides. A significant recent research activity is centered in the area of the transition metal-mediated coupling reactions of the alkenyl-, aryl-, and alkynyliodonium salts. 

Alkynyl(phenyl)iodonium salts have attracted a significant interest as stable and readily available powerful alkynylating reagents. The preparation, structure, and chemistry of alkynyliodonium salts was extensively covered in a recent review [4]. 

Likewise, the reaction of the lithium enolate of aminomalonate 126 with alkynyliodonium triflates 127 affords alkynylmalonates 128 in good yields (Scheme 52) [111]. The best yields in this reaction are observed when a freshly prepared solution of the lithium enolate in THF is added to a stirred cold solution of the iodonium salt. The use of potassium enolate instead of lithium, or addition of the reagents in a different order, results in lower yields of products 128. 

Alkynyl(phenyl)iodonium salts can be efficiently coupled with various organo-copper reagents. Direct coupling of alkynyliodonium tosylates 132 with vinyl-... 

Alkynyliodonium ions, 1 and 2, are hypervalent iodine species in which one or two alkynyl ligands are bound to a positively charged iodine(III) atom. They are sensitive to nucleophiles, especially at the /1-carbon atom(s) of the alkynyl ligand(s), and for that reason, the isolation of stable alkynyliodonium salts generally requires the incorporation of nucleofugic anions. A list of known alkynyliodonium compounds (i.e. as of 4/1/94), containing 134 iodonium salts derived from 103 iodonium ions, and references (5-45) to their preparation and characterization are presented in Table 1. Among these compounds, alkynyl(phenyl)iodonium sulfonates and tetrafluoroborates are the most common, while alkynyl(alkyl)iodonium salts of any kind are unknown. 

Single-crystal X-ray structures of six alkynyliodonium compounds, all containing oxyanions and including four alkynyl(phenyl)iodonium salts, one alkynylbenziodoxolone and one dialkynyliodonium salt, have been reported. Selected structural data for these compounds are given in Table 3. 

The reactions of the lithium enolate of diethyl 2-[(diphenylmethylene)amino]malonate with several alkynyliodonium triflates are rare examples of enolate alkynylations with iodonium species other than the ethynyl(phenyl)- and (phenylethynyl)phenyliodonium ions (equation 125)16. Two experimental protocols were followed, i.e. addition of the enolates to the iodonium salts and vice versa, the former procedure giving higher yields of alkynylmalonates. As with other enolate alkynylations, these reactions are thought to involve alkylidenecarbene intermediates. It has been proposed, however, that the carbenes rearrange with migration of the diethyl 2-[(diphenyl) amino] malonate anion 16. 

Vinyliodonium ions, 35 and 36, are hypervalent iodine species in which one or two alkenyl ligands are bound to a positively charged iodine(III) atom. Although they are reactive with nucleophilic reagents, they are less labile than alkynyliodonium ions, and stable halide salts of vinyliodonium ions can be prepared. The first vinyliodonium compounds [i.e. (a, / -dichlorovinyl)iodonium salts] were synthesized by the treatment of silver acetylide-silver chloride complexes with (dichloroiodo)arenes or l-(dichloroiodo)-2-chloroethene in the presence of water (equation 152). The early work was summarized by Willgerodt in 1914115. This is, of course, a limited and rather impractical synthetic method, and some time elapsed before the chemistry of vinyliodonium salts was developed. Contemporary synthetic approaches to vinyliodonium compounds include the treatment of (1) vinylsilanes and vinylstannanes with 23-iodanes, (2) terminal alkynes with x3-iodanes, (3) alkynyliodonium salts with nucleophilic reagents and (4) alkynyliodonium salts with dienes. 

Although mechanisms for the production of (/ -sulfonyloxyvinyl)iodonium salts from terminal alkynes via alkynyliodonium salts can be envisioned (e.g. equation 174), they are not consistent with similar transformations of internal alkynes. The generation of vinyl cations, or iodine-bridged counterparts78, and their capture with sulfonate ions to give... 

Reaction of trimethylsilylalkynes with 16 in dichloromethane in the presence of BF3 OEt2 at room temperature followed by heating in methanol at 60 °C results in the stable heterocyclic alkynyliodonium salts 17 [Eq. (9)] [31]. These species represent intramolecular iodonium salts where the counterion is a carboxylate. Unlike the acyclic alkynyl(phenyl)iodonium carbox-ylates 18, that are unstable to isolation and decompose to the corresponding alkynyl benzoates 19 [Eq. (10)] [32], the cyclic analogs 17 are readily isolable. 

The stability of alkynyliodonium species is highly dependent upon both the counter-anion and the -substituent on the alkyne. The more nucleophilic the counter-ion, the less stable the iodonium salt. Hence, the order of stability as a function of counterion is approximately ... 

To date, six single-crystal X-ray molecular structures of alkynyliodonium compounds have been reported four aIkynyl(phenyl)iodonium salts including the substituted cyanoethynyl salt, one heterocyclic and one dialkynyliodonium salt, all with oxyanions. Key structural data for these compounds are summarized in Table 3-1. 

Reaction of P-functionalized alkynyliodonium triflates, 11, with LiNPh2 results in various push-pull ynamines, 67, in 43-66% isolated yields [56] [Eq. (27)]. Treatment of alkynyliodonium tetrafluoroborates with Me3SiN3 in wet CH2CI2 results in the stereoselective formation of (Zy-P-azidovinyl iodonium salts 68 [Eq. (28)] in 50-91 % isolated yields [57]. 

Various cyclohexadienyl(phenyl)iodonium salts have been prepared by the [4- -2] Diels-Alder cycloadditions of alkynyliodonium salts 319, functionalized with electron-withdrawing substituents in the p-position, with a wide range of dienes. Scheme 2.95 shows several examples of these cycloadditions, affording adducts 320-322 as stable microcrystalline solids [458]. 

Yoshida and coauthors have reported a facile preparation of iodonium salts 367 by the reaction of potassium organotrifluoroborates 366 with (difluoroiodo)arenes under mild conditions (Scheme 2.104) [396]. A similar approach to alkynyliodonium salts by the reaction of alkynyldifluoroboranes with polyfluoroorganyliodine difluorides was developed by Frohn and Bardin [501]. 

Alkynyl(phenyl)iodonium salts have found synthetic application for the preparation of various substituted alkynes by the reaction with appropriate nucleophiles, such as enolate anions [980,981], selenide and telluride anions [982-984], dialkylphosphonate anions [985], benzotriazolate anion [986], imidazolate anion [987], N-functionalized amide anions [988-990] and transition metal complexes [991-993]. Scheme 3.291 shows several representative reactions the preparation of Ai-alkynyl carbamates 733 by alkynylation of carbamates 732 using alkynyliodonium triflates 731 [989], synthesis of ynamides 735 by the alkyny-lation/desilylation of tosylanilides 734 using trimethylsilylethynyl(phenyl)iodonium triflate [990] and the preparation of Ir(III) a-acetylide complex 737 by the alkynylation of Vaska s complex 736 [991]. 

An alkynyliodonium salt, namely, phenyl(phenylethynyl)iodonium hexafluorophosphate, has been tested for application as cationic photoinitiator [38]. The high activity of phenyl(phenylethynyl)iodonium salt as a photoinitiator was verified by photo differential scanning calorimetry (photo-DSC) experiments in direct irradiation and in photosensitized initiation using 9,10-dibutylanthracene, 2-isopropylthioxanthone and benzophenone as sensitizers [38]. 

The cross-coupling reactions of organoboronic acids and carbon monoxide with hyper-valent iodonium salts affords unsymmetrical ketones (Scheme 30). The reaction proceeds smoothly at room temperature and in most cases completes within 0.5 h. Aryl-, alkenyl-, and alkynyliodonium salts react with arylboronic adds in the presence of 0.5% of Pd(PPh3)4 and 1.2 equiv of K2CO3 in DME to provide unsymmetrical aromatic ketones in high yields (Scheme 30). Phenylboronic acid dimethyl ester can be utilized as efficiently as phenylboronic acid. In most cases, a small amount of the direct crosscoupling product (R—Ph, less than 7-8%) is produced. 

The regiochemistry of the hydrozirconation of disubstituted stannyl- [24, 167-170] and silyl- [171] acetylenes and boron- [118, 172-175] and zinc- [34, 126] alkynyl derivatives result in the formation of 1,1-dimetallo compounds. Hydrozirconation of alkynyliodonium salts affords alkenylchlorozirconocenes with the Zr-C bond geminal to the iodonium moiety [176]. These zirconocene complexes allowed the preparation of ( )-trisubstituted olefins (Scheme 8-20). 

The use of alkynyliodonium salts in the synthesis of 2,3-disubstituted 4,5-dihydrofurans was reported by Feldman. In this conversion, the addition of p-toluenesulfinate to ethers of 1-hydroxybut-3-ynyl(phenyl)iodonium triflates 79 induces a series of reactions that afford eventually 2-substituted 3-p-toIuenesulfonyl-4,5-dihydrofurans 80 . 

Alkynylphenyl tellurides from arylteUurolates and alkynyliodonium salts (general procedure) To a stirred solution of PhLi in Et20/cyclohexane at room temperature under N2, tellurium powder was added and the solution was stirred for 1 h. The appropriate iodonium triflate was added and the solution was stirred for 2 h. The product was eluted through a small portion of silica gel with CHjCN and the volume was reduced in vacuo followed by purification via radial chromatography. 

Michael-type addition of an enolate anion to an alkynyliodonium salt probably produces the unstable iodonium ylide 34 34a. Loss of Phi from... 

Stang etal. (94JA93) have developed another alkynyliodonium salt mediated approach for the synthesis of y-lactams including bicyclic systems containing the pyrrole moiety. This method is based on the formation of 2-cyclopentenones 114 via intramolecular 1,5-carbon-hydrogen insertion reactions of [/3-(p-toluenesulfonyl)alkylidene]carbenes 113 derived from Michael addition of sodium p-toluenesulfinate to /3-ketoethynyl(phenyl) iodonium triflates 112 (Scheme 32). Replacing 112 by j8-amidoethynyl (phenyl)iodonium triflates 115-119 provides various y-lactams as outlined in Eqs. (26)-(30). 

A variety of five-membered nitrogen heterocycles can be prepared efficiently by inter- or intramolecular addition/cyclizations of sulfonamide anions with alkynyliodonium salts. The intermolecular variant employs the combination of the amides 172 or anilides 174 with propynyl(phenyl)iodonium triflate (Scheme 65) [131,132]. The yield of dihydropyrroles 173 in this cyclization is extremely sensitive to the nature of the protective group P the tosyl group in 172 proved... 

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