1 iodonium salts reactions with bases

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 O-arylation of appropriate phenols using symmetrical iodonium salts has been employed in the synthesis of hydroxylated and methoxylated polybrominated diphenyl ethers, some of which are related to natural products [872,873]. For example, several polybrominated diphenyl ethers 680 have been prepared by the reaction of iodonium salt 678 with phenols 679 in iV,iV-dimethylacetamide (DMAC) solution in the presence of base (Scheme 3.272) [872]. 

Cyclohexyne intermediates 709 have been observed as the result of 3-elimination in the reactions of 1-cyclohexenyl(phenyl)iodonium salts 708 with mild bases, such as tetrabutylammonium acetate, fluoride ion,... 

It has also been shown that the disproportionation reaction, with the generation of the ionic componnd from thioamide-iodine complexes, exhibits pressure dependence [2]. A pressnre increase, leads to the ionic iodonium salt (iii) from (ii) (Scheme 13.2). The favouring of [MBZIM) ] [I3] (24a) formation, is also proven by compntational stndies, based on energetic gronnds [6]. 

Silyl ethers of aliphatic alcohols are inert towards strong bases, oxidants (ozone [81], Dess-Martin periodinane [605], iodonium salts [610,611], sulfur trioxide-pyridine complex [398]), and weak acids (e.g., 1 mol/L HC02H in DCM [605]), but can be selectively cleaved by treatment with HF in pyridine or with TBAF (Table 3.32). Phenols can also be linked to insoluble supports as silyl ethers, but these are less stable than alkyl silyl ethers and can even be cleaved by treatment with acyl halides under basic reaction conditions [595], Silyl ether attachment has been successfully used for the solid-phase synthesis of oligosaccharides [600,601,612,613] and peptides [614]. 

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 alkylidenecarbene generated from alkenyl(phenyl)iodonium tetrafluoroborate by base adds irreversibly to THT to form a sulfonium ylide, which further gives the sulfonium salt along with a small amount of a thioether (Scheme 40). This was in contrast to the corresponding oxonium ylide where the reaction was found to be reversible <1996JA10141>. 

A very mild and general method for the preparation of diaryl- and heteroaryliodonium triflates is based on iodonium transfer reactions of iodine(III) cyanides with the respective aryl- or heteroarylstannanes [146,148, 399-401]. Specifically, (dicyano)iodonium triflate (277), generated in situ from iodosyl triflate and MesSiCN, reacts with tributyltin derivatives of aromatic and heteroaromatic compounds to afford the corresponding symmetrical iodonium salts under very mild conditions (Scheme 2.80) [389,390]. 

Preparation First representatives of alkenyliodonium salts, dichlorovinyl(phenyl)iodonium species, were reported by Thiele and Haakh in the early 1900s [436]. The first general synthetic approach to alkenyl(phenyl)iodonium salts was developed by Ochiai in the mid-1980s [437,438], This method is based on the reaction of silylated alkenes 299 with iodosylbenzene in the presence of Lewis acids, leading to the stereoselective formation of various alkenyliodonium tetrafluoroborates 300 in good yield (Scheme 2.85). 

Aggarwal and Olofsson have developed a direct asymmetric a-arylation of prochiral ketones using chiral lithium amide bases and diaryliodonium salts [881]. In a representative example, the deprotonation of cyclohexanone derivative 684 using chiral Simpkins (/ ,/ )-base followed by reaction with the pyridyl iodonium salt gave the arylated product 685 in 94% ee (Scheme 3.275). This reaction has been employed in a short total synthesis of the alkaloid (-)-epibatidine [881]. 

Jeffery has reported an alternative additive-based solution to yield Hy-abstracted products. Mizoroki-Heck reaction of allylic alcohols with aryl or alkenyl hahdes in the presence of silver salts (AgOAc or Ag2C03) results in selective Hy -abstraction [7]. Similar hydroxy-coordination to the cationic organopalladium intermediates are believed to be involved in this system. In this regard, the use of hypervalent iodonium salts is also effective for generating cationic palladium species [8]. 

The initiation mechanism of a similar three-component system, consisting of eosin, methyldiethanolamine, and diphenyliodonium chloride was also studied in the initiation of the polymerization of 2-hydroxyethyl methacrylate. The fastest polymerization occurs when all three components were present The next fastest is a combination of the dye and the amine. The slowest is a combination of the dye with the iodonium salt. In this case, it was also observed that the reaction between eosin and the iodonium salt bleaches the dye more rapidly than when the iodonium salt is included with eosin and the amine. Although a direct eosin and amine reaction can produce active radicals they are formed from the reaction with eosin in the original state. Simultaneously active initiating amine-based radicals are formed... 

The arylation of sodium cyanide can be achieved in moderate yields with electron-withdrawing iodonium salts [87]. The synthesis of esters was achieved by palladium-catalyzed carbonylative reaction of alcohols with diaiyliodonium salts under a CO atmosphere [262]. More recently, a base-mediated arylation of qui-nones with electron-donating iodonium salts in refluxing DCE was reported in moderate to good yields [263]. Quinoline anilides could be arylated at the P-carbon by a Pd- or Ni-catalyzed reaction proceeding via activation of sp C-H bonds (Scheme 22a) [264, 265]. Vinyl isocyanides were arylated at room temperature in a photoredox-catalyzed system with an iridium catalyst and visible light, followed by cyclizatimi to give isoquinoline derivatives [266]. 

The reaction of sulfinates with alkynyl iodonium salts was successful, as these substrates are less easy to oxidize. Nevertheless, Waser and Chen demonstrated that EBX reagents can also be useful to synthesize alkynyl sulfones, as they allow a new one-pot procedure starting directly from Grignard reagents (Scheme 36) [161]. In this protocol, DABSO (DABCO-S02) is added after formation of the Grignard reagent. Addition of DME and TIPS-EBX 52 gives aryl alkynyl sulfones in 46-85% yield. Eor base sensitive substrates, it was also possible to start from aryl iodides and use a palladium catalyst. 

Stereoselective carbon-carbon bond formations with hypervalent iodine reagents are also prominently described in the literature. Direct asynunetric a-arylation reactions are not easy to perform. Ochiai et al. synthesized chiral diaryliodonium salts such as [l,l -binaphthalen]-2-yl(phenyl)iodonium tetrafluoroborate derivatives 21 via a BFs-catalyzed tin-X -iodane exchange reaction and developed the direct asymmetric a-phenylation of enolate anions derived from cyclic p-ketoesters (Scheme 7) [37]. A beautiful example of direct asymmetric a-arylation of cyclohexanones in the course of a natural product synthesis was presented through the desymmetrization of 4-substituted cyclohexanones using Simpkin s base, followed by coupling with diaryliodonium salts [38]. Other binaphthyl iodonium salts related to 21 have also been reported [39]. 

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