Iodoarenes

If an electron is transferred from a reducing agent to an arenediazonium ion, an aryldiazenyl radical (8.47) is formed. As discussed in this section, the latter dissociates rapidly into an aryl radical and N2 (Scheme 8-28). This type of dediazoniation was observed by Griess (1864 c), albeit not in our present formulation. He found that arenediazonium ions formed iodoarenes and N2 in the presence of iodide ions. More important for synthetic organic chemistry were some dediazonia-tions discovered in the late 19th and early 20th centuries, which are catalyzed by metals and metal ions, namely the Sandmeyer, Pschorr, Meerwein, and related syntheses (see Ch. 10). 

In the Figure 23 are summarized the different transformations, discussed before, of the bromoarenes into aromatic hydrocarbons, or more interestingly into arylamines, aryl ethers, phenols or iodoarenes. 

In 1980 Sonogashira reported a convenient synthesis of ethynylarenes - the Pd-catalyzed cross-coupfing of bromo- or iodoarenes with trimethylsilylacetylene followed by protiodesilylation in basic solution [15]. Prior to this discovery, formation of terminal acetylenes required manipulation of a preformed, two-carbon side chain via methods that include halogenation/dehydrohalogenation of vinyl- and acetylarenes, dehalogenation of /1,/1-dihaloalkenes, and the Vils-meier procedure [ 14]. With the ready availability of trialkylsilylacetylenes, the two-step Sonogashira sequence has become the cornerstone reaction for the construction of virtually all ethynylated arenes used in PAM and PDM synthesis (vide infra). 

The in situ deprotection/alkynylation protocol has proven to be exceedingly useful. In addition to graphdiyne models, an array of PAM/PDM hybrids have been prepared (76 (R=H), 81, 97-99) [66]. Extension of the simple, one-pot procedure to various iodoarenes has allowed preparation of a series of bis(tri-isopropylsilyl)-protected a,m-polyynes in very good yields. Subsequent depro-... 

The protocol offers a direct and efficient method for the synthesis of the boronic ester in the solid phase, which hitherto met with little success using classical methodology (Scheme 1-42). A solid-phase boronate (113 [155], 114 [156]) is quantitatively obtained by treating a polymer-bound iodoarene with the diboron (82). The subsequent coupling with haloarenes furnishes various biaryls. The robot synthesis or the parallel synthesis on the surface of resin is the topic of further accounts of the research. 

We have also attempted to study the reactions of the tetrafluoro-o-phenylene di-radical (32) with benzene, by carrying out the photolysis of 1,2-di-iodotetrafluorobenzene in the presence of benzene. It is known that 1,2-di-iodoarenes give arynes on photolysis 70-72>. The only product derived immediately from o-dehydrotetrafluorobenzene was the 1,4-cyclo-adduct (24) which was, as expected, partially photoisomerised to (27) and a trace of (26) 73>. The photolysis resulted in the appearance of (24) and (27) before (26) was detected and hence we conclude that (26) was not a primary product. 

A palladium-catalyzed one-step synthesis of dihydrobenzo[fc]furan-based fused aromatic heterocycles from bifunctional bromoenoates or bromoalkyl indoles and iodoarenes was reported, and an example is provided in the scheme below <060L3601>. 2-Alkyl- or 2-aryl-substituted benzo[ >]furans were synthesized by a copper-TMEDA catalyzed intramolecular annulation from the corresponding ketones <06OL1467>. 

Scheme 7 shows that the method of sequential arylation with a high selectivity, using 2-phenylimidazole motif, proves to be applicable for pharmaceuticals and fluorescent and chemiluminescent probes.85 The direct 4-arylation of free 2-phenylimidazole is achieved with iodoarenes as the aryl donors in the presence of palladium catalyst (Pd/PPh3) and MgO as the base. A complete switch from G4 to C2 arylation is accomplished using a ruthenium catalyst [CpRu(PPh3)2Cl] and Gs2G03. 

The oxidative C-arylation of five- to eight-membered (NH)-heterocycles such as pyrrolidine, piperidine, morpholine, etc., is observed in the reaction with iodoarenes in the presence of a rhodium catalyst, RhCl(CO)[P(Fur)3]2.95... 

Innumerable aryl- and heteroarylstannanes take part in Stille couplings with halopyridines. In one such example, the union of arylstannane 106 and 4-bromopyridine furnished arylpyridine 107 [90], Arylstannane 106 was prepared from the Pd-catalyzed reaction of hexabutylditin with iodoarene 105, which arose from aminobenzolactam 104 via a Sandmeyer reaction. 

Comparisons of product distributions in thermal and photochemical solvolyses show that the primary vinyl cation is not involved in thermolysis but is formed photochemically. The chirality probe approach using optically active 4-methylcyclohexylidenmethyl(aryl)iodonium tetrafluoroborate 19 was applied to the photosolvolysis.24 The rearranged product 4-methylcycloheptanone retained some optical activity, but the enantiomeric product in slight excess has a different structure depending on the iodoarene leaving group Arl of the substrate. The results indicate that the primary vinyl cation involved is not in a free, dissociated achiral form. 

In an alternative strategy functionalized phenols, such as iodophenol, were involved in palladium-catalyzed carbonylation of alkynes or allenes, producing coumarin or chromone derivatives (Scheme 23) [130-133]. After oxidative addition of the iodoarene to the Pd(0) catalyst the order of insertion of either CO or the unsaturated substrate mainly depends on the nature of the substrate. In fact, Alper et al. reported that CO insertion occurs prior to allene insertion leading to methylene- or vinyl-benzopyranone derivatives [130]. On the contrary, insertion of alkynes precedes insertion of CO, affording couma-rine derivatives, as reported by Larock et al. According to the authors, this unusual selectivity can be explained by the inability of the acyl palladium species to further react with the alkyne, hence the decarbonylation step occurs preferentially [131-133]. 

Activated haloarenes react with potassium thiocyanate under the influence of a quaternary ammonium salt to form the corresponding aryl thiocyanates [61]. Aliquat is preferred over tetra-n-butylammonium bromide for the reactions of fluoro- and iodoarenes but, in all cases, yields are extremely high. 

Palladium-catalysed C-C bond formation under Heck reaction conditions, which normally requires anhydrous conditions and the presence of copper(I) salts, is aided by the addition of quaternary ammonium salts. It has been shown that it is frequently possible to dispense with the copper catalyst and use standard two-phase reactions conditions [e.g. 18, 19]. Tetra-/i-butylammonium salts catalyse the palladium-catalysed reaction of iodoarenes with alkynes to yield the arylethynes in high yield [20, 21], whereas the reaction with 3-methylbut-1 -yn-3-ol (Scheme 6.30) provides a route to diarylethynes [22]. Diarylethynes are also formed from the reaction of an iodoarene with trimethylsilylethyne [23], Iodoalkynes react with a,p-unsaturated ketones and esters to produce the conjugated yne-eneones [19],... 

The Heck reaction on polymer-bound iodoarenes is assisted by the addition of a catalytic amount of tetra-n-butylammonium bromide and has been employed in the synthesis of 4-carboxycinnamic esters and amides [33], and 4-aminosulphonyl-cinnamic esters [34], It has also been reported that the presence of an equimolar equivalent of benzyltriethylammonium chloride aids the Pd(II)-mediated reaction of A -acyl-2-iodoanilines with vinylidene carbonate, which leads to A -acyl-2-hydroxy-indolines providing a convenient route to the indoles (80-90%) [35], The catalysed reaction of 2-hydroxy- and 2-tosylaminoiodobenzene with 1,2-dienes produces 1,2-dihydrobenzofurans and 1,2-dihydroindoles, respectively [36]. 

The consecutive reaction of vinyl halides and alkenes with activated methylene systems [42] in the presence of a palladium catalyst and phase-transfer catalyst results from the addition of the methylene carbanion with the initially formed Heck product (Scheme 6.31) an intramolecular version of the reaction leads to the formation of bicycloalk-l-enes (Scheme 6.31) [42], The analogous combined coupling reaction of iodoarenes and activated methylene compounds with non-conjugated dienes under similar conditions forms the monoalkene (Scheme 6.31) [43]. 

Na2CO, (0.13 g), TB A-Cl (0.15 g, 0.55 mmol), Pd(0)(PhCH=CHCOCH=CHPh)2 (14 mg, 0.025 mmol) and CH2=CH(CH2)2CH=CH2 (85 mg, I mmol) are added to the iodoarene (0.5 mmol) and the activated methylene compound (CH2XY) (l mmol) in DMSO (I ml) and the mixture is stirred at 80°C under N2 until all of the iodoarene is consumed, as shown by GLC analysis. Et20 (20 ml) is added and the filtered ethereal solution is washed well with aqueous NH4CI (sat. soln), dried (MgS04), and evaporated to yield the hept-3-ene. 

Optimum yields of (3-vinyl-y-butyrolactols from the Pd(II) promoted reaction of vinyl triflates with Z-but-2-en-l,4-diol (Scheme 6.33) are attained when tetra-n-butylammonium chloride is added (47]. The lactol is conveniently oxidized to the lactone with celite-supported silver carbonate. The corresponding arylbutyrolactols are obtained in high yield (70-80%) from an analogous reaction of iodoarenes with the enediol. The yields of 2-alkenyl-2,5-dihydrofurans, resulting from the Pd(0) catalysed reaction of cyclic alkynylcarbonates with acrylic esters via tandem C-C and C-0 bond forming reactions, are enhanced by the presence of tetra-n-butyl-ammonium fluoride (e.g. Scheme 6.33) (48]. 

Triazenes are disguised diazonium ions which can be released under very mild acidic conditions. Inspired by the use of triazenes in natural product synthesis by Nicolaou et al. [127] and the pioneering work of Moore et al. [128, 129] and Tour et al. [130] in the synthesis of triazenes on a solid support and the final detachment to give iodoarenes, a whole set of triazene-based linkers has been developed (Tab. 3.10) [131]. The arene diazonium salts generated from the triazene linkers offer diverse opportunities for multifunctional cleavage. Two linkers based on tria-... 

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