Iodobenzenes, substituted

Iodobenzene substitutes more easily than benzene. In this case, however, Sx is comparatively small, and the discrepancy does slot exist. 

The iodine atom in iodobenzene (unlike that in the corresponding aliphatic compounds) is very resistant to the action of alkalis, potassium cyanide, silver nitrite, etc. This firm attachment of the iodine atom to the benzene ring is typical of aromatic halides generally, although in suitably substituted nitio-compounds, such as chloro-2,4-dinitrobenzene, the halogen atom does possess an increased reactivity (p. 262). 

Methyl iodide ethyl bromide ethyl iodide, higher alkyl halides, chloroform, iodoform, carbon tetrachloride, chlorobenzene, bromobenzene, iodobenzene, benzyl chloride (and nuclear substituted derivatives)... 

Pentamethylcyclopentadienyl substituted boron complexes arc obtamed by the reaction of the pentamethylcyclopentadienyl anion with boron tnfluonde [109] (Table 27) Similarly, the Gngnard reagent prepared from 3,5-bis(tnfluorometh-yl)iodobenzene reacts with sodium tetrafluoroborate to form the phase-transfer eatalyst 2 under anhydrous eonditions [110] (equation 87)... 

The coupling of bromo- or iodobenzene to styrene yields regioselectively a mixture of E- and Z-stilbenes 12 and 13. An electron-withdrawing substituent at the olefinic double bond often improves the regioselectivity, while an electron-donor-substituted alkene gives rise to the formation of regioisomers. 

Besides benzyl chloride, methyl- and/or chlorine-substituted benzyl chlorides, phenethyl chloride, etc. are also successfully employed to give 2 -diaralkylaminofluorans in excellent yield. However, aryl halides such as chlorobenzene and bromobenzene hardly enable the reaction, though aryl iodides such as iodobenzene give 2 -diarylaminofluorans in low yield. 

The most straightforward route toward 15 is likely to be the Friedel-Crafts reaction of 3-benzyloxyphenylacetic acid (19) with iodobenzene (18), as shown in Scheme 5.4. However, preliminary attempts at this type of reaction were met with the very low reactivity of iodobenzene (18) toward Friedel-Crafts substitutions. 

Recently, Pal et al. found that (.S )-prolinol could facilitate the coupling reaction of terminal alkynes with 3-iodoflavone under palladium-copper catalysis in aqueous DMF to give 3-alkynyl substituted flavones of potential biological interest (Eq. 4.17). The coupling of iodobenzene with terminal alkynes at room temperature in water without any cosolvent was completed within 30 minutes, affording the desired product in good yield.36... 

Several approaches to the 1,2,3-triazole core have been published in 2000. Iodobenzene diacetate-mediated oxidation of hydrazones 152 led to fused 1,2,3-triazoloheterocycles 153 <00SC417>. Treatment of oxazolone 154 with iso-pentyl nitrite in the presence of acetic acid gave 1,2,3-triazole 155, a precursor to 3-(W-l,2,3-triazolyl)-substituted a,P-unsaturated a amino acid derivatives <00SC2863>. Aroyl-substituted ketene aminals 156 reacted with aryl azides to provide polysubstituted 1,23-triazoles 157 <00HC387>. 2-Aryl-2T/,4/f-imidazo[43-d][l,2,3]triazoles 159 were prepared from the reaction of triethyl AM-ethyl-2-methyl-4-nitro-l//-imidazol-5-yl phosphoramidate (158) with aryl isocyanates <00TL9889>. 

The product 46 from the Rh(I)-catalysed [2+2+2] cycloaddition of the diynyl ether 44 to the substituted iodobenzene 45 undergoes a Pd-catalysed cyclisation to the fused chromans 47 <00TL3003>. 

The intramolecular arylation of sp3 C-H bonds is observed in the reaction of l-/ r/-butyl-2-iodobenzene under palladium catalysis (Equation (71)) 94 94a 94b The oxidative addition of Arl to Pd(0) gives an ArPdl species, which undergoes the electrophilic substitution at the tert-butyl group to afford the palladacycle. To this palladacycle, another molecule of Arl oxidatively adds, giving the Pd(iv) complex. 

In one possible mechanism, oxidative addition of iodobenzene to Pd(0) gives Pd(II) intermediate 74, which subsequently inserts into thiazole regioselectively at the C(5) position to form the a-adduct of arylpalladium(II) 75. The order of reactivity is similar to the electrophilic substitution, which is known to be C(5) > C(4) > C(2) [74]. Treatment of the insertion adduct 75 with a base regains the aromaticity after deprotonation, giving rise to 73 along with Pd(0) for the next catalytic cycle. 

The N-pyrrolylzinc chloride 53 undergoes Pd-catalyzed coupling with perfluoroalkyl iodides to afford the 2-substituted pyrroles 54 in good yield [52], Smaller amounts (15-20%) of 2-perfluoroalkanoyl pyrroles, which presumably arise by hydrolysis of the benzylic difluoromethylene group, are also formed. This reaction, which is performed in one pot, also affords 2-phenylpyrrole (75%) and 3-phenylpyrrole (5%) with iodobenzene. Some biphenyl (15%) is also formed. 

When 4-/-butylcyclohex-1 -enyl(phenyl)iodonium tetrafluoroborate (3) is heated at 60 °C in chloroform, 1-fluorocyclohexene 4, 1-chlorocyclohexene 5 and l-(o-iodophenyl)cyclohexene 6 are formed with accompanying iodobenzene leaving group (eq 2).3 These three substitution products are best accounted for by formation of an ion pair involving cyclohexenyl cation 7. The cyclohexenyl cation 7 formed picks up fluoride from tetrafluoroborate and chloride from chloroform solvent, and recombines with the iodobenzene generated (eq 3). This kind of reactions with a counteranion and solvent are characteristic of unstable carbocations and are known in the case of phenyl cation generated from the diazonium salt in the Schiemann-type reaction.4... 

Additional examples of palladium-catalyzed cross-couplings, in particular with allenylzinc compounds, can be found elsewhere [11, 15, 36]. A systematic study comparing several chiral palladium phosphine catalysts in the reaction of 4,4-di-methyl-1,2-pentadienylzinc chloride and iodobenzene revealed that an enantiomeric excess of only 25% was obtained from the best catalyst combination PdCl2 and (R,R)-DIOP [15]. The synthetic value of these transformations of donor-substituted allenes as precursors is documented by the preparation of a/l-unsaturatcd carbonyl... 

Fused isooxazolidines can be prepared efficiently in a one-pot procedure, which involves a sequence of a Pd-catalyzed reaction of iodobenzene with allene, nucleophilic substitution and nitrone 1,3-dipolar cycioaddition (1,3-DC) (Scheme 16.14) [18]-... 

Reactions of (ii)-l-decenyl(phenyl)iodonium salt (6a) with halide ions have been examined under various conditions. The products are those of substitution and elimination, usually (Z)-l-halodec-l-ene (6b) and dec-l-yne (6c), as well as iodobenzene (6d), but F gives exclusively elimination. In kinetic studies of secondary kinetic isotope effects, leaving-group substituent effects, and pressure effects on the rate, the results are compatible with the in-plane vinylic mechanism for substitution with inversion. The reactions of four ( )-jS-alkylvinyl(phenyl)iodonium salts with CP in MeCN and other solvents at 25 °C have been examined. Substitution with inversion is usually in competition with elimination to form the alk-l-yne. 

Coupling of 1 with iodobenzene under Heck reaction conditions gave the phenyl-substituted diene 242-Ph which was isolated in up to 78% yield [146-148]. When heated at 80 °C in DMF or MeCN with various dienophiles 244-R (acrylate, maleate, or fumarate), 242-Ph and its analogs 242-Ar obtained from 1 and other haloarenes cleanly gave the spiro[2.5]octene derivatives 245-Ar (Scheme 57). 

Addition of methyllithium to the lactone 1219, followed by reduction with sodium borohydride in refluxing ethanol, afforded, almost quantitatively, ellipticine (228). Reaction of the compound 1219 with the lithio derivative of formaldehyde diethylmercaptal, and reduction with sodium borohydride in refluxing ethanol, led to the mercaptal 1221. Cleavage of the mercaptal 1221 with bis(trifluoroacetoxy) iodobenzene [Phl(OCOCF3)2] in aqueous acetonitrile gave the 11-formyl derivative, which was reduced with sodium cyanoborohydride (NaBHsCN) to 12-hydroxyellipticine (232) (710,711) (Scheme 5.202). The same group also reported the synthesis of further pyiido[4,3-fc]carbazole derivatives by condensation of 2-substituted indoles with 3-acetylpyridine (712). 

The Heck reaction is a C-C coupling reaction where an unsaturated hydrocarbon or arene halide/triflate/sulfonate reacts with an alkene in presence of a base and Pd(0) catalyst so as to form a substituted alkene. Kaufmann et al. showed that the Heck reaction carried out in presence of ILs such as tetra-alkyl ammonium and phosphonium salts without the phosphine ligands, resulted in high yields of product. They attributed the activity to the stabilizing effect of ammonium and phosphonium salts on Pd(0) species. Carmichael et al. used ionic liquids containing either A,A -dialkylimidazolium and A-alkylpyridinium cations with anions such as halide, hexafluorophosphate or tetrafiuoroborate to carry out reactions of aryl halide and benzoic anhydride with ethyl and butyl acrylates in presence of Pd catalyst. An example of iodobenzene reacting with ethyl acrylate to give trans-et vy cinnamate is shown in Scheme 14. 

JCS(P1)249>. In an interesting alternative to direct acylation of this heterocycle, Pierini and Rossi examined the photostimulated SrnI reaction of the enolate of 2-acetyl-1-methylpyrrole 36 with haloarenes (e.g., iodobenzene, 37) as well as neopentyl iodides to afford a-substituted acetyl pyrroles 38 <99JOC6487>. 

Similar decomposition is observed in p-bromoacetophenone, o-bromo-, p-bromo, and p,p -dibromobenzophenone, and p-iodobenzophenone44 but not in the fluoro- and chloro-substituted compounds. This order of reactivity follows the bond dissociation energies for aromatic halides which are about 90 kcal/mole for chlorobenzene, 70 kcal/mole for bromobenzene, and 60 kcal/ mole for iodobenzene. The lowest-lying triplet of p-bromoacetophenone is 71.2 kcal45 while that of the substituted benzophenones is slightly lower since benzophenone itself has a lower triplet energy than acetophenone. p,p Dibromobenzophenone was the least reactive of the compounds that photoeliminated halogen atoms. 

The palladium catalysed sequential alkylation-alkenylation of 5-iodoquinoline leads to the formation of the quinolooxepin ring system (5.20.), The process, closely related to the Catellani reaction,19 runs through an ort/zo-alkylation - Heck reaction sequence. The preparation of a series of benzoxepines has also been achieved in this manner, starting from such iodobenzene derivatives, where one of the or/7 o-positions was blocked by substitution.20... 

To overcome problems associated with the removal of iodobenzene and its derivatives formed upon fluorination of arylalkenes and arylalkynes with (difluoroiodo)arenes, polymer-supported (difluoroiodo)arenes were proposed.139 With these agents, the separation procedures are reduced to filtration of the iodinated polymer. For this purpose popcorn polystyrene is io-dinated and then transformed into the difluoroiodide by treatment with xenon difluoride in the presence of hydrogen fluoride in dichloromelhane at 25 C. The amount of active fluorine bonded to iodine atoms on the polymer support is estimated by iodometric titration. The reactions with phenyl-substituted alkenes result in rearranged gew-difluorides. The procedure provides the same fluorination products as with (difluoroiodo)benzenc (see Section 4.13.) but in much higher yields, e.g. PhCF2CH2Ph (96%), PhCF2CH(Me)Ph (95%). PhCH2CF2H (86%), and l,l-difluoro-2-phenylcyclopentanc (91 %). 

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