Aryl iodides reactivity

The diazonium salts 145 are another source of arylpalladium com-plexes[114]. They are the most reactive source of arylpalladium species and the reaction can be carried out at room temperature. In addition, they can be used for alkene insertion in the absence of a phosphine ligand using Pd2(dba)3 as a catalyst. This reaction consists of the indirect substitution reaction of an aromatic nitro group with an alkene. The use of diazonium salts is more convenient and synthetically useful than the use of aryl halides, because many aryl halides are prepared from diazonium salts. Diazotization of the aniline derivative 146 in aqueous solution and subsequent insertion of acrylate catalyzed by Pd(OAc)2 by the addition of MeOH are carried out as a one-pot reaction, affording the cinnamate 147 in good yield[115]. The A-nitroso-jV-arylacetamide 148 is prepared from acetanilides and used as another precursor of arylpalladium intermediate. It is more reactive than aryl iodides and bromides and reacts with alkenes at 40 °C without addition of a phosphine ligandfl 16]. 

Chlorination is carried out m a manner similar to brommation and provides a ready route to chlorobenzene and related aryl chlorides Fluormation and lodmation of benzene and other arenes are rarely performed Fluorine is so reactive that its reaction with ben zene is difficult to control lodmation is very slow and has an unfavorable equilibrium constant Syntheses of aryl fluorides and aryl iodides are normally carried out by way of functional group transformations of arylammes these reactions will be described m Chapter 22... 

Formation of aryl Grignard reagents (Section 14.4) Aryl halides react with magnesium to form the corresponding arylmagnesium halide. Aryl iodides are the most reactive, aryl fluorides the least. A similar reaction occurs with lithium to give aryllithium reagents (Section 14.3). 

Reactivity and yields are greatly enhanced by the presence of 0.5-1% Na in the Li. The reaction is also generally available for the preparation of metal alkyls of the heavier Group 1 metals. Lithium aryls are best prepared by metal-halogen exchange using LiBu" and an aryl iodide, and transmetalation is the most convenient route to vinyl, allyl and other unsaturated derivatives ... 

Another successful approach to catalyst immobilisation involves attachment of the carbene precursor to a peptide on solid support. Treatment with base generates the corresponding carbenes that undergo in situ complexation to Pd(ll) centres (Scheme 6.33). Again, the main drawback of this approach was the low reactivity of the catalytic system that only allowed the coupling of aryl iodides and bromides [116], The reasons for this outcome are in need of further studies. 

Several hindered phosphine ligands give enhanced reactivity. Aryl iodides can be coupled at low temperature using Pd2(dba)3 and tr .v-(mcsityl)phosphinc. 

Thallium(III), particularly as the trifluoroacetate salt, is also a reactive electrophilic metallating species, and a variety of synthetic schemes based on arylthallium intermediates have been devised.75 Arylthallium compounds are converted to chlorides or bromides by reaction with the appropriate cupric halide.76 Reaction with potassium iodide gives aryl iodides.77 Fluorides are prepared by successive treatment with potassium fluoride and boron trifluoride.78 Procedures for converting arylthallium compounds to nitriles and phenols have also been described.79... 

As seen in the retro-synthetic Scheme 5.3, intermediate 15 is useful for both routes. The choice of benzyl protection group was made based on the robust stability of benzyl phenol ethers toward most reactions and several possible avenues to remove it, although it was reported from Medicinal Chemistry that benzyl group removal via hydrogenolysis posed challenges in this compound. The choice of iodide substitution was born out of the known high reactivity of iodides in the Ullmann-type coupling reaction with alcohols and the robust stability of aryl iodides in many other common reactions. 

The direct reaction of zinc metal with organic iodides dates back to the work of Frankland(67). Several modifications have been suggested since that time to increase the reactivity of the metal. The majority of these modifications have employed zinc-copper couples(68-72), sodium-zinc alloys(73), or zinc-silver couples(77). Some recent work has indicated that certain zinc-copper couples will react with alkyl bromides to give modest yields of dialkylzinc compounds(74,73). However, all attempts to react zinc with aryl iodides or bromides have met with failure. The primary use of zinc couples has been in the Simmons-Smith reaction. This reaction has been primarily used with diiodomethane as 1,1-dibromides or longer chain diiodides have proven to be too unneactive even with the most reactive zinc couples. 

The order of reactivity of halides with magnesium is RI > RBr > RC1 (very few organomagnesium fluorides have been prepared), i) Aryl Grignard reagents are more easily prepared from aryl bromides and aryl iodides than from aryl chlorides, which react very sluggishly. 

This is a very rare metal in cross-coupling reactions. Direct comparison of similar methylating reagents derived from Al, Ga, and In showed that the Ga derivative is the least reactive.165 Vinylgallium dichlorides underwent cross-coupling with aryl iodides in the presence of Pd catalysts with P(o-tol)3 the reaction is moderately tolerant to acidic functional groups.166... 

The conversion of aryl iodides into aryl phosphonates, a useful precursor to aryl phosphonic acids, was performed in a Teflon autoclave by Villemin [51]. A domestic microwave oven was used for these experiments and the reaction times for classic heating were effectively reduced from 10 h to 4-22 min. The reactivity of iodides was good whereas the use of bromides resulted in lower yields and reactions with tri-flates were very slow (Eq. 11.35). It is notable that the reactions were brought to completion with short reaction times in a non-polar solvent. 

A prototypical study for this section has been obtained as early as in 1983 for carbonylative cross-coupling of the mixture of aryl iodide and alkyl iodide in the presence of Zn metal and palladium catalyst. This system apparently works due to differences of reactivity of aryl versus alkyl iodide toward metallation by Zn. Further studies were rather scarce to involve only preformed functionalized alkylzincs. Carbonylative cross-coupling of functionalized organozinc reagents with allylic esters and GO (1 atm) can be carried out in THF in the presence of HMPA, which suppresses side-reactions (Scheme 4). ... 

This procedure has been utlilized successfully with a variety of aryl iodides, but aryl bromides are much less reactive. Bromoiodobenzenes and o- and p-chloroiodobenzene give the corresponding phenylenediphosphonate esters.2,3... 

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