Aryl iodides hydrogenolysis

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 alkyne insertion reaction is terminated by anion capture. As examples of the termination by the anion capture, the alkenylpalladium intermediate 189, formed by the intramolecular insertion of 188, is terminated by hydrogenolysis with formic acid to give the terminal alkene 192. Palladium formate 190 is formed, and decarboxylated to give the hydridopalladium 191, reductive elimination of which gives the alkene 192 [81]. Similarly the intramolecular insertion of 193 is terminated by transmetallation of 194 with the tin acetylide 195 (or alkynyl anion capture) to give the dienyne 196 [82], Various heterocyclic compounds are prepared by heteroannulation using aryl iodides 68 and 69, and internal alkynes. Although the mechanism is not clear, alkenylpalladiums, formed by insertion of alkynes, are trapped by nucleophiles... 

This group is stable to metalation of the aromatic ring hy metal halogen exchange, Grignard formation, LiAlLL, reduction, NaOH, PDC, hydrogenolysis, NaBLL, and LDA. Reaction of an aromatic triazene with Mel at 120°C gives the aryl iodide. ... 

In the reaction of Q,/3-unsaturated ketones and esters, sometimes simple Michael-type addition (insertion and hydrogenolysis, or hydroarylation, and hydroalkenylation) of alkenes is observed[53,54]. For example, a simple addition product 56 to methyl vinyl ketone was obtained by the reaction of the heteroaromatic iodide 55[S5]. The corresponding bromide affords the usual insertion-elimination product. Saturated ketones are obtained cleanly by hydroarylation of o,/3l-unsaturated ketones with aryl halides in the presence of sodium formate, which hydrogenolyses the R—Pd—I intermediate to R— Pd—H[56]. Intramolecular hydroarylation is a useful reaction. The diiodide 57 reacts smoothly with sodium formate to give a model compound for the afla-toxin 58. (see Section 1.1.6)[57]. Use of triethylammonium formate and BU4NCI gives better results. 

An interesting case is the hydrogenolysis of aryl chlorides, bromides and iodides in respective yields of 72%, 72% and 82% on irradiation in isopropyl alcohol [310]. 

Another method for the hydrogenolysis of aryl bromides and iodides is to use MeONa[696]. The removal of chlorine and bromine from benzene rings is possible with MeOH under basic conditions by use of dippp as a ligand[697]. The reduction is explained by the formation of the phenylpalladium methoxide 812, which undergoes elimination of /3-hydrogen to form benzene, and MeOH is oxidized to formaldehyde. Based on this mechanistic consideration, reaction of alcohols with aryl halides has another application. For example, cyclohex-anol (813) is oxidized smoothly to cyclohexanone with bromobenzene under basic conditions[698]. 

The hydrogenolysis of aryl halides proceeds more readily than the cleavage of alkyl-halogen bonds. Aryl chlorides are rather stable to hydrogenolysis in neutral medium and bromides are dehalogenated only to a moderate extent 24,132 but iodides are readily lost. Aryl fluorides, however, are hydrogenolyzed only under... 

Under ligandless conditions PdCl2 catalyzed the hydrogenolysis of several 4-substituted aryl chlorides in alkaline aqueous solutions using NaH2P02 as reductant (Scheme 3.40) [275]. In case of certain ortho-substituted substrates, such as 2-chlorophenolate and 2-chloroaniline, strong chelation in the intermediate palladacycle completely inhibited the reaction. On the other hand, in case of 2-chlorobenzoic acid addition of iodide led to 86 % yield of benzoic acid. 

This method offers high functional group tolerance as electron-withdrawing groups and free hydro)g ls are tolerated. In addition to aryl and vinyl iodides, aiyl bromides may also be used but typically provide lower yields. A variant employing aryl boronic acids in place of aryl halides was also reported. Additionally, primary sulfonamides are accessible by a hydrogenolysis/Zn reduction sequence (Scheme 13.18). ... 

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