Iodine-metal exchange

Barrett and co-workers also found that a-iodoalkylsilanes can be prepared by reaction with methyl(triphenoxy)phosphonium iodide (e.g., 23 24, Scheme 7).]" " ] These compounds are of limited S5mthetic value in the Peterson reaction, since iodine/metal exchange is difficult. Nevertheless the method for their preparation is a rare and potentially important one. 

Iodobenzofuran was readily prepared by lithiation of benzofuran followed by iodine quench [8]. Bromination of benzofuran with bromine gave 2,3-dibromobenzofuran, which, when subjected to a regioselective halogen/metal exchange at the C(2) position with n-BuLi followed by quenching with methanol furnished 3-bromobenzofuran [9]. 

The stereospecific construction of the trisubstituted double bond of the side chain at C-1 of carbazomadurins A (253) and B (254) was achieved using Negishi s zirconium-catalyzed carboalumination of alkynes 758 and 763, respectively. Reaction of 5-methyl-l-hexyne (758) with trimethylalane in the presence of zirconocene dichloride, followed by the addition of iodine, afforded the vinyl iodide 759 with the desired E-configuration of the double bond. Halogen-metal exchange with ferf-butyllithium, and reaction of the intermediate vinyllithium compound with tributyltin chloride, provided the vinylstannane 751a (603) (Scheme 5.79). 

Similarly, nitroarenes can also be lithiated (Scheme 5.43), but reactions of meta-lated nitroarenes with electrophiles only proceed cleanly if the metalation is performed in the presence of the electrophile [403], Otherwise, the metalated arene can reduce nitro groups to nitroso groups, which quickly react with additional organo-metallic reagent to yield hydroxylamines [404, 405], Nitroarylmagnesium halides can be prepared by iodine-magnesium exchange at -80 °C to -40 °C, and react with electrophiles in the expected way [6] (Scheme 5.43). 

Compounds containing two halogen atoms will undergo halogen-metal exchange and cyclisation provided that the cyclisation step is faster than the second halogen-metal exchange. This is the case if both are iodine, or if one is iodine and the other bromine, or if one is a vinyl or aryl bromide or iodide. 

Cascade reactions using alkyne cyclisations have not been explored, and the isolated example of 416 is unique in a number of ways.145 For a start, 5-exo-dig cyclisation onto the alkyne to give 417 must be sufficiently fast that it competes with halogen-metal exchange of the second iodine atom, which instead traps the product vinyllithium 417, giving the bicyclic product 418 in 47% yield. 

These results suggest an unprecedented halogen nucleofugality (Br>I) for a halogen-metal exchange (HME) or ET reaction. However, competition experiments of 1-iodo and l-bromobicyclo[2.2.2]octanes established that the iodine is ca twice as reactive as the bromine derivative131. 

The very fast metal-halogen exchange allows intramolecular cyclization reactions, which are known as Parham cyclizations171. The potential of Parham cyclizations as a useful stereoselective cyclization procedure has proven to be extremely interesting172. Thus, it has been recently demonstrated that iodinated IV-phenethylimides tolerate iodine-lithium exchange, giving rise to the isoquinoline nucleus 304, via a Parham-... 

Numerous modifications of the direct zinc insertion procedure can be found in the hterature. For example, simple diaUcylzincs can be used as reagents instead of metallic Zn, bnt in this case the reaction is accelerated by catalytic qnantities of zinc salts or transition metal see Transition Metals) salts. Whereas the Cu -catalyzed iodine-zinc exchange reaction provides diorganozincs, the Pd, Mn and nF catalyzed iodine- or bromine-zinc exchange leads to organozinc halides. 

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