Intramolecular halogen-metal exchange

An example of intramolecular conjugate addition of aryllithium generated by halogen metal exchange reaction of 92 is illustrated in equation 7966. 

Several examples of intramolecular additions to carbonyl groups by organo-lithium reagents generated by halogen-metal exchange have been reported, such as the two examples shown below. What relative reactivity relationships must hold in order for such procedures to succeed ... 

In addition to deprotonation with strong bases, halogen-metal exchange, or trans-metalation, a-heteroatom-substituted carbanions can also be prepared by 1,5-hydro-gen transfer to vinyl radicals, followed by reduction [204, 205] (Scheme 5.21) or by a related intramolecular 1,4-proton transfer [206]. 

When Me3SiSnBu3 is treated with CsF, the fluoride anion should coordinate to the silyl group and not the stannyl group to produce a hypervalent silicate, and as a result, a stannyl anion would be generated.282 The stannyl anion reacts with vinyl iodide to produce a vinyl anion via a halogen-metal exchange and it reacts with the carbonyl group intramolecularly (Equation (113)). Aryl halides or allyl halides are also used in similar cyclizations.283,284... 

Intramolecular cyclisation following halogen-metal exchange in the benzonitrile derivatives 25 provides a route to xanthones and thioxanthones. Incorporation of a second aryl halide function into the benzonitrile substrate allows an anionic cascade ring-closing sequence and the formation of pentacyclic xanthene derivatives 26 <03JOC4091>. 

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-... 

Recently, a metal-halogen exchange method was described for the synthesis of isatins by lithiation of o/7/ o-bromophenylureas, carbonylation and subsequent intramolecular cyclisation to give the desired products in 71-79% yield51 (Scheme 14). 

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