New Route For Halide Addition | Chemical & Engineering News
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Web Date: April 2, 2007

New Route For Halide Addition

Reaction allows nucleophilic halide anion addition to aromatic rings
Department: Science & Technology, ACS News
Halide anion adds to an enediyne-derived p-benzyne biradical and the resulting intermediate is then protonated.
Halide anion adds to an enediyne-derived p-benzyne biradical and the resulting intermediate is then protonated.

A new halide addition reaction represents a means by which halides can be incorporated into biomolecules.

The reaction was discovered by chemistry professors Charles L. Perrin and Joseph M. O'Connor and graduate student Betsy L. Rodgers at the University of California, San Diego. They reported their findings before the Division of Organic Chemistry at last week's American Chemical Society national meeting in Chicago and in a publication (J. Am. Chem. Soc., DOI: 10.1021/ja070023e).

Halogens add to organic molecules by nucleophilic substitution reactions at saturated carbons. Halogens also add biosynthetically to electron-rich aromatic rings by electrophilic substitution reactions catalyzed by haloperoxidases or halogenases.

Perrin, O'Connor, and Rodgers have now expanded the repertoire of halide additions with the discovery of a reaction in which a nucleophilic halide anion can be attached to an aromatic ring.

They got the idea for the reaction when oceanography professor William Fenical of UC San Diego and coworkers isolated two pairs of chlorinated marine natural products, the sporolides and cyanosporasides, and suggested that they were derived from an enediyne precursor that cycloaromatizes to a p-benzyne biradical. But the mechanism by which chlorine was incorporated was unknown.

The team has now reproduced such a process experimentally. By heating a model enediyne in the presence of chloride, bromide, or iodide and a weak acid, they were able to show that the enediyne cyclizes to a p-benzyne biradical, which quickly adds halide and is then protonated. This mechanism differs from the usual radical chemistry of p-benzynes, and it can account for the biosynthesis of the sporolides and cyanosporasides. A halogen atom and hydrogen have not previously been introduced into a substrate experimentally in this way, according to the researchers.

The reaction has important implications for incorporating halides into aromatics and biomolecules. "We believe these results will open a new chapter in the widely followed chemistry of enediynes and p-benzynes," Perrin said.

Fenical commented that the group's discovery "is truly important in fundamental organic chemistry and will significantly expand understanding of the reactivity of enediynes."

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