A Lewis acid-triggered zincation allows the regioselective metalation of various chromones and quinolones. In the absence of MgCl(2), a C(3) zincation is observed, whereas in the presence of MgCl(2) or a related Lewis acid, C(2) zincation occurs. Applications to a natural flavone, isoflavone, and quinolone are shown.

A wide range of functional aryl and heteroaryl zinc reagents have been efficiently prepared via regio- and chemoselective zincation using TMPZnCl.LiCl and microwave irradiation. Sensitive functional groups like esters are compatible with the high temperatures of the reactions. The resulting zinc species undergo a number of subsequent reactions, providing highly functionalized aromatics and heteroaromatics in high yields.

A broad range of functionalized aryl- and heteroarylzinc reagents were prepared via directed zincation of sensitive and moderately activated aromatics and heteroaromatics using TMPZnCl.LiCl under various reaction conditions. Diverse sensitive functional groups such as a nitro group, an aldehyde, an ester, and a nitrile are readily tolerated and are compatible with high metalation temperatures. Furthermore, the resulting zinc organometallics display an excellent reactivity toward various classes of electrophiles providing functionalized aromatics and heteroaromatics in high yields.

Successive regio- and chemoselective metalations of chloropyrazines using TMPMgCl x LiCl and TMPZnCl x LiCl furnish, after trapping with electrophiles, highly functionalized pyrazines in high yields. Application to a synthesis of coelenterazine, a bioluminescent natural product in jellyfish Aequorea victoria, in nine steps (9% overall yield) is reported.

A range of functional aryl and heteroaryl zinc reagents were prepared in THF via directed zincation using the previously reported amide base tmpZnCl • LiCl. These metalation reactions were carried out on 50 mmol scale. Diverse sensitive functional groups such as a nitro group, an aldehyde, an ester, and a nitrile are tolerated. Furthermore, the resulting zinc intermediates show excellent reactivity towards various classes of electrophiles, e.g. Pd-catalyzed cross-coupling reactions or Cu-catalyzed acylations and allylations. In all cases, the metalation rates have been compared with those of the corresponding small-scale reactions (1-2 mmol). Moreover, the recovery of the valuable tmp-H from the aqueous phase has been demonstrated.