Preparation and Applications of Functionalized Organozinc Compounds

Knochel, Paul; Millot, Nicolas; Rodriguez, Alain L.; Tucker, Charles E.


Organozinc compounds have been known for more than 150 years. With the exception of zinc enolates (Reformatsky reagents) and iodomethylzinc derivatives (Simmons-Smith, Furukawa, and Sawada reagents), their synthetic potential has only been recently recognized. This is certainly due to their low reactivity and to the absence of general methods of preparation. Although the carbon-zinc bond in diethylzinc has a dissociation energy of 34.5 kcal/mol, it has, because of the similar electronegativities of zinc and carbon, a highly covalent character (ca. 85 %), which is comparable to a carbon-tin bond. The carbon-zinc bond is therefore inert to moderately polar electrophiles such as aldehydes, ketones, esters, or nitriles. On the other hand, the presence of empty low-lying p orbitals at the zinc center allows transmetallations with a number of transition metal complexes. This is favored for both kinetic and thermo-dynamic reasons. The availability of d orbitals at the metal center in these compounds allows for new reaction pathways with electrophilic reagents that were not available for the corresponding zinc reagents. This reactivity has been exploited for the formation of new carbon-carbon bonds and efficient cross-coupling reactions between organozinc derivatives and unsaturated organic halides, as Negishi has demonstrated using catalytic amounts of palladium(0) salts. Similar catalytic processes have been reported with copper(I) and titanium(IV) complexes, which can mediate numerous reactions of organozinc reagents with organic electrophiles.

The scope and synthetic applications of zinc organometallics were greatly extended when it was found that these species can accommodate a wide range of functional groups. They are ideally suited for the construction of polyfunctional organic molecules without the use of multiple protection and deprotection steps. Although some functionalized organozinc compounds bearing ester groups such had been reported, it was only recently that systematic studies have shown the synthetic potential of these reagents. This chapter describes methods for the preparation of functionalized organozinc halides, diorganozincs, and organozincates and their reactions with electrophilic reagents in the presence of transition metal catalysts, as well as synthetic applications demonstrating their synthetic utility for natural product synthesis. Only the preparation and reactivity of zinc organometallics bearing relatively reactive functional groups are covered. Thus, the chemistry of organozinc compounds bearing an ether, acetal, ketal, trialkylsilyl, or polyfluoroalkyl group is, in general, not covered.