Directed metalation Orthometalation

Many of the ferrocene ligand families described above are derived from a resolved chiral precursor (i.e. 289). Efforts to (76) prepare planar chiral ferrocenes also employ other strategies that rely on a directed metalation (see Orthometalation). Sulfoxide (338), acetal (339), and oxazolines of type (321)... 

The ortho substituent stabilizes the molecule by coordination to the lithium as shown in 2. This process is only possible when the lithium occupies the 2-position and so lithiation occurs exclusively at this site. Substituents that can behave in this way are known as directing metal-lation groups (DMG). The coordinating ability of a substituent varies and hence their effectiveness in directing metallation to the ortho position is variable. The process is known as directed orthometallation and is a significant development in the field of aromatic chemistry. 

Orthometallation of substituted arenes has been re-viewed. The ortho-directing ability of substituents in ( ) -arene)Cr(CO)3 complexes decreases as F > CONHR > NHCOR > CH2NR2 OMe CH20Me. Heavier alkali metal arenes can be formed from the reaction of phenyl lithium with sodium or potassium aUcoxides. 

Salts of mercury(II) and thallium(HI), such as mercury(II) acetate, Hg(OAc)2, and thallium trifluoroacetate, Tl(OCOCF3)3, are reactive electrophilic metallating species which attack benzene directly. Electron-donating groups in the aromatic ring accelerate the reaction in the conventional manner and direct attack to the ortho and para positions. In addition, metal-chelating substituents, such as amide, promote the reaction and direct attack to the 2-position in a manner similar to that seen in the directed orthometallation reaction. 

Many examples of orthometallation of aryl phosphines and phosphites are known. The phosphines produce four-membered rings when phosphorus is attached directly to the ring being metallated ... 

In their paper describing the direct hydroxylation of arene sp C—H bonds with a ruthenium catalyst, Rao and co-workers demonstrated that a simple thiophene was also compatible with these reaction conditions (Scheme 10.21). It is proposed that under acidic conditions, [RuCl2(p-cymene)]2 facilitates C—H bond cleavage of 67 via an orthometalation process throngh chelation with the ester carbonyl group (kinetic isotope experiments also support a kinetically relevant C—H metalation step). Snbseqnent reductive elimination afforded the hydroxylated thiophene 68 in 41% yield. 

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