Orthometalation, directed

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. 

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. 

As an extension of this work, the same authors recently reported the direct orthometallation of several SchifTs bases according to (158) ... 

This group was used as a bulky protective group to the intramolecular C-H insertion of a-diazo acetamides and in directed orthometalation reactions of aryl amides. The cumyl group is readily cleaved with CF3CO2H. Formic acid has also been used to remove a cumyl group. 

Stable orthometallated complexes with nitrogen donors in four-membered rings are made by exchange reactions from ortholithium derivatives, but not by direct orthometallation. 

The first direct orthometallation products of /ra r-azobenzene with Co(lll) 95 were observed and fully characterized (Equation (10)). ... 

Typically, superbases care little for coordination effects, and simply remove the most acidic proton on offer this provides useful alternative selectivities in the lithiation of aromatic rings, for example. With groups that direct principally by acidification, orthometallation occurs, and treatment with BuLi-KO/-Bu is the most efficient way of orthofunctionalising fluorobenzene or trifluoromethylbenzene.442... 

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. 

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)... 

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 ... 

Thermolysis of either 4a or 4b in the presence of ethylene led to isolable products 13a and 13b in which efficient trapping of B (the orthometalated analog ofB) or B, respectively, with ethylene occurs as shown in Scheme 7. Analysis of the rates of reaction of 4a with respect to ethylene concentration showed that ethylene can bind to the five-coordinate Pt(lV) species and inhibit C-C reductive elimination. These results support direct C-C coupling from the five-coordinate complexes and establish the validity of these species as functional models for the intermediates... 

Electrophilic Addition to Aromatics. Aromatic compounds are fluorinated with 1 by heating without a solvent to about 100-150 °C, or, for low-boiUng compounds, up to reflux temperature. Activated aromatics, such as anlsole or N-acetylaniline, react smoothly, whereas toluene requires considerably longer reaction times and gives low yields (eqs 9 11). In all cases, the regioselectivities are consistent with an electrophilic addition mechanism ortho- and para-substituted products predominate over the meta-isomers. 1 has recently been used in orthometalation-directed fluorination of aromatics. ... 

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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