Aromatic rings, regioselective metalation

Aromatic hydrocarbons with two or more rings are hydrogenated in a stepwise manner permitting regioselective saturation of one of the rings. Individual metals have a marked influence on selectivity. Biphenyl, for example, is transformed to cyclohexylbenzene with 97% selectivity on palladium, which is the least active to catalyze saturation of benzene under mild conditions.11 12 Even better selectiv-ities are achieved in transfer hydrogenation.105... 

The last transformation accomplishes the regioselective reduction of an aromatic ring. An alkali metal is utilized in this reaction. 

In the alkyne dimerization catalyzed by palladium systems, all proposed mechanisms account for an alkynyl/alkyne intermediate with cis addition of the alkynyl C-Pd bond to the alkyne in a Markovnikov fashion, in which the palladium is placed at the less-substituted carbon, both to minimize steric hindrance and to provide the most stable C-Pd bond (Scheme 2a). The reverse regioselectivity in the palladium-catalyzed dimerization of aryl acetylenes has been attributed to an agostic interaction between the transition metal and ortho protons of the aromatic ring in the substrate (Scheme 2b) [7, 8],... 

The finding that lithiation of la took place selectively at the aromatic ring rather than the benzyl position opened a way for the functionalization of la in a regioselective manner by means of metalation [58]. Thus la was treated with 3 equiv. of the Lochmann s base (t-BuOK, n-BuLi) in hexane and then the reaction was quenched with appropriate electrophiles, giving monosubstituted products lb, II, Ip, and Iq (Structures 2 and 22, Scheme 14) in good yields. When more excess base was employed, para-disubstitution products Ic, Im, and Ir... 

While the regioselective metallation of aromatic rings generally requires the presence of heteroatom substituents, the inductive electron-withdrawing effect of the aromatic nitrogen activates the ortho-hydrogens to strong bases. 

Although reasonable from an acid-base perspective (stronger acid on the left, weaker acid on the right), reactions such as this are inconveniently slow and not practical as a general method for making aryllithiums. Certain substitutents on an aromatic ring, however, both promote metalation and control its regioselectivity. 

In traditional electrophilic aromatic snbstitntions the reaction is governed by the electronic properties of the snbstitnents on the aromatic ring. In transition-metal-catalyzed reactions, the regiochemistry can be controlled by nnmerous inter-molecular interactions. Sometimes the regiocontrol has been achieved by substituents on the arene, which bind to the catalyst and direct the reaction to either the ortho- or meta- positions. In other examples the regioselectivity results from the steric interactions of the snbstitnents ortho to a reacting C—H bond. ... 

Polysubstituted benzenes are widely used both in industry and in research laboratories. Regioselective construction of polysubstituted benzenes is usually achieved through the gradual introduction of substituents in the aromatic ring by Friedel-Crafts reaction or similar reactions of electrophilic substitution or through organometallic synthesis. In 1948, Reppe reported the [2+2+2] trimerization of substituted acetylenes in the presence of transition metals to form polysubstituted benzenes (Scheme 1.1) [1]. 

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