Heteroatomic coupling palladium® catalysis

As described in Section III.1.4.1.1, the catalytic direct arylation reactions of aromatic compounds occurs effectively via C-H bond cleavage when the substrates are appropriately functionalized. On the other hand, various five-membered heteroaromatic compounds involving one or two heteroatoms, even without a functional group, are known to undergo arylation, usually at their 2- and/or 5-posi-tion(s), on treatment with aryl halides under the action of palladium catalysis. The coupling has recently been developed significantly [1, 2]. Representative examples with some mechanistic discussion are summarized in this section. 

While the major use for palladium catalysis is to make carbon-carbon bonds, which are difficult to make using conventional reactions, the success of this approach has recently led to its application to forming carbon-heteroatom bonds as well. The Overall result is a nucleophilic substitution at a vinylic or aromatic centre, which would not normally be possible. A range of aromatic amines can be prepared direcdy from the corresponding bromides, iodides, or triflates and the required amine in the presence of palladium(O) and a strong alkoxide base. Similarly, lithium thiolates couple with vinylic triflates to give vinyl sulfides provided lithium chloride is present. 

Magnesium Reagents. Nickel catalysis is conunonly used for cross-coupling reactions involving organomagnesium reagents. Palladium catalysis is often less efficient but more selective. In 2,3-dibromothiophene selective reaction in the 2-position gives the monocoupled product 48 (Scheme 24). Selectivity is rationalized by activation of the 2-position by the annular heteroatom. Monosubstitution can also be effected in 2,5-dibromothiophene to yield the bithienyl 4,9... 

The same transition metal systems which activate alkenes, alkadienes and alkynes to undergo nucleophilic attack by heteroatom nucleophiles also promote the reaction of carbon nucleophiles with these unsaturated compounds, and most of the chemistry in Scheme 1 in Section 3.1.2 of this volume is also applicable in these systems. However two additional problems which seriously limit the synthetic utility of these reactions are encountered with carbon nucleophiles. Most carbanions arc strong reducing agents, while many electrophilic metals such as palladium(II) are readily reduced. Thus, oxidative coupling of the carbanion, with concomitant reduction of the metal, is often encountered when carbon nucleophiles arc studied. In addition, catalytic cycles invariably require reoxidation of the metal used to activate the alkene [usually palladium(II)]. Since carbanions are more readily oxidized than are the metals used, catalysis of alkene, diene and alkyne alkylation has rarely been achieved. Thus, virtually all of the reactions discussed below require stoichiometric quantities of the transition metal, and are practical only when the ease of the transformation or the value of the product overcomes the inherent cost of using large amounts of often expensive transition metals. 

In recent decades much effort has been devoted to extending the scope of palladium, copper, and nickel-catalyzed reactions proceeding via aryl or vinyl metal intermediates [12]. These coupling reactions have enabled the formation of many kinds of carbon-carbon and carbon-heteroatom connections that were previously very difficult to realize. Metal-mediated transformations have proven especially valuable for introduction of substituents to aromatic core structures. They allow the presence of a wide variety of functional groups and perform equally well in both inter and intramolecular applications. Furthermore, in homogeneous catalysis,... 

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