Coupling reactions definition

Homocoupling of halobenzenes. lodo- and bromobenzene couple to biphenyls in the presence of this activated Ni(0). Yields are definitely higher with the former substrate. ort/io-Substituents, particularly nitro groups, inhibit coupling. The main by-products result from reduction. This coupling reaction is generally superior to the Ullmann reaction. 

A cross-coupling reaction can be partially defined by equation (1), where Nu is a carbon (or heteroatom) nucleophile see Nucleophile), R X is an electrophilic substrate, X is a halogen or other appropriate leaving group, and M is a metal or metalloid. At first glance, it would appear that simple nucleophihc substitution reactions should fall under this definition. However, what makes the cross-coupling chemistry special is its ability to perform transformations that cannot be accomplished with simple substitution chemistry. 

Consequently, to narrow the definition a bit further, we will adhere to Negishi s suggestion and define cross-coupling reactions as those that follow some variation of the mechanism depicted in Scheme 1 (where Mt is a transition metal, L is an ancillary hgand see Ancillary Ligand), and n is the oxidation state of the reduced metal in the catalytic cycle). This mechanism is supported by stoichiometric studies on isolated metal complexes (mostly where Mt = Pd, n = 0, L = triphenylphosphine) thought to be the intermediates in this cycle. 

Since all ligase reactions are coupled by definition, the reactions that are coupled are shown. 

Because of coupling (see Chapter 7) there are relationships between the thermodynamic properties of reactions in some of the EC classes. All oxidoreductase reactions can be considered to be coupled reactions because each one can be divided into two, or in a some cases, three half reactions that do not share atoms but are connected by formal electrons. Transferase reactions can each be considered to result from the coupling of two oxidoreductase reactions or two hydrolase reactions. Fifteen examples are discussed in reference (6). Each of the coupled reactions contributes its A, G ° and A, A h to the coupled reaction. Hydrolase reactions and isomerase reactions are never coupled reactions. Some lyase reactions are coupled. Ligase reactions are all coupled by definition because they join together two reactions with the hydrolysis of a pyrophosphate bond in ATP or a similar triphosphate. A spectacular example of coupling is provided by EC 6.3.5.4 because there are seven reactants. This never happens in chemistry. 

Schilow recognized that induced reactions fall into two classes. The first class now is called an induced chain reaction, which can be described in terms of an initiation step, a propagation sequence, and a termination step. The other class is the coupled reaction, which can be distinguished from an induced chain reaction by the behavior of the induction factor defined by the ratio equivalents of induced reaction/ equivalents of primary reaction. In an induced chain reaction the induction factor increases without limit as the propagation chain length is increased. In a coupled reaction the induction factor approaches some definite small value such as 1, 2, or 1/2 as the induction reaction is favored. 

Coupled reactions A coupled reaction involves two oxidants with a single reduc-tant, where one reaction taken alone would be thermodynamically unfavorable. The induction factor approaches some small definite value as the induced reaction is favored. An illustration is the oxidation of Mn(II) by dichromate to give Mn02 ... 

Although evidence has been presented that protection of the exocyclic amino group is not necessary to direct the coupling reactions for adenosine and guan-osine (but it is definitely necessary for cytosine), the use of A -protected monomeric units is almost universally observed. The main reasons have to do with increased solubility, but one should be aware of complications during the phosphorylation reaction. Amino protection is evidently not necessary with the phosphite-coupling method at lower temperature. ... 

Glassical oxidative addition of a fluorinated alkane at a transition metal center still remains elusive. However, such a step is conceivable in catalytic cross-coupling reactions of primary alkyl fluorides. The reactions of lanthanoid cations with GH3F to form LnF and -GH3 have been described as oxidative additions, but do not conform to our definition of oxidative addition. ... 

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