Nucleophilic/electrophilic catalysis

ELECTRON TRANSEER REACTIONS ELECTRON TRANSPORT ELECTROPHILE ELECTROPHILICITY NUCLEOPHILE ELECTROPHILIC CATALYSIS ELECTROPHILICITY NUCLEOPHILICITY ELECTROPHILE ELECTROPHILIC SUBSTITUTION REACTION Electrophoretic mobility,... 

Buffer, General Acid-Base, and Nucleophilic-Electrophilic Catalysis... 

Nucleophilic/electrophilic catalysis substrate activation by Lewis bases via electron pair donor complexes or by Lewis acids via electron pair acceptor complexes... 

From the mechanistic viewpoint, there are numerous reported examples of base (nucleophile)-catalyzed addition, simultaneously promoted by electrophilic metal ions. A typical example of nucleophilic-electrophilic catalysis is provided by the addition of hydrochlorosilanes to alkenes, which occurs in the presence of Cu(II) and/or Cu(I) salts, and tertiary amines (3), such as CU2O-tetramethylethylenediamine system (134) catalyzes exclusively j8-hydrosilylation of acrylates. 

The acid-catalyzed additions of bromide and chloride ion to thiiranes occurs readily, with halide preferentially but not exclusively attacking the most substituted carbon atom of the thiirane. The reaction of 1-substituted thiiranes with acetyl chloride shows a slight preference for halide attack at the less substituted carbon atom (80MI50601). For further discussion of electrophilic catalysis of halide ion attack see Section 5.06.3.3.2. The reaction of halogens with thiiranes involves electrophilic attack on sulfur (Section 5.06.3.3.6) followed by nucleophilic attack of halide ion on carbon. 

The factors in carboaromatic nucleophilic displacements summarized in this section are likely to be characteristic of heteroaromatic reactions and can be used to rationalize the behavior of azine derivatives. The effect of hydrogen bonding and of complexing with metal compounds in providing various degrees of electrophilic catalysis (cf. Section II, C) would be expected to be more extensive in heteroaromatics. 

Nucleophilic chlorination of 1,5-naphthyridine mono- and di-N-oxides yields 2-chloro- and 2,6-dichloro-naphthyridines via electrophilic catalysis of the reaction of intermediates such as 430 with chloride ion. An interesting example of electrophilic catalysis is the... 

It has also been argued10,40 that the second mechanism (rapid, reversible interconversion of II and IV) cannot be general. The basis for this contention is the fact that electrophilic catalysis is rare in nucleophilic aromatic substitution of non-heterocyclic substrates, an exception being the 2000-fold acceleration by thorium ion of the rate of reaction of 2,4-dinitrofluorobenzene with thiocyanate... 

A recently developed general procedure for the synthesis of cyclic nitroso acetals is based on the reaction of cyclic nitronates with C-nucleophiles under conditions of electrophilic catalysis (Scheme 3.153 for more details, see Section 3.5.2.3). 

In principle, reactions which are subject to electrophilic catalysis by protons can be catalysed by metal ions also (e.g. Tee and Iyengar, 1988 Suh, 1992). However, metal ions may function in other ways, such as to deliver a hydroxide ion nucleophile to the reaction centre (e.g. Dugas, 1989 Chin, 1991), and it is often difficult to decide between kinetically equivalent mechanisms without resorting to extensive (and intensive) model studies. Use of the Kurz approach may help to resolve such ambiguities, as shown below. 

Schultz and coworkers (Jackson et a ., 1988) have generated an antibody which exhibits behaviour similar to the enzyme chorismate mutase. The enzyme catalyses the conversion of chorismate [49] to prephenate [50] as part of the shikimate pathway for the biosynthesis of aromatic amino acids in plants and micro-organisms (Haslam, 1974 Dixon and Webb, 1979). It is unusual for an enzyme in that it does not seem to employ acid-base chemistry, nucleophilic or electrophilic catalysis, metal ions, or redox chemistry. Rather, it binds the substrate and forces it into the appropriate conformation for reaction and stabilizes the transition state, without using distinct catalytic groups. 

In earlier days it was fairly common to suggest that sulfenium ions, RS+, were involved as intermediates in a number of these substitutions, particularly those in which sulfenyl halides RSX reacted with very weak nucleophiles, or those where electrophilic catalysis of the substitution was observed (Parker and Kharasch, 1959). However, it has since become evident (Owsley and Helmkamp, 1967 Helmkamp et al., 1968 Capozzi et al., 1975) that sulfenium ions are almost impossible to generate as intermediates. For example, Capozzi et al., (1975) showed that although treatment of a sulfenyl chloride RSC1 with the powerful Lewis acid antimony pentafluoride led to the complete conversion of the sulfenyl chloride to a cation, what was formed was, not the sulfenium ion RS+, but rather the cation [59] in reaction (172). These results, and others... 

The effect is interpreted as evidence of the operation of the homo-/hetero-conjugate mechanism. The authors presume that for the mechanism given by equation 1, for additives P which are much less basic than the nucleophile N, electrophilic catalysis also occurs both with the hetero-conjugate N+HP formed between the conjugate acid of the nucleophile, N, and P, as well as with the homo-conjugate Nu+HNu. For more basic additives, electrophilic catalysis is possible by the species PH+ and its homo-conjugate PHP+153 162 182. 

Hirst s proposal for the fourth-order kinetics implies an electrophilic catalysis of the second step by the homoconjugate acid of the nucleophile, BH+B (where B stands for the nucleophile). The simplified equation would be... 

Direct coordination of a metal ion to the non-bridging oxygen might render the phosphorus center more susceptible to nucleophilic attack (electrophilic catalysis Fig. 3e) or, alternatively, hydrogen bonding between a metal-... 

Note how the key interaction boosting the catalytic effect is the protonation of the carbonyl group on the TG. Such catalyst-substrate interaction increases the electrophilicity of the adjacent carbonyl carbon atom, making it more susceptible to nucleophilic attack. Compare this to the base-catalyzed mechanism where the base catalyst takes on a more direct route to activate the reaction, creating first an alkoxide ion that directly acts as a strong nucleophile (Figure 4). Ultimately, it is this crucial difference, i.e., the formation of a more electrophilic species (acid catalysis) v.s. that of a stronger nucleophile (base catalysis), that is responsible for the differences in catalytic activity. 

Calixcrown 5, featuring two diethylaminomethyl side-arms at the polyether bridge, testifies an attempt at a higher order multifunctional catalysis of ester cleavage, namely, from nucleophilic-electrophilic to nucleophilic-electrophilic-general acid catalysis [20]. 

In (65) only electrophilic catalysis of the scission of the S-S bond is involved, a situation also encountered in the acid-catalyzed hydrolysis in weekly nucleophilic media (acetic acid-1% water) of certain aryl sulfinyl sulfones substituted with electron-donating substituents (66)164, viz. 

Nucleophilic catalysis is a specific example of covalent catalysis the substrate is transiently modified by formation of a covalent bond with the catalyst to give a reactive intermediate. There are also many examples of electrophilic catalysis by covalent modification. It will be seen later that in the reactions of pyridoxal phosphate, Schiff base formation, and thiamine pyrophosphate, electrons are stabilized by delocalization. 

Effective concentration 65-72 entropy and 68-72 in general-acid-base catalysis 66 in nucleophilic catalysis 66 Elastase 26-30, 40 acylenzyme 27, 40 binding energies of subsites 356, 357 binding site 26-30 kinetic constants for peptide hydrolysis 357 specificity 27 Electrophiles 276 Electrophilic catalysis 61 metal ions 74-77 pyridoxal phosphate 79-82 Schiff bases 77-82 thiamine pyrophosphate 82-84 Electrostatic catalysis 61, 73, 74,498 Electrostatic effects on enzyme-substrate association rates 159-161... 

General-Base and General-Acid Catalysis Avoids the Need for Extremely High or Low pH Electrostatic Interactions Can Promote the Formation of the Transition State Enzymatic Functional Groups Provide Nucleophilic and Electrophilic Catalysis Structural Flexibility Can Increase the Specificity of Enzymes... 

In this Chapter are described the possible mechanisms of electrophilic substitution at saturated carbon, as a preliminary to the discussion of the kinetics of substitution. Additionally, there is a description of the nomenclature that has been used to date. There has been no general agreement on the nomenclature of the mechanisms of electrophilic substitution at saturated carbon, and the notation used in subsequent chapters in the present work can thus usefully be enumerated here. We deal first of all with the fundamental mechanisms, that is with mechanisms that do not involve rearrangement or nucleophilic (anionic) catalysis. 

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