Nucleophilic Addition and Substitution

The iV-oxide function enhances the rate of nucleophilic displacement of halogen from a- and y-positions. The relative rates 4 2 3 found for pyridines are echoed for the A-oxides (but signihcantly are 2 4 3 in pyridinium salts). 

The direct introduction of an acetylide moiety, using pyridine A-oxide (or quinoline, diazine and triazine iV-oxides) can be achieved in a comparable way, by reaction with potassium phenylacetylide reaction with the lithium salt requires addition of acetyl chloride at the end of the reaction to aromatise. At low temperature, and using i-PrMgCl, 2-metallation of pyridine iV-oxides can be achieved, and thus, the introduction of electrophiles at the 2-position.  

As in the previous volume, this chapter reviews kinetic and mechanistic studies of the stoichiometric reactions of coordinated hydrocarbons with nucleophiles and electrophiles, together with some related processes such as cycloadditions. Nucleophilic addition and substitution, in particular, continue to attract considerable interest, especially with dienyl- and arene-metal substrates. Even here, however, quantitative studies still lag far behind the extensive synthetic literature. However, fundamental reactivity patterns and parameters are beginning to emerge from the mechanistic studies which should assist in the design of rational syntheses. 

Related catalytic processes are discussed elsewhere (Chapter 14), as are intramolecular ligand rearrangements (Chapter 13). 

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Chiral oxazolines developed by Albert I. Meyers and coworkers have been employed as activating groups and/or chiral auxiliaries in nucleophilic addition and substitution reactions that lead to the asymmetric construction of carbon-carbon bonds. For example, metalation of chiral oxazoline 1 followed by alkylation and hydrolysis affords enantioenriched carboxylic acid 2. Enantioenriched dihydronaphthalenes are produced via addition of alkyllithium reagents to 1-naphthyloxazoline 3 followed by alkylation of the resulting anion with an alkyl halide to give 4, which is subjected to reductive cleavage of the oxazoline moiety to yield aldehyde 5. Chiral oxazolines have also found numerous applications as ligands in asymmetric catalysis these applications have been recently reviewed, and are not discussed in this chapter. ... 

Carbonyl condensation reactions take place between two carbonyl partners and involve a combination of nucleophilic addition and -substitution steps. One partner is converted into an enolate-ion nucleophile and adds to the... 

Other types of reactions have been studied as, for example, a mixture of nucleophilic addition and substitution reactions.3296-3298 An interesting reaction due to the potential catalytic applications is the reversible addition of H2 to [Pt(AuPPh3)8]2+ to give the 18-electron dihydrido cluster [Pt(H)2(AuPPh3)8]2+.3299,3300 In nonbasic solvents the dihydrido cluster is stable and upon removal of the H2 atmosphere, it rapidly loses H2 to reform [Pt(AuPPh3kl2+. These reactions are completely reversible in pyridine solutions as shown in Equation (50) 3... 

Chiral oxazolines employed as activating groups and/or chiral auxiliaries in nucleophilic addition and substitution reactions that lead to the asymmetric construction of carbon-carbon bonds. 

Other reactions for which a discussion of their structure-reactivity behavior in terms of the PNS has provided valuable insights include nucleophilic addition and substitution reactions on electrophilic alkenes, vinylic compounds, and Fischer carbene complexes reactions involving carbocations and some radical reactions. 

In recent years, particular attention focuses on reactivity of nitrobenzofuroxans and nitrobenzofurazans [531], The latest are represented as a class of neutral 10-ii-elec-tron-deficient heteroaromatic substrates that exhibit an extremely high electrophilic character in many covalent nucleophilic addition and substitution processes. 

Scheme 5. Enamine catalysis of nucleophilic addition- and substitution reactions (arrows may be considered equilibria)...

Here are a few reminders for drawing the mechanisms of nucleophilic addition and substitution reactions. (1) When a reaction is acid-catalyzed, none of the intermediates are negatively charged, although, occasionally, a few may be neutral. Check your mechanisms for charge balance. (2) Make sure you have drawn arrows correctly. The point of the arrow shows the new location of the electron pair at the base of the arrow. (3) In a polar reaction, two arrows never point at each other. If you find two arrows pointing at each other, redraw the mechanism. 

We begin with reduction, because the mechanisms of reduction reactions follow directly from the general mechanisms for nucleophilic addition and substitution. 

Electrophilic substitution Nucleophilic addition and substitution Nucleophilic displacement of nitro groups Jackson-Meisenheimer reaction and complexes Practical significance and application of Jackson-Meisenheimer reaction Reaction potential map(RPM)... 

Jackson-Meisenheimcr reaction and Janovsky reaction 103 ( /207) mycellar nucleophilic reactions 102 nucleophilic addition and substitution 97-98(1/197)... 

A carbonyl condensation reaction takes place between two carbonyl partners and involves both nucleophilic addition and ( -substitution steps. One carbonyl partner (the donor) is converted by base into a nucleophilic enolate ion, which adds to the electrophilic carbonyl group of the second partner (the acceptor). The donor molecule undergoes an a substitution, while the acceptor molecule undergoes a nucleophilic addition. 

The chemistry of fluorinated olefins is dominated by nucleophilic addition and substitution reactions (Section 2.1.4). Depending on the acidity or basicity of the reaction medium, after a primary addition step the resulting anion is either quenched by protonation or by -elimination of fluoride (Scheme 2.187). 

The smaller TON (calculated for ethylbenzene oxidation) and the lower conversion in ethanol is due to the oxidation of the solvent itself, as already reported [18]. The main product of ethanol oxidation is diethylacetal formed by initial oxidation of the alcohol to acetaldehyde and further nucleophilic addition and substitution with other alcohol molecules. Some amount of acetic acid and acetaldehyde are also observed in the reaction mixture. However, the... 

The generation of metallated aromatics has become extremely important for the introduction of substituents, especially carbon substituents, by subsequent reaction with an electrophile. It is very important, in the light of the discussion above on the ease of nucleophilic addition and substitution, to realise that iodine and bromine at all positions of a pyridine can be exchanged at low temperature without nucleophilic displacement or addition, with formation of the pyridyllithium. 

Whereas pyrroles are resistant to nucleophilic addition and substitution, they are very susceptible to attack by electrophilic reagents and react almost exclusively by substitution. Pyrrole itself, N- and C-monoalkyl and to a lesser extent C, C -dialkylpyrroles, are polymerised by strong acids so that many of the electrophilic... 

Table 1. Nucleophilic Addition and Substitution Reaction Patterns.

Indole is a ti-excessive heterocyclic ring system and, as such, it is more likely to act as a nucleophile than as an electrophile. Despite this tendency, there are numerous examples of nucleophilic additions and substitutions on indoles, including a few... 

The coordination of transition metal moieties to arenes alters the reactivity of the aromatic ring, making it more susceptible to nucleophilic addition and substitution reactions and also making substituents on the arene more readily deprotonated. Some of the first examples of polymers containing arenes n-coordinated to transition... 

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