Subject nucleophilic addition, substitution

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. ... 

The stereochemical outcome of nucleophilic addition reactions to cyclic ketones is the subject of numerous experimental and theoretical studies, with substituted cyclohexanones and cy-clopcntanones having been intensively studied. In addition reactions to substituted cyclohexanones 1 the problem of simple diastereoselectivity is manifested in the predominance of cither axial attack of a nucleophile, leading to the equatorial alcohol 2 A. or equatorial attack of the nucleophile which leads to the axial alcohol 2B. 

Compared with the variety of existing carbon or nitrogen nucleophiles that were subjected to nucleophilic addition to there are few examples for phosphorus nucleophiles. Neutral trialkylphosphines turn out to be to less reactive for an effective addihon to Cjq even at elevated temperatures [114], Trialkylphosphine oxides show an increased reactivity. They form stable fullerene-substituted phosphine oxides [115] it is not yet clear if the reaction proceeds via a nucleophilic mechanism or a cycloaddition mechanism. Phosphine oxide addition takes place in refluxing toluene [115], At room temperature the charge-transfer complexes of with phosphine oxides such as tri-n-octylphosphine oxide or tri-n-butylphosphine oxide are verifiable and stable in soluhon [116],... 

Compounds with a low HOMO and LUMO (Figure 5.5b) tend to be stable to selfreaction but are chemically reactive as Lewis acids and electrophiles. The lower the LUMO, the more reactive. Carbocations, with LUMO near a, are the most powerful acids and electrophiles, followed by boranes and some metal cations. Where the LUMO is the a of an H—X bond, the compound will be a Lowry-Bronsted acid (proton donor). A Lowry-Bronsted acid is a special case of a Lewis acid. Where the LUMO is the cr of a C—X bond, the compound will tend to be subject to nucleophilic substitution. Alkyl halides and other carbon compounds with good leaving groups are examples of this group. Where the LUMO is the n of a C=X bond, the compound will tend to be subject to nucleophilic addition. Carbonyls, imines, and nitriles exemplify this group. 

Substituted 1,2,3-triazole 1-oxides 448 have been reported to undergo electrophilic and nucleophilic aromatic substitution and are subject to debromination, proton-metal exchange, and halogen-metal exchange followed by electrophilic addition. Transmetallation and cross-coupling have not been described. 3-Substituted 1,2,3-triazole 1-oxides 448 can be proton-ated or alkylated at the O-atom and they can be deoxygenated and deal-kylated. The individual reactions are described in Section 4.2.7.1-4.2.7.14. 

Oxazolidines 288 are subject to ring-chain tautomerism. The process can be considered as a reversible intramolecular nucleophilic addition to the C=N bond. A variety of substituted oxazolidines exist in the open-chain form 289 in the solid state <1985T5919, 1992T4979>. In solution, the two forms are in equilibrium, the position of which depends on the solvent and the substituents. 

The nucleophilic reactivity of dithiocarbamate anions has been the subject of a variety of papers, describing the reactions of alkali-metal dithiocarbamate salts with the common organic solvents methylene chloride, chloroform, and acetonitrile, with alkyl halides, a-halogeno-ketones and -aldehydes, chloroacetates, chloro-substituted j-triazines, phthaloyl chloride, oxalyl chloride, and with AW-dimethyl-5 S -dimethyldithiocarbamidium perchlorate. The nucleophilic addition reaction of dialkylammonium NN-dialkyldithiocarbamates with olefins, yielding alkyl dithiocarbamates, has also been described. ... 

In spite of the faet that the nucleophilic aromatic substitution in electron-deficient aromatic rings (SNAr) is one of the most venerable organic reactions, it is still a subject of debate. The generally accepted meehanism for this reaction is the classical addition-elimination sequence that involves the formation of a Meisenhei-mer-type intermediate 1 (Scheme 33.1). 

Aldol addition and related reactions of enolates and enolate equivalents are the subject of the first part of Chapter 2. These reactions provide powerful methods for controlling the stereochemistry in reactions that form hydroxyl- and methyl-substituted structures, such as those found in many antibiotics. We will see how the choice of the nucleophile, the other reagents (such as Lewis acids), and adjustment of reaction conditions can be used to control stereochemistry. We discuss the role of open, cyclic, and chelated transition structures in determining stereochemistry, and will also see how chiral auxiliaries and chiral catalysts can control the enantiose-lectivity of these reactions. Intramolecular aldol reactions, including the Robinson annulation are discussed. Other reactions included in Chapter 2 include Mannich, carbon acylation, and olefination reactions. The reactivity of other carbon nucleophiles including phosphonium ylides, phosphonate carbanions, sulfone anions, sulfonium ylides, and sulfoxonium ylides are also considered. 

A diverse group of organic reactions catalyzed by montmorillonite has been described and some reviews on this subject have been published.19 Examples of those transformations include addition reactions, such as Michael addition of thiols to y./bunsatu rated carbonyl compounds 20 electrophilic aromatic substitutions,19c nucleophilic substitution of alcohols,21 acetal synthesis196 22 and deprotection,23 cyclizations,19b c isomerizations, and rearrangements.196 24... 

Some derivatives of the [l,2,4]triazolo[4,3-3]pyridazine ring system 33 were subjected to a special type of nucleophilic substitution called vicarious nucleophilic substitution (VSN) <2006TL4259>. In the course of this transformation a formal substitution of az aromatic hydrogen atom - occurring via an addition-elimination mechanism - takes place. 

Allene is a versatile functionality because it is useful as either a nucleophile or an electrophile and also as a substrate for cycloaddition reactions. This multi-reactivity makes an allene an excellent candidate for a synthetic manipulations. In addition to these abilities, the orthogonality of 1,3-substitution on the cumulated double bonds of allenes enables the molecule to exist in two enantiomeric configurations and reactions using either antipode can result in the transfer of chirality to the respective products. Therefore, the development of synthetic methodology for chiral allenes is one of the most valuable subjects for the synthetic organic chemist. This chapter serves as an introduction to recent progress in the enantioselective syntheses of allenes. Several of the earlier examples are presented in excellent previous reviews [ ] ... 

Azide ion is a modest leaving group in An + Dn nucleophilic substitution reactions, and at the same time a potent nucleophile for addition to the carbocation reaction intermediate. Consequently, ring-substituted benzaldehyde g m-diazides (X-2-N3) undergo solvolysis in water in reactions that are subject to strong common-ion inhibition by added azide ion from reversible trapping of an o -azido carbocation intermediate (X-2 ) by diffusion controlled addition of azide anion (Scheme... 

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