Nucleophilic addition Subject

In most reviews of enamine chemistry the reactions of iminium salts are scattered throughout the review and are consequently not covered in a comprehensive manner. This chapter will be an attempt to look at reactions that, at one stage or another, proceed by nucleophilic addition to the iminium intermediate. The subject of enamines has been reviewed 1-4) and certain aspects of iminium salt chemistry such as reduction of aromatic quaternary salts have been treated in detail (5). Consequently, the reduction of aromatic quaternary salts with complex hydrides will be presented here only briefly. Although the literature (especially 1950-1967) has been checked with care, the author can make no claim to completeness. The... 

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. 

The alkenylcopper adducts can be worked up by protonolysis, or they can be subjected to further elaboration by alkylation or nucleophilic addition. Some examples are given in Scheme 8.6. 

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],... 

The present review is intended to highlight the use of acetylenic esters in the synthesis of different heterocycles, primarily involving nucleophilic additions. The reactions of heterocyclic bases with acetylenic esters, however, will not be covered here, except in a few cases where it is more appropriate for inclusion here, depending on the type of reactions. The reactions of heterocyclic bases form the subject matter of a separate article. The survey covers the literature up to December 1973. 

Recall that the LUMO shows which regions of a molecule are most electron deficient, and hence most subject to nucleophilic attack. One such region is over the carbonyl carbon, consistent with the observation that carbonyl compounds undergo nucleophilic addition at the carbonyl carbon. Another region is over the P carbon, again consistent with the known chemistry of a,P-unsaturated carbonyl compounds, in this case conjugate or Michael addition. 

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. 

It seems obvious that electron-withdrawing groups enhance nucleophilic addition and inhibit electrophilic addition because they lower the electron density of the double bond. This is probably true, and yet similar reasoning does not always apply to a comparison between double and triple bonds.70 There is a higher concentration of electrons between the carbons of a triple bond than in a double bond, and yet triple bonds are less subject to electrophilic attack and more subject to nucleophilic attack than double bonds.71 This statement is not universally true, but it does hold in most cases. In compounds containing both double and triple bonds (nonconjugated), bromine, an electrophilic reagent, always adds... 

The first step in this multistage reaction is the nucleophilic addition of sulfone anion 28 to aldehyde 8 (Scheme 14.6). This produces a p-alkoxysulfone intermediate 29 which is trapped with acetic anhydride. The resulting P acetoxysulfone mixture 22 is then subjected to a reductive elimination with Na/Hg amalgam to obtain alkene 23. The tendency of Julia-Lythgoe-Kocienski olefinations to provide ( )-1,2-disubstituted alkenes can be rationalised if one assumes that an a-acyloxy anion is formed in the reduction step, and that this anion is sufficiently long-lived to allow the lowest energy conformation to be adopted. Clearly, this will... 

Transferring the results, obtained from the reactions of RSC1 with H20, from parachlorine to chlorine we get a suggestive mechanism which remains speculative till further results on this subject are available. One piece of support for this mechanism can already be provided. Kinetic studies on the reaction Cl2 + H20 — H+ + Cl" + HCIO show that the most probable first step is the nucleophilic addition of H20 at the electrophile atom in Cl2, forming the intermediate... 

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. 

Eberson and co-workers have recently discussed the probability that the interaction of ion-radicals with nucleophiles and electrophiles is subject to orbital symmetry constraints.31,32 This follows the observation that with perylene the cation-radical (18) the preferred course of reaction with halide ions is electron transfer rather than nucleophilic addition, whereas with the phenothiazine cation-radical (19) nucleophilic attack by Cl" and Br occurs. 

Nucleophilic additions to carbon-carbon triple bonds are also subject to solvent influence, as shown by the example given in Eq. (5-32) [88],... 

Vinyl sulphones (384) are subjected to nucleophilic addition by a-lithionitriles and give cyclopropanes (385) together with 3-oxothian-1,1-dioxides (386). The mechanism is given in equation 127 . It is remarkable that reaction of the sulphone with sodium... 

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