Reactions, with nucleophiles

For reasons not yet completely understood, only soft nucleophiles react well with alkynyliodonium salts. Hard nucleophiles such as alkyllithium, alkoxides, simple enolates, etc., give only decomposition products. A possible explanation for this observation might be that hard nucleophiles either attack directly on the iodine or undergo electron transfer pro- 

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The most characteristic feature of the Pd—C bonds in these intermediates of both the stoichiometric and catalytic reactions is their reaction with nucleophiles, and Pd(0) is generated by accepting two electrons from the nucleophiles as exemplified for the first time by the reactions of 7r-allylpalladium chloride[2] or PdCl2-COD[3] complex with malonate and acetoacetate. It should be noted... 

TT-Aliylpalladium chloride reacts with a soft carbon nucleophile such as mal-onate and acetoacetate in DMSO as a coordinating solvent, and facile carbon-carbon bond formation takes place[l2,265], This reaction constitutes the basis of both stoichiometric and catalytic 7r-allylpalladium chemistry. Depending on the way in which 7r-allylpalladium complexes are prepared, the reaction becomes stoichiometric or catalytic. Preparation of the 7r-allylpalladium complexes 298 by the oxidative addition of Pd(0) to various allylic compounds (esters, carbonates etc.), and their reactions with nucleophiles, are catalytic, because Pd(0) is regenerated after the reaction with the nucleophile, and reacts again with allylic compounds. These catalytic reactions are treated in Chapter 4, Section 2. On the other hand, the preparation of the 7r-allyl complexes 299 from alkenes requires Pd(II) salts. The subsequent reaction with the nucleophile forms Pd(0). The whole process consumes Pd(ll), and ends as a stoichiometric process, because the in situ reoxidation of Pd(0) is hardly attainable. These stoichiometric reactions are treated in this section. 

There are three general reactions of perfluoroepoxid.es pyrolyses (thermal reactions), electrophilic reactions, and by far the most important, reactions with nucleophiles and bases. 

Chemical Properties. The presence of both a carbocycHc and a heterocycHc ring faciUtates a broad range of chemical reactions for (1) and (2). Quaternary alkylation on nitrogen takes place readily, but unlike pyridine both quinoline and isoquinoline show addition by subsequent reaction with nucleophiles. Nucleophilic substitution is promoted by the heterocycHc nitrogen. ElectrophiHc substitution takes place much more easily than in pyridine, and the substituents are generally located in the carbocycHc ring. 

Sulfates. The chemistry of alkyl sulfates is dominated by two fundamental process types reaction with nucleophiles and reaction as acids. Reaction with nucleophiles results in alkylation. 

Relatively little work has been carried out on NMR spectra of jjyridopyrazines, but some have been utilized during studies of the covalent hydration (q.v.) of both parent bases (66JCS(C)999, 75AG356, 79JHC301) and their reaction with nucleophiles (79JHC305). 

Halogenomethyl, hydroxymethyl and aminomethyl groups readily undergo displacement reactions with nucleophilic reagents. Both side-chain and nuclear substitution products have been obtained (Scheme 57). These two possibilities are exemplified by the reaction of furfuryl chloride with sodium cyanide (Scheme 58). 

Aminomethylindoles are particularly important synthetic intermediates. 3-Dimethyl-aminomethylindole (gramine) (153) and especially its quaternary salts readily undergo displacement reactions with nucleophiles (Scheme 60). Indole-2,3-quinodimethanes, generated from 2-methylgramine as shown in Scheme 61, undergo intermolecular cycloaddition reactions with dienophiles to yield carbazole derivatives (82T2745). 

Methyl-3,4-dinitropyrrole (170) undergoes some interesting reactions with nucleophilic reagents. With methanolic sodium methoxide it yields a product (171) which on treatment with trifluoroacetic acid gives the 2-methoxypyrrole (172) 78CC564). 

Unsubstituted 2,1-benzisoxazoles undergo C(3)-proton abstraction with base to give an intermediate iminoketene which can undergo further reaction with nucleophiles. However, alternative Michael addition pathways are possible and these have been discussed (81AHC(29)l,p.56). 

When 6-diazopenicillanates are irradiated in the presence of sulfur nucleophiles, predominantly 6/3-substitution products are obtained (77JOC2224). When BFs-EtiO is used to catalyze the reaction with nucleophiles, however, the products are primarily the 6a-isomers (78TL995). The use of rhodium or copper catalysis led primarily to ring-opened thiazepine products, presumably by way of the intermediate (56 Scheme 39) (80CC798). 

The LUMO, which is the frontier orbital in reactions with nucleophiles, has a larger coefficient on the /3-carbon atom, whereas the two occupied orbitals are distorted in such a way as to have larger coefficients on oxygen. The overall effect is that the LUMO is relatively low-lying and has a high coefficient on the /3-carbon atom. The frontier orbital theory therefore predicts that nucleophiles will react preferentially at the /3-carbon atom. 

Sulfonates react with a variety of nucleophiles. Synthesis of M A -bis(trifluoro-methyl)aminotnfluoromethanesulfonate and its reactions with nucleophiles were investigated [33] (equation 31) (Table 13). Nucleophilic attack occurs at either nitrogen or sulfur amines give complex mixtures [33]. Polyfluoroalkyl fluorosul-fates react with amines, alcohols, or alkoxides to yield polyfluoroalkyl sulfamates and dialkyl sulfates, respectively [34] (equation 32) (Table 13). In these reactions. 

The most common types of aryl halides in nucleophilic aromatic substitutions are those that bear- o- or p-nitro substituents. Among other classes of reactive aryl halides, a few merit special consideration. One class includes highly fluorinated aromatic compounds such as hexafluorobenzene, which undergoes substitution of one of its fluorines on reaction with nucleophiles such as sodium methoxide. 

The reactions of NSF3 have been investigated in considerable detail. They can be classified under the following categories (a) reactions with electrophiles (b) addition to the SN triple bond and (c) reactions with nucleophiles. Some examples of these different types of behaviour are discussed below. 

The presence of iminium salts can be detected by chemical means or by spectroscopic methods. The chemical means of detecting iminium salts are reactions with nucleophiles and are the subject of this review. The spectroscopic methods are more useful for rapid identification because with the large number of model compounds available now the spectroscopic methods are fast and reliable. The two methods that are used primarily are infrared and nuclear magnetic resonance spectroscopy. Some attempts have been made to determine the presence of iminium salts by ultraviolet spectroscopy, but these are not definitive as yet (14,25). 

The reactions with nucleophiles include a wide variety such as amines, sulfides (133,135), diazomethane (111), and others. Of particular interest were the reactions of such intermediate iminium salts with 2,3-dimethyl-butadiene to give cyclic products as shown in the reaction of N-bromo-methylpiperidine and N-bromo- and N-chloromethyldiethylamine (134). 

Cyanoallene, when treated with the morpholine enamine of cyclohexanone, undergoes a 1,3-cycloaddition reaction to form 72 (89). The reaction between cyanoallene and diendiamine 73a produces di-1,2-cycloaddition adduct 73 (i 9). The 4a-azonioanthracene ion (73b) readily undergoes a 1,4-cycloaddition reaction with nucleophilic dienophiles such as enamines (89a). The cycloaddition is stereoselective so that the a- and... 

This approach to carbonyl protection uses the relative differences in basicity and the differences in steric effects to protect selectively either the more basic carbonyl group or the less hindered carbonyl group from reactions with nucleophiles such as DIB AH and MeLi. ... 

Cycloadditions of oxa-aromatics and their reactions with nucleophiles 96AHC(65)283. 

D. Reactions with Nucleophiles and Reducing Agents 1. Deoxygenation... 

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