Reactions of Other Nucleophiles

In the preceding chapters we have dealt with a variety of nucleophilic species which have been utilized under phase transfer catalytic conditions. In each of these chapters, we believe that enough information has been accumulated or the chemistry is individual enough to justify this approach. There are, however, a number of cases in which the reactivity is more or less that which might have been anticipated or there are relatively few examples of the process. We have, of necessity, combined them in this chapter in the hope that the information will thereby be available. 

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Contents Introduction and Principles. - The Reaction of Dichlorocarbene With Olefins. - Reactions of Dichlorocarbene With Non-Olefinic Substrates. -Dibromocarbene and Other Carbenes. - Synthesis of Ethers. - Synthesis of Esters. - Reactions of Cyanide Ion. - Reactions of Superoxide Ions. - Reactions of Other Nucleophiles. - Alkylation Reactions. - Oxidation Reactions. - Reduction Techniques. - Preparation and Reactions of Sulfur Containing Substrates. -Ylids. - Altered Reactivity. - Addendum Recent Developments in Phase Transfer Catalysis. 

The reaction of other nucleophiles such as amines 123,124), hydroxyl-amines, various carbanions, and hydroxide 120) have been tried but not examined in detail. Hydrolysis of iminium salts is covered elsewhere 123). 

In a solution that contains both an aldehyde and its enolate ion, the enolate undergoes nucleophilic addition to the carbonyl group. This addition is analogous to the addition reactions of other nucleophilic reagents to aldehydes and ketones described in Chapter 17. 

Piperidine, which is common to the three series, serves as the standard. Comparison of the Tois piperidine ratios show a very large variation, which is not reflected to the same extent in reactions of other nucleophiles. For most other systems studied (31, 36), these ratios are very appreciable. Moreover, PhO- appears in a different relative position in the second and the third series. 

The obvious extension of this work to hexabromobenzene has been investigated, where it is found that the SMe anion will not react . Study of the reactions of other nucleophiles with hexabromobenzene leads to photodebromination and some nucleophilic substitution . Pentabromo-benzenethiol has recently been prepared from the pentabromophenyl Grignard reagent and sulphur . 

These reaction conditions were also applied to the domino Michael/cyclisation reactions of other nucleophiles, such as 4-hydroxy-6-methyl-2-pyrone 43, 4-hydroxycoumarin 44, and 3-hydroxyperinaphthenone 45, as shown in Scheme l. hlF By reaction with variously substituted l-(alk-2-enoyl)-4-bromo-3,5-dimethylpyrazoles, these compounds afforded the corresponding chiral domino products 46a-c, 46d-h, and 47, respectively. These products arose from domino Michael/cyclisation reactions and were obtained in moderate to good yields and with good to high enantioselectivities of up to 98% ee. 

Generally, isolated olefinic bonds will not escape attack by these reagents. However, in certain cases where the rate of hydroxyl oxidation is relatively fast, as with allylic alcohols, an isolated double bond will survive. Thepresence of other nucleophilic centers in the molecule, such as primary and secondary amines, sulfides, enol ethers and activated aromatic systems, will generate undesirable side reactions, but aldehydes, esters, ethers, ketals and acetals are generally stable under neutral or basic conditions. Halogenation of the product ketone can become but is not always a problem when base is not included in the reaction mixture. The generated acid can promote formation of an enol which in turn may compete favorably with the alcohol for the oxidant. 

The reaction of a large number of other nucleophiles with iminium salts will at least be mentioned in this section. Among the nucleophiles which react with iminium salts are cyanide 48,115-119), mercaptide 48), alkoxide 48), amine 120), azide 44), phosphine 44), and phosphate ester 44). One can say with little reservation that almost all nucleophiles will react... 

Reactions with other nucleophiles follow a similar mechanism. For the reaction of Cl with poly(3-methylthiophene) in acetonitrile, the reaction stops at structure 5 (Scheme 2).128 A fully conjugated, Cl-substi-tuted product 6 can subsequently be obtained by electrochemical or chemical dehydrogenation.128 With Br and alcohols, the overoxidation... 

Nucleophilic reactivity toward Pt(II) complexes may be conveniently systematized via linear free energy relationships established between reactions of trans Ptpy2Cl2 (py = pyridine) with various nucleophiles and reactions of other Pt(II) complexes with the same nucleophiles. First, each nucleophile is characterized by a nucleophilicity parameter, derived from its reactivity toward the common substrate, trans Ptpy2Cl2. Reactivity toward other Pt(II) substrates is then quite satisfactorily represented by an equation of the form (21), wherein ky is the value of in the reaction with nucleophile Y... 

It is intriguing to note that this reaction scheme for the reduction of a sulphone to a sulphide leads to the same reaction stoichiometry as proposed originally by Bordwell in 1951. Which of the three reaction pathways predominates will depend on the relative activation barriers for each process in any given molecule. All are known. Process (1) is preferred in somewhat strained cyclic sulphones (equations 22 and 24), process (2) occurs in the strained naphtho[l, 8-hc]thiete 1,1-dioxide, 2, cleavage of which leads to a reasonably stabilized aryl carbanion (equation 29) and process (3) occurs in unstrained sulphones, as outlined in equations (26) to (28). Examples of other nucleophiles attacking strained sulphones are in fact known. For instance, the very strained sulphone, 2, is cleaved by hydride from LAH, by methyllithium in ether at 20°, by sodium hydroxide in refluxing aqueous dioxane, and by lithium anilide in ether/THF at room temperature. In each case, the product resulted from a nucleophilic attack at the sulphonyl sulphur atom. Other examples of this process include the attack of hydroxide ion on highly strained thiirene S, S-dioxides , and an attack on norbornadienyl sulphone by methyllithium in ice-cold THF . ... 

Entries 4 and 5 involve formation of ethers using alcohols as solvents, whereas the reaction in Entry 6 forms an amide in acetonitrile. Entries 7 and 8 show use of other nucleophiles to capture the mercurinium ion. 

Introduction of Other Nucleophiles Using Diazonium Ion Intermediates. Cyano and azido groups are also readily introduced via diazonium intermediates. The former involves a copper-catalyzed reaction analogous to the Sandmeyer reaction. Reaction of diazonium salts with azide ion gives adducts that smoothly decompose to nitrogen and the aryl azide.56... 

The cleavage of epoxides by water is a classical reaction. Such epoxide cleavage can be catalyzed by both acids and bases in aqueous media. In the presence of other nucleophiles, the corresponding nucleophilic ringopening products are obtained with the nucleophiles being incorporated into the products.68 Examples include azides, iodides, and thiols in the presence or absence of metal salts in aqueous media. The pH of the reaction medium controls the reactivity and regioselectivity of the... 

The reaction with carboxylates occurs over a range of pH values, but is optimal at pH 5.0. Unfortunately, the diazoalkyl compounds will cross-react with sulfhydryl groups at this pH. At higher pH conditions, the reaction is even less specific due to reaction with other nucleophiles. In aqueous solution, the most-likely side reaction is hydrolysis. 

Hydrosilanes react with butadiene by the catalysis of palladium compounds, but the nature of the reaction is somewhat different from that of the telomerization of other nucleophiles described before. Different products are obtained depending on both the structure of silanes and the reaction conditions. Trimethylsilane and other trialkylsilanes reacted with butadiene to give the 1 2 adduct, l-trialkylsilyl-2,6-octadienes (65), in high yield (98%) (62-64). Unlike other telomers which have the 1,6-octadienyl chain, the telomers of silanes have the 2,6-octadienyl chain. As catalysts, Pd(PPh3)2 (maleic anhydride), PdCl2(PhCN)2, PdCl2, and 7r-allylpalladium chloride were used. Methyldiethoxysilane behaved similarly to give the 1 2 adduct. 

An impressive body of evidence supports these generalizations. This evidence has been reviewed (Romsted, 1984) and it does not seem necessary to discuss it in detail here, but some examples will be given and some exceptions to these generalizations will be mentioned. Some reactions of OH- are shown in Table 3 for both inert and reactive ion surfactants, and Table 4 gives data for reactions of other hydrophilic ions. Reactions of hydrophobic nucleophiles are shown in Table 2. For all these reactions second-order rate constants in the micellar pseudophase are compared with those in water. For some reactions we also give values of krcl, i.e. the rate constant relative to that in water. These values depend upon the reactant concentration and are included merely to provide an indication of the micellar rate effects. Other examples of micellar rate effects are given in the Appendix. 

It is more difficult to interpret micellar effects upon reactions of azide ion. The behavior is normal , in the sense that k /kw 1, for deacylation, an Sn2 reaction, and addition to a carbocation (Table 4) (Cuenca, 1985). But the micellar reaction is much faster for nucleophilic aromatic substitution. Values of k /kw depend upon the substrate and are slightly larger when both N 3 and an inert counterion are present, but the trends are the same. We have no explanation for these results, although there seems to be a relation between the anomalous behavior of the azide ion in micellar reactions of aromatic substrates and its nucleophilicity in water and similar polar, hydroxylic solvents. Azide is a very powerful nucleophile towards carboca-tions, based on Ritchie s N+ scale, but in water it is much less reactive towards 2,4-dinitrohalobenzenes than predicted, whereas the reactivity of other nucleophiles fits the N+ scale (Ritchie and Sawada, 1977). Therefore the large values of k /kw may reflect the fact that azide ion is unusually unreactive in aromatic nucleophilic substitution in water, rather than that it is abnormally reactive in micelles. 

SOME UNUSUAL SULFINYL DERIVATIVES AND THEIR BEHAVIOR Reaction of a number of the nucleophiles in Table 6 with a sulfinyl sulfone (139) leads to substitution products ArS(0)Nu that are known from other studies to exhibit interesting and unusual chemical behavior of their own. These same sulfinyl derivatives can also be generated by reaction of the nucleophile with a sulfinyl chloride (142). Let us now discuss what is known about such compounds as sulfinyl azides, ArS(0)N3, sulfinyl hydrazides, ArS(0)NHNH2, etc. 

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