Nucleophiles dicarbonyl anions

The cyclopentadienyliron dicarbonyl anion was reacted with an optically active chlorosilane giving rise to an optically active iron complex58 (equation 8) which was isolated in 98% optical purity. On the basis of the known stereochemistry of nucleophilic displacement of chlorine nucleofuge, the reaction was assumed to occur with inversion of configuration at silicon. 

Reactions of thioketones with nucleophilic reagents have been studied to some extent. Thiobenzophenone (20) and its 4,4 -substituted derivatives react with cyclopentadienyliron dicarbonyl anion and cyclopentadienyl-molybdenum or -tungsten tricarbonyl anion at room temperature to give fulvenes. Phase-transfer catalysis conditions improve the yields. An electron-transfer mechanism has been proposed for this desulphurization and coupling reaction. An electron-transfer mechanism has also been proposed for the reduction of thiopivalophenone (54) by 1-benzyl-1,4-dihydronicotinamide in acetonitrile. 2,3-Diphenylcyclopropene-thione (55) reacts with 7V-methylarylamines to give the bicyclic thioamides (56). The formation of a thioketen as an intermediate has been suggested. A similar reaction scheme has also been proposed for the reaction of (55) with 3,4-dihydroisoquinoline. ... 

Treating pentacarbonyliron with dicyclopentadiene affords the dicarbonyl (ri -cyclopentadienyl)iron dimer [Cp(CO)2pe]2. Reduction of the latter with sodium amalgam provides the nucleophilic dicarbonyl(r -cyclopentadienyl)iron anion [Cp(CO)2Fe]. Allylic halides or tosylates can be reacted with this Fe(0) complex to afford ri -allyl-Fp-iron complexes (Fp = Fe(CO)2Cp, Scheme... 

The most general methods for the syntheses of 1,2-difunctional molecules are based on the oxidation of carbon-carbon multiple bonds (p. 117) and the opening of oxiranes by hetero atoms (p. 123fl.). There exist, however, also a few useful reactions in which an a - and a d -synthon or two r -synthons are combined. The classical polar reaction is the addition of cyanide anion to carbonyl groups, which leads to a-hydroxynitriles (cyanohydrins). It is used, for example, in Strecker s synthesis of amino acids and in the homologization of monosaccharides. The ff-hydroxy group of a nitrile can be easily substituted by various nucleophiles, the nitrile can be solvolyzed or reduced. Therefore a large variety of terminal difunctional molecules with one additional carbon atom can be made. Equally versatile are a-methylsulfinyl ketones (H.G. Hauthal, 1971 T. Durst, 1979 O. DeLucchi, 1991), which are available from acid chlorides or esters and the dimsyl anion. Carbanions of these compounds can also be used for the synthesis of 1,4-dicarbonyl compounds (p. 65f.). 

In addition, Hashida et al. (1971 a) found a linear correlation between log k and the pof fifteen 1,3-dicarbonyl compounds. This indicates that in these cases the nucleophilicity and the basicity of the anions are closely related. The same result was obtained by Hashida et al. (1971b) for the azo coupling reactivity of substituted phenoxide ions. 

Hydroxycoumarin can be considered as an enol tautomer of a 1,3-dicarbonyl compound conjugation with the aromatic ring favours the enol tautomer. This now exposes its potential as a nucleophile. Whilst we may begin to consider enolate anion chemistry, no strong base is required and we may formulate a mechanism in which the enol acts as the nucleophile, in a simple aldol reaction with formaldehyde. Dehydration follows and produces an unsaturated ketone, which then becomes the electrophile in a Michael reaction (see Section 10.10). The nucleophile is a second molecule of 4-hydroxycoumarin. 

Stetter expanded Umpolung reactivity to include the addition of acyl anion equivalents to a,P-unsaturated acceptors to afford 1,4-dicarbonyls Eq. 5a [57-60]. Utilizing cyanide or thiazolylidene carbenes as catalysts, Stetter showed that a variety of aromatic and aliphatic aldehydes act as competent nucleophilic coupling partners with a wide range of a,p-unsaturated ketones, esters, and nitriles [61]. The ability to bring two different electrophilic partners... 

Compounds whose structures are similar to (3-dicarbonyl compounds also have active hydrogens. These compounds have a CH2 sandwiched between two electron-withdrawing groups, some examples of which are in Figure 15-21. The loss of a hydrogen ion from the sandwiched carbon leaves an anion, which can then behave as a nucleophile similar to other nucleophiles seen in this chapter. 

Alternatively, an anion stabilizing group alpha to the carbonyl group of the cyclo-butanone provides a pathway for cleavage by attack of a nucleophile on the cyclo-butanone carbonyl carbon. C-Acylation creates the familiar 1,3-dicarbonyl system which, by deacylation involving attack at the cyclobutanone carbonyl group, leads to a geminal alkylation as shown in Eq. 115 b 47,79). 

They are, however, reactive carbon nucleophiles. Examples of enolates include anionic derivatives of aldehydes, ketones, acid derivatives, and dicarbonyl compounds. 

When stabilized (and consequently less reactive) anions are employed as the nucleophile, more reactive electrophiles are needed for successful carbon-carbon bond formation. Nitronate anions, which are highly resonance stabilized, fail to react widi simple alkyl hahde electrophiles. On the other hand, /3-dicarbonyl compounds react effectively with primary and some secondary alkyl bromides and iodides to give monoalkylated products. 

In contrast, 1,2-dicarbonyl compounds or 1,4-dicarbonyl compounds are more difficult to disconnect by valid retrosynthetic steps. Consider a 1,2-diketone. Disconnection of die bond between die carbonyl groups requires that one of the carbonyl groups has the normal electrophilic character, but die other carbonyl carbon must have nucleophilic character (an acyl anion or its equivalent), which is not die normal polarity of a carbonyl group. 

It is not usually possible to form mixed JVO-donor ligands by direct reaction of co-ordinated 1,3-diketonates with amines. In part, this is due to the delocalised charge of the formally anionic ligand rendering the diketonate less prone to attack by a nucleophile. This deactivation towards attack by nucleophiles should be contrasted with the facile reactions with electrophiles which have been discussed in Section 5.3. It is possible, however, to form complexes of conjugated /VO-donor ligands by direct reaction of the metal-free, 1,3-dicarbonyl with amine, followed by co-ordination (Fig. 5-48). 

Alkynyl(phenyl)iodonium salts can be used for the preparation of substituted alkynes by the reaction with carbon nucleophiles. The parent ethynyliodonium tetrafluoroborate 124 reacts with various enolates of /J-dicarbonyl compounds 123 to give the respective alkynylated products 125 in a high yield (Scheme 51) [109]. The anion of nitrocyclohexane can also be ethynylated under these conditions. A similar alkynylation of 2-methyl-1,3-cyclopentanedione by ethynyliodonium salt 124 was applied in the key step of the synthesis of chiral methylene lactones [110]. 

When the pentamer (66) reacts with alkoxide anions at low temperatures (-30 to -40°C), then the products of kinetic control (102) are isolated, whereas at higher temperatures, thermodynamic control prevails and the products (103) are obtained [131,132] (Scheme 68). Similar observations have been made with sulphur nucleophiles [132], and complex products are obtained with amines, including the formation of heterocycles [132]. Reaction of (66) with ethyl acetoacetate gave a pyran derivative (104) in a reaction that may be rationalised as shown in Scheme 69 [133]. In an analogous way.furan derivatives are formed from perfluoro-2-butene and -cyclohexene in base-induced reaction with 1,3-dicarbonyl derivatives [133]. 

Since simple ketones 22 are less reactive compared to 1,3-dicarbonyl compounds 19, improvement of the nucleophilicity of the a-carbon is required by conversion to enamines. When dinitropyridone 1 is treated with acetone 22a in the presence of amines, 2,6-disubstituted 4-nitroanilines 23a-c are produced in good yields (Table 1). In this reaction, the enamine is formed in situ, and attacks stepwise at the 4- and the 6-position of pyridone 1 to afford bicyclic intermediate from which anionic nitroacetamide is eliminated leading to nitroaniline derivative 23. It is possible to synthesize unsymmetri-cal nitroanilines having different substituents at the 2- and the 6-positions by changing ketones 22, and modification of the amino group is also achieved by using other amines [41]. 

Carbanions from hydrocarbons, nitriles, ketones, esters, TV./V-dialkyl acetamides and thioamides, and mono and dianions from (3-dicarbonyl compounds are some of the most common nucleophiles through which a new C-C bond can be formed. This C-C bond formation is also achieved by reaction with aromatic alkoxides. Among the nitrogen nucleophiles known to react are amide ions to form anilines however, the anions from aromatic amines, pyrroles, diazoles and triazoles, react with aromatic substrates to afford C-arylation. 

Ambident anions are mesomeric, nucleophilic anions which have at least two reactive centers with a substantial fraction of the negative charge distributed over these cen-ters ) ). Such ambident anions are capable of forming two types of products in nucleophilic substitution reactions with electrophilic reactants . Examples of this kind of anion are the enolates of 1,3-dicarbonyl compounds, phenolate, cyanide, thiocyanide, and nitrite ions, the anions of nitro compounds, oximes, amides, the anions of heterocyclic aromatic compounds e.g. pyrrole, hydroxypyridines, hydroxypyrimidines) and others cf. Fig. 5-17. 

Several classes of carbon nucleophiles have been successfully used in these systems, reflecting the utility of Reissert chemistry for derivatizing azines via carbon-carbon bond formation. Apart from cyanide anion, other classes of carbon nucleophiles have been explored. For instance, addition of indole (51) to A-acyla-zinium salts proceeds selectively at the a-position (Scheme 9). Pyrrole, quinolines and isoquinolines all behave similarly [73-76]. A related reaction, yielding adduct 70 (Scheme 12b) has also been described. In this case, azine activation is promoted by Vilsmeier reagents (generated by reaction of amides with POCI3) [77]. p-Dicarbonyls are reactive inputs in this chemistry, and dialkyl malonates 53... 

In addition to MeOH and AcOH nucleophiles such as pyridine [4,53-58], azide ion [59], chloride ion [60], and cyanide ion [61], as well as the anions of 1,3-dicarbonyl compounds and aliphatic nitro compounds [59], and even Grignard reagents [59], have been employed. 

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