Nucleophiles, carbonylate anions

The mechanism of intramolecular aldol reactions is similar to that of inter-molecular reactions. The only difference is that both the nucleophilic carbonyl anion donor and the electrophilic carbonyl acceptor are now in the same molecule. One complication, however, is that intramolecular aldol reactions might lead to a mixture of products, depending on which eiiolate ion is formed. For example, 2,5-hexanedione might yield either the five-membered-ring product 3-methyl-2-cyclopentenone or the three-membered-ring product (2-methyl-cyclopropenyl)ethanone (Figure 23.4). In practice, though, only the cycio-pentenone is formed. 

The methyl transfer reactions are envisoned as arising from SN2 displacement of a less nucleophilic metal carbonyl anion by a more nucleophilic carbonyl anion. CpFe(CO)2 is the more basic species (69) and therefore abstracts methyl from the less basic CpMo(Me)(CO)3. CpMo(CO)3 and Mn(CO)5 are bases of comparable strength, and, therefore, the reaction either of MnMe(CO)s with CpMo(CO)3" or of CpMo(Me)(CO)3 with Mn(CO)5 gave mixtures of CpMo(Me)(CO)3 and Mn(Me)(CO)s. 

Electron deficient carbon-carbon double bonds are resistant to attack by the electrophilic reagents of Section 5.05.4.2.2(t), and are usually converted to oxiranes by nucleophilic oxidants. The most widely used of these is the hydroperoxide ion (Scheme 79). Since epoxidation by hydroperoxide ion proceeds through an intermediate ct-carbonyl anion, the reaction of acyclic alkenes is not necessarily stereospecific (Scheme 80) (unlike the case of epoxidation with electrophilic agents (Section 5.05.4.2.2(f)) the stereochemical aspects of this and other epoxidations are reviewed at length in (B-73MI50500)). 

As with the reduction of carbonyl compounds discussed in the previous section, we ll defer a detailed treatment of the mechanism of Grignard reactions until Chapter 19. For the moment, it s sufficient to note that Grignard reagents act as nucleophilic carbon anions, or carbanions ( R ), and that the addition of a Grignard reagent to a carbonyl compound is analogous to the addition of hydride ion. The intermediate is an alkoxide ion, which is protonated by addition of F O"1 in a second step. 

It has been noted (Section II,B,1) that reactions between transition metal carbonyl anions and silicon halides often fail to produce species containing silicon-transition metal bonds, and that such failure has been ascribed to nucleophilic attack by carbonyl oxygen. It is therefore interesting that compounds containing Si—O—C—transition metal linkages have recently been isolated from such reactions [Eqs. (105) (R = Me, Ph) 183) and (106)... 

The cyclobutane ring was then cleaved by hydrolysis of the enamine and ring opening of the resulting (3-diketone. The relative configuration of the chiral centers is unaffected by subsequent transformations, so the overall sequence is stereoselective. Another key step in this synthesis is Step D, which corresponds to the transformation 10-IIa => 10-la in the retrosynthesis. A protected cyanohydrin was used as a nucleophilic acyl anion equivalent in this step. The final steps of the synthesis in Scheme 13.11 employed the C(2) carbonyl group to introduce the carboxy group and the C(l)-C(2) double bond. 

Figure I indicates the approach used to synthesize poly(oxyethylene)-b-poly(pivalolactone) telechelomers. An acetal capped anionic initiator, X (13) polymerizes ethylene oxide (EO) to give 2> a potassium alkoxide of a masked polyether, and this "new" initiator is to be used to polymerize pivalolactone (PVL). Since potassium alkoxides are strong nucleophiles, they can randomly attack at both the carbonyl carbon and the 3-methylene carbon in lactones, (Figure 2) such a random attack would result in a pivalolactone segment containing irregularities. Lenz (15), and Hall (16), and Beaman (17) have investigated PVL polymerization and have shown that the less nucleophilic carboxylate anion is preferable in polymerizing PVL smoothly. The weaker carboxylate anion will attack only at the methylene...

Aromatic halides (example 21, Table VII) also react in the presence of Ni(0) complexes in alkaline media. Complex nickel carbonyl anions, such as Ni5(CO),22, Ni6(CO)122, Ni9(CO)182 (194) are formed which, being more nucleophilic, can attack aromatic halides. 

Nucleophilicity, of metal carbonyl anions, 25 3 Nucleophilic substimtion reactions, in high-nuclearity carbonyl clusters, 30 187-202... 

Stabilisation of the tetrahedral forms of fluoroalkyl ketones The presence of a fluoroalkyl group in a position of a carbonyl strongly enhances its electrophilicity, and hence its reactivity, towards nucleophiles. The anionic tetrahedral intermediates are stabilised by the electron-withdrawing group Rf (Fig. 20) [69,70]. This phenomenon is illustrated by the ability of fluoroketones to afford stable hydrates in aqueous medium. 

Neither the palladium nor nickel catalyst described will promote the carbonylation of saturated aliphatic halides as noted above. However, this reaction can be catalyzed with cobalt (17) or iron (77) and probably with manganese (18) carbonyl anion salts. These carbonyl anions are strongly nucleophilic species and readily displace halide or other good leaving groups from primary or secondary positions giving alkyl metal carbonyl complexes. 

The nucleophilic displacement of halide ions from M—X bonds by carbonylate anions (either mononuclear or polynuclear) is a general synthetic route to metal-metal bonded species (1,2), and numerous hetero-Pt clusters have been obtained in this way. The resulting products are not often those of expected stoichiometry, although under optimized experimental conditions this method can provide very useful syntheses, particularly of high-nuclearity clusters. Some examples are shown in Eqs. (7)—(11) (5,51-54). 

The use of masked acyl anion equivalents in a synthetic protocol requires additional steps to unmask the carbonyl unit. Sometimes the deprotection procedures are incompatible with sensitive compounds thus, a direct nucleophilic acylation protocol is desirable. While C-nucleophilic carbonyl groups do not... 

The meta acylation of anisole, using a carbonyl anion equivalent as the nucleophile, illustrates the unique regioselectivity available with the Cr(CO)3 activation (equation 31). 

This process has been coupled with meta addition of a carbonyl anion equivalent and the controlled exo addition of the incoming nucleophile to generate acorenone and acorenone B stereospecifically from [(o-methylanisole)Cr(CO)3] (63 Scheme 14).123 The first step is addition of a cyanohydrin acetal anion (64) to the less-hindered meta position in [(o-methylanisole)Cr(CO)3]. Addition of allylMgBr to the resulting ketone, anti-Markovnikov addition of HBr to the alkene, substitution for Br by CN, and coordina-... 

The topic of nucleophilic attack at an sp2 carbon would be too wide a field to review in one chapter, if one were to discuss all facets and outcomes, some of which are shown in Figure 1. If the nucleophile is anionic an anion is formed, but if the nucleophile is neutral a zwitterion is produced. If X is oxygen or nitrogen, then the outcome can be carbonyl addition, substitution or a Darzens-type reaction. If the X is another carbon then addition leads to conjugate additions or polymerization. Alternatively the nucleophile could be expelled after rotation about the C—C bond to give overall isomerization. Both substitution and cyclization are also observed. 

While silyl metal carbonyl derivatives are unreactive towards neutral metal carbonyls (7), metal carbonyl anions give rise to various displacement processes (entries 1-3). The order of displacing ability seems generally similar to that noted earlier for nucleophilicities (Section II, A,1) ... 

Compounds like the ester 56 were briefly mentioned in chapter 4 and we can now show how they can be made by a two-group disconnection. The electrophile will be the a-halo carbonyl compound 57 and the nucleophile the anion of a carboxylic acid. 

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