Acylations heteroatom-stabilized carbanions

Additions of a-Heteroatom-stabilized Carbanions (Non-acyl Anion Equivalents) 115... 

Fig. 6.40. On the chemo-selectivity of the reactions of hydride donors, organometallic compounds, and heteroatom-stabilized "carbanions with acylating agents (kM t refers to the rate constant of the addition of the nucleophile to the carboxyl carbon, and kadd2 refers to the rate constant of the addition of the nucleophile to the carbonyl carbon).

For the reaction of hydride donors, organometallic compounds and heteroatom-stabilized carbanions with acylating agents or carbonyl compounds one encounters a universal reactivity order RC(=0)C1 > RC(=0)H > R2C=0 > RC(=0)0R > RC C NR It applies to both good and poor nucleophiles, but—in agreement with the reactivity/selectivity principle (Section 1.7.4)—the reactivity differences are far larger for poor nucleophiles. 

Fig. 6.41. Three strategies for the chemoselective acylation of hydride donors, organometallics and heteroatom-stabilized "carbanions" with carboxylic acid derivatives.

Acylation of Organometallic Compounds and Heteroatom-Stabilized Carbanions With Carboxylic Acid (Derivative)s Synthesis of Ketones... 

In Figure 6.41, the reaction of certain heteroatom-stabilized carbanions with carboxylic acid derivatives is presented as strategy 3 of Figure 6.32 for achieving chemoselective acylations. This strategy can be used to convert esters into /i-ketophosphomc acid esters with... 

Most SN reactions of hydride donors, organometallic compounds, and heteroatom-stabilized carbanions at the carboxyl carbon follow the mechanism shown in Figure 6.2. Thus the substitution products, i.e., the aldehydes and ketones C, form in the presence of the nucleophiles. Thus, when the nucleophile and the acylating agent are used in a 2 1 ratio, alcohols F are always produced. 

The SN reaction under consideration is not terminated until water, a dilute acid, or a dilute base is added to the crude reaction mixture. The tetrahedral intermediate B is then protonated to give the compound E. Through an El elimination it liberates the carbonyl compound C (cf. discussion of Figure 6.4). Fortunately, at this point in time no overreaction of this aldehyde with the nucleophile can take place because the nucleophile has been destroyed during the aqueous workup by protonation or hydrolysis. In Figure 6.32 this process for chemoselective acylation of hydride donors, organometallic compounds, and heteroatom-stabilized carbanions has been included as strategy 1. ... 

Related chemistry not covered in this chapter includes the acylation of stabilized organometallics and the broad category of enolate or metalloenamine C-acylation (Volume 2), the Claisen or Dieckman condensations (Chapter 3.6, Volume 2), the acylation of heteroatom-stabilized carbanions (Part 2, Volume... 

Heteroatom-stabilized Carbanions. Heteroatom-stabilized and allylic carbanions serve as homoenolate anions and acyl anion equivalents, e.g. a-anions of protected cyanohydrins of aldehydes and Q ,/3-unsaturated aldehydes are intermediates in general syntheses of ketones and Q ,/3-unsaturated ketones (eq 36). Allylic anions of cyanohydrin ethers may be a-alkylated (eq 37) or, if warmed to —25°C, may undergo 1,3-silyl migration to cyanoenolates which may be trapped with TMSCl. Metalated Q -aminonitriles of aldehydes are used for the synthesis of ketones and enamines (eq 38). Similarly, allylic anions from 2-morpholino-3-alkenenitriles undergo predominantly a-C-alkyl-ation to give, after hydrolysis, a,/3-unsaturated ketones (eq 39). ... 

Not only alky] groups, but also aryl [492, 493], vinyl [494], acyl [276, 495—497], alkoxycarbonyl [498], aminocarbonyl [499-501], silyl [502-504], or phosphoryl groups [279, 280] can migrate to a vicinal carbanion (Scheme 5.68). Because some of these groups can be used to stabilize a-heteroatom-substituted carbanions by chelate formation, migration of these groups to the carbanion is a potential side reaction in the generation and alkylation of chelate-stabilized carbanions. 

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