Hydride donors acylation

Bimetallic activation of acetyl and alkoxyacetyl ligands — through formation of cationic P2 acyl complexes — to reaction with nucleophilic hydride donors was established. Cationic transition metal compounds possessing an accessible coordination site bind a neutral T -acyl ligand on another complex as a cationic P2 acyl system. These i2 3icyl systems activate the acyl ligand to reduction analogous to carbocation activation. Several examples of i2-acyl complexation have been reported previously. 

Hydride donor Iminium ion Acyl halide Aldehyde Ketone Ester Amide Carboxy- late salt... 

Figure 4.12. Second-order rate constants for reactions of hydrogen atom donors with various radical types at ambient temperature. Data sources group 14 (IV A) hydrides (15) aminyl radicals (69) amidyl radicals (70) alkyl radials with group 16 (VI A) hydrides (71) acyl radical with PhSeH (72).

Most SN reactions of hydride donors, organometallic compounds, and heteroatom-stabi-lized 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. 

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. 

To make as much carboxylic acid derivative as possible available to the nucleophile at all stages of the reaction, the nucleophile is added dropwise to the carboxylic acid derivative and not the other way around. In Figure 6.41, the approach to chemoselective acylations of hydride donors and organometallic compounds, which we have just described, is labeled as strategy 2 and compared to two other strategies, which we will discuss in a moment. 

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

Acylation of Hydride Donors Reduction of Carboxylic Acid Derivatives to Aldehydes... 

In Section 6.5 you learned that the acylations of hydride donors or of organometallic compounds, which give aldehydes or ketones, often are followed by an unavoidable second reaction the addition of the hydride or organometallic compound to the aldehyde or the ketone. In this chapter, we will study the intentional execution of such addition reactions. 

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. ... 

Following strategy 2 from Figure 6.32, chemoselective SN reactions of hydride-donors with carboxylic acid derivatives also succeed starting from carboxylic chlorides. For the reasons mentioned further above, weakly nucleophilic hydride donors are used for this purpose preferentially and should be added dropwise to the acylating agent in order to achieve success ... 

Keto esters can be obtained by acylation of enamines of acyclic and cyclic ketones with ethyl chloroform ate Surprisingly no -keto ester was obtained when the reaction was carried out in the presence of triethylamine and an extra mole of enamine or a tertiary aromatic amine must therefore be used to neutralize the acid liberated. The intermediate enamino ester can be isolated and reduced by hydride donors (Scheme 92). 

The donor-acceptor acyl chloride-aluminium chloride complex is not only an electrophilic reagent but also a hydride ion acceptor (oxidizing reagent). The best hydride donors are the saturated hydrocarbons, specially those containing a tertiary carbon atom. The acylation of cyclohexane is an old and well-known reaction giving acetyl-methyl-cyclopentene and/or -cyclopentane. 26,27 the yields are low because the solvent used was either cyclohexane itself or small quantities of chloroform. in our hands, we found that the reaction carried out in methylene chloride solution ( IM) led to the l-acetyl-2-methylcyclopentene and l,3-diacetyl-2-methylcyclopentene Z in good yields. A cleaner reaction also occurred from methylcyclopentane. The ratio of ys could be changed by modification of the reaction conditions (see Table 1) (overall yields of the hydrocarbons functionalization were around 75-80 %). 

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