Activation of the carbonyl group

Activation of the carbonyl group by protonation of the carbonyl oxygen... 

Conventional conversion of amide, lactam, imide, and urea carbonyl groups into enaminones, enamino esters, or enamino nitriles requires prior activation of the carbonyl groups either by alkylation to imino ethers, followed by reaction with activated methylene groups, or by thiation, e.g. with P2S5, to thiocarbonyl groups followed by alkylation (and possibly also oxidation), and, again, subsequent reac-... 

The mechanism by which the Group III hydrides effect reduction involves activation of the carbonyl group by coordination with a metal cation and nucleophilic transfer of hydride to the carbonyl group. Hydroxylic solvents also participate in the reaction,59 and as reduction proceeds and hydride is transferred, the Lewis acid character of boron and aluminum becomes a factor. 

This must reflect activation of the carbonyl group by magnesium ion, since ketones are less reactive to pure dialkylzinc reagents and tend to react by reduction rather than addition.141 The addition of alkylzinc reagents is also promoted by trimethylsilyl chloride, which leads to isolation of silyl ethers of the alcohol products.142... 

These reactions involve activation of the carbonyl group by the Lewis acid. A nucleophile, either a ligand from the Lewis acid or the solvent, assists in the desilylation step. 

In this study butyl acetate (AcOBu) was hydrogenolysed to butanol over alumina supported Pt, Re, RePt and Re modified SnPt naphtha reforming catalysts both in a conventional autoclave and a high throughput (HT) slurry phase reactor system (AMTEC SPR 16). The oxide precursors of catalysts were characterized by Temperature-Programmed Reduction (TPR). The aim of this work was to study the role and efficiency of Sn and Re in the activation of the carbonyl group of esters. 

When the reaction with substituted benzaldehydes is conducted in the presence of ammonia, the a-amino carboxylic acids are formed [11], The corresponding reaction involving bromoform is less effective and, for optimum yields, the addition of lithium chloride, which enhances the activity of the carbonyl group, is required. In its absence, the overall yields are halved. The reaction of dichlorocarbene with ketones or aryl aldehydes in the presence of secondary amines produces a-aminoacetamides [12, 13] (see Section 7.6). 

This type of addition reaction shown in Eq. 2 and 3 [8,9] is expected to be accelerated either through activation of the carbonyl group of a, 0 -acetylenic ester (ynoates) by acid, or through enhancement of nucleophilicity of ester enolate with a strong base, for example, by use of a lithium enolate. 

In line the with the chemistry of dialkylzinc [36], the zinc homoenolate is inert to carbonyl compounds in a variety of solvents, Eq. (33). Slow addition accurs only in an HMPA/THF mixture. When the reaction is conducted in halomethane in the presence of Me3SiCl, however, a very rapid addition reaction occurs [33], Control experiments indicate that the acceleration is due to the activation of the carbonyl group by Me3SiCl. The activating effect of the chlorosilane disappears in ethereal solvents. 

Figure 8.4 Proposed transition state to explain the double activation of the carbonyl group and the nucleophile by the gold catalyst.

Answer. Three factors combine to make this reaction facile (a) activation of the carbonyl group toward nucleophilic addition as a result of coordination to the Lewis acid (aluminum triisopropoxide), as discussed in Chapter 8 (b) activation of the secondary C—H bond as a donor by the presence of the very good X substituent (— —Al, which resembles —O), as discussed in Chapter 4 and (c) opportunity presented by the coordination within the complex shown in Figure B.4,... 

A variety of N-O-chelated glycine amide and peptide complexes of the type [CoN4(GlyNR R2)]3+ have been prepared and their rates of base hydrolysis studied.169 The kinetics are consistent with Scheme 8. Attack of solvent hydroxide occurs at the carbonyl carbon of the chelated amide or peptide. Amide deprotonation gives an unreactive complex. Rate constants kOH are summarized in Table 16. Direct activation of the carbonyl group by cobalt(III) leads to rate accelerations of ca. 104-106-fold. More recent investigations160-161 have dealt with... 

A further example is seen in the rapid hydrolysis of benzylpenicillin (3.6) by cop-per(n) which is thought to proceed through an intermediate of type 3.7. Notice that in this case the activation of the carbonyl group to nucleophilic attack seems to be through... 

Oligopeptides are more reactive than the a-amino acids, which do not carry any additional electrophilic factional groups. It has been pointed out in Section I that the enhanced reactivity of oligopeptides may be attributed to the activation of the carbonylic group, which is even further enhanced when the amino-group is protonated. 

One means of stereoselective cleavage of biaryl lactones [53] is activation of the carbonyl group with a Lewis acid and subsequent attack with a chiral nucleophile. Conversely, activation can be effected with a chiral Lewis acid followed by attack of an achiral nucleophile. Complexation of a biaryl lactone to the chiral fragment [CpRe (NO)(PPh3)j then reduction with K(s-Bu)3BH (K-selectride) and ring opening of the intermediate rhenium lactolate gives the metalated aldehyde (dr = 75 25) which is converted to the alcohol without essential loss of optical purity (Sch. 6) [54]. 

Hydrostannation of carbonyl compounds with tributyltin hydride is promoted by radical initiation and Lewis or protic acid catalysis.The activation of the carbonyl group by the acidic species allows the weakly nucleophilic tin hydride to react via a polar mechanism. Silica gel was a suitable catalyst allowing chemoselective reduction of carbonyl groups under conditions that left many functional groups unchanged. Tributyltin triflate generated in situ from the tin hydride and triflic acid was a particularly efficient catalyst for the reduction of aldehydes and ketones with tributyltin hydride in benzene or 1,2-di-chloromethane at room temperature. Esters and ketals were not affected under these conditions and certain aldehydes were reduced selectively in preference to ketones. 

On the other hand, it was found that the molar rotations of 1,1-diphenylcyclopropanes with CHO and COPh groups cannot be described with the procedure used so far. It was suggested that in these compounds an additional rotation contribution in the sense of equation 1 is necessary. This additional rotation term is assumed to be due to a non-negligible optical activity of the carbonyl group (iigand optical activity ) in the particular molecular environment. In terms of the TTOR approach in such cyclopropanes XIX a further element of optical activity transforming like a polar plane is relevant. The... 

---