Condensation reactions, carbonyl compounds conjugate addition

These reversible reactions are cataly2ed by bases or acids, such as 2iac chloride and aluminum isopropoxide, or by anion-exchange resias. Ultrasonic vibrations improve the reaction rate and yield. Reaction of aromatic aldehydes or ketones with nitroparaffins yields either the nitro alcohol or the nitro olefin, depending on the catalyst. Conjugated unsaturated aldehydes or ketones and nitroparaffins (Michael addition) yield nitro-substituted carbonyl compounds rather than nitro alcohols. Condensation with keto esters gives the substituted nitro alcohols (37) keto aldehydes react preferentially at the aldehyde function. 

Conjugate reduction.1 This stable copper(I) hydride cluster can effect conjugate hydride addition to a,p-unsaturated carbonyl compounds, with apparent utilization of all six hydride equivalents per cluster. No 1,2-reduction of carbonyl groups or reduction of isolated double bonds is observed. Undesirable side reactions such as aldol condensation can be suppressed by addition of water. Reactions in the presence of chlorotrimethylsilane result in silyl enol ethers. The reduction is stereoselective, resulting in hydride delivery to the less-hindered face of the substrate. 

Conjugate addition of methanol to a,/l-unsaturated carbonyl compounds forms a new carbon-oxygen bond to yield valuable ethers (Scheme 26). Kabashima et al. (12) reported the conjugate addition of methanol to 3-buten-2-one on alkaline oxides, hydroxides, and carbonates at a temperature of 273 K. The activities of the catalyst follow the order alkaline earth metal oxides > alkaline earth metal hydroxides > alkaline earth metal carbonates. All alkaline earth metal oxides exhibited high catalytic activities and, as in alcohol condensations and nitroaldol reactions, their catalytic activities were not much affected by exposure to CO2 and air. 

Aldol addition and condensation reactions involving two different carbonyl compounds are called mixed aldol reactions. For these reactions to be useful as a method for synthesis, there must be some basis for controlling which carbonyl component serves as the electrophile and which acts as the enolate precursor. One of the most general mixed aldol condensations involves the use of aromatic aldehydes with alkyl ketones or aldehydes. Aromatic aldehydes are incapable of enolization and cannot function as the nucleophilic component. Furthermore, dehydration is especially favorable because the resulting enone is conjugated with the aromatic ring. 

A large number of reactions have been presented in this chapter. However, all of these reactions involve an enolate ion (or a related species) acting as a nucleophile (see Table 20.2). This nucleophile reacts with one of the electrophiles discussed in Chapters 8, 18, and 19 (see Table 20.3). The nucleophile can bond to the electrophilic carbon of an alkyl halide (or sulfonate ester) in an SN2 reaction, to the electrophilic carbonyl carbon of an aldehyde or ketone in an addition reaction (an aldol condensation), to the electrophilic carbonyl carbon of an ester in an addition reaction (an ester condensation) or to the electrophilic /3-carbon of an a,/3-unsaturated compound in a conjugate addition (Michael reaction). These possibilities are summarized in the following equations ... 

Finally, the Lewis acid activation of a,)6-unsaturated carbonyl compounds and Q -nitroalkenes is sufficient to induce productive Sr reactions with allenylstannanes (Scheme 5.2.70). Haruta and Kita have successfully achieved condensation reactions with 326 and 328 in the presence of TiCU, and cyclo-hexenones 330 and 332 also serve as synthetically effective substrates for the 1,4-conjugate addition. In the case of enone 332, activation with TBSOTf led to the isolation of silyl enol ether 333. ... 

Asymmetric conjugate addition reactions of carbonyl compounds with a, -unsaturated systems are known. The simple amine a-methylbenzylamine 68 acts as both the activator (to give the imine and hence the enamine required for alkylation) and as the chiral auxiliary to effect neutral asymmetric conjugate-addition reactions. " Thus, condensation of (5)-a-methylbenzylamine 68 with 2-methylcyclohexanone, followed by addition of methyl acrylate (and hydrolysis of the product imine), gave the 2,2-disubstituted cyclohexanone 69 with high enantiomeric purity (1.78). 

Condensation and Conjugate Addition Reactions of Carbonyl Compounds More... 

Conjt te addition reactions involve a nucleophile, which is often an enolate, adding to the /3 position of an a,j8-unsaturated carbonyl compound. One of the most common conjugate addition reactions is the Michael addition. As we shall see, the aldol condensation provides a way to synthesize a,j8-unsaturated carbonyl compounds that we can then use for subsequent conjugate addition reactions. 

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