Amine conjugate carbonyl addition

Coniine, molecular model of. 28 structure of, 294 Conjugate acid, 49 Conjugate base, 49 Conjugate carbonyl addition reaction, 725-729 amines and, 727 enamines and, 897-898 Gilman reagents and, 728-729 mechanism of, 725-726 Michael reactions and, 894-895 water and. 727 Conjugated diene, 482... 

The formation of the activated intermediate for the AE with R -NH-R is accelerated by the addition of a proton or Lewis acid to the 2-carbonyl group in 151. This is necessary for aminations of uridine (150) or thymidine (162) with weakly basic amines such as aniline, e.g., to 161e (Section III, A). Silylated hydroxy-N-heterocycles lacking such an activating conjugated carbonyl group, however, usually react only with amines when a Lewis acid is present (Section III,A). 

Conjugated carbonyl compounds react via conjugate addition with amines to give p-amino derivatives (see 15-31) As expected, on Michael-type substrates the nitrogen goes to the carbon that does not carry the Z. With substrates of the form RCH=CZZ, the same type of cleavage of the adduct can take place as in 15-3. ... 

The conjugate addition of an amine to an a,p-unsaturated carbonyl com-pound/nitrile has been achieved in water without any catalyst at room temperature (Scheme 5.15). The rate acceleration of the reaction was explained by H-bonding of H2O to the amine and carbonyl group of alkene. 

Conjugate addition of a nucleophile to an alkynyl ketone unit ortho to amino allows interaction of the amine and carbonyl groups and thus the formation of a quinoline. ... 

Ammonia and amines undergo conjugate addition to a 3 unsaturated carbonyl compounds (Section 18 12) On the basis of this information predict the pnncipal organic product of each of the following reactions... 

Michael additions are conjugate 1,4-additions of enolates or amines to a,y9-unsatu-rated carbonyl compounds carried out under basic conditions. Up to now there are only a few examples for the solid-phase Michael addition (Scheme 3.17). 

In conjunction with the Knoevenegal reaction, a Michael addition (Figure 22) reaction was also described by Jaekson et al. using the same siliea supported tertiary amines for the catalysis of conjugate addition of nitroalkenes to a,y9-unsaturated carbonyl compounds. At a flow rate of 6.6 pL/min the eonversion rate was constant with a high yield for 7 hours reaction time. 

In a series of reports between 1991 and 1997 Yamaguchi showed that rubidium salts of L-proline (9) catalysed the conjugate addition of both nitroalkanes [29, 30] andmalonates [31-33] to prochiral a,p-unsaturated carbonyl compounds in up to 88% ee (Scheme 1). Rationalisation of the selectivities observed involved initial formation of an iminium ion between the secondary amine of the catalyst and the a,p-unsaturated carbonyl substrate. Subsequent deprotonation of the nucleophile by the carboxylate and selective delivery using ion pair... 

Formation of C-C bonds remains the ultimate challenge to the synthetic chemist. The employment of new synthetic methods in complex target synthesis can be frustrated by a lack of functional group tolerance and substrate specificity. These problems can be somewhat alleviated within conjugate addition reactions by the use of secondary amine catalysts where a number of important and highly selective methods have been developed. Two principle classes of nucleophile have been shown to be effective in the iminium ion activated conjugate addition of carbon nucleophiles to a,P-unsaturated carbonyl systems aryl, heteroaromatic and vinyl... 

Methylbenzoic acid 513 can be laterally lithiated with two equivalents of lithium amide base (LDA" or L1TMP °) or alkyllithium provided the temperature is kept low to avoid addition to the carbonyl group (Scheme 201). It is usually preferable to carry out the lithiation using aUcyllithiums", since with lithium amides the subsequent reaction of 514 with electrophiles is disrupted by the presence of the amine by-product (diisopropylamine, for example) . The dilithio species 514 is stable in THF even at room temperature, and (as with the amide 483) since LDA will also dilithiate 515 stabilization presumably comes principally from conjugation with the carboxylate. 

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