Conjugated compounds, reaction with enamines

Enamines react with acceptor-substituted alkenes (Michael acceptors) in a conjugate addition reaction for example with o ,/3-unsaturated carbonyl compounds or nitriles such as acrylonitrile 8. With respect to the acceptor-substituted alkene the reaction is similar to a Michael addition ... 

Enamine (235) obtained from cyclic ketones and the acetal of /V-methyl-2-pyrrolidone gave a fused 2-pyrone [83IJC(B)1083]. 2//-Chromenes were obtained from of 3,5-dichlorosalicylaldehyde and enamines (94RRC183) (Scheme 42). The pyran ring is formed by a reaction of aminals of conjugated w-dimethylaminoaldehydes with cyclic /1-dicarbonyl compounds (94IZV285) (Scheme 43). 

The conjugated double bond of enamines readily undergoes many reactions. The reactions of imines with a double bond between the nitrogen and carbon atoms are also discussed to allow comparison. Some reactions of heterocyclic compounds containing the enamine grouping as a part of the aromatic ring are also considered. The reactions of these compounds can be divided on a mechanistic basis into three groups ... 

Compound A is clearly the enamine from the aldehyde and piperidine and its reaction with unsaturated ketone would be expected to lead to conjugate addition (Chapter 29). Evidently, in [Pg.402]

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). 

When the enamine is in conjugation with a carbonyl function, as in a-aminomethylene aldehydes (528,529), ketones (530), or esters (531), a Michael addition is found in vinylogous analogy to the reactions of amides. An application to syntheses in the vitamin A series employed a vinyl lithium compound (532). 

Scheme 2.11 shows some examples of Robinson annulation reactions. Entries 1 and 2 show annulation reactions of relatively acidic dicarbonyl compounds. Entry 3 is an example of use of 4-(trimethylammonio)-2-butanone as a precursor of methyl vinyl ketone. This compound generates methyl vinyl ketone in situ by (3-eliminalion. The original conditions developed for the Robinson annulation reaction are such that the ketone enolate composition is under thermodynamic control. This usually results in the formation of product from the more stable enolate, as in Entry 3. The C(l) enolate is preferred because of the conjugation with the aromatic ring. For monosubstituted cyclohexanones, the cyclization usually occurs at the more-substituted position in hydroxylic solvents. The alternative regiochemistry can be achieved by using an enamine. Entry 4 is an example. As discussed in Section 1.9, the less-substituted enamine is favored, so addition occurs at the less-substituted position. 

In recent years The Chemistry of Functional Groups series has included three volumes on composite functional groups in which a C=C double bond was attached to another group. The chemistry of enones (edited by S. Patai and Z. Rappoport) appeared in 1989 The chemistry of enols (edited by Z. Rappoport) appeared in 1990 and The chemistry of enamines (edited by Z. Rappoport) appeared in 1994. We believe that the time has arrived for a book dealing with the combination of C=C double bonds, namely dienes and polyenes. The two double bonds can be conjugated, and conjugated dienes have a chemistry of their own, but even non-conjugated dienes show certain reactions that involve both double bonds. Allenes and cumulenes, which represent a different combination of the double bonds were treated in The chemistry ofketenes, allenes and related compounds, edited by S. Patai in 1980. 

Enamine nucleophiles react readily with soft conjugated electrophiles, such as a, 3-unsaturated carbonyl, nitro, and sulfonyl compounds [20-22], Both aldehydes and ketones can be used as donors (Schemes 27 and 28). These Michael-type reactions are highly useful for the construction of carbon skeletons and often the yields are very high. The problem, however, is the enantioselectivity of the process. Unlike the aldol and Mannich reactions, where even simple proline catalyst can effectively direct the addition to the C = O or C = N bond by its carboxylic acid moiety, in conjugate additions the charge develops further away from the catalyst (Scheme 26) ... 

With conjugated dienes, photocycloaddition of carbonyl compounds occurs at one of the double bonds to give vinyloxetanes. An interesting example is the reaction of acetone with 2-methyl-l,3-butadiene, which gave the two oxetanes (60) and (61) in a ratio of 3 1 and a total yield of about 20% (72JA8761). Other alkenes which have been used for photosynthesis of oxetanes include enol ethers, ketene acetals, enamines, allenes and diketene, with the reaction of the last compound with benzaldehyde illustrated in equation (105) (75CPB365). 

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