Enamine Enaminoesters

V. Compounds With C = C Double Bond Enamines, Enaminoesters and Ketones, Enamides, and Enecarbamates... 

Triazines on reaction with enamines followed by loss of a nitrogen from the intermediates give pyridine derivatives (85H2789) (Scheme 56). The reaction of 1,3,5-triazine with enamine and enaminoester hydrochlorides in acetonitrile leads to mixtures containing pyrimidines and pyridines... 

Nitropyrimidine reacts in analogous fashion with enamines based on macrocyclic ketones (94TL2075). Quaternization makes it possible for 1-methylpyridinium iodide to react with enaminoesters with the formation of... 

And finally, acylating agents can also be used as electrophiles to react with enamines. Following the hydrolysis of the enaminoketones (i.e., compounds with the substructure R2N-C=C-C(=0)-R ) or enaminoesters (i.e., compounds with the substructure R2N-C=C-C(=0)-0R ) the acylation products of the corresponding ketones are obtained. Figure 12.21 gives the mechanistic details of the acylation with an acid chloride, and Figure 12.22 shows the acylation with ethyl chloroformate. The first acylation yields /1-diketones, the second furnishes a /1-ketoester. 

The term enaminones is used in this section to designate enamines having at C(2) a carbonyl function conjugated with the carbon-carbon double bond. The two main groups of these compounds, 2-acylenamines (enaminoketones) and 2-alkoxycarbonyle-namines (enaminoesters), are discussed in the following subsections. 

Although the reactivity of enaminones is not always the same as that of typical enamines due to the additional conjugative interaction with the carbonyl group, the anodic oxidation of enaminones seems useful in organic synthesis since they yield dimerized or cyclized products upon anodic oxidation. In anodic oxidation of the enaminones or enaminoesters in methanol containing sodium perchlorate, for instance, derivatives of pyrrole are formed via initial dimerization (equation 4)5. 

The use of quinone monoketals in the reaction with an exocyclic enaminoester is a new variation150. It is not a typical Nenitzescu reaction since an enamine anion is used. Tricyclic intermediates are obtained, which nevertheless formally give typical Nenitzescu products in high yield and regioselectively (equation 58). In this way annelated indoles of mitomycin type become accessible. 

Some enamines have been shown to form inter- and intra-molecular hydrogen bonds in the solid state77. Thus, a-tetrahydropyrrolidinylidene-2 (44) and ethyl a-hexahydroaze-pirylidene acetate (45) have been shown to occur as / -enaminoesters of configuration Z in the solid state, i.e. the same configuration as they have in solution78. 

Enaminoesters, -ketones, and -nitriles have also successfully been applied in electro-chemically induced radical cation cycloaddition reactions, especially with 2-vinylindoles or 2-vinylpyrroles. Some examples are given in Eq. (31). Depending on the structures, the reaction starts with the formation of either the vinylindole or vinylpyrrole radical cation or the radical cation of the enamidoester, -ketone, or -nitrile. In Eq. (32), a representative reaction pathway for the cycloaddition between a 2-vinylpyrrole and an acceptor-substituted enamine is formulated via the enamine radical cation [159]. 

An important reaction is the condensation of amines with 1,3-diketones or 3-ketoesters yielding -enaminoesters which are important intermediates for the synthesis of natural products (Scheme 10.10). The step preceding the formation of the enamine involves zwitterionic intermediates such as those in the addition of amines to a,yS-unsaturated compounds. The electrostrictive effect contributes to the magnification of the pressure effect. Lanthanide catalysis and use of 300 MPa pressure can be an excellent way to produce enamino compounds in high yields [39] (Table 10.10). 

Mechanistically, the authors proposed that 852 was first converted to an enaminoester 854 by the in situ generated Vilsmeier reagent (Scheme 1.230). Nucleophilic addition of this enamine to C(2) of the oxazole would generate the oxazabicyclo[2.2.1]heptane 855, which ring opened to a 3H-pyrrole 856. Subsequent proton transfer in 856 then yielded 853. The authors also noted that direct attack of an enamine on a heterocycle was most interesting. 

This MCR domino process involves initial CFsCOOH-promoted propargylation of the 1,3-dicarbonyl system and subsequent condensation between the resulting y-ketoalkyne 89 and the primary amine to afford the propargylated P-enaminoester 90, which undergoes an Ru-catalyzed 5-exo-dig aimulation to form the cyclic enamine 91, finally tautomerizing to the pyrrole 88. 

---