Aminocrotonates configuration

At least two pathways have been proposed for the Nenitzescu reaction. The mechanism outlined below is generally accepted." Illustrated here is the indolization of the 1,4-benzoquinone (4) with ethyl 3-aminocrotonate (5). The mechanism consists of four stages (I) Michael addition of the carbon terminal of the enamine 5 to quinone 4 (II) Oxidation of the resulting hydroquinone 10 to the quinone 11 either by the starting quinone 4 or the quinonimmonium intermediate 13, which is generated at a later stage (HI) Cyclization of the quinone adduct 11, if in the cw-configuration, to the carbinolamine 12 or quinonimmonium intermediate 13 (IV) Reduction of the intermediates 12 or 13 to the 5-hydroxyindole 6 by the initial hydroquinone adduct 7 (or 8, 9,10). 

The modified Hantzsch condensation of nitroacetone, 2,l,3-benzoxadiazol-4-carboxaldehyde 253, and ( S,ZR)-Z-(3,5-dinitrophenylcarbonylamino)-2-methoxycarbonyl-l-methylethyl 3-aminocrotonate afforded a mixture of the two diastereomers that differ in configuration (S or R) at the C-4 position of the 1,4-DHP ring (DHP - dehydropeptidase) (Equation 49) <2004JME254>. 

N-Substituted 3-aminocrotonic esters (67) tend to adopt a planar or near-planar structure. As a consequence of their push-pull nature these molecules show an increased facility for Z-67-is-67 isomerization around the C=C double bond as well as restricted rotation around the C—N and C—COOR2 single bonds. The IR and XH-NMR spectra of simple 3-(alkylamino)crotonic esters have shown that these substances exist either in the liquid state or in solution as equilibrium mixtures of the Z and E configurations, respectively. The position of the equilibrium is solvent-dependent, and the energy difference between the isomers varies from ca 7.3 kJ mol-1 in non-polar solvents to ca 0.8 kJ mol"1 in dimethyl sulphoxide, the intramolecularly bonded Z-form 68 or 69 being the most stable111-113. 

Similarly, / -aminocrotonates of Z configuration afforded the corresponding pyrroles71. In contrast, with /Taminocinnamates (R1 = Ph) the yields of the corresponding... 

Ethyl 3-(benzylamino)crotonate (67) R = CH2ph, R = Et) can be obtained in two crystalline forms, which on the basis of their spectra and other physical evidence were shown to be the Z- and fi-isomers. On the other hand, 3-aminocrotonic esters with primary amino groups exist in the liquid state and in solution almost exclusively as the isomers with the chelated 68 Z (R H) configuration" . 

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