Push-pull enamines

Imidazo [1,2-fl]pyrimidines can be obtained from enediaminonitriles and A-acyliminoethers (96SC453). The unusual transformation of push-pull enamines into 4,6-dimethylamino-5-nitropyrimidine has been carried out (97KGS343). A facile synthetic method for pyrimidine derivatives based on fluorine-containing enaminoketones has recently been published (97H349). 

The crystal structures of a large number of push-pull enamines (10-16) have been determined, and C=C bond lengths between 133.0 and 141.2 pm have been observed45 (Table 4). The fundamental information about the geometry of the enamine moiety has... 

In push-pull enamines the groups X1 and X2 are capable of stabilizing a negative charge, while the nitrogen atom, on the second trigonal carbon, bears a positive charge. The structure of 27 clearly implies reduction of the bond order of the formally localized double bond in 26 and a concomitant increase in the orders of the C—N and the C—X1 and C—X2 bonds. 

TABLE 11. Barriers to rotation about the C—N and C—C bonds of push-pull enamines... 

Another way to avoid the difluorination can be achieved by using of push-pull enamines aud Selectfluor or NFSI as fluorine source (Scheme 17) [92,94]. 

Resin-bound amines can be converted into imines [710,711] or enamines by reaction with carbonyl compounds (Entries 6 and 7, Table 3.39). Resin-bound enamines have also been prepared by Michael addition of resin-bound secondary amines to acceptor-substituted alkynes [712], by Hg(II)-catalyzed addition of resin-bound secondary amines to unactivated alkynes [713], by addition of C-nucleophiles to resin-bound imino ethers [714], and by chemical modification of other resin-bound enamines [712,713,715], Acceptor-substituted enamines ( push-pull alkenes) are not always susceptible to hydrolytic cleavage by TFA alone and might require aqueous acids to undergo hydrolysis [716]. 

Electron withdrawing substituents such as aldehyde or imonium functions at the other end of the alkene or the 1,3-diene transform enamines and 1,3-dienamines into push-pull systems characteristic of dyes. Electron release (push) of the donor group shields the / , S, e,... carbons and electron withdrawal (pull) of the acceptor group (carbonyl oxygen or imonium nitrogen) deshields in the a, y,... position [343],... 

Indoles, which are especially electron-rich and thus unsuitable for ordinary Diels-Alder reactions, have performed successfully in the cation-radical reaction as dienophiles (Scheme 44)107 and as dienes (Scheme 45)126. Interestingly, the site of annulation (across the C—C or the C—N bond) in vinylindole cation radicals (functioning as dienes for eneamine dienophiles) may be manipulated by varying the substituent on the enamine and thereby altering its push-pull nature (Scheme 45). 

In the case of primary (and secondary60) jff-keto enamines, the enamino keto form 30a or 31a is stabilized by its push-pull conjugated mesomeric form 30b or 31b and by an intramolecular hydrogen bridge which dominates over the tautomeric imino enol form 30c or 31c (equation 3). Similar results are reported for jft-thioketone enamines61. 

X-ray determinations of the molecular structures of thirteen / -enaminones 84 to 96 with the formal possibility of push-pull conjugation and the formulae shown in Scheme 3 cover the range of tertiary 84 to 86, and 89 to 92, secondary 87,88 and 93, and primary 94 to 96 / -keto enamines. Relevant distances are given in Table 1 and angles in Table 2. 

In the case of doubly push-pull substituted enamines 88 to 92 and 106 to 107, instead of through conjugation a tendency to adopt a zwitterionic form is observed. This form is characterized by a very long C=C distance between 1.407 to 1.482 A, very short C—N lengths of 1.312 to 1.352 A and shows various angles of twist around the C=C bond. 

F4—enamines with push-pull through-conjugation effect. 

A push-pull through-conjugation effect on some of the enamine geometrical parameters was detected. 

The spectral properties of enamines having one or two electron-withdrawing groups, usually acyl, phenyl, nitro, cyano or ester substituents, so called push-pull enamines92-94, have been extensively investigated due to the information they provide on the electronic distribution in such mesomeric systems, and on their static and dynamic conformational properties95 NMR spectroscopy has been the most popular technique for these studies. 

Important classes of enamines are those having electron-withdrawing substituents, R2 and/or R3, at C(2), particularly when the substituent(s) act(s) by a +R effect, as in aminoenones and nitroenamines. The stronger and more extensive electron delocalization and the concomitant changes in bond orders of the resulting push-pull systems is well reflected in the NMR spectra and have been extensively investigated in this way. 

Experimental and theoretical studies on the solvent influence on molecular geometries and cis/trans isomerization processes of other so-called push-pull ethenes, R2N CH=CH A R2N+=CH CH=A- (with A = NO2, CHO, CN, etc.), have been collected in references [287, 288], The barriers to isomerization about the C=C bonds of these acceptor-substituted enamines are considerably smaller than those for simple ethenes such as 2-butene Ea = 259 kJ/mol [82]), owing to a significant contribution of the mesomeric zwitterionic structure to the electronic ground state. Increasing solvent polarity increases the contribution of this dipolar mesomeric structure, and hence leads to a decrease in the barrier to C=C isomerization and a simultaneous increase in the barrier to rotation about the C—N bond [288], The calculated sequence of solvent stabilization for such acceptor-substituted enamines is (activated complex for C=C rotation) E form > Z form > (activated complex for C—N rotation). Obviously, the activated complex for isomerization about the C=C bond corresponds to a full zwitterion with maximal solvent stabilization [288]. 

Another classical approach to 3-carbolines involves Bischler-Napieralski reaction of indoles, the intramolecular cyclization of iminium chlorides derived from tryptamides. Triphenylphosphite proved to be a mild reagent capable of promoting this reaction <05SL661>. The cyclization of ketene iV,S-acetals derived from tryptamine produced push-pull P-carboline enamines <05SL309>. 

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