Imines Enamine tautomerism

L-idose 293, 311 ff. imine formation 57 imine-enamine tautomerization 467 iminium-RhH jt complex 351 f. imipenem 348 indoline ligands 681, 684 indolizomycin 47 Iff. -.retrosynthetic analysis 472ff. 

In marked contrast to the other hetero atom multiple bond functions cited in this section the >C=N- imine bond was not found to undergo hydrometalation. Imines with neighboring C-H bonds as in PhCH=NMe do react with 1 via imine/enamine tautomerism, but not by hydrozirconation [197]. 

Reactions of Halogenation and Nitrosation Nitrones with protons in the a-alkyl group can occur in tautomeric nitrone-hydroxylamine equilibrium (Scheme 2.117) similar to keto-enol and imine-enamine tautomerisms. 

We shall consider the sequence as firstly imine formation (an abbreviated form of this mechanism is shown), followed by imine-enamine tautomerism. This provides a nucleophilic centre and allows a subsequent aldol-type reaction with enamine plus ketone. The pyrrole ring is produced by proton loss and a dehydration. 

The solid-state interaction of enamines (428, 333a) with trans-l,2-diben-zoylethene (87) provides quantitative yields of the pyrrole derivatives 445 or 446 [140]. These remarkable 5-cascades consist of initial vinylogous Michael addition, enol/keto tautomerism, imine/enamine tautomerism, cyclization, and elimination, all within the crystal without melting. A waste-free extraordinary atom economy is achieved that cannot nearly be obtained in solution. The milling times are unusually long here (3 h) but it s certainly worth the effort... 

List later reported the asymmetric reductive amination of a wide spectrum of aromatic and aliphatic a-branched aldehydes via dynamic kinetic resolution (Scheme 5.27) [49]. The initial imine condensation product is believed to undergo fast racemization in the presence of the acid catalyst Ih through an imine/enamine tautomerization pathway. Preferential reductive amination of one of the imine enantiomers furnishes the optically pure P-branched amine. 

Although azides cannot undergo addition to imines (Schiff bases),16,214 when the possibility of imine-enamine tautomerism exists, reaction occurs with the enamine to yield 5-aminotriazolines.35,43,81,180,208,214,223-226 In fact, Alder s N-4 compounds were obtained as shown in Scheme 49. 

The infrared spectrum has been employed mainly to establish the presence22 or absence23 of the NH function in the A3- and A4-triazolines in 10 the NH absorption appears at 3300 cm 1.22 Absence of imine-enamine tautomerization in 7 is also established by IR.6... 

The A-acylimine-enamide tautomerism of methyl 2-acetamidoacrylate has been studied641 by means of ab initio calculations. A 13C NMR investigation has been undertaken to study the tautomerism between the hydrazone imine and diazenylen-amine forms of 3-(arylhydrazono)methyl-2-oxo-l,2-dihydroquinoxalines,642 and the effects of temperature and side-chain on the imine-enamine tautomerism in quinoxalinone and pyridopyrazinone systems have been studied.643 A detailed... 

The imine-enamine tautomerism of 9-aminotetrahydro-4//-pyrido[l,2-a]pyrimidin-4-ones 32 (R = NR3Ph, R3 = H, Me) were studied by H and... 

The reaction with 1-azabutadiene is also unfavorable for other reasons. To begin with, the 4 + 2 cyclization is inherently less exothermic than with 2-azabutadiene (see Exercise 20, p. 123). Furthermore, the enamine product will rapidly undergo side-reactions with adventitious electrophiles. An imine-enamine tautomerism which transforms R-N=CH-CH=CH-CH3 into RNH-CH=CH-CH=CH2 also contributes to lowering the yield. Finally, electron-poor dienophiles may undergo a competing reaction with the nitrogen lone pair. 

Spectroscopic studies of imine-enamine tautomerism have shown that the equilibrium is almost completely in favour of the imine form for simple aldehydes and ketones372-374. Nevertheless, some secondary enamines are sufficiently stable to exist in detectable amounts in equilibrium with the corresponding imines for example, the f-butylamine imine of cyclohexanone shows signals due to the secondary enamine tautomer in the NMR spectrum (<5=CH 4.6)375. Studies of the imine-enamine equilibria have shown, as expected, that the enamine form is stabilized by methyl or aryl substituents at the -position (Scheme 189). 

When treated with lead tetraacetate (LTA) enamines (and also imines capable of imine-enamine tautomerism) underwent either a- or -elimination, depending on the nature of the substrate, furnishing 2-acetoxy ketones and 2-amino ketones as final products67 (Scheme 47). 

At the onset of this study, we hypothesized that under our reductive amination conditions an a-branched aldehyde substrate would undergo a fast racemization in the presence of the amine and acid catalyst via an imine/enamine tautomerization. The reductive amination of one of the two imine enantiomers would then have to be faster than that of the other, resulting in an enantiomerically enriched product via a dynamic kinetic resolution (Scheme 15 for reviews, see Noyori et al. 1995 Ward 1995 Caddick and Jenkins 1996 Stecher and Faber 1997 Huerta et al. 2001 Perllissier 2003). 

The ketimine (13a), prepared from desoxybenzoin and aniline, is also subject to a solvent-dependent tautomerism called imine/enamine tautomerism. The enamine content of a solution of (13a) increases in the order tetrachloromethane (31 cmol/mol at 35 °C), [Dsjpyridine (47.5 cmol/mol at 55 °C), and [Dejdimethyl sulfoxide (67 cmol/mol at 55 °C) [69], Hydrogen-bond acceptor solvents favour the enamine form (13b) due to hydrogen-bonding, whereas in less polar and apolar solvents the equilibrium is shifted towards the imine form / 13a) [69]. 

Other remarkable cases of solvent-dependent imine/enamine tautomerism have been reported by Ahlbrecht et al. [147], Schefifold et al [69a], and Perez-Ossorio et al. [211]. 

---