Enamine-imine shift

Extensive studies have shown that the enamine-imine tautomeric equilibrium of equation 1 shifts almost completely to the enamine side when an unsaturated electron-withdrawing group including nitrile nitro °, carbonyl, thiocarbonyP etc. ° is attached to the -carbon. Reviews related to these enamines which include enaminoni-triles 2, nitroenamines 3, enaminones 4 and the enaminothioketones 5, have appeared in the literature, ... 

In direct analogy to Solladi6 s work with P-ketosulfoxides, Ruano has investigated the DIBAL reduction of A-benzyl-P-iminosulfoxides (30) [27]. DIBAL alone was found to be inactive toward (30) however in the presence of ZnBr2 as Lewis acid, the reduction was observed to be highly diastereoselective (Scheme 4.18, Table 4.6). This behaviour can be explained by assuming that the Lewis acid stabilizes the (E) regioisomer of the P-iminosulfoxide tautomer by formation of a chelate which shifts the enamine-imine equilibrium toward the latter. This chelated tautomer is now readily reduced by DIBAL. To verify this proposal, the influence of the Lewis acid on the enamine-imine equilibrium was studied by NMR spectroscopy (R = Ph). It was observed that the initially formed enaminic tautomer was converted completely into the iminic form by addition of the ZnBrj. 

The intramolecular Heck reaction presented in Scheme 8 is also interesting and worthy of comment. Rawal s potentially general strategy for the stereocontrolled synthesis of the Strychnos alkaloids is predicated on the palladium-mediated intramolecular Heck reaction. In a concise synthesis of ( )-dehydrotubifoline [( )-40],22 Rawal et al. accomplished the conversion of compound 36 to the natural product under the conditions of Jeffery.23 In this ring-forming reaction, the a-alkenylpalladium(n) complex formed in the initial oxidative addition step engages the proximate cyclohexene double bond in a Heck cyclization, affording enamine 39 after syn /2-hydride elimination. The latter substance is a participant in a tautomeric equilibrium with imine ( )-40, which happens to be shifted substantially in favor of ( )-40. 

Surprisingly, imino carbon shifts of strained 2 7/-azirines [431] do not differ substantially from those of open-chain imines (Section 4.9.3). On the other hand, the alkene carbon shifts of l-azabicyclo[2.2.2]oct-2-ene do not reflect the polarization characteristic of other enamines (Section 4.9.2) (+ )-M electron donation of the bridgehead enamino nitrogen cannot take place since the lone-pair orbital and the p orbitals of the it bond are... 

The UV spectra of 9-(phenylamino)tetrahydro-4f/-pyrido[ 1,2-a] pyrimidin-4-ones 23 indicated the presence of an imine-enamine type of tautomerism in solution. A carboxyl or ester group in position 3 (R1 = COOR3 R3 = H, Et) and a methyl group in position 6 (R = Me) shifted the equilibrium toward the enamine form in a polar solvent [85JCS(P1) 1015]. For the imine tautomer, UV maxima at 235-250 nm and 280-300 nm and for the enamine absorbances at 260-265 nm and 355— 365 nm are characteristic. 

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]. 

Horvath et reported that the tricyclic formyl derivatives 390 n = 0-2) exhibit triple tautomerism between forms 451 and 453. The imine-enamine-enol tautomerism depends greatly on the ring size ( ). A significant solvent dependence was observed only for the pyirolo[2,l-i ]-quinazolinones 390 n = 0), which in ethanolic solution exist predominantly in the imino form (451), and in chloroform in the enol form (453). H-NMR spectroscopy showed that in chloroform the proportion of the imine tautomer 451 was about 5%. The fast equilibrium between the en-amine and enol forms 452 and 453 was shifted considerably toward the enamine tautomer 452 in the case of the pyrido[2,l-fi]quinazolinones 390 ( = 1). The azepino[2,1 -6]quinazoline ( = 2, R = 2-NO2) is a 2 3 mixture of the imine and the enamine tautomers 451 and 452. 

There are other types of proton shift tautomers, such as phenol/dienone, nitroso/oxime and imine/enamine, but these are less often encountered. There are also valence tautomers that exhibit fluxional structures, which undergo rapid sigmatropic rearrangements. Molecules that exhibit this type of isomerism are very interesting, but are not often encountered in undergraduate courses. An example of a valence tautomer is illustrated by the Cope system. 

Tautomerization is the shift of an H from a carbon adjacent to a carbon-heteroatom double bond to the heteroatom itself (and the reverse). It is an acid- or base-catalyzed equilibrium. Two examples are the keto/enol pair (Z = oxygen) and the imine/enamine pair (Z = nitrogen). Base catalysis goes via the enolate anion. 

A detailed investigation of the photolysis mechanism of enamines has been conducted by Hoffmann and Eicken The rearrangement proceeds through radical processes. When A -acylenamine 73 was irradiated at the wavelength corresponding to the n n -transition of the amide at approximately 200 nm, the amide bond was cleaved to the radical pair. This radical pair could either recombine and revert back to the reactant or undergo a [l,3]-acyl shift to give the imine 74. In turn 74 underwent rapid tautomerization to the enaminone 75, which was in photochemical equilibrium with its isomer 75 (Scheme 6). 

Unfortunately the nitrogen atom lowers the HOMO energy of the diene 24 and it is not a good match with the LUMO of maleic anhydride. Instead the imine 24 is in equilibrium with the enam-ine 27 and, in conformation 27b, this has a high energy HOMO and so the product2 of the reaction is 28. The tautomerism between 24 and 27 may be especially easy as it can be drawn as a [1,5]H sigmatropic shift. This conflict between weakly electrophilic imines and their tautomers, the nucleophilic enamines, is one of the themes of this chapter.1... 

Instead of homoaromaticity in the CDC13 spectra of 4,6-diphenyl-1,2-dihydropyrimidine, two new triplets were observed at 8 3.56 (J = 6.6 Hz) and 8 5.79 (J = 6.6 Hz). These were assigned to 4,6-diphenyl-2,5-dihydropyrimidine (21b) (Fig. 8), the second tautomeric form of the imine-enamine tautomeric equilibrium. The ratio of 21a to 21b is 2 1. In DMSO-d6 solution, the equilibrium shifts completely toward 1,2-dihydropyrimidine 21a because of strong intermolecular hydrogen bonding with the solvent. An analogous effect was observed in 1,6-dihydropyrazine.46... 

Existence of this imine-enamine tautomerism is clearly indicated in the 13C-NMR spectrum of 21a in CDC13 (Fig. 9). A simple calculation using the concentrations of the two tautomers in CDC13 gives the value of AG° in this solvent as 0.41 kcal mol-1.184 Unsymetrically substituted 1,2-dihydropyrim-idines undergo tautomeric equilibration via [l,5]-hydrogen shift.49... 

Asymmetric Michael reactions have heen conducted with assistance of C2-symmetric malonamides derived from (5)-ptohne esters/ 2-Methyl-3,4,5,6-tetrahydropyridine and 2-cyclopentenone are condensed to afford a tricyclic alcohol. The reaction starts from Michael reaction of the endocychc enamine isomer and as the double bond shifts to the exo-cychc position an intramolecular aldol reaction follows. If the imine is hthiated, the initial Michael reaction (CuBr-catalyzed) then involves the exocyclic carbon. ... 

We propose the biosynthetic pathway of the carbon framework of matrine as shown in Fig. 4. This scheme also indicates the pathway for the formation of sparteine and lupanine. The former part of this scheme was proposed by Wink et al. [63], with minor modification by Leete [64], from the in vitro experiments using isolated chloroplasts of leaves of Lupinus. They postulated the presence of 17-oxosparteine as the first key intermediate for the formation of lupanine and sparteine [63]. However, this hypothesis involving 17-oxosparteine synthase was not confirmed by the tracer experiments using and independently conducted by the groups of Spenser [65, 66] and Robins [67]. They, in turn, hypothesized the pathway involving the diiminium cation (73) as the tetracyclic intermediate [68, 69]. The postulation of the presence of this reactive intermediate is consistent with the results of isotope incorporation into lupanine and sparteine. The biosynthetic scheme of matrine can be also drawn by involving the electronically equivalent diiminium cation (76) preceded by additional 1,3-hydride shift or imine-enamine isomerization (74 75). All these reactions take... 

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