Enamines tautomers

Extensions of 1,3-dipolar additions of aromatic azides (720,721) to other enamines (636), and particularly to the enamine tautomer of SchilTs bases, were explored (722,723). Further nitrone additions were reported (724,725) and a double nitrile oxide added to an endiamine (647). Cyanogen azide and enamines gave cyanoamidines through rearrangement (726). 

Another approachl2a e makes use of bilenimincs which can be photochemically cyclized to isobacteriochlorins. A plausible mechanism for this ring-closure process involves the formation of an enamine tautomer from the imine at the 1-position, which is then cyclized in a photochemical 1 STc-n-isomcrization process followed by elimination of the leaving group at the 19-... 

Enamines are normally stable only when there is no hydrogen on the nitrogen (R2C=CR—NR2). Otherwise, the imine form predominates. The energy of various imine-enamine tautomers has been calculated. ... 

Under the same reaction conditions, -keto esters which have been alkylated on the a-carbon atom (thus leading to 3,4-disubstituted 5-pyrazolones upon treatment with hydrazine) give allenic esters in good (50-70%) yield (158). The mechanism (Scheme 36) again appears to involve thallation of the enamine tautomer of the 5 -pyrazolone, but deprotonation now takes place... 

The spiro compound 206 was prepared in five steps from (S)-l-naphthyl-ethylamine and was composed of a mixture of imine and enamine tautomers. Reduction of the imine function by sodium borohydride occurred on the less hindered si face, leading to the diamine with the R configuration of the newly formed stereo center, then the N-benzyl substituent was removed by hydrogenolysis to give 207 with good overall yield [98] (Scheme 30). 

Hansen et al.52 measured the deuterium isotope effects for the Schiff base being a derivative of racemic gossypol [7]. The high negative value of deuterium isotope effect observed at carbon C-7 linked with proton donor group (—190 — 240 ppb), solvent and temperature independent, clearly indicated the existence of this compound as enamine-enamine tautomer. 

The reaction of 2-polyfluoroalkylchromones (e.g., 323) with l,3,3-dimethyl-3,4-dihydroisoquinolines (e.g., 324) gave zwitterionic 6,7-dihydrobenzo[ ]quinolizinium compounds such as 326 (Scheme 70). The mechanism proposed for this transformation involves an addition-elimination displacement of the chromane heterocyclic oxygen by the enamine tautomer of the dihydroisoquinoline, followed by intramolecular cyclization of the intermediate 325 <20030L3123>. 

Condensation of aryl halides with various active methylene compounds is readily promoted by catalytic action of palladium to give the corresponding arene derivatives containing a functionalized ethyl group [7]. Yamanaka et al. extended this chemistry to haloazoles including oxazoles, thiazoles and imidazoles [8]. Thus, in the presence of Pd(Ph3P)4,2-chlorooxazole was refluxed with phenylsulfonylacetonitrile and NaH to form 4,5-diphenyl-a-phenylsulfonyl-2-oxazoloacetonitrile, which existed predominantly as its enamine tautomer. In a similar fashion, 4-bromooxazole and 5-bromooxazole also were condensed with phenylsulfonylacetonitrile under the same conditions. 

Since 1960, almost all papers have provided at least some spectroscopic evidence that these compounds (1 and 2) exist as the enamine tautomer in solid phase or in solution. Imine tautomers have been detected for only those aminomethylenemalonates in which R2 and R3 formed a ring (e.g., 83IZV1687, 83MI2 88ZOR1793). This chapter will examine only certain papers in which details of spectroscopic investigations or quantum-chemical calculations are given. 

The prototropic tautomerism of 8-azaadenine has been studied theoretically in both the gas phase and aqueous solution by means of ab initio methods. It has been shown that dehydrovaline (399 R =Me, R = H, R = Me), dehydrophenylalanine (399 R = Ph, R, R = H), and dehydropipecolinic acid [399 R R = (CH2)3, R = H] hydrolyse rapidly via the imine tautomer (400) even when the corresponding esters and sodium salts exist as the enamine tautomers. The 3-methoxy-substituted deriva-... 

Imines derived from ketones with an a-methylene group can react via their enamine tautomers, and mixtures of triazoles are also isolated from these systems. The triazoline adducts of the enamine tautomers are aromatized by treating with acid, and in these conditions the triazoline appears to undergo a Dimroth rearrangement before elimination of the amine, because two triazoles are obtained, one of which has... 

The reaction is exactly analogous to the chemical aldol reaction (also shown), but it utilizes an enamine as the nucleophile, and it can thus be achieved under typical enzymic conditions, i.e. around neutrality and at room temperature. There is one subtle difference though, in that the enzyme produces an enamine from a primary amine. We have indicated that enamine formation is a property of secondary amines, whereas primary amines react with aldehydes and ketones to form imines (see Section 7.7.1). Thus, a further property of the enzyme is to help stabilize the enamine tautomer relative to the imine. 

Surtabie iFTiines are commortiy ir equtiibrn,jnn with enamine tautomers ... 

A way forward might be to form the imine 7.3 [and hence its enamine tautomer 7.4] by reacting the phenylamine 7.2 with cyclohexanone (Scheme 7.18). Then to generate the benzyne anion 7.5 by treating the tautomers with sodamide and sodium fcr/-buloxide in THF. Cydization to the required indole 7.1 occurs through nucleophilic addition to the benzyne, followed by protonation during work-up. 

A recent report on trifluoromethylsulfenylation of (3-keto acids and derivatives describes isolation of 29 in good yield from reaction of 27 with trifluoromethyl-sulfenyl chloride (Scheme 6.10). Mechanistically, this was rationalized via electrophilic attack of trifluoromethylsulfenyl chloride on the enamine tautomer 27a to generate 28 followed by intramolecular cyclization through the imide oxygen with concomitant loss of CF3SH to produce 29. The product was characterized spectroscopically. 

Reaction of aryl hydrazines and hydrazine with dimethyl acetylene dicarboxylate to afford imine-enamine tautomers [192]. 

The oxidation of 2,3-dimethylindole with peroxodisulfate and peroxomonosulfate yields 3-methy-lindole-2-carbaldehyde (136) (88JCS(P2)1065). The reaction proceeds in three steps, namely electrophilic attack of the peroxide at C-3 to give an indolenine intermediate (134), then peroxide attack on the enamine tautomer (135), and hydrolysis (Scheme 26) (93JOC7469). 

A -Arylimincs (21a) can be oxidatively rearranged to fonnamides (21b) with sodium perborate.42 The reaction works best for secondary or aryl R groups. An oxaziridine intermediate is proposed. Results with chiral secondary R groups indicate epimeriza-tion, suggested to occur via equilibration of (21a) with its enamine tautomer. 

Tautomeric equilibrium of dihydro-l,2,4-triazolopyrimidines is practically insensitive to the electronic character of substituent R [156, 428, 432] (Scheme 3.139), but in some cases the tendency to shift the equilibrium to the dihydroform B is observed with increasing donor properties. The influence of the size of the substituent R on tautomerism is described in [427, 433]. The most probable reason for the increase in the concentration of form A with increasing size of the substituent at position 7 is the flexibility of the enamine tautomer allowing the R group to occupy a more favorable conformation that in the case of form B. 

It is of interest to comment on the position of the equilibrium between 5-alkyldehydrohydantoins and the 5-methylene (enamine) tautomers. The isolation of the 5-methylene isomers exclusively under what must have been equilibrating conditions indicates that the equilibrium lies very far to the right. 

Now consider condensation of ammonia with ketoester 1.18. The isolated product is not imine 1.19 but the thermodynamically more stable enamine tautomer 1.20 which has a conjugated double bond system and a strong intramolecular hydrogen-bond. Although not a heterocyclic example, 1.20 illustrates that an enamine-like linkage, as in generalised heterocycle 1.21, is also accessible by a condensation reaction. 

As a-aminoketones are prone to self-condensation (see page 22 for a discussion of a-aminoketones), the initial condensation step is facilitated by R2 in 2.22 being an electron-withdrawing group. This enhances the electrophilic nature of the ketone carbonyl group thereby increasing the rate of the desired reaction, and favours enamine tautomer 2.24 over the imino... 

Deprotonation of the imine 86 (R1 = H, R2 = Bn, entry 1) with LDA (1 equiv.) at -35 °C afforded an azaenolate which was diastereoselectively attacked at -78 °C by the electrophilic reagent DBAD (1.5 equiv.). After 3 min the reaction was quenched with a 10 % aqueous NH4C1 solution. After classical work-up and flash chromatography, the aminated product 87 was obtained in 66% yield as a 7 3 mixture of diastereomers 87a 87b (method A). The major diastereomer was characterized by NMR spectroscopy (DMSO-d6,100 °C). Due to an imine-enamine tautomer-ism, 86 could be aminated without previous deprotonation 86 reacted with DBAD (1.4 equiv.) in THF at 0 °C for 1 h. After evaporation of the solvent and flash chromatography, 87a and 87b were isolated in 72 % yield with a diastereomeric ratio of 75 25 (method B). 

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