Enamines structures

The rearrangement discovered by Kolosova et al. probably involves such reactivit (159). This reaction provides a good preparative method for various 5-amino-methylthiazoles (Scheme 43). No mechanism is proposed in the report, and it is not easy to understand how the C-5 enamine-like position competes with the very nucleophilic thiocarbonyl group of the formed A-4-thiazoline-2-thione. An alternative mechanism could start with ethanol addition at C-2. leading to the A-4-thiazoline (90) (Scheme 44). In this intermediate, C-5 nucleophilic reactivity would be favored bv the true enaminic structure. After alkylation on C-5,... 

Since Stork et al. introduced as a new synthetic method the alkylation and acylation of carbonyl compounds via enamines, this class of compounds has been the subjeet of intensive studies 1-3). The exceptional physical and chemical behavior of the enamine structure can be ascribed to resonance by conjugation of the unshared pair of electrons of the nitrogen atom with the 77 electrons of the double bond ... 

The addition of ethyl acrylate to both possible enamine structures of... 

The piperideine derivatives have not been studied as extensively as the analogous pyrrolines (151,152). The imino structure has been established, for example, for the alkaloid y-coniceine (146) (46). The great influence of conjugation on the structure is seen with l-(a-picolyl)-6,7-methylenedioxy-3,4-dihydroisoquinoline (47), possessing an enamine structure, whereas the analogous 1-methyl derivative (48) possesses an imine structure according to infrared spectra (152,153). 

The addition of ethyl acrylate to 1,2-dimethyl- -piperideine 163), l-methyl-2-ethyl-zJ -piperideine 164), and 1,2-dimethyl- -pyrrolidine 216,217) occurs, yielding both possible enamine structures (138 and 139, n=I,2). 

Until recently the products of all nitrile cyclizations by the Thorpe reaction had been formulated as imines, although the products were found in 1955 to be better written as the enamine structure. In order to verify the reaction mechanism of the Thorpe reaction, the solid-state reaction of 84 and Bu OK was monitored by measurement of IR spectra in Nujol mulls. As the reaction proceeds (Scheme 14), the CN absorption of 84 at 2250 cm" decreases and a new CN absorption of the imine intermediate (87) arises at 2143 cm As 87 is converted into 88 by a proton migration, the CN absorption of 87 at 2143 cm" disappears, and only the CN absorption of 88 at 2189 cm remains finally [13]. 

Phenylsulphine prepared in situ from phenylmethanesulphinyl chloride and triethyl-amine reacted with 1-morpholinocyclohexene to form the addition product 169 having the enamine structure A similar experiment with phenylsulphine and 2-pyrrolidinocyclo-hexene gave only 2-phenylmethanesulphinyl cyclohexanone 170. The latter is most probably formed by hydrolysis of the corresponding enamine sulphoxide upon isolation. The reaction of sulphines with enamines is apparently a stepwise process involving the transient formation of the dipolar intermediate 171 which is stabilized by proton transfer, giving the enamine sulphoxide. 

In 2008, the same group employed chiral dicarboxylic acid (R)-5 (5 mol%, R = 4- Bu-2,6-Me2-CgHj) as the catalyst in the asymmetric addition of aldehyde N,N-dialkylhydrazones 81 to aromatic iV-Boc-imines 11 in the presence of 4 A molecular sieves to provide a-amino hydrazones 176, valuable precursors of a-amino ketones, in good yields with excellent enantioselectivities (35-89%, 84-99% ee) (Scheme 74) [93], Aldehyde hydrazones are known as a class of acyl anion equivalents due to their aza-enamine structure. Their application in the field of asymmetric catalysis has been limited to the use of formaldehyde hydrazones (Scheme 30). Remarkably, the dicarboxylic acid-catalyzed method applied not only to formaldehyde hydrazone 81a (R = H) but also allowed for the use of various aryl-aldehyde hydrazones 81b (R = Ar) under shghtly modified conditions. Prior to this... 

Electron transfer reduction of pyridines in both acid and alkaline solution generates the protonated radical-anion. This rapidly accepts a further electron and a proton to give a mixture of dihydropyridines. Enamine structures in these dihydro-pyridines can tautomerise to the imine, which is more readily reduced than the original pyridine molecule. Further reaction of the 1,4-dihydropyridine leads to piperidine while reduction of the t, 2-dihydropyridine leads to a tetrahydropyridine in which the alkene group cannot tautomerise to the imine and which is not therefore reduced to the piperidine stage. The reaction sequence is illustrated for 2,6-dimethyl-pyridine 18 which yields the thermodynamically favoured cis-2,6-dimethylpiperidine in which the two alkyl substituents occupy equatorial conformations. 

Oxidation of the enamine 74 via the anion of enolamine 75 yields 76 which cannot be formed from 77 in alkaline medium. Cleavage of 76 according to Abramovitch s hypothesis is the last step of the reaction. If formation of the enolamine is prevented by alkylation of the 2-a-methylene group as in 78, oxidation of the pseudobase 79 in equilibrium with the enamine structure leads to the formation of 80-82. In addition, C-6 pseudobases are dehydrated to give 83 (86ZN(B)655) (Scheme 17). 

From a more synthetic perspective, reaction of the aUtenylmagnesium derivatives with electrophiles is very interesting. Indeed, if the intermediates could be trapped with electrophiles, the reaction would provide a novel route to the preparation of nitrogen-containing heterocycles having a fully substituted enamine structure. This expectation proved to be possible (Table... 

TABLE 11. Synthesis of phenothiazine having a fully substituted enamine structure (181)... 

TPP (40). Loss of CO2 from (40) is facilitated by the thiazolium ring which acts as an electron sink. (41) has an enamine structure thus, the original a-carbon atom of pyruvate has a considerable amount of carbanion character, and should therefore add to electrophilic reagents readily. Protonation of (41) at this carbon to give hydroxyethyl-TPP (42), followed by elimination of (39), produces acetaldehyde. 

In the absence of a trichloromethyl group in the enamine structure, the process follows a different route. Thus, the cyanoacetic ester dimer reacts with cyanogen bromide at its active methylene group with a ring closure... 

An enamine structure written for compound 96 shown in the sequence of Eq. (70) puts this rearrangement of an oxadiazole into the... 

In streptocyanine dyes both ends of the methine chain are joined directly to nitrogen atoms, and a double enamine structure is thus present. The dyes are extremely susceptible to hydrolysis, particularly if they contain secondary nitrogen atoms. Stable dyes are obtained if the nitrogen is part of a heterocyclic ring system. Streptocyanine dyes are brilliant yellow dyes that dye polyacrylonitrile and acid-modified polyamide fibers with outstanding lightfastness [1],... 

The mechanism of the thermal decomposition of NMMO and Lyocell solutions is extremely complex since the reaction, initiated by the action of carbenium-iminium ions, quickly enters an uncontrollable course. A central question was whether the heterocyclic ring of NMMO was cleaved during the reaction and whether products of this cleavage, having either vinyl ether or enamine structures, could be detected. Employing the trapping agents... 

Scheme 13 In situ trapping of vinyl ether and enamine structures in the mixture of uncontrolled thermal decomposition of NMMO...

Origin and formation pathways of the different vinyl ether and enamine structures in mixtures from the uncontrolled NMMO degradation were difficult to assess, since the high temperatures during such processes also allowed disfavored decomposition processes to proceed, which are thermodynamically forbidden or disfavored under the usual Lyocell process conditions. 

The typical behavior of enamines has been mainly observed for compounds possessing a tertiary nitrogen atom.1 The analogous derivatives with a secondary amino group (the a,j8-unsaturated secondary amines) could, in principle, possess either the imino or the tautomeric enamine structure, but the first possibility is preferred practically without exception. In the text, some examples of their properties are quoted for the sake of comparison with those of tertiary enamines on these occasions, the group designation imines is used. Nucleophilic reactions of a limited number of aromatic heterocyclic systems are also included when they are similar to the reactions of enamines and illustrate the specific character of the enamine grouping. 

The double bond is kept in the exocyclic position by conjugation with the carbonyl group (the free base absorbs at 3270 cm-1). The free base of l-(a-picolyl)-6,7-methylenedioxy-3,4-dihydroisoquinoline also possesses the stabilized enamine structure, whereas the imino structure is exhibited by the 1-methyl analog, as shown by comparison of the... 

The study of the enamine structure may be associated, to a certain degree, with the problem of the so-called pseudobases an instructive, but somewhat specialized, review of these compounds was contributed by the late Professor Beke 47 to the first volume of this series. The name pseudobases was given by Hantzsch,48 towards the end of the last century, to those a-aminocarbinols which undergo a structural change during salt formation and yield salts with the loss of one molecule of water. The liberation of pseudobases from their salts is accompanied by rehydration. This behavior has been observed with a,/3-unsaturated heterocyclic compounds and, to a certain degree, with aromatic heterocyclic pyridine derivatives. As formulated by Gadamer,49 the pseudobases represent a potential tautomeric system of three components, the quaternary hydroxide A, the carbinolamine B, and the open-chain amino-carbonyl derivative C, in which all three components exist in a mobile equilibrium ... 

C. Physical and Chemical Methods Used to Study the Enamine Structure... 

The monoarylated enamine can then be acylated to form a mixture of 2-acyl-2-arylcyclohexanone and 2-aryl-6-acylcyclohexanone. This was held to indicate that arylation affords two enamines, 62 and 63, which differ only in the position of the double bond. The reaction involving acyl halides could be explained under the assumption that in the more probable enamine structure (with conjugation through the free electron pair on nitrogen, the double bond, and the aromatic ring) it is the hydrogen atom on C(6) which is more acidic. 

A. G. Cook, Enamines, Structures and Reactions, Second Edition, Marcel Dekker, New York and Basel, 1988. 

IR, UV and NMR spectra obtained so far are compatible with the structure of the secondary enamines. The tautomeric enamine structure of some enaminones in the solid state has also been established unambiguously by single-crystal X-ray diffraction analyses21. In agreement with the experimental evidence, theoretical calculations22,23 performed on enaminones 6-8 and nitroenamine 9 indicate that the enamine forms are... 

The modern era of enamine chemistry is considered to have begun with Stork and coworkers in 19545. Stork and others initiated programs in which the controlled /Lcarbon nucleophilicity of the vinylamine functional group was exploited. Reviews of this work and of other aspects of enamine structure and function were not long in coming50,6. 

Enamines have been recognized in organic chemistry as useful synthetic reagents since the early reports from Stork s laboratory1. At almost the same time similar chemical moieties were being implicated in biochemical systems. Because of their intrinsic instability in water, the biochemical enamines exist primarily as intermediates, although, some well-known coenzymes that participate in oxidation-reduction reactions also incorporate enamine structures in one of their oxidation states. The electronic structure of enamines involves two extreme resonance contributions as shown in equation 1. 

The formation of stereogenic C-N bonds by hydrogenation of the enamine structure is not only limited to amino acids. Likewise, chiral 1,2-aminoalcohols or 1,2-diamines can be produced by the enantioselective hydrogenation of dehydro-p-amino alcohols (or their esters) and of dehydro-a-amino aldoximes, respectively (eq 6 and eq 7, Thble 2). Esters and aldoximes thus obtained can be converted into the corresponding alcohols or diamines by standard methods. By this means, simple amines with one aryl group attached to the double bond can also be hydrogenated with high enantioselectivity. ... 

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