Enamine salts, structure protonation

In the case of enamines protonation on nitrogen or carbon is possible and gives the conjugate acids 4 and 5, respectively. Whereas the final isolated product has the iminium salt structure (5), recent work 10-12) has shown... 

In the thiazolium cation the proton in the 2-position is acidic and its removal gives rise to the ylide/carbene 227. This nucleophilic carbene 227 can add, e.g., to an aldehyde to produce the cationic primary addition product 228. The latter, again via C-deprotonation, affords the enamine-like structure 229. Nucleophilic addition of 229 to either an aldehyde or a Michael-acceptor affords compound(s) 230. The catalytic cycle is completed by deprotonation and elimination of the carbene 227. Strictly speaking, the thiazolium salts (and the 1,2,4-triazolium salts discussed below) are thus not the actual catalysts but pre-catalysts that provide the catalytically active nucleophilic carbenes under the reaction conditions used. This mechanism of action of thiamine was first formulated by Breslow [234] and applies to the benzoin and Stetter-reactions catalyzed by thiazolium salts [235-237] and to those... 

For an immonium structure of the enamine salt, protonation of the polarized mesomeric form on the j3-carbon atom is necessary. The behavior of dienamines shows59-61 that primary formation of an... 

Indole and alkyl-indoles (38) are protonated in position 3 by the action of strong mineral acids.198,197 The tendency of the enamine salts to assume the immonium structure is very general the salts of ethyl j3-aminoerotonate are derived from the imino form at the expense of the conjugation between the carbonyl group and the double bond.12,198... 

The N NMR spectroscopy of A -pyrazolines and their salts has been reported <87MI 301-01 >. Using as model A, A -dimethylaniline (for protonation on N,) and pyridine (for protonation on N2), the protonation effects were calculated (+ 8 ppm and — 111 ppm, respectively). Since the protonation effects in C-unsubstituted AUpyrazolines are —12 ppm to —20 ppm on N, and —20 ppm to —30 ppm on N2 (it depends on the nature of R ), it was concluded that AUpyrazolines (52) protonates on N, (53) but, owing to the conjugated aza-enamine structure, protonation on N, affects both nitrogen chemical shifts. 

The close agreement of the three methods supports the contention that protonation at low temperatures first occurs at nitrogen and is followed by a proton shift to give the iminium salt (M). The rate of this rearrangement is dependent on temperature, the nature of the amine, and the nature of the carbonyl compound from which the enamine was made. Even with this complication the availability of iminium salts is not impaired since the protonation reaction is usually carried out at higher temperatures than —70°. Structurally complicated enamines such as trichlorovinyl amine can be readily protonated (17,18). 

A recent adaptation of the procedure employing perchlorate and fluoro-borate salts has been reported by Leonard and Paukstelis (J5). This report includes proof of structure by direct comparison to iminium salts prepared by protonation of enamines. The general reaction reported was that of a ketone or aldehyde with a secondary amine perchlorate to give iminium salts. A large structural variety of carbonyl compounds and several amine... 

Physicochemical investigations of enamines and their salts have shown that the addition of a proton occurs almost exclusively at the /3-carbon atom of the enamine grouping. This means that salts of pyrrolines (82), piperideines (83), and enamines of 1-azabicycloalkanes (84) possess immon-ium structures. 

With the procedure for constructing the quaternary carbon stereocenter in hand, the conversion of the ris-form to the trans form was explored in accordance with the synthetic plan shown in Scheme 9. The ketone moiety of the 1,4-conjugated adduct 61 was protected by an acetal group, followed by decarboxylation of compound 65 using sodium ethylthiolate to yield lactam trans-62 and cis-62 as an 8 1 diastereomixture [31]. The reason why the lactam trans-62 was obtained as a major product is that the subsequent protonation after decarboxylation proceeded kinetically. This assertion is supported by experimental results in which the trans- and cis-lactam diastereomixture (8 1) in ethanol was refluxed in the presence of potassium hydroxide to afford a 1 5 mixture [15,32,33]. The mixture of the lactam trans-62 and cis-62 was reduced with DIBALH, followed by treatment with sodium hydroxide to give bicyclic enamine 63. The kinetic iminium salt prepared from bicyclic enamine 63 with hydrochloric acid was reduced with sodium cyanoborohydride, leading to the frans-decahydroisoquinoline structure [22], The acetal moiety of the resultant 67 was removed to provide the objective ketones 68a and 2c. This method enabled the construction of the tra s-decahydroisoquinoline structure without an intermediate resembling the neurotoxic MPTP, and in fewer steps. 

In the formation of salts, addition of a proton occurs at the free electron pair of one of the mesomerie forms of the enamine. The salts are usually derived from the immonium structure. With tertiary enamines, there is a substantial difference between the free bases which possess a fixed vinylamine structure and their immonium salts. 

The mechanism of this cyclization involves a conjugate addition of the enamine (100) to the nitroallyl ester (101) to give 102, which on elimination produced 103. The immonium salt 103 undergoes proton transfer to give enamino nitro olefin 104, which cyclizes to an enamine (107) via 105 and 106. Hydrolysis of 107 produces the ketone (108). Depending on the reaction conditions and the structure of the enamine and nitroolefin components employed, intermediates can be isolated (equation 19). 

In determinations of the structure of the protonation products of enamines IR spectroscopy is very helpful N-protonation to the ammonium structure (6) should lead to N—H valence and N—H deformation vibrations which are both absent in the experimental IR spectrum of immonium salts of enamines. Consequently, these C-protonation products (7) show strong C=N vibration bands in the region of 1644 to 1691 cm which are shifted hypsochromically by 7-69 cm" from the C=C vibration of corresponding enamines. For example, the perchlorate of protonated 247b shows a C=N vibration at 1686 cm "S which is 36cm" higher than that of the parent enamine. On the contrary,, y-unsaturated allylamines show no shift of their C=C vibration on protonation ... 

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