Enamine salts

B. Reactions of Enamine Salts with Nucleophilic Reagents. . 286... 

Dehydrogenation of amino alcohols of type 40 affords even bicyclic compounds 41, the formation of which can be explained by nucleophilic attack of the hydroxyl group on the formed enamine salt (133,134). 

Stretching vibration in the infrared region. The imine salts possess an active hydrogen, whereas their quaternization products exhibit the same spectral properties as the enamine salts (187). 

Enamines are also reduced with formic acid (247). Distillation of 1,2-dimethyl-.d -pyrroline formate (156) affords 1,2-dimethylpyrrolidine (248). The reaction is usually carried out by heating of the enamine salt with... 

Reactions of Enamine Salts with OrganometalUc Compounds Organolithium and organomagnesium compounds react with enamine salts to give amines substituted on the ix-carbon atoms. The treatment of. -dehydroquinolizidinium perchlorate (163) with alkylmagnesium halides gives 9-alkylated quinolizidines (164) (252,256). Formation of... 

Reaction of organometallic compounds with enamine salts have been successfully used for the synthesis of some natural products (256). Thus reaction of the immonium salt of 0-alkylated enamino ketone 122 with isobutyllithium affords the compound 169. 

Enamine salts react with many nucleophilic reagents. The reaction with the cyanide ion is noteworthy. l-Methyl-2-ethyl-2-cyanopyrrolidine (170) is formed on treatment of alkali cyanide with l-methyl-2-ethyl-.d -pyrrolin-ium perchlorate (242). The reduction of the tertiary nitrile (170) with... 

Primary and secondary halides do not perform well, mostly because N-alkylation becomes important, particularly with enamines derived from aldehydes. An alternative method, which gives good yields of alkylation with primary and secondary halides, is alkylation of enamine salts, which are prepared by treating an imine with ethylmagnesium bromide in THF ... 

The imines are prepared by 16-12. The enamine salt method has also been used to give good yields of mono a alkylation of a,P-unsaturated ketones. Enamines prepared from aldehydes and butylisobutylamine can be alkylated by simple primary alkyl halides in good yields. N-alkylation in this case is presumably prevented by steric hindrance. 

When the nitrogen of the substrate contains a chiral R group, both the Stork enamine synthesis and the enamine salt method can be used to perform enantio-selective syntheses. " ... 

ALKYLATIONS OF ALDEHYDES via REACTION OF THE MAGNESIO-ENAMINE SALT OF AN ALDEHYDE ... 

Carbonyl alkylation and condensation reactions are always of great value in synthesis, and the formation of o-ANIS ALDEHYDE via 4,4-dimethyl-2-oxazoline, 2,2-DIMETHYL-3-PHENYLPROPION-ALDEHYDE via alkylation of the magnesio-enamine salt and threo-4-HYDROXY-3-PHENYL-2-HEPTANONE via a directed aldol... 

Enol alkylation of cyclohexanone by oxetane has been achieved by the reaction of oxetane with an enamine salt, bromomagnesium Af-cyclohexyliminocyclohexane, in THF. An 80%... 

D. E. Bergbreiter and M. Newcombe (1983). Alkylation of imine and enamine salts , in Asymmetric Synthesis, Ed. J. D. Morrison. Orlando, Florida Academic Press. Vol. 2A, p. 243 D. Enders (1984). Alkylation of chiral hydrazones , in Asymmetric Synthesis. Ed. J. D. Morrison. Orlando, Florida Academic Press, Vol. 3, p. 275. 

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... 

B. Reactions of enamine salts with nucleophilic reagents. 

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... 

C-Alkylation affords monoalkylated products as a result of the lower reactivity of the monoalkylated enamines. Enamine salts obtained by alkylation can afford new enamines capable of further alkylation only by the loss of a proton. In some cases, dialkylation can be achieved by the addition of the more basic ethyldicyclohexylamine. Monoalkylation of the pyrrolidine enamine of cyclohexanone is due to a considerable energy difference between the transition states caused... 

Organomagnesium compounds react with enamine salts to give bases substituted on the a-carbon atom. These reactions may be regarded as an extension of Freund s observations on quaternary quinolinium and isoquinolinium salts. The reaction of hydrastinine with methylmagnesium bromide 318 (Eq. 10) is a typical example. The... 

Alkyllithium compounds and alkali cyanides, mercaptides, and alkoxides,322,323 etc. have been used as nucleophilic reagents in reactions with the enamine salts. Nitrile groups can be removed by reduction or by treatment with acids. Treatment of cotarnine (100)... 

Diene addition328 occurs on treatment of dienes with a-halogeno-amines (which are tautomers of enamine salts) (Scheme 15). 

Figure 1. Hydrolysis of the enamine salt of an optically active acid...

Illustrated in Table II are the effects of different optically active acids used for producing the piperidine enamine salt of a-phenylpropionaldehyde. Based on the rate of hydrolysis and the asymmetric transformation of the recovered substances, a strong acid is most effective. 

Table II. Results of Acid Hydrolysis to Form the Piperidine Enamine Salt of a-Phenylpropionaldehyde (1)...

The overall bonding changes which occur upon hydrolysis of enamines are shown by equation 2. Experimental studies on the protonation of enamines revealed that enamine salts are formed prior to attachment of a nucleophilic moiety. That is, protonation of enamines occurs before attack by water or any other nucleophile8,9. As is the case for alkylation7 and acylation5fl,c, protonation can occur either on nitrogen or on the / -carbon (equation 3). 

Similarly, the enamine salt 15 is obtained by lithiation of 14 (equation 5). In both cases the lower steric hindrance leads to higher stability of the enaminic system33 where the double bond is formed on the less substituted carbon. The Af-metalated enamines 11 and 15 are enolate analogs and their contribution to the respective tautomer mixture of the lithium salts of azomethine derivatives will be discussed below. Normant and coworkers34 also reported complete regioselectivity in alkylations of ketimines that are derived from methyl ketones. The base for this lithiation is an active dialkylamide—the product of reaction of metallic lithium with dialkylamine in benzene/HMPA. Under these conditions ( hyperbasic media ), the imine compound of methyl ketones 14 loses a proton from the methyl group and the lithium salt 15 reacts with various electrophiles or is oxidized with iodine to yield, after hydrolysis, 16 and 17, respectively (equation 5). 

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