Aldehyde enamine

More recently the acylation of aldehyde enamines has been reinvestigated (75) and shown to proceed normally when the enamine is added to the acid chloride. The morpholine enamine of isobutyraldehyde (98), on being added to an ether solution of acetyl chloride, afforded the iminium salt (99), from which the ketoaldehyde (100) was obtained in 66% yield by hydrolysis (75). 

Aldehyde enamines react with aromatic diazonium salts in two ways, depending on the degree of substitution at the enamine earbon (130). Thus the piperidine enamine of butyraldehyde (60) reacted with p-nitrophenyl-diazonium chloride to give the p-nitrophenylhydrazone of the a-keto aldehyde (190). 

Methyl vinyl sulfone forms 1,2-cycloaddition adducts with aldehydic enamines, both with and without 3 hydrogens (37). Simple alkylation was reported to take place when phenyl vinyl sulfone was allowed to react with cyclohexanone enamines (58,60), but it has recently been shown that phenyl vinyl sulfone also forms cyclobutane adducts (60a). 

The initial reaction between a ketene and an enamine is apparently a 1,2 cycloaddition to form an aminocyclobutanone adduct (58) (68-76a). This reaction probably occurs by way of an ionic zwitterion intermediate (75). The thermal stability of this adduct depends upon the nature of substituents Rj, R2, R3, and R. The enolic forms of 58 can exist only if Rj and/or R4 are hydrogens. If the enamine involved in the reaction is an aldehydic enamine with no 3 hydrogens and the ketene involved is di-substituted (i.e., R, R2, R3, and R4 are not hydrogens), then the cyclo-butanone adduct is thermally stable. For example, the reaction of dimethyl-ketene (61) with N,N-dimethylaminoisobutene (10) in isopropyl acetate... 

The reaction between an aldehydic enamine with no (3 hydrogens and ketene yields a cyclobutanone adduct which is not thermally stable (Rj and R4 H, Ri = R2 = H) (67,70,72). Thermal decomposition gives just one... 

A by-product of the reaction between an enamine, elemental sulfur, and carbon disulfide is an a-dithiopyrone. This by-product is the result of the condensation of two enamine molecules with one carbon disulfide molecule. In the case of aldehydic enamines, the reaction probably proceeds through... 

Disubstituted pyridines [86] 87 have been prepared by catalyzed cycloaddition of 4-methyl-1,2,3-triazine 85 with aldehyde enamines 86 (Equation 3.29). The best yields were obtained when ZnBr2 was used as catalyst. 

A biomimetic synthesis of benzo[c]phenanthridine alkaloids from a protoberberine via the equivalent of a hypothetical aldehyde enamine intermediate has been developed (130,131). The enamide 230 derived from berberine (15) was subjected to hydroboration-oxidation to give alcohol 231, oxidation of which with pyridinium chlorochromate afforded directly oxyche-lerythrine (232) instead of the expected aldehyde enamide 233. However, the formation of oxychelerythrine can be rationalized in terms of the intermediacy of 233 as shown in Scheme 41. An alternative and more efficient... 

Intramolecular [4 + 2]cycloaddition of an enaminelenal(enone). Generation in situ of an aldehyde enamine of a substrate also containing an enal or enone group can result in a facile intramolecular [4 + 2]cycloaddition resulting in bicyclic dihydropyrans. Although several sec-amines can be used, N-methylaniline is particularly suitable because of the stability of the adducts. 

Keywords Aldol, Direct, Ketone, Asymmetric catalysis, Enantioselective reaction, Diastereo-selectivity, 1,2-Diol, Aldehyde, Enamine, Lewis acid, Bronsted base, Organocatalysis, Bimetal-... 

In contrast, morpholine enamines from higher alkyl ketones do not dimerise but undergo disproportionation to the reduced enamine and various oxidation products. Aldehyde enamines dimerise, but with more difficulty at higher temperatures544. Cross-conjugated545 and linear dienamines (e.g. 132)546 have been prepared by condensation of amide acetals with alkynyl alcohols (equation 37). 

A significant improvement in the alkylation of ketone and aldehyde enamines involves the use of sterically hindered amines63. N-Alkylation is prevented with consequent increase in C-alkylation. For example, reaction of the w-butylisobutylamine enamine of cyclohexanone (29) with methyl iodide in boiling acetonitrile (Scheme 16), or trimethy-loxonium tetrafluoroborate at room temperature gave 2-methylcyclohexanone in increased yields of 56% and 74%, respectively63 (compare Scheme 10). 

Only allyl and benzyl halides give good yields of C-alkylated aldehydes unless hindered enamines are used64. Otherwise N-alkylation or aldocondensation are often the only reactions observed54a,54ft 6 5. Hindered aldehyde enamines may also be prepared... 

Alkylidenecyclopentanones (68 and 69), formed by condensation of the morpholine enamine and the corresponding aldehyde with azeotropic removal of water, may be isomerized to the thermodynamically stable 2-alkyl-2-cyclopentenones by heating with hydrochloric acid in butanol152 (Scheme 56). Condensation of glyoxylic esters with aldehyde enamines gives a mixture of (E)- and (Z)-3-alkyl-4-oxo-2-butenoic esters (70 and 71). The Z-isomers (71) cyclysed to the butenolide (72) under neutral conditions,... 

Mono-benzoyldiimides such as 177 behave in a relatively normal manner, reaction with the pyrrolidine enamine of cyclohexanone (or cyclopentanone) giving the oxadiazine 178355 (Scheme 181). Reaction of dimethyl azodicarboxylate with / -disubstituted aldehyde enamines is reported to give the 1,2-diazetidine 179 and hence the aldehyde 180 on hydrolysis356", dibenzoyldiimide gives the oxadiazine 1813566 (Scheme 181). The ethoxycarbonyl aroyl diimide 182 reacts to give oxadiazine 183 exclusively357 (Scheme 182). 

In the case of monomeric aldehyde enamines (31), it was possible to show that the products are formed via the dienamine (32) which can be converted directly with carbon disulfide, requiring a shorter reaction time and giving higher yields.43 Starting from the dienamine (32) (R = H) the parent compound (8) is formed the yield, however, is maximally about 10%.43... 

C-Alkylations of hindered aldehyde enamines can be effected with a variety of alkylating agents, but only allylic and benzylic reagents are useful for alkylations of unhindered systems.Acyclic, homoan-nular and heteroannular dienamines undergo alkylation primarily at the a-positions. ° As discussed above, reactions of enamines with electrophiles containing sp -hybridized carbon atoms have numerous limitations. On the other hand, enamine reactions with electrophilic alkenes are highly useful and have received wide coverage in the literature. 

A large number of cyclopropanes have been synthesized from cyclopropyl sulfones, cyclopropyl sulfoxides and cyclopropyl sulfides by taking advantage of the acidity of the cyclopropyl proton a to the C-S bond. Butyllithium is used almost exclusively as the base. The cyclopropyl anions obtained are capable of reacting with alkyl halides, aldehydes, enamines, epoxides, esters. 

The aminal can be isolated in some cases ". Both Wittig and Meyer and Curphey and coworkers have questioned the need for the initial formation of the aminal and have developed procedures for the preparation of aldehyde enamines by using equimolar amounts of amine and aldehyde. For enamines of straight-chain aldehydes or acyclic amines, the Mannich-Davidsen procedure may be modified by using ether as a solvent and one equivalent of amine. Experiments designed to clarify the situation were carried out by Wittig and Meyer, and evidence that a dynamic equilibrium exists between an... 

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