Butyraldehydes, enamines

Kuehne and Foley (29) have found that the reaction of the pyrrolidine enamine of butyraldehyde with 2 equivalents of (8-nitrostyrene also led to a bis adduct with the structure as shown in 48. 

Experiments designed to clarify the situation were carried out by Wittig and Mayer (40). It was shown that changing the molar ratio of amine (diethylamine, di- -butylamine, or diisobutylamine) to -butyraldehyde from 1 1 to 2 1 did not affect the yield of enamine (53- 64%, based on the aldehyde). Contrariwise, changing the ratio of amine (morpholine, piperidine, or pyrrolidine) to n-butyraldehyde from 1 1 to 2 1 boosted the yields from 52-57 % to 80-85 %. The authors interpret these data as indicating that the cyclic amines form aminals with n-butyraldehyde, while the open-chain do not. Infrared evidence is stated as having shown that the aminal originates not from attack of excess amine on the enamine, which is stable under the conditions of the reaction, but from the N-hemiacetal (17). 

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). 

The reaction between the pyrrolidine enamine of butyraldehyde (52) and )3-nitrostyrene (53) provides cyclobutane adduct 54 quantitatively in either petroleum ether or acetonitrile solvent, but in the more polar ethanol solvent a 2 1 condensation product occurred. The structure of the product was shown to be 55 (57). 

Rearrangement of an enamine to a Sehiff s base through N- to C-alkyl migration was reported 729). These authors also found that enamines, rather than aminals, were formed from butyraldehyde and seeondary amines (730). Chloramines and aeetylenes reacted to give chloroenamine intermediates, which hydrolyzed on work-up of the reactions (731). 

For the general condensation reaction of secondary amines with ketones to yield enamines, pyrrolidine, piperidine, or morpholine is generally used. The rate of enamine formation depends on the basicity of the secondary amine and the steric environment of the carbonyl group [12a, b, 29], Pyrrolidine, which is more basic, usually reacts faster than morpholine. The investigation of piperazine, a disecondary amine, has only been reported recently by Benzing [45, 46] and Sandler [41]. Surprisingly, the reaction of excess -butyraldehyde with piperazine in tetrahydrofuran at — 20°C to 0°C gave mainly AM-butenyl-piperazine [41] (see Eq. 13). 

Diazadienes 370 and 371, formed in situ from the corresponding silyl imine and phenylisocyanate, readily undergo [4 + 2] cycloadditions with enamines derived from butyraldehyde and cyclohexanone leading, after deamination, to pyrimidone 372 and pyrimidothione 373, respectively224. 

An illustrative example for the strength of this methodology was reported by Kim et al. who used an enamine-catalyzed a-oxidation in the synthesis of the bark beetle pheromones (+)-exo- and (-)-enrfo-brevicomin (124) (111). The asymmetric proline-catalyzed a-hydroxylation of butyraldehyde (125) with 123 gave the crude anilinooxy compound 126 in excellent enantioselectivity (>98%). Compound 126 was used directly further to give (+)-exo- and (-)-endo-brevicomin (124) in just three more steps (Scheme 29) (111). 

When aromatic amines are condensed with n-butyraldehyde in the absence of even trace amounts of acid, SchifF bases are not the exclusive condensation products. Dimers have been isolated from the reaction medium and investigation has shown them to have an enamine structure . 

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