Formation of Enamines

A very efficient one-pot procedure for the production of 3-hydroxy-3-cephems (45) has been developed which gives the desired product in almost 80% overall yield from (43a) which is readily available from penicillin. TTie sequence of reactions is (1) mesylation to give (43b), (2) formation of enamine (43c), (3) bromination to afford (44) and (4) hydroly-sis/cyclization with hydrochloric acid in methanol to afford (45) which, in some cases, crystallizes directly from the reaction mixture (B-82MI51000). 

The intermediacy of an aminal in the formation of enamines from ketones and secondary amines is not usually proposed. The only direct evidence for this is the infrared spectra of the reaction mixtures produced when dimethyl-or diethylamine was allowed to react with cyclohexanone or cyclopentanone... 

The addition of secondary amines to 1-cyanoallenes (161) results in the formation of enamines in 80-90% yield (124). Addition can occur at the 1,2 or 2,3 double bonds so that a mixture of isomeric enamines (162 and 163) is formed. The ratio of products is influenced by the alkyl substituents on the cyanoallenes and the structure of the secondary amine. 

In the generation of 3,5-dibenzylpyridine from piperidine and benzalde-hyde, the formation of enamine and dienamine intermediates must also be involved (191-193). 

The formation of enamines from carbonyl compounds and secondary amines usually entails as only questionable structural feature, the possible isomeric position of double bonds in the product. Molecular rearrangements have not presented synthetic limitations. A notable exception is the generation of o-aminophenols on distillation of enamines derived from 2-acylfurans 620,621). 

From a mechanistic standpoint, ammonia serves two functions 1) it behaves as a base to catalyze an aldol reaction between 2 equivalents of 31 to generate the corresponding enal 33, and 2) it is the source of nitrogen for the resultant pyridyl ring. This occurs through formation of enamine 34 with a third equivalent of 31. The Michael addition of 34 to 33 followed by cyclization gives rise to 32. 

The reaction of 2-phenyl-1,1-dicyanoallyl anion 20 with Af-methy 1-2,2-dimethylpropionitrilinm ion in acetonitrile solution resulted in formation of enamine 21, which on heating undergoes a ring closure to pyridine 22 <96SC A(50)623>. 

Drivers for Performing Formation of Enamines in Micro Reactors... 

Beneficial Micro Reactor Properties for Formation of Enamines... 

Formation of Enamines Investigated in Micro Reactors Organic synthesis 73 [OS 73] Stork enamine formation from cyclohexanone and pyrrolidine... 

Scheme 6.21 Clay-catalyzed formation of enamines under solvent-free conditions.

Sands M, Haswell SJ, Kelly SM, Skelton V, Morgan DO, Styring P, Warrington B (2001) The investigation of an equilibrium dependent reaction for the formation of enamines in a microchemical system. Lab Chip 1 64—65... 

Formation of enamines (addition of amines to aldehydes or ketones)... 

The formation of oxygen-containing heterocyclic compounds is also a consequence of the Maillard reaction. Amines and amino acids have a catalytic effect upon the formation of 2-furaldehyde (5), 5-(hydroxy-methyl)-2-furaldehyde (11),2-(2-hydroxyacetyl)furan (44),2 and 4-hy-droxy-5-methyl-3(2//)-furanone (111) (see Ref. 214). This catalytic effect can be observed with several other non-nitrogenous products, including maltol. The amino acid or amine catalysis has been attributed to the transient formation of enamines or immonium ions, or the 1,2-2,3 eno-lization of carbohydrates. Of interest is the detection of A -(2-furoyl-... 

Catalytic Formation of Enamines 2.1 A Brief History of Enamine Catalysis... 

Ji-Toluenesulfonic acid, as catalyst, for formation of enamines, 41, 65 for reaction of dihydroresorcinol with ethanol, 40, 41... 

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