Enamine enaminonitrile

Reaction of 1,3-dicarbonyl compounds with IVJV-dimethylformamide dimethyl acetal followed by malonamide in the presence of sodium hydride gives 5,6-disubstituted 1,2-dihydro-2-oxopyridine-3-carboxamides, whereas reaction of the intermediate enamines with cyanothioacetamide or cyanoacetamide in the presence of piperidine provides 2-thioxopyridine-3-carboxamides and 4,5-disubstituted l,2-dihydro-2-oxopyridine-3-carboxamides, respectively <95S923>. P-Enaminonitriles 14 react with p-ketoesters and alkyl malonates, in the presence of stoichiometric amounts of tin(IV) chloride, to afford 4-aminopyiidines 15 and 4-amino-2-pyridones 16 <95T(51)12277>. 

Enaminonitriles (154) easily react with esters of acetylenedicarboxylic acid or propiolic acid. The first step is an electrophilic attack of the reactant on the /3-position of the enamine, and this is followed by cyclization with... 

The synthesis of the pyrimidine ring represents a well-studied group of heterocyclization reactions based on enamines. One of the important approaches involves the reaction of enamines with assorted isocyanates and isothiocyanates. Thus, a reaction of enaminonitriles with benzyl isocyanate or phenyl isocyanate gives C- and N-adducts (190a and 190b, respectively) or their mixtures, which are transformed in a single step into 4-pyrimidinone (191) and 2-pyrimidinone (192) derivatives (94JHC329). The... 

Condensation of cyclic enaminoamides (246) with dimethyl acetylene-dicarboxylate gives 2-azepinone derivatives (247) (85AJC1847). Similarly, immonium salts (248) when treated with bases give enamines, which subsequently react with dimethyl acetylenedicarboxylate or unsaturated ketones and give azepines (81AP787). The reaction of primary enaminonitriles with dimethyl acetylenedicarboxylate proceeds in a similar fashion (84CPB2596). Another route to azepines has been described (95JHC57) (Scheme 51). 

Condensation of the pyrrolidine enamine of cyclohexanone with l,l-dicyano-2,2-dimethylcyclopropane proceeds smoothly in refluxing dry xylene and gives the expected adduct in 76% yield. Recrystallisation of the adduct from 95% ethanol, however, gave a 91% yield of a product which no longer contained the pyrrolidine group but whose spectral data clearly showed the presence of a ketone group and an enaminonitrile function. Hydrolysis of this latter product with phosphoric acid/acetic acid gave 5-(2-oxo-4,4-dimethylcyclopentyl)pentanoic acid in 83% yield. 

The photo Diels-Alder reaction of a-acetylnaphthalene 82 with the chiral oc-enaminonitril 83 yielded the cycloadduct 84 with excellent diastereoselec-tivity (Sch. 16) [57]. The intermediary formed biradical Y is particular stable due to delocalization of the radical on the aromatic moiety and to a captodative effect on the enamine part. The chiral induction occurred in two steps [58]. In the first step, a stereogenic center is created in the a-position of the acyl group. In the second step of the diastereoselection, one of the two diasteromeric intermediates undergoes preferentially cyclization to yield the final product 84, while the other one is more readily decomposed to form the starting material. For a more detailed discussion of the mechanism see Ref. [59]. 

The condensation of substituted acetonitriles XCH2CN (X = CN, COOR, COPh) with trichloroacetonitrile, using a base catalyst, gives the /i-enaminonitriles in good yields after only short reaction times671,672. Spectroscopic studies of / -enaminonitriles also showed that the enamine tautomeric structure is preferred over the imino structure673"679. 

The photochemical behavior of enamines and their derivatives has been the subject of extensive mechanistic and synthetic investigations. The goal of this chapter is to summarize the photochemistry of enamines as well as enamides, enaminones, en-amidones and enaminonitriles, with particular emphasis on the application of the photochemistry of these chromophores in the synthesis of natural products. 

Cyclization of 168 in methanol, however, led to the formation of the epimeric (/ -anomer) product 172, as outlined in Scheme 39. Irradiation of 168 in methanol leads, via the triplet excited state of the enaminonitrile, to the formation of 170, the product of addition of methanol to the enamine double bond. On standing in the dark, 170 reverted to the starting enaminonitrile as a mixture of isomers 168 and 171 at the anomeric center, presumably via equilibration at the anomeric center prior to elimina-... 

In the case of the enaminonitrile XVIIa, coupling through the phenyl ring is observed [127a]. Enamines related to the key intermediate in thiamine diphosphate-dependent enzymatic pathways lead to dimers in a one-electron oxidation via a thiazolium cation radical as intermediate [127b]. Anodic oxidation of enaminones, prepared from / -substituted acetophenones and A,A-dimethylformamide dimethylacetal, afford dimers and substituted furans in fair yield [127c]. 

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