Enamines formamides

Hydrolytic cleavage of vinylogous formamides and ureas has been applied to the generation of enamines (56-58). 

The condensation of a vinylogous formamide with an enamine has been applied to an aza azulene synthesis (351). The point of attachment of the aldehyde to the enamine in condensations with indolenin derived poly-enamines was found to favor the second double bond (352,353). 

Greater stereoselectivity for the formation of equatorial amines has been found in the reduction of enamines with formic acid or formamides (553-559). The selective formation of 3-a-amino-5- -steroids by this method and of 3- 3-amino-5- 3-steroids by catalytic reduction (5<50) of the corresponding enamines is of interest. 

Alkylation of enamines Addition of amines to triple-bond compounds Addition of amines to aldehydes or ketones Reaction between Grignard reagents and formamides Reaction of phosphonates with aldehydes or ketones... 

The Vilsmeier reaction has been applied to indolizines to yield a variety of products. The normal reaction conditions with jV,jV-dimethyl-formamide and phosphorus oxychloride can give the indolizine-1-aldehyde,168 e.g., with 6-ethyl-2,3-dimethylindolizine. However, N,N-dimethylacetamide with 5-methyl-2-phenylindolizine gave a mixture of isomers, 105 and 106, with the former predominating.165 Hydrolysis of 105 gave enamine 107 instead of the acetyl compound. 

A -Arylimincs (21a) can be oxidatively rearranged to formamides (21b) with sodium perborate.42 The reaction works best for secondary or aryl R groups. An oxaziridinc intermediate is proposed. Results with chiral secondary R groups indicate epimeriza-tion, suggested to occur via equilibration of (21a) with its enamine tautomer. 

C—C—O—C+N. The formation of oxazoles from a-acyloxy ketones and ammonium salts was discovered in 1937 when it was found that treatment of benzoin benzoate with ammonium acetate in hot acetic acid gave triphenyloxazole in excellent yield. It has been shown that the reaction proceeds by way of intermediate enamines (equation 113). The synthesis is quite general and it is only.limited by the difficulty of obtaining the starting keto esters, particularly formates. The latter are probably intermediates in the preparation of cycloalkenooxazoles from acyloins and formamide in hot sulfuric acid (equation 114). Another variation is to heat a mixture of an a-bromo ketone, the sodium salt of a carboxylic acid and ammonium acetate in acetic acid (equation 115). 

This type of reaction with A N-disubstituted formamides, giving aldehydes, was an early application of Grignard reagents, sometimes known as the Bouveault reaction [A]. Dimethylformamide and N-methylformanilide, PhN(Me)CHO, have been most commonly used, but more recently iV-formylpiperidine and 2-(/V-formylmethylamino)pyridine have been recommended examples are listed in Table 6.5, and a recent example of the traditional procedure follows. It should be noted that these reactions are subject to a number of side-reactions [A]. One useful one is the formation of enamines by elimination from the initial adduct [9] ... 

Formamide converts the primary enamine 359 into 4-oxo-4,5,6,7-tetrahydro-3//-thiopyrano[2,3-d]pyrimidine 360 (equation 146)178. 

Anilines and heterocyclic amines react with 1,3,5-triazine to furnish formamidines, e.g. (363) and (364) (Scheme 64). CH2-acidic compounds, e.g. nitriles, can be formylated by heating with 1,3,5-triazine. In the course of such reactions the enamines thus obtained can be converted to formamid-... 

Fig. 16.2 Solvents in tbe study on enamine reduction. Selected test items Formamide...

The reaction between carbanion and a formamide, R2NCHO [R = Me or R2 = 0(CH2CH2)2] yields a complex (Scheme 60, which again, depending on the hydrolysis medium, may be hydrolysed to jS-phosphorylated acetaldehyde (611) or to the enamine 612, and as before, 612 may be acidolysed to Azeotropic removal of water... 

Imidazoles.—Formation. Several new syntheses of imidazoles from isocyanides have been reported these include the formation of 1-alkyl-imidazoles (396) by the action of primary amines on 2-isocyano-2-tosylstyrene, PhCH=C-(NOTos, the cyclization of the enamine Me2NCH=C(NC)C02Me to compound (397) in the presence of methyl iodide,and the preparation of the ethers or thioethers (398) from isocyano-cyanides R CH(NC)CN by their reaction with alcohols or thiols R XH, respectively.Aromatic aldehydes are converted into 2-aryl-4,5-dichloroimidazoles (399) by the combined action of cyanogen and hydrochloric acid. 5-Acetyl-4-methylimidazole (400) results when form-amido-acetylacetone, AC2CHNHCHO, is heated with formamide and formic acid. Exhaustive chlorination of tetramethyldithio-oxamide leads to the tri-chloro-imidazolium cation (401). ... 

Tetrachloropyrimidine is formed in quantitative yield by the cyclization (with FeCla, at 200 °C) of perchloro-l-cyano-3-azabutadiene (Cl2C=N—CC1=CC1CN), itself formed by successive treatment of cyanoethyl)formamide with phosphorus pentachloride and chlorine. j8-Iminoyl-enamines (222), prepared by the reaction of the appropriate anils with nitriles, condense with ethyl chloroformate and carbon disulphide to give excellent yields of 2-oxo- and 2-thioxo-pyrimidines (223 X = O or S). Aldehydes, acetals, and ketals (but not ketones) also react with these enamines (222) to give 1,2-dihydropyrimidines (224) (70—93%). In similar fashion, malondiamidines condense with a large variety of aromatic aldehydes to give 2-aryl-5-arylmethyl-4,6-diaminopyrimidines. °... 

In another context, an L-valine-derived formamide was applied by Kocov-sky s group as an organocatalyst to the asymmetric hydrosilylation of enam-ines, allowing a direct access to a range of jS-amino add derivatives. This method relied on the fast equilibration between the enamine and the imine... 

Scheme 2.114 DKR hydrosilylation of enamines catalysed by L-valine-derived formamide.

The same authors report two other novel reactions of this allene, with phenylacetylene to give a [2 + 2] cycloadduct, and with A AT-dimethyl-formamide, which cleaves the allene to yield an enamine ... 

Reaction of 10 with 4-pentenyllithium gave 11. Enolization of 10 competed with imine addition and thus, recycling of this material was needed to achieve a respectable overall yield of 11 from ketone 9. Acid hydrolysis of 11 furnished enamine 12 after neutralization. An acid-mediated Mannich reaction converted 12 to a mixture of epimeric ketones 13. Oxidation of the 27-methyl group provided formamide 14. 

Neutral nucleophiles are also alkenylated to give alkenylonium salts (Scheme 6). Examples include secondary amines (with concomitant deprotonation to afford enamines) and tertiary amines, acetic acid (with deprotonation to give alkenylacetates) formamides (that give alkenylformates), " sulphur-centred nucleophiles such as sulphides,thioamides (to give thioalkenes), thioureas and heterocyclic thiols group 15 nucleophiles triphenylphosphine, -arsine... 

Benhaliliba et al. (1998) successfully oxidized 3,(3-disubstituted enamines into ketones and formamides with KMn0yAl203 in domestic (255 W, 82 °C) as well as in focused (330 W, 140 °C) microwave ovens under solvent-free conditions. Oxidation yields were higher under focused microwave oven as compared to domestic oven as well as classical heating. 

A slurry of 3-ketobisnor-4-cholen-22-al 22-morpholine enamine in dimethyl-formamide containing rose bengal as sensitizer photooxygenated 17.5 hrs. at 15° progesterone. Y ca. 100%. J. E. Huber, Tetrah. Let. 1968, 3271. 

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