Amides, acidity enamides

Thermal decomposition of capsaicin yields capsaicin dimer ( )-JV-vanillyl-di(8-methylnon-6-en)imide (10-35), various amides, acids, hydrocarbons and phenols. The main product is E)-S-methylnon-6-enamide, nonanamide, pentanamide and other amides, ( )-8-methylnon-6-enoic acid, nonanoic acid, ( )-hept -2-ene, vanillin and other substituted phenols (2-methoxy-4-methylphenol and 2-methoxyphenol), which are produced by decomposition of vanillin. Roasting of peppers in oil may produce fatty acid amides. For example, reaction with oleic acid yields (Z)-N-vanillyloctadec-9-enamide reaction of oleic acid with ammonia, originating from capsaicin, gives rise to (Z)-octadec-9-enamide (oleamide). 

The photochemical rearrangement of enamides to vinylogous amides was described (65],652). Rearrangement of cyclopropyl ketimines to enamines with acid was applied to syntheses of myosamine, apoferrosamine, mesembrine, and desmethoxymesembrine (653-656). 

Reactions of benzoylperoxide with morpholinocyclohexene and morpho-linocyclopentene furnished the corresponding a-benzoyloxyketones in modest yields (480,481). This oxidation has also been applied to some vinylogous amides (482), and the expected faster rate of reaction of the enamine system as compared with enamides has been noted in derivatives of 20-ketosteroids, in reactions with perbenzoic acid (59,483). 

A wide range of substrates have been reported to proceed successfully to conjugate addition products with the monobasic forms of phosphorous acids, including esters,371415416 amides,417-419 nitriles,415 420 acid chlorides,421 enamides,375 and nitro compounds.422-424... 

The low ee-values obtained with simple unsaturated acids as compared to the enamides of dehydroamino acid derivatives show that the oxygen atoms of the amide is a key to complex formation with the metal center. Knowles also proposed a quadrant model that has been adapted for many reactions [5, 22]. The mechanism of the reaction has been investigated, and it is known that the addition of the substrate to the metal is regioselective and that competing catalytic cycles can occur [5, 10, 22, 25, 27, 30-46]. 

Rhodium-catalyzed enantioselective hydrogenation of N-acyl enamides provides access to enantioenriched amides which can be hydrolyzed to the free amines. The synthesis of the substtates is considerably less sttaightforward than that of N-acyl dehydroamino acids, which explains the smaller number of reports devoted to N-acyl enamides. 

Only few general methods allow for the introduction of a substituent at the C-7 position. However, treatment of cyano-enamide 335 with LiTMP followed by reaction with electrophiles has been successfully used to introduce an alkyl chain at G-7. It is worth noting that the amide obtained by acidic hydrolysis of the cyano-enamide group can be further alkylated to form tricyclic hexahydro-oxazolo[3,2- ]pyridin-5-ones 337 (Scheme 92) <1998JOC1619>. 

Mechanistically, the Brpnsted acid-catalyzed Friedel-Crafts reaction presumably involves a tantomerism of enamide 127 to the corresponding A -acetyl-protected imine. Snbseqnent addition of indole 29 affords amide 128 (Scheme 52). 

Several syntheses of indiplon have been described and two routes are shown in Scheme 15.5 (Sorbera et al., 2003 Dusza et al., 2002). Treatment of acetophenone 26 with refluxing dimethylformamide dimethylacetal (DMF-DMA) provided enamide 27. Alkylation of the amide with methyl iodide using NaH in DMF afforded 28. 3-Ketonitrile 29 was treated with DMF-DMA to give enamide 30. Cychzation with aminoguanidine produced aminopyrazole 31. The condensation of enamide 28 with aminopyrazole 31 in acetic acid furnished indiplon (4). Alternatively, enamine 28... 

Secondary and tertiary (3-hydroxy amides can be cyclized to oxazolines in the presence of strong acids such as methanesulfonic acid or p-toluenesulfonic acid. For tertiary (3-hydroxy amides, elimination to the enamide can often be a competing... 

Allyl amides (enamides), for example, 225, 228, and 230 cyclize to oxazolines, for example, 226, 229, and 231 when the double bond is activated by an electrophile. The double bond can also be conjugated to a ketone, or present as an allylic epoxide. Reagents commonly used to promote the cyclization include acids,iodine,selenium reagents,and trimethylsilyl triflate (Scheme 8.63). ... 

Condensation of an amino acid-derived anilide and a /3-ketoamide afforded l,4-benzodiazepin-2-ones in which the initially formed imine tautomerizes to an exocyclic enamide (Scheme SO) <2001TL3227>. Only the (Z)-isomer of the enamide was isolated, assigned based on NOE data, and presumably reflecting stabilization by an intramolecular H-bond between the ring NH and exocyclic amide carbonyl. 

Rhodium-BisP and -MiniPHOS catalysts are capable of high enantioselective reductions of dehydroamino acids in 96-99.9% ee.109 A variety of aryl enamides give optically active amides with 96-99% ee with the exception of ort/jo-substituted substrates.111 Despite the high enantio-selectivity, the rate of reaction in this transformation is slow. Rhodium-BisP and -MiniPHOS catalysts perform excellently in the asymmetric reduction of ( >P-(acylamino)acrylates to the corresponding protected-P-amino esters in 95-99% ee.112 Within the family of BisP and MiniPHOS, the ligands that contain t-Bu groups were found to be the most effective in a variety of asymmetric hydrogenations. 

Enamides R2C=CHNRCOR (N-acylated enamines) are thermally stable compounds under neutral or basic conditions. However, they show sensitivity to aqueous acid, hydrolysing to form aldehydes or ketones and amides. The photocyclization of enamides has been used to form a wide variety of natural products because it gave higher yields than the conventional thermal syntheses620-623. 

Amides reacted with acetals of aldehydes and ketones to form JV-(a-alkoxyalk-yl)amides, which upon pyrolysis over alumina at 290-300 °C yielded enamides643. It was found that it was possible to obtain the enamide directly from the acetal by refluxing it in the presence of an acid (equation 48). 

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