Amides, vinylogous, cyclization

The general method for preparation of heterocyclic enamino ketones, amide vinylogs, consists of a cyclization reaction (Scheme 6). The most convenient technique involves heating the starting substance in acetonitrile in the presence of silver perchlorate 137-139). 

Vinylogs (Vinylogous) s. azolides, vinylogous carboxylic acid amides, -Dieckmann cyclization, -l,2-dithiole-3-thiones, -urethans, -... 

The alkylation of enamines with nitroolefins, which gives intermediates for reductive cyclization (6S2), also provided an example of a stable cycliza-tion product derived from attack of the intermediate imonium function by the nitro anion (683). A previously claimed tetrasubstituted enamine, which was obtained from addition of a vinylsulfone to morpholinocyclohexene (314), was shown to be the corresponding cyclobutane (684). Perfluoro-olefins also gave alkylation products with enamines (685). Reactions of enamines with diazodicarboxylate (683,686) have been used diagnostically for 6-substituted cyclohexenamines. In a reaction of 2-penten-4-one with a substituted vinylogous amide, stereochemical direction was seen to depend on solvent polarity (687). 

The formation of 3-acylpyridinium compounds (59/) from primary amines and l-methoxybutene-3-one can be regarded as the enamine alkylation of a vinylogous amide followed by cyclization and loss of methanol and water. 

For a Lewis-acid-mediated cyclization reaction of a tryptamine-derived vinylogous amide that affords the Aspidosperma skeleton, see Huizenga RH, Pandit UK (1991) Tetrahedron 47 4155 1164... 

CAN). Fortunately, using CAN [30] with vinylogous amide 54 under short reaction times provided the desired, cyclized product 53 (in yields ranging from 45 to 58 %, Scheme 6.11). 

A concise free radical cyclization process has been applied to the synthesis of new cyclopentanone-annulated azepines 204 from chiral vinylogous amides (Scheme 26). The free radical was generated from the phenylselenide group in 203 (made in turn by N-acylation of 202) using Bu3SnH and l,l -azobis(cyclohexanecarbonitrile) (ACN), as the initiator <2004SL1917>. 

While some of the mechanistic details for the examples described in this chapter have not yet been fully elucidated, it is clear from the scope of the examples discussed herein that the photochemistry of enaminones and enamidones is a fascinating research area. The novel sequence for the annelation of imidazole rings onto a preexisting structure, the synthesis of perhydroindoles via vinylogous amide [2 + 2] photocycloaddition chemistry and the enamide cyclization reactions all underscore the enormous utility of these chromophores in the development of new reactions and novel synthetic methods. 

Winkler and his co-workers have previously reported the vinylogous amide photocycloaddition. In their present account, the highly diastereoselec-tive cyclization of (73) to afford (74) is described. This product affords a basis for a synthetic strategy towards the manzanine alkaloids. 

A third application of the Eschenmoser reaction in the synthesis of racemic perhydrogephyrotoxin (76) is based on an extension of the chemistry developed during the pumiliotoxin C synthesis. - Beginning with the bicyclic thiolactam (73), the sulfide-contraction reaction was used to append to the decahydro-isoquinoline a functionalized five-carbon side chain that would later be cyclized and become the a-hy-droxyethylpyrrolidine portion of the molecule. Alkylation of the thiolactam (73) with methyl 5-bromolevulinate followed by treatment with the Eschenmoser dual base-thiophile reagent (28) produced the vinylogous carbamate (74) in 81% yield from the starting thiolactam (73 Scheme 17). Reduction of the vinylogous amide (74), followed by equilibration of the amino ketones in the presence of... 

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