5-Acyl-3-pyrrolin-2-ones

Volume 75 concludes with six procedures for the preparation of valuable building blocks. The first, 6,7-DIHYDROCYCLOPENTA-l,3-DIOXIN-5(4H)-ONE, serves as an effective /3-keto vinyl cation equivalent when subjected to reductive and alkylative 1,3-carbonyl transpositions. 3-CYCLOPENTENE-l-CARBOXYLIC ACID, the second procedure in this series, is prepared via the reaction of dimethyl malonate and cis-l,4-dichloro-2-butene, followed by hydrolysis and decarboxylation. The use of tetrahaloarenes as diaryne equivalents for the potential construction of molecular belts, collars, and strips is demonstrated with the preparation of anti- and syn-l,4,5,8-TETRAHYDROANTHRACENE 1,4 5,8-DIEPOXIDES. Also of potential interest to the organic materials community is 8,8-DICYANOHEPTAFULVENE, prepared by the condensation of cycloheptatrienylium tetrafluoroborate with bromomalononitrile. The preparation of 2-PHENYL-l-PYRROLINE, an important heterocycle for the synthesis of a variety of alkaloids and pyrroloisoquinoline antidepressants, illustrates the utility of the inexpensive N-vinylpyrrolidin-2-one as an effective 3-aminopropyl carbanion equivalent. The final preparation in Volume 75, cis-4a(S), 8a(R)-PERHYDRO-6(2H)-ISOQUINOLINONES, il lustrates the conversion of quinine via oxidative degradation to meroquinene esters that are subsequently cyclized to N-acylated cis-perhydroisoquinolones and as such represent attractive building blocks now readily available in the pool of chiral substrates. 

The gross structural features, presence of a tetramic acid and E-decenoyl side chain, could be inferred from NMR studies. Methanolysis (HCl/MeOH) of 47 and pentane extraction of the quenched reaction mixture gave two compounds that were determined to be the methyl esters of decenoic acid and N-(2-decenoyl)leucine. The nature of the 3-acyl tetramic acid was deduced from the identification of 48 and 49 in the aqueous portion of the methanolysis reaction mixture following treatment with trifluoroacetic acid anhydride. The unusual C-C bond fragmentation under acidic conditions, and the structure of the antibiotic was confirmed by synthesis of racemic 47 [86]. The configuration at the lone chiral centre was established as R by chiral GC. The carbon NMR spectrum of 47 indicated an equilibrium between three tautomers in which the A2-pyrrolin-4-one form is preferred (60%) and the two internal tautomers (50, 51) make equal contributions (20% each). 

Sorangium cellulosum is an ubiquitous soil bacterium that belongs to the order Myxococcales. It has the ability to glide over solid surfaces, to live in a biofilm and form fruiting bodies. Members of this taxon are a particularly rich source of metabolites with remarkable biological activities [177]. From one strain, another example of N-acyl-4-methoxy-3-pyrrolin-2-ones has been isolated. Eliamid (110) has been claimed to have cytostatic, nematocidal and fungicidal activities [178]. 

Treatment of esters of aromatic acids with l-alkyl-2-pyrrolidones and l-methyl-2-piperidones is an useful method for the preparation of simple pyrrolines and piperidines, respectively. The l-alkyl-3-aroyl-2-pyrrolidones (110, n = 1) and l-alkyl-3-aroyl-2-piperidones (110, n = 2) thus formed are cleaved by the action of concentrated hydrochloric acid to give l-methyl-2-aryl-2-pyrrolines453 (111, n = 1) and l-alkyl-2-aryl-2-piperidines454 (111, n = 2), respectively. After blocking the secondary nitrogen atom in a lactam by means of acylation, one can prepare 2-aryl-1-pyrrolines (112, n = 1) and 2-aryl-1 -piperidines4 55-457 (112, n = 2). 

Harkin, S.A., Singh, O., and Thomas, E.J., Approaches to cytochalasan synthesis. Preparation and Diels-Alder reactions of 3-alkyl- and 3-acyl-A -pyrrolin-2-ones, J. Chem. Soc., Perkin Trans. 1, 1489, 1984. 

Other types of tetramic acid derivatives are A-acyl-4-methoxy-3-pyrrolin-2-ones or 4-O-methyl ethers of A-acylated tetramic acids. The only metabolites of this type containing a dienic structure are pukeleimides A (87), G (88), B (89) and F (90). They are nontoxic compounds isolated from the marine cyanophyte Lyngbya majuscula [158], a blue-green algae. 

Armande and Pandit. 3-Pyrroline was acylated with 1-chloro-octen-3-one to give the vinylogous amide (163) this compound was alkylated with the ortho-ester (164) to furnish, after sodium borohydride reduction and hydrolysis, the - prostanoid (165). 

One of the oldest reports of a synthesis of a highly substituted 3-pyrrolin-2-one involved a type e cyclization. Bashour and Lindwall treated y-oxo-P-hydroxycarboxamide 205 with HCl and obtained a product presumed to be 5-hydroxy-3-pyrrolin-2-one 206 (Scheme 46 1935JA178). Given the similarity of reactions that have been reported since then (e.g.. Scheme 42), this probably was the correct structural assignment. Moon later reported a synthesis of 4-acyl-3-pyrrolin-2-ones via thermal cyclization of y-ketocar-boxamides (1977JOC2219). 

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