3-Alkylated 3-pyrrolin-2-ones

Complex reactions occur on the autoxidation of pyrroles (see Section 3.05.1.4) predictably, susceptibility to autoxidation increases with increasing alkyl substitution, llie photosensitized reaction of pyrrole and oxygen yields 5-hydroxy-A -pyrrolin-2-one, probably by way of an intermediate cyclic peroxide (Scheme 28) (76JA802). 

Pyrrolin-3-ones alkylation, 4, 301 oxidative dimerization, 4, 304 synthesis, 4, 365... 

A-Acyliminium precursors in tetracarbonyliron-mediated stereoselective alkylations of 5-(R)-isopropoxy-3-pyrrolin-3-ones 98EJ01729. 

This method for preparing 2-phenyl-1-pyrroline, and assorted 2-substituted 1-pyrrolines, is one of the best currently available, particularly because it reproducibly affords clean materials. Generally, the procedure is amenable to various aromatic esters 2 it has also been applied successfully to aliphatic esters (Table I).3 An advantage of this method is the use of readily available, inexpensive N-vinyl-pyrrolidin-2-one as a key starting material. This compound serves effectively as a 3-aminopropyl carbanion equivalent. The method illustrated in this procedure has been extended to include the synthesis of 2,3-disubstituted pyrrolines. Thus, alkylation of the enolate of the intermediate keto lactam, followed by hydrolysis, leads to various disubstituted pyrrolines in good yields (see Table II).3... 

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. 

Additional communications deal with the synthesis of pyrrolo[l,2-cjquinazolines by treatment of methyl 3-alkyl-l,3-dihydro-2-oxo-3-(triphenylphosphoranylidenamino)-2//-indole-l-carboxylates (275) with ketones to afford A -pyrrolin-4-ones (276). As Scheme 100 shows, 276 can... 

Reaction of the 2-acetoxy-3(2//)-furanones (526) with monosubstituted hydrazines gives good yields of the pyridazinium-5-olates (527) together with varying amounts of isomeric products. Alkyl derivatives (527 R = alkyl) have also been prepared by base-catalyzed alkylation (Mel, Me2SO4, PhCH2Cl) of 3-methyl-6-phenyl-5-ethoxycarbonyl-4( 1 //)-pyridazinone. Reduction of the diphenyl compound 527 (R = Ar = Ph) by zinc and hydrochloric acid gives 3-ethoxycarbonyl-5-hydroxy-5-methyl-l,2-diphenyl-2-pyrrolin-4-one (528 R = Ar = Ph) (Scheme 21... 

Photoreaction of l-vinyl-4-alkyl-5-aminotriazolines leads to unexpected pyrrolines and pyrroles.459 The 1-vinylaziridine formed by ring closure of the 1,3-diradical undergoes a selective ring cleavage at one of the C—N bonds (bearing the amino group) followed by cyclization with the j -vinyl carbon to give the products (Scheme 157)459... 

These low selectivities were improved by changing the amine substituents of the catalysts 34 from diisopropyl/dicyclohexyl to C2-symmetric 2,5-dimethyl-pyrroline ring, leading to two diastereomeric catalysts 35 (Scheme 6.14), which were synthesized in the same way as catalysts 34 [9]. The catalytic competency of 35 was established using standard phase-transfer alkylation conditions to afford the alkylation product with up to 37% ee. Enantioselectivities obtained using diastereomers of the catalyst 35 were different, but not opposite, which suggests that the stereocenters function cooperatively in one diastereomer, but not in the other. 

Complex 9 and [CpFe(o-BPXCO)CH 2C1 ] [o-BP = tri(o-biphenyl)-phosphite] were also prepared by the reaction of HC1 with [CpFe(L)-(CO)CH2OEt] (L = PPh3, o-BP) (47). Alkylation of the two complexes with sodium /crt-butyl acetoacetate and pyrroline cyclohexanone enamine yielded six of the eight possible alkylation products. The two products where L was o-BP and the nucleophile was tort-butyl acetoacetate did not form, presumably because of excessive steric hindrance. The excess of one diastereomer over the other ranged from 10 to 64%. 

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). 

The final series of five procedures presents optimized preparations of a variety of useful organic compounds. The first procedure in this group describes the preparation of 3-BROMO-2(H)-PYRAN-2-ONE, a heterodiene useful for (4+2] cycloaddition reactions. An optimized large scale preparation of 1,3,5-CYCLOOCTATRIENE, another diene useful for [4+2] cycloaddition, is detailed from the readily available 1,5-cyclooctadiene. Previously, the availability of this material has depended on the commercial availability of cyclooctatetraene at reasonable cost. A simple large scale procedure for the preparation of 3-PYRROLINE is then presented via initial alkylation of hexamethylenetetramine with (Z)-1,4-dichloro-2-butene. This material serves as an intermediate for the preparation of 2,5-disubstituted pyrroles and pyrrolidines via heteroatom-directed metalation and alkylation of suitable derivatives. The preparation of extremely acid- and base-sensitive materials by use of the retro Diels-Alder reaction is illustrated in the preparation of 2-CYCLOHEXENE-1.4-DIONE, a useful reactive dienophile and substrate for photochemical [2+2] cycloadditions. Functionalized ferrocene derivatives... 

The products first formed are usually unsaturated y-lactams (d3-and/or d4-pyrrolin-2-ones). If alkyl substituents are present at the 5-position, the structure d4 is preferred.50,58 These can react further in neutral or weakly acidic media46 to give addition products with unreacted pyrrole (see compounds 43,44, and 55) or with hydrogen peroxide (see compounds 47, 48, 53, and 54). On the other hand, substituents at the 3- and/or 4-positions, as well as the lack of alkyl substituents, tends to stabilize the d8 structure.50... 

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. 

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