5.5- Disubstituted 3-pyrrolin-2-ones

The flash vacuum pyrolysis of isopropylidene N./V-disubstituted ami-nomethylenemalonates (e.g., 1235, 1237) was studied by McNab et al. [83CC957 85CC213 86JCS(P1)1465 87CC138 88JCS(PI)863, 88JCS(P1)869, 88JCS(P2)759], They obtained 1,5,5-trisubstituted 2-pyrrolin-4-ones (e.g., 1236, 1238) in 38-75% yields. 

Flash vacuum pyrolysis of other isopropylidene /V,/V-disubstituted aminomethylenemalonates (1244) also gave 1-substituted pyrrolin-4-ones (1245) [84HCA1402 85CC213 88JCS(P 1)863]. 

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... 

Oxidation of conjugated dienes in CH3CN-NaC104 in the presence of 1,3-dimethylurea gives a mixture of the possible 4,5-disubstituted 1,3-di-methylimidazolidin-2-ones in about 40% yield.103 Anodic oxidation of 2,4-hexadiene, 1,3-butadiene, and 1,3-cyclohexadiene in CH3CN-H20-NaC104 yields diols, 2-oxazolines, and 3-pyrrolines.104 The product distribution is influenced by the supporting electrolyte. 

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... 

Since then researchers in the field of nitrone cycloaddition seem to have more or less tacitly assumed that secondary interactions play an important role in determining endo/exo selectivity also in the case of N-alkyl and N-arylnitrone cycloaddi-tions.2 However, our experimental endo/exo selectivity studies " for the reactions of cyclic and open-chain nitrones with Z-disubstituted dipolarophiles revealed a clear-cut dominance (77% in benzene) of the endo mode only in one case the reaction of 1-pyrroline-l-oxide with maleonitrile, a reaction where the steric effects... 

A weU-explored method for the preparation of 3.4-disubstituted 3 pyrrolin-2-ones, first reported by PHeninger and coworkers, involves th... 

Starting from 3,4-disubstituted maleic anhydride, Klopfleisch and coworkers synthesized the bilirubin oxidation end-product BOX A and isomers in four or six steps (20130L4608). Within this synthesis they transformed 5-alkylidene-furan-2-ones to the corresponding substituted 3-pyrrolin-2-ones using ammonium acetate and glacial acetic acid. Seidel and coworkers employed a similar approach to BOX B analogs (2014TL6526). 

Padwa and coworkers realized the synthesis of 2,4-disubstituted pyrroles using rearrangements of 2-fiiranyl carbamates via 5-methoxy-3-pyrrolin-2-one intermediates. 2-Furanyl carbamate 593 was treated with iodine and sodium bicarbonate followed by methyl iodide and silver oxide to give the N-substituted 5-methoxy-3-pyrrolin-2-one 595 via the iodinated intermediate 594 (Scheme 173 20090L1233). Padwa employed this method to synthesize 5-methoxypyrrol-2-ones, which were then treated with alkyl hthiates to give tricycHc products (2009T6720). 

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