4-Aryl-3-pyrrolin-2-ones

The De Kimpe group prepared 4-aryl-3-pyrrolin-2-ones starting with cyclobutanones (Scheme 47 2004SL1059). Treatment of cyclobutanone 207 with isopropylamine followed by sodium methoxide led to the amide 208 via a ring-opening reaction and substitution—ehmination. 

Jayaprakash, K. Venkatachalam, C. S. Balasu-bramanian, K. K. A convenient one-pot synthesis of N-aryl-3-pyrrolines. Tetrahedron Lett. 1999, 40, 6493-6496. 

The regioselectivity of the 1,3-dipolar cycloadditions of azides to alkenes is usually difficult to predict due to the similar energies for the transition states which involve either the HOMO (dipole) or the LUMO (dipole). The results of a study which utilized 5-alkoxy-3-pyrrolin-2-ones as dipolar-ophiles in reactions with a variety of aryl azides seemed to reflect this problem the results suggested that the low regioselectivity observed was due to the frontier molecular orbital interactions between dipole and dipolarophile, and not any steric hindrance offered by the 5-alkoxy function <84H(22)2363>. 

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). 

Nitrogen Heterocycles.- Intramolecular Wittig reactions have been used to construct heterocyclic rings in, for example, the synthesis of N-alkyl-3-pyrrolines (193) (Scheme 18) and that of 2-methyl-3-(aryl/alkyl)-l-oxo-l,2-dihydroisoquinolines (195) by a one-pot synthesis from the amides (194) (Scheme 19). ... 

Clayden and coworkers reported intramolecular Michael-addition— fragmentation leading to 3-vinyl- and 3-aryl-substituted 3-pyrrolin-2-ones (20040L609). For example, treatment of the carboxamide 178 (DEB = 1,1-diethylbutylcarbonyl) with LDA gives 3-pyrrolin-2-one 180 through a fragmentation of the initial Michael adduct 179 (Scheme 39). 

Acid-mediated cyclocondensation of208 then leads to the 3-pyrrolin-2-one 210 via the corresponding 4-aryl-4-pyrrohn-2-one intermediate 209. 

Quai and coworkers utilized a [4+1] cycloaddition with isocyanide to prepare highly substituted 3-pyrroHn-2-ones (Scheme 60 2004TL1413). Treatment of benzylidene-1,3-diketone 243 with tert-butyl isocyanide (244) gives 5-hydroxy-3-pyrrolin-2-ones 246 (Scheme 24). The authors propose an oxidative rearrangement mechanism for the conversion of initial adduct 245 to the observed product 246. Similar reactions have been reported by others in the synthesis of 3-aryl-4-carboethoxy-5-hydroxy-3-pyrrolin-2-ones (2007T8987) and 3,5-diaryl-5-hydroxy-3-pyrrolin-2-ones (2007TL8056). 

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