5.5- Diaryl 3-pyrrolin-2-ones

Anionic/oxidative reaction sequences have been developed in addition to the domino anionic/reductive processes. For example, with regard to the synthesis of novel diaryl heterocycles as COX-2 inhibitors [500], including rofecoxib (Vioxx) 2-972 [501] (which has recently been withdrawn from the market) or the pyrrolin-2-one derivative 2-973 [494], Pal and coworkers reported on a so-far unique domino aldol condensation/oxidation sequence (Scheme 2.218) [503]. 

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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