Fused 3-pyrrolin-2-ones

In an attempt to prepare fused pyrrohdinones such as 108, Balci and coworkers inadvertently prepared fused 3-pyrrolin-2-ones (Scheme 16 ... 

Stephenson and Tucker discovered an approach to fused 3-pyrrolin-2-ones via a tandem Ir-mediated radical cyclization and Cope rearrangement (Scheme 36 20110L5468). Treatment of cyclopropane-substituted propar-gylamide 170 with an iridium reagent and triethylamine led to the formation of fused 3-pyrrohn-2-one 172. The reaction manifold that explains the outcome of the reaction includes a radical cyclization to the spirocyclic intermediate 171, Cope rearrangement and re-aromatization. 

Reversing the position of the aldol electrophile, Enders and coworkers developed a type ce approach to complex 3-pyrrolin-2-ones that involved a quadruple cascade process (Scheme 91 2014S1539). Treatment of cinnamaldehyde (353) and the a-ketoamide 354 with pyrrolidine catalyst 355 and NaOAc gives the fused 3-pyrrolin-2-one 357. The mechanism of the reaction includes a Michael addition by the amide followed by aldol condensation to generate the 3-pyrrolin-2-one intermediate 356 subsequent Michael and aldol transformations with a second equivalent of 353 then gives the fused cyclopentene ring. 

The aza-Pauson—Khand reaction ([2+2+1] cycloaddition), where one of the TC-bond-containing components contains a nitrogen atom in place of a carbon atom (e.g., imine in place of alkene), is a powerful strategy for preparing 3-pyrrolin-2-ones and fused 3-pyrrolin-2-ones. One of the earliest... 

Ghan(ii and coworkers used o-salicaldehyde as the aldehyde component in this reaction and obtained chromane-fused 3-pyrrolin-2-ones (2013T3054). 

The reaction of NSBV 6-la with terf-butyl isocyanide (f-BuNC) in toluene was first monitored by NMR spectra. No reaction took place even when the reaction mixture was heated to 120 °C for 12 h in a sealed tube. However, in the presence of a catalytic amount of zinc triflate (5 mol%), reaction of the above mixture proceeded smoothly at room temperature. The reaction was very clean and finished within 2 h, affording the 5,8-diaza-4,8-brexadiene derivative 6-12a as a tetracyclic triimine in 93 % isolated yield (Scheme 6.2). No formation of the C-N bond insertion product 6-11 was detected. Single-crystal X-ray structural analysis of 6-12a revealed a cage-shaped skeleton containing a cyclopentanimine core fused with one cyclohexane ring and two pyrroline rings (Fig. 6.6). 

Finally, Jones and coworkers reported that fused isoxazoles are useful precursors to 4-amino-3-pyrrolin-2-ones (Scheme 163 2014CC1588). Hydrogenation of pyrrolo[3,4-c]isoxazole 570 gives 3-pyrrolin-2-one 571. 

---