Pyrrolo 2,l-a isoindol-5-one

For example, McNab and coworkers have discovered that flash-vacuum pyrolysis (FVP) (1000 °C, 0.01 Torr) of pyrrole 10-114 led to the formation of pyrrolo[2,l-a]isoindol-5-one 10-117 in 79% (Scheme 10.29) [44]. The transformation is proposed to proceed via an initial 1,5-aryl shift to give intermediate 10-115, which then undergoes an elimination of methanol. Finally, electrocydization of the ketene 10-116 results in the formation of 10-117. 

Aikten et al. described the pyrolysis of chiral phthalimido thioxo-stahilised phosphonium ylides. Such compounds were prepared from (5 )-alanine and (5 )-phenylalanine, and underwent an intramolecular Wittig reaction leading to pyrrolo[2,l-a]isoindol-5-one-2-thiones, rather than the expected P to 5 migration of a phenyl group (Scheme 14). 

The Michael adduct can be the precursor of several cyclizations giving rise to new tandem sequences. This has been mainly due to the mechanistic aspects of the process itself and to the synthetic potential of the resultant products. A new stereoselective synthesis of pyrrolo[2,l-c/]isoindol-5-ones has been described. It consisted of a sequential Michael addition to the in situ generated anion of methyl IV-phthaloylalaninate 289, onto a series of conjugate acceptors. Cyclization of the resultant anion intermediate by condensation with one of the carbonyl imido groups gave the desired products 291 in good yields as single isomers in only one step (Scheme 89). 

FVP of l-(2-methoxycarbonylphenyl)pyrrole 19 at925°C (0.001 Torr) gives the unusual 5//-pyrrolo[2,l- 7]isoindol-5-one system 21 (79%) by a novel three-step cascade process involving rate-determining [l,5]-aryl migration. 

The thiocarbonyl-stabilized ylides 76, derived in a few steps from alanine and phenylalanine, undergo an intramolecular Wittig reaction involving one carbonyl group of the phthalimide function to give products 77, which are derivatives of the previously unknown pyrrolo[2,l-d]isoindol-5-one-2-thione ring system (Scheme 17 2014H(88)1135). 

Dihydro-17/-pyrrolo[l,2-< ][l,3,5]oxadiazocin-6(5/7)-one ring system 78 can be obtained from 2,3-dihydro-3-hydroxy-2-(pyrrol-l-ylmethyl)-17/-isoindol-l-one 76. No intermediate acyl chloride was observed during the cyclization of 77a, and product 78 (X = O) was isolated in low 15% yield. Yields were not improved after addition of Lewis acids or use of polyphosphoric acid as a condensation reagent (Scheme 16 <1998JHC9>). Similarly, 2,3-dihydro-l/7-pyrrolo[l,2-< ][l,3,5]thiadiazocin-6(577)-one ring system 19 (X = S) was obtained in low yield. Key intermediate 77b was prepared from 76 in one step under acidic catalysis. 

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