Isoindolinones as versatile new chiral templates for use in asymmetric synthesis

Reaction of β-aminothiols with 2-acylbenzoic acids affords the thiazoloisoindolinones (1) as single diastereoisomers when using chiral non-racemic aminothiol substrates. Attempted diastereoselective enolate alkylation of (1) led to the formation of the S-alkylated products (2). Treatment of the sulphoxides of (1) with common Pummerer activators gave novel ring expanded compounds (3). [Illustration omitted.] A cyclisation reaction has been used to generate the pyridoisoquinoline ring system (4) from readily available bicyclic lactam precursors (5). Enamides (6) were accessed upon cyclisation of the appropriate lactam precursors instead of the desired tetracyclic isoquinolines (7). [Illustration omitted.] The cyclisation of isoindolinone (8) furnished isoindoloisoquinoline (9), the further manipulation of which accessed an isomer of nuevamine (10). [Illustration omitted.]