Enantiodivergent synthesis of pyrrolo[2,1-a]isoquinolines based on diastereoselective Parham cyclization and alpha-amidoalkylation reactions.
Enantiodivergent synthesis of C-10b-substituted pyrrolo[2,1-a]isoquinolines starting from an enantiomerically pure N-phenethylnorborn-5-en-endo-2,3-dicarboxyimide 3a, with a 2-exo-hydroxy-10-bornylsulfinyl group as a chiral auxiliary, has been developed. The key transformations are derived from diastereoselective intramolecular cyclization of aryllithiums and alpha-amidoalkylation reactions, with the ethylidene bridge of the norbornene moiety dictating the stereochemical outcome in both types of reactions. Thus, the organolithium addition-intramolecular alpha-amidoalkylation sequence on imide 3a afforded stereoselectively the R configuration at C-12b, whereas the tandem Parham cyclization-intermolecular alpha-amidoalkylation reactions on the corresponding iodinated imide 3b occurred with complete control of stereoselectivity, leading to the epimer at C-12b. Subsequent reductive removal of the chiral auxiliary and retro-Diels-Alder reaction afforded (10bS)- and (10bR)-pyrroloisoquinolines 1 in high yields and optical purities (>99% ee).
González-Temprano
Inés
I
Departamento de Química Orgánica II, Facultad de Ciencia y Tecnología, Universidad del País Vasco/Euskal Herriko Unibertsitatea, Apdo 644, 48080 Bilbao, Spain.
Osante
Iñaki
I
Lete
Esther
E
Sotomayor
Nuria
N