Isoquinoline core construction

A new approach for the asymmetric creation of the pyrrolo[2,3,i]isoquinoline core was described starting with >-(-)-quinic acid (Scheme 21) and featuring an optimized intramolecular Mannich reaction as the central key step [82]. The final keto-aldehyde was constructed in enantiopure fashion and serves as a platform for the... 

Electrocyclization or [4 + 2] processes have been reported for the construction of isoquinoline core either from aza-diene intermediates (as in the case of quinolines) or from benzyne intermediates. 

Synthesis of tetrahydroimidazo[2,l-a]isoquinolines is another example of the reaction s utility in a fused core synthesis. Formation of compounds of structure 57 starts with 7-phenyl-5,6,7,8-tetrahydroiso-quinoline (56) amination in either DMA or tetralin in autoclave at 220 C for 18 h, which gives 53 in 41-48% yield, consecutively, although a higher yield is achieved when heating the starting material in DMA in the microwave for 12 h, which gives 58 in a 59% yield. The product is then used to construct the tetrahydroimidazo[2,l-a]isoquinoline framework using chloroacetone or 3-bromobutanone, which affords 58a,b in 46% and 75% yields, respectively... 

---