Highly Enantioselective Synthesis of [1,2,4]Triazino[5,4-a]isoquinoline Derivatives via (3+3) Cycloaddition Reactions of Diazo Compounds and Isoquinolinium Methylides

An array of chiral [1,2,4]triazino[5,4-a]isoquinoline derivatives were obtained in excellent yields (up to 98%) and with excellent enantioselectivities (up to 99% ee) via a new highly asymmetric (3 + 3) cycloaddition reaction of diazo compounds and isoquinolinium methylides, with a bifunctional chiral phasetransfer catalyst (PTC). Density functional theory calculations show that PTC has a bridge role in the deprotonation/protonation process. The obtained products were transformed into densely functionalized polycyclic heterocompounds with multiple stereocenters.

Automated summary

An array of chiral [1,2,4]triazino[5,4-a]isoquinoline derivatives were synthesized in excellent yields and enantioselectivities through a new highly asymmetric (3 + 3) cycloaddition reaction. The reaction was facilitated by a bifunctional chiral phasetransfer catalyst and density functional theory calculations revealed the catalyst's role in the deprotonation/protonation process. The obtained products were transformed into densely functionalized polycyclic heterocompounds with multiple stereocenters.