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

Wei Wu, Xiao Yan, Xiaofeng Li, Yanqiang Ning, Lei Hu, Lei Zhu, Qin Ouyang, Yungui Peng

2022Organic Letters17 citationsDOI

Abstract

]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 phase-transfer 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.

Topics & Concepts

IsoquinolineChemistryDiazoStereocenterCycloadditionEnantioselective synthesisProtonationDeprotonationBifunctionalDensity functional theoryCombinatorial chemistryCatalysisComputational chemistryStereochemistryMedicinal chemistryOrganic chemistryIonCyclopropane Reaction MechanismsSynthesis and Catalytic ReactionsFluorine in Organic Chemistry
Highly Enantioselective Synthesis of [1,2,4]Triazino[5,4-<i>a</i>]isoquinoline Derivatives via (3 + 3) Cycloaddition Reactions of Diazo Compounds and Isoquinolinium Methylides | Litcius