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Total Synthesis of (+)-Hinckdentine A: Harnessing Noncovalent Interactions for Organocatalytic Bromination

Zhuwei Ruan, Min Wang, Yang Chen, Lili Zhu, Zhishan Su, Ran Hong

2022JACS Au25 citationsDOIOpen Access PDF

Abstract

]quinazoline skeleton, was completed in 12 steps featuring the construction of the Nα-quaternary carbon center by asymmetric azo-ene cyclization. A novel organocatalyst was developed to promote high-yielding tribromination, which represents a challenging process encountered in previous syntheses. Density functional theory calculations scrutinized viable substrates and deciphered the origin of the enhancement of C8 electrophilic bromination with a bifunctional organocatalyst. Moreover, the application of organocatalyst-enabled bromination on various substrates was demonstrated to highlight future late functionalizations of biologically intriguing targets.

Topics & Concepts

HalogenationBifunctionalChemistryElectrophileCarbon skeletonOrganocatalysisBiomimetic synthesisCombinatorial chemistryOrganic chemistryStereochemistryEnantioselective synthesisCatalysisAxial and Atropisomeric Chirality SynthesisCatalytic C–H Functionalization MethodsAlkaloids: synthesis and pharmacology
Total Synthesis of (+)-Hinckdentine A: Harnessing Noncovalent Interactions for Organocatalytic Bromination | Litcius