Catalytic Asymmetric Dearomative 1,3-Dipolar Cycloaddition of 2-Nitrobenzothiophenes and Isatin-Derived Azomethine Ylides
Jian‐Qiang Zhao, Zhou Shun, Lei Yang, Hongyan Du, Yong You, Zhen‐Hua Wang, Ming‐Qiang Zhou, Wei‐Cheng Yuan
Abstract
An enantioselective dearomative 1,3-dipolar cycloaddition of 2-nitrobenzothiophenes and isatin-derived azomethine ylides with a bifunctional hydrogen-bonding thiourea catalyst was established, giving polyheterocyclic compounds in excellent results (up to 99% yield, >20:1 dr for all cases and up to 99% ee). The enantioselectivity could be reversed by the bifunctional hydrogen-bonding squaramide catalyst containing the same chiral source as in the thiourea catalyst. DFT calculations revealed the origin of the observed stereochemistry and the reversal of enantioselectivity.
Topics & Concepts
BifunctionalChemistryIsatinThioureaSquaramideEnantioselective synthesisCycloadditionCatalysis1,3-Dipolar cycloadditionYield (engineering)Hydrogen bondOrganocatalysisCombinatorial chemistryAzomethine ylideBifunctional catalystMedicinal chemistryOrganic chemistryMoleculeMaterials scienceMetallurgySynthesis and Catalytic ReactionsOrganic Chemistry Cycloaddition ReactionsAsymmetric Synthesis and Catalysis