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A reaction intermediate is a key molecular entity that has been used in explaining how starting materials converts into the final products in the reaction, and it is usually unstable, highly reactive, and short-lived. Extensive efforts have been devoted in identifying and characterizing such species via advanced physico-chemical analytical techniques. As an appealing alternative, trapping experiments are powerful tools in this field. This trapping strategy opens an opportunity to discover multicomponent reactions. In this work, we report various highly diastereoselective and enantioselective four-component reactions (containing alcohols, diazoesters, enamines/indoles and aldehydes) which involve the coupling of in situ generated intermediates (iminium and enol). The reaction conditions presented herein to produce over 100 examples of four-component reaction products proceed under mild reaction conditions and show high functional group tolerance to a broad range of substrates. Based on experimental and computational analyses, a plausible mechanism of this multicomponent reaction is proposed.
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http://dx.doi.org/10.1038/s41467-022-34913-2 | DOI Listing |
J Am Chem Soc
June 2025
State Key Laboratory of Anti-Infective Drug Discovery and Development, Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Multicomponent reactions (MCRs) provide a robust platform for the modular assembly of structurally complex molecules, while higher-order MCRs (≥4 components) exponentially expand the accessible chemical space. Although Rh-carbynoids exhibit significant potential for developing higher-order MCRs due to their unique reactivity, their application in asymmetric four-component reactions (4CRs) has been hindered by competing nucleophilic reactivities and stereochemical control. Herein, we overcome these challenges by integrating - and -nucleophiles and report an asymmetric 4CR involving hypervalent iodine diazo reagents, carbamates, -dialkylanilines, and imines.
View Article and Find Full Text PDFOrg Biomol Chem
April 2025
Department of Applied Chemistry, Anhui Province Engineering Laboratory for Green Pesticide Development and Application, and Anhui Province Key Laboratory of Crop Integrated Pest Management, Anhui Agricultural University, Hefei 230036, China.
A one-pot synthesis of chiral multifunctional oxazole frameworks is accomplished a cascade reaction involving an anionic stereogenic cobalt(III) complex-catalyzed enantioselective Ugi four-component/Wittig process. This approach tolerates a complex reaction system that includes aldehydes, amines, carboxylic acids, and isocyano-(triphenylphosphoranylidene)acetates, yielding chiral 2,4,5-trisubstituted oxazoles with good enantioselectivities (up to 93 : 7 er).
View Article and Find Full Text PDFAngew Chem Int Ed Engl
January 2025
Key Laboratory of Green Chemistry & Technology, Ministry of Education, College of Chemistry, Sichuan University, Chengdu, 610064, China.
The efficient construction of chalcogen-atom-based chiral compounds remains a challenge, despite the importance of organoselenium and organosulfur compounds in life and materials science. Chalcogen atoms can form net attractive interactions called chalcogen bonds, but it is an undeveloped tool to assist asymmetric catalysis. Herein, we report an enantioselective insertion platform to install a stereogenic center bearing selenyl and thiocyano functional groups.
View Article and Find Full Text PDFNat Commun
November 2022
Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, PR China.
A reaction intermediate is a key molecular entity that has been used in explaining how starting materials converts into the final products in the reaction, and it is usually unstable, highly reactive, and short-lived. Extensive efforts have been devoted in identifying and characterizing such species via advanced physico-chemical analytical techniques. As an appealing alternative, trapping experiments are powerful tools in this field.
View Article and Find Full Text PDFNat Commun
November 2022
Department of Applied Chemistry, Anhui Agricultural University, Hefei, 230036, China.
Ugi reactions and related variations are proven to be atom and step-economic strategies for construction of highly valuable peptide-like skeletons and nitrogenous heterocycles. The development of structurally diverse range of novel catalytic systems and the discovery of new approaches to accommodate a broader scope of terminating reagents for asymmetric Ugi four-component reaction is still in high demand. Here, we report a strategy that enables enantioselective Ugi four-component and Ugi-azide reactions employing anionic stereogenic-at-cobalt(III) complexes as catalysts.
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