Herein, we report a highly efficient synthesis of enantioenriched aza-[3.3.1]-bicyclic enamines and ketones, a class of structural cores in many natural products, via asymmetric dearomatization of indoles with azodicarboxylates. The reaction is initiated by electrophilic amination and followed by aza-Prins cyclization/phenonium-like rearrangement. A newly developed fluorine-containing chiral phosphoric acid displays excellent activity in promoting this cascade reaction. The absence or presence of water as the additive directs the reaction pathway toward either enamine or ketone products in high yields (up to 93%) with high enantiopurity (up to 98% ee). Comprehensive density functional theory (DFT) calculations reveal the energy profile of the reaction and the origins of enantioselectivity and water-induced chemoselectivity.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/jacs.3c02773 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Dearomative Addition-Hydrogen Autotransfer for Branch-Selective -Heteroaryl C-H Functionalization via Ruthenium-Catalyzed C-C Couplings of Diene Pronucleophiles.
J Am Chem Soc
January 2025
Department of Chemistry, University of Texas at Austin, Austin 78712, Texas, United States.
Article Synopsis
- A new method for C-H functionalization of heteroaryl compounds is introduced, which involves a process called dearomative addition followed by hydrogen autotransfer.
- This process starts with the hydroruthenation of dienes to create allylruthenium nucleophiles, leading to branched C-C coupling products through addition and β-hydride elimination.
- The study also details the formation of enantiomerically enriched heteroarylethyl alcohols and amines through oxidative cleavage and dynamic kinetic asymmetric reduction, supported by density functional theory calculations linking regioselectivities to molecular factors.
Asymmetric Total Synthesis of (+)-Hyperbeanol A.
Org Lett
January 2025
State Key Laboratory of Applied Organic Chemistry & College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China.
A bioinspired alkylation dearomatization reaction was developed to construct the 5/6/6 fused-spiro tricyclic core framework and spiro-quaternary carbon chiral center. The usage of this approach for assembling these natural products of spirocyclic polycyclic polyprenylated acylphloroglucinols with an octahydrospiro-[cyclohexan-1,5'-indene] core is demonstrated by the first asymmetric total synthesis of highly oxidized hyperbeanol A.
View Article and Find Full Text PDFCopper-Catalyzed Enantioselective Skeletal Editing through a Formal Nitrogen Insertion into Indoles to Synthesize Atropisomeric Aminoaryl Quinoxalines.
Angew Chem Int Ed Engl
December 2024
State key laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, 15 Yu Cai Road, Guilin, 541004, China.
Skeletal editing represents an attractive strategy for adding complexity to a given molecular scaffold in chemical synthesis. Isodesmic reactions provide a complementary skeletal editing approach for the redistribution of chemical bonds in chemical synthesis. However, catalytic enantioselective isodesmic reaction is extremely scarce and enantioselective isodesmic reaction to synthesize atropisomeric compounds is unknown.
View Article and Find Full Text PDFDevelopment of a Synthetic Platform for Ent-Pimaranes Reveals their Potential as Novel Non-Redox Active Ferroptosis Inhibitors.
Chemistry
December 2024
Department of Organic Chemistry and Center for Molecular Biosciences, University of Innsbruck, Innrain 80-82, 6020, Innsbruck, Austria.
We present a comprehensive account on the evolution of a synthetic platform for a subfamily of ent-pimaranes. For the most complex member, norflickinflimiod C, five distinct strategies relying on either cationic or radical polyene cyclizations to construct the requisite tricyclic carbon scaffold were explored. Insights from early and late stage oxidative and reductive dearomatization studies ultimately led to a mild, rhodium-catalyzed arene hydrogenation for the final synthetic route.
View Article and Find Full Text PDFOrganocatalyzed Enantioselective Double Dearomatization of Tricyclic Phenols and Alkoxybenzenes.
Org Lett
December 2024
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences & Research Unit of Peptide Science, Chinese Academy of Medical Sciences, 2019RU066, Lanzhou University, Lanzhou 730000, China.
To advance more efficient dearomatization approaches, we present herein an organocatalyzed asymmetric double dearomatization reaction of tricyclic phenols and alkoxybenzenes by leveraging a novel steric hindrance-regulated dearomatization strategy for nonfunctionalized phenols. This protocol allows the efficient synthesis of structurally complex polycyclic diketones with four tertiary carbon centers under mild conditions while also showcasing the potential of multiple dearomatizations for building intricate molecular frameworks from simple starting materials.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!