ArticleJournal of the American Chemical Society2020
A Computational and Experimental Investigation of the Origin of Selectivity in the Chiral Phosphoric Acid Catalyzed Enantioselective Minisci Reaction.
Article in Journal of the American Chemical Society, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Phosphonium Ions as Activating Groups for the Selective Alkylation of Pyridines and Polyazines.Journal of the American Chemical Society · 2026Article
- Photocatalytic Minisci Approach to Chiral 2-Hetaryl-1,2-aminoalcohols from β-Hydroxy-α-amino Acid-Derived Redox Active Esters.The Journal of organic chemistry · 2025Article
- Bioinspired transfer methylation enabled by a photoactive reagent.Nature communications · 2025Article
- Expanding the Chemical Space of Electrophilic β-Glycosyl β-Lactams through Photoinduced Diastereoselective Functionalization.Organic letters · 2024Article
- Photocatalytic Enantioselective Radical Cascade Multicomponent Minisci Reaction of β-Carbolines Using Diazo Compounds as Radical Precursors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Mechanisms for radical reactions initiating fromBeilstein journal of organic chemistry · 2024Article
- Development of a flow photochemical process for a π-Lewis acidic metal-catalyzed cyclization/radical addition sequence: in situ-generated 2-benzopyrylium as photoredox catalyst and reactive intermediate.Beilstein journal of organic chemistry · 2024Article
- Discovery and Development of the Enantioselective Minisci Reaction.Accounts of chemical research · 2023Article
- Hydrogen Bond Assisted Three-Component Tandem Reactions to AccessMolecules (Basel, Switzerland) · 2023Article
- Molecular Understanding and Practical In Silico Catalyst Design in Computational Organocatalysis and Phase Transfer Catalysis-Challenges and Opportunities.Molecules (Basel, Switzerland) · 2023Review
- Photocatalytic enantioselective Minisci reaction of β-carbolines and application to natural product synthesis.Chemical science · 2023Article
- Enantioselective Giese Additions of Prochiral α-Amino Radicals.Journal of the American Chemical Society · 2022Article
- Asymmetric Photochemical [2 + 2]-Cycloaddition of Acyclic Vinylpyridines through Ternary Complex Formation and an Uncontrolled Sensitization Mechanism.Journal of the American Chemical Society · 2022Article
- Noncovalent Stabilization of Radical Intermediates in the Enantioselective Hydroamination of Alkenes with Sulfonamides.Journal of the American Chemical Society · 2022Article
- Strategies That Utilize Ion Pairing Interactions to Exert Selectivity Control in the Functionalization of C-H Bonds.Journal of the American Chemical Society · 2022Review
- Probing the Free Energy Landscape of Organophotoredox-Catalyzed Anti-Markovnikov Hydrofunctionalization of Alkenes.Journal of the American Chemical Society · 2022Article
- Hydrogen Atom Transfer Driven Enantioselective Minisci Reaction of Alcohols.Angewandte Chemie (International ed. in English) · 2022Article
- Asymmetric Photocatalysis Enabled by Chiral Organocatalysts.ChemCatChem · 2022Article
- Identifying the true origins of selectivity in chiral phosphoric acid catalyzedChemical science · 2021Article
- Radical chain monoalkylation of pyridines.Chemical science · 2021Article
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Minisci reaction is one of the most valuable methods for directly functionalizing basic heteroarenes to form carbon-carbon bonds. Use of prochiral, heteroatom-substituted radicals results in stereocenters being formed adjacent to the heteroaromatic system, generating motifs which are valuable in medicinal chemistry and chiral ligand design. Recently a highly enantioselective and regioselective protocol for the Minisci reaction was developed, using chiral phosphoric acid catalysis. However, the precise mechanism by which this process operated and the origin of selectivity remained unclear, making it challenging to develop the reaction more generally. Herein we report further experimental mechanistic studies which feed into detailed DFT calculations that probe the precise nature of the stereochemistry-determining step. Computational and experimental evidence together support Curtin-Hammett control in this reaction, with initial radical addition being quick and reversible, and enantioselectivity being achieved in the subsequent slower, irreversible deprotonation. A detailed survey via DFT calculations assessed a number of different possibilities for selectivity-determining deprotonation of the radical cation intermediate. Computations point to a clear preference for an initially unexpected mode of internal deprotonation enacted by the amide group, which is a crucial structural feature of the radical precursor, with the assistance of the associated chiral phosphate. This unconventional stereodetermining step underpins the high enantioselectivities and regioselectivities observed. The mechanistic model was further validated by applying it to a test set of substrates possessing varied structural features.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.