Chiral Phosphoric Acid-Catalyzed Enantioselective Synthesis of 2,2-Disubstituted 2,3-Dihydro-4-quinolones from Isatins and 2′-Aminoacetophenones DOI

Hidenori Andatsu,

Yuto Terashima,

Ryota Kawamura

et al.

Organic Letters, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 24, 2024

Herein, we present the enantioselective synthesis of 2,3-dihydro-4-quinolones bearing chiral tetrasubstituted carbons from isatins and 2′-aminoacetophenones. The transformation is mediated by a phosphoric acid catalyst proceeds via an in situ generated ketimine subsequent intramolecular cyclization. methodology features broad scope functional group tolerance with yields enantioselectivities up to 99% 98% ee. Detailed density theory (DFT) calculations support proposed reaction mechanism origin asymmetric induction.

Language: Английский

Revealing the nature of covalently tethered distonic radical anions in the generation of heteroatom-centered radicals: evidence for the polarity-matching PCET pathway DOI Creative Commons
Kang Fu,

Xihui Yang,

Zhiyou Yu

et al.

Chemical Science, Journal Year: 2024, Volume and Issue: 15(31), P. 12398 - 12409

Published: Jan. 1, 2024

The philicity-regulation and PCET mechanism of tether-tunable distonic radical anion-mediated generation heteroatom-centered radicals has been explored via experimental theoretical investigations.

Language: Английский

Citations

8
Controlling Stereoselectivity with Noncovalent Interactions in Chiral Phosphoric Acid Organocatalysis DOI
Isaiah O. Betinol, Yutao Kuang,

Brian P. Mulley

et al.

Chemical Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: March 18, 2025

Chiral phosphoric acids (CPAs) have emerged as highly effective Brønsted acid catalysts in an expanding range of asymmetric transformations, often through novel multifunctional substrate activation modes. Versatile and broadly appealing, these benefit from modular tunable structures, compatibility with additives. Given the unique types noncovalent interactions (NCIs) that can be established between CPAs various reactants─such hydrogen bonding, aromatic interactions, van der Waals forces─it is unsurprising catalyst systems become a promising approach for accessing diverse chiral product outcomes. This review aims to provide in-depth exploration mechanisms by which impart stereoselectivity, positioning NCIs central feature connects broad spectrum catalytic reactions. Spanning literature 2004 2024, it covers nucleophilic additions, radical atroposelective bond formations, highlighting applicability CPA organocatalysis. Special emphasis placed on structural mechanistic features govern CPA-substrate well tools techniques developed enhance our understanding their behavior. In addition emphasizing details stereocontrolling elements individual reactions, we carefully structured this natural progression specifics broader, class-level perspective. Overall, findings underscore critical role catalysis significant contributions advancing synthesis.

Language: Английский

Citations

0
Ni(II)-Catalyzed Site- and Regioselective α-Alkenylation of Cyclic Ketones with Alkenes DOI

Tongtong Ni,

Xuefeng Xu,

Man Cao

et al.

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: April 29, 2025

Herein, a nickel-catalyzed α-alkenylation reaction of asymmetric cyclic ketones at the sterically hindered α-position with alkenes is disclosed. The high regioselectivity might originate from acid-catalyzed enolization reaction, selectively generating thermodynamically favored enol. nickel catalyst facilitates preferential alkenylation polysubstituted enolates rather than monosubstituted enolates, thereby reversing conventional ketones. This method encompasses broad range applicable substrates alkenes.

Language: Английский

Citations

0
Total Synthesis of Brevitaxin DOI
Yang Lü,

Tingting Cao,

Kang Li

et al.

Organic Letters, Journal Year: 2024, Volume and Issue: 26(25), P. 5237 - 5242

Published: June 10, 2024

Brevitaxin was prepared in nine steps from commercially available carnosic acid. The construction of the 1,4-benzodioxin moiety involved an unique stepwise ortho-quinone-engaged [4+2] cycloaddition. Two strategic stages were employed to prepare highly unsaturated cycloaddition precursor 3: (1) synthesizing diene (C1–C2 and C10–C20 double bonds) by regioselective ortho-quinone tautomerization, (2) installing four sp2-hybridized carbon atoms (C3, C5, C6 C7) one step using a SeO2-promoted chemo- oxidation reaction.

Language: Английский

Citations

2
Asymmetric Three-Component Radical Cascade Reactions Enabled by Synergistic Photoredox/Brønsted Acid Catalysis: Access to α-Amino Acid Derivatives DOI Creative Commons
Chao Che,

Yi‐Nan Lu,

Ting Fang

et al.

ACS Central Science, Journal Year: 2024, Volume and Issue: 11(1), P. 36 - 45

Published: Aug. 16, 2024

Multicomponent reactions (MCRs), highly sought-after methods to produce atom-, step-, and energy-economic organic syntheses, have been developed extensively. However, catalytic asymmetric MCRs, especially those involving radical species, remain largely unexplored owing the difficulty in stereoselectively regulating extraordinarily high reactivity of open-shell species. Herein, we report a conceptually novel three-component cascade reaction readily accessible glycine esters, α-bromo carbonyl compounds 2-vinylcyclopropyl ketones via synergistic photoredox/Brønsted acid catalysis, which three sequential C–C (σ/π/σ) bond-forming events occurred through addition/ring-opening/radical–radical coupling protocol, affording an array valuable enantioenriched unnatural α-amino derivatives bearing two contiguous stereogenic centers alkene moiety moderate good yield with diastereoselectivity, excellent enantioselectivity E-dominated geometry under mild conditions. The relay process, unique proton-coupled electron transfer (PCET)-promoted radical–radical coupling, is supported by mechanistic investigations quantum mechanics calculations should garner broad interest further inspire development multicomponent reactions.

Language: Английский

Citations

2
Organocatalytic asymmetric tandem reaction for the enantioselective synthesis of chiral oxindoles to construct CyK dyes DOI
Le Wang,

Zi-Hao Li,

Di Wu

et al.

Chem Catalysis, Journal Year: 2024, Volume and Issue: unknown, P. 101188 - 101188

Published: Nov. 1, 2024

Language: Английский

Citations

2
1,6‐Addition Reactions of Difluoroenol Silyl Ethers with Benzoquinones and Quinonediimines To Access Difluorooxymethyl and Difluoroaminomethyl Compounds DOI
Hong Peng, Jǐnjīng Xǔ, Jinshan Li

et al.

Advanced Synthesis & Catalysis, Journal Year: 2023, Volume and Issue: 365(24), P. 4550 - 4555

Published: Nov. 14, 2023

Abstract The etherification and amination of difluoroenol silyl ethers with benzoquinones quinonediimines were achieved by using hexafluoroisopropanol (HFIP) as the solvent. This 1,6‐addition reaction could construct difluorooxymethyl difluoroaminomethyl compounds under metal‐free conditions. It is preliminarily speculated that took place through a single electron transfer (SET) process.

Language: Английский

Citations

2
Understanding the Nonlinear Hammett Relationship in Osmylation of Olefins with OsO4–Amine Ligands: Importance of Singlet-Diradical Character DOI

Yi-Hui Deng,

Tian‐Yu Sun, Yun‐Dong Wu

et al.

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 89(16), P. 11173 - 11182

Published: July 29, 2024

Although the concerted [3 + 2] mechanism of osmium-catalyzed asymmetric dihydroxylation has been generally accepted, unusual nonlinear Hammett relationship induced by amine-type ligands remains unexplained. To understand this, we carried out a density functional theory (DFT) study for osmylation substituted styrenes following: OsO4, OsO4–pyridine, OsO4–4-cyanopyridine, OsO4–4-pyrrolidinopyridine, and OsO4–quinuclidine. Calculations using M06 successfully reproduce experimentally observed relationships. The transition states exhibit considerable singlet-diradical character, which causes relationship. Regardless presence or absence an ligand, electron donation from styrene to OsO4 is observed, indicating no mechanistic change. indicate that electronic interaction between ligand also influences reaction rate.

Language: Английский

Citations

0
Mechanism of Iron-Catalyzed Oxidative α-Amination of Ketones with Sulfonamides DOI Creative Commons

Gloria M. Parrales,

Nina C. Hollin,

Fubin Song

et al.

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 89(17), P. 12462 - 12466

Published: Aug. 16, 2024

We report the mechanism of iron-catalyzed oxidative α-amination ketones with sulfonamides. Using linear free energy relationships, competition experiments, and identification reaction intermediates, we have found that this proceeds through rate-limiting electron transfer to 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) from an iron enolate in process forming α-DDQ adduct. The adduct then serves as electrophile for substitution sulfonamide nucleophiles, accelerated by additional DDQ. This mechanistic study rules out formation α-carbocation intermediate purely radical hypotheses.

Language: Английский

Citations

0
Chiral Phosphoric Acid-Catalyzed Enantioselective Synthesis of 2,2-Disubstituted 2,3-Dihydro-4-quinolones from Isatins and 2′-Aminoacetophenones DOI

Hidenori Andatsu,

Yuto Terashima,

Ryota Kawamura

et al.

Organic Letters, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 24, 2024

Herein, we present the enantioselective synthesis of 2,3-dihydro-4-quinolones bearing chiral tetrasubstituted carbons from isatins and 2′-aminoacetophenones. The transformation is mediated by a phosphoric acid catalyst proceeds via an in situ generated ketimine subsequent intramolecular cyclization. methodology features broad scope functional group tolerance with yields enantioselectivities up to 99% 98% ee. Detailed density theory (DFT) calculations support proposed reaction mechanism origin asymmetric induction.

Language: Английский

Citations

0