Discovery and Development of the Enantioselective Minisci Reaction DOI Creative Commons
P. David Bacoş, Antti S. K. Lahdenperä, Robert J. Phipps

et al.

Accounts of Chemical Research, Journal Year: 2023, Volume and Issue: 56(14), P. 2037 - 2049

Published: July 5, 2023

ConspectusThe class of reactions now known as Minisci is broadly defined the addition nucleophilic carbon-based radicals to basic heteroarenes with subsequent rearomatization form a new carbon–carbon bond. Since pioneering work in 1960s and 1970s, these are widely used medicinal chemistry due ubiquity heterocycles druglike molecules. One long-standing challenges has been that regioselectivity mixtures positional isomers commonly obtained on many substrates if there choice between similarly activated sites. At outset described herein, we hypothesized it may be possible tackle this using catalytic strategy whereby bifunctional Brønsted acid catalyst simultaneously activates heteroarene engages attractive non-covalent interactions incoming nucleophile, resulting proximal attack. Using chiral BINOL-derived phosphoric acids, not only were able achieve goal regiocontrol but also discovered could control absolute stereochemistry at stereocenter formed when prochiral α-amino employed. time, discovery was unprecedented context reactions.This Account details protocol further development, expansion, investigations into mechanism have carried out since then, several collaboration other research groups. Collaborative efforts involved an expansion scope diazines guided by multivariate statistical analysis through development predictive model (collaboration Sigman). Also, mechanistic study involving detailed DFT Goodman Ermanis) unveiled selectivity-determining step being deprotonation key cationic radical intermediate associated phosphate anion. We additionally number synthetic developments such removing need prefunctionalize nucleophile; hydrogen-atom transfer can enable formal coupling two C–H bonds C–C bond while retaining high enantio- regioselectivity. Most recently, expand so α-hydroxy used: until point, all examples had concerned radicals. Again, HAT generate radicals, studies (Ermanis) provided insights.Since our original report, appeared exciting from groups applied or different precursors requisite radical. There which alternative photocatalyst systems reduce redox-active esters enantioselective protocol. While primarily Account, contributions will covered briefly for toward end article.

Language: Английский

Development of a Quinolinium/Cobaloxime Dual Photocatalytic System for Oxidative C–C Cross-Couplings via H2 Release DOI
Jianbin Li, Chia‐Yu Huang, Jing‐Tan Han

et al.

ACS Catalysis, Journal Year: 2021, Volume and Issue: 11(22), P. 14148 - 14158

Published: Nov. 8, 2021

Designing molecular photocatalysts for potent photochemical reactivities ranks among the most challenging but rewarding endeavors in synthetic photochemistry. Herein, we document a quinoline-based organophotoredox catalyst, 2,4-bis(4-methoxyphenyl)quinoline (DPQN2,4-di-OMe), that could be assembled via facile aldehyde–alkyne–amine (A3) couplings. Unlike reported photocatalysts, which impart their photoreactivities as covalently linked entities, our mechanistic studies suggested distinct proton activation mode of DPQN2,4-di-OMe. Simply upon protonation, DPQN2,4-di-OMe reach highly oxidizing excited state under visible-light irradiation (E*1/2 = +1.96 V vs standard calomel electrode, SCE). On this basis, synergistic merger and cobaloxime formulated an oxidative cross-coupling platform, enabling Minisci alkylation various C–C bond-forming reactions with diverse pool radical precursors absence chemical oxidants. The catalytic loading minimized to 0.025 mol % (TON 3360), polymer-supported photocatalyst, DPQN2,4-di-OR@PS, was prepared facilitate catalyst recycling (at 0.50 mmol up five times without significant loss photosynthetic efficiency).

Language: Английский

Citations

59
Enantioselective C2–H Alkylation of Pyridines with 1,3-Dienes via Ni–Al Bimetallic Catalysis DOI

Jiang‐Fei Li,

Deng Pan, Hao-Rui Wang

et al.

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(41), P. 18810 - 18816

Published: Oct. 7, 2022

A chiral phosphine oxide-ligated Ni–Al bimetallic catalyst was used to realize an enantioselective C2–H alkylation of pyridines without the need a C2-block. wide range pyridines, including unsubstituted pyridine, C3, C4, and C2-substituted even complex pyridine-containing bioactive molecules are well compatible with reaction, providing up 81% yield 97% ee.

Language: Английский

Citations

54
Enantioselective functionalization at the C4 position of pyridinium salts through NHC catalysis DOI Creative Commons
Hangyeol Choi, Gangadhar Rao Mathi, Seonghyeok Hong

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: April 1, 2022

Abstract A catalytic method for the enantioselective and C4-selective functionalization of pyridine derivatives is yet to be developed. Herein, we report an efficient asymmetric β-pyridylations enals that involve N-heterocyclic carbene (NHC) catalysis with excellent control over enantioselectivity pyridyl C4-selectivity. The key strategy precise stereocontrol involves enhancing interactions between chiral NHC-bound homoenolate pyridinium salt in presence hexafluorobenzene, which effectively differentiates two faces radical. Room temperature sufficient this transformation, reaction efficiency further accelerated by photo-mediation. This methodology exhibits broad functional group tolerance enables facile access a diverse range enantioenriched β-pyridyl carbonyl compounds under mild metal-free conditions.

Language: Английский

Citations

50
Hydrogen Atom Transfer Driven Enantioselective Minisci Reaction of Alcohols DOI
Avene C. Colgan, Rupert S. J. Proctor, David C. Gibson

et al.

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(25)

Published: April 14, 2022

Abstract Catalytic enantioselective Minisci reactions have recently been developed but all instances so far utilize α‐amino radical coupling partners. We report a substantial evolution of the reaction that enables α‐hydroxy radicals to be used, providing valuable enantioenriched secondary alcohol products. This is achieved through direct oxidative two C−H bonds on simple and pyridine partners hydrogen atom transfer (HAT)‐driven approach: challenging process achieve due numerous side can occur. Our approach highly regioselective as well enantioselective. Dicumyl peroxide, upon irradiation with 390 nm light, serves both HAT reagent oxidant whilst selectivity controlled by use chiral phosphoric acid catalyst. Computational experimental evidence provide mechanistic insight origin selectivity, revealing stereodetermining deprotonation step distinct from analogous amide‐containing substrates.

Language: Английский

Citations

45
A practical and sustainable two-component Minisci alkylation via photo-induced EDA-complex activation DOI Creative Commons
Mohammed Sharique, Jadab Majhi,

Roshan K. Dhungana

et al.

Chemical Science, Journal Year: 2022, Volume and Issue: 13(19), P. 5701 - 5706

Published: Jan. 1, 2022

An operationally simple, open-air, and efficient light-mediated Minisci C-H alkylation method is described, based on the formation of an electron donor-acceptor (EDA) complex between nitrogen-containing heterocycles redox-active esters. In contrast to previously reported protocols, this does not require a photocatalyst, external single transfer agent, or oxidant additive. Achieved under mildly acidic open-air conditions, reaction incorporates primary-, secondary-, tertiary radicals, including bicyclo[1.1.1]pentyl (BCP) along with various generate products in moderate good yields. Additionally, exploited stereo-enriched, hetereoaryl-substituted carbohydrate.

Language: Английский

Citations

41
Photochemical Organocatalytic Functionalization of Pyridines via Pyridinyl Radicals DOI Creative Commons
Emilien Le Saux,

Eleni Georgiou,

Igor A. Dmitriev

et al.

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 145(1), P. 47 - 52

Published: Dec. 27, 2022

We report a photochemical method for the functionalization of pyridines with radicals derived from allylic C–H bonds. Overall, two substrates undergo to form new C(sp2)–C(sp3) bond. The chemistry harnesses unique reactivity pyridinyl radicals, generated upon single-electron reduction pyridinium ions, which effective coupling radicals. This novel mechanism enables distinct positional selectivity pyridine that diverges classical Minisci chemistry. Crucial was identification dithiophosphoric acid masters three catalytic tasks, sequentially acting as Brønsted protonation, single electron transfer (SET) reductant ion reduction, and hydrogen atom abstractor activation C(sp3)–H resulting then couple high regioselectivity.

Language: Английский

Citations

41
Strategies That Utilize Ion Pairing Interactions to Exert Selectivity Control in the Functionalization of C–H Bonds DOI Creative Commons

James E. Gillespie,

Alexander Fanourakis,

Robert J. Phipps

et al.

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(40), P. 18195 - 18211

Published: Sept. 30, 2022

Electrostatic attraction between two groups of opposite charge, typically known as ion-pairing, offers unique opportunities for the design systems to enable selectivity control in chemical reactions. Catalysis using noncovalent interactions is an established and vibrant research area, but it noticeable that hydrogen bonding are still main interaction choice system design. Opposite charges experience powerful force Coulombic have ability exert fundamental influence on outcome reactions involve charged reagents, intermediates or catalysts. In this Perspective, we will examine how ion-pairing been used C-H bond functionalization processes. This broad class provides interesting thought-provoking lens through which application strategies because one encompasses great mechanistic diversity, poses significant challenges, perhaps most importantly immense interest synthetic chemists both industry academia. We survey proceed via radical ionic mechanisms alongside those transition metal catalysis deal with site-selectivity enantioselectivity. anticipate emerging area develops, become ever-more important strategy control.

Language: Английский

Citations

39
Asymmetric C3-Allylation of Pyridines DOI
Zhong Liu,

Zhu-Jun Shi,

Lu Liu

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: unknown

Published: May 17, 2023

Asymmetric intermolecular C–H functionalization of pyridines at C3 is unprecedented. Herein, we report the first examples such transformations: specifically, C3-allylation via tandem borane and iridium catalysis. First, borane-catalyzed pyridine hydroboration generates nucleophilic dihydropyridines; then, dihydropyridine undergoes enantioselective iridium-catalyzed allylation; finally, oxidative aromatization with air as oxidant gives C3-allylated pyridine. This protocol provides direct access to excellent enantioselectivity (up >99% ee) suitable for late-stage pyridine-containing drugs.

Language: Английский

Citations

39
The green chemistry paradigm in modern organic synthesis DOI
Sergei G. Zlotin, Ksenia S. Egorova, Valentine P. Ananikov

et al.

Russian Chemical Reviews, Journal Year: 2023, Volume and Issue: 92(12), P. RCR5104 - RCR5104

Published: Dec. 1, 2023

After the appearance of green chemistry concept, which was introduced in vocabulary early 1990s, its main statements have been continuously developed and modified. Currently, there are 10–12 cornerstones that should form basis for an ideal chemical process. This review analyzes accumulated experience achievements towards design products processes reduce or eliminate use generation hazardous substances. The presents views leading Russian scientists specializing various fields this subject, including homogeneous heterogeneous catalysis, fine basic organic synthesis, electrochemistry, polymer chemistry, based on bio-renewable feedstocks energetic compounds materials. A new approach to quantitative evaluation environmental friendliness by authors is described. <br> bibliography includes 1761.

Language: Английский

Citations

39
An update on chiral phosphoric acid organocatalyzed stereoselective reactions DOI
Eddy I. Jiménez

Organic & Biomolecular Chemistry, Journal Year: 2023, Volume and Issue: 21(17), P. 3477 - 3502

Published: Jan. 1, 2023

This review article presents an in-depth analysis of the strategies and methodologies for using chiral phosphoric acids as organocatalysts in asymmetric syntheses from recent literature.

Language: Английский

Citations

32