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

Photons or Electrons? A Critical Comparison of Electrochemistry and Photoredox Catalysis for Organic Synthesis DOI
Nicholas E. S. Tay, Dan Lehnherr, Tomislav Rovis

et al.

Chemical Reviews, Journal Year: 2021, Volume and Issue: 122(2), P. 2487 - 2649

Published: Nov. 9, 2021

Redox processes are at the heart of synthetic methods that rely on either electrochemistry or photoredox catalysis, but how do and catalysis compare? Both approaches provide access to high energy intermediates (e.g., radicals) enable bond formations not constrained by rules ionic 2 electron (e) mechanisms. Instead, they 1e mechanisms capable bypassing electronic steric limitations protecting group requirements, thus enabling chemists disconnect molecules in new different ways. However, while providing similar intermediates, differ several physical chemistry principles. Understanding those differences can be key designing transformations forging disconnections. This review aims highlight these similarities between comparing their underlying principles describing impact electrochemical photochemical methods.

Language: Английский

Citations

357
Photoelectrochemical asymmetric catalysis enables site- and enantioselective cyanation of benzylic C–H bonds DOI

Chen-Yan Cai,

Xiao‐Li Lai, Yu Wang

et al.

Nature Catalysis, Journal Year: 2022, Volume and Issue: 5(10), P. 943 - 951

Published: Oct. 10, 2022

Language: Английский

Citations

157
Late-Stage C–H Functionalization of Azines DOI

Celena M. Josephitis,

Hillary M. H. Nguyen, Andrew McNally

et al.

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(12), P. 7655 - 7691

Published: May 3, 2023

Azines, such as pyridines, quinolines, pyrimidines, and pyridazines, are widespread components of pharmaceuticals. Their occurrence derives from a suite physiochemical properties that match key criteria in drug design is tunable by varying their substituents. Developments synthetic chemistry, therefore, directly impact these efforts, methods can install various groups azine C–H bonds particularly valuable. Furthermore, there growing interest late-stage functionalization (LSF) reactions focus on advanced candidate compounds often complex structures with multiple heterocycles, functional groups, reactive sites. Because factors electron-deficient nature the effects Lewis basic N atom, distinct arene counterparts, application LSF contexts difficult. However, have been many significant advances reactions, this review will describe progress, much which has occurred over past decade. It possible to categorize radical addition processes, metal-catalyzed activation transformations occurring via dearomatized intermediates. Substantial variation reaction within each category indicates both rich reactivity heterocycles creativity approaches involved.

Language: Английский

Citations

108
The interplay of polar effects in controlling the selectivity of radical reactions DOI
Alessandro Ruffoni, Rory C. Mykura, Massimo Bietti

et al.

Nature Synthesis, Journal Year: 2022, Volume and Issue: 1(9), P. 682 - 695

Published: Aug. 1, 2022

Language: Английский

Citations

97
Catalytic Asymmetric Construction of Axially and Centrally Chiral Heterobiaryls by Minisci Reaction DOI
Dong Liang, Jia‐Rong Chen, Liping Tan

et al.

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(13), P. 6040 - 6049

Published: March 24, 2022

Axially chiral biaryls and heterobiaryls constitute the most represented subclass of atropisomers with prevalence in natural products, bioactive compounds, privileged ligand/catalysts, optically pure materials. Despite many ionic protocols for their construction, radical-based variants represent another highly desirable intriguing strategy but are far less developed. Moreover, efficient synthesis axially heterobiaryl molecules, especially ones having multiple heteroatoms other types elements, through radical routes remains extremely limited. We herein disclose first catalytic asymmetric, metal-free construction centrally by Minisci reaction 5-arylpyrimidines α-amino acid-derived redox-active esters. This is enabled use 4CzIPN as an organic photoredox catalyst conjunction a phosphoric acid catalyst. The achieved variety interesting featuring union α-branched amine generally excellent regio-, diastereo-, enantioselectivity (up to 82% yield; >19:1 dr; >99% ee). finding also builds up new platform development desymmetrization methods via radical-involved atroposelective functionalization at heteroarene prochiral heterobiaryls.

Language: Английский

Citations

78
Site- and enantioselective cross-coupling of saturated N-heterocycles with carboxylic acids by cooperative Ni/photoredox catalysis DOI Creative Commons
Xiaomin Shu,

De Zhong,

Qian Huang

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Jan. 9, 2023

Abstract Site- and enantioselective cross-coupling of saturated N -heterocycles carboxylic acids—two the most abundant versatile functionalities—to form pharmaceutically relevant α-acylated amine derivatives remains a major challenge in organic synthesis. Here, we report general strategy for highly site- α-acylation with situ-activated acids. This modular approach exploits hydrogen-atom-transfer reactivity photocatalytically generated chlorine radicals combination asymmetric nickel catalysis to selectively functionalize cyclic α-amino C−H bonds presence benzylic, allylic, acyclic α-amino, α-oxy methylene groups. The mild scalable protocol requires no organometallic reagents, displays excellent chemo-, enantioselectivity, is amenable late-stage diversification, including synthesis previously inaccessible Taxol derivatives. Mechanistic studies highlight exceptional versatility chiral catalyst orchestrating (i) catalytic elimination, (ii) alkyl radical capture, (iii) cross-coupling, (iv) induction.

Language: Английский

Citations

57
Photocatalyzed Enantioselective Functionalization of C(sp3)–H Bonds DOI
Guo‐Qiang Xu, Wei David Wang, Peng‐Fei Xu

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(2), P. 1209 - 1223

Published: Jan. 3, 2024

Owing to its diverse activation processes including single-electron transfer (SET) and hydrogen-atom (HAT), visible-light photocatalysis has emerged as a sustainable efficient platform for organic synthesis. These provide powerful avenue the direct functionalization of C(sp3)–H bonds under mild conditions. Over past decade, there have been remarkable advances in enantioselective bond via combined with conventional asymmetric catalysis. Herein, we summarize involving discuss two main pathways this emerging field: (a) SET-driven carbocation intermediates are followed by stereospecific nucleophile attacks; (b) photodriven alkyl radical further enantioselectively captured (i) chiral π-SOMOphile reagents, (ii) stereoselective transition-metal complexes, (iii) another distinct stereoscopic species. We aim key reaction design, catalyst development, mechanistic understanding, new insights into rapidly evolving area research.

Language: Английский

Citations

36
Asymmetric Photocatalysis Enabled by Chiral Organocatalysts DOI
Wang Yao,

Emmanuel A. Bazan‐Bergamino,

Ming‐Yu Ngai

et al.

ChemCatChem, Journal Year: 2021, Volume and Issue: 14(1)

Published: Oct. 21, 2021

Abstract Visible‐light photocatalysis has advanced as a versatile tool in organic synthesis. However, attaining precise stereocontrol photocatalytic reactions been longstanding challenge due to undesired photochemical background and the involvement of highly reactive radicals or radical ion intermediates generated under conditions. To address this problem expand synthetic utility reactions, number innovative strategies, including mono‐ dual‐catalytic approaches, have recently emerged. Of these, exploiting chiral organocatalysis, such enamine catalysis, iminium‐ion Brønsted acid/base N ‐heterocyclic carbene induce chirality transfer widely explored. This Review aims provide current, comprehensive overview asymmetric enabled by organocatalysts published through June 2021. The substrate scope, advantages, limitations, proposed reaction mechanisms each are discussed. review should serve reference for development visible‐light‐induced promote improvement chemical reactivity stereoselectivity these reactions.

Language: Английский

Citations

76
Catalytic Asymmetric Reductive Azaarylation of Olefins via Enantioselective Radical Coupling DOI
Yajuan Li, Cuijie Han, Yanyan Wang

et al.

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(17), P. 7805 - 7814

Published: April 26, 2022

Visible-light-driven photocatalytic reductive azaarylation has been widely used to construct the important imine-containing azaarene derivatives. In addition direct use of various commercially available cyanoazaarenes as feedstocks, synthetic advantages include precise regioselectivity, high efficiency, mild reaction conditions, and good functional group tolerance. However, although many efficient methods have established, example an enantioselective manner is still unmet, which most likely can be ascribed highly reactive radical coupling key step forming stereocenters. Exploring feasibility enantiocontrol thus constitutes attractive but challenging task. Here, we demonstrate that chiral hydrogen-bonding/photosensitizer catalysis a viable platform it enables realization first manifold. A variety acyclic cyclic enones partners are compatible with dual catalyst system, leading wide array valuable enantioenriched variants yields ees. Regulating types catalysts represents one manners success, in several readily accessible Cinchona alkaloid-derived bifunctional introduced asymmetric photochemical reactions.

Language: Английский

Citations

69
Copper‐Catalyzed Intermolecular Enantioselective Radical Oxidative C(sp3)−H/C(sp)−H Cross‐Coupling with Rationally Designed Oxazoline‐Derived N,N,P(O)‐Ligands DOI
Lin Liu,

Kaixin Guo,

Yu Tian

et al.

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(51), P. 26710 - 26717

Published: Oct. 5, 2021

The intermolecular asymmetric radical oxidative C(sp3 )-C(sp) cross-coupling of )-H bonds with readily available terminal alkynes is a promising method to forge chiral because the high atom and step economy, but remains underexplored. Here, we report copper-catalyzed (hetero)benzylic (cyclic)allylic C-H that occurs excellent enantioselectivity. Critical success rational design oxazoline-derived N,N,P(O)-ligands not only tolerate strong conditions which are requisite for hydrogen abstraction (HAA) processes also induce challenging enantiocontrol. Direct access range synthetically useful benzylic 1,4-enynes, site-selectivity among similar bonds, facile synthesis enantioenriched medicinally relevant compounds make this approach very attractive.

Language: Английский

Citations

61