Photocatalytic Late-Stage C–H Functionalization

Chemical Reviews, Год журнала: 2023, Номер 123(8), С. 4237 - 4352

Опубликована: Янв. 24, 2023

The emergence of modern photocatalysis, characterized by mildness and selectivity, has significantly spurred innovative late-stage C–H functionalization approaches that make use low energy photons as a controllable source. Compared to traditional strategies, photocatalysis paves the way toward complementary and/or previously unattainable regio- chemoselectivities. Merging compelling benefits with workflow offers potentially unmatched arsenal tackle drug development campaigns beyond. This Review highlights photocatalytic strategies small-molecule drugs, agrochemicals, natural products, classified according targeted bond newly formed one. Emphasis is devoted identifying, describing, comparing main mechanistic scenarios. draws critical comparison between established ionic chemistry photocatalyzed radical-based manifolds. aims establish current state-of-the-art illustrate key unsolved challenges be addressed in future. authors aim introduce general readership functionalization, specialist practitioners evaluation methodologies, potential for improvement, future uncharted directions.

Язык: Английский

---

Streamlined Alkylation via Nickel-Hydride-Catalyzed Hydrocarbonation of Alkenes

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(16), С. 7015 - 7029

Опубликована: Апрель 12, 2022

Compounds rich in sp3-hybridized carbons are desirable drug discovery. Nickel-catalyzed hydrocarbonation of alkenes is a potentially efficient method to synthesize these compounds. By using abundant, readily available, and stable as pro-nucleophiles, reactions can have broad scope high functional group tolerance. However, this methodology still an early stage development, the first examples were reported only 2016. Herein, we summarize progress emerging field, with emphasis on enantioselective reactions. We highlight major developments, critically discuss wide range possible mechanisms, offer our perspective state challenges field. hope Perspective will stimulate future works area, making widely applicable organic synthesis.

Язык: Английский

---

Radical Carbonyl Umpolung Arylation via Dual Nickel Catalysis

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(4), С. 1899 - 1909

Опубликована: Янв. 18, 2022

The formation of carbon-carbon bonds lies at the heart synthetic organic chemistry and is widely applied to construct complex drugs, polymers, materials. Despite its importance, catalytic carbonyl arylation remains comparatively underdeveloped, due limited scope functional group tolerance. Herein we disclose an umpolung strategy achieve radical via dual catalysis. This redox-neutral approach provides a complementary method Grignard-type products from (hetero)aryl bromides aliphatic aldehydes, without need for pre-functionalization. A sequential activation, hydrogen-atom transfer, halogen atom transfer process could directly convert aldehydes corresponding ketyl-type radicals, which further react with aryl-nickel intermediates in overall polarity-reversal process. tolerates─among others─acidic groups, heteroaryl motifs, sterically hindered substrates has been late-stage modification drugs natural products.

Язык: Английский

---

Direct synthesis of unprotected aryl C-glycosides by photoredox Ni-catalysed cross-coupling

Nature Synthesis, Год журнала: 2023, Номер 2(3), С. 251 - 260

Опубликована: Янв. 16, 2023

Язык: Английский

---

Carbon-centered radical capture at nickel(II) complexes: Spectroscopic evidence, rates, and selectivity

Chem, Год журнала: 2023, Номер 9(5), С. 1295 - 1308

Опубликована: Март 13, 2023

Язык: Английский

---

Dual Nickel/Photoredox-Catalyzed Asymmetric Carbosulfonylation of Alkenes

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(23), С. 12532 - 12540

Опубликована: Май 30, 2023

An asymmetric three-component carbosulfonylation of alkenes is presented here. The reaction, involving the simultaneous formation a C-C and C-S bond across π-system, uses dual nickel/photoredox catalytic system to produce both β-aryl β-alkenyl sulfones in high yields with excellent levels stereocontrol (up 99:1 er). This protocol exhibits broad substrate scope functional group tolerance its synthetic potential has been demonstrated by successful applications toward pharmacologically relevant molecules. A array control experiments supports involvement secondary alkyl radical intermediate generated through addition sulfonyl double bond. Moreover, stoichiometric cross-over further suggest an underlying Ni(0)/Ni(I)/Ni(III) pathway operative these transformations.

Язык: Английский

---

Ligand-controlled stereodivergent alkenylation of alkynes to access functionalized trans- and cis-1,3-dienes

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Янв. 4, 2023

Precise stereocontrol of functionalized alkenes represents a long-standing research topic in organic synthesis. Nevertheless, the development catalytic, easily tunable synthetic approach for stereodivergent synthesis both E-selective and even more challenging Z-selective highly substituted 1,3-dienes from common substrates remains underexploited. Here, we report photoredox nickel dual catalytic strategy sulfonylalkenylation terminal alkynes with vinyl triflates sodium sulfinates under mild conditions. With judicious choice simple catalyst ligand, this method enables efficient divergent access to Z- E-sulfonyl-1,3-dienes same set starting materials. This features broad substrate scope, good functional compatibility, excellent chemo-, regio-, stereoselectivity. Experimental DFT mechanistic studies offer insights into observed stereoselectivity controlled by ligands.

Язык: Английский

---

Nickel-catalysed enantioselective alkene dicarbofunctionalization enabled by photochemical aliphatic C–H bond activation

Nature Catalysis, Год журнала: 2024, Номер 7(6), С. 655 - 665

Опубликована: Апрель 29, 2024

Abstract The development of novel strategies to rapidly construct complex chiral molecules from readily available feedstocks is a long-term pursuit in the chemistry community. Radical-mediated alkene difunctionalizations represent an excellent platform towards this goal. However, asymmetric versions remain highly challenging, and more importantly, examples featuring simple hydrocarbons as reaction partners are elusive. Here we report three-component dicarbofunctionalization capitalizing on direct activation C( sp 3 )–H bonds through combination photocatalysed hydrogen atom transfer nickel catalysis. This protocol provides efficient for installing two vicinal carbon–carbon across alkenes atom-economic fashion, providing wide array high-value α-aryl/alkenyl carbonyls phosphonates, well 1,1-diarylalkanes ubiquitous alkane, ether alcohol feedstocks. method exhibits operational simplicity, broad substrate scope regioselectivity, chemoselectivity enantioselectivity. compatibility with bioactive motifs expedient synthesis pharmaceutically relevant highlight synthetic potential protocol.

Язык: Английский

---

Iron-catalyzed fluoroalkylative alkylsulfonylation of alkenes via radical-anion relay

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Фев. 17, 2024

Abstract Transition metal-catalyzed reductive difunctionalization of alkenes with alkyl halides is a powerful method for upgrading commodity chemicals into densely functionalized molecules. However, super stoichiometric amounts metal reductant and the requirement installing directing group to suppress inherent β-H elimination bring great limitations this type reaction. We demonstrate herein that two different accessible via radical-anion relay Na 2 S O 4 as both sulfone-source. The together electron-shuttle catalyst crucial divert mechanistic pathway toward formation sulfone anion instead previously reported alkylmetal intermediates. Mechanistic studies allow identification carbon-centered radical sulfur-centered radical, which are in equilibrium capture or extrusion SO could be converted accelerated by iron catalysis, leading observed high chemoselectivity.

Язык: Английский

---

Three-component 1,2-dicarbofunctionalization of alkenes involving alkyl radicals

Chemical Communications, Год журнала: 2021, Номер 58(6), С. 730 - 746

Опубликована: Дек. 8, 2021

This article provides a comprehensive perspective on three-component 1,2-dicarbofunctionalization of alkenes involving alkyl radicals, which generated from structurally diverse electrophilic and nucleophilic precursors under mild conditions.

Язык: Английский

---