Transition-Metal-Catalyzed C–H Bond Activation for the Formation of C–C Bonds in Complex Molecules

Chemical Reviews, Год журнала: 2023, Номер 123(12), С. 7692 - 7760

Опубликована: Май 10, 2023

Site-predictable and chemoselective C–H bond functionalization reactions offer synthetically powerful strategies for the step-economic diversification of both feedstock fine chemicals. Many transition-metal-catalyzed methods have emerged selective activation bonds. However, challenges regio- chemoselectivity with application to highly complex molecules bearing significant functional group density diversity. As molecular complexity increases within structures risks catalyst intolerance limited applicability grow number groups potentially Lewis basic heteroatoms. Given abundance bonds already diversified such as pharmaceuticals, natural products, materials, design selection reaction conditions tolerant catalysts has proved critical successful direct functionalization. such, innovations formation carbon–carbon been discovered developed overcome these limitations. This review highlights progress made metal-catalyzed C–C forming including alkylation, methylation, arylation, olefination targets.

Язык: Английский

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From C4 to C7: Innovative Strategies for Site-Selective Functionalization of Indole C–H Bonds

Accounts of Chemical Research, Год журнала: 2021, Номер 54(7), С. 1723 - 1736

Опубликована: Март 12, 2021

The widespread presence of hydrocarbons makes C-H functionalization an attractive alternative to traditional cross-coupling methods. As indole is important heteroarene in a plethora natural products and pharmaceuticals, moieties has emerged as one the most topics this field. Due multiple bonds indoles, site selectivity long-standing challenge. Much effort been devoted indoles at C3 or C2 position, while accessing benzene core (from C4 C7) considerably more challenging.This Account summarizes our recent efforts toward site-selective based on innovative strategies. A common method solve issue involves development directing groups (DGs). Our early studies establish that installation N-P(O)tBu2 group N position can produce C7 C6 arylation using palladium copper catalysts, respectively. developed system also be extended direct C5 positions by installing pivaloyl position. Further investigation bearing N-PtBu2 shows diverse reactivity for functionalizations including arylation, olefination, acylation, alkylation, silylation, carbonylation with different coupling partners. Compared P(V) DG, P(III) easily attached substrates detached from products. However, these reactions rely mostly precious metal catalysts ligands; requirement significant limitation, particularly large-scale syntheses necessity removal toxic trace metals pharmaceutical We have uncovered general strategy chelation-assisted aromatic borylation just simple BBr3 under mild conditions, which N1 selectively deliver boron species unfavorable allow subsequent without any metal. This transition-metal-free synthesize hydroxylated boron-mediated directed hydroxylation reaction conditions broad functional compatibility.In Account, we describe contributions topic since 2015. These provide efficient methods divergent synthesis valuable substituted insights into exploration new strategies directives other heteroarenes.

Язык: Английский

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Transition metal-catalyzed alkene isomerization as an enabling technology in tandem, sequential and domino processes

Chemical Society Reviews, Год журнала: 2020, Номер 50(2), С. 1391 - 1406

Опубликована: Дек. 10, 2020

One-pot reactions based on catalytic isomerization of alkenes not only offer the inherent advantages atom-, step- and redox-economy but also enable preparation value-added products that would be difficult to access by conventional methods.

Язык: Английский

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Site-selective C–H functionalization to access the arene backbone of indoles and quinolines

Chemical Society Reviews, Год журнала: 2021, Номер 50(20), С. 11249 - 11269

Опубликована: Янв. 1, 2021

The site-selective C-H bond functionalization of heteroarenes can eventually provide chemists with great techniques for editing and building complex molecular scaffolds. During the past decade, benzo-fused N-heterocycles such as indoles quinolines have been among most widely investigated organic templates. Early developments led to on pyrrole pyridine cores quinolines; however, benzenoid ring has remained a challenge in catalysis. In this review, we elaborate recent highly challenging bonds less-reactive core quinolines. These findings are mainly described selective directing group assisted strategies, remote their reaction mechanisms. underlying principle each strategy is elucidated, which aims facilitate design more advanced structure heterocycles based bioactive molecules, synthetic drugs, material aspects. Moreover, challenges perspectives catalytic access arene backbone also proposed conclusion section.

Язык: Английский

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P^III‐Chelation‐Assisted Indole C7‐Arylation, Olefination, Methylation, and Acylation with Carboxylic Acids/Anhydrides by Rhodium Catalysis

Angewandte Chemie International Edition, Год журнала: 2018, Номер 58(5), С. 1504 - 1508

Опубликована: Дек. 6, 2018

Rhodium-catalyzed C7-selective decarbonylative arylation, olefination, and methylation of indoles with carboxylic acids or anhydrides by C-H C-C bond activation have been developed. Furthermore, C7-acylation products can also be generated selectively at a lower reaction temperature in the developed system. The key to high reactivity regioselectivity this transformation is appropriate choice an indole N-PtBu2 chelation-assisted group. This method has many advantages, including easy access removal directing group, use cheap widely available coupling agents, no requirement external ligand oxidant, broad substrate scope, efficiency, formation sole regioisomer.

Язык: Английский

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Transition-metal-catalyzed site-selective C7-functionalization of indoles: advancement and future prospects

Chemical Communications, Год журнала: 2018, Номер 55(5), С. 572 - 587

Опубликована: Дек. 5, 2018

C7-Decorated indoles are important structural motifs present in a plethora of bioactive and pharmaceutical compounds. Early stage developments for C7 modifications were realized through directed metallation (DOM) subsequent quenching with suitable electrophiles or by halogenation Cu(ii) halides. Direct C-7 functionalization is comparatively difficult compared to at C-2 C-3 positions owing the inherent reactivity pyrrole-type ring. However, recently transition-metal-catalyzed auxiliary assisted site-selective has emerged as an elegant synthetic tool carbon-carbon carbon-heteroatom bond formation diversify indoles. This article covers advancement, application mechanistic underpinnings evolved transformations otherwise inert C7-H up October 2018.

Язык: Английский

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Beyond Friedel and Crafts: Directed Alkylation of C−H Bonds in Arenes

Angewandte Chemie International Edition, Год журнала: 2018, Номер 58(22), С. 7202 - 7236

Опубликована: Авг. 14, 2018

Abstract Alkylation of arenes is one the most fundamental transformations in chemical synthesis and leads to privileged scaffolds many areas science. Classical methods for introduction alkyl groups are mostly based on Friedel–Crafts reaction, radical additions, metalation, or prefunctionalization arene: these methods, however, suffer from limitations scope, efficiency, selectivity. Moreover, they innate reactivity starting arene, favoring alkylation at a certain position rendering chains other positions much more challenging. This can be addressed by use directing group that facilitates, presence metal catalyst, regioselective C−H bond. These directed alkylations bonds will comprehensively summarized this Review.

Язык: Английский

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Nickel‐Catalyzed Regioselective Hydroalkylation and Hydroarylation of Alkenyl Boronic Esters

Angewandte Chemie International Edition, Год журнала: 2019, Номер 58(39), С. 13854 - 13859

Опубликована: Июль 8, 2019

Abstract Metal hydride catalyzed hydrocarbonation reactions of alkenes are an efficient approach to construct new carbon–carbon bonds from readily available alkenes. However, the regioselectivity remains challenging be controlled. In nickel (NiH) hydrocarbonation, linear selectivity is most often obtained because relative stability Ni–alkyl intermediate over its branched counterpart. Herein, we show that boronic pinacol ester (Bpin) group directs a Ni‐catalyzed occur at adjacent carbon center, resulting in formal branch selectivity. Both alkyl and aryl halides can used as electrophiles this providing access wide range secondary Bpin derivatives, which valuable building blocks synthetic chemistry. The utility method demonstrated by late‐stage functionalization natural products drug molecules, synthesis anticancer agent, iterative syntheses.

Язык: Английский

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Ligand‐Controlled Regiodivergent Hydroalkylation of Pyrrolines

Angewandte Chemie International Edition, Год журнала: 2019, Номер 58(51), С. 18519 - 18523

Опубликована: Окт. 23, 2019

Abstract Nickel hydride (NiH) catalyzed hydrocarbonation has emerged as an efficient approach to construct new C−C bonds containing at least one C(sp 3 ) center. However, the regioselectivity of this reaction is by far dictated substrates. Described here a strategy achieve two different regioselectivites hydroalkylation same substrates using ligand control. This enables first regiodivergent 3‐pyrrolines, yielding both 2‐ and 3‐alkylated pyrrolidines, valuable synthetic intermediates common motifs in many bioactive molecules. method demonstrates broad scope high functional‐group tolerance, can be applied late‐stage functionalizations.

Язык: Английский

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Ni-catalyzed migratory fluoro-alkenylation of unactivated alkyl bromides with gem-difluoroalkenes

Chemical Science, Год журнала: 2018, Номер 10(4), С. 1144 - 1149

Опубликована: Ноя. 9, 2018

A migratory fluoro-alkenylation of unactivated alkyl bromides is reported; the reaction enabled by fluorine effects and involves an nickel chain-walking mechanism.

Язык: Английский

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