Halogen-bonding-promoted Photo-induced C–X Borylation of Aryl Halide using Phenol Derivatives

AbstractHydrofunctionalization, the direct addition of an X–H (e.g., X=O, N) bond across an alkene, is a desirable strategy to make heterocycles that are important structural components of naturally occurring molecules. Described here is the design and discovery of “donor–acceptor”-type platinum catalysts that are highly effective in both hydroalkoxylation and hydroamination of unactivated alkenes over a broad range of substrates under mild conditions. A number of alkene substitution patterns are accommodated, including tri-substituted, 1,1-disubstituted, (E)-disubstituted, (Z)-disubstituted and even mono-substituted double bonds. Detailed mechanistic investigations suggest a plausible pathway that includes an unexpected dissociation/re-association of the electron-deficient ligand to form an alkene-bound “donor–acceptor”-type intermediate. These mechanistic studies help understand the origins of the high reactivity exhibited by the catalytic system, and provide a foundation for the rational design of chiral catalysts towards asymmetric hydrofunctionalization reactions.

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Intermolecular Diastereoselective Annulation of Azaarenes into Fused N-heterocycles by Ru(II) Reductive Catalysis

10.21203/rs.3.rs-963422/v1 ◽

2021 ◽

Author(s):

He Zhao ◽

Yang Wu ◽

Chenggang Ci ◽

Zhenda Tan ◽

Jian Yang ◽

...

Keyword(s):

Building Block ◽

Transfer Rate ◽

Hydrogen Transfer ◽

Functional Group ◽

Critical Role ◽

Hydride Transfer ◽

Mechanistic Studies ◽

Mild Conditions ◽

Excellent Selectivity ◽

Coupling Sequence

Abstract Despite the important advances in azaaryl C−H activation/functionalization, reductive functionalization of ubiquitously distributed but weakly reactive azaarenes remains to date a challenge. Herein, by a strategy incorporating a tandem coupling sequence into the reduction of azaarenes, we present a dearomative annulation of azaarenes into promising fused syn-N-heterocycles by combination with a large variety of aniline derivatives and paraformaldehyde under ruthenium(II) reductive catalysis, proceeding with excellent selectivity, mild conditions, and broad substrate and functional group compatibility. Mechanistic studies reveal that the products are formed via hydride transfer-initiated β-aminomethylation and α-arylation of the pyridyl core in azaarenes, paraformaldehyde serves as both the C1-building block and reductant precursor, and the use of Mg(OMe)2 base plays a critical role in determining the reaction chemo-selectivity by lowering the hydrogen transfer rate. The present work opens a door to further develop valuable reductive functionalization of unsaturated systems by taking profit of formaldehyde-endowed two functions.

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Acetic Acid-Promoted Rhodium(III)-Catalyzed Hydroarylation of Terminal Alkynes

Synlett ◽

10.1055/s-0037-1611780 ◽

2019 ◽

Vol 30 (08) ◽

pp. 932-938 ◽

Cited By ~ 4

Author(s):

Chang-Lin Duan ◽

Xing-Yu Liu ◽

Yun-Xuan Tan ◽

Rui Ding ◽

Shiping Yang ◽

...

Keyword(s):

Acetic Acid ◽

Functional Group ◽

Bond Activation ◽

Side Reactions ◽

Terminal Alkynes ◽

Terminal Alkyne ◽

Mechanistic Studies ◽

Mild Conditions ◽

Reaction Proceeds

Rhodium(III)-catalyzed hydroarylation of terminal alkynes has not previously been achieved because of the inevitable oligomerization and other side reactions. Here, we report a novel Cp*Rh(III)-catalyzed hydroarylation of terminal alkynes in acetic acid as solvent to facilitate the C–H bond activation and subsequent transformations. This reaction proceeds under mild conditions, providing an effective approach to the synthesis of alkenylated heterocycles in high to excellent yields (31–99%) with a broad substrate scope (37 examples) and good functional-group compatibility. In this transformation, the loading of the alkyne can be reduced to 1.2 equivalents, which indicates the significant role of HOAc in lowering the reaction temperature and suppressing the oligomerization of the terminal alkyne. Preliminary mechanistic studies are also presented.

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(4+3)-Cycloaddition of Donor-Acceptor Cyclopropanes with Thiochalcones: A Diastereoselective Access to Tetrahydrothiepines

10.26434/chemrxiv.9955202.v1 ◽

2019 ◽

Author(s):

André U. Augustin ◽

J. Luca Merz ◽

Peter G. Jones ◽

Grzegorz Mloston ◽

Daniel Werz

Keyword(s):

Lewis Acid ◽

Functional Group ◽

Cycloaddition Reaction ◽

Building Blocks ◽

Mild Conditions ◽

Donor Acceptor ◽

Acid Catalyzed ◽

Sulfur Containing

A general approach is described for the formation of tetrahydrothiepines using donor-acceptor cyclopropanes. Thiochalcones, functioning as sulfur-containing four-atom building blocks, were reacted in a Lewis-acid-catalyzed formal (4+3)-cycloaddition reaction with donor-acceptor cyclopropanes as three-atom building blocks. Under mild conditions various tetrahydrothiepines were synthesized in good yields in a stereosepecific reaction with high functional group tolerance.

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Development of Highly Efficient Platinum Catalysts for Hydroalkoxylation and Hydroamination of Unactivated Alkene

10.21203/rs.3.rs-82534/v1 ◽

2020 ◽

Author(s):

Yali Zhou ◽

Xingjun Xu ◽

Hongwei Sun ◽

Guanyu Tao ◽

Xiaoyong Chang ◽

...

Keyword(s):

Catalytic System ◽

Rational Design ◽

Platinum Catalysts ◽

High Reactivity ◽

Structural Components ◽

Mechanistic Studies ◽

Mild Conditions ◽

Naturally Occurring ◽

Donor Acceptor ◽

Type Intermediate

Abstract Hydrofunctionalization, the direct additon of an X–H (e.g., X = O, N) bond across an alkene, is a desirable strategy to make heterocycles that are important structural components of naturally occurring molecules. Described here is the design and discovery of “donor–acceptor”-type platinum catalysts that are highly effective in both hydroalkoxylation and hydroamination of unactivated alkenes over a broad range of substrates under mild conditions. A number of alkene substitution patterns were accommodated, including tri-substituted, 1,1-disubstituted, (E)-disubstituted, (Z)-disubstituted and even mono-substituted double bonds. Detailed mechanistic investigations suggest a plausible pathway that includes an unexpected dissociation/re-association of the electron-deficient ligand to form an alkene-bound “donor–acceptor”-type intermediate. These mechanistic studies help understand the origins of the high reactivity exhibited by the catalytic system, and provide a foundation for the rational design of chiral catalysts towards asymmetric hydrofunctionalization reactions.

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Direct C–H Functionalization of Heteroarenes via Redox-Neutral Radical Process: A Facile Route to C–C Bonds Formation

Synthesis ◽

10.1055/s-0036-1588493 ◽

2017 ◽

Vol 49 (15) ◽

pp. 3407-3421 ◽

Cited By ~ 19

Author(s):

Pin Gao ◽

Yu-Rui Gu ◽

Xin-Hua Duan

Keyword(s):

Functional Group ◽

Radical Reactions ◽

Neutral Radical ◽

Alkyl Radicals ◽

Aryl Radicals ◽

Mild Conditions ◽

Wide Range ◽

Carbon Radicals ◽

Facile Route ◽

Radical Functionalization

Aromatic heterocycles are an important class of compounds found in a wide range of natural products, pharmaceutically active molecules and organic materials. Recently, the direct radical functionalization of heteroaromatic C–H bonds has become an efficient and attractive method to access substituted heteroarenes. Especially, redox-neutral radical reactions have attracted much attention of chemists due to their potential advantages such as mild conditions, free of external oxidants, and good functional group tolerance. So far, a series of redox-neutral radical reactions have been developed. In this review, we mainly focus on the recent advance in direct redox-neutral radical C–H functionalization of heteroarenes. Herein, the direct C–H arylation, C–H alkylation, and C–H fluoroalkylation of heteroarenes are represented respectively, providing practical routes to C–C bond formation.1 Introduction2 C–H Arylation of Heteroarenes with Aryl Radicals3 C–H Alkylation of Heteroarenes with Alkyl Radicals4 C–H Fluoroalkylation of Heteroarenes with Fluorine-Containing Carbon Radicals5 Concluding Remarks

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(4+3)-Cycloaddition of Donor-Acceptor Cyclopropanes with Thiochalcones: A Diastereoselective Access to Tetrahydrothiepines

10.26434/chemrxiv.9955202 ◽

2019 ◽

Cited By ~ 1

Author(s):

André U. Augustin ◽

J. Luca Merz ◽

Peter G. Jones ◽

Grzegorz Mloston ◽

Daniel Werz

Keyword(s):

Lewis Acid ◽

Functional Group ◽

Cycloaddition Reaction ◽

Building Blocks ◽

Mild Conditions ◽

Donor Acceptor ◽

Acid Catalyzed ◽

Sulfur Containing

A general approach is described for the formation of tetrahydrothiepines using donor-acceptor cyclopropanes. Thiochalcones, functioning as sulfur-containing four-atom building blocks, were reacted in a Lewis-acid-catalyzed formal (4+3)-cycloaddition reaction with donor-acceptor cyclopropanes as three-atom building blocks. Under mild conditions various tetrahydrothiepines were synthesized in good yields in a stereosepecific reaction with high functional group tolerance.

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Metal-Free Photoinduced Hydroalkylation Cascade Enabled by an Electron-Donor-Acceptor Complex

10.26434/chemrxiv.11912073 ◽

2020 ◽

Author(s):

José Tiago Menezes Correia ◽

Gustavo Piva da Silva ◽

Camila Menezes Kisukuri ◽

Elias André ◽

Bruno Pires ◽

...

Keyword(s):

Electron Donor ◽

Functional Group ◽

Photoexcited Electron ◽

One Pot ◽

Quaternary Centers ◽

Metal Free ◽

Acceptor Complex ◽

Catalyst Free ◽

Donor Acceptor ◽

Radical Cascade

A metal- and catalyst-free photoinduced radical cascade hydroalkylation of 1,7-enynes has been disclosed. The process is triggered by a SET event involving a photoexcited electron-donor-aceptor complex between NHPI ester and Hantzsch ester, which decomposes to afford a tertiary radical that is readily trapped by the enyne. <a>The method provides an operationally simple, robust and step-economical approach to the construction of diversely functionalized dihydroquinolinones bearing quaternary-centers. A sequential one-pot hydroalkylation-isomerization approach is also allowed giving access to a family of quinolinones. A wide substrate scope and high functional group tolerance was observed in both approaches</a>.

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Dual Nickel/Palladium-Catalyzed Reductive Cross-Coupling Reactions Between Two Phenol Derivatives

10.26434/chemrxiv.12448970.v1 ◽

2020 ◽

Author(s):

Baojian Xiong ◽

Yue Li ◽

Yin Wei ◽

Søren Kramer ◽

Zhong Lian

Keyword(s):

Functional Group ◽

Low Cost ◽

Cross Coupling ◽

Coupling Reactions ◽

Phenol Derivatives ◽

Cross Coupling Reactions ◽

Palladium Catalyzed ◽

One Step ◽

Aryl Tosylates ◽

Low Sensitivity

Cross-coupling between substrates that can be easily derived from phenols is highly attractive due to the abundance and low cost of phenols. Here, we report a dual nickel/palladium-catalyzed reductive cross-coupling between aryl tosylates and aryl triflates; both substrates can be accessed in just one step from readily available phenols. The reaction has a broad functional group tolerance and substrate scope (>60 examples). Furthermore, it displays low sensitivity to steric effects demonstrated by the synthesis of a 2,2’disubstituted biaryl and a fully substituted aryl product. The widespread presence of phenols in natural products and pharmaceuticals allow for straightforward late-stage functionalization, illustrated with examples such as Ezetimibe and tyrosine. NMR spectroscopy and DFT calculations indicate that the nickel catalyst is responsible for activating the aryl triflate, while the palladium catalyst preferentially reacts with the aryl tosylate.

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Iridium-Catalyzed Silylation of C-H bonds in Unactivated Arenes: A Sterically-Encumbered Phenanthroline Ligand Accelerates Catalysis Enabling New Reactivity

10.26434/chemrxiv.7744175 ◽

2019 ◽

Author(s):

Caleb Karmel ◽

Zhewei Chen ◽

John Hartwig

Keyword(s):

High Activity ◽

Functional Group ◽

Activity Analysis ◽

High Reactivity ◽

High Yield ◽

Phen Ligand ◽

Mechanistic Studies ◽

Phenanthroline Ligand ◽

First Time ◽

New System

We report a new system for the silylation of aryl C-H bonds. The combination of [Ir(cod)(OMe)]2 and 2,9-Me2-phenanthroline (2,9-Me2phen) catalyzes the silylation of arenes at lower temperatures and with faster rates than those reported previously, when the hydrogen byproduct is removed, and with high functional group tolerance and regioselectivity. Inhibition of reactions by the H2 byproduct is shown to limit the silylation of aryl C-H bonds in the presence of the most active catalysts, thereby masking their high activity. Analysis of initial rates uncovered the high reactivity of the catalyst containing the sterically hindered 2,9-Me2phen ligand but accompanying rapid inhibition by hydrogen. With this catalyst, under a flow of nitrogen to remove hydrogen, electron-rich arenes, including those containing sensitive functional groups, undergo silylation in high yield for the first time, and arenes that underwent silylation with prior catalysts react over much shorter times with lower catalyst loadings. The synthetic value of this methodology is demonstrated by the preparation of key intermediates in the synthesis of medicinally important compounds in concise sequences comprising silylation and functionalization. Mechanistic studies demonstrate that the cleavage of the aryl C-H bond is reversible and that the higher rates observed with the 2,9-Me2phen ligand is due to a more thermodynamically favorable oxidative addition of aryl C-H bonds.

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