Transition-Metal (Cu, Pd, Ni)-Catalyzed Difluoroalkylation via Cross-Coupling with Difluoroalkyl Halides

Accounts of Chemical Research, Journal Year: 2018, Volume and Issue: 51(9), P. 2264 - 2278

Published: Aug. 22, 2018

Difluoroalkylated compounds play a remarkably important role in life and materials sciences because of the unique characteristics difluoromethylene (CF2) group. In particular, precise introduction CF2 group at benzylic position can dramatically improve biological properties corresponding molecules. As consequence, difluoroalkylation aromatic has become powerful strategy modulating bioactivities organic However, efficient strategies to selectively synthesize difluoroalkylated arenes had been very limited before 2012. Traditional synthetic methods this regard suffer from either harsh reaction conditions or narrow substrate scope, significantly restricting their widespread applications, particularly for late-stage bioactive To overcome these limitations, straightforward route access valuable skeletons is direct (CF2R) onto rings through transition-metal-catalyzed cross-coupling. instability some metal species, which are prone protonation, dimerization, and/or generation other unknown byproducts, it difficult control catalytic cycle suppress side reactions. context, we proposed use low-cost widely available difluoroalkyl halides as fluoroalkyl sources reactions via Account, summarize our major efforts on copper-, palladium-, nickel-catalyzed difluoroalkylations aromatics with sources. Four modes reactions, including nucleophilic difluoroalkylation, electrophilic radical metal-difluorocarbene coupling (MeDiC), have demonstrated careful modulation systems. Among MeDiC represents new mode fluoroalkylation. These processes enable variety aryl arylboron reagents under mild conditions. A wide range halides, activated (Cl/BrCF2R, R = π system), unactivated (BrCF2R, alkyl, H), especially inert inexpensive industrial chemical chlorodifluoromethane (ClCF2H), applicable providing facile routes diverse (hetero)arenes. halide-based also be applied prepare alkenes, alkynes, alkanes feature impressive advantages over conventional synthesis terms efficiency, functional tolerance, structural diversity. molecules offers good opportunities development medicinal agents without need multistep de novo syntheses.

Language: Английский

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Recent Progress toward the Introduction of Functionalized Difluoromethylated Building Blocks onto C(sp²) and C(sp) Centers

Chemistry - A European Journal, Journal Year: 2015, Volume and Issue: 21(37), P. 12836 - 12865

Published: July 14, 2015

Fluorine chemistry is a field undergoing tremendous expansion. Although much attention has been paid to the introduction of fluorine atom and CF3 group, less interest devoted functionalized fluorinated building blocks, in sharp contrast with high versatility products. In this Minireview, most relevant methods for difluoromethylated blocks are summarized. Access arenes, alkenes, alkynes highlighted special explanation reaction mechanism.

Language: Английский

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Visible Light‐Induced Room‐Temperature Heck Reaction of Functionalized Alkyl Halides with Vinyl Arenes/Heteroarenes

Angewandte Chemie International Edition, Journal Year: 2017, Volume and Issue: 56(45), P. 14212 - 14216

Published: Sept. 22, 2017

The first visible light-induced Pd-catalyzed Heck reaction of α-heteroatom substituted alkyl iodides and -bromides with vinyl arenes/heteroarenes has been developed. This transformation efficiently proceeds at room temperature enables synthesis valuable functionalized allylic systems, such as silanes, boronates, germanes, stannanes, pivalates, phosphonates, phthalimides, tosylates from the corresponding α-substituted methyl iodides. Notably, latter substrates failed under existing thermally induced conditions, which highlights importance light for this transformation.

Language: Английский

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Pd-Catalyzed Stereoselective Carboperfluoroalkylation of Alkynes

Journal of the American Chemical Society, Journal Year: 2015, Volume and Issue: 137(36), P. 11610 - 11613

Published: Aug. 26, 2015

A Pd-catalyzed three component reaction involving terminal alkynes, boronic acids, and perfluoroalkyl iodides is presented here. Trisubstituted perfluoroalkenes can be obtained in a highly regio- stereocontrolled manner by the simultaneous addition of both aryl CnFm groups across triple bond radical-mediated process. The operationally simple offering broad scope functional group tolerance.

Language: Английский

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Recent Advances on Palladium Radical Involved Reactions

ACS Catalysis, Journal Year: 2015, Volume and Issue: 5(10), P. 6111 - 6137

Published: Sept. 8, 2015

Transformations involving Pd(I) and Pd(III) have received growing attention over the past few years, providing various methodologies for construction of numerous carbocyclic heterocyclic ring systems. Compared with Pd(0)/(II)/(IV) chemistry, Pd(I)/(III)-mediated reactions are generally conducted through a single electron transfer process, leading to so-called palladium radical involved reactions. This review gives an up-to-date overview catalytic intermediates, which sorted into two categories: (i) (ii) For most these transformations, plausible mechanisms demonstrated in detail. Clarification issues is key point understanding developing new high-performance methodologies.

Language: Английский

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Practical Photocatalytic Trifluoromethylation and Hydrotrifluoromethylation of Styrenes in Batch and Flow

Angewandte Chemie International Edition, Journal Year: 2016, Volume and Issue: 55(50), P. 15549 - 15553

Published: Nov. 15, 2016

Styrenes represent a challenging class of substrates for current radical trifluoromethylation and hydrotrifluoromethylation methods due to myriad potential side reactions. Herein, we describe the development mild, selective broadly applicable photocatalytic protocols these substrates. The use fac-Ir(ppy)3 , visible light inexpensive CF3 I can be applied diverse set vinylarene continuous-flow photochemical reaction conditions allowed reduce time increase selectivity.

Language: Английский

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Radical‐Mediated 1,2‐Formyl/Carbonyl Functionalization of Alkenes and Application to the Construction of Medium‐Sized Rings

Angewandte Chemie International Edition, Journal Year: 2016, Volume and Issue: 55(48), P. 15100 - 15104

Published: Oct. 28, 2016

Abstract A novel radical 1,2‐formylfunctionalization of alkenes involving 1,2(4,5)‐formyl migration triggered by addition various carbon‐ and heteroatom‐centered radicals to has been developed for the first time, thus providing straightforward access diverse β‐functionalized aldehydes with good efficiency, remarkable selectivity, excellent functional group tolerance. Analogous transformations mediated a keto‐carbonyl have also effected under similar conditions. This method was used ring systems including benzannulated nine‐, ten‐, eleven‐membered rings, complex 6‐5(6,7)‐6(5) fused bridged rings functionalities.

Language: Английский

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Recent Advances in Alkenyl sp² C–H and C–F Bond Functionalizations: Scope, Mechanism, and Applications

Chemical Reviews, Journal Year: 2022, Volume and Issue: 122(24), P. 17479 - 17646

Published: Oct. 14, 2022

Alkenes and their derivatives are featured widely in a variety of natural products, pharmaceuticals, advanced materials. Significant efforts have been made toward the development new practical methods to access this important class compounds by selectively activating alkenyl C(sp2)–H bonds recent years. In comprehensive review, we describe state-of-the-art strategies for direct functionalization sp2 C–H C–F until June 2022. Moreover, metal-free, photoredox, electrochemical also covered. For clarity, review has divided into two parts; first part focuses on currently available using different alkene as starting materials, second describes bond easily accessible gem-difluoroalkenes material. This includes scope, limitations, mechanistic studies, stereoselective control (using directing groups well metal-migration strategies), applications complex molecule synthesis where appropriate. Overall, aims document considerable advancements, current status, emerging work critically summarizing contributions researchers working fascinating area is expected stimulate novel, innovative, broadly applicable functionalizations coming

Language: Английский

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Transition-Metal-Catalyzed Functionalization of Alkynes with Organoboron Reagents: New Trends, Mechanistic Insights, and Applications

ACS Catalysis, Journal Year: 2021, Volume and Issue: 11(12), P. 7513 - 7551

Published: June 9, 2021

Catalytic functionalization of alkynes with organoboron reagents provides a straightforward access to stereochemically defined multisubstituted alkenes, which are structural motifs commonly found in bioactive compounds and organic materials. Recent progress has substantially broadened the scope this field on several fronts. Strategies for regioselectivity control 1,2-migratory insertion across unsymmetrical internal alkynes, as well direct products anti-insertion stereochemistry, have been devised. The alkenyl-to-aryl 1,4-metal migration upon metal recently exploited powerful cascade sequences leading complex polycyclic scaffolds, including development enantioselective processes. Elegant enantiospecific dynamic kinetic resolution methods developed accessing chiral allenes from propargylic alcohol derivatives. Mechanistic manifolds emerged based single-electron transfer (SET) that provided fresh impetus alkyne 1,2-difunctionalization complementary stereoselectivity processes relying 1,2-insertion R–M species. Herein, we discuss most recent advances transition-metal-catalyzed using reagents, categorized according type mechanistic outcome. Emphasis is placed aspects, synthetic utility, limitations, challenges future research.

Language: Английский

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Deaminative (Carbonylative) Alkyl‐Heck‐type Reactions Enabled by Photocatalytic C−N Bond Activation

Angewandte Chemie International Edition, Journal Year: 2018, Volume and Issue: 58(8), P. 2402 - 2406

Published: Dec. 19, 2018

The palladium-catalyzed Heck reaction is a well-known, Nobel Prize winning transformation for producing alkenes. Unlike the alkenyl and aryl variants of reaction, alkyl-Heck still underdeveloped owing to competitive side reactions alkyl-palladium species. Herein, we describe development deaminative alkyl-Heck-type that proceeds through C-N bond activation by visible-light photoredox catalysis. A variety aliphatic primary amines were found be efficient starting materials this new process, affording corresponding alkene products in good yields under mild conditions. Moreover, strategy was successfully applied carbonylative reactions.

Language: Английский

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