Controlling Reactivity and Selectivity in the Nondirected C–H Activation of Arenes with Palladium

Accounts of Chemical Research, Journal Year: 2023, Volume and Issue: 56(18), P. 2459 - 2472

Published: Aug. 24, 2023

ConspectusAromatic structures are widespread motifs throughout organic chemistry, and C-H activation has been recognized as a major tool for enabling their sustainable efficient functionalization. Through activation, arenes can be modified without the need prefunctionalization, leading to inherent atom- step-economic advantages over traditional methods. However, development of synthetically useful methods, several hurdles have overcome. The strength bonds necessitates sufficiently reactive catalysts, while presence multiple within substrate poses challenges in terms site-selectivity. Traditionally these addressed by control. By attaching different directing groups (DGs), reactivity respective arene was significantly enhanced DG guided metal close proximity specific bonds, resulting high introduction removal add additional steps synthetic sequence, scope reaction is limited class. complementary nondirected methods that applied broad range necessity carry functional group coordinates Pd (referred simple arenes) therefore highly desirable. intrinsically lower such substrates absence selectivity-determining pose significant solved only catalysts. Consequently, field especially with respect Pd-catalyzed remained comparatively underdeveloped when we initiated our research program 2017. At time, state-of-the-art required used large excess, precluding its use late-stage Since organopalladium species among most versatile intermediates, realized developing system, which effectively selectively activate limiting reagent, would powerful chemistry. This account summarizes groups' toward application catalytic systems offering this desired focuses explicitly on functionalization reactions arenes, where employed reagent. After an state before 2017 associated challenges, experimental mechanistic details about first arene-limited, palladium will discussed. enabled identification combination two ligands, N-heterocycle amino acid-derived ligand. Afterward discuss expansion dual-ligand approach further arene-limited transformations. Finally, describe methodologies originated from observations made during studies, namely, deuteration selective olefination method uses noncovalent interactions induce meta selectivity.

Language: Английский

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Noncovalent interaction with a spirobipyridine ligand enables efficient iridium-catalyzed C–H activation

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: April 17, 2024

Abstract Exploitation of noncovalent interactions for recognition an organic substrate has received much attention the design metal catalysts in synthesis. The CH–π interaction is especially interest molecular because both C–H bonds and π electrons are fundamental properties molecules. However, their weak nature, these have been less utilized control reactions. We show here that can be used to kinetically accelerate catalytic activation arenes by directly recognizing π-electrons arene substrates with a spirobipyridine ligand. Computation ligand kinetic isotope effect study provide evidence between backbone substrate. rational exploitation will open new avenues catalysis.

Language: Английский

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Ir-Catalyzed, Nitrogen-Directed C(sp³)–H and C(sp²)–H Borylation with a Spiro-Fluorene-Indenoindenyl Ligand

ACS Catalysis, Journal Year: 2025, Volume and Issue: unknown, P. 4061 - 4068

Published: Feb. 21, 2025

Language: Английский

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Room Temperature Fluoranthene Synthesis through Cationic Rh(I)/H₈-BINAP-Catalyzed [2 + 2 + 2] Cycloaddition: Unexpected Acceleration due to Noncovalent Interactions

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(3), P. 1604 - 1613

Published: Jan. 12, 2023

The fluoranthene skeleton is a structure often found in natural products and fluorescent materials, thus developing an operationally simple method for diversity-oriented synthesis important research topic organic synthesis. However, existing synthetic methods require harsh reaction conditions or limited substrate applicability both. Here, we report the room temperature of substituted fluoranthenes azafluoranthenes through cationic Rh(I)/H8-BINAP complex-catalyzed [2 + 2 2] cycloaddition using 1,8-dialkynylnaphthalenes. DFT calculations reveal that H8-BINAP ligand stabilizes intermediates, allowing reaction. Among substrates examined, 1,8-bis(phenylethynyl)naphthalene diarylacetylenes show high reactivity, contrary to reactivity predicted by their steric bulkiness. Theoretical experimental mechanistic studies have demonstrated noncovalent interactions phenyl groups on both accelerate present sterically demanding reactions stabilizing transition states rather than inducing repulsions.

Language: Английский

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Enabling Site-Selective C–H Functionalization of Aliphatic Alcohols and Amines with exo-Directing Groups by Tether-Tunable Design of Pd^II/Pd^IV Catalysis

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(22), P. 17077 - 17083

Published: Nov. 5, 2024

We report herein a general platform for palladium catalysis using library of cyclic diacyl peroxides, achieving site-selective C–H functionalization aliphatic alcohols and amines. Experimental studies theoretical calculations indicate that bystanding peroxides minimize unwanted reductive elimination events enable controlled cleavage. The protocol is simple scalable offers high selectivity broad range substrates nucleophiles, including complex molecules. findings advance understanding high-valent chemistry, providing tool creating chemically diverse vicinal diols amino opening new possibilities in functionalization.

Language: Английский

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Site‐Selective C−H Arylation of Diverse Arenes Ortho to Small Alkyl Groups

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(39)

Published: July 13, 2022

Catalytic systems for direct C-H activation of arenes commonly show preference electronically activated and sterically exposed sites. Here we that a range functionally rich pharmaceutically relevant arene classes can undergo site-selective arylation ortho to small alkyl substituents, preferably endocyclic methylene groups. The is experimentally supported as being the selectivity-determining step, while computational studies transition state models indicate relevance non-covalent interactions between catalyst group substrate. Our results suggest C(sp

Language: Английский

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Palladium‐Catalyzed Remote C–H Functionalization: Non‐Covalent Interactions and Reversibly Bound Templates

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(44)

Published: July 27, 2024

Abstract Pd‐catalysis has stood as a pivotal force in synthetic transformations for decades, maintaining its status paramount tool the realm of C−H bond activation. While functionalization at proximal positions become commonplace, achieving selective and sustainable access to distal continues captivate scientific endeavors. Recently, noteworthy trend emerged, focusing on utilization non‐covalent interactions address challenges associated with remote functionalization. The integration these into palladium catalysis stands justified response demands positions. This review delves latest advancements trends surrounding incorporation within field catalysis. Furthermore, it is emphasize that multifunctional templates, particularly those harnessing hydrogen bonding, present an elegant sophisticated approach activate bonds highly directed fashion. These templates showcase versatility demonstrate potential applications across diverse contexts area

Language: Английский

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Nondirected C–H/C–F Coupling for the Synthesis of α-Fluoro Olefinated Arenes

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(21), P. 14000 - 14011

Published: Oct. 17, 2023

The fluorinated entities are considered a privileged structure class in the field of medicinal chemistry because amplified bioactivity they exhibit. In this regard, developments C–H fluorination and trifluoromethylation have been mostly targeted. α-fluoro olefins also show potential applications as bioisosteres amides prevalent drug candidates, but their synthetic accessibility by activation strategy remains an elusive domain. assistance directing group (DG) does enable fluoroalkenylation constrains scope terms expansion chemical space for development programs. nondirected is "one-shot" solution to existing issues on use DGs. With perspective, we herein report protocol Pd-catalyzed C–H/C–F coupling accessing regioselective fashion. transformation governed dual control pyridine amino acid-based ligand, which dictate complementary selectivity achieved. allows late-stage derivatization drugs natural products enables conjugation with product means fluoro-olefin bridge. incorporation these moieties can potentially modulate parent drugs. Mechanistic investigations DFT calculations suggest vital role monoprotected acid ligand step through concerted metalation deprotonation, overall turnover frequency-determining state catalytic cycle.

Language: Английский

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Mechanistic studies of the palladium-catalyzed S,O-ligand promoted C–H olefination of aromatic compounds

Chemical Science, Journal Year: 2023, Volume and Issue: 14(11), P. 2943 - 2953

Published: Jan. 1, 2023

A mechanistic study of the role S,O-ligand in promoting palladium catalyzed C–H activation arenes is described. The data indicate that triggers formation more reactive cationic species.

Language: Английский

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Remote Steric Control for Site-Selective Synthesis

Synlett, Journal Year: 2023, Volume and Issue: 34(18), P. 2110 - 2116

Published: July 10, 2023

Abstract Control of site selectivity for organic synthesis in general, and transition-metal-catalyzed C–H functionalization particular, is an important challenging task. Steric interactions have been widely used to control reaction selectivity, but these strategies are largely limited proximity sites. Recently, through remote steric has emerged as attractive strategy that can enable selective reactions at distal sites from a marker. This review will cover recent developments this area, with focus on borylation activation.

Language: Английский

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