Quantitative Reactivity Models for Oxidative Addition to L2Pd(0): Additional Substrate Classes, Solvents, and Mechanistic Insights DOI Creative Commons

Jingru Lu,

Holly Celuszak,

Irina Paci

et al.

Chemistry - A European Journal, Journal Year: 2024, Volume and Issue: 30(62)

Published: Aug. 20, 2024

Abstract Quantitative molecular structure‐reactivity models are useful for generating predictions to guide synthesis design, and in formulating testing mechanistic hypotheses. We report an expanded multivariate linear regression (MLR) model the rate of (hetero)aryl ( pseudo )halide oxidative addition L 2 Pd(0), here exemplified by Pd(PCy 3 ) . This builds on a prior from our group, with additional substrate classes (aryl chlorides iodides) reaction solvents (THF, toluene, THF/DMF mixture). Overall solvent effects across entire set minimal under these conditions, enabling unified MLR without introduction new descriptors beyond original five. Examining origin two electrostatic potential ESP led generation simpler, four descriptor that is suitable aryl halides, but not 2‐halopyridines. Using this we identified outlier, 2‐pyridyl triflate, which undergoes nucleophilic displacement does involve adjacent nitrogen atom. Finally, discuss relationship between C−X bond strength rates, compare intrinsic index IBSI dissociation enthalpy BDE as descriptor.

Language: Английский

Enantioselective Synthesis of Planar Chiral Macrocyclic Metacyclophanes by Pd-Catalyzed C–O Cross-Coupling DOI

Shengkai Wei,

Liang-Yü Chen, Junqi Li

et al.

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(11), P. 7450 - 7456

Published: May 18, 2023

Despite the presence of planar chiral elements in natural products and ligands for asymmetric catalysis, catalytic enantioselective methods installing chirality remain underdeveloped relative to central axial chirality. Here, we report an Pd-catalyzed C–O bond-forming macrocyclization access enantioenriched macrocyclic metacyclophanes incorporating 2,3,4-trisubstituted pyridines. A variety bridging chains substituents can be incorporated under same reaction conditions (14 examples, 59–85% yields, 79–92% ee) generate meta-, metaortho-, metapara- cyclophanes. The syn-/anti-conformational preferences were elucidated by X-ray structures, 1H NMR analyses, computational studies. We also found that two enantiomers metacyclophane obtained using enantiomer ligand starting from regioisomeric linear precursors. This work provides entry into design cross-coupling macrocyclizations structures applications medicinal chemistry catalysis.

Language: Английский

Citations

25
Oxidative Addition of (Hetero)aryl (Pseudo)halides at Palladium(0): Origin and Significance of Divergent Mechanisms DOI
Matthew J. Kania, Albert Reyes, Sharon R. Neufeldt

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(28), P. 19249 - 19260

Published: July 3, 2024

Two limiting mechanisms are possible for oxidative addition of (hetero)aryl (pseudo)halides at Pd(0): a 3-centered concerted and nucleophilic displacement mechanism. Until now, there has been little understanding about when each mechanism is relevant. Prior investigations to distinguish between these pathways were limited few specific combinations the substrate ligand. Here, we computationally evaluated over 180 transition structures in order determine mechanistic trends based on substrate, ligand(s), coordination number. Natural abundance

Language: Английский

Citations

10
Ligand Substitution, Catalyst Activation, and Oxidative Addition Studies of a Stable Dialkyl Palladium Precatalyst DOI
Ian C. Chagunda,

Antonia Kropp,

David C. Leitch

et al.

Organometallics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 6, 2025

Palladium-catalyzed cross-coupling reactions are indispensable in chemical synthesis, but efficient situ catalyst activation remains a persistent challenge. Current Pd(II) precatalysts often lead to inefficient activation, necessitating higher loadings and limiting selectivity. We investigated the ligand substitution mechanism of stable dialkyl complex (DMPDAB)Pd(CH2SiMe3)2 real-time using mass spectrometric monitoring. The introduction charge-tagged phosphine ligands enabled detection key catalytic intermediates identification off-cycle species. Our findings demonstrate low energy for dissociation DMPDAB reductive elimination (Me3SiCH2)2 resulting rapid formation monoligated LPd(0) species, active species oxidative addition. These mechanistic insights offer path toward developing more selective Pd-catalyzed processes, offering valuable guidance future design with improved performance.

Language: Английский

Citations

1
C2-Selective Palladium-Catalyzed C–S Cross-Coupling of 2,4-Dihalopyrimidines DOI
Oliver D. Jackson, Albert Reyes, Collin D. Stein

et al.

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 19, 2025

Under most conditions, 2,4-dihalopyrimidines undergo substitution reactions at C4. Here we report that Pd(II) precatalysts supported by bulky N-heterocyclic carbene ligands uniquely effect C2-selective cross-coupling of 2,4-dichloropyrimidine with thiols. The regioselectivity this reaction stands in stark contrast to ∼1500 previously reported Pd-catalyzed cross-couplings favor C4 the absence other substituents on pyrimidine ring. Selectivity catalytic system herein is extremely sensitive structure precatalyst, largely due competing C4-selective nucleophilic aromatic substitution. C2-selectivity high 1° thiols and thiophenols, a range substituted dichloropyrimidines can be used. atypical selectivity transformation may facilitate diversity-oriented synthesis, as demonstrated for derivatives an antiviral agent. these C2─Cl cleavage not take place through typical oxidative addition pathway.

Language: Английский

Citations

1
We Already Know Everything about Oxidative Addition to Pd(0): Do We? DOI
Jordan Rio,

Haosheng Liang,

Lionel Perrin

et al.

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(17), P. 11399 - 11421

Published: Aug. 15, 2023

The oxidative addition (OA) of organic electrophiles to Pd(0) is a fundamental step in organopalladium chemistry and plays key role palladium-catalyzed cross-coupling reactions. This perspective summarizes selected mechanistic studies the Pd(0)-to-Pd(II) OA process involving halides pseudohalides with focus on systems relevant catalytic results are organized according nature supporting ligands, extracting general trends, describing most examples. formation active species from precatalysts surveyed, as well influence different that could be present under conditions process, providing guidelines facilitate understanding improvement

Language: Английский

Citations

19
Evidence for Suzuki–Miyaura cross-couplings catalyzed by ligated Pd3-clusters: from cradle to grave DOI Creative Commons
Neda Jeddi, Neil W. J. Scott, Theo F. N. Tanner

et al.

Chemical Science, Journal Year: 2024, Volume and Issue: 15(8), P. 2763 - 2777

Published: Jan. 1, 2024

Pd

Language: Английский

Citations

7
The Road Less Traveled: Unconventional Site Selectivity in Palladium-Catalyzed Cross-Couplings of Dihalogenated N-Heteroarenes DOI
Jacob P. Norman, Sharon R. Neufeldt

ACS Catalysis, Journal Year: 2022, Volume and Issue: 12(19), P. 12014 - 12026

Published: Sept. 19, 2022

The vast majority (≥90%) of literature reports agree on the regiochemical outcomes Pd-catalyzed cross-coupling reactions for most classes dihalogenated N-heteroarenes. Despite a well-established mechanistic rationale typical selectivity, several examples reveal that changes to catalyst can switch site leading unconventional product. In this Perspective, we survey these unusual cases in which divergent selectivity is controlled by ligands or speciation. some cases, origin inverted has been established, but others mechanism remains unknown. This Perspective concludes with discussion remaining challenges and opportunities field site-selective cross-coupling. These include developing better understanding oxidative addition mechanisms, role speciation establishing an explanation influence ring substituents outcome, inverting "stubborn" substrates, minimizing unwanted over-reaction di- polyhalogenated substrates.

Language: Английский

Citations

24
Mechanisms and Site Selectivity of (Het)Ar–X Oxidative Addition to Pd(0) Are Controlled by Frontier Molecular Orbital Symmetry DOI Creative Commons

Jingru Lu,

Nathan D. Schley, Irina Paci

et al.

Published: May 28, 2024

We report how the reaction mechanism and site-selectivity of 2-halopyridine oxidative addition to L2Pd(0) are both controlled by frontier molecular orbital symmetry. Comparing rates for pairs 2-chloro-3-EDG-pyridines / 2-chloro-5-EDG-pyridines (EDG = electron-donating group: NH2, OMe F) Pd(PCy3)2 reveals 3-EDG isomers undergo ~100 times faster than their 5-EDG counterparts (∆ΔG‡OA 10.4-11.6 kJ mol-1). Experimental computational mechanistic studies reveal that LUMO symmetries substrates control mechanism. For derivatives, high coefficients at reactive C2 position, antibonding symmetry through C2=N bond pyridine lead a nucleophilic displacement oxida-tive Conversely, derivatives has node C5–C2 plane, lead-ing minimal contribution carbon. The higher energy LUMO+1 substantial density C2, but nitrogen. This leads undergoing 3-centered insertion These effects also multihalogenated pyridines, which we investigate electron-withdrawing substituents. Incorporating simple fron-tier based descriptors quantitative multivariate linear model im-proved prediction accuracy relative substituted L2Pd(0).

Language: Английский

Citations

5
Experimental Evidence for Zerovalent Pd(NHC) as a Competent Catalyst in C–N Cross-Coupling (NHC = DiMeIHeptCl) DOI
Volodymyr Semeniuchenko, Sepideh Sharif, Neha Rana

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(42), P. 29224 - 29236

Published: Oct. 10, 2024

Use of the branched N-heterocyclic carbene (NHC) ligand 1,3-bis(2,6-bis(3-methyl-1-(2-methylpropyl)butyl)phenyl)-4,5-dichloro-1,3-dihydro-2

Language: Английский

Citations

4
ortho‐Selective Suzuki Coupling of Dichlorophenol and Dichlorobenzylalcohol in Water under Palladium Catalysis Directed by Noncovalent Interactions and Computational Analysis DOI Open Access

Shangxun Zhao,

Shuo Wen,

H Chen

et al.

Asian Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 14, 2025

Abstract The use of attractive noncovalent interactions is emerging as a versatile approach to address site‐selectivity challenges. Herein, we report ortho‐selective Suzuki coupling reactions in water 2,3‐dichloroarenes and 2,4‐dichloroarenes bearing hydroxy group the presence palladacycle catalyst directed by interactions. Various ortho‐substituted arylphenols arylbenzyl alcohols were obtained good excellent yields with high selectivity. Density functional theory (DFT) calculations ab initio molecular dynamics (AIMD) simulations suggested that ortho ‐selective dichlorophenols dichlorobenzyl occurred through electrostatic hydrogen bonding interactions, respectively.

Language: Английский

Citations

0