A Thermally Stable, Alkene-Free Palladium Source for Oxidative Addition Complex Formation and High-Turnover Catalysis DOI
Jingjun Huang,

Dang Binh Ho,

Gregory Gaube

et al.

Organometallics, Journal Year: 2024, Volume and Issue: 43(20), P. 2403 - 2412

Published: May 8, 2024

Oxidative addition complexes play a crucial role in Pd-catalyzed transformations. They are not only key catalytic intermediates but also powerful and robust precatalysts, effective reactants for late-stage functionalization of complex molecules. However, accessing given oxidative is often challenging due to lack stable palladium sources with the correct reactivity. Herein, we report an easily prepared bench-stable Pd(II) dialkyl complex, DMPDAB–Pd–BTSM (DMPDAB = N,N′-bis(2,6-dimethylphenyl)diazabutadiene; BTSM bis(trimethylsilylmethyl)), that versatile precursor generating highly active as Pd source situ catalyst formation cross-coupling reactions. A aspect this structure absence alkene-based stabilizing ligands common other precursors. We demonstrate utility several complexes, including phosphine diimine-ligated high-turnover-number catalysis C–O, Suzuki, Heck coupling

Language: Английский

Synthetic Advantages of Defluorinative C−F Bond Functionalization DOI Creative Commons
Leidy V. Hooker, Jeffrey S. Bandar

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(49)

Published: Aug. 22, 2023

Abstract Much progress has been made in the development of methods to both create compounds that contain C−F bonds and functionalize bonds. As such, are becoming common versatile synthetic functional handles. This review summarizes advantages defluorinative functionalization reactions for small molecule synthesis. The coverage is organized by type carbon framework fluorine attached mono‐ polyfluorinated motifs. main challenges, opportunities advances discussed each class organofluorine. Most text focuses on case studies illustrate how defluorofunctionalization can improve routes targets or properties enable unique mechanisms reactions. broader goal showcase incorporating exploiting design routes, improvement specific advent new methods.

Language: Английский

Citations

60
Polyaniline-supported nano metal-catalyzed coupling reactions: Opportunities and challenges DOI
Zhigang Zeng, Ying Chen,

Zhu Xiaoming

et al.

Chinese Chemical Letters, Journal Year: 2022, Volume and Issue: 34(2), P. 107728 - 107728

Published: Aug. 10, 2022

Language: Английский

Citations

52
A reactivity model for oxidative addition to palladium enables quantitative predictions for catalytic cross-coupling reactions DOI Creative Commons

Jingru Lu,

Sofia Donnecke, Irina Paci

et al.

Chemical Science, Journal Year: 2022, Volume and Issue: 13(12), P. 3477 - 3488

Published: Jan. 1, 2022

Making accurate, quantitative predictions of chemical reactivity based on molecular structure is an unsolved problem in synthesis, particularly for complex molecules. We report approach to prediction catalytic reactions structure-reactivity models a key step common many mechanisms. demonstrate this with mechanistically model the oxidative addition (hetero)aryl electrophiles palladium(0), which myriad processes. This links simple descriptors relative rates 79 substrates, including chloride, bromide and triflate leaving groups. Because often controls rate and/or selectivity palladium-catalyzed reactions, can be used make about reaction outcomes. Demonstrated applications include multivariate linear initial Sonogashira coupling successful site-selectivity Suzuki, Buchwald-Hartwig, Stille multihalogenated substrates relevant synthesis pharmaceuticals natural products.

Language: Английский

Citations

46
Collaboration as a Key to Advance Capabilities for Earth-Abundant Metal Catalysis DOI
Paul J. Chirik, Keary M. Engle, Eric M. Simmons

et al.

Organic Process Research & Development, Journal Year: 2023, Volume and Issue: 27(7), P. 1160 - 1184

Published: March 20, 2023

Earth-abundant metal (EAM) catalysis can have profound impact in the pharmaceutical industry terms of sustainability and cost improvements from replacing precious metals like palladium as well harnessing differential reactivity first-row that allows for novel transformations to enable more efficient routes clinical candidates. The strategy building these capabilities within process group at Bristol Myers Squibb is described herein, with general plan a reaction screening platform, demonstrating scalability, increasing mechanistic understanding catalyst activation. development catalytic utilizing nickel, cobalt, iron while highlighting importance collaboration internal external groups advance EAM our portfolio. challenges benefits working transition metals, including metrics implementation catalysis, such cost, mass intensity, commercial availability catalysts ligands, are discussed.

Language: Английский

Citations

43
Orthogonal C–O Bond Construction with Organogermanes DOI

Amit Dahiya,

Avetik G. Gevondian, Franziska Schoenebeck

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(14), P. 7729 - 7735

Published: March 30, 2023

We report a fully orthogonal C-O bond formation strategy, which involves the selective coupling of arylgermanes with alkyl alcohols (primary, secondary and tertiary) as well carboxylic acids, tolerating otherwise widely employed handles, such aromatic (pseudo)halogens (C-I, C-Br, C-Cl, C-F, C-OTf, C-OFs), silanes boronic acid derivatives. This unprecedented [Ge]-based construction is rapid (15 min to few hours reaction time), air-tolerant, operationally simple mild, it base-free proceeds at room temperature.

Language: Английский

Citations

24
Direct C–H Hydroxylation of N-Heteroarenes and Benzenes via Base-Catalyzed Halogen Transfer DOI

Kendelyn I. Bone,

Thomas R. Puleo,

Jeffrey S. Bandar

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(14), P. 9755 - 9767

Published: March 26, 2024

Hydroxylated (hetero)arenes are valued in many industries as both key constituents of end products and diversifiable synthetic building blocks. Accordingly, the development reactions that complement address limitations existing methods for introduction aromatic hydroxyl groups is an important goal. To this end, we apply base-catalyzed halogen transfer (X-transfer) to enable direct C–H hydroxylation mildly acidic N-heteroarenes benzenes. This protocol employs alkoxide base catalyze X-transfer from sacrificial 2-halothiophene oxidants aryl substrates, forming SNAr-active intermediates undergo nucleophilic hydroxylation. Key process use 2-phenylethanol inexpensive hydroxide surrogate that, after substitution rapid elimination, provides hydroxylated arene styrene byproduct. Use simple 2-halothiophenes allows 6-membered 1,3-azole derivatives, while a rationally designed 2-halobenzothiophene oxidant extends scope electron-deficient benzene substrates. Mechanistic studies indicate reversible, suggesting deprotonation, halogenation, steps operate synergy, manifesting unique selectivity trends not necessarily dependent on most position. The utility method further demonstrated through streamlined target molecule syntheses, examples regioselectivity contrast alternative methods, scalable recycling thiophene oxidants.

Language: Английский

Citations

10
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
Regioselective Suzuki–Miyarua Cross-Coupling for Substituted 2,4-Dibromopyridines Catalyzed by C3-Symmetric Tripalladium Clusters DOI

Zhixin He,

Meng Chen,

Yingrui Song

et al.

The Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: 90(5), P. 1895 - 1904

Published: Jan. 24, 2025

Multipalladium clusters possess peculiar structures and synergistic effects for reactivity selectivity. Herein, C3-symmetric tripalladium (1, 0.5 mol %) afford C2-regioselective SMCC of 2,4-dibromopyridine with phenylboronic acids or pinacol esters (C2:C4 up to 98:1), in contrast Pd(OAc)2 ligand-free conditions. In addition, similar C2-selectivity was achieved Sonogashira, Negishi, Kumada coupling reactions. This method highlights their powerful catalytic ability, exclusive C2-selectivity, broad substrate scope, efficient amplification, multiple ligand-exchange feasibility demonstrates that the conventional sites could be successfully regulated even reversed by catalysts.

Language: Английский

Citations

1
Different Oxidative Addition Mechanisms for 12- and 14-Electron Palladium(0) Explain Ligand-Controlled Divergent Site Selectivity DOI
Jacob P. Norman, Nathaniel G. Larson, Sharon R. Neufeldt

et al.

ACS Catalysis, Journal Year: 2022, Volume and Issue: 12(15), P. 8822 - 8828

Published: July 8, 2022

In cross-coupling reactions, dihaloheteroarenes are usually most reactive at C─halide bonds adjacent to a heteroatom. This selectivity has been previously rationalized. However, no mechanistic explanation exists for anomalous reports in which specific ligands effect inverted with dihalopyridines and -pyridazines. Here we provide evidence that these uniquely promote oxidative addition 12e- Pd(0). Computations indicate 14e- Pd(0) can favor different mechanisms due differences their HOMO symmetries. These shown lead site preferences, where an atypical distal nitrogen.

Language: Английский

Citations

34
Atroposelective Desymmetrization of Resorcinol-Bearing Quinazolinones via Cu-Catalyzed C–O Bond Formation DOI
Hyung Yoon, Alexandra Galls, Soren D. Rozema

et al.

Organic Letters, Journal Year: 2022, Volume and Issue: 24(2), P. 762 - 766

Published: Jan. 10, 2022

Enantioselective Cu-catalyzed C–O cross coupling reactions yielding atropisomeric resorcinol-bearing quinazolinones have been developed. Utilizing a new guanidinylated dimeric peptidic ligand, set of products were generated in good yields with excellent stereocontrol. The transformation was readily scalable, and range product derivatizations performed.

Language: Английский

Citations

33