Pursuit of C–H Borylation Reactions with Non-Precious Heterobimetallic Catalysts: Hypothesis-Driven Variations on a Design Theme

This article presents a retrospective account of our group’s heterobinuclear (NHC)Cu-[MCO] catalyst design concept (NHC = N-heterocyclic carbene, [MCO] = metal carbonyl anion), the discovery of its application towards UV-light-induced dehydrogenative borylation of unactivated arenes, and the subsequent pursuit of thermal reaction conditions through structural modifications of the catalysts. The account highlights advantages of using a hypothesis-driven catalyst design approach that, while often fruitless with regard to the target transformation in this case, nonetheless vastly expanded the set of heterobinuclear catalysts available for other applications. In other words, curiosity-driven research conducted in a rational manner often provides valuable products with unanticipated applications, even if the primary objective is viewed to have failed.1 Introduction to Heterobinuclear Catalysts for C–H Borylation2 Pursuit of Thermal Borylation Conditions3 Catalysts beyond Copper Carbenes4 Conclusions

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Iterative Supervised Principal Component Analysis-Driven Ligand Design for Regioselective Ti-Catalyzed Pyrrole Synthesis

10.26434/chemrxiv.12284378 ◽

2020 ◽

Author(s):

Xin Yi See ◽

Benjamin Reiner ◽

Xuelan Wen ◽

T. Alexander Wheeler ◽

Channing Klein ◽

...

Keyword(s):

Principal Component Analysis ◽

De Novo ◽

Principal Component ◽

Component Analysis ◽

Catalyst Design ◽

Data Driven ◽

Initial Reaction ◽

Training Set ◽

Reaction Conditions ◽

Component Loadings

<div> <div> <div> <p>Herein, we describe the use of iterative supervised principal component analysis (ISPCA) in de novo catalyst design. The regioselective synthesis of 2,5-dimethyl-1,3,4-triphenyl-1H- pyrrole (C) via Ti- catalyzed formal [2+2+1] cycloaddition of phenyl propyne and azobenzene was targeted as a proof of principle. The initial reaction conditions led to an unselective mixture of all possible pyrrole regioisomers. ISPCA was conducted on a training set of catalysts, and their performance was regressed against the scores from the top three principal components. Component loadings from this PCA space along with k-means clustering were used to inform the design of new test catalysts. The selectivity of a prospective test set was predicted in silico using the ISPCA model, and only optimal candidates were synthesized and tested experimentally. This data-driven predictive-modeling workflow was iterated, and after only three generations the catalytic selectivity was improved from 0.5 (statistical mixture of products) to over 11 (> 90% C) by incorporating 2,6-dimethyl- 4-(pyrrolidin-1-yl)pyridine as a ligand. The successful development of a highly selective catalyst without resorting to long, stochastic screening processes demonstrates the inherent power of ISPCA in de novo catalyst design and should motivate the general use of ISPCA in reaction development. </p> </div> </div> </div>

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Pd Catalyzed N1/N4 Arylation of Piperazine for Synthesis of Drugs, Biological and Pharmaceutical Targets: An Overview of Buchwald Hartwig Amination Reaction of Piperazine in Drug Synthesis

Current Organic Synthesis ◽

10.2174/1570179415666171206151603 ◽

2018 ◽

Vol 15 (2) ◽

pp. 208-220 ◽

Cited By ~ 3

Author(s):

Vaibhav Mishra ◽

Tejpal Singh Chundawat

Keyword(s):

Bond Formation ◽

Catalyst Design ◽

Biologically Active ◽

Reaction Conditions ◽

Biological Targets ◽

Amination Reaction ◽

Drug Synthesis ◽

Substituted Piperazine ◽

Approved Drugs ◽

Fda Approved Drugs

Background: Substituted piperazine heterocycles are among the most significant structural components of pharmaceuticals. N1/N4 substituted piperazine containing drugs and biological targets are ranked 3rd in the top most frequent nitrogen heterocycles in U.S. FDA approved drugs. The high demand of N1/N4 substituted piperazine containing biologically active compounds and U.S. FDA approved drugs, has prompted the development of Pd catalyzed C-N bond formation reactions for their synthesis. Buchwald-Hartwig reaction is the key tool for the synthesis of these compounds. Objective: This review provides strategies for Pd catalyzed C-N bond formation at N1/N4 of piperazine in the synthesis of drugs and biological targets with diverse use of catalyst-ligand system and reaction parameters. Conclusion: It is clear from the review that a vast amount of work has been done in the synthesis of N1/N4 substituted piperazine containing targets under the Pd catalyzed Buchwald-Hartwig amination of aryl halides by using different catalyst-ligand systems. These methods have become increasingly versatile as a result of innovation in catalyst design and improvements in reaction conditions. This review gives an overview of recent utilization of Buchwald-Hartwig amination reaction in drug/target synthesis.

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The influence of physical parameters on the in-situ metal carbonyl complex formation studied with the Fast On-line Reaction Apparatus (FORA)

Radiochimica Acta ◽

10.1515/ract-2020-0035 ◽

2021 ◽

Vol 109 (4) ◽

pp. 261-281

Author(s):

Yves Wittwer ◽

Robert Eichler ◽

Dominik Herrmann ◽

Andreas Türler

Keyword(s):

Gas Flow ◽

Metal Carbonyl ◽

Fission Products ◽

Reaction Chamber ◽

Single Atom ◽

Physical Parameters ◽

Carbonyl Complex ◽

Reaction Conditions ◽

On Line ◽

The Impact

Abstract The Fast On-line Reaction Apparatus (FORA) was used to investigate the influence of various reaction parameters onto the formation and transport of metal carbonyl complexes (MCCs) under single-atom chemistry conditions. FORA is based on a 252Cf-source producing short-lived Mo, Tc, Ru and Rh isotopes. Those are recoiling from the spontaneous fission source into a reaction chamber flushed with a gas-mixture containing CO. Upon contact with CO, fission products form volatile MCCs which are further transported by the gas stream to the detection setup, consisting of a charcoal trap mounted in front of a HPGe γ-detector. Depending on the reaction conditions, MCCs are formed and transported with different efficiencies. Using this setup, the impact of varying physical parameters like gas flow, gas pressure, kinetic energy of fission products upon entering the reaction chamber and temperature of the reaction chamber on the formation and transport yields of MCCs was investigated. Using a setup similar to FORA called Miss Piggy, various gas mixtures of CO with a selection of noble gases, as well as N2 and H2, were investigated with respect to their effect onto MCC formation and transport. Based on this measurements, optimized reaction conditions to maximize the synthesis and transport of MCCs are suggested. Explanations for the observed results supported by simulations are suggested as well.

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Visible Light-Enabled Paternò-Büchi Reaction via Triplet Energy Transfer for the Synthesis of Oxetanes

10.26434/chemrxiv.12606377 ◽

2020 ◽

Author(s):

Katie Rykaczewski ◽

Corinna Schindler

Keyword(s):

Energy Transfer ◽

Visible Light ◽

Uv Light ◽

Cycloaddition Reaction ◽

High Energy ◽

Triplet Energy ◽

Reaction Conditions ◽

Triplet Energy Transfer

<div> <p>One of the most efficient ways to synthesize oxetanes is the light-enabled [2+2] cycloaddition reaction of carbonyls and alkenes, referred to as the Paternò-Büchi reaction. The reaction conditions for this transformation typically require the use of high energy UV light to excite the carbonyl, limiting the applications, safety, and scalability. We herein report the development of a visible light-mediated Paternò-Büchi reaction protocol that relies on triplet energy transfer from an iridium-based photocatalyst to the carbonyl substrates. This mode of activation is demonstrated for a variety of aryl glyoxylates and negates the need for both, visible light-absorbing carbonyl starting materials or UV light to enable access to a variety of functionalized oxetanes in up to 99% yield.</p> </div> <br>

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Natural lead-enriched biochar modifies TiO2 photocatalytic activation of sodium persulfate to degrade 2,4-dichlorophenol

E3S Web of Conferences ◽

10.1051/e3sconf/202123301111 ◽

2021 ◽

Vol 233 ◽

pp. 01111

Author(s):

Xiangxin Lu ◽

Wenbing Tan ◽

Beidou Xi ◽

Xiuyun Zhao

Keyword(s):

Uv Light ◽

Rapid Development ◽

Advanced Oxidation ◽

Ecological Environment ◽

Sodium Persulfate ◽

Active Sodium ◽

Reaction Conditions ◽

Combination System ◽

Modern Chemical ◽

Treatment Technologies

Due to the rapid development of the modern chemical industry, a large amount of chlorophenol pollutants remain in the environment. It poses a serious threat to the ecological environment and human health. Advanced oxidation technologies (AOPs) have the characteristics of mild reaction conditions and strong oxidation capacity, and are currently recognized as safe and effective pollutant treatment technologies. In this study, natural lead-rich biochar materials were used to activate sodium persulfate to degrade 2,4-dichlorophenol, and natural lead-rich biochar modified TiO2 photocatalytically degraded 2,4-dichlorophenol. Then, using natural lead-rich metal biochar/TiO2 material, photocatalysis combined with active sodium persulfate to degrade 2,4-dichlorophenol. The experimental results show that the combination of photocatalysis and activated sodium persulfate reaction can completely degrade 100 mg/L 2,4-dichlorophenol under UV light for 3 h, and the degradation efficiency is much higher than the sum of the two separate reactions. Quenching experiments show that SO4- • radicals play the most important role in the three free radicals (SO4- •, •OH and •O2- ) in the advanced oxidation combination system. Finally, the reaction mechanism of the two advanced oxidation combined systems are speculated.

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Synthesis of Yuehchukene Analogues, Murrapanine and Normurrapanine Utylizing Thermal Reaction of b-(1-Hydroxybutenyl)indoles under Neutral Reaction Conditions

Heterocycles ◽

10.3987/com-96-7507 ◽

1996 ◽

Vol 43 (8) ◽

pp. 1751 ◽

Cited By ~ 7

Author(s):

Jyh-Horng Sheu ◽

Yua-Kuang Chen ◽

Huey-Fen Chung ◽

Ping-Jyun Sung ◽

Song-Fong Lin

Keyword(s):

Thermal Reaction ◽

Reaction Conditions ◽

Neutral Reaction

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ChemInform Abstract: Synthesis of Yuehchukene Analogues, Murrapanine and Normurrapanine Utilizing Thermal Reaction of β-(1-Hydroxybutenyl)indoles under Neutral Reaction Conditions.

ChemInform ◽

10.1002/chin.199651192 ◽

2010 ◽

Vol 27 (51) ◽

pp. no-no

Author(s):

J.-H. SHEU ◽

Y.-K. CHEN ◽

H.-F. CHUNG ◽

P.-J. SUNG ◽

S.-F. LIN

Keyword(s):

Thermal Reaction ◽

Reaction Conditions ◽

Neutral Reaction

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Photooxidation of Cyclohexane by Visible and Near-UV Light Catalyzed by Tetraethylammonium Tetrachloroferrate

Catalysts ◽

10.3390/catal8090403 ◽

2018 ◽

Vol 8 (9) ◽

pp. 403

Author(s):

Kira Fahy ◽

Adam Liu ◽

Kelsie Barnard ◽

Valerie Bright ◽

Robert Enright ◽

...

Keyword(s):

Acetic Acid ◽

Reaction Rate ◽

Uv Light ◽

Incident Light ◽

Reaction Conditions ◽

Primary Products ◽

Photonic Efficiency ◽

Quenching By Oxygen

Tetraethylammonium tetrachloroferrate catalyzes the photooxidation of cyclohexane heterogeneously, exhibiting significant photocatalysis even in the visible portion of the spectrum. The photoproducts, cyclohexanol and cyclohexanone, initially develop at constant rates, implying that the ketone and the alcohol are both primary products. The yield is improved by the inclusion of 1% acetic acid in the cyclohexane. With small amounts of catalyst, the reaction rate increases with the amount of catalyst employed, but then passes through a maximum and decreases, due to increased reflection of the incident light. The reaction rate also passes through a maximum as the percentage of dioxygen above the sample is increased. This behavior is due to quenching by oxygen, which at the same time is a reactant. Under one set of reaction conditions, the photonic efficiency at 365 nm was 0.018 mol/Einstein. Compared to TiO2 as a catalyst, Et4N[FeCl4] generates lower yields at wavelengths below about 380 nm, but higher yields at longer wavelengths. Selectivity for cyclohexanol is considerably greater with Et4N[FeCl4], and oxidation does not proceed past cyclohexanone.

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