Synthesis of <scp>4‐Trifluoromethylated</scp> 1,<scp>3‐Butadienes</scp> via Palladium Catalyzed Heck Reaction

Li, Yang; Meng, Hao; Chang, Yu‐Chen; Liu, Yuan; Wang, Wen-Fei; Sun, Ning; Zhu, Wen-Qing; Gao, Ziwei

doi:10.1002/cjoc.202100313

Cited by 13 publications

(7 citation statements)

References 38 publications

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“…This however, including variations in the solvent and base, led to a complex mixture of products. Evidently, the classical or newly developed Heck conditions with electroneutral or electrondeficient substrates [26b,c] may not be transferable to electron rich alkene substrates such as the N‐Boc‐allylamine and we considered that this transformation shares similarities with coupling processes proceeding via a C−H activation step. Accordingly we decided to include pivalic acid in the reaction as this has been shown to benefit such reactions for a number of reasons such as increased solubility, support of monomeric rather than dimeric Pd species, reduction of Pd(II) to Pd(0), and promotion of the β‐hydride elimination step due to its steric bulk and basicity [27–30] .…”

Section: Resultsmentioning

confidence: 99%

Scalable Synthesis of Cinnamylamines Via the Heck Reaction: Application in the Synthesis of Abamine, Naftifine and Reboxetine

Moschona,

Tsitopoulou,

Efstratiou

et al. 2024

Eur J Org Chem

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Following an extensive screening of reaction parameters such as the nature and amount of bases, Pd pre‐catalysts, ligands, additives, solvents and temperature range, we succeeded in developing a Heck reaction using N‐Boc‐allylamine and commercially available aryl bromides, capable of delivering a wide range of Boc‐protected trans‐cinnamylamines with 75–85 % regio‐ and stereoselectivity over other isomers. Optimisation of the Boc‐deprotection step and its work‐up procedure allowed for all minor isomers and impurities to be purged thus isolating pure trans‐cinnamylamines typically in 55–65 % yield without need for chromatography. We have successfully performed this chemistry in up to 5 g scale and demonstrated its usefulness by applying it to the synthesis of abamine, naftifine hydrochloride and a formal synthesis reboxetine mesylate.

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Section: Resultsmentioning

confidence: 99%

Scalable Synthesis of Cinnamylamines Via the Heck Reaction: Application in the Synthesis of Abamine, Naftifine and Reboxetine

Moschona,

Tsitopoulou,

Efstratiou

et al. 2024

Eur J Org Chem

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“…Based on its structural formula, HCFO‐1233zd is also a good trifluoromethylation reagent; thus, simple and efficient conversion of HCFO‐1233zd into useful fluorine‐containing chemicals is highly important. Based on the above information, relevant reports have been published on coupling reactions involving ( E )‐1‐chloro‐3,3,3‐trifluoro‐propylene, [27] and good progress has been achieved by our research group [28] and other research groups [29–30] . A literature search also revealed other relevant reports on the carbonylation reactions that HCFO‐1233zd participates in, such as the synthesis of esters, [31] amides, [32] and carboxylic acids [33] .…”

Section: Introductionmentioning

confidence: 99%

Palladium‐Catalyzed Carbonylation Reaction of Indole/Pyrrole Involving HCFO‐1233zd (E)

Zhao,

Zhu,

Yu‐Jing

et al. 2024

Chemistry A European J

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3‐Idolenone is a key intermediate in the synthesis of many drugs and plays an important role in synthetic chemistry and biochemistry. A new method for the synthesis of trifluoromethylated 3‐indolenones by carbonylation catalyzed by Pd(0) is described. In the absence of an additive, 1‐chloro‐3,3,3‐trifluoro‐propylene (an inexpensive ozone‐friendly CF3 structural unit) reacts with indole and carbon monoxide to synthesize trifluoromethylatedindolenone in good yield, regioselectivity and chemoselectivity and with strong resistance to basal functional groups such as alkynes, aldehydes and esters. Notably, in addition to indole compounds being well transformed into the corresponding products, pyrrole, heteroindole can also is also suitable for the corresponding chemical transformation. This study provides a scientific method for the late construction of trifluoromethylated indole/pyrrole 3‐ketene.

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“…The Heck reaction of halogenated aromatics with olefins is among the most direct effective methods for forming C-C bonds and has been extensively applied for the synthesis of drugs and intermediates, natural products, and functional materials. [1][2][3][4] Since the discovery of the Heck reaction, reaction selectivity, catalyst types, and catalytic mechanisms have been intensively studied. [5][6][7] Among the investigated catalysts, traditional homogeneous palladium catalysts show excellent catalytic activity but also have some limitations such as air-sensitivity, poor recyclability and reusability, and cumbersome post-treatment.…”

Section: Introductionmentioning

confidence: 99%

Continuous-flow Heck coupling reactions catalyzed by Pd complexes of amidoxime fibers

Xie

Zhang

et al. 2023

Journal of Chemical Research

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Improving production efficiency and developing green catalytic systems are key issues for applying Heck coupling reactions in the chemical industry. In this study, an amidoxime-fiber-supported Pd catalyst is prepared from polyacrylonitrile fiber, hydroxylamine hydrochloride, and PdCl2. The morphology and structure of amidoxime-fiber-supported Pd are characterized by scanning electron microscopy, energy-dispersive spectroscopy, X-ray photoelectron spectrometer, X-ray diffraction, and inductively coupled plasma-optical emission spectrometer. A packed-bed flow reactor is designed and employed for catalysis of the Heck reaction of iodobenzene and styrene based on the amidoxime-fiber-supported Pd catalyst. The effects of reaction temperature, flow rate, cycle time, and reactant concentration on the conversion and yield are investigated. The results show that the optimal conditions for the continuous-flow single reactor are 70 °C, iodobenzene concentration of 30 mmol L−1 in a solution of N,N-dimethylformamide (100 mL) under continuous flow at a flow rate of 2 mL min−1. The catalyst showed good activity and stability after a continuous operation time of 50 h, with catalytic activity 2.21 times higher than that obtained with traditional batch reaction. Furthermore, we have established a new flow reaction system based on the numbering-up of reactors with a parallel connection. The catalytic efficiency of four parallel reactors is four times higher than that of a single reactor. Kinetic studies reveal that the reaction has low activation energy (8.8771 kJ mol−1), indicating that amidoxime-fiber-supported Pd has good catalytic activity. This research provides an alternative pathway for highly efficient Heck coupling in continuous flow.

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Synthesis of 4‐Trifluoromethylated 1,3‐Butadienes via Palladium Catalyzed Heck Reaction

Cited by 13 publications

References 38 publications

Scalable Synthesis of Cinnamylamines Via the Heck Reaction: Application in the Synthesis of Abamine, Naftifine and Reboxetine

Scalable Synthesis of Cinnamylamines Via the Heck Reaction: Application in the Synthesis of Abamine, Naftifine and Reboxetine

Palladium‐Catalyzed Carbonylation Reaction of Indole/Pyrrole Involving HCFO‐1233zd (E)

Continuous-flow Heck coupling reactions catalyzed by Pd complexes of amidoxime fibers

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