Selected Applications of Pd‐ and Cu‐Catalyzed Carbon–Heteroatom Cross‐Coupling Reactions in the Pharmaceutical Industry

Yin, Jingjun

doi:10.1002/9781118309872.ch3

Cited by 11 publications

(5 citation statements)

References 311 publications

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“…The emergence of reliable cross-coupling protocols has had a substantial effect on the pharmaceutical industry . Transition-metal catalyzed reactions, particularly those involving palladium and copper catalysts, are widely used to synthesize libraries of compounds for SAR studies. , The prominence of cross-coupling reactions is due to in part to the generality of the methods, the broad functional group tolerance, and the commercial availability of the starting materials. However, the ubiquity of C sp 2 –C sp 2 cross-couplings can cause a bias toward planar compounds that lack complex stereochemical information .…”

mentioning

confidence: 99%

Stereospecific Nickel-Catalyzed Cross-Coupling Reactions of Benzylic Ethers with Isotopically-Labeled Grignard Reagents

Dawson

Jarvo

2015

Org. Process Res. Dev.

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In this manuscript we highlight the potential of stereospecific nickel-catalyzed cross-coupling reactions for applications in the pharmaceutical industry. Using an inexpensive and sustainable nickel catalyst, we report a gram-scale Kumada cross-coupling reaction. Reactions are highly stereospecific and proceed with inversion at the benzylic position. We also expand the scope of our reaction to incorporate isotopically labeled substituents.

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confidence: 99%

Stereospecific Nickel-Catalyzed Cross-Coupling Reactions of Benzylic Ethers with Isotopically-Labeled Grignard Reagents

Dawson

Jarvo

2015

Org. Process Res. Dev.

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“…Though the LSI is often slow in their uptake of catalytic methodologies, transition-metal-catalyzed cross-coupling reactions including the Suzuki–Miyaura, Buchwald–Hartwig, and Heck cross-coupling reactions are now common place. − As PRC finds increasing application in industry, photocatalytic cross-coupling reactions are arguably among the most widely used photoredox reactions.…”

Section: Methodology Developmentmentioning

confidence: 99%

Photocatalysis in the Life Science Industry

et al. 2021

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In the pursuit of new pharmaceuticals and agrochemicals, chemists in the life science industry require access to mild and robust synthetic methodologies to systematically modify chemical structures, explore novel chemical space, and enable efficient synthesis. In this context, photocatalysis has emerged as a powerful technology for the synthesis of complex and often highly functionalized molecules. This Review aims to summarize the published contributions to the field from the life science industry, including research from industrial-academic partnerships. An overview of the synthetic methodologies developed and strategic applications in chemical synthesis, including peptide functionalization, isotope labeling, and both DNA-encoded and traditional library synthesis, is provided, along with a summary of the state-of-the-art in photoreactor technology and the effective upscaling of photocatalytic reactions.

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“…Palladium-catalyzed C–X (X = C, N, O, S) coupling reactions are powerful bond-forming tools routinely utilized in academic laboratories and the pharmaceutical and agrochemical industries. − Critical to the success of these transformations has been the discovery of effective phosphane ligands. − One particularly significant class of ligands, out of the many developed for these reactions, − is the biaryl phosphanes popularized by Buchwald and co-workers. , The biaryl moiety has proven to be a privileged substructure that generates versatile ligands for a variety of cross-coupling reactions. Numerous elegant applications of biaryl phosphanes as ligands to manufacture molecules on multikilogram scale have been reported. , …”

Section: Introductionmentioning

confidence: 99%

Pd-Catalyzed Cross-Coupling Reactions Promoted by Biaryl Phosphorinane Ligands

et al. 2019

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We report the use of biaryl phosphorinanes as ligands for Pd-catalyzed cross-coupling reactions. A modular synthesis was developed that employs a double conjugate addition of primary biaryl phosphines into 1,1,5,5-tetraalkyl penta-1,4-diene-3-ones. Notably, this synthesis does not require the use of copper, a known contaminant in structurally related biaryl phosphane ligands. Using the synthetic strategy described above, we synthesized a library of biaryl phosphorinanes, varying their substitution about phosphorus and the steric and electronic nature of the biaryl motif. We then benchmarked their performance as ligands in Pd-catalyzed cross coupling reactions such as aryl sulfonamidation, aryl alkoxylation, and aryl amination in the presence of soluble organic bases. In each reaction studied, many ligands outperformed biaryl phosphanes known to promote the given transformation. Detailed substrate scopes were determined using high-throughput screening technology. Several biaryl phosphorinanes and their corresponding Pd(II) oxidative-addition complexes were extensively characterized using NMR spectroscopy and X-ray crystallography. General observations support that biaryl phosphorinanes promote reductive elimination and form robust catalysts with palladium. In many cases the use of these biaryl phosphorinanes may be advantageous over the use of biaryl phosphanes with respect to lower catalyst loadings, shorter reaction times, and robustness.

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Selected Applications of Pd‐ and Cu‐Catalyzed Carbon–Heteroatom Cross‐Coupling Reactions in the Pharmaceutical Industry

Cited by 11 publications

References 311 publications

Stereospecific Nickel-Catalyzed Cross-Coupling Reactions of Benzylic Ethers with Isotopically-Labeled Grignard Reagents

Stereospecific Nickel-Catalyzed Cross-Coupling Reactions of Benzylic Ethers with Isotopically-Labeled Grignard Reagents

Photocatalysis in the Life Science Industry

Pd-Catalyzed Cross-Coupling Reactions Promoted by Biaryl Phosphorinane Ligands

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