Synthesis of C-15 Vindoline Analogues by Palladium-Catalyzed Cross-Coupling Reactions

Johnson, Peter; Sohn, Jae Hak; Rawal, Viresh H.

doi:10.1021/jo061243y

Cited by 35 publications

(16 citation statements)

References 36 publications

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“…As shown below, Rawal used the SMC of alkenyl boronic acids with C15-bromovindoline, a heavily functionalized coupling counterpart that proceeded in good yield using XPhos ( L8 ) as a supporting ligand (Figure 11). 47 It is worth mentioning that only XPhos allowed for an efficient coupling process with alkenyl boronic acids; other ligands tested by the authors gave the desired product in low yield. Despite the high catalyst loading required, this example illustrates the applicability of the method to the derivatization of highly functionalized molecules.…”

Section: Selected Synthetic Applicationsmentioning

confidence: 99%

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Palladium-Catalyzed Suzuki−Miyaura Cross-Coupling Reactions Employing Dialkylbiaryl Phosphine Ligands

2008

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ConspectusThe cores of many types of polymers, ligands, natural products, and pharmaceuticals contain biaryl or substituted aromatic structures, and efficient methods of synthesizing these structures are crucial to the work of a broad spectrum of organic chemists. Recently, Pd-catalyzed carbon-carbon bondforming processes, particularly the Suzuki-Miyaura cross-coupling reaction (SMC), have risen in popularity for this purpose. The SMC has many advantages over other methods for constructing these moieties, including mild conditions, high tolerance toward functional groups, the commercial availability and stability of its reagents, and the ease of handling and separating byproducts from its reaction mixtures.Until 1998, most catalysts for the SMC employed triarylphosphine ligands. More recently, new bulky and electron-rich phosphine ligands, which can dramatically improve the efficiency and selectivity of such cross-coupling reactions, have been introduced. In the course of our studies on carbonnitrogen bond-forming reactions, we found that the use of electron-rich and bulky phosphines enhanced the rate of both the oxidative addition and reductive elimination processes; this was the beginning of our development of a new family of ligands, the dialkylbiarylphosphines L1-L12. These ligands can be used for a wide variety of palladium-catalyzed carbon-carbon, carbon-nitrogen, and carbon-oxygen bond-forming processes as well as serving as supporting ligands for a number of other reactions.The enhanced reactivity of these catalysts has expanded the scope of cross-coupling partners that can be employed in the SMC. Using such dialkylbiarylphosphine ligands, the coupling of unactivated aryl chlorides, aryl tosylates, heteroaryl systems, and very hindered substrate combinations have become routine. The utility of these ligands has been successfully demonstrated in a wide number of synthetic applications, including industrially relevant processes.In this account, we provide an overview of the use and impact of dialkylbiarylphosphine ligands in the SMC. We discuss our studies on the mechanistic framework of the reaction, which have allowed us to rationally modify the ligand structures in order to tune their properties. We also describe selected applications in the synthesis of natural products and new materials to illustrate the utility of these dialkylbiarylphosphine ligands in various "real-world" synthetic applications. IntroductionThe impact of the Suzuki-Miyaura reaction (SMC) on academic and industrial research as well as on production has been immense. 1 Over the past two decades, it has become arguably one of the most efficient methods for the construction of biaryl or substituted aromatic moieties; compounds that contain these substructures constitute important building blocks of polymers, sbuchwal@mit.edu. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript 2 ligands, 3 a wide range of natural products such as alkaloids, as well as in numerous biologically active pharmaceutic...

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Section: Selected Synthetic Applicationsmentioning

confidence: 99%

“…Recently, Newman has designed a series of heterobicyclic templates with essential features of the pharmacophores of mGluR5 antagonists 47. His approach relied on the SMC of heteroaryl halides and heteroarylboronic acids or esters.…”

Section: Selected Synthetic Applicationsmentioning

confidence: 99%

Palladium-Catalyzed Suzuki−Miyaura Cross-Coupling Reactions Employing Dialkylbiaryl Phosphine Ligands

2008

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“…170 More recently, Rawal et al have used this protocol to prepare compound 128 from silyl ketene acetal 126 and aryl bromide 127 (Figure 7). 174 …”

Section: Arylation Of Silyl Ketene Acetalsmentioning

confidence: 99%

Transition Metal-Catalyzed Direct Arylation of Substrates with Activated sp³-Hybridized C−H Bonds and Some of Their Synthetic Equivalents with Aryl Halides and Pseudohalides

2009

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“…Unexpectedly, the dichlorocyclopropano derivative ( 12 ) could not be detected in the reaction. However, a formyl group was built in at position 10, resulting in 10-formylvindoline ( 13 ), a compound that is already known in the literature [20,21,22]. …”

Section: Resultsmentioning

confidence: 99%

Attempted Synthesis of Vinca Alkaloids Condensed with Three-Membered Rings

Keglevich

Mayer

Pápai³

et al. 2018

Molecules

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Our successful work for the synthesis of cyclopropanated vinblastine and its derivatives by the Simmons–Smith reaction was followed to build up further three-membered rings into the 14,15-position of the vindoline part of the dimer alkaloid. Halogenated 14,15-cyclopropanovindoline was prepared by reactions with iodoform and bromoform, respectively, in the presence of diethylzinc. Reactions of dichlorocarbene with vindoline resulted in the 10-formyl derivative. Unexpectedly, in the case of the dimer alkaloids vinblastine and vincristine, the rearranged products containing an oxirane ring in the catharanthine part were isolated from the reactions. The attempted epoxidation of vindoline and catharanthine also led to anomalous rearranged products. In the epoxidation reaction of vindoline, an o-quinonoid derivative was obtained, in the course of the epoxidation of catharanthine, a hydroxyindolenine type product and a spiro derivative formed by ring contraction reaction, were isolated. The coupling reaction of vindoline and the spiro derivative obtained in the epoxidation of catharanthine did not result in a bisindole alkaloid. Instead, two surprising vindoline trimers were discovered and characterized by NMR spectroscopy and mass spectrometry.

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Synthesis of C-15 Vindoline Analogues by Palladium-Catalyzed Cross-Coupling Reactions

Cited by 35 publications

References 36 publications

Palladium-Catalyzed Suzuki−Miyaura Cross-Coupling Reactions Employing Dialkylbiaryl Phosphine Ligands

Palladium-Catalyzed Suzuki−Miyaura Cross-Coupling Reactions Employing Dialkylbiaryl Phosphine Ligands

Transition Metal-Catalyzed Direct Arylation of Substrates with Activated sp³-Hybridized C−H Bonds and Some of Their Synthetic Equivalents with Aryl Halides and Pseudohalides

Attempted Synthesis of Vinca Alkaloids Condensed with Three-Membered Rings

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Synthesis of C-15 Vindoline Analogues by Palladium-Catalyzed Cross-Coupling Reactions

Cited by 35 publications

References 36 publications

Palladium-Catalyzed Suzuki−Miyaura Cross-Coupling Reactions Employing Dialkylbiaryl Phosphine Ligands

Palladium-Catalyzed Suzuki−Miyaura Cross-Coupling Reactions Employing Dialkylbiaryl Phosphine Ligands

Transition Metal-Catalyzed Direct Arylation of Substrates with Activated sp3-Hybridized C−H Bonds and Some of Their Synthetic Equivalents with Aryl Halides and Pseudohalides

Attempted Synthesis of Vinca Alkaloids Condensed with Three-Membered Rings

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Transition Metal-Catalyzed Direct Arylation of Substrates with Activated sp³-Hybridized C−H Bonds and Some of Their Synthetic Equivalents with Aryl Halides and Pseudohalides