Ring walking as a regioselectivity control element in Pd-catalyzed C-N cross-coupling

Deem, Madeleine C.; Derasp, Joshua S.; Malig, Thomas C.; Legard, Kea; Berlinguette, Curtis P.; Hein, Jason E.

doi:10.1038/s41467-022-30255-1

Cited by 18 publications

(31 citation statements)

References 48 publications

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“…For example, Larosa et al found that IPent enables efficient “exhaustive arylation” of various dihalogenated arenes despite a deficit of nucleophile . Further, Hein et al have reported that both IPr and RuPhos are effective di- or polyamination catalysts for regioselective elaborations of tetrabromospirobifluorenes . When a monofunctionalized product is desired, competitive overarylation detracts from the yield, in part because diarylated products can be challenging to separate from monofunctionalized product.…”

Section: Discussionmentioning

confidence: 99%

The Road Less Traveled: Unconventional Site Selectivity in Palladium-Catalyzed Cross-Couplings of Dihalogenated N-Heteroarenes

Norman

Neufeldt

2022

ACS Catal.

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The vast majority (≥90%) of literature reports agree on the regiochemical outcomes of Pd-catalyzed cross-coupling reactions for most classes of dihalogenated N-heteroarenes. Despite a well-established mechanistic rationale for typical selectivity, several examples reveal that changes to the catalyst can switch site selectivity, leading to the unconventional product. In this Perspective, we survey these unusual cases in which divergent selectivity is controlled by ligands or catalyst speciation. In some cases, the mechanistic origin of inverted selectivity has been established, but in others the mechanism remains unknown. This Perspective concludes with a discussion of remaining challenges and opportunities for the field of site-selective cross-coupling. These include developing a better understanding of oxidative addition mechanisms, understanding the role of catalyst speciation on selectivity, establishing an explanation for the influence of ring substituents on regiochemical outcome, inverting selectivity for some “stubborn” classes of substrates, and minimizing unwanted over-reaction of di- and polyhalogenated substrates.

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Section: Discussionmentioning

confidence: 99%

The Road Less Traveled: Unconventional Site Selectivity in Palladium-Catalyzed Cross-Couplings of Dihalogenated N-Heteroarenes

Norman

Neufeldt

2022

ACS Catal.

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“…Characterization is consistent with that in the literature. 20 1 H NMR (400 MHz, THF): δ 7.58–7.46 (m, 3H), 7.39 (dd, J = 8.1, 1.8 Hz, 1H), 7.04 (dd, J = 9.2, 2.1 Hz, 5H), 6.88–6.80 (m, 5H), 3.76 (s, 6H), 1.36 (s, 6H). 13 C{ 1 H} NMR (101 MHz, THF): δ 157.2, 156.6, 155.6, 150.1, 142.1, 139.6, 131.7, 130.8, 127.3, 126.8, 121.5, 121.29, 120.9, 120.2, 115.7, 115.5, 55.6, 47.8, 27.2.…”

Section: Methodsmentioning

confidence: 99%

“…Characterization is consistent with that in the literature. 20 1 H NMR (400 MHz, THF): δ 7.39 (d, J = 8.3 Hz, 3H), 7.03 (d, J = 9.0 Hz, 8H), 6.82 (d, J = 9.0 Hz, 8H), 3.74 (s, 16H), 1.28 (s, 6H). 13 C{ 1 H} NMR (101 MHz, THF): δ 156.9, 155.5, 148.5, 142.5, 133.5, 126.9, 121.3, 120.3, 116.5, 115.4, 55.6, 47.3, 27.5.…”

Section: Methodsmentioning

confidence: 99%

“…The time course data show the formation of the monoaminated intermediate ( 5 ) before the diaminated product ( 6 ) (Figure ). The time course reaction profile of this reaction has been previously reported, but the treatment of the data is novel …”

Section: What Is the Solver Tool?mentioning

confidence: 98%

“…The time course reaction profile of this reaction has been previously reported, but the treatment of the data is novel. 20 …”

Section: What Is the Solver Tool?mentioning

confidence: 99%

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A Method for Converting HPLC Peak Area from Online Reaction Monitoring to Concentration Using Nonlinear Regression

Deem

Hein

2023

J. Org. Chem.

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Online HPLC reaction progress monitoring provides detailed data-rich profiles; however, extracting kinetic information requires ultraviolet–visible response factors to determine concentrations from peak areas. If the reaction’s overall mass balance is known and some analytical trend for all relevant species can be recorded, it is possible to estimate the absolute response factors of all species using a system of linear equations. We delineate a method using the Microsoft Solver plug-in to convert time course profiles to reagent concentrations without analytical standards.

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Octalithium, Tetrasodium, and Decalithium Compounds Based on Pyrrolyl Ligands: Synthesis, Structures, and Activation of the C–H Bonds of Pyrrolyl Rings and C═N Bonds of a Series of Ligands by Organolithium Reagents

Jia

She

et al. 2023

Inorg. Chem.

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The organometallic compounds of lithium ions have garnered continuous interest as indispensable precursors for the syntheses of organometallic complexes of main-group metals, transition metals, lanthanide metals, and actinide metals. In this work, we present a strategy for the preparation of a series of polynuclear lithium complexes. This methodology features the utilization of organolithium reagents both as metal sources to coordinate with the ligands and as nucleophilic reagents to undergo nucleophilic addition to the C�N bonds of the ligands. Reaction of a ligand HL1amino)phenol]. One prominent feature regarding the formation of 1•1.5Tol is the occurrence of nucleophilic addition of n-BuLi to the C�N bond of HL1, leading to the generation of a new [L1a] 2− ligand that contains both aminophenol and 1-(2-pyrrolyl)alkylamine scaffolds. The developed protocol can be adapted to a series of organolithium reagents. Compounds [Li 8 (L1b) 4 ] (2) and [Li 8 (L1c) 4 ] (3) were afforded by treatment of HL1 with sec-BuLi and LiCH 2 SiMe 3 , respectively. Reaction of an analogous ligand HL2 [HL2 = 2-(((1-(2-(dimethylamino)ethyl)-1H-pyrrol-2yl)methylene)amino)-4-methylphenol] with n-BuLi generated compound [Li 8 (L2a) 4 ] ( 4). C�N bond activation was not observed in the reaction of HL1 with NaO t Bu, and the complex [Na 4 (L1) 4 ]•Tol (5•Tol) was obtained. A decanuclear complex [Li 10 (L3a) 2 (L3b) 2 ] (6) was also prepared via the reaction of HL3 [HL3 = 2-(2-((((1H-pyrrol-2-yl)methylene)amino)methyl)-1Hpyrrol-1-yl)-N,N-dimethylethan-1-amine] with t-BuLi. A remarkable feature in terms of the synthesis of 6 is the simultaneous occurrence of hydrogen atom abstraction from the C−H bond of the pyrrolyl ring and nucleophilic addition to the C�N bond of the HL3 ligand by t-BuLi. A series of amines containing biologically and physiologically important moieties were achieved by hydrolysis of the crude products from the reactions of the HL1−HL3 ligands and organolithium reagents. This work provides an efficient approach to high-nuclearity lithium compounds as well as a series of amines.

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Ring walking as a regioselectivity control element in Pd-catalyzed C-N cross-coupling

Cited by 18 publications

References 48 publications

The Road Less Traveled: Unconventional Site Selectivity in Palladium-Catalyzed Cross-Couplings of Dihalogenated N-Heteroarenes

The Road Less Traveled: Unconventional Site Selectivity in Palladium-Catalyzed Cross-Couplings of Dihalogenated N-Heteroarenes

A Method for Converting HPLC Peak Area from Online Reaction Monitoring to Concentration Using Nonlinear Regression

Octalithium, Tetrasodium, and Decalithium Compounds Based on Pyrrolyl Ligands: Synthesis, Structures, and Activation of the C–H Bonds of Pyrrolyl Rings and C═N Bonds of a Series of Ligands by Organolithium Reagents

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