Article
Chemistry, Multidisciplinary
William G. Whitehurst, Junho Kim, Stefan G. Koenig, Paul J. Chirik
Summary: Cationic bis(phosphine) cobalt (III) metallacycle complexes with five and six coordination were successfully synthesized, which exhibited high selectivity towards ortho-alkylated products in C(sp2)-H activation reactions. The direct observation of C-H activation by cobalt(III) metallacycles provided experimental support for their role as intermediates in catalytic C-H functionalization reactions, and deuterium labeling and kinetic studies further revealed the nature of C-H bond cleavage and C-C bond reductive elimination from isolable cobalt(III) precursors.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Physical
Connor S. MacNeil, Hongyu Zhong, Tyler P. Pabst, Michael Shevlin, Paul J. Chirik
Summary: The cobalt-catalyzed asymmetric hydrogenation of dehydro-sitagliptin was studied and applied to the synthesis of sitagliptin. The discovery of catalysts was accelerated by the synthesis of cationic bis(phosphine) cobalt eta 6-arene complexes. The optimal catalyst showed high yield and enantioselectivity, and maintained excellent activity and selectivity after standing in air for 2 weeks.
Article
Chemistry, Multidisciplinary
Shreemoyee Kumar, Akshay M. Nair, Chandra M. R. Volla
Summary: This study reported the Ru(ii)-catalyzed C(sp(2))-H arylation of N-tosylbenzamides to access multi-substituted allenylamides, which were further converted to isoquinolone derivatives via base mediated annulation. The protocol features low catalyst loading, mild reaction conditions, high functional group compatibility, and scalability. The unique functionality of the produced allenes allowed for further transformations, expanding the practicality of the protocol.
CHEMICAL COMMUNICATIONS
(2021)
Article
Chemistry, Organic
Guoxiang Zhang, Hui He, Xiaoxiao Chen, Shao-Fei Ni, Rong Zeng
Summary: Here, we demonstrate an efficient catalytic system for the intermolecular anti-Markovnikov hydrophosphinylation of olefins using disulfide as a photocatalyst and a hydrogen atom shuttle. This metal-free, base-free, and redox-neutral condition allows alkenes with diverse electronic properties to efficiently proceed with the anti-Markovnikov P-H addition. A plausible mechanism involving the hydrogen atom transfer process between ArS and P(O)-H is proposed.
Article
Chemistry, Organic
Yunlong Li, Wenchao Jiang, Jie Lin, Juan Ma, Bao-Hua Xu, Yong-Gui Zhou, Zhengkun Yu
Summary: In this study, triple C-H bond activation of aryl enaminones was achieved to access naphtho[1,8-bc]pyrans through oxidative annulation. Depending on the steric and/or electronic environment around the aryl moiety of the enaminones or the electronic impact from the alkynes, 1-naphthols might be formed as the sole products. By using propargyl alcohols as masked terminal alkynes, functionalized but-2-ene-1,4-diones were obtained through rhodium(III)- or rhodium(I)-catalyzed internal alkenyl C-H bond activation. The resulting naphtho[1,8-bc]pyrans exhibited high fluorescence and could be further transformed by chlorination, bromination, and difluoromethylation, demonstrating the potential applicability of the synthetic protocol.
Article
Chemistry, Inorganic & Nuclear
Michael P. Bubnov, Alexey Zolotukhin, Konstantin A. Kozhanov, Evgeny V. Baranov, Artem S. Bogomyakov, Maxim V. Arsenyev, Sergey Yu. Ketkov, Vladimir K. Cherkasov
Summary: Three novel five-coordinated bisdioxolene cobalt complexes with triphenylphosphine were synthesized. These complexes have similar geometry and magnetic properties, but different dioxolene ligands. DFT calculations correctly predict the structures and spectroscopic properties of the complexes.
Article
Chemistry, Organic
Vincenzo Marsicano, Antonio Arcadi, Massimiliano Aschi, Marco Chiarini, Giancarlo Fabrizi, Antonella Goggiamani, Fabio Marinelli, Antonia Iazzetti
Summary: Experimental results and computational insights explain the key role of transition-metal catalysis/Bronsted acid synergism in the sequential regioselective direct heteroarylation/cyclocondensation reactions. These reactions can afford quinoline-(hetero)aromatic hybrids by reacting beta-(2-aminophenyl)-alpha,beta-ynones with various electron-rich aromatic heterocyclic/arenes. The first synthesis approach to 4-(1H-pyrrol-2-yl)quinolines is described and the effectiveness of different transition metals is compared.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Han Gao, Wujie Wang, Xiangying Lv, Gang Lu, Yuliang Li
Summary: The mechanism of Co(iii)-catalyzed annulation of N-chlorobenzamide with styrene was computationally studied, focusing on the effects of chiral cyclopentadienyl (Cp) ligands on enantioselectivity using energy decomposition analysis (EDA). The study revealed a spin-crossover event of Co complexes in the computed energy profile, with the triplet state of Co species being favored in most intermediates and transition states. The irreversible styrene migratory insertion was identified as the enantioselectivity-determining step, with steric effects being the dominant factor for high-level enantiocontrol, emphasizing the importance of additional bulky substituents on the Cp ring of trisubstituted BINOL-Cp ligands.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Multidisciplinary
Chu-Xia Han, Zi-Mo Shao, Li Li, Kun Zhou, Chun-Hui Xue, Bao-Kuan Chen, Jiu-Yu Ji, Yan-Feng Bi
Summary: Three trinuclear silver nanoclusters with different structures were synthesized and characterized, indicating that their properties are influenced by the structure, providing guidance for further design and synthesis of functional silver cluster materials.
NEW JOURNAL OF CHEMISTRY
(2021)
Article
Chemistry, Organic
Chikkabagilu Nagaraju Shambhavi, Masilamani Jeganmohan
Summary: This article describes a Ru(II)-catalyzed C-H alkenylation of benzimidates with unactivated alkenes, providing ortho-alkenylated benzonitriles with high regio- and stereoselectivity. The imidate group was converted into a nitrile under the reaction conditions. The alkenylation reaction was compatible with various substituted benzimidates and functionalized unactivated olefins, including ibuprofen, neproxen, coumarin, and cholesterol-substituted alkenes. A feasible reaction mechanism was proposed to explain the alkenylation reaction in this study.
Article
Chemistry, Organic
Jing Jiang, Dandan Yuan, Congzhe Ma, Wanbin Song, Yaoyu Lin, Lihong Hu, Yinan Zhang
Summary: An efficient divergent approach of Pd-catalyzed C-H oxygenation of polyaromatic rings is described, utilizing reversible directing groups to achieve regiospecific oxygenation. Mechanistic investigation, including deuterium-labeling experiments and DFT calculations, reveals the crucial role of tunable ligand-assisted C-H bond cleavage during the reaction process.
Article
Chemistry, Organic
Fabian Seifert, Denis Drikermann, Johannes Steinmetzer, You Zi, Stephan Kupfer, Ivan Vilotijevic
Summary: Phosphine-mediated reductions of substituted propynoic esters and amides in the presence of water yield partially reduced alpha,beta-unsaturated esters and amides with high Z-selectivity, but the competitive in situ Z to E-isomerization of the product may reduce Z to E ratios of the isolated alpha,beta-unsaturated carbonyl products. Key experimental factors controlling selectivity include reaction time and the amounts of phosphine and water.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Review
Chemistry, Multidisciplinary
Daniel S. Brandes, Jonathan A. Ellman
Summary: Sequential multicomponent C-H bond addition is a powerful approach for the rapid generation of complex molecules. This approach involves adding C-H bonds across pi-bonds or pi-bond isosteres and coupling them with another type of functionality to form two sigma-bonds in a single reaction sequence. These atom-economical reactions transform ubiquitous C-H bonds into more complex structures with precise control over regiochemical and stereochemical properties. The development of these reactions has revealed surprising connectivities and diverse mechanisms. The vast number of possible coupling partners offers significant opportunities for the discovery of new sequential C-H bond addition reactions.
CHEMICAL SOCIETY REVIEWS
(2022)
Article
Chemistry, Organic
Maneesh Kumar Reddy Singam, Undamatla Suri Babu, Vavilapalli Suresh, Jagadeesh Babu Nanubolu, Maddi Sridhar Reddy
Summary: This study presents a simple and practical method for the synthesis of isochromenones through dual activation, which does not require the use of oxidants, exhibits a wide substrate scope, and has good functional group tolerance.
Article
Chemistry, Inorganic & Nuclear
Sebastian Scharf, Sebastian Notz, Janine Jeschke, Andrea Preuss, Tobias Rueffer, Alexander Wiese, Andy Kuenzel-Tenner, Steffen Schulze, Michael Hietschold, Heinrich Lang
Summary: This study discusses the synthesis of [M(O2CCH2(OCH2CH2)nOMe)2(PR3)2] complexes and their thermal decomposition. The structures of the complexes in the solid state were determined by X-ray crystallography, revealing trans or cis configurations of the ligands. Thermal decomposition of the complexes led to the formation of metal nanoparticles. The Pd nanoparticles exhibited good catalytic performance in the Suzuki-Miyaura C,C cross-coupling reaction, while the Pt nanoparticles showed minor activity in the hydrosilylation reaction.
Article
Chemistry, Multidisciplinary
Gabriele Hierlmeier, Paolo Tosatti, Kurt Puentener, Paul J. J. Chirik
Summary: This study reports a new molybdenum ligand for catalyzing the hydrogenation of benzene, which is formed by the coordination of phosphino(imino)pyridine and cyclooctadiene. The experimental results indicate that the ligand can selectively generate cyclohexane catalyst in the presence of benzene, and the formation of the insertion product is a key step.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Physical
Paul O. Peterson, Matthew Joannou, Eric M. Simmons, Steven R. Wisniewski, Junho Kim, Paul J. Chirik
Summary: The synthesis and characterization of phenoxy(imine) iron(II) alkyl precatalysts for C(sp2)-C(sp3) Suzuki-Miyaura cross-coupling reaction is reported. This method utilizes mild alkoxide bases and nonpolar solvents to achieve high efficiency C(sp2)-C(sp3) bond formation with various aryl boronic esters and alkyl bromides. The study also highlights the compatibility of the precatalysts with base-sensitive functionality and the role of boronate intermediates in transmetalation.
Article
Chemistry, Organic
Lauren N. Mendelsohn, Connor S. MacNeil, Madison R. Esposito, Tyler P. Pabst, David K. Leahy, Ian W. Davies, Paul J. Chirik
Summary: The cobalt-catalyzed asymmetric hydrogenation of indazole-containing enamides relevant to the synthesis of Zavegepant, a CGRP receptor antagonist, which is approved for the treatment of migraines, is described. Both neutral and cationic bis(phosphine)cobalt complexes were efficient precatalysts, providing excellent yield and enantioselectivities for related substrates, with key reactivity differences observed. The hydrogenation of the indazole-containing enamide was successfully scaled up to 20 g.
Article
Chemistry, Applied
Paul J. Chirik, Keary M. Engle, Eric M. Simmons, Steven R. Wisniewski
Summary: Earth-abundant metal (EAM) catalysis has significant impact on the sustainability and cost improvement in the pharmaceutical industry. It replaces precious metals like palladium and utilizes the reactivity of first-row metals to enable more efficient routes to clinical candidates. This article describes the strategy for building these capabilities within the process group, including the development of a reaction screening platform, scalability demonstration, and increasing mechanism understanding.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2023)
Article
Chemistry, Inorganic & Nuclear
Boran Lee, Tyler P. Pabst, Gabriele Hierlmeier, Paul J. Chirik
Summary: Cobalt complexes with 2,6-diaminopyridinesubstituted PNP pincer ligand were synthesized and studied. The PNP pincer ligand showed higher rigidity and electron-donating properties compared to the iPrPNP ligand. The coordination sphere of the metal was completed by a fourth ligand, resulting in planar, diamagnetic, four-coordinate complexes. Computational studies indicated that the increased rigidity of the pincer ligand led to a higher barrier for C-H oxidative addition. The reduced reactivity of (iPrPNMeNP)CoMe enabled it to be an efficient precatalyst for alkene hydroboration.
Article
Chemistry, Multidisciplinary
L. Reginald Mills, Francesca Di Mare, David Gygi, Heejun Lee, Eric M. Simmons, Junho Kim, Steven R. Wisniewski, Paul J. Chirik
Summary: The relative rates of the cobalt-catalyzed C(sp(2))-C(sp(3)) Suzuki-Miyaura cross-coupling were evaluated, and it was found that smaller N-alkyl substituents on the phenoxyimine ligand accelerated the reaction. This inspired the design of optimal cobalt catalysts with phenoxyoxazoline and phenoxythiazoline ligands. The catalyst lifetime was improved by adding excess KOMe•B(O-iPr)3, which attenuated alkoxide basicity and prevented demetallation of the ligand.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Gabriele Hierlmeier, Paolo Tosatti, Kurt Puentener, Paul J. Chirik
Summary: This study describes the synthesis of phosphino(oxazoline)pyridine-supported molybdenum(0) cycloocta-1,5-diene complexes and their reactions with dihydrogen and arenes. The study found that the site selectivity of arene insertion reactions depended on the size of the substituent, and electron-rich arenes had faster insertion rates. Additionally, through mechanistic studies, the synthesis of enantioenriched cyclohexa-1,3-diene was achieved.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
L. Reginald Mills, David Gygi, Eric M. Simmons, Steven R. Wisniewski, Junho Kim, Paul J. Chirik
Summary: The mechanism of phenoxyimine (FI)-cobalt-catalyzed C(sp(2))-C(sp(3)) Suzuki-Miyaura cross-coupling was studied using kinetic measurements and catalytic and stoichiometric experiments. Dimeric (FI) cobalt(II) bromide complexes were isolated and characterized, and one complex was used as a single-component precatalyst for the cross-coupling reaction. The involvement of boronate intermediates in transmetalation was confirmed by Hammett studies of aryl boronic esters. A cobalt(II)/cobalt(III) catalytic cycle was proposed that proceeds through a boronate-type mechanism.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Inorganic & Nuclear
Coralie Duchemin, Amelia I. Liu, Junho Kim, Paul J. Chirik
Summary: This study describes the synthesis, characterization, and reactivity of a series of quinoline pyridine(imine) iron dichloride complexes. The complexes were found to be effective catalysts for the hydrovinylation reaction of butadiene with ethylene, showing high selectivity for the hexa-1,4-diene isomer.
Article
Chemistry, Multidisciplinary
Coralie Duchemin, Junho Kim, Paul J. J. Chirik
Summary: A series of C-S-symmetric (aryl,alkyl)-substituted pyridine(dimine) iron methyl ((Cy)ARPDI)FeCH3 complexes have been synthesized and used as precatalysts for [2+2] cycloaddition. The chemoselectivity of the reaction is affected by the stability and resting state of the catalyst, leading to the formation of vinylcyclobutane and (Z)-hexa-1,4-diene.
Article
Chemistry, Inorganic & Nuclear
Junho Kim, Yoonsu Park, Paul J. Chirik
Summary: Piano-stool iridium hydride complexes with phenylpyridine ligands are effective in promoting element-hydrogen bond formation using H-2 as a H-atom source. Blue light irradiation enhances the catalyst turnover for iridium-catalyzed hydrogenation of aryloxyl radicals. The reaction involves proton-coupled electron transfer and formation of an iridium compound. Blue light irradiation with H-2 releases a free heterocycle and regenerates the iridium hydride precatalyst, leading to increased turnover.
INORGANIC CHEMISTRY
(2023)
