2019

33. Nickel-catalyzed exo-selective hydroacylation/Suzuki cross-coupling reaction

Shao-Chi Lee, Lin Guo and Magnus Rueping

Chem. Commun., 2019, 55, 14984-14987

ABSTRACT:

The first nickel-catalyzed intramolecular hydroacylation/Suzuki cross coupling cascade of o-allylbenzaldehydes with a broad range of phenylboronic acid neopentyl glycol esters has been developed. This strategy shows high regioselectivity and step economy in the construction of two C–C bonds via aldehyde C–H bond activation, affording valuable indanones with high efficiency.

32. Asymmetric Hydroboration of Heteroaryl Ketones by Aluminum Catalysis

Yury Lebedev, Iuliia Polishchuk, Bholanath Maity, Miguel Dinis Veloso Guerreiro, Luigi Cavallo, and Magnus Rueping

J. Am. Chem. Soc. 2019, 141, 19415-19423

ABSTRACT:

A series of methyl aluminum complexes bearing chiral biphenol-type ligands were found to be highly active catalysts in the asymmetric reduction of heterocyclic ketones (S/C = 100–500, ee up to 99%). The protocol is suitable for a wide range of substrates and has a high tolerance to functional groups. The formed 2-heterocyclic-alcohols are valuable building blocks in drug discovery or can be used as ligands in asymmetric catalysis. Isolation and comprehensive characterization of the reaction intermediates support a catalysis cycle proposed by DFT calculations.

31. Nickel-Catalyzed Synthesis of Silanes from Silyl Ketones

Watchara Srimontree, Waranya Lakornwong, and Magnus Rueping

Org. Lett. 2019, 21, 9330-9333

ABSTRACT:

An unprecedented nickel-catalyzed decarbonylative silylation via CO extrusion intramolecular recombination fragment coupling of unstrained and nondirecting group-assisted silyl ketones is described. The inexpensive and readily available catalyst performs under mild reaction conditions and enables the synthesis of structurally diverse arylsilanes, including heterocyclic and natural product derivatives.

30. Robust and Versatile Host Protein for the Design and Evaluation of Artificial Metal Centers

Johannes Fischer, Dominik Renn, Felix Quitterer, Anand Radhakrishnan, Meina Liu, Arwa Makki, Seema Ghorpade, Magnus Rueping, Stefan T. Arold, Michael Groll, and Jörg Eppinger

ACS Catal. 2019, 9, 11371-11380

ABSTRACT:

Artificial metalloenzymes (ArMs) have high potential in biotechnological applications as they combine the versatility of transition-metal catalysis with the substrate selectivity of enzymes. An ideal host protein should allow high-yield recombinant expression, display thermal and solvent stability to withstand harsh reaction conditions, lack nonspecific metal-binding residues, and contain a suitable cavity to accommodate the artificial metal site. Moreover, to allow its rational functionalization, the host should provide an intrinsic reporter for metal binding and structural changes, which should be readily amendable to high-resolution structural characterization. Herein, we present the design, characterization, and de novo functionalization of a fluorescent ArM scaffold, named mTFP*, that achieves these characteristics. Fluorescence measurements allowed direct assessment of the scaffold’s structural integrity. Protein X-ray structures and transition metal Förster resonance energy transfer (tmFRET) studies validated the engineered metal coordination sites and provided insights into metal binding dynamics at the atomic level. The implemented active metal centers resulted in ArMs with efficient Diels–Alderase and Friedel–Crafts alkylase activities.

29. Reduction of Cyclic and Linear Organic Carbonates Using a Readily Available Magnesium Catalyst

Marcin Szewczyk, Marc Magre, Viktoriia Zubar, and Magnus Rueping

ACS Catal. 2019, 9, 11634-11639

ABSTRACT:

Efficient reduction of cyclic and linear organic carbonates catalyzed by a readily available earth alkaline catalyst has been achieved. The described homogenous reaction based on a ligand-free magnesium catalyst provides an indirect route for the conversion of CO2 into valuable alcohols. The reaction proceeds with high yields under mild reaction conditions, with low catalyst loading and short reaction times, and shows a broad applicability toward various linear and cyclic carbonates. Additionally, it can be applied for the depolymerization of polycarbonates.

28. Chemo- and Regioselective Magnesium-Catalyzed ortho-Alkenylation of Anilines

Adisak Chatupheeraphat, Magnus Rueping, and Marc Magre

Org. Lett. 2019, 21, 9153-9157

ABSTRACT:

A simple and efficient catalytic system for a chemo- and regioselective ortho-alkenylation of anilines is presented. The new magnesium-catalyzed reaction allows the use of a wide range of alkynes and anilines with different electronic and steric properties and provides free as well as protected anilines with excellent yields.

27. A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

Munmun Ghosh, Valmik S. Shinde and Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746

ABSTRACT:

The direct exploitation of ‘electrons’ as reagents in synthetic organic transformations is on the verge of a renaissance by virtue of its greenness, sustainability, atom economy, step economy and inherent safety. Achieving stereocontrol in such organic electrochemical reactions remains a major synthetic challenge and hence demands great expertise. This review provides a comprehensive discussion of the details of stereoselective organic electrochemical reactions along with the synthetic accomplishments achieved with these methods.

26. Anchorene is a carotenoid-derived regulatory metabolite required for anchor root formation in Arabidopsis

Kun-Peng Jia, Alexandra J. Dickinson, Jianing Mi, Guoxin Cui, Ting Ting Xiao, Najeh M. Kharbatia, Xiujie Guo, Erli Sugiono, Manuel Aranda, Ikram Blilou, Magnus Rueping, Philip N. Benfey and Salim Al-Babili

Sci. Adv. 2019, 5, eaaw6787

ABSTRACT:

Anchor roots (ANRs) arise at the root-shoot junction and are the least investigated type of Arabidopsis root. Here, we show that ANRs originate from pericycle cells in an auxin-dependent manner and a carotenogenic signal to emerge. By screening known and assumed carotenoid derivatives, we identified anchorene, a presumed carotenoid-derived dialdehyde (diapocarotenoid), as the specific signal needed for ANR formation. We demonstrate that anchorene is an Arabidopsis metabolite and that its exogenous application rescues the ANR phenotype in carotenoid-deficient plants and promotes the growth of normal seedlings. Nitrogen deficiency resulted in enhanced anchorene content and an increased number of ANRs, suggesting a role of this nutrient in determining anchorene content and ANR formation. Transcriptome analysis and treatment of auxin reporter lines indicate that anchorene triggers ANR formation by modulating auxin homeostasis. Together, our work reveals a growth regulator with potential application to agriculture and a new carotenoid-derived signaling molecule.

25. Asymmetric Magnesium‐Catalyzed Hydroboration by Metal‐Ligand Cooperative Catalysis

Alban Falconnet, Marc Magre, Bholanath Maity, Luigi Cavallo, Magnus Rueping

Angew. Chem. Int. Ed. 2019, 58, 17567-17571

ABSTRACT:

Asymmetric catalysis with readily available, cheap, and non-toxic alkaline earth metal catalysts represents a sustainable alternative to conventional synthesis methodologies. In this context, we describe the development of a first MgII-catalyzed enantioselective hydroboration providing the products with excellent yields and enantioselectivities. NMR spectroscopy studies and DFT calculations provide insights into the reaction mechanism and the origin of the enantioselectivity which can be explained by a metal-ligand cooperative catalysis pathway involving a non-innocent ligand.

24. Chemoselective Luche-Type Reduction of α,β-Unsaturated Ketones by Magnesium Catalysis

Yoon Kyung Jang, Marc Magre, and Magnus Rueping

Org. Lett. 2019, 21, 8349-8352

ABSTRACT:

The chemoselective reduction of α,β-unsaturated ketones by use of an economic and readily available Mg catalyst has been developed. Excellent yields for a wide range of ketones have been achieved under mild reaction conditions, short times, and low catalyst loadings (0.2–0.5 mol %).

ABSTRACT:

A mild, environment-friendly protocol has been developed to carry out the [4+2] annulation of aryl amides with unactivated olefins. A range of sterically and electronically diverse aryl amides and unactivated olefins were successfully employed under the developed conditions to get a variety of dihydroisoquinolinones in good-to-excellent yields.

ABSTRACT:

The Pyrrolysyl-tRNA synthetase (PylRS) and its cognate tRNAPyl are extensively used to add non-canonical amino acids (ncAAs) to the genetic code of bacterial and eukaryotic cells. However, new ncAAs often require a cumbersome de novo engineering process to generate an appropriate PylRS/tRNAPyl pair. We here report a strategy to predict a PylRS variant with novel properties. The designed polyspecific PylRS variant HpRS catalyzes the aminoacylation of 31 structurally diverse ncAAs bearing clickable, fluorinated, fluorescent, and for the first time biotinylated entities. Moreover, we demonstrated a site-specific and copper-free conjugation strategy of a nanobody by the incorporation of biotin. The design of polyspecific PylRS variants offers an attractive alternative to existing screening approaches and provides insights into the complex PylRS-substrate interactions.

ABSTRACT:

The superoxide (O2•–) ion is a highly reactive oxygen species involved in many diseases; hence, its noninvasive detection is desirable to identify the onset of pathological processes. Here, we employed photoacoustic (PA) spectroscopy, which enables imaging at ultrasound resolution with the sensitivity of optical modality, for the first time to detect O2•–, using stimuli-responsive contrast agents. meso-(3,5-Di-tert-butyl 4-hydroxyphenyl) porphyrins and oxoporphyrinogens were used as PA contrast agents, which trap the O2•– and enable its detection. The trapped O2•– increased the PA signal amplitude of chromophores up to 9.6-fold, and induced a red-shift in the PA signal maxima of up to 225 nm. Therefore, these trigger-responsive probes may be highly valuable as smart diagnostic PA probes to investigate pathological events stimulated by O2•– species.

ABSTRACT:

Unsaturated carbon–carbon bonds are one of the most common and important structural motifs in many organic molecules, stimulating the continuous development of general, efficient and practical strategies for their functionalization. Here, we report a one-pot difunctionalization of alkynes via a photoredox/nickel dual-catalysed three-component cross-coupling reaction under mild conditions, providing access to a series of highly important tri-substituted alkenes. Notably, in contrast to traditional methods that are based on the steric hindrance of the substrates to control the reaction selectivity, both E- and Z-isomers of tri-substituted alkenes, which are often energetically close, can be obtained by choosing an appropriate photocatalyst with a suitable triplet state energy. Beyond the immediate practicality of this transformation, this newly developed methodology might inspire the development of diverse and important one-pot functionalizations of carbon–carbon multiple bonds via photoredox and transition-metal dual-catalysed multicomponent reactions.

ABSTRACT:

The application of heterogeneous semiconductors as catalysts for C–H functionalization reactions is presented. Visible light enables electron transfer processes for transition metal catalyzed olefination reactions providing important synthesis core structures in generally good yields. The methodology provides an elegant and sustainable alternative to otherwise stoichiometrically applied transition metal additives.

ABSTRACT:

The hydrogenation of carbonyl compounds over a solid Pd/C catalyst to the corresponding alcohols and of N-heterocycles over a solid Ir@CNT catalyst to the corresponding amines with gaseous hydrogen from water electrolysis without human interaction is presented. This is achieved in three-dimensional parameter space (flow rate, temperature and hydrogen pressure) through an integration of inline FTIR-analysis, a simplex control algorithm and an H-Cube microreactor setup. The simplex method can cope with an initial transient behaviour which is characteristic for heterogeneous catalysis.

ABSTRACT:

The cyclization of acetanilides with alkyne derivatives has been accomplished via a direct C–H functionalization/cyclization pathway in the presence of a photoredox catalyst. The combination of a readily available Rh(III) and photoredox catalyst under irradiation with 11 W CFL afforded not only indoles but also pyrrole derivatives in good yields. Mechanistic studies provide evidence for the independent role of each catalyst. In addition, a similar efficiency of the cyclization reaction was achieved with a heterogeneous photoredox catalyst.

ABSTRACT:

The biotin–streptavidin interaction is among the strongest known in nature. Herein, the site-directed incorporation of biotin and 2-iminobiotin composed of noncanonical amino acids (ncAAs) into proteins is reported. 2-Iminobiotin lysine was employed for protein purification based on the pH-dependent dissociation constant to streptavidin. By using the high-affinity binding of biotin lysine, the bacterial protein RecA could be specifically isolated and its interaction partners analyzed. Furthermore, the biotinylation approach was successfully transferred to mammalian cells. Stringent control over the biotinylation site and the tunable affinity between ncAAs and streptavidin of the different biotin analogues make this approach an attractive tool for protein interaction studies, protein immobilization, and the generation of well-defined protein–drug conjugates.

ABSTRACT:

A new base metal catalyzed sustainable multicomponent synthesis of pyrroles from readily available substrates is reported. The developed protocol utilizes an air- and moisture-stable catalyst system and enables the replacement of themutagenic α-haloketones with readily abundant 1,2-diols. Moreover, the presented method is catalytic in base and the sole byproducts of this transformation are water and hydrogen gas. Experimental and computational mechanistic studies indicate that the reaction takes place through a combined acceptorless dehydrogenation hydrogen autotransfer methodology.

ABSTRACT:

A new Mn-catalyzed alkylation of secondary alcohols with non-activated alcohols is presented. The use of a stable and well-defined manganese pincer complex, stabilized by a PNN ligand, together with a catalytic amount of base enabled the conversion of renewable alcohol feedstocks to a broad range of higher-value alcohols in good yields with water as the sole byproduct. The strategy eliminates the need for exogenous and detrimental alkyl halides as well as the use of noble metal catalysts, making the C-alkylation through double hydrogen autotransfer a highly sustainable and environmentally benign process. Mechanistic investigations support a hydrogen autotransfer mechanism in which a non-innocent ligand plays a crucial role.

ABSTRACT:

A general and chemoselective catalytic alkylation of nitriles using a homogeneous nonprecious manganese catalyst is presented. This alkylation reaction uses naturally abundant alcohols and readily available nitriles as coupling partners. The reaction tolerates a wide range of functional groups and heterocyclic moieties, efficiently providing useful cyanoalkylated products with water as the only side product. Importantly, methanol can be used as a C1 source and the chemoselective C-methylation of nitriles is achieved. The mechanistic investigations support the multiple role of the metal–ligand manganese catalyst, the dehydrogenative activation of the alcohol, α-C–H activation of the nitrile, and hydrogenation of the in-situ-formed unsaturated intermediate.

ABSTRACT:

A hydrogen atom transfer-directed electrochemical intramolecular C−H amination has been developed in which the N-radical species are generated at the anode, and the base required for the reaction is generated at the cathode. A broad range of valuable pyrrolidines were prepared in good yields and with high chemoselectivity. The reaction was easily scaled up in both batch and continuous flow systems.

ABSTRACT:

A magnesium-catalyzed hydroboration of alkynes providing good yields and selectivities for a wide range of terminal and symmetrical and unsymmetrical internal alkynes has been developed. The compatibility with many functional groups makes this magnesium catalyzed procedure attractive for late stage functionalization. Experimental mechanistic investigations and DFT calculations reveal insights into the reaction mechanism of the magnesium catalyzed protocol.

ABSTRACT:

Transition-metal-catalyzed cross-couplings have been extensively used in the pharmaceutical and agrochemical industries for the construction of diverse C–C bonds. Conventional cross-coupling reactions require reactive electrophilic coupling partners, such as organohalides or sulfonates, which are not environmentally friendly and not naturally abundant. Another disadvantage associated with these transformations is the need for an exogenous base to facilitate the key transmetalation step, and this reagent inevitably induces side reactions and limits the substrate scope. Here, we report an unconventional Suzuki-type approach to the synthesis of biaryls, through nickel-catalyzed deformylative cross coupling of aldehydes with organoboron reagents under base-free conditions. The transformation tolerates structurally diverse (hetero)aryl substituents on both coupling partners and shows high reactivity and excellent functional group tolerance. Furthermore, the protocol was carried out on gram scale and successfully applied to the functionalization of complex biologically active molecules. Mechanistic investigations support a catalytic cycle involving the oxidative addition of the nickel into the aldehyde C(acyl)–H bond with subsequent hydride transfer, transmetalation, decarbonylation and reductive elimination processes.

ABSTRACT:

Nickel-catalyzed reductive cross coupling of activated primary amines with aryl halides under mild reaction conditions has been achieved for the first time. Due to the avoidance of stoichiometric organometallic reagents and external bases, the scope regarding both coupling partners is broad. Thus, a wide range of substrates, natural products and drugs with diverse functional groups are tolerated. Moreover, experimental mechanistic investigations and density functional theory (DFT) calculations in combination with wavefunction analysis have been performed to understand the catalytic cycle in more detail.

ABSTRACT:

A combined palladium/photoredox catalytic system for the efficient oxidation of terminal olefins to the corresponding methyl ketones is presented. The interplay of air, water, and light leads to a protocol in which the stoichiometric oxidants required for oxidative palladium catalysis are substituted with catalytic, single-electron transfer processes. Detailed mechanistic investigations revealed the role of the key components, in situ generated species, and catalysts. A broad range of substrates was examined in homogeneous as well as heterogeneous photoredox protocols, delivering the desired products in good yields.

ABSTRACT:

Visible-light induced, palladium catalyzed alkylations of α,β-unsaturated acids with unactivated alkyl bromides are described. A variety of primary, secondary, and tertiary alkyl bromides are activated by the photoexcited palladium metal catalyst to provide a series of olefins at room temperature under mild reaction conditions. Mechanistic investigations and density functional theory (DFT) studies suggest that a photoinduced inner-sphere mechanism is operative in which a barrierless, single-electron transfer oxidative addition of the alkyl halide to Pd0 is key for the efficient transformation.

ABSTRACT:

A dual catalytic protocol for the direct arylation of non-activated C(sp3)−H bonds has been developed. Upon photochemical excitation, the excited triplet state of a diaryl ketone photosensitizer abstracts a hydrogen atom from an aliphatic C−H bond. This inherent reactivity was exploited for the generation of benzylic radicals which subsequently enter a nickel catalytic cycle, accomplishing the benzylic arylation.

ABSTRACT:

Enzymes originating from hostile environments offer exceptional stability under industrial conditions and are therefore highly in demand. Using single-cell genome data, we identified the alcohol dehydrogenase (ADH) gene, adh/a1a, from the Atlantis II Deep Red Sea brine pool. ADH/A1a is highly active at elevated temperatures and high salt concentrations (optima at 70 °C and 4 mKCl) and withstands organic solvents. The polyextremophilic ADH/A1a exhibits a broad substrate scope including aliphatic and aromatic alcohols and is able to reduce cinnamyl-methyl-ketone and raspberry ketone in the reverse reaction, making it a possible candidate for the production of chiral compounds. Here, we report the affiliation of ADH/A1a to a rare enzyme family of microbial cinnamyl alcohol dehydrogenases and explain unique structural features for halo- and thermoadaptation.

ABSTRACT:

A metal-catalyzed methylation process has been developed. By employing an air- and moisture-stable manganese catalyst together with isotopically labeled methanol, a series of D-, CD3-, and 13C-labeled products were obtained in good yields under mild reaction conditions with water as the only byproduct.

ABSTRACT:

A general and selective metal-catalyzed conversion of biomass-derived primary diols and amines to the highly valuable 2,5-unsubstituted pyrroles has been developed. The reaction is catalyzed by a stable nonprecious manganese complex (1 mol %) in the absence of organic solvents whereby water and molecular hydrogen are the only side products. The manganese catalyst shows unprecedented selectivity, avoiding the formation of pyrrolidines, cyclic imides, and lactones.