Sulfonyl Radical Triggered Selective Iodosulfonylation and Bicycli-zations of 1,6-Dienes

Value-added utilization of biomass-derived 5-hydroxymethylfurfural (HMF) to produce useful derivatives is of great interest. In this work, extremely radiation resistant Deinococcus wulumuqiensis R12 was explored for the first time as a new robust biocatalyst for selective oxidation of HMF to 5-hydroxymethylfuroic acid (HMFCA). Its resting cells exhibited excellent catalytic performance in a broad range of pH and temperature values, and extremely high tolerance to HMF and the HMFCA product. An excellent yield of HMFCA (up to 90%) was achieved when the substrate concentration was set to 300 mM under the optimized reaction conditions. In addition, 511 mM of product was obtained within 20 h by employing a fed-batch strategy, affording a productivity of 44 g/L per day. Of significant synthetic interest was the finding that the D. wulumuqiensis R12 cells were able to catalyze the selective oxidation of other structurally diverse aldehydes to their corresponding acids with good yield and high selectivity, indicating broad substrate scope and potential widespread applications in biotechnology and organic chemistry.

Download Full-text

Iridium-Catalyzed Silylation of C-H bonds in Unactivated Arenes: A Sterically-Encumbered Phenanthroline Ligand Accelerates Catalysis Enabling New Reactivity

10.26434/chemrxiv.7744175 ◽

2019 ◽

Author(s):

Caleb Karmel ◽

Zhewei Chen ◽

John Hartwig

Keyword(s):

High Activity ◽

Functional Group ◽

Activity Analysis ◽

High Reactivity ◽

High Yield ◽

Phen Ligand ◽

Mechanistic Studies ◽

Phenanthroline Ligand ◽

First Time ◽

New System

We report a new system for the silylation of aryl C-H bonds. The combination of [Ir(cod)(OMe)]2 and 2,9-Me2-phenanthroline (2,9-Me2phen) catalyzes the silylation of arenes at lower temperatures and with faster rates than those reported previously, when the hydrogen byproduct is removed, and with high functional group tolerance and regioselectivity. Inhibition of reactions by the H2 byproduct is shown to limit the silylation of aryl C-H bonds in the presence of the most active catalysts, thereby masking their high activity. Analysis of initial rates uncovered the high reactivity of the catalyst containing the sterically hindered 2,9-Me2phen ligand but accompanying rapid inhibition by hydrogen. With this catalyst, under a flow of nitrogen to remove hydrogen, electron-rich arenes, including those containing sensitive functional groups, undergo silylation in high yield for the first time, and arenes that underwent silylation with prior catalysts react over much shorter times with lower catalyst loadings. The synthetic value of this methodology is demonstrated by the preparation of key intermediates in the synthesis of medicinally important compounds in concise sequences comprising silylation and functionalization. Mechanistic studies demonstrate that the cleavage of the aryl C-H bond is reversible and that the higher rates observed with the 2,9-Me2phen ligand is due to a more thermodynamically favorable oxidative addition of aryl C-H bonds.

Download Full-text

Modern Organic Synthesis in the Laboratory

10.1093/oso/9780195187984.001.0001 ◽

2008 ◽

Cited By ~ 1

Author(s):

Jie Jack Li ◽

Chris Limberakis ◽

Derek A. Pflum

Keyword(s):

Organic Chemistry ◽

Graduate Students ◽

Organic Synthesis ◽

Functional Group ◽

Bond Formation ◽

Reaction Conditions ◽

Carbon Bond ◽

Oxidation Reduction ◽

Carbon Carbon Bond ◽

Daunting Task

Searching for reaction in organic synthesis has been made much easier in the current age of computer databases. However, the dilemma now is which procedure one selects among the ocean of choices. Especially for novices in the laboratory, it becomes a daunting task to decide what reaction conditions to experiment with first in order to have the best chance of success. This collection intends to serve as an "older and wiser lab-mate" one could have by compiling many of the most commonly used experimental procedures in organic synthesis. With chapters that cover such topics as functional group manipulations, oxidation, reduction, and carbon-carbon bond formation, Modern Organic Synthesis in the Laboratory will be useful for both graduate students and professors in organic chemistry and medicinal chemists in the pharmaceutical and agrochemical industries.

Download Full-text

Nickel-Catalyzed Multicomponent Coupling Reaction of Alkyl Halides, Isocyanides and H2O: An Expedient Way to Access Alkyl Amides

Synthesis ◽

10.1055/s-0040-1707229 ◽

2020 ◽

Vol 52 (22) ◽

pp. 3466-3472

Author(s):

Yunkui Liu ◽

Bingwei Zhou ◽

Qiao Li ◽

Hongwei Jin

Keyword(s):

Functional Group ◽

Coupling Reaction ◽

Alkyl Halides ◽

Previous Literature ◽

Catalytic Cycle ◽

Reaction Conditions ◽

Multicomponent Coupling ◽

Easy Operation

We herein describe a Ni-catalyzed multicomponent coupling reaction of alkyl halides, isocyanides, and H2O to access alkyl amides. Bench-stable NiCl2(dppp) is competent to initiate this transformation under mild reaction conditions, thus allowing easy operation and adding practical value. Substrate scope studies revealed a broad functional group tolerance and generality of primary and secondary alkyl halides in this protocol. A plausible catalytic cycle via a SET process is proposed based on preliminary experiments and previous literature.

Download Full-text

Rh(III)-Catalyzed Olefination and Alkylation of Arenes with Maleimides: A Tunable Strategy for C(sp2)–H Functionalization

Synthesis ◽

10.1055/s-0037-1610765 ◽

2021 ◽

Author(s):

Hongji Li ◽

Wenjie Zhang ◽

Xueyan Liu ◽

Zhenfeng Tian

Keyword(s):

Room Temperature ◽

Functional Group ◽

Reaction Conditions ◽

Bond Functionalization ◽

Alkylation Process ◽

Coupling Partner

AbstractWe herein report a new nitrogen-directed Rh(III)-catalyzed C(sp2)–H bond functionalization of N-nitrosoanilines and azoxybenzenes with maleimides as a coupling partner, in which the olefination/alkylation process can be finely controlled at room temperature by variation of the reaction conditions. This method shows excellent functional group tolerance, and presents a mild access to the resulting olefination/alkylation products in moderate to good yields.

Download Full-text

A Sustainable Improvement of ω-Bromoalkylphosphonates Synthesis to Access Novel KuQuinones

Organics ◽

10.3390/org2020010 ◽

2021 ◽

Vol 2 (2) ◽

pp. 107-117

Author(s):

Mattia Forchetta ◽

Valeria Conte ◽

Giulia Fiorani ◽

Pierluca Galloni ◽

Federica Sabuzi

Keyword(s):

Metal Oxides ◽

Phosphonic Acid ◽

Organic Molecules ◽

Building Blocks ◽

Reaction Conditions ◽

Phosphonic Acids ◽

Sustainable Improvement ◽

Phosphonate Esters ◽

First Time ◽

Complex Organic

Owing to the attractiveness of organic phosphonic acids and esters in the pharmacological field and in the functionalization of conductive metal-oxides, the research of effective synthetic protocols is pivotal. Among the others, ω-bromoalkylphosphonates are gaining particular attention because they are useful building blocks for the tailored functionalization of complex organic molecules. Hence, in this work, the optimization of Michaelis–Arbuzov reaction conditions for ω-bromoalkylphosphonates has been performed, to improve process sustainability while maintaining good yields. Synthesized ω-bromoalkylphosphonates have been successfully adopted for the synthesis of new KuQuinone phosphonate esters and, by hydrolysis, phosphonic acid KuQuinone derivatives have been obtained for the first time. Considering the high affinity with metal-oxides, KuQuinones bearing phosphonic acid terminal groups are promising candidates for biomedical and photo(electro)chemical applications.

Download Full-text

Engineered Phage Endolysin Eliminates Gardnerella Biofilm without Damaging Beneficial Bacteria in Bacterial Vaginosis Ex Vivo

Pathogens ◽

10.3390/pathogens10010054 ◽

2021 ◽

Vol 10 (1) ◽

pp. 54

Author(s):

Christine Landlinger ◽

Lenka Tisakova ◽

Vera Oberbauer ◽

Timo Schwebs ◽

Abbas Muhammad ◽

...

Keyword(s):

Bacterial Vaginosis ◽

Bactericidal Activity ◽

High Selectivity ◽

Ex Vivo ◽

Vaginal Microbiome ◽

Wild Type ◽

Wild Type Enzyme ◽

Promising Alternative ◽

First Time

Bacterial vaginosis is characterized by an imbalance of the vaginal microbiome and a characteristic biofilm formed on the vaginal epithelium, which is initiated and dominated by Gardnerella bacteria, and is frequently refractory to antibiotic treatment. We investigated endolysins of the type 1,4-beta-N-acetylmuramidase encoded on Gardnerella prophages as an alternative treatment. When recombinantly expressed, these proteins demonstrated strong bactericidal activity against four different Gardnerella species. By domain shuffling, we generated several engineered endolysins with 10-fold higher bactericidal activity than any wild-type enzyme. When tested against a panel of 20 Gardnerella strains, the most active endolysin, called PM-477, showed minimum inhibitory concentrations of 0.13–8 µg/mL. PM-477 had no effect on beneficial lactobacilli or other species of vaginal bacteria. Furthermore, the efficacy of PM-477 was tested by fluorescence in situ hybridization on vaginal samples of fifteen patients with either first time or recurring bacterial vaginosis. In thirteen cases, PM-477 killed the Gardnerella bacteria and physically dissolved the biofilms without affecting the remaining vaginal microbiome. The high selectivity and effectiveness in eliminating Gardnerella, both in cultures of isolated strains as well as in clinically derived samples of natural polymicrobial biofilms, makes PM-477 a promising alternative to antibiotics for the treatment of bacterial vaginosis, especially in patients with frequent recurrence.

Download Full-text

Ligand-Driven Advances in Iridium Catalyzed sp3 C-H Borylation: 2,2’-Dipyridylarylmethane

Synlett ◽

10.1055/a-1344-1904 ◽

2020 ◽

Author(s):

Margaret R Jones ◽

Nathan D. Schley

Keyword(s):

Recent Work ◽

Organic Synthesis ◽

Functional Group ◽

Reaction Conditions ◽

Recent Advances ◽

Additional Ligand ◽

Limited Application ◽

Hydrocarbon Substrates ◽

Phenanthroline Ligands

The field of catalytic C-H borylation has grown considerably since its founding, providing a means for the preparation of synthetically versatile organoborane products. While sp2 C-H borylation methods have found widespread and practical use in organic synthesis, the analogous sp3 C-H borylation reaction remains challenging and has seen limited application. Existing catalysts are often hindered by incomplete consumption of the diboron reagent, poor functional group tolerance, harsh reaction conditions, and the need for excess or neat substrate. These challenges acutely affect C-H borylation chemistry of unactivated hydrocarbon substrates, which has lagged in comparison to methods for the C-H borylation of activated compounds. Herein we discuss recent advances in sp3 C-H borylation of undirected substrates in the context of two particular challenges: (1) utilization of the diboron reagent and (2) the need for excess or neat substrate. Our recent work on the application of dipyridylarylmethane ligands in sp3 C-H borylation has allowed us to make contributions in this space and has presented an additional ligand scaffold to supplement traditional phenanthroline ligands.

Download Full-text

Ring-Opening Copolymerization of Cyclohexene Oxide and Cyclic Anhydrides Catalyzed by Bimetallic Scorpionate Zinc Catalysts

Polymers ◽

10.3390/polym13101651 ◽

2021 ◽

Vol 13 (10) ◽

pp. 1651

Author(s):

Felipe de la Cruz-Martínez ◽

Marc Martínez de Sarasa Buchaca ◽

Almudena del Campo-Balguerías ◽

Juan Fernández-Baeza ◽

Luis F. Sánchez-Barba ◽

...

Keyword(s):

Catalytic Activity ◽

Reaction Mechanism ◽

Catalytic System ◽

Phthalic Anhydride ◽

Ring Opening ◽

High Selectivity ◽

Zinc Complexes ◽

Cyclohexene Oxide ◽

Reaction Conditions ◽

Cyclic Anhydrides

The catalytic activity and high selectivity reported by bimetallic heteroscorpionate acetate zinc complexes in ring-opening copolymerization (ROCOP) reactions involving CO2 as substrate encouraged us to expand their use as catalysts for ROCOP of cyclohexene oxide (CHO) and cyclic anhydrides. Among the catalysts tested for the ROCOP of CHO and phthalic anhydride at different reaction conditions, the most active catalytic system was the combination of complex 3 with bis(triphenylphosphine)iminium as cocatalyst in toluene at 80 °C. Once the optimal catalytic system was determined, the scope in terms of other cyclic anhydrides was broadened. The catalytic system was capable of copolymerizing selectively and efficiently CHO with phthalic, maleic, succinic and naphthalic anhydrides to afford the corresponding polyester materials. The polyesters obtained were characterized by spectroscopic, spectrometric, and calorimetric techniques. Finally, the reaction mechanism of the catalytic system was proposed based on stoichiometric reactions.

Download Full-text

New opportunities in the stereoselective dearomatization of indoles

Pure and Applied Chemistry ◽

10.1515/pac-2016-0101 ◽

2016 ◽

Vol 88 (3) ◽

pp. 207-214 ◽

Cited By ~ 23

Author(s):

Elisabetta Manoni ◽

Assunta De Nisi ◽

Marco Bandini

Keyword(s):

Acid Catalysis ◽

Bronsted Acid ◽

Brønsted Acid ◽

Reaction Conditions ◽

Brönsted Acid ◽

High Yields ◽

First Time ◽

Tailored Design ◽

Bronsted Acid Catalysis

AbstractThe regio- and stereoselective dearomatization of indoles is realized for the first time by combining readily available indolyl precursors and electron-rich allenes, namely allenamides and aryloxyallenes. Inter- as well as intramolecular condensations were realized under gold and Brønsted acid catalysis providing a range of densely functionalized indoline and indolenine cores in high yields and excellent stereochemical outcome. Chemodivergent reaction profiles (Micheal-type addition vs. [2+2]-cycloaddition) were realized by a tailored design of both reaction conditions and functionalization of the reaction partners.

Download Full-text