A5005766874- Asymmetric Hydrogenation and Catalysis
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Catalytic C–H Functionalization Methods
- Chemical Synthesis and Analysis
- Mentoring and Academic Development
- HIV/AIDS drug development and treatment
- Career Development and Diversity
- Asymmetric Synthesis and Catalysis
- Diversity and Career in Medicine
- Biochemical and Molecular Research
- Synthetic Organic Chemistry Methods
- Synthesis and Catalytic Reactions
- Catalytic Cross-Coupling Reactions
- Innovative Microfluidic and Catalytic Techniques Innovation
- Hepatitis C virus research
- Advanced Synthetic Organic Chemistry
- Cyclopropane Reaction Mechanisms
- Machine Learning in Materials Science
- Click Chemistry and Applications
- Chemistry and Chemical Engineering
- Radical Photochemical Reactions
- Chemical Reactions and Isotopes
- Surface Chemistry and Catalysis
- Catalysis for Biomass Conversion
Merck & Co., Inc., Rahway, NJ, USA (United States)
2015-2024
Merck Institute for Science Education
2017-2021
MSD K.K. (Japan)
2018
Merck (Japan)
2018
University of California, Berkeley
2004-2005
Harvard University
2002-2004
Princeton University
1998
Identifying catalyst activation modes that exploit one-electron chemistry and overcome associated deactivation pathways will be transformative for developing first-row transition metal catalysts with performance equal or, ideally, superior to precious metals. Here we describe a zinc-activation method compatible high-throughput reaction discovery identified scores of cobalt-phosphine combinations the asymmetric hydrogenation functionalized alkenes. An optimized prepared from (R,R)-Ph-BPE...
The combination of nickel metallaphotoredox catalysis, hydrogen atom transfer and a Lewis acid activation mode, has led to the development an arylation method for selective functionalization alcohol α-hydroxy C-H bonds. This approach employs zinc-mediated deprotonation activate bonds while simultaneously suppressing C-O bond formation by inhibiting alkoxide species. use Zn-based acids also deactivates other hydridic such as α-amino α-oxy facilitates rapid access benzylic alcohols, important...
Tied up nicely: A novel tandem reaction involving an intramolecular Heck with subsequent functionalization of unactivated CH bond to generate spiro-fused indane-oxindoles is described (see scheme; PMB=p-methoxybenzyl).
Getting phosphorus into healthy shape ProTide therapeutics play a trick on the body, getting nucleoside analogs where they need to be by decorating them with unnatural phosphoramidates in place of ordinary phosphates. These compounds pose an unusual synthetic challenge because their configuration must controlled at phosphorus; most methods have been refined manipulate geometry carbon. DiRocco et al. report metal-free, small-molecule catalyst that attains high selectivity for...
MK-7655 (1) is a β-lactamase inhibitor in clinical trials as combination therapy for the treatment of bacterial infection resistant to β-lactam antibiotics. Its unusual structural challenges have inspired rapid synthesis featuring an iridium-catalyzed N-H insertion and series late stage transformations designed around reactivity labile bicyclo[3.2.1]urea at core target.
A Rh-catalyzed enantioselective hydroamination of allylamines using a chiral BIPHEP-type ligand is reported. Enantioenriched 1,2-diamines are formed in good yields and with excellent enantioselectivities. diverse array nucleophiles amine directing groups demonstrated, including deprotectable motifs. Finally, the methodology was demonstrated toward rapid synthesis 2-methyl-moclobemide.
Tridentate Schiff base chromium(III) complex 1 catalyzes the asymmetric hetero-ene reaction between aryl aldehydes and either 2-methoxypropene or 2-trimethylsilyloxypropene to provide a series of β-hydroxyenol ether products in high yields enantioselectivities. X-ray crystallographic analysis closely related chromium reveals bridged, dimeric structure bearing aquo-bound six-coordinate CrIII centers. A mechanism is proposed wherein water dissociation effected by means chemical desiccant (BaO...
A microscale chemistry improvement engine: pre-dosed high-throughput experimentation additives platform enables rapid, serendipitous reaction improvement. This allowed one chemist to set up 475 experiments and analyze the results using MISER chromatography in a single day, thus resulting two high-quality catalytic systems for construction of title compound 1. Support single-electron transfer mechanism was obtained. Microscale multiparallel technologies enable modern synthetic chemists...
Chiral chroman derivatives are important pharmacophores in natural and synthetic bioactive molecules. The discovery of catalytic asymmetric methods for the synthesis these compounds is an goal. Ruthenium-catalyzed transfer hydrogenation under strongly basic conditions has been found to induce dynamic kinetic resolution β-substituted chromanones, producing valuable chromanols high yields with levels stereocontrol. reaction proceeds by base-catalyzed racemization β-stereocenter through a...
α- and β-substitution of dihydrocinnamates has been shown to increase the biological activity various drug candidates. Recently, we identified enantio- diastereopure α-methyl-β-cyclopropyldihydrocinnamates be important pharmacophores in one our discovery programs endeavored devise an asymmetric hydrogenation strategy improve access this valuable framework. We used high throughput experimentation define stereoconvergent Suzuki-Miyaura cross-coupling conditions affording...
Abstract The combination of nickel metallaphotoredox catalysis, hydrogen atom transfer and a Lewis acid activation mode, has led to the development an arylation method for selective functionalization alcohol α‐hydroxy C−H bonds. This approach employs zinc‐mediated deprotonation activate bonds while simultaneously suppressing C−O bond formation by inhibiting alkoxide species. use Zn‐based acids also deactivates other hydridic such as α‐amino α‐oxy facilitates rapid access benzylic alcohols,...
We describe the research that led to discovery of compound 40 (ruzasvir, MK-8408), a pan-genotypic HCV nonstructural protein 5A (NS5A) inhibitor with "flat" GT1 mutant profile. This NS5A contains unique tetracyclic indole core while maintaining imidazole-proline-valine Moc motifs our previous inhibitors. Compound is currently in early clinical trials and under evaluation as part an all-oral DAA regimen for treatment chronic infection.
A concerted ene reaction between silyl enol ethers and simple aldehydes is catalyzed by chiral (Schiff base) CrIII complexes with high stereoselectivity (see scheme). This method leads directly to enantioenriched β-hydroxy ether derivatives, which are known be useful intermediates for the stereocontrolled synthesis of substituted polyol frameworks.
A big plus for addition reactions: catalytic amount of an azazirconacyclobutene is used in a novel carboamination reaction that involves net aldimine across symmetrical alkyne to generate highly substituted α,β-unsaturated ketimine products (see scheme; Cp=C5H5). Supporting information this article available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2004/z461063_s.pdf or from author. Please note: The publisher not responsible content functionality any supporting supplied by...
Verknotet: Eine neuartige Tandemsequenz aus intramolekularer Heck-Reaktion und anschließender Funktionalisierung einer nichtaktivierten C-H-Bindung ergibt spirocyclisch verknüpfte Indan-Oxindole (siehe Schema; PMB=p-Methoxybenzyl). Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2001/2008/z800549_s.pdf or from author. Please note: The publisher not responsible content functionality of any supporting supplied by authors. Any queries...
Insights and mechanistic studies into biphasic reactions are often challenging due to difficulty in deploying situ reaction-monitoring or sampling procedures. Herein, we describe the development application of an automated monitoring platform capable delineating time course reaction progress reactions. The system was applied toward a case study enantioselective spirocyclization catalyzed by doubly quaternized cinchona alkaloid. A combination heterogeneous phase-selective sampling, coupled...
A robust, green, and sustainable manufacturing process has been developed for the synthesis of gefapixant citrate, a P2X3 receptor antagonist that is under investigation treatment refractory unexplained chronic cough. The newly commercial features low mass intensity (PMI), short synthetic sequence, high overall yield, minimal environmental impact, significantly reduced API costs. key innovations are implementation highly efficient two-step methoxyphenol synthesis, an innovative pyrimidine in...
A weak Brønsted acid-catalyzed asymmetric guanidine aza-conjugate addition reaction has been developed. C2-symmetric, dual hydrogen-bond donating bistriflamides are shown to be highly effective in activating α,β-unsaturated esters toward the intramolecular of a pendant guanidinyl nucleophile. Preliminary mechanistic investigation, including density functional theory calculations and kinetics studies, support conjugate pathway as more favorable energetically than an alternative...
We have been focused on identifying a structurally different next generation inhibitor to MK-5172 (our Ns3/4a protease currently under regulatory review), which would achieve superior pangenotypic activity with acceptable safety and pharmacokinetic profile. These efforts led the discovery of novel class HCV NS3/4a inhibitors containing unique spirocyclic-proline structural motif. The design strategy involved molecular-modeling based approach, optimization series obtain pan-genotypic coverage...
3-(Hetero)arylindazoles are important motifs in several biologically active compounds. Mild and flexible palladium-mediated Negishi reaction conditions reported for the introduction of (hetero)aryl moieties at 3-position N(2)-SEM-protected indazoles high yields. The requisite Zn-species readily obtained via regioselective deprotonation subsequent transmetalation. methodology tolerates a variety functional groups on both coupling partners has been extended to bis-haloarene heteroarene where...
Significant catalyst loading reduction and increased reaction robustness have been achieved for a Pd-catalyzed asymmetric intramolecular C-N coupling through comprehensive mechanistic studies. Detailed kinetic, spectroscopic, crystallographic analyses revealed that the mono-oxidation of bis-phosphine ligand is critical successful transformation.
Hybrid QSAR modeling predicts improved catalysts for the synthesis of Prevymis™ (letermovir).
ADVERTISEMENT RETURN TO ISSUEEditorialNEXTGender Diversity in Process ChemistryRebecca T. Ruck*Rebecca RuckMRL, Merck & Co., Inc., 126 East Lincoln Avenue, Rahway, New Jersey 07065, United States*E-mail: [email protected]. Telephone: 732-594-6263.More by Rebecca Ruckhttp://orcid.org/0000-0001-9980-9675 and Margaret M. Faul*Margaret FaulProcess Development, Amgen Thousand Oaks, California 91320, 805-447-0599.More FaulCite this: Org. Res. Dev. 2019, 23, 2, 109–113Publication Date...