A5076187842- Asymmetric Synthesis and Catalysis
- Scheduling and Optimization Algorithms
- Catalytic C–H Functionalization Methods
- Chemical Synthesis and Analysis
- Synthetic Organic Chemistry Methods
- Asymmetric Hydrogenation and Catalysis
- Catalytic Cross-Coupling Reactions
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Supply Chain and Inventory Management
- Advanced Queuing Theory Analysis
- Advanced Control Systems Optimization
- Chemical Synthesis and Reactions
- Multicomponent Synthesis of Heterocycles
- Chemical synthesis and alkaloids
- Cyclopropane Reaction Mechanisms
- Organoboron and organosilicon chemistry
- Axial and Atropisomeric Chirality Synthesis
- Advanced Synthetic Organic Chemistry
- Optimization and Search Problems
- Fluorine in Organic Chemistry
- Carbohydrate Chemistry and Synthesis
- Advanced Manufacturing and Logistics Optimization
- Oceanographic and Atmospheric Processes
- Synthesis and Biological Activity
Bristol-Myers Squibb (United States)
2014-2024
Tongji University
2010-2024
China Three Gorges University
2024
The Bristol-Myers Squibb Children's Hospital
2014-2015
Bristol-Myers Squibb (Germany)
2013
Ningbo Institute of Industrial Technology
2011
Chinese Academy of Sciences
2011
Massachusetts Institute of Technology
2003-2010
IIT@MIT
2010
Boston University
2004-2009
The first asymmetric Kumada reactions of alkyl electrophiles are described, specifically, cross-couplings racemic α-bromoketones with aryl Grignard reagents. Several features this investigation interest. First, the couplings proceed at remarkably low temperature (−40 or −60 °C), which enables synthesis racemization-prone α-arylketones. Second, dialkyl ketones undergo enantioselective coupling in good ee and yield. Third, readily available bis(oxazolines) shown for time to be effective...
Chiral BINOL-derived diols catalyze the enantioselective asymmetric allylboration of ketones. The reaction requires 15 mol % 3,3'-Br2-BINOL as catalyst and allyldiisopropoxyborane nucleophile. products are obtained in good yields (76−93%) high enantiomeric ratios (95:5−99.5:0.5). High diastereoselectivities (dr ≥ 98:2) enantioselectivities (er reactions acetophenone with crotyldiisopropoxyboranes.
Chiral BINOL-derived diols catalyze the enantioselective asymmetric allylboration of acyl imines. The reaction requires 15 mol % (S)-3,3'-Ph2-BINOL as catalyst and allyldiisopropoxyborane nucleophile. products are obtained in good yields (75−94%) high enantiomeric ratios (95:5−99.5:0.5) for aromatic aliphatic High diastereoselectivities (diastereomeric ratio > 98:2) enantioselectivities (enantiomeric reactions imines with crotyldiisopropoxyboranes. This transformation is directly applied to...
Cinchona alkaloids catalyze the enantioselective Mannich reaction of β-keto esters with acyl aryl imines. The requires 10 mol % cinchonine or cinchonidine. products are obtained in good yields (81−99%), high enantioselectivities (80−96% ee), and diastereoselectivities that range from 1:1 to >95:5. cinchonine-catalyzed provides access highly functionalized building blocks used asymmetric synthesis a dihydropyrimidone β-amino alcohol.
Chiral biphenols catalyze the enantioselective Petasis reaction of alkenyl boronates, secondary amines, and ethyl glyoxylate. The requires use 15 mol % (S)-VAPOL as catalyst, boronates nucleophiles, glyoxylate aldehyde component, 3 Å molecular sieves an additive. chiral α-amino ester products are obtained in good yields (71−92%) high enantiomeric ratios (89:11−98:2). Mechanistic investigations indicate single ligand exchange acyclic boronate with VAPOL tetracoordinate intermediates.
A new family of organometallic compounds, organozirconium reagents, are shown to serve as suitable partners in cross-coupling reactions (activated) secondary alkyl electrophiles. Thus, the first catalytic method for coupling α-bromoketones with alkenylmetal reagents has been developed, specifically, a mild, versatile, and stereoconvergent carbon−carbon bond-forming process that generates potentially labile β,γ-unsaturated ketones good enantioselectivity.
Ring-closing metathesis (RCM) has become indispensable in organic synthesis for both academic investigations and industrial applications. This review provides an overview of RCM reactions, focusing on the practical aspects that researchers environment may find interest. Key elements reaction design lessons learned from these applications are discussed to help those considering implementing reactions scale, particularly manufacturing active pharmaceutical ingredients (APIs). Advances...
Four different sized gold nanoparticles (14 nm, 16 35 nm and 38 nm) were prepared to conjugate an antibody for a nanoparticle-based immunochromatographic assay which has many applications in both basic research clinical diagnosis. This study focuses on the conjugation efficiency of with nanoparticles. The effect factors such as pH value concentration been quantificationally discussed using spectra methods after adding 1 wt% NaCl induced nanoparticle aggregation. It was found that had...
The highly enantioselective cinchona alkaloid-catalyzed Mannich reaction of dicarbonyl compounds with α-amido sulfones as acyl imine precursors is described. requires 10 mol % the alkaloid catalyst, which serves a general base to generate imines in situ, and aqueous Na2CO3 maintain concentration free catalyst. products are obtained good yields high enantioselectivities, diastereoselectivities that range from 1:1 >95:5. cinchonine-catalyzed reactions provide practical access functionalized...
The process optimization of a key step in the synthesis NLRP3 (nucleotide-binding domain and leucine-rich repeat-containing protein 3) agonist BMS-986299 is reported. convergent three-stage telescope featuring four discrete chemical transformations: Pd-catalyzed Miyaura borylation, followed by Suzuki–Miyaura cross-coupling, then concurrent acid-mediated cyclization THP (tetrahydropyran) cleavage. Through targeted development focused on safety, sustainability, robustness, we developed safer...
The cinchona alkaloids catalyze direct asymmetric Mannich reactions of cyclic 1,3-dicarbonyl compounds with acyl imines to afford α-quaternary carbon-bearing reaction products in yields up 98%, a diastereomeric excess 90% or greater, and enantioselectivities 99% ee. A model is proposed that accounts for both the observed diastereoselectivities reactions.
Abstract On the big screen : A chiral biphenol catalyst screening protocol was developed for rapid identification of enantioselective nucleophilic boronate reactions with acyl imines (see scheme). The approach successfully identified a unique reaction aryl, vinyl, and alkynyl boronates. Mechanistic studies demonstrate ligand exchange is necessary activation towards addition. magnified image
Abstract Dipalladiumtris(dibenzylideneacetone)/tris( tert ‐butyl)phosphonium tetrafluoroborate/potassium fluoride dihydrate [Pd 2 (dba) 3 /[HP( t‐ Bu) ]BF 4 /KF⋅2 H O] serves as a mild, robust, and user‐friendly method for the efficient Suzuki cross‐coupling of diverse array aryl heteroaryl halides with aryl‐ heteroarylboronic acids.
Mild and selective heterobimetallic-catalyzed decarboxylative aldol reactions involving allyl beta-keto esters have been developed. The reaction is promoted by Pd(0)- Yb(III)-DIOP complexes at room temperature involves the in situ formation of a ketone enolate from followed addition to aldehydes. new example heterobimetallic catalysis which optimized conditions require both metals.
The invention of a commercial route to the Bruton's tyrosine kinase inhibitor branebrutinib (BMS-986195) in four total chemical steps is described. execution high-throughput experimentation (HTE) coupled with first-principles approach across proposed synthetic enabled identification novel indolization reaction that rapidly generated high complexity, as centerpiece synthesis. A parallel HTE strategy during design efficient and rapid evaluation multiple options within short timeframe complete...
A simulation model based on a real wafer fabrication is used to investigate the robustness of two-boundary (TB) production control strategy existing uniform loading policy in semiconductor fab. Our findings confirm that TB most robust all when random interference, such as machine breakdowns and demand variations, exist. It also observed performance facility under investigation can be improved significantly terms reducing cycle time, decreasing work-in-progress (WIP), cutting down inventory cost.
Abstract Schnell gefunden : Ein Screening chiraler Biphenolkatalysatoren ermöglichte die rasche Identifizierung enantioselektiver nucleophiler Reaktionen von Boronaten mit Acyliminen (siehe Schema). Damit konnte ein einzigartiger Katalysator für Reaktion Aryl‐, Vinyl‐ und Alkinylboronaten werden. Mechanistische Studien ergaben, dass Ligandenaustausch zwischen Boronat Aktivierung notwendig ist. magnified image
The development and demonstration of short, robust chromatography-free sequences for the preparation a (1R,2S)-1-amino-2-vinylcyclopropane-carboxylic acid-derived sulfonamide ethyl ester in ≥99% ee are described. Both compounds common building blocks multiple preparations potent HCV NS3 protease inhibitors. robustness asymmetric cyclopropanation (E)-N-benzylideneglycine under phase transfer catalysis conditions is significantly improved based on detailed mechanistic investigation that...
A single machine processing different types of parts is considered. Switching from one type to another involves a setup time. The part may have times. resulting scheduling problem treated as dynamical system for which several feedback policies that are implementable in real time and stabilize the discussed. main results characterization dynamics induced by clear-the-largest-work derivation bounds on total work-in-process better than those available literature.< <ETX...
The development of a convergent route to the NLRP3 (nucleotide-binding domain and leucine-rich repeat-containing protein 3) agonist BMS-986299 is reported. synthesis relies on key Miyaura borylation tandem Suzuki–Miyaura coupling between an iodoimidazole o-aminochloroarene, followed by acid-mediated cyclization afford aminoquinoline core. subsequent Boc cleavage regioselective acylation target compound. Two routes intermediate are presented, along with o-aminochloroarene via Negishi...
Abstract We have developed highly diastereoselective silver‐catalyzed direct aldol reactions of benzophenone glycine imines with aromatic, heteroaromatic and aliphatic aldehydes. Protection the secondary alcohol in product situ di‐ tert ‐butyl dicarbonate was applied to effectively circumvent retro‐aldol process resulting improved yields products. Only a catalytic amount base, lithium ‐butoxide, is required since ‐butoxide regenerated during Boc protection. Computational studies support...