A5090782065- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Asymmetric Hydrogenation and Catalysis
- Organoboron and organosilicon chemistry
- Catalytic Cross-Coupling Reactions
- Chemical Synthesis and Analysis
- Catalytic C–H Functionalization Methods
- Asymmetric Synthesis and Catalysis
- Synthetic Organic Chemistry Methods
- Advanced Synthetic Organic Chemistry
- Boron Compounds in Chemistry
- Radical Photochemical Reactions
- Nanomaterials for catalytic reactions
- Fluorine in Organic Chemistry
- Phosphorus compounds and reactions
- Catalysis and Oxidation Reactions
- Catalytic Processes in Materials Science
- Ionic liquids properties and applications
- Cyclopropane Reaction Mechanisms
- Chemical synthesis and alkaloids
- Chemical Reactions and Isotopes
- Luminescence and Fluorescent Materials
- Synthesis and Catalytic Reactions
- Advanced Polymer Synthesis and Characterization
- Crystallography and molecular interactions
Bristol-Myers Squibb (United States)
2017-2024
The Bristol-Myers Squibb Children's Hospital
2022
Boston College
2013-2018
Fordham University
2015
A highly stereoselective boron-Wittig reaction between stable and readily accessible 1,1-bis(pinacolboronates) aldehydes furnishes a variety of synthetically useful di- trisubstituted vinyl boronate esters.
The catalytic enantioselective diboration of vinyl boronate esters furnishes chiral tris(boronates) in a selective fashion. Subsequent deborylative alkylation occurs diastereoselective fashion, both for intermolecular and intramolecular processes.
The Pt-catalyzed enantioselective diboration of terminal alkenes can be accomplished in an fashion the presence chiral phosphonite ligands. Optimal procedures and substrate scope this transformation are fully investigated. Reaction progress kinetic analysis isotope effects suggest that stereodefining step catalytic cycle is olefin migratory insertion into a Pt–B bond. Density functional theory analysis, combined with other experimental data, suggests reaction positions platinum at internal...
Abstract We report the development of palladium(0)‐catalyzed syn ‐selective 1,2‐carboboration and ‐silylation reactions alkenes containing cleavable directing groups. With B 2 pin or PhMe Si‐Bpin as nucleophiles aryl/alkenyl triflates electrophiles, a broad range mono‐, di‐, tri‐ tetrasubstituted are compatible in these transformations. further describe directed dearomative electron‐rich heteroarenes by employing this approach. Through use removable chiral group, we demonstrate viability...
A Pt-catalyzed enantioselective hydrosilylation of alkenylboronates is described. This reaction occurs with high regio- and enantioselectivity, providing a convenient route to chiral non-racemic geminal silylboronates. These compounds are useful reagents in stereoselective synthesis.
Abstract Terminale Alkene sind leicht verfügbare Verbindungen, die in der chemischen Industrie Form von α‐Olefinen sowie als Produkte vieler gängiger Synthesereaktionen anfallen. Die organischen Transformationen solcher gehören zu den am besten untersuchten Reaktionen Synthese, allerdings kennt man nur relativ wenige Reaktionen, denen nichtaktivierte terminale katalytisch und enantioselektiv umgesetzt werden. In diesem Kurzaufsatz stellen wir diejenigen Fälle vor, Stereokontrolle...
The palladium-catalyzed coupling of aryl and heteroaryl chlorides with primary amides under mild homogeneous reaction conditions is reported. Successful C–N enabled by the use a unique "dual-base" system consisting DBU NaTFA, which serve as proton acceptor halide scavenger, respectively, using low catalyst loadings (0.5 mol %) readily available, air-stable palladium precatalysts. DBU/NaTFA also enables room-temperature amines tolerant variety base-sensitive functional groups.
A general method for the Ni-catalyzed Buchwald–Hartwig amination of (hetero)aryl chlorides using both anilines and aliphatic amines under homogeneous conditions has been developed. Key to success this is implementation a dual-base strategy that utilizes an amine base combined with soluble halide scavenger allows use single air-stable, commercially available Ni(II)-precatalyst phosphine ligand [(R,S)-Josiphos] combination promote aminations across broad scope pharmaceutically relevant...
Abstract We report the development of palladium(0)‐catalyzed syn ‐selective 1,2‐carboboration and ‐silylation reactions alkenes containing cleavable directing groups. With B 2 pin or PhMe Si‐Bpin as nucleophiles aryl/alkenyl triflates electrophiles, a broad range mono‐, di‐, tri‐ tetrasubstituted are compatible in these transformations. further describe directed dearomative electron‐rich heteroarenes by employing this approach. Through use removable chiral group, we demonstrate viability...
Investigations into nickel-catalyzed borylation reactions have led to the development of an experimental design 24 reaction conditions for rapid lead identification. A case study on a model aryl bromide with B2(OH)4 prompted series mechanistic and stability studies better understand catalytic cycle factors that affect robustness. HTEx was employed effect scavengers remediation nickel from stream. These combined results generated increased understanding set stage their expanded use in process...
Conditions have been developed for the palladium-catalyzed cyanation of aryl bromides utilizing air-stable XantPhos-PdCl2 precatalyst. By employing a trialkylamine as reducing agent, active Pd(0) species is generated in situ, alleviating need to employ air-sensitive Pd2(dba)3. Twenty-two substituted benzonitriles synthesized using this method.
Aryl electrophiles containing tethered allylboronate units undergo efficient intramolecular coupling in the presence of a chiral palladium catalyst to give enantioenriched carbocyclic products. The reaction is found be quite general, affording 5, 6, and 7-membered products as single regioisomers with moderate enantioselectivities. Examination differential partners points rapid allyl-equilibration key stereodefining feature.
This communication highlights the use of chiral sulfinamides as nitrogen nucleophiles in intermolecular aza-Michael reactions. When are coupled to a chloroethyl group, corresponding novel annulating reagents can be used streamline stereoselective synthesis complex pyrrolidine-containing molecules. As result, it has enabled medicinal chemistry campaign for biologically active RORγt inverse agonists.
We have discovered and developed a highly chemoselective O-benzylation of ambident 2-quinolinone nucleophiles via Pd-catalysis. Detailed reaction analysis using direct-injection high resolution mass spectrometry (DI-HRMS) combined with in situ 31P NMR implicate phosphine mono-oxide Pd(II) η1-benzyl complex as key intermediate on the catalytic cycle. Extrapolation this method to selectively O-alkylate series substituted 2-quinolinones several benzylic electrophiles is demonstrated providing...
We report herein the development and scale up of an Ir-catalyzed N-alkylation reaction between a 4-bromopyridin-2-amine (1) (4-(5-(1,1-difluoroethyl)-1,2,4-oxadiazol-3-yl)bicyclo[2.2.2]octan-1-yl)methanol (2) proceeding via borrowing hydrogen process. The traditional approach alcohol oxidation followed by reductive amination posed challenges that are attributed to poor nucleophilicity 2-aminopyridine derivative resulting in lower isolated yields. Several catalysts bases were evaluated for...
The decomposition of primary sodium alkoxide salts under ambient storage conditions and the effects this phenomenon on commonly employed transition-metal-catalyzed cross-coupling reactions are described. By utilizing NMR, IR, Raman spectroscopy, along with a modified Karl Fischer analysis, main inorganic degradants were characterized, CO2 in air was found to be critical reactant within process. evaluated, preliminary experiments understand kinetics process performed.
The cyclohexane dicarboxylate unit of BMS-986251 (1), a potent and efficacious RORγt inverse agonist, was synthesized starting from Hagemann's ester in seven chemical transformations with five isolated intermediates. synthesis involved an enzymatic kinetic resolution, two-step telescoped enol tosylation followed by carboxylation using benign CO surrogate for the installation second carboxylate functionality, Crabtree catalyst-mediated diastereoselective olefin hydrogenation. This process...
The use of sodium dithionite with perfluoroalkyl iodides under basic conditions facilitates the direct perfluoroalkylation arenes pendant benzylic electron-withdrawing groups. This occurs via attack arene on electrophilic radical, through donation electron density from a anion. substrate scope was expanded beyond nitriles cyclic substrates bearing groups at position—enforcing to aromatic ring and enabling radical.
The cyclohexyl fragment 1 in BMS-986251 was synthesized starting from Hagemann's ester 2 7 steps and 5 isolations. route is highlighted by a dynamic kinetic resolution (DKR), telescoped enol nonaflation followed palladium-catalyzed carbonylation, rhodium-catalyzed directed diastereoselective olefin hydrogenation. optimized process demonstrated on kg scale, with an overall 51% yield >99% ee dr.
The use of the unprecedented annulating reagents methyl N-(tert-butylsulfinyl)-4-chlorobutanimidate and N-(tert-butylsulfinyl)-5-bromopentanimidate enables diastereoselective preparation 5- 6-membered carbocycles bearing three contiguous stereocenters. These synthons undergo cycloaddition with a variety Michael acceptors to form cyclopentane/cyclohexane rings excellent stereochemical control, generating only one eight possible diastereomers. This novel methodology has enabled highly...
We have devised an asymmetric route to the tricyclic core 10 of BMS-986251. The six-step synthesis utilizes readily available starting materials, involves one-step installation perfluoro isopropyl moiety through a radical mechanism, and leverages novel diastereoselective annulation build pyrrolidine ring. Overall, was obtained in 49% yield as single stereoisomer 6 steps 3 isolations using this new route.
A series of novel, structurally related AB 2 monomers was synthesized and incorporated into branched materials.Size exclusion chromatography used to compare these systems based on their relative hydrodynamic volumes.The results studies indicated an increased volume bis-benzyl amine monomer analogous ether structures.In order further explore the structural motif, additional were synthesized, leading new materials hyperbranched polymer structures.
Abstract A scalable, transition‐metal free Wittig reaction starting from geminally substituted and unsubstituted bis(boronates) a diverse range of alkyl, alkenyl, alkynyl aldehydes to 1,2‐ 1,2‐disubstitued as well trisubstituted vinyl boronates is elaborated.