A5026455504- Synthetic Organic Chemistry Methods
- Catalytic C–H Functionalization Methods
- Asymmetric Synthesis and Catalysis
- Crystallization and Solubility Studies
- Catalytic Cross-Coupling Reactions
- X-ray Diffraction in Crystallography
- Chemical Synthesis and Analysis
- Synthesis and Catalytic Reactions
- Sulfur-Based Synthesis Techniques
- Asymmetric Hydrogenation and Catalysis
- Diabetes Treatment and Management
- Cyclopropane Reaction Mechanisms
- Chemical Synthesis and Reactions
- Radical Photochemical Reactions
- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Crystallography and molecular interactions
- Marine Toxins and Detection Methods
- Fluorine in Organic Chemistry
- Coordination Chemistry and Organometallics
- Microfluidic and Capillary Electrophoresis Applications
- Synthesis of β-Lactam Compounds
- Inorganic Fluorides and Related Compounds
- Phosphorus compounds and reactions
- Analytical Chemistry and Chromatography
Pfizer (United States)
2016-2023
University of Pennsylvania
2013-2019
Foton Motors (China)
2016
Philadelphia University
2014-2015
High Throughput Biology (United States)
2014
College of the Holy Cross
2008-2009
A mild, efficient synthesis of sulfonyl fluorides from aryl and heteroaryl bromides utilizing palladium catalysis is described.
Peptide agonists of the glucagon-like peptide-1 receptor (GLP-1R) have revolutionized diabetes therapy, but their use has been limited because they require injection. Herein, we describe discovery orally bioavailable, small-molecule, GLP-1R agonist PF-06882961 (danuglipron). A sensitized high-throughput screen was used to identify 5-fluoropyrimidine-based that were optimized promote endogenous signaling with nanomolar potency. Incorporation a carboxylic acid moiety provided considerable...
The first described reaction between N-tosylhydrazone and SO2 is reported to provide alkyl sulfonamides in the presence of various amines. In this procedurally simple method, hydrazones both unsaturated aldehydes ketones proceed moderate excellent yields. Primary secondary aliphatic amines are accommodated reaction, which provides a novel route sulfonamides.
The first selective coupling of a carbon nucleophile with methyl, ethyl, propyl, and butyl arenes in the absence directing group is described. Pd(OAc)2 double C-H activation displays remarkable selectivity for terminal methyl sites alkyl arenes, rather than more commonly observed arene sp(2) activation. Mechanistic studies indicate intermediacy an azlactone dimer, obtained from oxidation Pd(OAc)2, are consistent Pd-catalyzed vs radical process. reactivity establishes that typical reaction...
Mechanism studies of a mild palladium-catalyzed decarboxylation aromatic carboxylic acids are described. In particular, reaction orders and activation parameters for the two stages transformation were determined. These guided development catalytic system capable turnover. Further evidence reinforces that second stage, protonation arylpalladium intermediate, is rate-determining step reaction. The first step, decarboxylative palladation, proposed to occur through an intramolecular...
The first asymmetric synthesis of α-allyl-α-aryl α-amino acids by means a three-component coupling α-iminoesters, Grignard reagents, and cinnamyl acetate is reported. Notably, the enolate from tandem process provides much higher level reactivity selectivity than same generated via direct deprotonation, presumably due to differences in solvation/aggregation state. A novel method for removal homoallylic amine protecting group delivers free congeners. α-allyl offers generate further valuable...
The oxidative activation of alkyl C–H bonds vs arene with Pd(OAc)2 has been found to be generalizable a number nucleophilic substrates, allowing the formation range hindered quaternary centers. substrates share common mechanistic path wherein Pd(II) initiates an dimerization. resultant dimer modifies palladium catalyst favor bonds, in contrast trends typically observed via concerted metalation–deprotonation mechanism. Notably, insertion occurs at terminus for substrates. Two different...
Allylating agents were explored for the asymmetric synthesis of α-allyl-α-aryl α-amino acids by tandem N-alkylation/π-allylation. Cross-metathesis product was developed to provide allylic diversity not afforded in parent reaction; homotyrosine and homoglutamate analogues completed. Cyclic acid derivatives could be accessed ring-closing metathesis presenting a viable strategy higher ring homologue enantioenriched α-substituted proline. The eight-membered proline analogue successfully...
Abstract Peptide agonists of the glucagon-like peptide-1 receptor (GLP-1R) have revolutionized diabetes therapy, but their use has been limited by requirement for injection. Here we describe first effective, orally bioavailable small molecule GLP-1R agonists. A sensitized high-throughput screen identified a series that were optimized to promote endogenous signaling with nM potency. These increased insulin levels in primates not rodents, which is explained cryo-EM structure revealed binding...
A chiral oxazaborolidine combined with SnCl4 has been found to promote the dearomative spirocyclization of electron-rich benzyl allenyl ketones. The reaction outcome is sensitive nature activating acid, which was rationalized using hard–soft acid–base (HSAB) theory. spirocyclic product obtained up 72% ee, best result reported date for these substrates. formation cross-conjugated or conjugated products readily controlled by changing oxygen-protecting groups.
Abstract For the first time, chemoselective coupling of a carbon nucleophile with methyl, ethyl, propyl, and butyl arenes in absence directing group is described.
Key words electrophilic amination - cobalt catalysis acridines quinolines
Key words imidazopyridines - nucleophilic aromatic substitution isonitriles alkylation
Key words pyrrolizines - asymmetric catalysis cascade reaction isothiourea
Abstract The recently published route towards α,α‐disubstituted α‐amino acids via umpolung N‐alkylation followed by asymmetric allylic alkylation is combined with cross‐metathesis and ring‐closing metathesis, respectively, broadening the diversity giving even access to higher ring homologes of α‐substituted prolines.
Abstract The first asymmetric tandem N‐alkylation/π‐allylation of α‐iminoesters (I) is described to allow the synthesis enantioenriched quaternary α‐amino acid derivatives (IV) and (VI).