A5072135340- Asymmetric Hydrogenation and Catalysis
- Synthetic Organic Chemistry Methods
- Chemical Synthesis and Analysis
- Asymmetric Synthesis and Catalysis
- Catalytic C–H Functionalization Methods
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Cyclopropane Reaction Mechanisms
- Advanced NMR Techniques and Applications
- Microbial Natural Products and Biosynthesis
- Fluorine in Organic Chemistry
- Magnetism in coordination complexes
- Synthesis and Catalytic Reactions
- Catalytic Alkyne Reactions
- Ferrocene Chemistry and Applications
- Organometallic Complex Synthesis and Catalysis
- Solid-state spectroscopy and crystallography
- Atomic and Subatomic Physics Research
- Fuel Cells and Related Materials
- Inorganic Chemistry and Materials
- Click Chemistry and Applications
- Catalytic Cross-Coupling Reactions
- Electron Spin Resonance Studies
- Peptidase Inhibition and Analysis
- Synthesis and Characterization of Heterocyclic Compounds
Duke University
2016-2024
Durham Technical Community College
2019-2020
Center for Child and Family Health
2016-2019
The Family Center
2019
Radboud University Nijmegen
2017
Boston College
2006-2015
Harvard University
2011-2013
Massachusetts Institute of Technology
2006-2009
Conventional magnetic resonance (MR) faces serious sensitivity limitations which can be overcome by hyperpolarization methods, but the most common method (dynamic nuclear polarization) is complex and expensive, applications are limited short spin lifetimes (typically seconds) of biologically relevant molecules. We use a recently developed method, SABRE-SHEATH, to directly hyperpolarize (15)N2 magnetization long-lived singlet order, with signal decay time constants 5.8 23 minutes,...
Catalytic enantioselective synthesis of small-molecule building blocks with allylic stereogenic centers is an important objective in organic synthesis, but preparing this motif wherein the adjacent olefin 1,2-disubstituted a single step tremendous challenge. Late-transition-metal-catalyzed intermolecular couplings nucleophiles and 1,3-dienes hydrofunctionalization reactions have quickly emerged as compelling approach to these related compounds. In Perspective, we illustrate how diene...
A total synthesis of the Aspidosperma alkaloid quebrachamine in racemic form is first described. key catalytic ring-closing metathesis an achiral triene used to establish all-carbon quaternary stereogenic center and tetracyclic structure natural product; transformation proceeds with reasonable efficiency through use existing Ru or Mo catalysts. Ru- Mo-based chiral olefin catalysts have proven be inefficient entirely nonselective cases where desired product observed. In present study, route...
We report a method for the catalytic, enantioselective intermolecular addition of aliphatic amines to acyclic 1,3-dienes. In most cases, reactions proceed efficiently at or below room temperature in presence 5 mol % Pd catalyst bearing PHOX ligand, generating allylic up 97:3 er. The an electron-deficient phosphine within ligand not only leads more active but also is critical achieving high site selectivity transformation.
The first catalytic route toward the title compounds by asymmetric ring-closing metathesis is described. A remarkable reversal of enantioselectivity observed when achiral imido ligand chiral molybdenum-catalyst changed (see scheme), thus highlighting importance and ligands in catalyst design. Detailed facts to specialist readers are published as "Supporting Information". Such documents peer-reviewed, but not copy-edited or typeset. They made available submitted authors. Please note:...
We report a highly enantioselective Pd-PHOX-catalyzed intermolecular hydroalkylation of acyclic 1,3-dienes. Meldrum's acid derivatives and other activated C-pronucleophiles, such as β-diketones malononitriles, react with variety aryl- alkyl-substituted dienes in ≤20 h at room temperature. The coupled products, obtained up to 96% yield 97.5:2.5 er, are easily transformed into useful chemical building blocks for downstream synthesis.
Signal Amplification by Reversible Exchange (SABRE) is a fast and convenient NMR hyperpolarization method that uses cheap readily available para-hydrogen as source. SABRE can hyperpolarize protons heteronuclei. Here we focus on the heteronuclear variant introduced SABRE-SHEATH (SABRE in SHield Enables Alignment Transfer to Heteronuclei) nitrogen-15 targets particular. We show 15N-SABRE works more efficiently wider range of substrates than 1H-SABRE, greatly generalizing approach. In addition,...
In this study, we establish that conjugated enynes undergo selective 1,4-hydroamination under Pd catalysis to deliver chiral allenes with pendant allylic amines. Several primary and secondary aliphatic aryl-substituted amines couple a wide range of mono- disubstituted in nonenantioselective reaction where DPEphos serves as the ligand for Pd. Benzophenone imine acts an ammonia surrogate afford two-step/one-pot process. Examination catalysts revealed high degree reversibility C–N bond...
We introduce a new strategy for synthesis of chiral amines: couplings α-aminoalkyl nucleophiles generated by enantioselective migratory insertion 2-azadienes to Cu-H. In this report, we demonstrate its application in catalytic reductive coupling and ketones furnish 1,2-amino tertiary alcohols with vicinal stereogenic centers.
Here we report highly efficient and chemoselective azadiene–imine reductive couplings catalyzed by (Ph-BPE)Cu–H that afford anti-1,2-diamines. In all cases, reactions take place with either aldimine or ketimine electrophiles to deliver a single diastereomer of product in >95:5 er. The products' diamines are easily differentiable, facilitating downstream synthesis.
Signal amplification by reversible exchange (SABRE) is an inexpensive, fast, and even continuous hyperpolarization technique that uses para-hydrogen as source. However, current SABRE faces a number of stumbling blocks for translation to biochemical clinical settings. Difficulties include inefficient polarization in water, relatively short-lived 1H-polarization, limited substrate scope. Here we use water-soluble transfer catalyst hyperpolarize nitrogen-15 variety molecules with SABRE-SHEATH...
We report the development of highly enantio- and regioselective Pd-catalyzed intermolecular hydroaminations challenging 1,4-disubstituted acyclic dienes. Several aryl/alkyl-disubstituted dienes a sterically differentiated alkyl/alkyl-disubstituted diene undergo coupling with variety secondary aliphatic amines, indoline, primary anilines to generate allylic amines myriad α-alkyl groups in up 78% yield, >98:2 rr, 98.5:1.5 er. A number experiments, including deuterium labeling transamination...
We describe the development of Pd–PHOX-catalysed enantioselective couplings internal dienes with malononitrile and other activated C-pronucleophiles.
Diazirines are an attractive class of potential molecular tags for magnetic resonance imaging owing to their biocompatibility and ease incorporation into a large variety molecules. As recently reported, 15 N2 -diazirine can be hyperpolarized by the SABRE-SHEATH method, sustaining both singlet magnetization states, thus offering path long-lived polarization storage. Herein, we show generality this approach illustrating that diazirine tag alone is sufficient achieving excellent signal...
The exploitation of the
Pacidamycins are a family of uridyl peptide antibiotics that inhibit the translocase MraY, an essential enzyme in bacterial cell wall biosynthesis to date has not been clinically targeted. The pacidamycin structural skeleton contains doubly inverted peptidyl chain with β-peptide and ureido linkage as well 3'-deoxyuridine nucleoside attached DABA(3) via enamide linkage. Although biosynthetic gene cluster for pacidamycins was identified recently, assembly line this group remained poorly...
Nitrogen heterocycles are the key functional and structural elements in both RNA DNA, half a dozen of most important coenzymes, many synthetic drug scaffolds. On other hand, only 3 20 proteinogenic amino acids have nitrogen heterocycles: proline, histidine, tryptophan. This inventory can be augmented microbial proteins by posttranslational modifications downstream leader peptide regions that convert up to 10 serine, threonine, cysteine residues, side chains backbones, into oxazoles,...
The present study provides spectroscopic and experimental evidence demonstrating that degenerate metathesis is critical to the effectiveness of this emerging class chiral catalysts. Isolation X-ray characterization both diastereomeric complexes, as well an examination reactivity enantioselectivity patterns exhibited by such initiating neophylidenes in promoting ring-closing processes, are disclosed. Only when sufficient amounts ethylene generated inversion at Mo through processes occurs a...
Berninamycin is a member of the pyridine-containing thiopeptide class antibiotics that undergoes massive posttranslational modifications from ribosomally generated preproteins. has 2-oxazolyl-3-thiazolyl-pyridine core embedded in 35-atom macrocycle rather than typical trithiazolylpyridine cores 26-atom and 29-atom peptide macrocycles. We describe cloning an 11-gene berninamycin cluster Streptomyces bernensis UC 5144, its heterologous expression lividans TK24 venezuelae ATCC 10712, detection...
We report the synthesis of α-trifluoromethyl benzylic amines through vicinal fluoroarylation gem-difluoro-2-azadienes. Our studies indicate that XPhos plays an important role as a phase transfer catalyst promotes addition AgF to difluoroazadiene, generating azaallyl-silver intermediate we have characterized by NMR spectroscopy. This likely transmetallates Pd, coupling several aryl iodides deliver products in up 90% yield. Modification azadiene's activating group facilitates challenging...
We describe a strategy for the enantio- and diastereoselective synthesis of homoallylic α-trifluoromethyl amines by catalytic hydroalkylation terminal dienes. Trifluoromethyl-substituted isatin-derived azadienolate nucleophiles undergo γ-selective alkylation with Pd–DTBM-SEGPHOS catalyst, which additionally promotes regioselective addition to diene delivers products in up 86% yield, 10:1 dr, 97.5:2.5 er.
We report the enantioselective formation of quaternary stereogenic centers by intermolecular addition malononitrile, an acyl anion equivalent, and related pronucleophiles to several 1,3-disubstituted acyclic 1,3-dienes in presence a Pd–PHOX catalyst. Products are obtained up 88% yield 99:1 er most cases formed as single regioisomer. The products' malononitrile unit undergoes oxidative functionalization afford β,γ-unsaturated carbonyls bearing internal olefins α-quaternary centers.
We introduce a new reagent class, 2-azatrienes, as platform for catalytic enantioselective synthesis of allylic amines. Herein, we demonstrate their promise by diastereodivergent syn- and anti-1,2-diamines through Cu-bis(phosphine)-catalyzed reductive couplings with imines. With Ph-BPE the supporting ligand, anti-diamines are obtained (up to 91% yield, >20:1 dr, >99:1 er), rarely utilized t-Bu-BDPP, syn-diamines generated 76% 1:>20 97:3 er).