35 results on '"Travis Dudding"'
Search Results
2. Carbonyl-Directed Aliphatic Fluorination: A Special Type of Hydrogen Atom Transfer Beats Out Norrish II
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John D. Tovar, Thomas Lectka, Travis Dudding, Joseph N. Capilato, Cody Ross Pitts, Ivor Smajlagic, Stefan Andrew Harry, Fereshte Ghorbani, Garvin N Peters, Maxime A. Siegler, and Jacob Joram
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chemistry.chemical_classification ,Reaction mechanism ,Ketone ,Intermolecular force ,General Chemistry ,Fluorine-19 NMR ,Hydrogen atom ,010402 general chemistry ,Hydrogen atom abstraction ,01 natural sciences ,Biochemistry ,Catalysis ,0104 chemical sciences ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,chemistry ,Computational chemistry ,Benzil ,Enone - Abstract
Recently, our group reported that enone and ketone functional groups, upon photoexcitation, can direct site-selective sp3 C-H fluorination in terpenoid derivatives. How this transformation actually occurred remained mysterious, as a significant number of mechanistic possibilities came to mind. Herein, we report a comprehensive study describing the reaction mechanism through kinetic studies, isotope-labeling experiments, 19F NMR, electrochemical studies, synthetic probes, and computational experiments. To our surprise, the mechanism suggests intermolecular hydrogen atom transfer (HAT) chemistry is at play, rather than classical Norrish hydrogen atom abstraction as initially conceived. What is more, we discovered a unique role for photopromoters such as benzil and related compounds that necessitates their chemical transformation through fluorination in order to be effective. Our findings provide documentation of an unusual form of directed HAT and are of crucial importance for defining the necessary parameters for the development of future methods.
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- 2020
3. Diversity-oriented synthesis of glycomimetics
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Louis-Charles Campeau, Milan Bergeron-Brlek, Bharanishashank Adluri, Hayden Foy, Rozhin Rowshanpour, Travis Dudding, Venugopal Rao Challa, Weiwu Ren, Gaelen Fehr, Victoria Rose, Johannes Lehmann, Steven M. Silverman, Robert Britton, Christopher Adamson, and Michael Meanwell
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chemistry.chemical_classification ,Steric effects ,010405 organic chemistry ,Carbasugars ,General Chemistry ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Aldehyde ,Combinatorial chemistry ,0104 chemical sciences ,Kinetic resolution ,Chemistry ,chemistry ,Aldol reaction ,Glycomimetic ,Materials Chemistry ,Environmental Chemistry ,QD1-999 - Abstract
Glycomimetics are structural mimics of naturally occurring carbohydrates and represent important therapeutic leads in several disease treatments. However, the structural and stereochemical complexity inherent to glycomimetics often challenges medicinal chemistry efforts and is incompatible with diversity-oriented synthesis approaches. Here, we describe a one-pot proline-catalyzed aldehyde α-functionalization/aldol reaction that produces an array of stereochemically well-defined glycomimetic building blocks containing fluoro, chloro, bromo, trifluoromethylthio and azodicarboxylate functional groups. Using density functional theory calculations, we demonstrate both steric and electrostatic interactions play key diastereodiscriminating roles in the dynamic kinetic resolution. The utility of this simple process for generating large and diverse libraries of glycomimetics is demonstrated in the rapid production of iminosugars, nucleoside analogues, carbasugars and carbohydrates from common intermediates. Glycomimetics are structural mimics of carbohydrates that can replicate their biological activity but have improved drug-like properties. Here, using proline-catalysed α-halogenation/aldol cascades, carbohydrate building blocks are readily assembled and then diversified into glycomimetics including imino- and carbasugars.
- Published
- 2021
4. A mechanistic study of oxygen atom transfer from N-sulfonyloxaziridine to enolates
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Travis Dudding, Adrian L. Schwan, and Hayden Foy
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Steric effects ,010405 organic chemistry ,Organic Chemistry ,chemistry.chemical_element ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Oxaziridine ,0104 chemical sciences ,Metal ,chemistry.chemical_compound ,Oxygen atom ,chemistry ,Computational chemistry ,visual_art ,Drug Discovery ,visual_art.visual_art_medium ,Reactivity (chemistry) ,Chelation ,Lithium - Abstract
Enolate additions to chiral N-sulfonyloxaziridines providing enantiomerically enriched α-hydroxy carbonyl compounds is a reaction of importance, yet a clear understanding of the factors governing stereoinduction in these transformations remains ambiguous. This is despite, previous computational studies, one by Bach et al. employing truncated model systems exploring oxygen atom transfer to an unsubstituted lithium enolate and another by our own group. In clarifying this reactivity we report here a computational study examining oxygen atom transfer from 1-S-(+)-(10-camphorsulfonyl)oxaziridine, viz., archetypal Davis chiral oxaziridine to substituted Li, Na, K enolates offering improved mechanistic understanding. From this investigation, a revised model is offered revealing the metal cation, chelation effects and sterics as decisive stereocontrolling factors in enolate additions to chiral N-sulfonyloxaziridines affording enantiomerically enriched α-hydroxy carbonyl compounds.
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- 2019
5. Direct Observation and Analysis of the Halo-Amino-Nitro Alkane Functional Group
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Michael S. Crocker, Kazuyuki Tokumaru, Travis Dudding, Jeffrey N. Johnston, Hayden Foy, and Maren Pink
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Stereochemistry ,General Chemical Engineering ,Biochemistry (medical) ,Reactive intermediate ,Nitroalkane ,02 engineering and technology ,General Chemistry ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,Biochemistry ,Article ,0104 chemical sciences ,Umpolung ,chemistry.chemical_compound ,Nucleophile ,chemistry ,Tetrahedral carbonyl addition compound ,Amide ,Electrophile ,Materials Chemistry ,Environmental Chemistry ,Nitronate ,0210 nano-technology - Abstract
Conventional amide synthesis is a mainstay in discipline-spanning applications, and it is a reaction type that historically developed as a singular paradigm when considering the carbon-nitrogen bond-forming step. Umpolung amide synthesis (UmAS) exploits the unique properties of an α-halo nitroalkane in its reaction with an amine to produce an amide. The "umpolung" moniker reflects its paradigm-breaking C-N bond formation on the basis of evidence that the nucleophilic nitronate carbon and electrophilic nitrogen engage to form a tetrahedral intermediate (TI) that is an unprecedented functional group, a 1,1,1-halo-amino-nitro alkane (HANA). Studies probing HANA transience have failed to capture this (presumably) highly reactive intermediate. We report here the direct observation of a HANA, its conversion thermally to an amide functionality, and quantitative analysis of this process using computational techniques. These findings validate the HANA as a functional group common to UmAS and diverted UmAS, opening the door to its targeted use and creative manipulation.
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- 2020
6. Synthesis of α-Borylated Ketones by Regioselective Wacker Oxidation of Alkenylboronates
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Hayden Foy, Shinya Adachi, Aleksandra Holownia, Travis Dudding, Victoria B. Corless, Rodrigo Mendoza-Sanchez, and Andrei K. Yudin
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010405 organic chemistry ,Organic Chemistry ,Regioselectivity ,chemistry.chemical_element ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Medicinal chemistry ,3. Good health ,0104 chemical sciences ,chemistry.chemical_compound ,Wacker process ,chemistry ,Functional group ,Group effect ,Molecule ,Dipolar bond ,Physical and Theoretical Chemistry ,Selectivity ,Boron - Abstract
As part of a program aimed at metal-catalyzed oxidative transformations of molecules with carbon-metalloid bonds, the synthesis of α-borylated ketones is reported via regioselective TBHP-mediated Wacker-type oxidation of N-methyliminodiacetic acid (MIDA)-protected alkenylboronates. The observed regioselectivity correlates with the hemilabile nature of the B-N dative bond in the MIDA boronate functional group, which allows boron to guide selectivity through a neighboring group effect.
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- 2018
7. Expanding the repertoire of cyclopropenium ion phase transfer catalysis: Benzylic fluorination
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Travis Dudding, Ivor Smajlagic, Katie Dempsey, and Roya Mir
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010405 organic chemistry ,Organic Chemistry ,Fluorine-19 NMR ,010402 general chemistry ,Photochemistry ,01 natural sciences ,Biochemistry ,0104 chemical sciences ,Ion ,Catalysis ,chemistry.chemical_compound ,chemistry ,Phase (matter) ,Drug Discovery ,Density functional theory ,Spectroscopy ,Phase-transfer catalyst ,Fluoride - Abstract
The application of cyclopropenium ion as a phase transfer catalyst for benzylic fluorination in high yields is reported. Integral to the mechanisms of these fluorination reactions was the role of in situ derived cyclopropenium fluoride complexes, the existence of which was supported by 1H, 19F NMR and UV–Vis spectroscopy. Density functional theory calculations were applied to gain insight into the mechanism of these reactions.
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- 2018
8. Charge-enhanced thiourea catalysts as hydrogen bond donors for Friedel‒Crafts Alkylations
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Travis Dudding, Brenden Carlson, Nicholas Rosano, Ivor Smajlagic, and Hayden Foy
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010405 organic chemistry ,Hydrogen bond ,Organic Chemistry ,Cationic polymerization ,Alkylation ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Combinatorial chemistry ,3. Good health ,0104 chemical sciences ,Catalysis ,chemistry.chemical_compound ,Thiourea ,chemistry ,Drug Discovery ,Moiety ,Density functional theory ,Friedel–Crafts reaction - Abstract
Charge-enhanced catalysis has emerged as a powerful alternative to the mainstream use of neutral catalysis. With this in mind, we report a catalytic Friedel‒Crafts alkylation method catalyzed by a charged thiourea incorporating a cationic cyclopropenium moiety. Mechanistic studies, including density functional theory computational calculations, variable time normalization analysis, and 1H NMR binding studies, collectively reveal this charge-enhanced reactivity proceeds by a dual hydrogen bond-mediated LUMO-lowering mode of substrate activation. Key to these findings is the observed steady-state concentration of the catalyst with in situ derived monomeric catalytic species predominating under the reaction conditions.
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- 2019
9. Expanding the Forefront of Strong Organic Brønsted Acids: Proton-Catalyzed Hydroamination of Unactivated Alkenes and Activation of Au(I) for Alkyne Hydroamination
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Roya Mirabdolbaghi and Travis Dudding
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Models, Molecular ,Alkyne ,Crystal structure ,Alkenes ,Crystallography, X-Ray ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Medicinal chemistry ,Catalysis ,Boric Acids ,Borates ,Organic chemistry ,Amines ,Physical and Theoretical Chemistry ,Amination ,chemistry.chemical_classification ,Aniline Compounds ,Molecular Structure ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,Intermolecular force ,Hydrogen-Ion Concentration ,0104 chemical sciences ,Alkynes ,Quantum Theory ,Gold ,Hydroamination ,Brønsted–Lowry acid–base theory - Abstract
The synthesis of a solid, bench-stable, strong organic Brønsted acid with a computed pKa of 0.9 is reported. An X-ray crystal structure and DFT calculations are provided which offer insight into the bonding of this acid. The application of this strong organic Brønsted acid as a catalyst for the intermolecular hydroamination of unactivated alkenes and as an activator for Au(I)-catalyzed alkyne hydroamination with anilines is described.
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- 2015
10. Hydroxyproline-Derived Pseudoenantiomeric [2.2.1] Bicyclic Phosphines: Asymmetric Synthesis of (+)- and (−)-Pyrrolines
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Tioga J. Martin, Qihai Xu, Ohyun Kwon, Lee Belding, Travis Dudding, Christopher E. Henry, and Yi Chiao Fan
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Bicyclic molecule ,Molecular Structure ,Chemistry ,Phosphines ,Communication ,Enantioselective synthesis ,Stereoisomerism ,General Chemistry ,Biochemistry ,Catalysis ,3. Good health ,Bridged Bicyclo Compounds ,Hydroxyproline ,Colloid and Surface Chemistry ,Organic chemistry ,Pyrroles - Abstract
We have prepared two new diastereoisomeric 2-aza-5-phosphabicyclo[2.2.1]heptanes from naturally occurring trans-4-hydroxy-l-proline in six chemical operations. These syntheses are concise and highly efficient, with straightforward purification. When we used these chiral phosphines as catalysts for reactions of γ-substituted allenoates with imines, we obtained enantiomerically enriched pyrrolines in good yields with excellent enantioselectivities. These two diastereoisomeric phosphines functioned as pseudoenantiomers, providing their chiral pyrrolines with opposite absolute configurations.
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- 2014
11. Diastereodivergent total synthesis of mosquito oviposition pheromone
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Travis Dudding and David Hurem
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chemistry.chemical_classification ,chemistry.chemical_compound ,chemistry ,Biochemistry ,Stereochemistry ,General Chemical Engineering ,Pheromone ,Fatty acid ,Total synthesis ,General Chemistry ,Undecanal - Abstract
The unnatural threo-6-acetoxy-5-hexadecanolide and the natural mosquito oviposition pheromone erythro-6-acetoxy-5-hexadecanolide were synthesized in a diastereodivergent fashion in 44% and 33% overall yield respectively from 5-bromovaleric acid and undecanal. The key step utilized a chemoenzymatic epoxidation-lactonization of a naturally available fatty acid to form the 6-hydroxy-5-hexadecanolide core.
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- 2014
12. Competitive hydrogen bonding of cyclopropenium ions: Implications of an anion switch
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Matt Guest, Melanie Pilkington, Lee Belding, Travis Dudding, and Richard Le Sueur
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Diffraction ,010405 organic chemistry ,Hydrogen bond ,Chemistry ,Organic Chemistry ,Intermolecular force ,010402 general chemistry ,Photochemistry ,01 natural sciences ,Biochemistry ,Fluorescence spectroscopy ,0104 chemical sciences ,Ion ,Intramolecular force ,Drug Discovery ,Proton NMR ,Spectroscopy - Abstract
This work demonstrates how modulating hydrogen bonding between intermolecular, bifurcated, and intramolecular interactions can be used to tune the structural, electronic, and photophysical properties of cyclopropenium ions and their respective fluorophores. The basis of this switchability was examined using X-ray diffraction analysis, 1 H NMR spectroscopy, DFT calculations, and fluorescence spectroscopy.
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- 2019
13. A synthetic route to chiral C(3)-functionalized phthalides via a Ag(I)-catalyzed allylation/transesterification sequence
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Travis Dudding and Roya Mirabdolbaghi
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chemistry.chemical_classification ,Chain length ,Chemistry ,Organic Chemistry ,Drug Discovery ,Organic chemistry ,Sequence (biology) ,Transesterification ,Enantiomeric excess ,Transesterification reaction ,Biochemistry ,Alkyl ,Catalysis - Abstract
A Ag(I)-catalyzed synthesis of chiral C(3)-substituted phthalides (8a–f) via a Sakurai–Hosomi allylation/transesterification reaction is described (ee ≤86%). A notable feature of this reaction is that it utilizes ortho-substituted aldehydes, which are a class of compounds that generally afford poor levels of stereoinduction when applying most known catalytic asymmetric allylation approaches. It was also found that elongation of the n-alkyl chain length (R1, up to n=6; R2=H) of the starting alkyl 2-formylbenzoates (7g–i) improved the enantiomeric excess (ee) of the product.
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- 2013
14. Application of<scp>D</scp>-chiro-Inositol as a Chiral Template for theDielsAlderReaction
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John F. Trant, Travis Dudding, Lee Belding, and Tomas Hudlicky
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Stereochemistry ,Organic Chemistry ,Cyclohexene ,Biochemistry ,Catalysis ,Cinnamic acid ,Cycloaddition ,Inorganic Chemistry ,chemistry.chemical_compound ,chemistry ,Drug Discovery ,Organic chemistry ,Physical and Theoretical Chemistry ,Enantiomer ,Derivative (chemistry) ,Diels–Alder reaction - Abstract
by John F. Trant, Lee Belding, Travis Dudding, and Tomas Hudlicky*Department of Chemistry and Centre for Biotechnology, Brock University, 500 Glenridge Avenue,St Catharines ON, L2S 3A1, Canada(phone: þ1905688-5550 (ext. 3406); fax: þ1905682-9020; e-mail: thudlicky@brocku.ca)DedicatedtoProfessorDieterSeebachontheoccasionofhis75thbirthdayandinrecognitionofhismanycontributions to our disciplineThe Diels Alder reaction can reliably provide the expected endo-product in the presence ofsecondary orbital overlap. It can be considerably more difficult to access a single enantiomer of the exo-product. In this paper, a d-chiro-inositol derivative is used as a chiral tether to facilitate the regio-,diastereo-, and enatioselective cycloaddition between cinnamic acid and hexa-3,5-dienoic acid. TheDiels Alder reaction between these two substrates, or their respective esters, does not occur underthermal conditions. Because of the ease of removal of the chiral tether from the resulting cyclohexene,this approach could provide a viable technique to access otherwise unavailable systems.
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- 2012
15. Studies on the ring opening reactions of 3-oxa-1-azabicyclo[3.1.0]hexan-2-ones. Synthesis of aminomethyl oxazolidinones and aziridinyl ureas
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Jeffery A. Frick, Travis Dudding, Junfeng Huang, Abhijit Nayek, Stephen C. Bergmeier, Steven J. Katz, Lee Belding, and Greggory M. Wells
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Reaction conditions ,Organic Chemistry ,Aziridine ,Ring (chemistry) ,Biochemistry ,Medicinal chemistry ,Solvent ,chemistry.chemical_compound ,chemistry ,Nucleophile ,Drug Discovery ,Urea ,Organic chemistry ,Amine gas treating ,Stoichiometry - Abstract
The reaction of fused ring aziridines, 3-oxa-1-azabicyclo[3.1.0]hexan-2-ones, with amine nucleophiles can provide either an aminomethyl oxazolidinone or an aziridinyl urea. The amine, reaction solvent, and aziridine substitution have been examined with the aid of computational studies to identify reaction conditions that provide a single product. Polar solvents provided only the aminomethyl oxazolidinone products. Formation of aziridinyl ureas required control of aziridine substitution, solvent, and reactant stoichiometry.
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- 2012
16. A catalytic asymmetric approach to C1-chiral 3-methylene-indan-1-ols
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Travis Dudding and Roya Mirabdolbaghi
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Organic Chemistry ,chemistry.chemical_element ,Biochemistry ,Medicinal chemistry ,Catalysis ,chemistry.chemical_compound ,chemistry ,Heck reaction ,Drug Discovery ,Triphenylphosphine ,Methylene ,Enantiomeric excess ,Palladium ,Sakurai reaction - Abstract
A sequential (R)-BINAP·AgIF (2,2′-bis(diphenylphosphino)-1,1′-binaphthyl) (6–10 mol %), and (Ph3P)2PdIICl2 (bis(triphenylphosphine)palladium(II) dichloride) (2 mol %) catalyzed asymmetric Sakurai–Hosomi–Yamamoto allylation/Mizoroki–Heck reaction that affords C1-chiral 3-methylene-indan-1-ols with enantiomeric excess (ee) up to 80% is reported. Notably, this protocol allows for the use of various o-substituted benzaldehydes and allyltrimethoxysilane. It was also discovered that the presence of electron-rich groups had no effect on the enantioselectivity of the reaction, whereas electron-withdrawing groups lead to erosion in product ee.
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- 2012
17. The enzymatic cleavage of Si–O bonds: A kinetic analysis of the biocatalyzed hydrolysis of phenyltrimethoxysilane
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Mark B. Frampton, Razvan Simionescu, Paul M. Zelisko, and Travis Dudding
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Reaction mechanism ,biology ,Chemistry ,Stereochemistry ,Process Chemistry and Technology ,Substrate (chemistry) ,Active site ,Bioengineering ,Trypsin ,Biochemistry ,Catalysis ,Chemical kinetics ,Hydrolysis ,Polymer chemistry ,Alkoxy group ,biology.protein ,medicine ,Moiety ,medicine.drug - Abstract
Previously we reported the ability of trypsin to mediate the cross-linking of alkoxysily-functionalized silicone polymers. Although enzymes and silicon-containing compounds are not necessarily incompatible species, the exact mechanism of how enzymes process silicon substrates is not fully understood. The focus of this current work was to examine the reaction kinetics associated with the processing of an alkoxysilane substrate by enzymes using 29 Si NMR so as to gain a greater insight into the actual reaction mechanism, especially those involving more complex silicone systems. A series of time course 29 Si NMR experiments using D 2 O revealed that the trypsin-mediated hydrolysis of a single alkoxy moiety in water is a pseudo-first order reaction. The relative effect of the enzyme was determined to be β = 3.549 while the relative effect of water was γ = 3.325. Prolonged contact with phenyltrimethoxysilane was not sufficiently deleterious to the enzyme and did not induce the complete and irreversible denaturation of trypsin. Computational evidence suggests that while in the active site of the enzyme, serine addition to silicon to forms a pentacoordinate species and is favoured over histidine addition.
- Published
- 2010
18. Inverse Temperature Dependence in the Diastereoselective Addition of Grignard Reagents to a Tetrahydrofurfural
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Baldip Kang, Branden Fonovic, Jeffrey Mowat, Travis Dudding, and Robert Britton
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Molecular Structure ,Chemistry ,Stereochemistry ,Organic Chemistry ,Temperature ,Diastereomer ,Inverse temperature ,Stereoisomerism ,Biochemistry ,Catalysis ,Models, Chemical ,Computational chemistry ,Reagent ,Furaldehyde ,Indicators and Reagents ,Physical and Theoretical Chemistry - Abstract
A remarkable example of inverse-temperature-dependent diastereoselectivity was uncovered while investigating the addition of Grignard reagents to a 3-hydroxytetrahydrofurfural. The free hydroxyl group in the tetrahydrofurfural was found to play a key role in these processes, a result corroborated through a series of DFT calculations that also highlighted an entropic preference for the formation of one diastereomer.
- Published
- 2009
19. Theory-guided design of Brønsted acid-assisted phosphine catalysis: synthesis of dihydropyrones from aldehydes and allenoates
- Author
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Travis Dudding, Ohyun Kwon, Branden Fonovic, Gardner S. Creech, and Xue-Feng Zhu
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chemistry.chemical_classification ,010405 organic chemistry ,Allene ,Organic Chemistry ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Combinatorial chemistry ,Aldehyde ,Article ,0104 chemical sciences ,Catalysis ,chemistry.chemical_compound ,chemistry ,Drug Discovery ,Organic chemistry ,Lewis acids and bases ,Triphenylphosphine ,Brønsted–Lowry acid–base theory ,Phosphine - Abstract
The phosphine-catalyzed addition of 2,3-butadienoates to aldehydes has been extended to the formation of disubstituted dihydro-2-pyrones. The requisite shift in equilibrium of the intermediate zwitterionic beta-phosphonium dienolates toward the s-cis intermediate was accomplished through the use of a Brønsted acid additive, which disrupts the favorable Coulombic interaction present in the s-trans intermediate. The detailed nature of the synergistic interactions involving the Brønsted acid additives and phosphine involved in the formation of s-cis beta-phosphonium dienolates was analyzed through a series of DFT calculations. Unlike previously reported annulations of aldehydes with allenoates, where trialkylphosphines are optimal catalysts, in this study triphenylphosphine was also found for the first time to be a suitable catalyst for the synthesis of dihydropyrones. This method provides a one-step route toward functionalized dihydropyrones from simple, stable starting materials. In addition, new reaction pathways of phosphine-catalyzed allene annulations are unveiled, with the formation of dihydropyrones being the first example of dual activation in this sphere.
- Published
- 2008
20. Phosphine triggered [3+2] allenoate–acrylate annulation: a mechanistic enlightenment
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Christopher E. Henry, Ohyun Kwon, Branden Fonovic, Evan Mercier, and Travis Dudding
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Acrylate ,chemistry.chemical_compound ,Annulation ,Chemistry ,Mechanism (philosophy) ,Stereochemistry ,Organic Chemistry ,Drug Discovery ,Product formation ,Biochemistry ,Cycloaddition ,Phosphine - Abstract
A mechanistic study of phosphine-mediated [3+2] annulation of allenoate and acrylate is presented. The insight gained has identified that (1) [3+2] cycloaddition proceeds through a stepwise mechanism and (2) the involvement of a molecule of water, which services as a proton-shuttle, is essential for annulated product formation.
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- 2007
21. Molecular mechanics calculations as predictors of enantioselectivity for chiral nucleophile catalyzed reactions
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Travis Dudding, Andrew E. Taggi, Ahmed M. Hafez, and Thomas Lectka
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Stereochemistry ,Organic Chemistry ,Enantioselective synthesis ,Ketene ,Biochemistry ,Molecular mechanics ,Cycloaddition ,Force field (chemistry) ,Catalysis ,chemistry.chemical_compound ,chemistry ,Nucleophile ,Computational chemistry ,Drug Discovery ,Selectivity - Abstract
We present molecular mechanics (MM) calculations as models of activated complexes for the β-lactam forming [2+2] cycloaddition between imino ester 4 and the zwitterionic intermediates derived from ketenes and various chiral nucleophilic catalysts. Our method employs the use of Monte Carlo conformational searches utilizing the MMFF force field contained within the Macromodel program. These models accurately predict the sense of stereochemical induction observed experimentally. Also, the predicted energetic differences for minima leading to (R) or (S)-derived ketene facial selectivity correlate in a general sense with the magnitude of the enantioselectivity. This work establishes that our approach represents a viable method for the design of new nucleophilic catalysts a priori using MM calculations.
- Published
- 2002
22. A Catalyst that Plays Multiple Roles: Asymmetric Synthesis of β-Substituted Aspartic Acid Derivatives through a Four-Stage, One-Pot Procedure
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Andrew E. Taggi, Ty R. Wagerle, Travis Dudding, Thomas Lectka, and Ahmed M. Hafez
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Aspartic Acid ,Chemistry ,Stereochemistry ,Organic Chemistry ,Enantioselective synthesis ,Ring (chemistry) ,Biochemistry ,Medicinal chemistry ,Catalysis ,Nucleophile ,Aspartic acid ,Dehydrohalogenation ,Physical and Theoretical Chemistry - Abstract
We report a new method for the catalytic, asymmetric synthesis of beta-substituted aspartic acid derivatives in which the nucleophilic catalyst serves up to four discrete roles in a one-pot procedure: catalytic dehydrohalogenation of acid chlorides to form ketenes; catalytic dehydrohalogenation of alpha-chloroamines to form the corresponding imines; catalyzed [2 + 2]-cycloaddition to produce intermediate acyl beta-lactams; and finally, nucleophilic ring opening to afford optically enriched beta-substituted aspartic acids in high enantioselectivity and diastereoselectivity.
- Published
- 2002
23. A class of phase-transfer catalyst with interionic strain: insight into the bonding of disubstituted N- vs carbene-stabilized N(I)-centered cations
- Author
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Roya Mirabdolbaghi, Travis Dudding, and Theocharis C. Stamatatos
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chemistry.chemical_classification ,Strain (chemistry) ,Chemistry ,organic chemicals ,Organic Chemistry ,Inorganic chemistry ,chemistry.chemical_element ,Ion pairs ,Biochemistry ,Nitrogen ,Divalent ,Catalysis ,chemistry.chemical_compound ,Crystallography ,Physical and Theoretical Chemistry ,Carbene ,Phase-transfer catalyst - Abstract
The straightforward synthesis of a class of nitrogen-based phase-transfer catalysts (PTCs) having markedly dissociated anions due to interionic donor-donor "ion pair strain" and use for catalyzing benzylation and benzylic fluorination is reported. Provided also is insight into the bonding of disubstituted N- vs so-called divalent carbene-stablized N(I)-centered cations and the unprecedented finding of a cyclopropenium based C-H···πaryl interaction.
- Published
- 2014
24. Catalytic, Enantioselective Alkylation of α-Imino Esters: The Synthesis of Nonnatural α-Amino Acid Derivatives
- Author
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Thomas Lectka, Brandon Young, Christopher Cox, Travis Dudding, William J. Drury, Andrew E. Taggi, Lev R. Ryzhkov, and Dana Ferraris
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chemistry.chemical_classification ,Alkylation ,Chemistry ,Alkene ,Stereochemistry ,Imino Acids ,Enantioselective synthesis ,Ketene ,Esters ,Stereoisomerism ,General Chemistry ,Biochemistry ,Enol ,Catalysis ,Amino acid ,chemistry.chemical_compound ,Acetals ,Colloid and Surface Chemistry ,Organic chemistry ,heterocyclic compounds ,Amino Acids - Abstract
Methodology for the practical synthesis of nonnatural amino acids has been developed through the catalytic, asymmetric alkylation of alpha-imino esters and N,O-acetals by enol silanes, ketene acetals, alkenes, and allylsilanes using chiral transition metal-phosphine complexes as catalysts (1-5 mol %). The alkylation products, which are prepared with high enantioselectivity (up to 99% ee) and diastereoselectivity (up to 25:1/anti:syn), are protected nonnatural amino acids that represent potential precursors to natural products and pharmaceuticals. A kinetic analysis of the catalyzed reaction of alkenes with alpha-imino esters is presented to shed light on the mechanism of this reaction.
- Published
- 2001
25. Asymmetric Catalysis on Sequentially-Linked Columns
- Author
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Ahmed M. Hafez, Andrew E. Taggi, and Travis Dudding, and Thomas Lectka
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Lactams ,Quinine ,Chemistry ,Chemistry, Organic ,Enantioselective synthesis ,Stereoisomerism ,General Chemistry ,Biochemistry ,Chemical reaction ,Catalysis ,Colloid and Surface Chemistry ,Yield (chemistry) ,Reagent ,Organic chemistry - Abstract
We report a catalytic asymmetric reaction process that involves the use of solid-phase reagents and catalysts that constitute the packing of a series of "reaction columns". This process was applied to the catalytic asymmetric synthesis of beta-lactams, to yield pure products with excellent enantio- and diastereoselectivity. We have identified several advantages to conducting chemical reactions on sequential columns, including ease of catalyst and reagent recovery and simplified purification steps that preclude the need for chromatography.
- Published
- 2001
26. Catalytic, enantioselective alkylations of N,O- and N, N-acetals and hemiacetals
- Author
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William J. Drury, Travis Dudding, Dana Ferraris, Brandon Young, and Thomas Lectka
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chemistry.chemical_classification ,Organic Chemistry ,Enantioselective synthesis ,Alkylation ,Biochemistry ,Enol ,Silane ,Amino acid ,Catalysis ,chemistry.chemical_compound ,chemistry ,Nucleophile ,Yield (chemistry) ,Drug Discovery ,Organic chemistry - Abstract
We report the first examples of catalytic, enantioselective alkylation of N,O-acetals to produce useful amino acid derivatives 5 in high yield (73–93%) and enantioselectivity (70–96%). We have extended the utility of our reaction to include a simple one-pot procedure from readily available starting materials. We also provide several different N-based protecting groups that greatly increase the flexibility of the reaction. In addition, we have elucidated novel mechanistic information including the discovery of unique transilylations that start off the catalytic reactions of enol silane nucleophiles with N,O-acetals. These details will guide us in further explorations of the reaction's scope and utility.
- Published
- 1999
27. Hydrogen Bonding Catalysis Operates by Charge Stabilization in Highly Polar Diels−Alder Reactions
- Author
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Travis Dudding, Christopher D. Anderson, Ruth Gordillo, and Kendall N. Houk
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Hydrogen bond catalysis ,Diene ,Hydrogen bond ,Methanol ,Organic Chemistry ,Molecular Conformation ,Hydrogen Bonding ,Stereoisomerism ,Homogeneous catalysis ,Crystallography, X-Ray ,Photochemistry ,Biochemistry ,Catalysis ,Article ,Benzaldehyde ,chemistry.chemical_compound ,Models, Chemical ,chemistry ,Alcohols ,Benzaldehydes ,Molecule ,Density functional theory ,Acrolein ,Physical and Theoretical Chemistry - Abstract
[reaction: see text] The alcohol-catalyzed Diels-Alder reactions of acrolein and benzaldehyde with Rawal's diene were evaluated with density functional theory (B3LYP/6-31G(d)). Several potential modes of catalysis with two methanol molecules were used to model catalysis by TADDOLs. In agreement with crystallographic data, cooperative catalysis with TADDOLs is predicted to be favorable.
- Published
- 2007
28. An indium-mediated allylative/transesterification DFT-directed approach to chiral C(3)-functionalized phthalides
- Author
-
Roya Mirabdolbaghi and Travis Dudding
- Subjects
Steric effects ,chemistry.chemical_classification ,Aldehydes ,Esterification ,Molecular Structure ,Organic Chemistry ,chemistry.chemical_element ,Transesterification ,Biochemistry ,Combinatorial chemistry ,Aldehyde ,Indium ,Catalysis ,Chain length ,chemistry ,Organic chemistry ,Quantum Theory ,Physical and Theoretical Chemistry ,Enantiomeric excess ,Transesterification reaction ,Benzofurans - Abstract
A one-pot synthesis of chiral C(3)-substituted phthalides via an indium-mediated allylation/transesterification reaction is described. The development of this reaction was facilitated through the applied use of DFT calculations to rationalize the stereoselection of a chiral In-mediated process. It was discovered that the enantiomeric excess of this reaction depended upon the steric size, chain length, and substitution of the aldehyde employed.
- Published
- 2012
29. From bifunctional to trifunctional (tricomponent nucleophile-transition metal-lewis acid) catalysis: the catalytic, enantioselective α-fluorination of acid chlorides
- Author
-
Jeremy Erb, Travis Dudding, Daniel H. Paull, Thomas Lectka, and Lee Belding
- Subjects
Halogenation ,Chemistry ,Metals, Alkali ,Electrophilic fluorination ,Enantioselective synthesis ,Carboxylic Acids ,Ketene ,Stereoisomerism ,General Chemistry ,Biochemistry ,Catalysis ,Article ,Lewis acid catalysis ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,Nucleophile ,Chlorides ,Transition Elements ,Organic chemistry ,Lewis acids and bases ,Bifunctional ,Lewis Acids - Abstract
We report in full detail our studies on the catalytic, asymmetric α-fluorination of acid chlorides, a practical method that produces an array of α-fluorocarboxylic acid derivatives in which improved yield and virtually complete enantioselectivity are controlled through electrophilic fluorination of a ketene enolate intermediate. We discovered, for the first time, that a third catalyst, a Lewis acidic lithium salt, could be introduced into a dually activated system to amplify yields of aliphatic products, primarily through activation of the fluorinating agent. Through our mechanistic studies (based on kinetic data, isotopic labeling, spectroscopic measurements, and theoretical calculations) we were able to utilize our understanding of this "trifunctional" reaction to optimize the conditions and obtain new products in good yield and excellent enantioselectivity.
- Published
- 2011
30. NHC-catalyzed intramolecular redox amidation for the synthesis of functionalized lactams
- Author
-
Karen Thai, Travis Dudding, Li Wang, François Bilodeau, and Michel Gravel
- Subjects
Lactams ,Molecular Structure ,Hydrogen bond ,Chemistry ,Organic Chemistry ,Leaving group ,Ring (chemistry) ,Biochemistry ,Redox ,Combinatorial chemistry ,Catalysis ,Deprotonation ,Heterocyclic Compounds ,Intramolecular force ,Organic chemistry ,Physical and Theoretical Chemistry ,Methane ,Oxidation-Reduction ,Stoichiometry ,Amination ,Hydrogen - Abstract
A very efficient NHC-catalyzed lactamization reaction is reported. For most cases, the ring expansion reaction proceeds to cleanly furnish five- and six-membered N-Ts and N-Bn lactams, without the need for further purification. Evidence is presented suggesting a dual role for the stoichiometric base: (1) deprotonation of the triazolium precatalyst and (2) activation of the nitrogen leaving group through hydrogen bonding.
- Published
- 2010
31. Desymmetrizations forming tetrasubstituted olefins using enantioselective olefin metathesis
- Author
-
Shawn K. Collins, Jolaine Savoie, Travis Dudding, Justin Timperio, and Brice Stenne
- Subjects
Olefin metathesis ,Chemistry ,Organic Chemistry ,Enantioselective synthesis ,Stereoisomerism ,Alkenes ,Biochemistry ,Catalysis ,chemistry.chemical_compound ,Cyclization ,Organic chemistry ,Physical and Theoretical Chemistry ,Carbene - Abstract
Highly reactive chiral Ru-based catalysts possessing C(1)-symmetric N-heterocyclic carbene ligands adorned with one N-alkyl group and one N-aryl group were evaluated in asymmetric desymmetrizations to form cyclic products possessing a tetrasubstituted olefin.
- Published
- 2010
32. A surprising mechanistic 'switch' in Lewis acid activation: a bifunctional, asymmetric approach to alpha-hydroxy acid derivatives
- Author
-
Daniel H. Paull, Travis Dudding, Ciby J. Abraham, Thomas Lectka, Tefsit Bekele, and Michael T. Scerba
- Subjects
Models, Anatomic ,Phosphites ,Molecular Structure ,Chemistry ,Stereochemistry ,Chloranil ,Ketene ,Stereoisomerism ,General Chemistry ,Nuclear magnetic resonance spectroscopy ,Biochemistry ,Catalysis ,Article ,Quinone ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,Spectrophotometry ,Yield (chemistry) ,Lewis acids and bases ,Bifunctional ,Hydroxy Acids ,Acids ,Palladium - Abstract
We report a detailed synthetic and mechanistic study of an unusual bifunctional, sequential hetero-Diels-Alder/ring-opening reaction in which chiral, metal complexed ketene enolates react with o-quinones to afford highly enantioenriched, alpha-hydroxylated carbonyl derivatives in excellent yield. A number of Lewis acids were screened in tandem with cinchona alkaloid derivatives; surprisingly, trans-(Ph(3)P)(2)PdCl(2) was found to afford the most dramatic increase in yield and rate of reaction. A series of Lewis acid binding motifs were explored through molecular modeling, as well as IR, UV, and NMR spectroscopy. Our observations document a fundamental mechanistic "switch", namely the formation of a tandem Lewis base/Lewis acid activated metal enolate in preference to a metal-coordinated quinone species (as observed in other reactions of o-quinone derivatives). This new method was applied to the syntheses of several pharmaceutical targets, each of which was obtained in high yield and enantioselectivity.
- Published
- 2008
33. Origin of enantioselection in Hetero-Diels-Alder reactions catalyzed by naphthyl-TADDOL
- Author
-
Christopher D. Anderson, Ruth Gordillo, Travis Dudding, and Kendall N. Houk
- Subjects
ONIOM ,Models, Molecular ,Aldehydes ,Molecular Structure ,Stereochemistry ,Methanol ,Organic Chemistry ,Combined use ,Stereoisomerism ,Dioxolanes ,Naphthalenes ,Biochemistry ,Catalysis ,Benzaldehyde ,chemistry.chemical_compound ,chemistry ,Computational chemistry ,Diels alder ,Naphthyl-TADDOL ,Molecule ,Physical and Theoretical Chemistry - Abstract
The asymmetric hetero-Diels-Alder reaction of benzaldehyde with 1-dimethylamino-3- tert-butyldimethylsiloxy butadiene catalyzed by ( R, R)-1-Np-TADDOL was studied using computational methods. A theoretical rationale was developed through the combined use of molecular mechanics and ONIOM(B3LYP/6-31G(d):AM1) calculations. The origins of stereoselection in this process were identified, and excellent correlation between experiment and theory was found.
- Published
- 2008
34. Theoretical rationale for regioselection in phosphine-catalyzed allenoate additions to acrylates, imines, and aldehydes
- Author
-
Ohyun Kwon, Travis Dudding, and Evan Mercier
- Subjects
Chemistry ,Hydrogen bond ,Organic Chemistry ,Biochemistry ,Transition state ,Catalysis ,chemistry.chemical_compound ,symbols.namesake ,Computational chemistry ,symbols ,Organic chemistry ,Lewis acids and bases ,Physical and Theoretical Chemistry ,van der Waals force ,Phosphine - Abstract
[reaction: see text] A rationale for regioselection in phosphine-promoted annulations of acrylates, imines, and aldehydes with allenoates has been developed using computation at the B3LYP/6-31G(d) level of theory. The computed transition states revealed that Lewis acid activation, strong hydrogen bonding (H-bonding), and minimization of unfavorable van der Waals contacts are the guiding factors responsible for regioselection. An excellent level of correlation between the calculated regioselectivities and experiment was observed.
- Published
- 2006
35. Phosphine-catalyzed synthesis of 1,3-dioxan-4-ylidenes
- Author
-
Christopher E. Henry, Ohyun Kwon, Travis Dudding, Jay Wang, and Xue-Feng Zhu
- Subjects
chemistry.chemical_compound ,Cascade reaction ,Chemistry ,Product (mathematics) ,Organic Chemistry ,Acetal ,Organic chemistry ,General Medicine ,Physical and Theoretical Chemistry ,Biochemistry ,Phosphine ,Catalysis - Abstract
[reaction: see text] A phosphine-catalyzed reaction of an allenoate with aldehydes furnished (2,6-diaryl-[1,3]dioxan-4-ylidene)-acetates 4 in excellent to moderate yields with complete diastereoselectivity and high E/Z-selectivities. Upon removal of the acetal functionality in this domino reaction product 4, delta-hydroxy-beta-ketoester 11 was obtained. The reported vinylphosphonium-based approach provides a new way to achieve a synthesis of delta-hydroxy-beta-ketoesters that differs from the classical dianion-based approach.
- Published
- 2005
Catalog
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