111 results on '"Travis Dudding"'
Search Results
2. Diversity-oriented synthesis of glycomimetics
- Author
-
Michael Meanwell, Gaelen Fehr, Weiwu Ren, Bharanishashank Adluri, Victoria Rose, Johannes Lehmann, Steven M. Silverman, Rozhin Rowshanpour, Christopher Adamson, Milan Bergeron-Brlek, Hayden Foy, Venugopal Rao Challa, Louis-Charles Campeau, Travis Dudding, and Robert Britton
- Subjects
Chemistry ,QD1-999 - Abstract
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
- Full Text
- View/download PDF
3. pKa Scale for Cyclopropenium Ions with Applications in CO2 Capture
- Author
-
Matt Guest, Ivor Smajlagic, Srini Vemulapalli, and Travis Dudding
- Subjects
Computational chemistry ,Chemistry ,Scale (chemistry) ,Organic Chemistry ,Reactivity (chemistry) ,Ion - Abstract
Molecular acid-base properties are core to understanding chemical systems and the prediction of reactivity. This axiom holds for cyclopropenium ions in terms of their broad use as (organo)catalysts, ligands, redox-flow batteries, and applications in materials sciences. In view of this significant status, and with it, the critical importance of acidity, we disclose in this report the first comprehensive computational study of the pKa values of cyclopropenium ions employing a subset of 70 structurally diverse cyclopropenium derivatives, density functional computations, and Hammett linear free-energy relationships. Capitalizing upon these computed findings, and with an eye toward greenhouse gas trapping, we further document the timely use of a cyclopropenium-cyclopropenylidene coupled platform for CO2 capture and light-triggered release.
- Published
- 2021
4. Brønsted Acid Organocatalyzed Three-Component Hydroamidation Reactions of Vinyl Ethers
- Author
-
Travis Dudding, Ivor Smajlagic, and Brenden Carlson
- Subjects
chemistry.chemical_classification ,Double bond ,Nitrogen ,010405 organic chemistry ,Organic Chemistry ,Regioselectivity ,010402 general chemistry ,01 natural sciences ,Combinatorial chemistry ,Chemical synthesis ,Carbon ,Catalysis ,0104 chemical sciences ,chemistry.chemical_compound ,chemistry ,Metals ,Amide ,Functional group ,Reactivity (chemistry) ,Brønsted–Lowry acid–base theory ,Ethers - Abstract
Hydroamidation of carbon-carbon double bonds is an attractive strategy for installing nitrogen functionality into molecular scaffolds and, with it, increasing molecular complexity. To date, metal-based approaches have dominated this area of chemical synthesis, despite the drawbacks of air and moisture sensitivity, limited functional group tolerance, toxicity, and/or high cost often associated with using metals. Here, in offering an alternative solution, we disclose an operationally simple, metal-free, one-pot, regioselective, multicomponent synthetic procedure for the hydroamidation of carbon-carbon double bonds. This method features mild reaction conditions and utilizes isocyanides and vinyl ethers for the rapid and modular synthesis of privileged α-oxygenated amide scaffolds. In unraveling the mechanistic underpinning of this non-metal-based reactivity, we present kinetic solvent isotope effect studies, variable time normalization analysis, and density functional theory computations offering insight into the mechanism of this multistep catalytic hydroamidation process.
- Published
- 2021
5. Oxidative Rearrangement of MIDA (N-Methyliminodiacetic Acid) Boronates: Mechanistic Insights and Synthetic Applications
- Author
-
Sherif J. Kaldas, Chieh-Hung Tien, martynas sirvinskas, Andrei K. Yudin, Gabriel dos Passos Gomes, Travis Dudding, Stephanie Meyer, and Hayden Foy
- Subjects
010405 organic chemistry ,Chemistry ,Organic Chemistry ,chemistry.chemical_element ,Oxidative phosphorylation ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Oxidative addition ,Combinatorial chemistry ,0104 chemical sciences ,Nucleophile ,Hemilability ,N-methyliminodiacetic acid ,Physical and Theoretical Chemistry ,Palladium - Abstract
Herein we report that coordinative hemilability allows the MIDA (N-methyliminodiacetic acid) nitrogen to behave as a nucleophile and intramolecularly intercept palladium π-allyl intermediates. A mechanistic investigation indicates that this rearrangement proceeds through an SN2-like displacement at tetrasubstituted boron to furnish novel DABN boronates. Oxidative addition into the N-C bond of the DABN scaffold furnishes borylated π-allyl intermediates that can then be trapped with a variety of nucleophiles, including in a three-component coupling.
- Published
- 2021
6. Generation and reactivity of an elusive base-stabilised phosphinidene
- Author
-
Travis Dudding, Georgii I. Nikonov, Denis M. Spasyuk, Brandon White, and Minh Tho Nguyen
- Subjects
Olefin fiber ,010405 organic chemistry ,Reactive intermediate ,010402 general chemistry ,01 natural sciences ,Toluene ,Medicinal chemistry ,0104 chemical sciences ,Inorganic Chemistry ,Electrophilic substitution ,chemistry.chemical_compound ,chemistry ,13. Climate action ,Phosphinidene ,Reactivity (chemistry) ,Carbene ,Phosphine - Abstract
Reduction of phosphorus dichloride 6, supported by the diaryloxyphenyl group (OCO) featuring two bulky phenoxy wingtips, by PMe3, generates a reactive intermediate that behaves as a base-stabilized phosphinidene (OCO)P (5). Warming up a solution of this species in toluene to room temperature results in trimerization to give the isolable cyclic triphosphine [(OCO)P]3, whereas in situ trapping with 2,3-dimethylbutadiene-1,3 afforded a 3,4-dimethylphospholene-3. Investigation of the reduction of 6 by the phosphine PMe3 by NMR led to the observation of a persistent species between -10 °C and 10 °C. DFT study of this process suggest that this compound cannot be the proposed phosphinidene 5, and is more likely the disphosphine (OCO)ClP-PCl(OCO) (12). Attempted reduction of 5 by the bulky carbene IPr resulted in unusual electrophilic substitution in the carbene olefin backbone by the chlorophosphinyl group.
- Published
- 2021
7. Trisaminocyclopropenium Cations as Small-Molecule Organic Fluorophores: Design Guidelines and Bioimaging Applications
- Author
-
Matt Guest, Roya Mir, Gregory Foran, Travis Dudding, Aleksandar Necakov, and Brianne Hickson
- Subjects
Fluorophore ,Ionophores ,Organic Chemistry ,Rational design ,Design elements and principles ,Nanotechnology ,Small molecule ,Imaging agent ,Photochromism ,chemistry.chemical_compound ,chemistry ,Cations ,Intramolecular force ,Molecule ,Fluorescent Dyes - Abstract
The discovery of fluorescence two centuries ago ushered in, what is today, an illuminating field of science rooted in the rational design of photochromic molecules for task-specific bio-, material-, and medical-driven applications. Today, this includes applications in bioimaging and diagnosis, photodynamic therapy regimes, in addition to photovoltaic devices and solar cells, among a vast multitude of other usages. In furthering this indispensable area of daily life and modern-day scientific research, we report herein the synthesis of a class of trisaminocyclopropenium fluorophores along with a systematic investigation of their unique molecular and electronic dependent photophysical properties. Among these fluorophores, tris[N(naphthalen-2-ylmethyl)phenylamino] cyclopropenium chloride (TNTPC) displayed a strong photophysical profile including a 0.92 quantum yield ascribed to intramolecular charge transfer and intramolecular through-space conjugation. Moreover, this cyclopropenium-based fluorophore functions as a competent imaging agent for DNA visualization and nuclear counterstaining in cell culture. To facilitate the broader use of these compounds, design principles supported by density functional theory calculations for engineering analogs of this class of fluorophores are offered. Collectively, this study adds to the burgeoning interest in cyclopropenium compounds and their unique properties as fluorophores with uses in bioimaging applications.
- Published
- 2020
8. Carbonyl-Directed Aliphatic Fluorination: A Special Type of Hydrogen Atom Transfer Beats Out Norrish II
- Author
-
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
- Subjects
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.
- Published
- 2020
9. DFT Case Study of the Mechanism of a Metal-Free Oxygen Atom Insertion into a p-Quinone Methide C(sp3)–C(sp2) Bond
- Author
-
Travis Dudding, Thomas Lectka, Muhammad Kazim, and Ivor Smajlagic
- Subjects
chemistry.chemical_compound ,Oxygen atom ,Chemistry ,Computational chemistry ,Mechanism (philosophy) ,Unique element ,Organic Chemistry ,Molecule ,Reactivity (chemistry) ,Quinone methide ,Chemical space - Abstract
The site-selective introduction of an oxygen atom into an organic molecule, without the assistance of metals, is a useful transformation, though understanding the mechanistic underpinning of such a process is oftentimes a challenging task. In exploring this chemical space and in building upon experimental precedents, we have utilized computational tools to delineate the mechanistic details of site-selective oxygen atom insertion into a p-quinone methide C(sp3)-C(sp2) bond. To this end, several different reaction pathways for oxygen atom insertion were explored-each encompassing a unique element qualifying the respective pathway as being more or less feasible. The findings of these investigations revealed several features that were vital to this reactivity, including the formation of a dimeric intermediate, interconversion between ground- and excited-state species, and strain. Notably, the latter finding adds to the portfolio of strain-release-driven reactions that have emerged as popular methods to achieve otherwise difficult chemical transformations.
- Published
- 2020
10. Stereoselective Synthesis of N ‐Propargyl Alkynes and Axial Chiral N ‐Allenes with Epimeric Pyrroloimidazolone Auxiliaries
- Author
-
Mateo Andrade, Travis Dudding, Costa Metallinos, Melanie Pilkington, Maria Laura Sechi, and Hayden Foy
- Subjects
Stereochemistry ,Chemistry ,Stereoselectivity ,General Chemistry ,N-propargyl - Published
- 2020
11. Development of an Unsymmetrical Cyclopropenimine‐Guanidine Platform for Accessing Strongly Basic Proton Sponges and Boron‐Difluoride Diaminonaphthalene Fluorophores
- Author
-
Matt Guest, Travis Dudding, Melanie Pilkington, and Richard Le Sueur
- Subjects
Boron Compounds ,ved/biology.organism_classification_rank.species ,Protonation ,010402 general chemistry ,Photochemistry ,Guanidines ,01 natural sciences ,Catalysis ,symbols.namesake ,chemistry.chemical_compound ,Stokes shift ,Molecule ,Fluorescent Dyes ,Ionophores ,Tetracoordinate ,010405 organic chemistry ,ved/biology ,Organic Chemistry ,Hydrogen Bonding ,General Chemistry ,Fluorescence ,0104 chemical sciences ,chemistry ,Intramolecular force ,symbols ,Protons ,BODIPY ,Conjugate acid - Abstract
An unsymmetrical guanidine-cyclopropenimine proton sponge DAGUN and the related BF2 -chelate DAGBO are reported. Insight into the structural, electronic, bonding and photophysical properties of these two molecules are presented. Joint experimental and theoretical studies reveal the protonated form of DAGUN possesses an intramolecular N⋅⋅⋅H-N hydrogen bond which affords a high experimental pKBH+ of 26.6 (computed=26.3). Photophysical studies show that in solution DAGUN displays a green emission at 534 nm, with a large Stokes shift of 235 nm (14,718 cm-1 ). In contrast, the conjugate acid DAGUN-H+ is only weakly emissive due to attenuated intramolecular charge transfer. X-ray diffraction studies reveal that DAGBO contains a stable tetracoordinate boronium cation, reminiscent of the well-established BODIPY family of dyes. In solution, DAGBO exhibits a strong blue emission at 450 nm coupled with a large Stokes shift (Δλ=158 nm, Δν=11,957 cm-1 ) and quantum yield of 62 %, upon excitation at 293 nm. DAGBO sets the stage as the first entry into a new class of boron-difluoride diaminonaphthalenes (BOFDANs) that represent highly fluorescent and tunable next-generation dyes with future promise for biosensing and bioimaging applications.
- Published
- 2020
12. Mechanistic Insight toward Understanding the Role of Charge in Thiourea Organocatalysis
- Author
-
Travis Dudding, Rocío Durán, Matt Guest, Ivor Smajlagic, and Bárbara Herrera
- Subjects
010405 organic chemistry ,Chemistry ,Hydrogen bond ,Organic Chemistry ,Oxocarbenium ,Cationic polymerization ,010402 general chemistry ,01 natural sciences ,Combinatorial chemistry ,0104 chemical sciences ,Catalysis ,chemistry.chemical_compound ,Thiourea organocatalysis ,Thiourea ,Kinetic isotope effect ,Brønsted–Lowry acid–base theory - Abstract
Pyranylation and glycosylation are pivotal for accessing a myriad of natural products, pharmaceuticals, and drug candidates. Catalytic approaches for enabling these transformations are of utmost importance and integral to advancing this area of synthesis. In exploring this chemical space, a combined experimental and computational mechanistic study of pyranylation and 2-deoxygalactosylation catalyzed by a cationic thiourea organocatalyst is reported. To this end, a thiourea-cyclopropenium organocatalyst was employed as a model system in combination with an arsenal of mechanistic techniques, including 13C kinetic isotope effect experiments, deuterated labeling studies, variable-temperature 1H NMR spectroscopy, and density functional theory calculations. From these studies, two distinct reaction pathways were identified for this transformation corresponding to either dual hydrogen bond (H-bond) activation or Bronsted acid catalysis. The former involving thiourea orchestrated bifurcated hydrogen bonding proceeded in an asynchronous concerted fashion. In contrast, the latter stepwise mechanism involving Bronsted acid catalysis hinged upon the formation of an oxocarbenium intermediate accompanied by subsequent alcohol addition.
- Published
- 2019
13. DFT-Based Stereochemical Rationales for the Bifunctional Brønsted Acid/Base-Catalyzed Diastereodivergent and Enantioselective aza-Henry Reactions of α-Nitro Esters
- Author
-
Jeffrey N. Johnston, Hayden Foy, Travis Dudding, Ivor Smajlagic, and Thomas J. Struble
- Subjects
010405 organic chemistry ,Hydrogen bond ,Chemistry ,Stereochemistry ,Ligand ,Organic Chemistry ,Enantioselective synthesis ,Substituent ,Esters ,Stereoisomerism ,010402 general chemistry ,01 natural sciences ,Catalysis ,Article ,0104 chemical sciences ,Amidine ,chemistry.chemical_compound ,Electrophile ,heterocyclic compounds ,Indicators and Reagents ,Bifunctional ,Acids - Abstract
A pair of chiral bis(amidine) [BAM] proton complexes provide reagent (catalyst)-controlled, highly diastereo- and enantioselective direct aza-Henry reactions leading to α-alkyl-substituted α,β-diamino esters. A C(2)-symmetric ligand provides high anti-selectivity, while a non-symmetric congener exhibits syn-selectivity in this example of diastereodivergent, enantioselective catalysis. A detailed computational analysis is reported for the first time, one that supports distinct models for selectivity resulting from the more hindered binding cavity of the C(1)-symmetric ligand. Binding in this congested pocket accommodates four hydrogen bond contacts among ligand and substrates, ultimately favoring a pre-syn arrangement highlighted by pyridinium-azomethine activation, and quinolinium-nitronate activation. The complementary transition states reveal a wide range of alternatives. Comparing the C(1) and C(2)-symmetric catalysts highlights distinct electrophile binding orientations despite their common hydrogen bond donor-acceptor features. Among the factors driving unusual high syn-diastereoselection are favorable dispersion forces that leverage the anthracenyl substituent of the C(1)-symmetric ligand.
- Published
- 2021
14. Diversity-oriented synthesis of glycomimetics
- Author
-
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
- Subjects
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
15. Discovery and Mechanistic Study of a Totally Organic C(aryl)–C(alkyl)Oxygen Insertion Reaction
- Author
-
Travis Dudding, Muhammad Kazim, Maxime A. Siegler, Thomas Lectka, and Hayden Foy
- Subjects
chemistry.chemical_classification ,010405 organic chemistry ,Aryl ,Organic Chemistry ,chemistry.chemical_element ,010402 general chemistry ,01 natural sciences ,Quinone methide ,Medicinal chemistry ,Oxygen ,0104 chemical sciences ,chemistry.chemical_compound ,chemistry ,Insertion reaction ,Alkyl - Abstract
We report an unprecedented photochemical oxygen insertion reaction into an aromatic quinone methide. Insertion happens specifically within a C(aryl)–C(alkyl) bond, whereas the quinone methide moiet...
- Published
- 2019
16. A mechanistic study of oxygen atom transfer from N-sulfonyloxaziridine to enolates
- Author
-
Travis Dudding, Adrian L. Schwan, and Hayden Foy
- Subjects
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.
- Published
- 2019
17. Selective Aerobic Oxidation of Benzylic Alcohols Catalyzed by a Dicyclopropenylidene–Ag(I) Complex
- Author
-
Rozhin Rowshanpour, Travis Dudding, Katie Dempsey, Melanie Pilkington, and Roya Mir
- Subjects
chemistry.chemical_classification ,Ketone ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,Molecular oxygen ,010402 general chemistry ,01 natural sciences ,Aldehyde ,Combinatorial chemistry ,0104 chemical sciences ,Catalysis - Abstract
The unprecedented synthesis, single-crystal X-ray structure, and first catalytic application of a dicarbene-Ag(I) complex [Ag(BAC)2][CO2CF3] (BAC = bis(diisopropyl)aminocyclopropenylidene) is reported. This novel complex provides a versatile catalytic platform for selective aerobic oxidation of benzylic alcohols to aldehyde or ketone products in high yields. Ease of experimental execution coupled with the use of abundant atmospheric molecular oxygen as an oxidant and low catalyst loading are inherit strengths of these oxidations.
- Published
- 2019
18. Azo synthesis meets molecular iodine catalysis
- Author
-
Rozhin Rowshanpour and Travis Dudding
- Subjects
Azo compound ,010405 organic chemistry ,General Chemical Engineering ,Hydrazine ,chemistry.chemical_element ,General Chemistry ,010402 general chemistry ,Iodine ,01 natural sciences ,Combinatorial chemistry ,0104 chemical sciences ,Catalysis ,chemistry.chemical_compound ,chemistry ,Density functional theory ,Reactivity (chemistry) ,Stoichiometry - Abstract
A metal-free synthetic protocol for azo compound formation by the direct oxidation of hydrazine HN–NH bonds to azo group functionality catalyzed by molecular iodine is disclosed. The strengths of this reactivity include rapid reaction times, low catalyst loadings, use of ambient dioxygen as a stoichiometric oxidant, and ease of experimental set-up and azo product isolation. Mechanistic studies and density functional theory computations offering insight into this reactivity, as well as the events leading to azo group formation are presented. Collectively, this study expands the potential of main-group element iodine as an inexpensive catalyst, while delivering a useful transformation for forming azo compounds.
- Published
- 2021
19. Direct Observation and Analysis of the Halo-Amino-Nitro Alkane Functional Group
- Author
-
Michael S. Crocker, Kazuyuki Tokumaru, Travis Dudding, Jeffrey N. Johnston, Hayden Foy, and Maren Pink
- Subjects
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.
- Published
- 2020
20. DABN Borazabicycles: Formation from MIDA Boronates and Synthetic Utility
- Author
-
Stephanie Meyer, Gabriel dos Passos Gomes, Sherif J. Kaldas, Andrei K. Yudin, Travis Dudding, Hayden Foy, Chieh-Hung Tien, and martynas sirvinskas
- Subjects
Steric effects ,chemistry ,Nucleophile ,Hemilability ,chemistry.chemical_element ,Regioselectivity ,Amine gas treating ,Selectivity ,Combinatorial chemistry ,Oxidative addition ,Palladium - Abstract
We report that coordinative hemilability allows the MIDA amine to behave as a nucleophile to intercept π-allyl intermediates. A mechanistic investigation indicates that this rearrangement proceeds through an SN2-like displacement at tetrasubstituted boron to furnish novel DABN (2,8- dioxa-5-aza-1-borabicyclo[3.3.1]nonane-3,7-dione) boronates. Oxidative addition into the N-C bond of the DABN scaffold reverses the reaction and furnishes borylated π-allyl intermediates that can then be trapped with complete linear selectivity. DFT calculations indicate that stabilizing interactions in the transition state, as well as the steric bulk of the MIDA unit, are the origins of the excellent regioselectivity. We further demonstrate the utility of our new reagents by way of a 3-component coupling that features allylammonium DABN boronates as linchpin reagents. This report disseminates a previously unknown aspect of MIDA boronates that can now be exploited.
- Published
- 2020
21. Organofluorine Compounds in Fluorine-18 Positron Emission Tomography Imaging
- Author
-
Travis Dudding, Rozhin Rowshanpour, Ivor Smajlagic, and Lea Milkin
- Subjects
Chemistry ,Viral transmission ,Fluorine ,chemistry.chemical_element ,General Medicine ,Organofluorine compounds ,Chemical synthesis ,Combinatorial chemistry - Abstract
Organofluorine compounds are abundant in medicine and society-largely by human design and chemical synthesis, not de novo in Nature...
- Published
- 2020
22. Site-Selective Photochemical Fluorination of Ketals: Unanticipated Outcomes in Selectivity and Stability
- Author
-
Cody Ross Pitts, Joseph N. Capilato, Travis Dudding, Thomas Lectka, and Rozhin Rowshanpour
- Subjects
010405 organic chemistry ,Chemistry ,Organic Chemistry ,Site selective ,Regioselectivity ,010402 general chemistry ,Selectivity ,Photochemistry ,01 natural sciences ,Acetonide ,3. Good health ,0104 chemical sciences - Abstract
We report a method for the regioselective photochemical sp3 C–H fluorination of acetonide ketals that presents interesting problems in chemical reactivity. The question of why certain products of t...
- Published
- 2020
23. Synthesis of α-Borylated Ketones by Regioselective Wacker Oxidation of Alkenylboronates
- Author
-
Hayden Foy, Shinya Adachi, Aleksandra Holownia, Travis Dudding, Victoria B. Corless, Rodrigo Mendoza-Sanchez, and Andrei K. Yudin
- Subjects
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.
- Published
- 2018
24. Amine hemilability enables boron to mechanistically resemble either hydride or proton
- Author
-
Graham E. Garrett, Travis Dudding, Sean K. Liew, Diego B. Diaz, Sherif J. Kaldas, Andrei K. Yudin, C. Frank Lee, and Aleksandra Holownia
- Subjects
Tetracoordinate ,010405 organic chemistry ,Chemistry ,Hydride ,General Chemical Engineering ,chemistry.chemical_element ,Migratory aptitude ,General Chemistry ,010402 general chemistry ,01 natural sciences ,0104 chemical sciences ,chemistry.chemical_compound ,Nucleophile ,Computational chemistry ,Hemilability ,Electrophile ,Boron ,Organometallic chemistry - Abstract
Tetracoordinate MIDA (N-methyliminodiacetic acid) boronates have found broad utility in chemical synthesis. Here, we describe mechanistic insights into the migratory aptitude of the MIDA boryl group in boron transfer processes, and show that the hemilability of the nitrogen atom on the MIDA ligand enables boron to mechanistically resemble either a hydride or a proton. The first case involves a 1,2-boryl shift, in which boron migrates as a nucleophile in its tetracoordinate form. The second case involves a neighbouring atom-promoted 1,4-boryl shift, in which boron migrates as an electrophile in its pseudo-tricoordinate form. Density functional theory studies and in situ NMR measurements all suggest that MIDA can act as a dynamic switch. These findings encouraged the development of novel migration processes involving boron that exploit the chameleonic behaviour of boron by acting as both a nucleophile and an electrophile, including the first report of a compound with a boronate functionality bound to carbon in the carboxylic acid oxidation state.
- Published
- 2018
25. Expanding the repertoire of cyclopropenium ion phase transfer catalysis: Benzylic fluorination
- Author
-
Travis Dudding, Ivor Smajlagic, Katie Dempsey, and Roya Mir
- Subjects
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.
- Published
- 2018
26. Bis(amino)cyclopropenium Trifluoroborates: Synthesis, Hydrolytic Stability Studies, and DFT Insights
- Author
-
Travis Dudding and Roya Mir
- Subjects
Hydrolysis ,010405 organic chemistry ,Chemistry ,Computational chemistry ,Reagent ,Organic Chemistry ,Atoms in molecules ,Density functional theory ,010402 general chemistry ,01 natural sciences ,3. Good health ,0104 chemical sciences ,Adduct - Abstract
A simple and direct two-step synthesis of bis(amino)cyclopropenium trifluoroborate (BAC–BF3) derivatives from readily available reagents is reported. Hydrolysis studies revealed these BAC–BF3 derivatives were remarkably stable toward defluorination. Notably, this first study of BAC–BF3 adduct hydrolytic stability establishes the compounds reported herein possess half-lives (t1/2) exceeding 0.23 × 106 min (∼160 days). Density functional theory (DFT) and quantum theory of atoms in molecules (QTAIM) calculations exploring the basis of this high stability are described.
- Published
- 2018
27. Zinc-Catalyzed Hydrosilylation and Hydroboration of N-Heterocycles
- Author
-
Bulat Gabidullin, Travis Dudding, John L. Lortie, and Georgii I. Nikonov
- Subjects
010405 organic chemistry ,Hydrosilylation ,Hydride ,Phenanthroline ,chemistry.chemical_element ,Regioselectivity ,NacNac ,Zinc hydride ,General Chemistry ,Zinc ,010402 general chemistry ,01 natural sciences ,Medicinal chemistry ,Catalysis ,0104 chemical sciences ,Hydroboration ,chemistry.chemical_compound ,chemistry ,Organic chemistry - Abstract
The zinc hydride NacNacZnH (2) (NacNac = [Ar′NC(Me)CHC(Me)NAr′]−, Ar′ = 2,6-Me2C6H3) catalyzes regioselective hydrosilylation and hydroboration of pyridines, including the hydroboration of phenanthroline. Mechanistic studies of hydrosilylation, including labeling, kinetic analysis, and density functional theory calculations, suggest the possibility of a reaction pathway based on hydride transfer from an out-of-sphere activated silane.
- Published
- 2017
28. Phase-Transfer Catalyzed O-Silyl Ether Deprotection Mediated by a Cyclopropenium Cation
- Author
-
Roya Mir and Travis Dudding
- Subjects
010405 organic chemistry ,Chemistry ,Organic Chemistry ,Atoms in molecules ,Ether ,010402 general chemistry ,01 natural sciences ,0104 chemical sciences ,Catalysis ,Silyl ether ,chemistry.chemical_compound ,Computational chemistry ,Phase (matter) ,Physics::Atomic and Molecular Clusters ,Organic chemistry ,Density functional theory ,Physics::Chemical Physics ,Taft equation - Abstract
The use of a cyclopropenium cation as a phase-transfer catalyst for O-silyl ether deprotection is reported. Mechanistic insight into this deprotection methodology derived by linear free-energy relationships (LFER), quantum theory of atoms in molecules (QTAIM), and density functional theory (DFT) calculations are also provided.
- Published
- 2016
29. Ligand Effect in Alkali-Metal-Catalyzed Transfer Hydrogenation of Ketones
- Author
-
Travis Dudding, Georgii I. Nikonov, Iryna D. Alshakova, and Hayden Foy
- Subjects
Coordination sphere ,010405 organic chemistry ,Ligand ,Organic Chemistry ,chemistry.chemical_element ,General Chemistry ,Tetramethylethylenediamine ,010402 general chemistry ,Transfer hydrogenation ,01 natural sciences ,Medicinal chemistry ,Catalysis ,0104 chemical sciences ,chemistry.chemical_compound ,chemistry ,Reactivity (chemistry) ,Lithium ,Lewis acids and bases ,Lithium Cation - Abstract
This work unveils the reactivity patterns, as well as ligand and additive effect on alkali-metal-base-catalyzed transfer hydrogenation of ketones. Crucially to this reactivity is the presence of a Lewis acid (alkali cation), as opposed to a simple base effect. With aryl ketones, the observed reactivity order is Na+ >Li+ >K+ , whereas for aliphatic substrates it follows the expected Lewis acidity, Li+ >Na+ >K+ . Importantly, the reactivity pattern can be drastically changed by adding ligands and additives. Kinetic, labelling, and competition experiments as well as DFT calculations suggested that the reaction proceeds through a concerted direct hydride-transfer mechanism, originally suggested by Woodward. The lithium cation was found to be intrinsically more active than heavier congeners, but in the case of aryl ketones a decrease in reaction rate was observed at ≈40 % conversion with lithium cations. Noncovalent-interaction analysis revealed that this deceleration effect originated from specific noncovalent interactions between the aryl moiety of 1-phenylethanol and the carbonyl group of acetophenone, which stabilize the product in the coordination sphere of lithium and thus poison the catalyst. The ligand/additive effect is a complicated phenomenon that includes a combination of several factors, such as the decrease of activation energy by ligation (confirmed by distortion/interaction calculations of N,N,N',N'-tetramethylethylenediamine, TMEDA) and the change in relative stabilization of reagents and substrates in the solution and the coordination sphere of the metal. Finally, we observed that lithium-base-catalyzed transfer hydrogenation can be further facilitated by the addition of an inexpensive and benign reagent, LiCl, which likely operates by re-initiating the reaction on a new lithium center.
- Published
- 2019
30. Investigation of a new chiral auxiliary derived chemoenzymatically from toluene: experimental and computational study
- Author
-
Ivan Šnajdr, Travis Dudding, Jordan Froese, Pavlína Horáková, and Tomáš Hudlický
- Subjects
Chiral auxiliary ,010405 organic chemistry ,Metabolite ,Organic Chemistry ,General Chemistry ,010402 general chemistry ,01 natural sciences ,Toluene ,Asymmetric induction ,Catalysis ,0104 chemical sciences ,chemistry.chemical_compound ,chemistry ,Biocatalysis ,Organic chemistry - Abstract
A tricyclic chiral auxiliary, prepared from the enzymatically derived cis-arene dihydrodiol metabolite of toluene, was investigated as a means of asymmetric induction in several different reactions. The auxiliary was converted to an oxaziridine, and its utility in hydroxylation, providing low levels of enantiomeric excess, was compared with that of Davis’s oxaziridine. Insight into the origin of stereoinduction in this reaction is provided and is based on computational Monte Carlo Multiple Minimum (MCMM) searches using the OPLS3 force field. The use of the auxiliary group in the alkylation of appended esters proved disappointing. Diels-Alder cycloaddition of an acrylate, derived from the auxiliary group, with cyclohexadiene furnished a mixture of diastereomeric adducts in essentially equal amounts. The adducts were separated and the corresponding enantiomeric residues were isolated with good enantiomeric excess. Evidence of reasonable levels of asymmetric induction in the above processes was lacking. Experimental and spectral data are provided for all key compounds.
- Published
- 2016
31. An Evolving Insight into Chiral H-Bond Catalyzed Aza-Henry Reactions: A Cooperative Role for Noncovalent Attractive Interactions Unveiled by Density Functional Theory
- Author
-
Seyedeh Maryamdokht Taimoory and Travis Dudding
- Subjects
inorganic chemicals ,Steric effects ,010405 organic chemistry ,Chemistry ,Hydrogen bond ,Organic Chemistry ,Binding pocket ,Substrate (chemistry) ,010402 general chemistry ,01 natural sciences ,0104 chemical sciences ,Catalysis ,Computational chemistry ,Pairing ,Density functional theory - Abstract
The role of cooperative effects arising from noncovalent attractive interactions as a vital factor governing stereoinduction in chiral H-bond catalyzed aza-Henry reactions is reported. Supporting this finding were density functional theory (DFT) calculations which revealed a shape and size dependency existed between the catalyst and substrates that when matched lead to high enantioselectivity, as reflected by favorable activation parameters. Associated with optimal catalyst and substrate pairing were a closed catalytic binding pocket and a synclinal orientation of the substrates that reinforced favorable stereoelectronic effects and dispersive type forces. Meanwhile, unfavorable steric interactions were found to be a dominant effect controlling diastereoselection.
- Published
- 2016
32. A Au(I)-Precatalyst with a Cyclopropenium Counterion: An Unusual Ion Pair
- Author
-
Travis Dudding and Roya Mir
- Subjects
chemistry.chemical_classification ,010405 organic chemistry ,Organic Chemistry ,Intermolecular force ,Alkyne ,Crystal structure ,Ion pairs ,010402 general chemistry ,Photochemistry ,01 natural sciences ,0104 chemical sciences ,Crystallography ,chemistry ,Non-covalent interactions ,Density functional theory ,Hydroamination ,Counterion - Abstract
The synthesis and X-ray crystal structure of a novel Au(I)-precatalyst applied to intermolecular alkyne hydroamination is reported. Density functional theory (DFT) calculations revealed the cyclopropenium counterion of this Au(I)-precatalyst imparts stability through H-bonding and other noncovalent interactions.
- Published
- 2016
33. Unique molecular geometries of reduced 4- and 5-coordinate zinc complexes stabilised by diiminopyridine ligand
- Author
-
Terry Chu, Travis Dudding, Prashanth K. Poddutoori, Ilia Korobkov, Art van der Est, Georgii I. Nikonov, and Lee Belding
- Subjects
010405 organic chemistry ,Ligand ,Imine ,Inorganic chemistry ,chemistry.chemical_element ,Zinc ,010402 general chemistry ,01 natural sciences ,0104 chemical sciences ,law.invention ,Inorganic Chemistry ,Crystallography ,chemistry.chemical_compound ,Delocalized electron ,Molecular geometry ,chemistry ,law ,Electron paramagnetic resonance ,Diiminopyridine ,Methyl group - Abstract
Stepwise reduction of the diiminopyridine (dimpyr) complex, dimpyrZnCl2, by KC8 leads to molecular zinc compounds dimpyrZnCl (2) and dimpyrZnCl(DMAP) (3, DMAP = 4-dimethylaminopyridine), which were characterized by X-ray diffraction and EPR spectroscopy. Compound 2 shows an unusual nearly square planar geometry of the zinc atom equally ligated by two imine groups. X-ray crystallographic and EPR data suggest significant delocalization of the zinc 4p electron onto the non-innocent dimpyr ligand. The chloride in 2 can also be substituted by a methyl group upon addition of methyl lithium to generate compound 4, dimpyrZnMe. The novel alkylzinc compound displayed approximate square planar geometry around the zinc centre and significant delocalization of electron density onto the dimpyr ligand, as revealed by X-ray crystallographic studies and EPR spectroscopy, akin to 2. Further reduction of 3 leads to compound 5, dimpyrZn(DMAP)2. X-ray diffraction study of 5 revealed an unprecedented see-saw geometry around the four-coordinate zinc center with significant electron density transfer to the dimpyr ligand, supported by DFT calculations.
- Published
- 2016
34. Front Cover Picture: Stereoselective Synthesis of N ‐Propargyl Alkynes and Axial Chiral N ‐Allenes with Epimeric Pyrroloimidazolone Auxiliaries (Adv. Synth. Catal. 20/2020)
- Author
-
Hayden Foy, Travis Dudding, Maria Laura Sechi, Mateo Andrade, Costa Metallinos, and Melanie Pilkington
- Subjects
Front cover ,Chemistry ,Stereochemistry ,Stereoselectivity ,General Chemistry ,N-propargyl - Published
- 2020
35. Cyclopropenium Enhanced Thiourea Catalysis
- Author
-
Rocío Durán, Ivor Smajlagic, Melanie Pilkington, and Travis Dudding
- Subjects
010405 organic chemistry ,Chemistry ,Organic Chemistry ,Cationic polymerization ,010402 general chemistry ,01 natural sciences ,Combinatorial chemistry ,0104 chemical sciences ,Catalysis ,chemistry.chemical_compound ,Thiourea ,Organocatalysis ,Proton NMR ,Phenols ,Brønsted–Lowry acid–base theory ,Benzoic acid - Abstract
An integral part of modern organocatalysis is the development and application of thiourea catalysts. Here, as part of our program aimed at developing cyclopropenium catalysts, the synthesis of a thiourea-cyclopropenium organocatalyst with both cationic hydrogen-bond donor and electrostatic character is reported. The utility of the this thiourea organocatalyst is showcased in pyranylation reactions employing phenols, primary, secondary, and tertiary alcohols under operationally simple and mild reaction conditions for a broad substrate scope. The addition of benzoic acid as a co-catalyst facilitating cooperative Bronsted acid catalysis was found to be valuable for reactions involving phenols and higher substituted alcohols. Mechanistic investigations, including kinetic and 1H NMR binding studies in conjunction with density function theory calculations, are described that collectively support a Bronsted acid mode of catalysis.
- Published
- 2018
36. Charge-enhanced thiourea catalysts as hydrogen bond donors for Friedel‒Crafts Alkylations
- Author
-
Travis Dudding, Brenden Carlson, Nicholas Rosano, Ivor Smajlagic, and Hayden Foy
- Subjects
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.
- Published
- 2019
37. Fluorescence of Cyclopropenium Ion Derivatives
- Author
-
Matt Guest, Travis Dudding, Lee Belding, and Richard Le Sueur
- Subjects
010405 organic chemistry ,Organic Chemistry ,010402 general chemistry ,Ring (chemistry) ,01 natural sciences ,Fluorescence ,0104 chemical sciences ,Ion ,chemistry.chemical_compound ,chemistry ,Computational chemistry ,Intramolecular force ,Excited state ,Density functional theory ,Quantum ,Naphthalene - Abstract
The synthesis of cyclopropenium-substituted amino compounds and analysis of their photophysical properties is described. Systematic structural modifications of these derivatives lead to measurable and predictable changes in molar extinction coefficients, quantum yields, and Stokes shifts. Using time-dependent density functional theory (TD-DFT) calculations, the origin of these trends was traced to internal charge transfer (ICT) coupled with ensuing structural reorganization for select naphthalene functionalized derivatives. Associated with this structural reorganization was an inward gearing of the cyclopropenium ring and twisting of the peri-NMe2 group into coplanarity with the naphthalene ring system. Further, reinforcement of an intramolecular H-bond (IMHB) in the excited state of these derivatives alludes to the importance of photoinduced H-bonding in this new class of cyclopropenium based fluorophores.
- Published
- 2018
38. Design and synthesis of a chiral seven-membered ring guanidine organocatalyst applied to asymmetric vinylogous aldol reactions
- Author
-
Mohamed Hassan, Roya Mirabdolbaghi, and Travis Dudding
- Subjects
Inorganic Chemistry ,chemistry.chemical_compound ,chemistry ,Aldol reaction ,Organic Chemistry ,Organic chemistry ,Physical and Theoretical Chemistry ,Optically active ,Guanidine ,Ring (chemistry) ,Combinatorial chemistry ,Catalysis - Abstract
A computationally based design and synthesis of a point chiral seven-membered ring guanidine organocatalyst is reported. The application of this catalyst in asymmetric vinylogous aldol reactions, to form optically active γ-butenolide products with dr’s and er’s up to 90:10 and 97:3 is described.
- Published
- 2015
39. Expanding the Forefront of Strong Organic Brønsted Acids: Proton-Catalyzed Hydroamination of Unactivated Alkenes and Activation of Au(I) for Alkyne Hydroamination
- Author
-
Roya Mirabdolbaghi and Travis Dudding
- Subjects
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.
- Published
- 2015
40. Enantioselective synthesis of mosquito oviposition pheromone and its epimer from a naturally occurring fatty acid
- Author
-
Travis Dudding and David Hurem
- Subjects
chemistry.chemical_classification ,Ketone ,biology ,Stereochemistry ,General Chemical Engineering ,Enantioselective synthesis ,Fatty acid ,General Chemistry ,MOPS ,chemistry.chemical_compound ,chemistry ,Sex pheromone ,biology.protein ,Pheromone ,Organic chemistry ,Epimer ,Lipase - Abstract
The synthesis of Mosquito Oviposition Pheromones (MOP) (5R,6S)-5-acetoxy-6-hexadecanolide and its unnatural (5R,6R)-diastereomer in 68% and 54% overall yield by a route involving an organocatalyzed epoxidation of naturally occurring cis-5-hexadecenoic acid and diastereodivergent esterification is reported. The investigation of a dynamic kinetic asymmetric transformation (DYKAT) as an alternate strategy for preparing the target MOPs is also discussed, however this approach was unsuccessful due to the formation of a ketone by-product that inhibited the lipase mediated acetylation step of the DYKAT process.
- Published
- 2015
41. Mirroring Enzymes: The Role of Hydrogen Bonding in an Asymmetric Organocatalyzed Aza-Henry Reaction—a DFT Study
- Author
-
Seyedeh Maryamdokht Taimoory, Lee Belding, and Travis Dudding
- Subjects
Crystallography ,Nitroaldol reaction ,Deprotonation ,Nucleophile ,Hydrogen bond ,Chemistry ,Electrophile ,Low-barrier hydrogen bond ,General Chemistry ,Photochemistry ,Catalysis ,Homonuclear molecule - Abstract
The mechanism of the HQuin-BAM (1) catalyzed aza-Henry reaction between nitromethane and N-Boc-phenylaldimine was studied using density functional theory (DFT). Deprotonation of nitromethane by the catalyst was revealed to be the rate-limiting step, and C···C bond formation was found to be enantio-determining. The catalyst, in addition to acting as a Bronsted base, served to simultaneously activate both the electrophile and the nucleophile through hydrogen bonding during C···C bond formation and is thus essential for both reaction rate and selectivity. Analysis of the hydrogen bonding interactions revealed that there was a strong preference for the formation of a homonuclear positive-charge-assisted hydrogen bond (homonuclear (+)CAHB), which in turn governed the relative orientation of substrate binding. Furthermore, a direct correlation between the dihedral angle (θNCCN) of the reacting substrates and facial selectivity was found. This relationship between θ and facial selectivity was found to be a conse...
- Published
- 2014
42. Shifting the Energy Landscape of Multicomponent Reactions Using Aziridine Aldehyde Dimers: A Mechanistic Study
- Author
-
Serge Zaretsky, Benjamin H. Rotstein, Travis Dudding, Lee Belding, and Andrei K. Yudin
- Subjects
chemistry.chemical_classification ,Stereochemistry ,Dimer ,Isocyanide ,Organic Chemistry ,Aziridine ,Aldehyde ,chemistry.chemical_compound ,chemistry ,Computational chemistry ,Reagent ,Ugi reaction ,Stereoselectivity ,Carboxylate - Abstract
A multicomponent reaction between an aziridine aldehyde dimer, isocyanide, and l-proline to afford a chiral piperazinone was studied to gain insight into the stereodetermining and rate-limiting steps of the reaction. The stereochemistry of the reaction was found to be determined by isocyanide addition, while the rate-limiting step was found to deviate from traditional isocyanide-based multicomponent reactions. A first-order rate dependence on aziridine aldehyde dimer and a zero-order rate dependence on all other reagents have been obtained. Computations at the MPWPW91/6-31G(d) level supported the experimental kinetic results and provide insight into the overall mechanism and the factors contributing to stereochemical induction. These factors are similar to traditional isocyanide-based multicomponent reactions, such as the Ugi reaction. The computations revealed that selective formation of a Z-iminium ion plays a key role in controlling the stereoselectivity of isocyanide addition, and the carboxylate group of l-proline mediates stereofacial addition. These conclusions are expected to be applicable to a wide range of reported stereoselective Ugi reactions and provide a basis for understanding the related macrocyclization of peptides with aziridine aldehydes.
- Published
- 2014
43. Hydroxyproline-Derived Pseudoenantiomeric [2.2.1] Bicyclic Phosphines: Asymmetric Synthesis of (+)- and (−)-Pyrrolines
- Author
-
Tioga J. Martin, Qihai Xu, Ohyun Kwon, Lee Belding, Travis Dudding, Christopher E. Henry, and Yi Chiao Fan
- Subjects
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.
- Published
- 2014
44. A Coordination Compound of Ge0Stabilized by a Diiminopyridine Ligand
- Author
-
Lee Belding, Ilia Korobkov, Art van der Est, Georgii I. Nikonov, Terry Chu, and Travis Dudding
- Subjects
chemistry.chemical_classification ,Stereochemistry ,Chemistry ,Ligand ,Imine ,General Medicine ,General Chemistry ,Photochemistry ,Catalysis ,Coordination complex ,chemistry.chemical_compound ,Crystallography ,Pyridine ,Carbenoid ,Lone pair ,Carbene ,Diiminopyridine - Abstract
Reduction of the cationic Ge(II) complex [dimpyrGeCl][GeCl3] (dimpyr=2,6-(ArN=CMe)2NC5H3, Ar=2,6-iPr2C6H3) with potassium graphite in benzene affords an air sensitive, dark green compound of Ge(0), [dimpyrGe], which is stabilized by a bis(imino)pyridine platform. This compound is the first example of a complex of a zero-valent Group 14 element that does not contain a carbene or carbenoid ligand. This species has a singlet ground state. DFT studies revealed partial delocalization of one of the Ge lone pairs over the π*(C=N) orbitals of the imines. This delocalization results in a partial multiple-bond character between the Ge atom and imine nitrogen atoms, a fact supported by the X-ray crystallography and IR spectroscopy data.
- Published
- 2014
45. Diastereodivergent total synthesis of mosquito oviposition pheromone
- Author
-
Travis Dudding and David Hurem
- Subjects
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.
- Published
- 2014
46. Competitive hydrogen bonding of cyclopropenium ions: Implications of an anion switch
- Author
-
Matt Guest, Melanie Pilkington, Lee Belding, Travis Dudding, and Richard Le Sueur
- Subjects
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.
- Published
- 2019
47. Reversal of Stereoselectivity in Lithiation of Ferrocenyl-imidazolones: Epimeric Substrates lead to Planar Chiral Enantiomers
- Author
-
Travis Dudding, Costa Metallinos, Jonathan Nelson, Lee Belding, and Joshni John
- Subjects
chemistry.chemical_compound ,Chiral auxiliary ,Cyclopentadiene ,chemistry ,Stereochemistry ,Organic Chemistry ,Electrophile ,Moiety ,Stereoselectivity ,Planar chirality ,Enantiomer ,Catalysis ,Stereocenter - Abstract
Diastereoselective induction of planar chirality in ferrocenes often employs chiral sulfur-, carbon- or phosphorus-based directing groups. The origin of stereoselectivity in these reactions may be classified as (a) cyclopentadiene (Cp) ring-con- trolled or (b) base-controlled. These two categories are represented by auxiliaries that typically have stereogenic centers a or g to the ferrocene core, re- spectively. In this study, it is shown that (� )-2-ferro- cenyl-1S-triethylsilyloxy-7aS-hexahydropyrroloA c)imidazol-3-one, the anti-epimer of the previously reported syn-(1R,7aS) substrate, induces lithiation of the pro-Rp rather than the pro-Sp Cp hydrogen in > 95:5 dr, leading to enantiomers of the syn-derived planar chiral imidazolones upon electrophile quench and elimination. This outcome provides a practical way to prepare planar chiral enantio- mers in this series without having to synthesize a more expensive d-proline-derived starting materi- al, since both the syn and anti starting materials are available from a common l-proline-derived inter- mediate. The origin of stereoselectivity in lithiation of the syn and anti epimers, which have b,g-stereo- genic centers, appears to be driven primarily by the conformational bias exerted by the b-silyloxy moiety in each chiral auxiliary, which positions the urea carbonyl within the proximity of one of the two prochiral ortho Cp hydrogens. As such, stereo- selectivity is likely Cp ring-controlled for both com- pounds despite their lack of a-ferrocenyl stereogen- ic centers. This conclusion is supported by the in- sensitivity of lithiation selectivity to the bulkiness of the base, comparisons of enantiomers, deuteration experiments, nOe difference studies, and computa- tional modeling of the ground states and lithiation transition states for both substrates.
- Published
- 2013
48. A synthetic route to chiral C(3)-functionalized phthalides via a Ag(I)-catalyzed allylation/transesterification sequence
- Author
-
Travis Dudding and Roya Mirabdolbaghi
- Subjects
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.
- Published
- 2013
49. ChemInform Abstract: Synthesis of Chiral Piperazinones Using Amphoteric Aziridine Aldehyde Dimers and Functionalized Isocyanides
- Author
-
Sherif J. Kaldas, Lee Belding, Olga I. Shmatova, Niklas Heine, Andrei K. Yudin, Valentine G. Nenajdenko, Travis Dudding, and Armido Studer
- Subjects
chemistry.chemical_classification ,chemistry.chemical_compound ,chemistry ,Isocyanide ,Side chain ,Reactivity (chemistry) ,General Medicine ,Aziridine ,Combinatorial chemistry ,Aldehyde - Abstract
We have evaluated a range of functionalized isocyanides in the aziridine aldehyde-driven multicomponent synthesis of piperazinones. High diasteroselectivity for each isocyanide was observed. A theoretical evaluation of the reaction course corroborates the experimental data. Moreover, the reactivity of cis- and trans-configured aziridine aldehyde dimers has been compared. This study further probes the dimer-driven mechanism of cyclization and enables an efficient access to a wide range of chiral piperazinones bearing functionalized side chains.
- Published
- 2016
50. ChemInform Abstract: A Au(I)-Precatalyst with a Cyclopropenium Counterion: An Unusual Ion Pair
- Author
-
Travis Dudding and Roya Mir
- Subjects
chemistry.chemical_classification ,Crystallography ,chemistry ,Intermolecular force ,Alkyne ,Non-covalent interactions ,Density functional theory ,General Medicine ,Hydroamination ,Crystal structure ,Ion pairs ,Counterion - Abstract
The synthesis and X-ray crystal structure of a novel Au(I)-precatalyst applied to intermolecular alkyne hydroamination is reported. Density functional theory (DFT) calculations revealed the cyclopropenium counterion of this Au(I)-precatalyst imparts stability through H-bonding and other noncovalent interactions.
- Published
- 2016
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.