48 results on '"Jason E. Hein"'
Search Results
2. Stereospecific Csp3 Suzuki–Miyaura Cross-Coupling That Evades β-Oxygen Elimination
- Author
-
Antonio J. LaPorte, Yao Shi, Jason E. Hein, and Martin D. Burke
- Subjects
General Chemistry ,Catalysis - Published
- 2022
3. Ligand-Accelerated Catalysis in Scandium(III)-Catalyzed Asymmetric Spiroannulation Reactions
- Author
-
Nicolas R. Ball-Jones, Angel A. Cobo, Brittany M. Armstrong, Benjamin Wigman, James C. Fettinger, Jason E. Hein, and Annaliese K. Franz
- Subjects
General Chemistry ,Catalysis - Published
- 2022
4. Quantitative and convenient real-time reaction monitoring using stopped-flow benchtop NMR
- Author
-
Tristan Maschmeyer, Lars P. E. Yunker, and Jason E. Hein
- Subjects
Fluid Flow and Transfer Processes ,Chemistry (miscellaneous) ,Process Chemistry and Technology ,Chemical Engineering (miscellaneous) ,Catalysis - Abstract
We present a stopped-flow benchtop NMR system (composed of commercially available hardware components) that allows for quantitative reaction monitoring to be completed with relative ease, even with experimentally complex reaction systems.
- Published
- 2022
5. Guided optimization of a crystallization-induced diastereomer transformation to access a key navoximod intermediate
- Author
-
Andrew J. Kukor, Frédéric St-Jean, Andreas Stumpf, Thomas C. Malig, Katarzyna A. Piechowicz, Kenji Kurita, and Jason E. Hein
- Subjects
Fluid Flow and Transfer Processes ,Chemistry (miscellaneous) ,Process Chemistry and Technology ,Chemical Engineering (miscellaneous) ,Catalysis - Abstract
The crystallization-induced diastereomer transformation of a precursor to navoximod was investigated using online HPLC and optimized with inline racemization.
- Published
- 2023
6. Ring walking as a regioselectivity control element in Pd-catalyzed C-N cross-coupling
- Author
-
Madeleine C. Deem, Joshua S. Derasp, Thomas C. Malig, Kea Legard, Curtis P. Berlinguette, and Jason E. Hein
- Subjects
Multidisciplinary ,General Physics and Astronomy ,General Chemistry ,Ligands ,Catalysis ,Palladium ,General Biochemistry, Genetics and Molecular Biology ,Amination - Abstract
Ring walking is an important mechanistic phenomenon leveraged in many catalytic C-C bond forming reactions. However, ring walking has been scarcely studied under Buchwald-Hartwig amination conditions despite the importance of such transformations. An in-depth mechanistic study of the Buchwald-Hartwig amination is presented focussing on ligand effects on ring walking behavior. The ability of palladium catalysts to promote or inhibit ring walking is strongly influenced by the chelating nature of the ligand. In stark contrast, the resting state of the catalyst had no impact on ring walking behavior. Furthermore, the complexity of the targeted system enabled the differentiation between catalysts which undergo ring walking versus diffusion-controlled coupling. The insights gained in this study were leveraged to achieve desymmetrization of a tetrabrominated precursor. A small library of asymmetric 2,2′,7,7′-tetrakis[N,N-di(4-methoxyphenyl)amino]-9,9’spirobifluorene (SpiroOMeTAD) derivatives were successfully synthesized using this strategy highlighting the ease with which libraries of these compounds can be accessed for screening.
- Published
- 2022
7. A robust new tool for online solution-phase sampling of crystallizations
- Author
-
Andrew J. Kukor, Mason A. Guy, Joel M. Hawkins, and Jason E. Hein
- Subjects
Fluid Flow and Transfer Processes ,Supersaturation ,Materials science ,Fouling ,010405 organic chemistry ,business.industry ,Process Chemistry and Technology ,Sampling (statistics) ,010402 general chemistry ,01 natural sciences ,Solution phase ,Catalysis ,0104 chemical sciences ,law.invention ,Reliability (semiconductor) ,Chemistry (miscellaneous) ,law ,Filter (video) ,Chemical Engineering (miscellaneous) ,Process engineering ,business ,Saturation (chemistry) ,Filtration - Abstract
Current PAT tools struggle to provide real time solid-phase composition data for crystallizations. HPLC offers a variety of benefits over other solution-phase PATs and can be used to infer solid-phase composition when combining total (solid plus solution phase) sampling with solution-only sampling. However, the selective solution-phase sampling of supersaturated solutions is extremely challenging. We herein present a dynamically flushed in situ filtration device that attaches to the tip of Mettler-Toledo's EasySampler probe and makes use of its mechanical motion to avoid surface fouling. Filter functionality was tested under both increasing saturation (via cooling or antisolvent addition) as well as decreasing saturation (via heating or solvent addition), illustrating its accuracy, reliability and versatility. The utility of the filter tip was highlighted by monitoring the classical resolution of TBZ, an important drug precursor.
- Published
- 2021
8. Conversion of dilute CO2 to cyclic carbonates at sub-atmospheric pressures by a simple indium catalyst
- Author
-
Parisa Mehrkhodavandi, Hootan Roshandel, Jason E. Hein, and Hassan A. Baalbaki
- Subjects
Reaction mechanism ,Materials science ,010405 organic chemistry ,Commodity chemicals ,Inorganic chemistry ,chemistry.chemical_element ,Substrate (chemistry) ,Reaction intermediate ,010402 general chemistry ,7. Clean energy ,01 natural sciences ,Catalysis ,0104 chemical sciences ,chemistry.chemical_compound ,chemistry ,Selectivity ,Tribromide ,Indium - Abstract
The transformation of CO2 to value added commodity chemicals presents an impactful strategy to obtain products that are less dependent on fossil fuels. In this study, indium tribromide (InBr3) mixed with tetrabutylammonium bromide (NBu4Br) co-catalyst has been identified as a simple, highly efficient catalyst for the synthesis of cyclic carbonates from epoxides and CO2 at sub-atmospheric pressures, room temperature, and under solvent-free conditions. The InBr3/NBu4Br catalytic system is tolerant toward different functional groups with high conversions and >99% selectivity for cyclic carbonate without resorting to high pressures and temperatures. Moreover, a combination of in situ IR, NMR spectroscopy, and substrate labelling experiments enabled the proof of key catalytic steps and detection of reaction intermediates to elucidate the reaction mechanism. This technology represents a potential scalable system for the utilization of waste CO2.
- Published
- 2021
9. Online High-Performance Liquid Chromatography Analysis of Buchwald–Hartwig Aminations from within an Inert Environment
- Author
-
Lars P. E. Yunker, Jason E. Hein, Sebastian Steiner, and Thomas C. Malig
- Subjects
Inert ,010405 organic chemistry ,Chemistry ,Organic chemistry ,General Chemistry ,010402 general chemistry ,Inert gas ,01 natural sciences ,High-performance liquid chromatography ,Catalysis ,0104 chemical sciences - Abstract
Obtaining data-dense reaction profiles for reactions performed under an inert atmosphere remains a significant challenge obfuscating mechanistic analysis. To this end, we have developed a reaction ...
- Published
- 2020
10. Development of a telescoped synthesis of 4-(1H)-cyanoimidazole core accelerated by orthogonal reaction monitoring
- Author
-
Carolyn S. Higman, Adrian Ortiz, Geoffrey E. Purdum, Ronald Carrasquillo-Flores, Yichen Tan, Kolotuchin Sergei, Steven R. Wisniewski, Thomas C. Malig, and Jason E. Hein
- Subjects
Fluid Flow and Transfer Processes ,Reaction conditions ,Trifluoromethyl ,010405 organic chemistry ,Kinetic information ,Process Chemistry and Technology ,Substrate (chemistry) ,010402 general chemistry ,01 natural sciences ,Combinatorial chemistry ,Catalysis ,0104 chemical sciences ,chemistry.chemical_compound ,chemistry ,Cascade reaction ,Chemistry (miscellaneous) ,Hemiaminal ,Chemical Engineering (miscellaneous) ,Imidazole ,Selectivity - Abstract
We have developed a convenient two-step, one-pot method for the facile synthesis of cyanoimidazoles. By integrating a suite of reaction-monitoring techniques, we were able to interrogate each transformation independently. We observed that formation of a key hemiaminal intermediate is complicated via many equilibrium processes, creating oligomers and eventually resulting in unproductive dimerization. DoE experiments indicated that despite the complex equilibria of this substrate, high conversion to the trifluoromethyl imidazole can still be achieved. We also report the effects of temperature, pH, and substrate concentrations on the rate and selectivity of the elimination cascade reaction converting the trifluoromethyl imidazole to the cyanoimidazole. By leveraging kinetic information gathered from each step independently, we report reaction conditions to achieve high yields of the cyanoimidazole from carbonyl-containing substrate directly in one pot.
- Published
- 2020
11. Using an Automated Monitoring Platform for Investigations of Biphasic Reactions
- Author
-
Rebecca T. Ruck, Yuejun Guo, Jason E. Hein, and Jordan A. Daponte
- Subjects
010405 organic chemistry ,Computer science ,Sampling (statistics) ,General Chemistry ,Biochemical engineering ,010402 general chemistry ,01 natural sciences ,Catalysis ,0104 chemical sciences - Abstract
Insights and mechanistic studies into biphasic reactions are often challenging due to difficulty in deploying in situ reaction-monitoring or sampling procedures. Herein, we describe the development...
- Published
- 2019
12. Development of an automated kinetic profiling system with online HPLC for reaction optimization
- Author
-
John R. Naber, Shane T. Grosser, Kerstin Zawatzky, Jinchu Liu, Jon A. Jurica, Folarin Adedeji, Yining Ji, Melodie Christensen, and Jason E. Hein
- Subjects
Fluid Flow and Transfer Processes ,010405 organic chemistry ,Computer science ,business.industry ,Process Chemistry and Technology ,010402 general chemistry ,01 natural sciences ,High-performance liquid chromatography ,Catalysis ,0104 chemical sciences ,Reaction rate ,Chemistry (miscellaneous) ,Liquid handling robot ,Chemical Engineering (miscellaneous) ,Profiling (information science) ,Process engineering ,business - Abstract
Automated kinetic profiling is a valuable tool for providing insights into key mechanistic features of complex catalytic systems. In an attempt to optimize a palladium-catalyzed Suzuki cross-coupling reaction, automated kinetic profiling was utilized with offline liquid chromatography to monitor reaction progress. Upon uncovering analytical sample instability issues, an online HPLC capability was developed and implemented through integration of a Chemspeed liquid handling robot with an Agilent HPLC to facilitate automated reaction set-up and monitoring. Application of this capability resulted in the observation that precatalyst activation was a key factor influencing the reaction rate. Leveraging this mechanistic insight, a more efficient method to access the active catalyst was developed. This change resulted in a five-fold increase in the reaction rate.
- Published
- 2019
13. Automated solubility and crystallization analysis of non-UV active compounds: integration of evaporative light scattering detection (ELSD) and robotic sampling
- Author
-
Jason E. Hein and Ryan Chung
- Subjects
Fluid Flow and Transfer Processes ,Materials science ,Resolution (mass spectrometry) ,010405 organic chemistry ,Process Chemistry and Technology ,Analytical chemistry ,Sampling (statistics) ,010402 general chemistry ,01 natural sciences ,Solution phase ,Catalysis ,Light scattering ,0104 chemical sciences ,law.invention ,Chemistry (miscellaneous) ,law ,Chromatography detector ,Chemical Engineering (miscellaneous) ,Crystallization ,Solubility - Abstract
This article describes the integration of evaporative light scattering detection (ELSD) with automated robotic sampling to obtain reliable and data-rich solubility and crystallization profiles of minimally- or non-UV active compounds. The new technology allowed for the thermodynamic solubilities of various compounds to be profiled over broad temperature ranges without experimenter intervention. Two case studies are presented that illustrate the ability of the automated system to furnish solution phase composition of systems actively undergoing crystallization: first, the dynamic change in the solution phase concentration of multiple components during seeded preferential crystallization is monitored and time-course profiles showing the change in solution phase enantiomeric excess (e.e.) were created. Second, a diastereomeric resolution is profiled, illustrating the utility that monitoring the solution phase composition during crystallization has on reporting on the success of this classical resolution method. Validation of the sampling technology is provided by corroborating the ELSD data with in situ ReactIR monitoring.
- Published
- 2019
14. Online HPLC Analysis of Buchwald-Hartwig Aminations from Within an Inert Environment
- Author
-
Sebastian Steiner, Lars P. E. Yunker, Thomas C. Malig, and Jason E. Hein
- Subjects
Chemical kinetics ,chemistry.chemical_compound ,Reaction mechanism ,Polymerization ,chemistry ,Intramolecular force ,Iodobenzene ,Reactivity (chemistry) ,Combinatorial chemistry ,Coupling reaction ,Catalysis - Abstract
We have developed a reaction monitoring platform capable of automated sampling and online HPLC analysis to generate temporal profiles for reactions performed from within a glovebox. The device allows for facile reaction progress analysis to aid in mechanistic studies of air-sensitive chemical transformations. The platform has demonstrated high reproducibility regarding sample mixing, dilution, delivery, and analysis. We employed the sampling platform to acquire temporal profiles for a series of Buchwald-Hartwig aminations. Parallel coupling reactions using iodobenzene and bromobenzene both exhibit complex kinetics. A competition reaction including both aryl halides demonstrated high selectivity for iodobenzene indicative of catalyst monopoly. The temporal profile for the difunctionalized substrate 1,4-iodobromobenzene was unexpected based a priori and is indicative of a distinct underlying mechanism. We attribute this unanticipated reactivity to intramolecular catalysts transfer through the π system as seen in “living” polymerization transfer catalyst systems. This automated sampling platform has greatly increased mechanistic understanding by performing only a small subset of experiments.
- Published
- 2020
15. A Revised Mechanism for the Kinugasa Reaction
- Author
-
Jason E. Hein, Thomas C. Malig, and Diana Yu
- Subjects
Chemical substance ,Alkyne ,Ketene ,beta-Lactams ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Catalysis ,Nitrone ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,Computational chemistry ,chemistry.chemical_classification ,Cycloaddition Reaction ,010405 organic chemistry ,Chemistry ,General Chemistry ,Cycloaddition ,0104 chemical sciences ,Kinetics ,Models, Chemical ,Mechanism (philosophy) ,Alkynes ,Yield (chemistry) ,Imines ,Copper - Abstract
Detailed kinetic analysis for the Cu(I)-catalyzed Kinugasa reaction forming β-lactams has revealed an anomalous overall zero-order reaction profile, due to opposing positive and negative orders in nitrone and alkyne, respectively. Furthermore, the reaction displays a second-order dependence on the catalyst, confirming the critical involvement of a postulated bis-Cu complex. Finally, reaction progress analysis of multiple byproducts has allowed a new mechanism, involving a common ketene intermediate to be delineated. Our results demonstrate that β-lactam synthesis through the Kinugasa reaction proceeds via a cascade involving (3 + 2) cycloaddition, (3 + 2) cycloreversion, and finally (2 + 2) cycloaddition. Our new mechanistic understanding has resulted in optimized reaction conditions to dramatically improve the yield of the target β-lactams and provides the first consistent mechanistic model to account for the formation of all common byproducts of the Kinugasa reaction.
- Published
- 2018
16. Efficient and Selective Iron-Complex-Catalyzed Hydroboration of Aldehydes
- Author
-
Carolyn S. Higman, Bulat Gabidullin, R. Tom Baker, Uttam K. Das, and Jason E. Hein
- Subjects
010405 organic chemistry ,Chemistry ,Ligand ,Halide ,General Chemistry ,010402 general chemistry ,01 natural sciences ,Catalysis ,3. Good health ,0104 chemical sciences ,Hydroboration ,Organic chemistry ,Iron complex ,Selectivity ,Reaction progress kinetic analysis - Abstract
An imine-coupled [Fe–N2S2]2 complex, prepared from a readily available benzothiazolidine ligand, catalyzes selectively the hydroboration of aliphatic and aromatic aldehydes at low catalyst loadings (0.1 mol %) using pinacolborane. Both mono- and disubstituted aromatic and aliphatic aldehydes are hydroborated selectively in the presence of ketones, nitriles, alkenes, amines, and halides. Reaction of the [Fe–N2S2]2 complex with CO and preliminary reaction progress kinetic studies point to a complex mechanism.
- Published
- 2018
17. Mechanism of a No-Metal-Added Heterocycloisomerization of Alkynylcyclopropylhydrazones: Synthesis of Cycloheptane-Fused Aminopyrroles Facilitated by Copper Salts at Trace Loadings
- Author
-
Ethan L. Fisher, Diana Yu, Richmond Sarpong, Dean J. Tantillo, Phillip P. Painter, Jason E. Hein, and Sidney M. Wilkerson-Hill
- Subjects
chemistry.chemical_classification ,010405 organic chemistry ,Substituent ,chemistry.chemical_element ,Alkyne ,Hydrazone ,General Chemistry ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Copper ,Catalysis ,0104 chemical sciences ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,chemistry ,Computational chemistry ,Yield (chemistry) ,Organic chemistry ,Cycloheptane ,Isomerization - Abstract
A mechanistic study of a new heterocycloisomerization reaction that forms annulated aminopyrroles is presented. Density functional theory calculations and kinetic studies suggest the reaction is catalyzed by trace copper salts and that a Z- to E-hydrazone isomerization occurs through an enehydrazine intermediate before the rate-determining cyclization of the hydrazone onto the alkyne group. The aminopyrrole products are obtained in 36-93% isolated yield depending on the nature of the alkynyl substituent. A new automated sampling technique was developed to obtain robust mechanistic data.
- Published
- 2017
18. Reaction Progress Kinetics Analysis of 1,3-Disiloxanediols as Hydrogen-Bonding Catalysts
- Author
-
Annaliese K. Franz, Kayla M. Diemoz, James C. Fettinger, Sean O. Wilson, and Jason E. Hein
- Subjects
Addition reaction ,010405 organic chemistry ,Organic Chemistry ,Kinetics ,010402 general chemistry ,01 natural sciences ,0104 chemical sciences ,Catalysis ,Silanol ,chemistry.chemical_compound ,chemistry ,Thiourea ,Product inhibition ,Organic chemistry ,Reaction progress kinetic analysis ,Friedel–Crafts reaction - Abstract
1,3-Disiloxanediols are effective hydrogen-bonding catalysts that exhibit enhanced activity relative to silanediols and triarylsilanols. The catalytic activity for a series of 1,3-disiloxanediols, including naphthyl-substituted and unsymmetrical siloxanes, has been quantified and compared relative to other silanol and thiourea catalysts using the Friedel Crafts addition of indole to trans-β-nitrostyrene. An in-depth kinetic study using reaction progress kinetic analysis (RPKA) has been performed to probe the catalyst behavior of 1,3-disiloxanediols. The data confirm that the disiloxanediol-catalyzed addition reaction is first order in catalyst over all concentrations studied with no evidence of catalyst self-association. 1,3-Disiloxanediols proved to be robust and recoverable catalysts with no deactivation under reaction conditions. No product inhibition is observed, and competitive binding studies with nitro-containing additives suggest that 1,3-disiloxanediols bind weakly to nitro groups but are strongly activating for catalysis.
- Published
- 2017
19. Catalyst-Controlled Nitrene Transfer by Tuning Metal:Ligand Ratios: Insight into the Mechanisms of Chemoselectivity
- Author
-
Juliet M. Alderson, Cale D. Weatherly, John F. Berry, Jennifer M. Schomaker, and Jason E. Hein
- Subjects
Steric effects ,Denticity ,010405 organic chemistry ,Chemistry ,Nitrene ,Organic Chemistry ,Reactive intermediate ,Kinetics ,010402 general chemistry ,Photochemistry ,01 natural sciences ,0104 chemical sciences ,Catalysis ,Inorganic Chemistry ,Metal ,visual_art ,visual_art.visual_art_medium ,Physical and Theoretical Chemistry ,Chemoselectivity - Abstract
Catalyst-controlled, selective nitrene transfer is often challenging when both C–H and C═C bonds are present in a substrate. Interestingly, a simple change in the Ag(I):L ratio (L = bidentate N,N-donor ligand) enables tunable, chemoselective nitrene transfer that favors either C═C bond aziridination using an ∼1:1 Ag:L ratio (AgLOTf) or insertion into a C–H bond when the Ag:L ratio in the catalyst is 1:2 (AgL2OTf). In this paper, mechanistic studies, coupled with kinetic profiling of the entire reaction course, are employed to examine the reasons for this unusual behavior. Steady-state kinetics were found to be similar for both AgLOTf and AgL2OTf; both complexes yield electronically similar reactive intermediates that engage in nitrene transfer involving formation of a short-lived radical intermediate and barrierless radical recombination. Taken together, experimental and computational studies point to two effects that control tunable chemoselectivity: suppression of aziridination as the steric congestion ...
- Published
- 2017
20. Copper-Catalyzed Hydrogen/Iodine Exchange in Terminal and 1-Iodoalkynes
- Author
-
Anh Vo, Ryan Chung, and Jason E. Hein
- Subjects
chemistry.chemical_classification ,Hydrogen ,Proton ,010405 organic chemistry ,Chemistry ,Iodide ,chemistry.chemical_element ,General Chemistry ,010402 general chemistry ,Photochemistry ,Iodine ,01 natural sciences ,Catalysis ,0104 chemical sciences ,3. Good health ,Terminal (electronics) ,Computational chemistry ,Copper catalyzed - Abstract
Detailed kinetic profiles of the copper-catalyzed exchange between the acetylenic proton and iodide of terminal and 1-iodophenylacetylenes are reported. The electronic nature of the alkynes does not influence the equilibrium of the exchange (Keq = 1), only the rate of equilibration. Notably, the profiles are the same for electron-rich, methyl-substituted phenylacetylenes but are divergent for electron-deficient, trifluoromethyl-substituted variants. The heretofore unreported exchange process yields practical considerations regarding reactions involving iodo and terminal alkynes.
- Published
- 2017
21. Real-time HPLC-MS reaction progress monitoring using an automated analytical platform
- Author
-
Henry Situ, Philip G. Hultin, Thomas C. Malig, Navneet K. Chehal, Josh D. B. Koenig, and Jason E. Hein
- Subjects
Fluid Flow and Transfer Processes ,010405 organic chemistry ,Chemistry ,Process Chemistry and Technology ,Process analytical technology ,Monitoring system ,Nanotechnology ,010402 general chemistry ,01 natural sciences ,Catalysis ,Cycloaddition ,0104 chemical sciences ,Cascade reaction ,Chemistry (miscellaneous) ,Robustness (computer science) ,Reagent ,Chemical Engineering (miscellaneous) ,Biological system - Abstract
An automated reaction monitoring system capable of unattended sample aliquoting and dilution, as well as immediate quantification and identification of reaction components via HPLC-MS has been developed. The device allows for facile reaction progress analysis, enabling mechanistic studies and serving as a primary process analytical technology (PAT) for reaction monitoring. The sampling sequence utilizes in line mixing to provide highly reproducible and accurate reaction profiles. To demonstrate the flexibility and robustness of this tool, progress curves have been acquired for three distinct reactions; namely a Cu(I)-catalysed azide-alkyne cycloaddition which is difficult to quench due to very high catalyst activity, a Suzuki cross-coupling reaction that proves challenging to monitor due to heterogenous reagents, and a complex multicomponent cascade reaction that generates multiple regioisomers that are difficult to quantify by online spectroscopic methods.
- Published
- 2017
22. Automated reaction progress monitoring of heterogeneous reactions: crystallization-induced stereoselectivity in amine-catalyzed aldol reactions
- Author
-
Henry Situ, V. Vlachos, Blessing Huynh Cao, Céline Rougeot, and Jason E. Hein
- Subjects
Fluid Flow and Transfer Processes ,010405 organic chemistry ,Process Chemistry and Technology ,Cyclohexanone ,010402 general chemistry ,01 natural sciences ,Catalysis ,Pyrrolidine ,0104 chemical sciences ,law.invention ,chemistry.chemical_compound ,chemistry ,Aldol reaction ,Chemistry (miscellaneous) ,law ,Slurry ,Chemical Engineering (miscellaneous) ,Organic chemistry ,Stereoselectivity ,Amine gas treating ,Crystallization - Abstract
A prototype automated system has been developed, which is capable of acquiring accurate kinetic reaction profiles from heterogeneous reactions. The device is capable of monitoring the composition and concentration of either the dissolved components (solution phase) or slurry (solid and solution phases) in parallel. This prototype was used to study the diastereo- and enantioselectivity of the aldol reaction between 4-tert-butyl cyclohexanone and p-nitrobenzaldehyde, catalyzed by either pyrrolidine or L-proline. With both catalysts, the observed high diastereoselectivity involves an interplay between solution phase reaction/epimerization and crystallization. These observations were possible due to the facile method of tandem solution and slurry analysis.
- Published
- 2017
23. One-Pot 1,1-Dihydrofluoroalkylation of Amines Using Sulfuryl Fluoride
- Author
-
Paul J. Foth, Maxim Epifanov, Carolyn S. Higman, Jason E. Hein, Frances Gu, Charlotte Barrillon, Glenn M. Sammis, and Sahil S. Kanani
- Subjects
Primary (chemistry) ,010405 organic chemistry ,Substrate (chemistry) ,General Chemistry ,Alkylation ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Catalysis ,0104 chemical sciences ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,chemistry ,Reagent ,Functional group ,Organic chemistry ,Amine gas treating ,Organic synthesis ,Sulfuryl fluoride - Abstract
Sulfuryl fluoride, SO2F2, has been known and used as a fumigant for over 50 years but it has only recently gained widespread interest as a reagent for organic synthesis. Herein we report a novel application of sulfuryl fluoride gas in a new 1,1-dihydrofluoroalkylation reaction, which simply involves bubbling SO2F2 through a solution of amine, 1,1-dihydrofluoroalcohol, and diisopropylethylamine. The reaction is successful for a wide range of primary and secondary amines, as well as several 1,1-dihydrofluoroalcohols, to afford the 1,1-dihydrofluoroalkylated amines in 42% to 80% isolated yields. The reaction also displays excellent functional group tolerance. The ease of the one-pot activation and alkylation, combined with the wide substrate scope make this new procedure an attractive alternative to existing 1,1-dihydrofluoroalkylation methodologies.
- Published
- 2018
24. Measuring and Suppressing the Oxidative Damage to DNA During Cu(I)-Catalyzed Azide–Alkyne Cycloaddition
- Author
-
Jason E. Hein, Zachary A. Calabrese, Gary R. Abel, Tao Ye, and Jeffrey Ayco
- Subjects
Azides ,DNA damage ,Biomedical Engineering ,Pharmaceutical Science ,Alkyne ,Bioengineering ,010402 general chemistry ,01 natural sciences ,Catalysis ,chemistry.chemical_compound ,Organic chemistry ,Reactivity (chemistry) ,Pharmacology ,chemistry.chemical_classification ,Bioconjugation ,Cycloaddition Reaction ,010405 organic chemistry ,Chemistry ,Oligonucleotide ,Organic Chemistry ,Combinatorial chemistry ,Cycloaddition ,0104 chemical sciences ,3. Good health ,Oxidative Stress ,Alkynes ,Click chemistry ,Azide ,Copper ,DNA Damage ,Biotechnology - Abstract
We have used the quantitative polymerase chain reaction (qPCR) to measure the extent of oxidative DNA damage under varying reaction conditions used for copper(I)-catalyzed click chemistry. We systematically studied how the damage depends on a number of key reaction parameters, including the amounts of copper, ascorbate, and ligand used, and found that the damage is significant under nearly all conditions tested, including those commonly used for bioconjugation. Furthermore, we discovered that the addition of dimethyl sulfoxide, a known radical scavenger, into the aqueous mixture dramatically suppresses DNA damage during the reaction. We also measured the efficiency of cross-linking two short synthetic oligonucleotides via click chemistry, and found that the reaction could proceed reasonably efficiently even with DMSO present. This approach for screening both DNA damage and reactivity under a range of reaction conditions will be valuable for improving the biocompatibility of click chemistry, and should help to extend this powerful synthetic tool for both in vitro and in vivo applications.
- Published
- 2016
25. Tandem Reaction Progress Analysis as a Means for Dissecting Catalytic Reactions: Application to the Aza-Piancatelli Rearrangement
- Author
-
Javier Read de Alaniz, Diana Yu, Ryan Chung, Jason E. Hein, Alyssa F. Jones, Van T. Thai, and Gesine K. Veits
- Subjects
Reaction mechanism ,aza-Piancatelli rearrangement ,Tandem ,Stereochemistry ,Chemistry ,Organic Chemistry ,General Chemistry ,Chemical Engineering ,automated sampling ,homogeneous catalysis ,Combinatorial chemistry ,Catalysis ,Inorganic Chemistry ,reaction mechanisms ,transient intermediate tracking ,Cascade reaction ,tandem reaction progress analysis ,cascade rearrangement ,Cancer ,Piancatelli rearrangement - Abstract
© 2015 American Chemical Society. Continuing developments in the elucidation techniques of complex catalytic processes is of foremost importance to modern synthetic chemistry, and the identification of efficient synthetic techniques relies on precise, reliable, and adaptable methods to dissect the mechanism of a given transformation. Currently, methods of reaction development are grounded upon the systematic modification of specific variables - such as temperature, time, concentration, etc. - to account for and control the dynamic series of coupled equilibria within a catalytic environment. On the other hand, tandem reaction analytical methods that involve the concomitant use of different instruments to probe a reaction can provide time-resolved information regarding active chemical species and facilitate the interrogation and optimization of the system. Herein, we report our study applying tandem in situ ReactIR and HPLC-MS monitoring to the dysprosium(III) triflate-catalyzed aza-Piancatelli rearrangement of 2-furylcarbinols, a reaction that grants access to trans-4,5-disubstituted cyclopentenones - common motifs in important biologically relevant and natural compounds. With a prototype automated sampling apparatus, information was obtained about the intrinsic chemoselectivity of the reaction, and previously unseen intermediates were observed, allowing for a more detailed reaction mechanism to be substantiated. The advantages of applying this type of tandem measurement to study these types of systems are also discussed. (Figure Presented).
- Published
- 2015
26. Synthesis of Benzodihydrofurans by Asymmetric C-H Insertion Reactions of Donor/Donor Rhodium Carbenes
- Author
-
Dean J. Tantillo, Jason E. Hein, Srinivasa R. Chintala, Jared T. Shaw, Kellan N. Lamb, Joseph M. Fox, Olga Dmitrenko, Edward I. Balmond, Ryan Chung, James C. Fettinger, J. Bennett Addison, Marta Castiñeira Reis, Richard A. Squitieri, Cristian Soldi, and Ada J. Kwong
- Subjects
Steric effects ,Allylic rearrangement ,010405 organic chemistry ,Organic Chemistry ,Enantioselective synthesis ,Ether ,General Chemistry ,010402 general chemistry ,01 natural sciences ,Combinatorial chemistry ,Catalysis ,Cycloaddition ,0104 chemical sciences ,chemistry.chemical_compound ,chemistry ,Electrophile ,Organic chemistry ,Diazo ,Carbene - Abstract
Metal carbenes appended with two electron-donating groups, known as "donor/donor" carbenes, undergo diastereo- and enantioselective rhodium-catalyzed C-H insertion reactions with ether substrates to form benzodihydrofurans. Unlike the reactions of metal carbenes with electron-withdrawing groups attached, the attenuated electrophilicity enables these reactions to be conducted in Lewis basic solvents (e.g., acetonitrile) and in the presence of water. The diazo precursors for these species are prepared in situ from hydrazone using a mild and chemoselective oxidant (MnO2 ). Although this sequence often can be performed in one-pot, control experiments have elucidated why a "two-pot" process is often more efficient. A thorough screening of achiral catalysts demonstrated that sterically encumbered catalysts are optimal for diastereoselective reactions. Although efficient insertion into allylic and propargylic C-H bonds is observed, competing dipolar cycloaddition processes are noted for some substrates. The full substrate scope of this useful method of benzodihydrofuran synthesis, mechanisms of side reactions, and computational support for the origins of stereoselectivity are described.
- Published
- 2017
27. Predicting the Relative Solubilities of Racemic and Enantiopure Crystals by Density-Functional Theory
- Author
-
Erin R. Johnson, Blessing Huynh Cao, Alberto Otero-de-la-Roza, Jason E. Hein, and Ivy K. Price
- Subjects
Chemistry ,Enantioselective synthesis ,General Medicine ,General Chemistry ,Catalysis ,law.invention ,Enantiopure drug ,Computational chemistry ,law ,Organic chemistry ,Density functional theory ,Crystallization ,Solubility ,Enantiomer ,Dispersion (chemistry) ,Enantiomeric excess - Abstract
Isolation of chiral molecules as pure enantiomers remains a fundamental challenge in chemical research. Enantioselective enrichment through preferential crystallization is an efficient method to achieve enantiopure compounds, but its applicability depends on the relative stability of the enantiopure and racemic crystal forms. Using a simple thermodynamic model and first-principles density-functional calculations, it is possible to predict the difference in solubility between the enantiopure and racemic solid phases. This approach uses dispersion-corrected density functionals and is capable of accurately predicting the solution-phase entantiomeric excess to within about 10% of experimental measurements on average. The accuracy of the exchange-hole dipole moment (XDM) model of dispersion enables the viability of the proposed method. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
- Published
- 2014
28. Importance of Off-Cycle Species in the Acid-Catalyzed Aza-Piancatelli Rearrangement
- Author
-
Jason E. Hein, Diana Yu, Jonathan E. Cook, Van T. Thai, Gesine K. Veits, Leoni I. Palmer, and Javier Read de Alaniz
- Subjects
Aza Compounds ,Molecular Structure ,Chemistry ,Organic Chemistry ,Sigmatropic reaction ,Photochemistry ,Medicinal chemistry ,Catalysis ,Lewis acid catalysis ,Reaction rate ,Medicinal and Biomolecular Chemistry ,chemistry.chemical_compound ,Aniline ,Nucleophile ,Dysprosium ,Acids ,Trifluoromethanesulfonate ,Piancatelli rearrangement - Abstract
The observed rate of reaction in the dysprosium triflate catalyzed aza-Piancatelli rearrangement is controlled by a key off-cycle binding between aniline and catalyst. Deconvoluting the role of these ancillary species greatly broadens our understanding of factors affecting the productive catalytic pathway. We demonstrate that the rate of reaction is controlled by initial competitive binding between the furylcarbinol and nitrogen nucleophile using either a Brønsted or Lewis acid catalyst and that the resulting rearrangement proceeds without involving the Brønsted and Lewis acid catalyst. This shows conclusively that the rate-controlling step and selectivity of reaction are decoupled. © 2013 American Chemical Society.
- Published
- 2013
29. Preface
- Author
-
Jason E. Hein and Jordi Burés
- Subjects
General Chemistry ,Catalysis - Published
- 2017
30. Iterative in Situ Click Chemistry Assembles a Branched Capture Agent and Allosteric Inhibitor for Akt1
- Author
-
K. Barry Sharpless, Heather D. Agnew, Kaycie Deyle, James R. Heath, Jaehong Lim, Arundhati Nag, Su Seong Lee, Ryan K. Henning, Suresh M. Pitram, Steven W. Millward, Jessica A. Pfeilsticker, Gabriel A. Kwong, and Jason E. Hein
- Subjects
chemistry.chemical_classification ,In situ ,Chemistry ,medicine.drug_class ,Allosteric regulation ,Peptide ,General Chemistry ,Ligand (biochemistry) ,Monoclonal antibody ,Biochemistry ,Small molecule ,Combinatorial chemistry ,Article ,Catalysis ,Structure-Activity Relationship ,Colloid and Surface Chemistry ,medicine ,Click chemistry ,Structure–activity relationship ,Click Chemistry ,Protein Kinase Inhibitors ,Proto-Oncogene Proteins c-akt ,Allosteric Site - Abstract
We describe the use of iterative in situ click chemistry to design an Akt-specific branched peptide triligand that is a drop-in replacement for monoclonal antibodies in multiple biochemical assays. Each peptide module in the branched structure makes unique contributions to affinity and/or specificity resulting in a 200 nM affinity ligand that efficiently immunoprecipitates Akt from cancer cell lysates and labels Akt in fixed cells. Our use of a small molecule to preinhibit Akt prior to screening resulted in low micromolar inhibitory potency and an allosteric mode of inhibition, which is evidenced through a series of competitive enzyme kinetic assays. To demonstrate the efficiency and selectivity of the protein-templated in situ click reaction, we developed a novel QPCR-based methodology that enabled a quantitative assessment of its yield. These results point to the potential for iterative in situ click chemistry to generate potent, synthetically accessible antibody replacements with novel inhibitory properties.
- Published
- 2011
31. Enamine Carboxylates as Stereodetermining Intermediates in Prolinate Catalysis
- Author
-
Jordi Burés, Yu-hong Lam, Alan Armstrong, Kendall N. Houk, Matthew Hughes, Donna G. Blackmond, and Jason E. Hein
- Subjects
Aldehydes ,Molecular Structure ,Proline ,Organic Chemistry ,Carboxylic Acids ,Stereoisomerism ,Biochemistry ,Catalysis ,Enamine ,chemistry.chemical_compound ,chemistry ,Organic chemistry ,Carboxylate ,Physical and Theoretical Chemistry ,Oxazolidinones ,Amination - Abstract
Experimental and computational studies probing the nature of intermediates in the α-amination of aldehydes catalyzed by prolinate salts support an enamine carboxylate intermediate in the stereodetermining step.
- Published
- 2011
32. Synthesis of 7-Aza-5-deazapurine Analogues via Copper(I)-Catalyzed Hydroamination of Alkynes and 1-Iodoalkynes
- Author
-
Valery V. Fokin, Jason E. Hein, and Larissa B. Krasnova
- Subjects
chemistry.chemical_classification ,Aza Compounds ,Molecular Structure ,Intramolecular reaction ,Chemistry ,Stereochemistry ,Organic Chemistry ,chemistry.chemical_element ,Alkyne ,Copper ,Combinatorial chemistry ,Chemical synthesis ,Article ,Catalysis ,Isomerism ,Purines ,Alkynes ,Intramolecular force ,Hydroamination ,Hydrocarbons, Iodinated ,Amination - Abstract
A new method for the synthesis of dihydroimidazo[1,2-a][1,3,5]triazin-4(6H)-ones via copper(I)-catalyzed hydroamination was developed. In addition, for the first time, iodoalkynes were shown to participate in the copper(I)-catalyzed intramolecular hydroamination reaction with exclusive formation of E-isomers.
- Published
- 2010
33. Copper(I)-Catalyzed Cycloaddition of Organic Azides and 1-Iodoalkynes
- Author
-
Valery Fokin, Jason E. Hein, K. Barry Sharpless, Jonathan C. Tripp, and Larissa B. Krasnova
- Subjects
Azides ,Tertiary amine ,Triazole ,Substituent ,chemistry.chemical_element ,General Chemistry ,Triazoles ,Copper ,Catalysis ,Cycloaddition ,chemistry.chemical_compound ,chemistry ,Polymer chemistry ,Click chemistry ,Organic chemistry ,Azide ,Iodine - Abstract
This invention provides a method for preparing a 1,2,3-triazole compound comprising contacting an organic azide with a 2-substitued-1-haloalkyne, in the presence of a copper catalyst and a copper-coordinating ligand (preferably a tertiary amine) in a liquid reaction medium, thereby forming a 1,4,5-substituted-1,2,3-triazole compound including a halo substituent at the 5-position of the triazole, the organic portion of the organic azide at the 1-position of the triazole, and the substituent of the 1-iodoalkyne at the 4-position of the triazole. A method for preparing 1-iodoalkynes is also provided.
- Published
- 2009
34. Iterative In Situ Click Chemistry Creates Antibody-like Protein-Capture Agents
- Author
-
Vanessa M. Burns, Russell-John Krom, Woon-Seok Yeo, Steven W. Millward, James R. Heath, Abdul Ahad Tariq, Jason E. Hein, Rosemary D. Rohde, Arundhati Nag, K. Barry Sharpless, Heather D. Agnew, Suresh M. Pitram, and Valery V. Fokin
- Subjects
In situ ,chemistry.chemical_classification ,Ligand ,Proteins ,Peptide ,General Chemistry ,Triazoles ,Ligands ,Combinatorial chemistry ,Antibodies ,Article ,Catalysis ,Cycloaddition ,chemistry ,Peptide Library ,Click chemistry ,Peptides ,Peptide library ,Copper ,Protein Binding - Abstract
Special agents for protein capture: Iterative in situ click chemistry (see scheme for the tertiary ligand screen) and the one-bead-one-compound method for the creation of a peptide library enable the fragment-based assembly of selective high-affinity protein-capture agents. The resulting ligands are water-soluble and stable chemically, biochemically, and thermally. They can be produced in gram quantities through copper(I)-catalyzed cycloaddition.
- Published
- 2009
35. Cascade rearrangement of furylcarbinols with hydroxylamines: practical access to densely functionalized cyclopentane derivatives
- Author
-
Javier Read de Alaniz, Leoni I. Palmer, Donald R. Wenz, Gesine K. Veits, André H. St. Amant, and Jason E. Hein
- Subjects
Methanol ,Organic Chemistry ,Stereoisomerism ,Cyclopentanes ,Hydroxylamines ,Biochemistry ,Catalysis ,chemistry.chemical_compound ,Medicinal and Biomolecular Chemistry ,Hydroxylamine ,chemistry ,Nucleophile ,Cascade ,Organic chemistry ,Cyclopentene ,Physical and Theoretical Chemistry ,Cyclopentane ,Piancatelli rearrangement - Abstract
© The Royal Society of Chemistry 2015. This article describes the aza-Piancatelli rearrangement with hydroxylamines to 4-aminocyclopentenones and subsequent transformations that highlight the versatility of the cyclopentene scaffold and the value of the hydroxylamine nucleophile in this transformation.
- Published
- 2015
36. ChemInform Abstract: Oxidative Esterification of Aldehydes Using Mesoionic 1,2,3-Triazolyl Carbene Organocatalysts
- Author
-
Jason E. Hein, Matthew T. Berry, and Disnay Castrejon
- Subjects
chemistry.chemical_compound ,chemistry ,Organocatalysis ,Mesoionic ,Organic chemistry ,Reactivity (chemistry) ,General Medicine ,Oxidative phosphorylation ,Inverse correlation ,Carbene ,Catalysis ,Adduct - Abstract
The synthesis and catalytic activity of a new class of 1,2,3-triazolyl N-heterocyclic carbene organocatalysts is described. These new catalysts chemoselectively facilitate the oxidative esterification of aldehydes. NMR acidity studies show an inverse correlation between triazolium acidity and reactivity. Kinetic studies show that the resting state of the catalyst involves a NHC–aldehyde adduct. A catalytically active intermediate was synthesized and characterized by X-ray diffraction as the initial carbene–aldehyde adduct.
- Published
- 2014
37. Recyclable supports for stereoselective 1,3-dipolar cycloadditions: application of a fluorous oxazolidinone chiral auxiliary
- Author
-
Philip G. Hultin and Jason E. Hein
- Subjects
Inorganic Chemistry ,Chiral auxiliary ,chemistry.chemical_compound ,chemistry ,Reductive cleavage ,Organic Chemistry ,Organic chemistry ,Stereoselectivity ,Solid phase extraction ,Physical and Theoretical Chemistry ,Catalysis ,Cycloaddition - Abstract
The utility of a new fluorous-supported chiral auxiliary was tested using a series of catalyzed and uncatalyzed 1,3-dipolar cycloaddition reactions with diphenylnitrone. The yields and selectivities of the cycloadducts compare favourably with those obtained using the conventional Evans-type auxiliaries, while purification was greatly assisted by using fluorous solid phase extraction. Following characterization, the cycloadducts were released from the auxiliaries by reductive cleavage. The auxiliary was readily refunctionalized and reused in subsequent cycloaddition reactions, with no deterioration of the observed yields or selectivities.
- Published
- 2005
38. The mechanism of the reaction between an aziridine and carbon dioxide with no added catalyst
- Author
-
Allan R. Pinhas, Jason E. Hein, Dean J. Tantillo, and Chau Phung
- Subjects
chemistry.chemical_classification ,010405 organic chemistry ,Organic Chemistry ,Kinetics ,Salt (chemistry) ,Aziridine ,010402 general chemistry ,Photochemistry ,01 natural sciences ,0104 chemical sciences ,Catalysis ,chemistry.chemical_compound ,chemistry ,Carbon dioxide ,Ammonium ,Physical and Theoretical Chemistry - Abstract
The mechanism of the reaction at room temperature between an unactivated 2-alkyl aziridine and carbon dioxide to generate the corresponding oxazolidinone in glass has been studied. Theoretical calculations suggest that this reaction should not proceed at room temperature in the absence of a catalyst. In cases where a reaction was observed, kinetic studies show that the reaction displays a zero-order dependence with respect to aziridine, indicating that free aziridine is not involved in the rate-determining step. An ammonium salt generated in situ acts as a catalyst. The amount of this catalyst is diminutive, which prevented spectroscopic identification, and it is not readily removed from the starting material using chromatography.
- Published
- 2017
39. Covalent, sequence-specific attachment of long DNA molecules to a surface using DNA-templated click chemistry
- Author
-
Blessing Huynh Cao, Tao Ye, Jason E. Hein, and Gary R. Abel
- Subjects
Base pair ,Surface Properties ,Nanotechnology ,Sequence (biology) ,Microscopy, Atomic Force ,Catalysis ,chemistry.chemical_compound ,Microscopy ,Materials Chemistry ,Molecule ,Gene ,Base Pairing ,Quantitative Biology::Biomolecules ,Chemistry ,Organic Chemistry ,Metals and Alloys ,technology, industry, and agriculture ,Atomic Force ,General Chemistry ,DNA ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,Covalent bond ,Chemical Sciences ,Ceramics and Composites ,Click chemistry ,Biophysics ,Click Chemistry ,Copper - Abstract
We present a novel method that covalently and sequence-specifically attaches long DNA molecules to a surface that is compatible with high-resolution atomic force microscopy (AFM) imaging. Surfaces prepared with this approach are ideally suited for performing biophysical experiments on single DNA molecules. This journal is © the Partner Organisations 2014.
- Published
- 2014
40. Oxidative esterification of aldehydes using mesoionic 1,2,3-triazolyl carbene organocatalysts
- Author
-
Matthew T. Berry, Jason E. Hein, and Disnay Castrejon
- Subjects
chemistry.chemical_compound ,chemistry ,Organic Chemistry ,Mesoionic ,Organic chemistry ,Reactivity (chemistry) ,Oxidative phosphorylation ,Physical and Theoretical Chemistry ,Inverse correlation ,Biochemistry ,Carbene ,Catalysis ,Adduct - Abstract
The synthesis and catalytic activity of a new class of 1,2,3-triazolyl N-heterocyclic carbene organocatalysts is described. These new catalysts chemoselectively facilitate the oxidative esterification of aldehydes. NMR acidity studies show an inverse correlation between triazolium acidity and reactivity. Kinetic studies show that the resting state of the catalyst involves a NHC–aldehyde adduct. A catalytically active intermediate was synthesized and characterized by X-ray diffraction as the initial carbene–aldehyde adduct.
- Published
- 2014
41. Pasteur's tweezers revisited: on the mechanism of attrition-enhanced deracemization and resolution of chiral conglomerate solids
- Author
-
Jason E. Hein, Blessing Huynh Cao, Richard M. Kellogg, Cristobal Viedma, and Donna G. Blackmond
- Subjects
Chemistry ,Crystal growth ,General Chemistry ,Biochemistry ,Catalysis ,Chiral resolution ,Crystal ,Crystallography ,Colloid and Surface Chemistry ,Chemical physics ,Tweezers ,Molecule ,Homochirality ,Solubility ,Dissolution - Abstract
Insights into the mechanism of attrition-enhanced deracemization and resolution of solid enantiomorphic chiral compounds are obtained by crystal size and solubility measurements and by isotopic labeling experiments. Together these results help to deconvolute the various chemical and physical rate processes contributing to the phenomenon. Crystal size measurements highlight a distinct correlation between the stochastic, transient growth of crystals and the emergence of a single solid enantiomorph under attrition conditions. The rapid mass transfer of molecules between the solution and solid phases under attrition is demonstrated, and the concept of a crystal-size-induced solubility driving force is exploited to overcome the stochastic nature of the crystal growth and dissolution processes. Extension to non-racemizing conditions provides a novel methodology for chiral resolution. Implications both for practical chiral separations and for the origin of biological homochirality are discussed.
- Published
- 2012
42. Halogen exchange (Halex) reaction of 5-iodo-1,2,3-triazoles: synthesis and applications of 5-fluorotriazoles
- Author
-
Valery V. Fokin, Brady T. Worrell, and Jason E. Hein
- Subjects
Medical diagnostic ,Hydrocarbons, Fluorinated ,Hydrocarbons, Halogenated ,chemistry.chemical_element ,General Medicine ,General Chemistry ,Pet imaging ,Triazoles ,Combinatorial chemistry ,Catalysis ,Cycloaddition ,chemistry ,Halogen ,Click chemistry ,Fluorine ,Organic chemistry ,Molecule - Abstract
Fluorinated molecules are omnipresent in pharmaceuticals and agrochemicals, materials, and as imaging agents for positron emission tomography (PET) scanning. PET imaging has become a widely used technique in medical diagnostics in recent years. This method requires the use of a fluorinecontaining agent enriched with the F nucleus. This fluorine isotope has a notoriously short half-life of 109 minutes, thus imposing strict requirements for the speed and operational simplicity of reactions used for its introduction into imaging probes. Considerations of cost and practicality demand that the fluorine is derived from simple fluoride salts (such as KF and NaF). While methods for the late-stage introduction of fluorine into complex molecules have been reported, a new robust process would be a useful addition to the developing field of medical imaging, especially in light of the growing use of the CuAAC (see below). The copper(I)-catalyzed azide–alkyne cycloaddition reaction (CuAAC; Scheme 1a) has emerged as a powerful method for the creation of covalent links between diverse
- Published
- 2012
43. ChemInform Abstract: Synthesis of 7-Aza-5-deazapurine Analogues via Copper(I)-Catalyzed Hydroamination of Alkynes and 1-Iodoalkynes
- Author
-
Jason E. Hein, Larissa B. Krasnova, and Valery V. Fokin
- Subjects
Chemistry ,chemistry.chemical_element ,General Medicine ,Hydroamination ,Combinatorial chemistry ,Copper ,Catalysis - Abstract
Treatment of triazines of type (I) with catalytic amounts of Cu(I) salts allows new access to 7-aza-5-deazapurine derivatives.
- Published
- 2011
44. Copper-catalyzed azide-alkyne cycloaddition (CuAAC) and beyond: new reactivity of copper(I) acetylides
- Author
-
Valery V. Fokin and Jason E. Hein
- Subjects
chemistry.chemical_classification ,Azides ,Bioconjugation ,Alkyne ,chemistry.chemical_element ,General Chemistry ,Combinatorial chemistry ,Copper ,Cycloaddition ,Catalysis ,Article ,chemistry.chemical_compound ,chemistry ,Catalytic cycle ,Cyclization ,Alkynes ,Organic chemistry ,Organic synthesis ,Reactivity (chemistry) ,Azide ,Sulfones ,Iodine - Abstract
Copper-catalyzed azide–alkyne cycloaddition (CuAAC) is a widely utilized, reliable, and straightforward way for making covalent connections between building blocks containing various functional groups. It has been used in organic synthesis, medicinal chemistry, surface and polymer chemistry, and bioconjugation applications. Despite the apparent simplicity of the reaction, its mechanism involves multiple reversible steps involving coordination complexes of copper(I) acetylides of varying nuclearity. Understanding and controlling these equilibria is of paramount importance for channeling the reaction into the productive catalytic cycle. This tutorial review examines the history of the development of the CuAAC reaction, its key mechanistic aspects, and highlights the features that make it useful to practitioners in different fields of chemical science.
- Published
- 2010
45. ChemInform Abstract: Copper(I)-Catalyzed Cycloaddition of Organic Azides and 1-Iodoalkynes
- Author
-
Jason E. Hein, Valery V. Fokin, Jonathan C. Tripp, K. Barry Sharpless, and Larissa B. Krasnova
- Subjects
chemistry ,Triazole derivatives ,Organic chemistry ,chemistry.chemical_element ,General Medicine ,Copper ,Cycloaddition ,Catalysis - Published
- 2010
46. REGIOSELECTIVE SYNTHESIS OF EITHER 1H- OR 2H-1,2,3- TRIAZOLES VIA MICHAEL ADDITION TO α,ß-UNSATURATED KETONES
- Author
-
K. Barry Sharpless, Sen Wai Kwok, Jason E. Hein, and Valery V. Fokin
- Subjects
Pharmacology ,chemistry.chemical_classification ,Ketone ,Base (chemistry) ,Chemistry ,Organic Chemistry ,Regioselectivity ,Article ,Analytical Chemistry ,Catalysis ,Structural isomer ,Michael reaction ,Click chemistry ,Organic chemistry - Abstract
The Michael reaction of NH-1,2,3-triazole (1) with α,β-unsaturated ketones was studied. 1H-1,2,3-triazolyl-ketones were selectively generated when 1 was combined neat with a variety of enones. The use of aprotic solvents with catalytic base gave the corresponding 2H-regioisomers. Together, these two protocols provide direct access to either the N1- or N2-substituted 1,3-triazolyl ketone regioisomers.
- Published
- 2008
47. Enamine Carboxylates as Stereodetermining Intermediates in Prolinate Catalysis.
- Author
-
Jason E. Hein, Jordi Burés, Yu-hong Lam, Matthew Hughes, K. N. Houk, Alan Armstrong, and Donna G. Blackmond
- Subjects
- *
ENAMINES , *CARBOXYLATION , *CATALYSIS , *AMINATION , *ALDEHYDES , *SALTS - Abstract
Experimental and computational studies probing the nature of intermediates in the α-amination of aldehydes catalyzed by prolinate salts support an enamine carboxylate intermediate in the stereodetermining step. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
48. Kinetic Profiling of Prolinate-Catalyzed α-Amination of Aldehydes.
- Author
-
Jason E. Hein, Alan Armstrong, and Donna G. Blackmond
- Subjects
- *
CHEMICAL kinetics , *PROLINE , *CATALYSIS , *AMINATION , *ALDEHYDES , *CHEMICAL reactions - Abstract
Deconvolution of the role of off-cycle species from the desired catalytic cycle leads to an optimized protocol for the prolinate-catalyzed amination of aldehydes. The scope of complex reaction networks will be greatly broadened by understanding ancillary rate processes that influence the productive catalytic pathway. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.