Organic Chemistry

"Organic chemistry is the study of the structure, properties, composition, reactions, and preparation of carbon-containing compounds ..."

American Chemical Society

Organic sessions have been scheduled for Monday Late Afternoon, Tuesday Afternoon, Wednesday Morning, and Wednesday Afternoon.

If you find any errors in our listing please let us know at chemistrybuffalogss@gmail.com

Monday Late Afternoon

Session 3A - Room NSC 222 - Moderator: Zack Gregg

3:00 p.m. - 3:20 p.m.

Towards the synthesis of C-1 homologues of narciclasine

Korey Bedard, Tomas Hudlicky

Brock University

The Amaryllidaceae alkaloids are a class of compounds found in plants closely related to the common daffodil. Natural products of this class (most notably pancratistatin and narciclasine) have been found to possess impressive biological activity profiles, especially anti-tumor activity. Previous efforts to derivatize pancratistatin have shown that modification at the C-1 position leads to sustained or improved anti-cancer activity (single digit nM in vitro IC50 values). The current project involves the total synthesis of C-1 hydroxy- or aminomethyl homologues of narciclasine. The fully functionalized backbone of the target class has been assembled in a convergent manner starting from a chemoenzymatically-derived diene diol and o-vanillin. The key steps thus far include enzymatic cis-dihydroxylation, nitroso Diels-Alder cycloaddition, Stille coupling, and acylation of an allylic amine to join two advanced intermediates. Progress towards the synthesis of these narciclasine derivatives will be reported, as well as the projected route to complete their assembly via intramolecular Heck coupling followed by a short sequence of functional group interconversions.

3:20 p.m. - 3:40 p.m.

Copper-(II) Catalyzed Enantioselective Aryl Migration: Synthesis of Bridged Ketals

Ameya Burde, Shuklendu Karyakarte, Sherry Chemler

The State University of New York at Buffalo, Department of Chemistry

Radical migration has been a long studied methodology in organic synthesis. The radical based migration of pi-systems within a molecule allows us to access to novel scaffolds which cannot be accessed by conventional means. Though a large number of methods have been developed in which alkene difunctionalization is achieved with concomitant radical migration, the achievement of such a migration enantioselectively is still proving to be a very big challenge. Presented here is our copper(II)-catalysed alkene difunctionalization reaction which achieves enantioselctive aryl radical migration with the difunctionalization to give the bridged ketal moiety. At present we have a number of substrates which reacted favourably under our optimized conditions to give the ketals with good to excellent yields and generally good enantioselectivity.

3:40 p.m. - 4:00 p.m.

Re-thinking The 2-Electron Paradigm Through C-N Bond Formation

Joseph Parry, Juno Siu, Song Lin

Cornell University

The discovery of reactions mediated by organic radicals continues to provide solutions to challenging synthetic problems in traditional two-electron chemistry. In this context, design and implementation of new catalytic strategies have both expanded the toolbox available for accessing new synthetic targets and transformed the fundamental understanding of reactions involving open-shell pathways. Through careful reaction design and rationale we report the synthesis of a new aminoxyl radical catalyst, CHAMPO, for the electrochemical diazidation of alkenes. Mediated by an anodically generated charge-transfer complex in the form of CHAMPON₃ , radical diazidation was achieved across a diverse array of structurally unique alkenes bearing a breadth of various reactive functionalities without the need for transition metal catalysts, chemical oxidant or acid. Mechanistic data supports a dual role of CHAMPO-N₃ serving as both a single-electron oxidant and a radical transfer agent.

4:00 pm - 4:20 p.m.

Hypervalent Iodine(III) Salts as Initiators of Nazarov Cyclizations

Avery To, Graham Murphy

University of Waterloo, Department of Chemistry

Nazarov cyclizations (NCs), despite appearing simple at first glance, are capable of producing incredibly complex products. These cyclizations are synthetically powerful, with both regio- and stereoselective elements that have been exploited in natural product synthesis (1). A typical NC involves conrotatory 4pi-electrocyclization of a divinyl ketone substrate activated with a Brønsted or Lewis acid to afford a cyclopentenone product. Our aim is to utilize the NC as a tool to develop the synthetic utility and study the Lewis acidity of cyclic diaryliodonium salts. Diaryliodonium salts are hypervalent iodine(III) reagents which contain two aryl rings forming a hypervalent bond around a central iodine. Of the acyclic and cyclic diaryliodonium salt variants which exist, the acyclic variant has proven to be a synthetically useful arylating reagent, while the cyclic variant has found use as a synthetic precursor to polycyclic heteroarenes (2, 3). Despite extensive research in both areas, minimal research has been undertaken to exploit the Lewis acidic potential of diaryliodonium salts (4). This presentation will communicate the initial findings involving cyclic diaryliodonium salt-initiated NCs.

1. Vinogradov, M. G., et al., Org. Biomol. Chem. 2017, 15, 8245.

2. Merritt, E. A.; Olofsson, B., Angew. Chem. Int. Ed. 2009, 48, 9052.

3. Zhu, D. Q., et al., Org. Lett. 2018, 20, 4815.

4. For a [4+2] cycloaddition example see: Heinen, F., et al., Angew. Chem. Int. Ed. 2018, 57, 3830.

4:20 p.m. - 4:40 p.m.

Synthesis of Rhodamine Derivatives for Use in Solar Hydrogen Production

Michael Clark, David F. Watson, Michael R. Detty

The State University of New York at Buffalo, Department of Chemistry

Rhodamines are a highly tailorable class of organic dyes that can be used in a variety of applications. With the ability to absorb light in the visible region of the electromagnetic spectrum, these dyes are excellent photosensitizers for photodynamic therapy, solar hydrogen production, and Raman spectroscopy. In the case of solar hydrogen production, the dye is adsorbed to an electron acceptor such as TiO₂, and is then exposed to light. An electron is excited, and can be transferred to the TiO₂. These electrons can then be transported through an electrochemical cell to ultimately reduce protons to molecular hydrogen. By modifying the several different positions on the dye scaffold, it is possible to adjust the properties of these dyes to optimize its ability to not only absorb photons, but also to donate electrons to be used in the production of molecular hydrogen. Two main structural modifications were focused on in this research: the addition of an alkyne moiety into the core of the dye to facilitate H-aggregation on the TiO₂ surface, and the replacement of one of the external amino groups with a free hydroxyl group to increase the push-pull of electron density. Both of these effects have been shown to increase electron injection into the TiO₂, and therefor theoretically increase efficiency. Described herein is a series of dyes that have been synthesized to optimize the production of molecular hydrogen using solar energy.

Tuesday Afternoon

Session 5A - Room NSC 222 - Moderator: Zack Gregg

1:20 p.m. - 1:40 p.m.

Anion Dependent Hydrogen Bonding States: Resulting Fluorescence Implications in a

Proton Sponge Model System

Richard Le Sueur, Matt Guest, Lee Belding, Melanie Pilkington, Travis Dudding

Brock University

Through-space, non-covalent interactions, particularly the hydrogen bond, play an indispensable role in chemical and biochemical processes, such as those regulating the vast network of reactions controlling life. Several model systems have aided in our understanding of the H-bond, among which peri-disubstituted naphthalene-based compounds classified as “proton sponges”^1,2 hold particular historical significance. Our recent development of a cyclopropenium-based proton sponge has expanded the scope of interactions in these systems to include the generation of aromaticity, internal charge-transfer states, and ion-pair interactions.³ Additional properties of this molecule include high fluorescence in solution and solid state while containing an intermolecular hydrogen—counterion interaction, as opposed to a short, strong intramolecular H—bond to the peri-NMe₂ group typical of proton sponges.

Herein, in building upon the cyclopropenium based proton sponge platform, the counterion dependent nature of hydrogen bonding in this system has been studied by varying the anion component (refer to graphic). X-ray crystallography indicated that by changing the anion, we were able to switch between inter-molecular hydrogen bonding and intra-molecular hydrogen bonding. This switching between hydrogen bond states influenced the structural, electronic, and photophysical properties of this system leading to significant differences in quantum yield, while leaving the absorption and emission unaffected. Computations revealed this trend in quantum yield was attributed to diminished electron donation from the NMe₂ group into the naphthalene ring system, as a consequence of intramolecular hydrogen bond formation. Furthermore, the relatively large changes in electronic and geometric properties arising from these varying hydrogen bond states has obvious potential in terms of developing new molecular switches.

1. S. O. Shan, S. Loh, D. Herschlag, Science, 1996, 272, 97-101.

2. R. W. Alder, P. S. Bowman, W. R. S. Steele, D. R. Winterman, Chem. Commun. 1968, 452, 723-724.

3. L. Belding, M. Guest, R. Le Sueur, T. Dudding, J. Org. Chem. 2018, 83, 6489-6497.

1:40 p.m. - 2:00 p.m.

α-Ketol Rearrangement: Non- Enzymatic Approach to Elucidating MtDXR Mechanism

Yaroslaw Myshchuk, Andrew S. Murkin

The State University of New York at Buffalo, Department of Chemistry

Kinetic isotope effects (KIEs) are used as a powerful tool in the investigation of chemical reactions, providing mechanistic information as well as aiding in the elucidation of the geometry at the transition state (TS). Their application in probing enzyme-catalyzed reactions can reveal details that steer the design of potent inhibitors that may serve as antimicrobial agents. The non-mevalonate pathway, which is absent in mammals but present in Mycobacterium tuberculosis, the causative agent of tuberculosis, possesses the drug target 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXR). The reaction catalyzed by DXR consists of two successive chemical steps: isomerization and reduction. The two most favored mechanisms for the isomerization step include (1) an α-ketol rearrangement and (2) a stepwise retroaldol/aldol process. ²H, ¹³C, and ¹⁸O KIEs measured previously in our lab are insufficient in distinguishing between the two mechanisms unambiguously. To assist in interpreting the enzymatic reaction, the current study aims to characterize the aldol–ketol rearrangement of an α-hydroxy aldehyde that must proceed by a concerted mechanism (i.e., mechanism 1). Inter- and intramolecular ¹³C KIEs for this reaction were measured by ¹³C NMR spectroscopy at natural isotope abundance. Comparison of theoretical KIEs obtained from density functional theory to the experimental values will establish a model of the TS of this reaction, providing new insight into DXR-catalyzed reaction.

2:00 p.m. - 2:20 p.m.

Derivatization of natural narciclasine

Ringaile Lapinskaite, Tomas Hudlicky

Brock University

Narciclasine and pancratistatin, natural products from amaryllidaceae plants, and their synthetic derivatives have showed good activity and interesting selectivity towards several cancer cell lines. Challenging synthesis of these molecules is the bottle-neck for further research on their activity and development of these compounds as potential drugs. However, natural compounds can be used for the derivatization. In the Hudlicky’s group, amaryllidaceae alkaloids have been a synthetic targets for a number of years. Now we are using natural narciclasine as a starting material and looking into ways to convert it into various narciclasine and pancratistatin derivatives for further biological testing.

2:20 pm - 2:40 p.m.

Exploring Inverse Electron Demand Diels-Alder Substrates in an Activatable Cycloaddition

Wei-Siang Kao, Pratik Kumar, Ting Jiang, Wei Huang, Andrea Mayer, Frank M. Camarda, Scott T. Laughlin

Stony Brook University

Bioorthogonal chemistry has been used in fields ranging from cell imaging in chemical biology to drug release in pharmacology and protein targeting in clinical research. Generally, efforts for improving bioorthogonal reactions have focused on enhancing reaction rates. However, few efforts to improve bioorthogonal reactions have explored strategies for triggering reactivity in a spatiotemporal manner using an external stimulus like light or an enzyme. We propose that the cyclopropene can be caged by photolabile or enzyme labile protecting group to cage the reaction between cyclopropene and inverse electron demand Diels–Alder (iEDDA) substrates. These iEDDA substrates are designed to react with uncaged cyclopropene after the bulky group is removed by enzyme or light.

Here, we focus on two directions related to controlling bioorthogonal reactivity: First, we have synthesized a series of cyclopropenes with substituants that we hypothesized would accelerate the reactivity between the cyclopropene and its iEDDA substrates, most commonly, s-tetrazines. Second, we sought to identify improved iEDDA reaction partners for our reactivity caged cyclopropenes. To accomplish this, we screened several reported iEDDA substrates and examined the stability and reactivity of each substrate with either caged or uncaged cyclopropenes. Ultimately, we will investigate each substrate’s reaction rate with uncaged cyclopropene and further explore their utility for protein labeling and cell imaging.

2:40 p.m. - 3:00 p.m.

Synthesis and Evaluation of Novel Photosensitizers for Photodynamic Anti-Pancreatic Cancer Therapy

Mostafa Abdelaziz, David A. Modarel

University of Akron, Department of Chemistry

Photodynamic therapy (PDT) has attracted significant attention as an alternative approach to traditional cancer therapies such as radiotherapy, chemotherapy, and surgery. Porphyrin-based photosensitizers have been widely used in PDT. Porphyrins have a significant absorption in the visible region (400-700 nm), little dark toxicity, and long-lived triplet states. Although porphyrins are known to accumulate in tumor cells in high concentrations, aggregation resulting from π-π stacking leads to a reduction in fluorescence and 1O2 quantum yields. In addition, porphyrins are highly hydrophobic, so, they cannot be administered intravenously. The aim of the current research is to synthesize novel porphyrin-curcumin conjugates for use as effective photosensitizers in the photodynamic treatment of pancreatic ductal adenocarcinoma (PDAC). Curcumin has shown a significant anti-cancer activity against pancreatic cancer but has low bioavailability due to poor absorption from blood and fast metabolism. Porphyrin-curcumin conjugates have several advantages over porphyrins: (1) improvement of stability, bioavailability, and tumor site accumulation, (2) presence of two perpendicular chromophores that minimize aggregation and improve fluorescence and 1O2 quantum yields, (3) presence of two chromophores that may maximize triplet-triplet energy transfer with 3O2 and improve 1O2 generation efficiency The synthesis of two porphyrin-curcumin conjugates will be discussed in this talk.

3:00 p.m. - 3:20 p.m.

Syntheses and Analysis of Silica-Supported Isocyanide-Based Metal Scavengers

Elise Glickert, Zackary Gregg, Ruoshui Xu, Steven T. Diver

The State University of New York at Buffalo, Department of Chemistry

Transition metal catalysis is utilized in a variety of synthetic reactions, such as cross coupling and olefin metathesis. When the reactions are performed in the production of pharmaceuticals, low levels of the metal catalyst are required due to toxicity concerns. Traditionally, thiol and amine based scavengers have been used to remove the transition metals from solution. However, these scavengers require large equivalents and are limited in their binding ability to completely remove the metal complexes from solution. A library of isocyanide-based metal scavengers has been developed, which require significantly less equivalents and can take advantage of strong d-π* binding to completely remove the metal. These novel isocyanide scavengers are synthesized through a thiol ene click reaction, and they are assayed using UV-visible spectroscopy.

Wednesday Morning

Session 6 - Room NSC 222 - Moderator: Lauren Rosch

9:30 a.m. - 9:50 a.m.

Mild Chemoselective Isomerization of Conjugated Dienes Using HAT Chemistry

Kyle Delgado, Steven T. Diver

The State University of New York at Buffalo, Department of Chemistry

Conjugated dienes are present in many natural products ranging from pharmaceuticals to pesticides. Our lab has developed a one-pot ene-yne/dienyl isomerization reaction for the synthesis of highly substituted dienes via the Grubbs 2nd generation ruthenium catalyst. Further studies in our lab have showed the application of cobalt (III) complexes, provides us with a more efficient and milder diene isomerization reaction than the work previously mentioned. A wide range of E/Z-dienes underwent a 1, 5 hydride shift in a stereoconvergent manner, affording isomerized dienes in high isolated yields with modest geometric-isomer ratios, as high as 10: 1 E/Z. Mechanistic studies suggest a radical mechanism is responsible for the double bond migration described as a transition metal assisted hydrogen atom transfer (HAT) reaction. High chemoselectivity for the isomerization of 1, 3 dienes in the presence of terminal olefins was also seen. Application towards natural products and future directions of the research will also be discussed.

9:50 a.m. - 10:10 a.m.

Oxidative, Iodoarene‐Catalyzed Intramolecular Alkene Arylation in the Synthesis of

Polycyclic Aromatic Hydrocarbons

Liam Britt, Graham Murphy, Zhensheng Zhao

University of Waterloo, Department of Chemistry

Polyaromatic hydrcarbons (PAHs) are important structural motifs and in recent decades have found great utility in the future of electronics as organic semi-conducting materials in the form of acenes and phenacences. Reliable methods of synthesizing PAHs, especially of the phenacene type, are limited. Modern techniques employ expensive transition metal catalysts, but a less explored route is that of hypervalent iodine. Hypervalent iodine reagents hold potential in mediating reactions that normally employ late transition metals. In recent studies, a reaction was developed that could intramolecularly couple ortho-biphenylstyrenes in the synthesis of phenanthrenes, using only a catalytic amount of iodotoluene and m-CPBA as an oxidant, generating the hypervalent iodine species in situ.¹ This presentation will highlight the work done to explore the novel mechanism of this reaction, further understanding of the short-lived intermediates may provide clues in producing new reactivity.

1. Z. Zhao, L. H. Britt, G. K. Murphy, Chem. Eur. J. 2018, 24, 17002.

10:10 a.m. - 10:30 a.m.

Size-selective Olefin Metathesis using Macrocyclic N-Heterocyclic Carbene Ligated Ru Catalysts

Yutong Zhang, Steven T. Diver

The State University of New York at Buffalo, Department of Chemistry

Olefin metathesis is one of the most effective reactions to construct carbon-carbon double bonds. It has been widely employed in the synthesis of many complex molecules. Current selectivity principle in cross alkene metathesis refers to Grubbs’ model, where olefins are categorized into different types based on their local environments, electronic or steric. However, selective cross metathesis of alkenes within the same type remains challenging. We have designed and synthesized two novel macrocyclic NHC ligated Ru catalysts that differentiate electronically similar olefins (Type I) based on their steric bulkiness remote from the reaction center. In this talk, the synthesis and performance tests of our catalysts will be discussed, as well as their applications in size-selective enyne metathesis and cross alkene metathesis.

10:30 a.m. - 10:50 a.m.

Cyclopropenium Enhanced Thiourea Catalysis

Ivor Smajlagic, Rocio Durán, Melanie Pilkington, and Travis Dudding

Brock University

An integral part of modern organocatalysis is the development and application of thiourea catalysts. In contributing to this area of catalysis, we have developed a thiourea-cyclopropenium organocatalyst with both cationic H-bond donor and electrostatic character. In this talk, I will present our recent use of this thiourea organocatalyst in pyranylation reactions employing phenols, primary, secondary and tertiary alcohols under operationally simple and mild reaction conditions for a broad substrate scope. Furthermore, the addition of benzoic acid as a co-catalyst facilitating cooperative Brønsted acid catalysis was found to be valuable for reactions involving phenols and higher substituted alcohols. This presentation will also highlight computational, kinetic and NMR spectroscopic studies that were explored during the course of our research, which collectively provide insight into the mechanism of these pyranylations.

Wednesday Afternoon

Session 7B - Room NSC 218 - Moderator: Zack Gregg

1:20 p.m. - 1:40 p.m.

Transfer Hydrogenations of Ketones and Chalcones by well-defined Mn(I)-β-Aminophosphine Complexes

Vipulan Vigneswaran, David C. Lacy

The State University of New York at Buffalo, Department of Chemistry

Transfer hydrogenations (THs) add hydrogen across an unsaturated bond from a non-gaseous hydrogen source thereby eliminating the need for high-pressure H₂ or expensive and otherwise difficult reaction setups. While typically THs have been achieved with noble metal catalysts, recent reports have shown that similar transformations can be achieved efficiently with base metal catalysts, such as manganese. Herein, we report the synthesis and catalysis of a series of Mn(I)-β-aminophosphine complexes that can readily hydrogenate ketones using 2-propanol as a hydrogen source with catalyst loadings as low 0.5 mol%. The catalyst is tolerant of common functional groups and proceeds at mild conditions to near quantitative conversions. Moreover, the catalyst shows chemoselectivity in the reduction of chalcones to saturated ketones.

1:40 p.m. - 2:00 p.m.

Fluorescence of Cyclopropenium Ion Derivatives

Matt Guest, Richard Le Sueur, Lee Belding, Travis Dudding

Brock University

Small organic fluorescent molecules find applications as light-emitting diodes, chemical sensors, biological probes, cellular imaging agents, and light harvesting systems. Currently, several classes of small organic fluorophores are commercially available. These fluorophores and their derivatives, however, often do not meet the desired photo-physical properties. In adding to this area of research, we recently developed a cyclopropenium substituted aminonaphthalene derivative coined the “Janus sponge” that fluoresced in both the solid and solution states while maintaining a high quantum yield and large stokes shift. In view of these fascinating properties we recently synthesized a series of novel cyclopropenium-substituted amino compounds and investigated their photophysical properties. By systematic structural modifications of these compounds we were able to make 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. Associated with this structural reorganization was an inward gearing of the cyclopropenium ring and twisting of the peri-NMe₂ group into co-planarity with the naphthalene ring systems. The findings of these investigations, which provide valuable insight into the photophysical properties of these compounds, will be presented.

2:00 p.m. - 2:20 p.m.

Dynamic Kinetic Resolution of Alkenyl Cyanohydrins: Stereoselective Synthesis of E-Tetrasubstituted Olefins

Jadab Majhi, Ben W. H. Turnbull, Ho Ryu, Jiyong Park, Mu-Hyun Baik, P. Andrew Evans

Queen's University, Department of Chemistry

The development of novel methods for the construction of stereochemically pure compounds is an active area of investigation in modern synthetic organic chemistry. In this regard, the synthesis of geometrically defined tetrasubstituted olefins is a highly challenging endeavour. Nevertheless, this ubiquitous functional group is an important motif in pharmaceutical agents and materials research, where the geometry of the alkene often plays a critical role in the activity and properties of a specific compound. Despite the challenges associated with traditional olefination methods, many modern methods continue to employ the same general technique that involves the de novo installation of the carbon-carbon double bond. This strategy requires stereochemical control of the substituents within the newly formed olefin, a challenge that is often difficult to overcome and thus hampers the synthetic utility of these processes. Herein, we will describe a new approach that can prepare geometrically defined olefins through a novel dynamic kinetic resolution of olefin mixtures with excellent selectivity and broad substrate scope. Moreover, we will outline the mechanistic origin of stereocontrol, which was delineated using DFT calculations.

2:20 pm - 2:40 p.m.

Aromatic oligoamides as Anion Receptors

Ruikai Cao, Robert Rossdeutcher, Xiangxiang Wu, Bing Gong

The State University of New York at Buffalo, Department of Chemistry

In supramolecular chemistry, amide bond has been extensively adopted in molecular recognition partially due to formation of directional hydrogen bonds and strong interactions between amide bonds and cations and anions. We recently developed a novel synthetic protocol for amide bond formation based on the ring-opening of a 2-alkyl-3, 1-benzoxaza-4-one (benzoxazinone) moiety with amines. Benzoxazinone, which was formed from N-acyl 5-nitroanthranilic acid upon treating with acetyl chloride, was fully characterized by 1H-NMR and its crystal structure was determined by X-ray crystallography. The ring opening of benzoxazinone by the nucleophilic attack of amines afforded the desired amide bonds without needing coupling reagents that are typically required for amide bond formation. This ring-opening reaction was systematically studied by treating the 3, 1-benzoxaza-4-one reactant with aliphatic or aromatic amines, which gave from good to nearly quantitative yields of the corresponding amide products. Based on this new amide formation procedure, linear and macrocyclic pentaamides have been prepared. With their NH groups and aromatic CH bonds, these aromatic oligoamides such as pentaamides exhibited strong affinities to anions. Results from this preliminary work could pave the way for synthesizing amide-based linear and macrocyclic anion receptors with variable sidechains, adjustable number H-bond donors, and tunable cavity sizes.