18 research outputs found
Access to inaccessible 5-membered heteroarynes
No full textUniversity of Minnesota Ph.D. dissertation. June 2024. Major: Chemistry. Advisor: Courtney Roberts. 1 computer file (PDF); xxxii, 401 pages.Aryne chemistry is a powerful method for accessing difunctionalized products. Therefore, these intermediates have promising applications in discovery chemistry as they allow making iterative structural changes to targets using a common intermediate which can glean important insights on structure function relationships. Arynes have seen promising utility in the synthesis of heterocycles which are prevalent in the pharmaceutical industry, however, the field has been limited by the scope of heteroarynes which can be accessed using existing methods. Five-membered N- and O-heteroarynes are predicted to be “inaccessible” due to ring strain; yet heteroaryne intermediates would represent a promising common intermediate for installing heterocycles into target compounds. Herein we disclose the first examples of accessing 7-aza-2,3-indolynes and other N-heteroarynes using Ni-complexes. Work is underway to insights into the transmetallation step which is key for aryne formation. Additionally, work is underway to apply these complexes in difunctionalization reactions that would allow for rapid synthesis of heterocyclic compound libraries to be utilized in discovery chemistry.Humke, Jenna. (2024). Access to inaccessible 5-membered heteroarynes. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/278196
Access to inaccessible 5-membered heteroarynes
No full textUniversity of Minnesota Ph.D. dissertation. June 2024. Major: Chemistry. Advisor: Courtney Roberts. 1 computer file (PDF); xxxv, 401 pages.Aryne chemistry is a powerful method for accessing difunctionalized products. Therefore, these intermediates have promising applications in discovery chemistry as they allow making iterative structural changes to targets using a common intermediate which can glean important insights on structure function relationships. Arynes have seen promising utility in the synthesis of heterocycles which are prevalent in the pharmaceutical industry, however, the field has been limited by the scope of heteroarynes which can be accessed using existing methods. Five-membered N- and O-heteroarynes are predicted to be “inaccessible” due to ring strain; yet heteroaryne intermediates would represent a promising common intermediate for installing heterocycles into target compounds. Herein we disclose the first examples of accessing 7-aza-2,3-indolynes and other N-heteroarynes using Ni-complexes. Work is underway to insights into the transmetallation step which is key for aryne formation. Additionally, work is underway to apply these complexes in difunctionalization reactions that would allow for rapid synthesis of heterocyclic compound libraries to be utilized in discovery chemistry.Humke, Jenna. (2024). Access to inaccessible 5-membered heteroarynes. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/277366
Development of transition-metal catalyzed cross-coupling reactions involving amide electrophiles with heterocyclic nucleophiles
No full textThere are many technological challenges that face society today, one of which is the ability to develop precise control over chemical reactions. Many of the high-value molecules used as pharmaceuticals, agrochemicals, and important materials must be made using synthetic techniques. These industries require efficient and cost-effective methods to synthesize their products. Cross-coupling reactions are one such method that have become heavily used. Although amides are an extremely prevalent and important functional group, there has been little investigation into performing these cross-coupling reactions with amide as coupling partners. Thus, it remains a challenge in the field of organic synthesis. We have demonstrated reactivity for cross-coupling reactions with amide electrophiles and heterocycle nucleophiles in order to generate ketone products containing heterocyclic units. By targeting these medicinally-important heterocyclic compounds, this research will be useful in making important target compounds more accessible while also developing a new class of electrophiles to use in cross-coupling reactions.</p
Análise descritiva das duas traduções brasileiras do conto The invisible man de G. K. Chesterton
No full textDissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Comunicação e Expressão. Programa de Pós-Graduação em Estudos da TraduçãoO presente estudo almeja identificar as normas dominantes por trás das estratégias tradutórias em duas traduções brasileiras do conto policial The Invisible Man do autor inglês G.K.Chesterton, sendo uma edição de 1997 e a segunda de 2006; e consequentemente verificar o tipo e a extensão de equivalência entre as traduções. As traduções foram analisadas, comparadas entre si e com o texto em inglês a partir de ocorrências tabuladas confirmando as hipóteses levantadas nos três níveis de análise: preliminar, macroestrutural e microestrutural. O referencial teórico sustenta-se nos norteadores dos Estudos Descritivos da Tradução, em especial no conceito de normas desenvolvido por Gideon Toury (1995). Como metodologia para análise do objeto de estudo, utilizou-se o método descritivo, para analisar traduções, sugerido por José Lambert & Van Gorp (1985). O resultado da análise apontou tanto as normas tradutórias e editoriais quanto o tipo e a extensão de equivalência das edições traduzidas.The present study aims to identify prevailing norms behind the translational strategies of two Brazilian translations (1997 and 2006) of the detective story The Invisible Man by the British author G. K. Chesterton. The type and extent of equivalence will be analyzed by comparing the translations with each other and with the English text by means of occurrences arranged side by side in tables. The hypothesis was explored in three stages: preliminary, macro- and micro-levels. Descriptive Translation Studies serves as the theoretical basis for the study, especially the concept of norms introduced by Gideon Toury (1995). Lambert & Van Gorp.s (1985) descriptive approach was used as methodology for the object of analysis. The results indicated the influence of both translational and publishing norms as well as the type and extent of equivalence in the translations
Nickel-Bound 5-Membered N-Heterocyclic Arynes: Access to Previously “Inaccessible” 7-Aza-2,3-indolynes
No full textN-Heteroaromatics are key elements of life-saving pharmaceuticals, potent agrochemicals, and vital materials. N-Heteroarynes provide a scaffold to build these essential molecules but are underutilized because 5-membered N-heteroarynes have been computed to be inaccessible to synthetic chemists due to the strain of a triple bond in a 5-membered ring. Using principles of metal-ligand interactions that are foundational to organometallic chemistry, herein is reported the first access to a previously inaccessible 5-membered N-heteroaryne. A series of 1,2-bis(dicyclohexylphosphino)ethane nickel 7-azaindol-2,3-yne complexes are synthesized and characterized crystallographically and spectroscopically. In order to showcase the synthetic potential, a difunctionalization of N-methyl-7-azaindol-2,3-yne to form two new C-C bonds is performed. By overcoming a 120-year old limitation, we have unlocked a new synthon for the synthesis of difunctionalized N-heteroaromatics for transformative synthesis
N‑Heterocyclic Carbene Ligand-Controlled Chemodivergent Suzuki–Miyaura Cross Coupling
No full textTwo N-heterocyclic carbene ligands
provide orthogonal chemoselectivity
during the Pd-catalyzed Suzuki–Miyaura (SM) cross-coupling
of chloroaryl triflates. The use of SIPr [SIPr = 1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene]
leads to selective cross-coupling at chloride, while the use of SIMes
[SIMes = 1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene]
provides selective coupling at triflate. With most chloroaryl triflates
and arylboronic acids, ligand-controlled selectivity is high (≥10:1).
The scope of this methodology is significantly more general than previously
reported methods for selective SM coupling of chloroaryl triflates
using phosphine ligands. Density functional theory studies suggest
that palladium’s ligation state during oxidative addition is
different with SIMes compared to SIPr
Correction to N‑Heterocyclic Carbene Ligand-Controlled Chemodivergent Suzuki–Miyaura Cross Coupling
No full textCorrection to N‑Heterocyclic
Carbene Ligand-Controlled
Chemodivergent Suzuki–Miyaura Cross Couplin
N‑Heterocyclic Carbene Ligand-Controlled Chemodivergent Suzuki–Miyaura Cross Coupling
No full textTwo N-heterocyclic carbene ligands
provide orthogonal chemoselectivity
during the Pd-catalyzed Suzuki–Miyaura (SM) cross-coupling
of chloroaryl triflates. The use of SIPr [SIPr = 1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene]
leads to selective cross-coupling at chloride, while the use of SIMes
[SIMes = 1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene]
provides selective coupling at triflate. With most chloroaryl triflates
and arylboronic acids, ligand-controlled selectivity is high (≥10:1).
The scope of this methodology is significantly more general than previously
reported methods for selective SM coupling of chloroaryl triflates
using phosphine ligands. Density functional theory studies suggest
that palladium’s ligation state during oxidative addition is
different with SIMes compared to SIPr
Expanding Access to Previously Inaccessible 5-Membered N-Heteroarynes
No full textWe previously reported the synthesis of an inaccessible 7-aza-2,3-indolyne through stabilizing interactions with nickel. This was achieved via intramolecular Suzuki coupling (i.e. oxidative addition and transmetallation) with ortho-borylaryl bromide derivatives of 7-azaindole. Herein, we sought to use this same strategy to expand the scope of previously inaccessible five-membered heteroarynes. Five new classes of heteroarynes derived from indole, pyrrolopyrimidine, and the remaining isomers of azaindole were accessed. Transmetallation studies show that aryne formation depends on the electronics of the heteroarene. A borate complex of 4-azaindole was isolated and characterized via NMR spectroscopy and crystallographically. This hetero-cycle could be promoted to undergo transmetallation through the installation of an electron-donating substituent. Each class of heterocycles require a unique synthetic strategy. Thus, to demonstrate the utility of heteroarynes as a general synthon, a one-pot difunctionalization was achieved across these classes of heterocycles using the newly accessible heteroaryne complexes
