77 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
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
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
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
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
Multiple perspectives on multiple selves: investigating clinicians' knowledge, beliefs, and experiences related to dissociative identity disorder
No full textDissociative identity disorder (DID) is a complex, posttraumatic developmental disorder that has received varying research attention in the last 30 years (Brand & Loewenstein, 2010). Despite increased awareness and understanding of DID, patients with this disorder spend an average of nearly seven years in the mental health system before receiving an accurate diagnosis (Putnam et al., 1986). Delayed and incorrect diagnosis is associated with costly, ineffective, and/or inappropriate treatments (Leonard & Tiller, 2016). Clinician factors believed to contribute to delayed DID diagnosis include skepticism or disbelief as well as lack of training and knowledge (Brand et al., 2016). While significant research on this topic was conducted 15 to 30 years ago, few studies have assessed the current stance of practitioners, and even less research has explored factors underlying variation in their beliefs, knowledge, training, and experience. Accordingly, this study investigated clinicians’ knowledge, beliefs, training, and clinical experiences related to DID through a mixed-methods design. Eighty-three U.S. mental health professionals recruited from eight professional organizations completed an online survey that included demographic questions as well as a DID questionnaire. Descriptive analyses indicated that participants demonstrated varying levels of disbelief, knowledge, training, and experience related to DID. While most participants believed DID is a valid disorder (73.5%), only 38.4% were likely or extremely likely to believe a new patient who reports having the diagnosis. Thematic analyses (Braun & Clarke, 2006) revealed that, though stigma persists, most participants believed in the trauma model of DID. Findings suggest that many clinicians, especially those specializing in trauma, dissociative disorders, and/or psychodynamic therapy, find it challenging yet rewarding to work with DID, believe awareness about DID is an important area of research, and want to increase their awareness and knowledge about DID. Implications for DID assessment and treatment, as well as for future research, clinician training, and supervision are explored.Psy.D.Includes bibliographical referencesby Jenna N. Blewi
College students' health-seeking behavior plans in response to imagined abdominal pain
No full textPatient delay has been shown to be an important antecedent of mortality and medical complications. To design interventions to decrease delay it is imperative to understand the complex decisions and actions involved in the multifaceted process of health-care-seeking behavior. We used a simulation, i.e., asking participants how long they would wait to take specific actions if experiencing moderate abdominal pain, as an initial step to examine the sequences of responding and to gain insight into the processes underlying these decisions. Anticipated latency to specific actions, e.g., using a home remedy, communicating with family or friends, and seeking professional care, was investigated. We explored gender and health anxiety relations with anticipated action latencies as well. In addition to examining delay for oneself, we examined the advice the respondents would give to a friend facing an identical scenario. Participants were undergraduates from Rutgers University (n=145) who completed an online questionnaire including abdominal pain health scenarios. Overall, latencies were shorter to take OTC medications or talk to someone about symptoms than to seeking a health care professional and the most common behaviors reported were resting or waiting (31.1%), followed by taking OTC medication (22.7%), seeing a healthcare professional (18.2%), and taking a home remedy (11.4%). Consistent with hypotheses, higher health anxiety scores were associated with shorter anticipated latencies to take OTC medications or home remedies (B=-.07, SE=.032, Wald Χ2 (1)=4.81, p=.028). Additionally men anticipated longer latencies to taking any action than did women (B=.66, SE=.32, Wald X2 (1)=4.08, p=.043), as hypothesized. Comparing self-described action with advice to a friend, showed that respondents were more likely to advise friends to take OTC medications (X2 (1)=3.58, p=.059), but were less likely to advise friends to seek professional care, relative to their self-care plans (X2 (1)=12.42, p=.000). Implications of these findings are discussed.M.S.Includes bibliographical referencesby Jenna Herol
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
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