133 research outputs found
Synthesis and late-stage functionalization of complex molecules through C-H fluorination and nucleophilic aromatic substitution.
We report the late-stage functionalization of multisubstituted pyridines and diazines at the position α to nitrogen. By this process, a series of functional groups and substituents bound to the ring through nitrogen, oxygen, sulfur, or carbon are installed. This functionalization is accomplished by a combination of fluorination and nucleophilic aromatic substitution of the installed fluoride. A diverse array of functionalities can be installed because of the mild reaction conditions revealed for nucleophilic aromatic substitutions (S(N)Ar) of the 2-fluoroheteroarenes. An evaluation of the rates for substitution versus the rates for competitive processes provides a framework for planning this functionalization sequence. This process is illustrated by the modification of a series of medicinally important compounds, as well as the increase in efficiency of synthesis of several existing pharmaceuticals
Seeking and sharing: why the pulmonaryn fibrosis community engages the web 2.0 environment
Background
Pulmonary fibrosis (PF) is a rare, progressive disease that affects patients and their loved ones on many levels. We sought to better understand the needs and interests of PF patients and their loved ones (collectively “reader-participants”) by systematically analyzing their engagement with the World Wide Web (the current version referred to as Web 2.0).
Methods
Data were collected from three PF-focused, interactive websites hosted by physician-investigators with expertise in PF. All data generated by reader-participants for approximately 10 months were downloaded and then analyzed using qualitative content analysis methods.
Results
PF experts posted 38 blog entries and reader-participants posted 40 forum entries. Blogs received 363 responses, and forum entries received 108 responses from reader-participants. Reader-participants primarily used the three websites to seek information from or offer a contribution to the PF community. Information was sought about PF symptoms, diagnosis, prognosis, treatments, research, pathophysiology, and disease origin; reader-participants also made requests for new posts and pleas for research and sought clarification on existing content. Contributions included personal narratives about experiences with PF, descriptions of activities or behaviors found to be helpful with PF symptoms, resources or information about PF, and supportive comments to other PF sufferers.
Conclusions
PF patients and their loved ones engage the Web 2.0 environment at these PF-focused sites to satisfy their needs to better understand PF and its impacts and to support others facing similar challenges. Clinicians may find it beneficial to encourage PF patients’ involvement in internet forums that foster dynamic, bi-directional information sharing
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Synthesis and late-stage functionalization of complex molecules through C-H fluorination and nucleophilic aromatic substitution.
We report the late-stage functionalization of multisubstituted pyridines and diazines at the position α to nitrogen. By this process, a series of functional groups and substituents bound to the ring through nitrogen, oxygen, sulfur, or carbon are installed. This functionalization is accomplished by a combination of fluorination and nucleophilic aromatic substitution of the installed fluoride. A diverse array of functionalities can be installed because of the mild reaction conditions revealed for nucleophilic aromatic substitutions (S(N)Ar) of the 2-fluoroheteroarenes. An evaluation of the rates for substitution versus the rates for competitive processes provides a framework for planning this functionalization sequence. This process is illustrated by the modification of a series of medicinally important compounds, as well as the increase in efficiency of synthesis of several existing pharmaceuticals
Copper-Mediated Fluorination of Aryl Iodides
The synthesis of aryl fluorides has been studied intensively
because
of the importance of aryl fluorides in pharmaceuticals, agrochemicals,
and materials. The stability, reactivity, and biological properties
of aryl fluorides can be distinct from those of the corresponding
arenes. Methods for the synthesis of aryl fluorides, however, are
limited. We report the conversion of a diverse set of aryl iodides
to the corresponding aryl fluorides. This reaction occurs with a cationic
copper reagent and silver fluoride. Preliminary results suggest this
reaction is enabled by a facile reductive elimination from a cationic
arylcopper(III) fluoride
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Copper-mediated perfluoroalkylation of heteroaryl bromides with (phen)CuRF.
The attachment of perfluoroalkyl groups onto organic compounds has been a major synthetic goal over the past several decades. Previously, our group reported phenanthroline-ligated perfluoroalkyl copper reagents, (phen)CuRF, which react with aryl iodides and aryl boronates to form the corresponding benzotrifluorides. Herein the perfluoroalkylation of a series of heteroaryl bromides with (phen)CuCF3 and (phen)CuCF2CF3 is reported. The mild reaction conditions allow the process to tolerate many common functional groups. Perfluoroethylation with (phen)CuCF2CF3 occurs in somewhat higher yields than trifluoromethylation with (phen)CuCF3, creating a method to generate fluoroalkyl heteroarenes that are less accessible from trifluoroacetic acid derivatives
Copper-Mediated Difluoromethylation of Aryl and Vinyl Iodides
Selectively fluorinated molecules are important as materials,
pharmaceuticals,
and agrochemicals, but their synthesis by simple, mild, laboratory
methods is challenging. We report a straightforward method for the
cross-coupling of aryl and vinyl iodides with a difluoromethyl group
generated from readily available reagents to form difluoromethylarenes
and difluoromethyl-substituted alkenes. The reaction of electron-neutral,
electron-rich, and sterically hindered aryl and vinyl iodides with
the combination of CuI, CsF and TMSCF<sub>2</sub>H leads to the formation
of difluoromethyl-substituted products in high yield
with good functional group compatibility. This transformation is surprising,
in part, because of the prior observation of the instability of CuCF<sub>2</sub>H
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