| 1. |
- Colas, Kilian, et al.
(författare)
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Direct Addition of Grignard Reagents to Aliphatic Carboxylic Acids Enabled by Bulky turbo-Organomagnesium Anilides
- 2022
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Ingår i: Chemistry - A European Journal. - : Wiley. - 0947-6539 .- 1521-3765. ; 28:9
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Tidskriftsartikel (refereegranskat)abstract
- The synthesis of ketones through addition of organometallic reagents to aliphatic carboxylic acids is a straightforward strategy that is limited to organolithium reagents. More desirable Grignard reagents can be activated and controlled with a bulky aniline-derived turbo-Hauser base. This operationally simple procedure allows the straightforward preparation of a variety of aliphatic and perfluoroalkyl ketones alike from functionalized alkyl, aryl and heteroaryl Grignard reagents.
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| 2. |
- Colas, Kilian, et al.
(författare)
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i-Pr2-NMgCl·LiCl Enables the Synthesis of Ketones by Direct Addition of Grignard Reagents to Carboxylate Anions
- 2019
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Ingår i: Organic Letters. - : American Chemical Society (ACS). - 1523-7060 .- 1523-7052. ; 21:19, s. 7908-7913
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Tidskriftsartikel (refereegranskat)abstract
- The direct preparation of ketones from carboxylate anions is greatly limited by the required use of organolithium reagents or activated acyl sources that need to be independently prepared. Herein, a specific magnesium amide additive is used to activate and control the addition of more tolerant Grignard reagents to carboxylate anions. This strategy enables the modular synthesis of ketones from CO2 and the preparation of isotopically labeled pharmaceutical building blocks in a single operation.
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| 3. |
- Colas, Kilian, et al.
(författare)
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Indolylbenzothiadiazoles as highly tunable fluorophores for imaging lipid droplet accumulation in astrocytes and glioblastoma cells
- 2021
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Ingår i: RSC Advances. - : Royal Society of Chemistry. - 2046-2069. ; 11:39, s. 23960-23967
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Tidskriftsartikel (refereegranskat)abstract
- We present an extensive photophysical study of a series of fluorescent indolylbenzothiadiazole derivatives and their ability to specifically image lipid droplets in astrocytes and glioblastoma cells. All compounds in the series displayed positive solvatochromism together with large Stokes shifts, and π-extended derivatives exhibited elevated brightness. It was shown that the fluorescence properties were highly tunable by varying the electronic character or size of the N-substituent on the indole motif. Three compounds proved capable as probes for detecting small quantities of lipid deposits in healthy and cancerous brain cells. In addition, all twelve compounds in the series were predicted to cross the blood–brain barrier, which raises the prospect for future in vivo studies for exploring the role of lipid droplets in the central nervous system.
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| 4. |
- Colas, Kilian, et al.
(författare)
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Intermolecular Pummerer Coupling with Carbon Nucleophiles in Non-Electrophilic Media
- 2017
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Ingår i: Angewandte Chemie International Edition. - : Wiley-VCH Verlagsgesellschaft. - 1433-7851 .- 1521-3773. ; 56:50, s. 16042-16046
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Tidskriftsartikel (refereegranskat)abstract
- A new Pummerer-type C-C coupling protocol is introduced based on turbo-organomagnesium amides, which unlike traditional Pummerer reactions, does not require strong electrophilic activators, engages a broad range of C(sp(3))-, C(sp(2))-, and C(sp)-nucleophiles, and seamlessly integrates with C-H and C-X magnesiation. Given the central character of sulfur compounds in organic chemistry, this protocol allows access to unrelated carbonyls, olefins, organometallics, halides, and boronic esters through a single strategy.
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| 5. |
- Colas, Kilian, 1990-, et al.
(författare)
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Iterative Synthesis of Pluripotent Thioethers through Controlled Redox Fluctuation of Sulfur
- 2018
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Ingår i: Synlett. - : Georg Thieme Verlag KG. - 0936-5214 .- 1437-2096. ; 29:10, s. 1329-1333
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Tidskriftsartikel (refereegranskat)abstract
- Target- and diversity-oriented syntheses are based on diverse building blocks, whose preparation requires discrete design and constructive alignment of different chemistries. To enable future automation of the synthesis of small molecules, we have devised a unified strategy that serves the divergent synthesis of unrelated scaffolds such as carbonyls, olefins, organometallics, halides, and boronic esters. It is based on iterations of a nonelectrophilic Pummerer-type C-C coupling enabled by turbo -organomagnesium amides that we have recently reported. The pluripotency of sulfur allows the central building blocks to be obtained by regulating C-C bond formation through control of its redox state.
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| 6. |
- Colas, Kilian, 1990-
(författare)
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New C-C coupling Reactions Enabled by Main-group Organometallics
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The carbon-carbon bond has always been at the very core of chemical research. Strategies for the creation of C−C bonds are one of the keys to the construction game that organic chemists play with the building blocks provided by Nature, with the ultimate goal of producing useful molecular structures that will serve society as medicines, materials, imaging tools, catalysts, and ligands (to mention but a few). While very different in their structure, all of these molecules are often prepared by the same methods. However, efficiency could be improved with tailored chemical strategies that would serve an individual purpose. Ideally, these chemical manipulations should be efficient, selective, environmentally friendly and economic, in order to truly fulfill their final objective.However, despite the ever-expanding rule-book of chemical reactions, target molecules of increasing complexity often face chemists with daunting challenges, whose success rely on multi-step synthetic sequences. There is therefore a permanent need for new, specific methods and strategies that are capable of seamlessly creating C−C bonds, evading the synthesis of difficult or expensive substrates. In this regard, common organometallic reagents display a unique behavior as carbon precursors, in particular as powerful nucleophiles. Reagents based on main-group elements such as lithium or magnesium have therefore played a central role in organic synthesis ever since their discovery. The challenge often lies in controlling their high reactivity, as well as their basic character. Tuning and taming these properties provides chemists with a wide range of unique strategies for the selective synthesis of countless molecular targets.In the first part of this thesis, a scalable and stereoselective [3+3] homocoupling of imines in which two C−C bonds are formed in a single step is reported. This reaction relies on an unusual combination of visible-light irradiation and aluminum organometallics. This photochemical process enables the circumvention of the native [3+2] reactivity of these readily available starting materials, thus enabling rapid access to densely functionalized piperazines. Thanks to the congested environment they provide, these heterocyclic scaffolds can be used as ligands to prevent catalyst deactivation through oligomerization.The next chapter presents a novel Pummerer-type redox-neutral coupling of sulfoxides and Grignard reagents. This reaction is enabled by a unique turbo-magnesium amide base, and allows the use of a wide range of carbon nucleophiles in intermolecular Pummerer C−C coupling for the streamlined preparation of thioethers. Given the central character of sulfur in organic chemistry, these compounds can then be converted to a variety of unrelated functional groups for the streamlined preparation of diverse building blocks.In the final two chapters, the development of a method for the direct conversion of carboxylic acids to ketones with Grignard reagents is described. Using the above-mentioned combination of organometallics, a wide variety of carboxylic acids substrates and Grignard reagents can be coupled in a convenient, scalable and highly selective method that suppresses the need for activation and offers a straightforward approach to ketones from readily available starting materials.
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| 7. |
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| 8. |
- Colas, Kilian, et al.
(författare)
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Photophysical Characteristics of Polarity-Sensitive and Lipid Droplet-Specific Phenylbenzothiadiazoles
- 2021
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Ingår i: ChemPhotoChem. - : Wiley. - 2367-0932. ; 5:7, s. 632-643
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we present a series of solvatochromic phenylbenzothiadiazoles that display dual emission from the locally excited (LE) and intramolecular charge transfer (ICT) excited states. The donor-acceptor derivatives are highly sensitive to polarity changes, which can be monitored by differences in emission efficiency, spectroscopic shifts and variations of the LE/ICT ratio. One of the compounds in the series, containing a thiomethyl substituent, emerged as an excellent blue emitting stain for intracellular lipid droplets, a biomarker for various types of cancer. In addition, a non-emissive nitro derivative becomes fluorescent upon bioreduction in hypoxic cancer cells and accumulates in lipid droplets with a high signal-to-background ratio.
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| 9. |
- Colas, Kilian, et al.
(författare)
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Prevalent Bioimaging Scaffolds : Synthesis, Photophysical Properties and Applications
- 2021
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Ingår i: European Journal of Organic Chemistry. - : John Wiley & Sons. - 1434-193X .- 1099-0690. ; 2021:15, s. 2133-2144
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Forskningsöversikt (refereegranskat)abstract
- Coumarin, xanthene, BODIPY, and cyanine are four of the most prevalent bioimaging scaffolds in chemical biology. In this review, we summarize the synthesis, structure-photophysical properties relationships, and imaging applications of fluorophores based on these units. We review the advantages and disadvantages of each scaffold in bioimaging as well as the practical issues to consider when using small organic compounds in biological systems.This minireview describes the syntheses, structure-photophysical properties relationship, and bioimaging applications of fluorescent coumarins, xanthenes, BODIPYs, and cyanines. Advantages and disadvantages of the emissive units are also discussed, as are general practical issues that need to be considered when using fluorophores in a biological setting.
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| 10. |
- Mendoza, Abraham, et al.
(författare)
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Chemical Innovation through Ligand Total Synthesis
- 2016
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Ingår i: Synlett. - : Georg Thieme Verlag KG. - 0936-5214 .- 1437-2096. ; 27:12, s. 1753-1759
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Tidskriftsartikel (refereegranskat)abstract
- Natural products are an abundant source of synthetic challenges that foster crucial breakthroughs in organic chemistry. Despite the superior complexity of these targets, ligand total synthesis can inspire solutions to unsolved chemical problems and provide access to creative catalyst designs. This Synpacts article presents a comparative analysis of natural and ligand total synthesis to provide a context for our recent research and motivate the importance of future undertakings in this area.
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