Fluorine Compounds, Organic

Siegemund, G.; Schwertfeger, Werner; Feiring, Andrew E.; Smart, Bruce E.; Behr, Fred E.; Vogel, H. A.; McKusick, B. C.; Kirsch, Peer

doi:10.1002/14356007.a11_349.pub2

Cited by 37 publications

(43 citation statements)

References 220 publications

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“…Trifluoroacetic acid (CF 3 CO 2 H) has been known since 1922 [ 21 ], but its widespread application was only made possible sometime later, much due to the development of electrochemical fluorination processes (Simons process) for production of organofluorine compounds in the 1930s and 1940s [ 22 – 23 ]. It is a strong acid (p K a ≈ 0.5), quite volatile (bp.…”

Section: Reviewmentioning

confidence: 99%

Chemoselective O-acylation of hydroxyamino acids and amino alcohols under acidic reaction conditions: History, scope and applications

Kristensen¹

2015

Beilstein J. Org. Chem.

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SummaryAmino acids, whether natural, semisynthetic or synthetic, are among the most important and useful chiral building blocks available for organic chemical synthesis. In principle, they can function as inexpensive, chiral and densely functionalized starting materials. On the other hand, the use of amino acid starting materials routinely necessitates protective group chemistry, and in reality, large-scale preparations of even the simplest side-chain derivatives of many amino acids often become annoyingly strenuous due to the necessity of employing protecting groups, on one or more of the amino acid functionalities, during the synthetic sequence. However, in the case of hydroxyamino acids such as hydroxyproline, serine, threonine, tyrosine and 3,4-dihydroxyphenylalanine (DOPA), many O-acyl side-chain derivatives are directly accessible via a particularly expedient and scalable method not commonly applied until recently. Direct acylation of unprotected hydroxyamino acids with acyl halides or carboxylic anhydrides under appropriately acidic reaction conditions renders possible chemoselective O-acylation, furnishing the corresponding side-chain esters directly, on multigram-scale, in a single step, and without chromatographic purification. Assuming a certain degree of stability under acidic reaction conditions, the method is also applicable for a number of related compounds, such as various amino alcohols and the thiol-functional amino acid cysteine. While the basic methodology underlying this approach has been known for decades, it has evolved through recent developments connected to amino acid-derived chiral organocatalysts to become a more widely recognized procedure for large-scale preparation of many useful side-chain derivatives of hydroxyamino acids and related compounds. Such derivatives are useful in peptide chemistry and drug development, as amino acid amphiphiles for asymmetric catalysis, and as amino acid acrylic precursors for preparation of catalytically active macromolecular networks in the form of soluble polymers, crosslinked polymer beads or nanoparticulate systems. The objective of the present review is to increase awareness of the existence and convenience of this methodology, assess its competitiveness compared to newer and more elaborate procedures for chemoselective O-acylation reactions, spur its further development, and finally to chronicle the informative, but poorly documented history of its development.

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Section: Reviewmentioning

confidence: 99%

Chemoselective O-acylation of hydroxyamino acids and amino alcohols under acidic reaction conditions: History, scope and applications

Kristensen¹

2015

Beilstein J. Org. Chem.

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“…Compared to the corresponding hydrocarbon compounds, the fluorinated ones indeed, generally show enhanced thermal stability, viscosity and density, whereas surface tension, refractive index and dielectric constant are smaller, as are the boiling and melting points. 3 Furthermore, the fluorination also changes the solubility of the molecules towards higher hydrophobicity. 4,5 Because of their electron-withdrawing capability, the presence of fluorine atoms lowers the energy levels of the molecular orbitals (MOs); in particular, the decrease in the energy of the highest occupied molecular orbital (HOMO) confers to the molecules higher stability versus degradative oxidation processes.…”

Section: Introductionmentioning

confidence: 99%

Effect of fluorination on the crystal and electronic structure of organometallic cyclopentadienyl-phenylenediamino-cobalt complexes

Pilia

Shuku

Dalgleish

et al. 2020

Journal of Organometallic Chemistry

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The fluorinated half sandwich complex [CpCoLF] (Cp = cyclopentadiene; LF = o-perfluorophenylenediimine; 2F) shows a T-shaped geometry with the LF ligand coplanar with the metallocycle. The molecules are dimerized in a head-to-tail fashion and arranged in a herringbone manner in the crystal packing.The crystal structure of 2F is different from that of the corresponding hydrocarbon compound (2H).Moreover, the differences due to the presence of fluorine atoms are also highlighted by the analysis of the intermolecular contacts, which show that 2F exhibits several F•••F contacts, as well as aromatic intra-dimer π•••π interactions in addition to C−H•••π and C−H•••F contacts. No relevant π•••π interactions are observed in the case of 2H. Hirshfeld Surface (HS) analysis also depicted well the differences in the solid state interactions between the different crystal structures. In particular, HS has been useful in highlighting the differences observed between the crystal structure of 2H obtained from Rietveld refinement and that measured on single crystal (2HP and 2HSCH, respectively). The effect of the fluorination on the electronic structure has been investigated also by CV measurements and Density Functional Theory calculations. Both are consistent with a lowering in energy of the molecular orbitals. Data Mining Force Field calculations clearly indicate that the 2HSCH structure is more stable than the 2HP one. These findings can be explained in terms of the energy of the intermolecular interactions. The enhanced stability of the fluorine substitute can be easily explained by the large number of strong interactions involving fluorine atoms.

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“…4 Commodity trifluoromethylated arenes are produced industrially through direct halogen-fluoride exchange of benzotrichlorides; however, this process is limited to methylated arenes of significant oxidative and thermal stability, which are chlorinated before being subjected to anhydrous hydrogen fluoride at elevated temperatures. 5 Alternative strategies are required to produce electron-rich and acid-sensitive benzotrifluorides, and halogen-fluoride exchange is not effective for higher-order perfluoroalkyl groups such as C 2 F 5 . Because of the challenges and limited substrate scope associated with direct C–F bond formation, many reagents for the direct incorporation of fluorinated groups have found widespread synthetic utility and strategic relevance.…”

Section: Introductionmentioning

confidence: 99%

Photochemical Perfluoroalkylation with Pyridine N -Oxides: Mechanistic Insights and Performance on a Kilogram Scale

Beatty

Douglas

Miller

et al. 2016

Chem

243

160

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SUMMARY The direct trifluoromethylation of (hetero)arenes is a process of high importance to the pharmaceutical industry. Many reagents exist for this purpose and have found widespread use in discovery efforts; however, the step-intensive preparation of these reagents and their corresponding cost have resulted in minimal use of these methods in large-scale applications. For the ready transition of direct trifluoromethylation methodologies to large-scale application, the further development of processes utilizing inexpensive CF3 sources available on a metric ton scale is highly desirable. We report the use of pyridine N-oxide derivatives in concert with trifluoroacetic anhydride to promote a high-yielding and scalable trifluoromethylation reaction. Key mechanistic insights include the observation of electron donor-acceptor complexes in solution as well as a high dependence on photon flux. These observations have culminated in the application of this chemistry on a kilogram scale, demonstrating the utility of this reagent combination for preparative applications.

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Fluorine Compounds, Organic

Cited by 37 publications

References 220 publications

Chemoselective O-acylation of hydroxyamino acids and amino alcohols under acidic reaction conditions: History, scope and applications

Chemoselective O-acylation of hydroxyamino acids and amino alcohols under acidic reaction conditions: History, scope and applications

Effect of fluorination on the crystal and electronic structure of organometallic cyclopentadienyl-phenylenediamino-cobalt complexes

Photochemical Perfluoroalkylation with Pyridine N -Oxides: Mechanistic Insights and Performance on a Kilogram Scale

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