2968-93-6Relevant academic research and scientific papers
Regiodivergent Reductive Opening of Epoxides by Catalytic Hydrogenation Promoted by a (Cyclopentadienone)iron Complex
Tadiello, Laura,Gandini, Tommaso,Stadler, Bernhard M.,Tin, Sergey,Jiao, Haijun,de Vries, Johannes G.,Pignataro, Luca,Gennari, Cesare
, p. 235 - 246 (2022/01/03)
The reductive opening of epoxides represents an attractive method for the synthesis of alcohols, but its potential application is limited by the use of stoichiometric amounts of metal hydride reducing agents (e.g., LiAlH4). For this reason, the corresponding homogeneous catalytic version with H2 is receiving increasing attention. However, investigation of this alternative has just begun, and several issues are still present, such as the use of noble metals/expensive ligands, high catalytic loading, and poor regioselectivity. Herein, we describe the use of a cheap and easy-To-handle (cyclopentadienone)iron complex (1a), previously developed by some of us, as a precatalyst for the reductive opening of epoxides with H2. While aryl epoxides smoothly reacted to afford linear alcohols, aliphatic epoxides turned out to be particularly challenging, requiring the presence of a Lewis acid cocatalyst. Remarkably, we found that it is possible to steer the regioselectivity with a careful choice of Lewis acid. A series of deuterium labeling and computational studies were run to investigate the reaction mechanism, which seems to involve more than a single pathway.
Borane evolution and its application to organic synthesis using the phase-vanishing method
Soga, Nene,Yoshiki, Tomo,Sato, Aoi,Kawamoto, Takuji,Ryu, Ilhyong,Matsubara, Hiroshi
supporting information, (2021/03/26)
Although borane is a useful reagent, it is difficult to handle. In this study, borane was generated in situ from NaBH4 or nBu4NBH4 with several oxidants using a phase-vanishing (PV) method. The borane generated was directly reacted with alkenes, affording the desired alcohols in good yields after oxidation with H2O2 under basic conditions. The selective reduction of carboxylic acids with the evolved borane was examined. The organoboranes generated by the PV method successfully underwent Suzuki–Miyaura coupling. Using this PV system, reactions with borane can be carried out easily and safely in a common test tube.
Chemoselective Cleavage of Si-C(sp3) Bonds in Unactivated Tetraalkylsilanes Using Iodine Tris(trifluoroacetate)
Matsuoka, Keitaro,Komami, Narumi,Kojima, Masahiro,Mita, Tsuyoshi,Suzuki, Kimichi,Maeda, Satoshi,Yoshino, Tatsuhiko,Matsunaga, Shigeki
supporting information, p. 103 - 108 (2021/01/13)
Organosilanes are synthetically useful reagents and precursors in organic chemistry. However, the typical inertness of unactivated Si-C(sp3) bonds under conventional reaction conditions has hampered the application of simple tetraalkylsilanes in organic synthesis. Herein we report the chemoselective cleavage of Si-C(sp3) bonds of unactivated tetraalkylsilanes using iodine tris(trifluoroacetate). The reaction proceeds smoothly under mild conditions (-50 °C to room temperature) and tolerates various polar functional groups, thus enabling subsequent Tamao-Fleming oxidation to provide the corresponding alcohols. NMR experiments and density functional theory calculations on the reaction indicate that the transfer of alkyl groups from Si to the I(III) center and the formation of the Si-O bond proceed concertedly to afford an alkyl-λ3-iodane and silyl trifluoroacetate. The developed method enables the use of unactivated tetraalkylsilanes as highly stable synthetic precursors.
Structure-Activity Relationship Explorations and Discovery of a Potent Antagonist for the Free Fatty Acid Receptor 2
H?jgaard Hansen, Anders,Christensen, Henriette B.,Pandey, Sunil K.,Sergeev, Eugenia,Valentini, Alice,Dunlop, Julia,Dedeo, Domonkos,Fratta, Simone,Hudson, Brian D.,Milligan, Graeme,Ulven, Trond,Rexen Ulven, Elisabeth
, p. 3326 - 3341 (2021/09/14)
Free fatty acid receptor 2 (FFA2) is a sensor for short-chain fatty acids that has been identified as an interesting potential drug target for treatment of metabolic and inflammatory diseases. Although several ligand series are known for the receptor, the
Erbium-Catalyzed Regioselective Isomerization-Cobalt-Catalyzed Transfer Hydrogenation Sequence for the Synthesis of Anti-Markovnikov Alcohols from Epoxides under Mild Conditions
Liu, Xin,Longwitz, Lars,Spiegelberg, Brian,T?njes, Jan,Beweries, Torsten,Werner, Thomas
, p. 13659 - 13667 (2020/11/30)
Herein, we report an efficient isomerization-transfer hydrogenation reaction sequence based on a cobalt pincer catalyst (1 mol %), which allows the synthesis of a series of anti-Markovnikov alcohols from terminal and internal epoxides under mild reaction conditions (≤55 °C, 8 h) at low catalyst loading. The reaction proceeds by Lewis acid (3 mol % Er(OTf)3)-catalyzed epoxide isomerization and subsequent cobalt-catalyzed transfer hydrogenation using ammonia borane as the hydrogen source. The general applicability of this methodology is highlighted by the synthesis of 43 alcohols from epoxides. A variety of terminal (23 examples) and 1,2-disubstituted internal epoxides (14 examples) bearing different functional groups are converted to the desired anti-Markovnikov alcohols in excellent selectivity and yields of up to 98%. For selected examples, it is shown that the reaction can be performed on a preparative scale up to 50 mmol. Notably, the isomerization step proceeds via the most stable carbocation. Thus, the regiochemistry is controlled by stereoelectronic effects. As a result, in some cases, rearrangement of the carbon framework is observed when tri-and tetra-substituted epoxides (6 examples) are converted. A variety of functional groups are tolerated under the reaction conditions even though aldehydes and ketones are also reduced to the respective alcohols under the reaction conditions. Mechanistic studies and control experiments were used to investigate the role of the Lewis acid in the reaction. Besides acting as the catalyst for the epoxide isomerization, the Lewis acid was found to facilitate the dehydrogenation of the hydrogen donor, which enhances the rate of the transfer hydrogenation step. These experiments additionally indicate the direct transfer of hydrogen from the amine borane in the reduction step.
Iron-Catalyzed β-Alkylation of Alcohols
Bettoni, Leó,Gaillard, Sylvain,Renaud, Jean-Luc
supporting information, p. 8404 - 8408 (2019/10/16)
β-Branched alkylated alcohols have been prepared in good yields using a double-hydrogen autotransfer strategy in the presence of our diaminocyclopentadienone iron tricarbonyl complex Fe1. The alkylation of some 2-arylethanol derivatives was successfully addressed with benzylic alcohols and methanol as alkylating reagents under mild conditions. Deuterium labeling experiments suggested that both alcohols (2-arylethanol and either methanol or benzyl alcohol) served as hydrogen donors in this cascade process.
Structural hybridization of pyrrolidine-based T-type calcium channel inhibitors and exploration of their analgesic effects in a neuropathic pain model
Son, Woo Seung,Jeong, Kyu-Sung,Lim, Sang Min,Pae, Ae Nim
, p. 1168 - 1172 (2019/03/28)
Highly effective and safe drugs for the treatment of neuropathic pain are urgently required and it was shown that blocking T-type calcium channels can be a promising strategy for drug development for neuropathic pain. We have developed pyrrolidine-based T
CERAMIDE GALACTOSYLTRANSFERASE INHIBITORS FOR THE TREATMENT OF DISEASE
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Paragraph 00452-00454, (2019/06/11)
Described herein are compounds, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or disorders associated with the enzyme ceramide galactosyltransferase (CGT), such as, for example, lysosomal storage diseases. Examples of lysosomal storage diseases include, for example, Krabbe disease and Metachromatic Leukodystrophy.
Anti-Markovnikov alkene oxidation by metal-oxo–mediated enzyme catalysis
Hammer, Stephan C.,Kubik, Grzegorz,Watkins, Ella,Huang, Shan,Minges, Hannah,Arnold, Frances H.
, p. 215 - 218 (2017/10/19)
Catalytic anti-Markovnikov oxidation of alkene feedstocks could simplify synthetic routes to many important molecules and solve a long-standing challenge in chemistry. Here we report the engineering of a cytochrome P450 enzyme by directed evolution to catalyze metal-oxo–mediated anti-Markovnikov oxidation of styrenes with high efficiency. The enzyme uses dioxygen as the terminal oxidant and achieves selectivity for anti-Markovnikov oxidation over the kinetically favored alkene epoxidation by trapping high-energy intermediates and catalyzing an oxo transfer, including an enantioselective 1,2-hydride migration. The anti-Markovnikov oxygenase can be combined with other catalysts in synthetic metabolic pathways to access a variety of challenging anti-Markovnikov functionalization reactions.
Regioselective hydrosilylation of epoxides catalysed by nickel(II) hydrido complexes
Wenz, Jan,Wadepohl, Hubert,Gade, Lutz H.
supporting information, p. 4308 - 4311 (2017/04/21)
Bench-stable nickel fluoride complexes bearing NNN pincer ligands have been employed as precursors for the regioselective hydrosilylation of epoxides at room temperature. A nickel hydride assisted epoxide opening is followed by the cleavage of the newly formed nickel oxygen bond by σ-bond metathesis with a silane.
