50873-94-4Relevant academic research and scientific papers
Scalable and Phosphine-Free Conversion of Alcohols to Carbon-Heteroatom Bonds through the Blue Light-Promoted Iodination Reaction
Liu, Bin,Elder, W. Zachary,Miyake, Garret M.
, p. 3717 - 3727 (2020/03/04)
One of the fundamental and highly valuable transformations in organic chemistry is the nucleophilic substitution of alcohols. Traditionally, these reactions require strategies that employ stoichiometric hazardous reagents and are associated with difficulty in purification of the by-products. To overcome these challenges, here, we report a simple route toward the diverse conversion of alcohols via an SN2 pathway, in which blue light-promoted iodination is used to form alkyl iodide intermediates from simple unreactive alcohols. The scope of the process tolerates a range of nucleophiles to construct C-N, C-O, C-S, and C-C bonds. Furthermore, we also demonstrate that this method can be used for the preparation and late-stage functionalization of pharmaceuticals, as highlighted by the syntheses of thiocarlide, butoxycaine, and pramoxine.
Introduction of Cyclopropyl and Cyclobutyl Ring on Alkyl Iodides through Cobalt-Catalyzed Cross-Coupling
Andersen, Claire,Ferey, Vincent,Daumas, Marc,Bernardelli, Patrick,Guérinot, Amandine,Cossy, Janine
supporting information, p. 2285 - 2289 (2019/03/29)
A cobalt-catalyzed cross-coupling between alkyl iodides and cyclopropyl, cyclobutyl, and alkenyl Grignard reagents is disclosed. The reaction allows the introduction of strained rings on a large panel of primary and secondary alkyl iodides. The catalytic system is simple and nonexpensive, and the reaction is general, chemoselective, and diastereoconvergent. The alkene resulting from the cross-coupling can be transformed to substituted cyclopropanes using a Simmons-Smith reaction. The formation of radical intermediates during the coupling is hypothesized.
Catalyst-Free Reductive Coupling of Aromatic and Aliphatic Nitro Compounds with Organohalides
Rauser, Marian,Eckert, Raphael,Gerbershagen, Max,Niggemann, Meike
supporting information, p. 6713 - 6717 (2019/04/14)
A rare reductive coupling of nitro compounds with organohalides has been realized. The reaction is initiated by a partial reduction of the nitro group to a nitrenoid intermediate. Therefore, not only aromatic but also aliphatic nitro compounds are efficiently transformed into monoalkylated amines, with organohalides as the alkylating agent. Given the innate reactivity of the nitrenoid, a catalyst is not required, resulting in a high tolerance for aryl halide substituents in both starting materials.
Stereospecific Synthesis of E-Alkenes through Anti-Markovnikov Hydroalkylation of Terminal Alkynes
Hazra, Avijit,Chen, Jason,Lalic, Gojko
supporting information, p. 12464 - 12469 (2019/08/20)
We have developed a method for stereospecific synthesis of E-alkenes from terminal alkynes and alkyl iodides. The hydroalkylation reaction is enabled by a cooperative action of copper and nickel catalysts and proceeds with excellent anti-Markovnikov selectivity. We demonstrate the broad scope of the reaction, which can be accomplished in the presence of esters, nitriles, aryl bromides, ethers, alkyl chlorides, anilines, and a wide range of nitrogen-containing heteroaromatic compounds. Mechanistic studies provide evidence that the copper catalyst activates the alkyne by hydrocupration, which controls both the regio- and diastereoselectivity of the overall reaction. The nickel catalyst activates the alkyl iodide and promotes cross coupling with the alkenyl copper intermediate.
Optimization of the alkyl side chain length of fluorine-18-labeled 7α-alkyl-fluoroestradiol
Okamoto, Mayumi,Shibayama, Hiromitsu,Naka, Kyosuke,Kitagawa, Yuya,Ishiwata, Kiichi,Shimizu, Isao,Toyohara, Jun
, p. 512 - 519 (2016/06/14)
Introduction: Several lines of evidence suggest that 7α-substituted estradiol derivatives bind to the estrogen receptor (ER). In line with this hypothesis, we designed and synthesized 18F-labeled 7α-fluoroalkylestradiol (Cn-7α-[18F]FES) derivatives as molecular probes for visualizing ERs. Previously, we successfully synthesized 7α-(3-[18F]fluoropropyl)estradiol (C3-7α-[18F]FES) and showed promising results for quantification of ER density in vivo, although extensive metabolism was observed in rodents. Therefore, optimization of the alkyl side chain length is needed to obtain suitable radioligands based on Cn-7α-substituted estradiol pharmacophores. Methods: We synthesized fluoromethyl (23; C1-7α-[18F]FES) to fluorohexyl (26; C6-7α-[18F]FES) derivatives, except fluoropropyl (C3-7α-[18F]FES) and fluoropentyl derivatives (C5-7α-[18F]FES), which have been previously synthesized. In vitro binding to the α-subtype (ERα) isoform of ERs and in vivo biodistribution studies in mature female mice were carried out. Results: The in vitro IC50 value of Cn-7α-FES tended to gradually decrease depending on the alkyl side chain length. C1-7α-[18F]FES (23) showed the highest uptake in ER-rich tissues such as the uterus. Uterus uptake also gradually decreased depending on the alkyl side chain length. As a result, in vivo uterus uptake reflected the in vitro ERα affinity of each compound. Bone uptake, which indicates de-fluorination, was marked in 7α-(2-[18F]fluoroethyl)estradiol (C2-7α-[18F]FES) (24) and 7α-(4-[18F]fluorobutyl)estradiol (C4-7α-[18F]FES) (25) derivatives. However, C1-7α-[18F]FES (23) and C6-7α-[18F]FES (26) showed limited uptake in bone. As a result, in vivo bone uptake (de-fluorination) showed a bell-shaped pattern, depending on the alkyl side chain length. C1-7α-[18F]FES (23) showed the same levels of uptake in uterus and bone compared with those of 16α-[18F]fluoro-17β-estradiol. Conclusions: The optimal alkyl side chain length of 18F-labeled 7α-fluoroalkylestradiol was the shortest: C1-7α-[18F]FES. Our results indicate that shorter chain lengths within the 4-? ligand binding cavities of ERα are suitable for 7α-fluoroalkylestradiol derivatives.
Light-mediated deoxygenation of alcohols with a dimeric gold catalyst
McCallum, Terry,Slavko, Ekaterina,Morin, Mathieu,Barriault, Louis
supporting information, p. 81 - 85 (2015/02/18)
A new protocol for the reductive deoxygenation of primary alcohols was explored. This photo-mediated method combines a novel approach to bromination of alcohols merged with the powerful reducing capability of [Au2(dppm)2]Cl2 [dppm = 1,1-bis(diphenylphosphino)methane] as a photoredox catalyst. The highly efficient methods discussed are marked by the use of UVA light-emitting diodes, which have significantly reduced reaction times and lowered setup cost.
Electrochemical access to 8-(1-phenyl-ethyl)-1,4-dioxa-8-aza-spiro[4.5] decane-7-carbonitrile. Application to the asymmetric syntheses of (+)-myrtine and alkaloid (+)-241D
Vu, Van Ha,Louafi, Fadila,Girard, Nicolas,Marion, Ronan,Roisnel, Thierry,Dorcet, Vincent,Hurvois, Jean-Pierre
, p. 3358 - 3373 (2014/05/06)
The total syntheses of both enantiomers of trans-quinolizidine (+)-myrtine and cis-2,4,6-trisubstituted piperidine alkaloid (+)-241D are reported here. Our approach was based on the N-Boc-directed metalation of enantiopure 4-piperidone (-)-11, which was prepared in four steps from α-amino nitrile 6 through a stereoselective alkylation-reduction decyanation process. α-Amino nitrile 6 was prepared at the anode through electrochemical oxidation of 4-piperidone (+)-5. In our study, α-phenylethylamine (α-PEA) allowed an efficient 1-3 stereoinduction, and an orthogonal cleavage of the N-Boc protecting group in piperidone derivatives was carried out by stirring them in a suspension of SnCl4·(Et2O)2 complex in diethyl ether. When appropriate, the ers were determined by proton and carbon NMR spectroscopy utilizing (+)-tert-butylphenylphosphinothioic acid and (+)-DBTA as chiral solvating agents.
PROTEOLYSIS TARGETING CHIMERAS (PROTACS) DIRECTED TO THE MODULATION OF THE ESTROGEN RECEPTOR
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Page/Page column 83; 84, (2014/07/23)
A compound of formula (I): or a pharmaceutically acceptable salt thereof, compositions, combinations and medicaments containing said compounds and processes for their preparation. The invention also relates to the use of said compounds, combinations, compositions and medicaments, for example as inhibitors of the activity of the estrogen receptor, including degrading the estrogen receptor, the treatment of diseases and conditions mediated by the estrogen receptor
Intramolecular nitrone dipolar cycloadditions: Control of regioselectivity and synthesis of naturally-occurring spirocyclic alkaloids
Hodges, Alastair J.,Bond, Andrew D.,Holmes, Andrew B.,Roughley, Stephen D.,Smith, Catherine J.,Adams, Joseph P.,Ryan, John H.,Saubern, Simon,Newton, Annabella F.,Press, Neil J.,Turnbull, Michael D.
supporting information, p. 8963 - 8974,12 (2012/12/12)
The intramolecular nitrone dipolar cycloaddition of in situ-generated nitrones such as compound 26 has been used for the synthesis of cyclic isoxazolidines 27 and 29. The regioselectivity of the intramolecular cycloaddition depends on the nature of the terminal substituent on the dipolarophile. The influence of the substituent on the regioselectivity of the cycloaddition has been examined using several model systems and two methods of nitrone formation. These studies demonstrated that the cyano-substituent plays a special role in favouring the formation of the 6,6,5-ring fused adduct 27 under thermodynamically controlled conditions. The utility of the cyclo-adduct 57 (see Scheme 12) as a precursor for the naturally occurring histrionicotoxins is illustrated by the synthesis of three "unsymmetrical" (i.e. with each side chain bearing different functional groups) members of the histrionicotoxin family HTX-259A, HTX-285C and HTX-285E (2, 3 and 4 respectively).
Intramolecular nitrone dipolar cycloadditions: Control of regioselectivity and synthesis of naturally-occurring spirocyclic alkaloids
Hodges, Alastair J.,Adams, Joseph P.,Bond, Andrew D.,Holmes, Andrew B.,Press, Neil J.,Roughley, Stephen D.,Ryan, John H.,Saubern, Simon,Smith, Catherine J.,Turnbull, Michael D.,Newton, Annabella F.
supporting information, p. 8963 - 8974 (2013/01/15)
The intramolecular nitrone dipolar cycloaddition of in situ-generated nitrones such as compound 26 has been used for the synthesis of cyclic isoxazolidines 27 and 29. The regioselectivity of the intramolecular cycloaddition depends on the nature of the terminal substituent on the dipolarophile. The influence of the substituent on the regioselectivity of the cycloaddition has been examined using several model systems and two methods of nitrone formation. These studies demonstrated that the cyano-substituent plays a special role in favouring the formation of the 6,6,5-ring fused adduct 27 under thermodynamically controlled conditions. The utility of the cyclo-adduct 57 (see Scheme 12) as a precursor for the naturally occurring histrionicotoxins is illustrated by the synthesis of three "unsymmetrical" (i.e. with each side chain bearing different functional groups) members of the histrionicotoxin family HTX-259A, HTX-285C and HTX-285E (2, 3 and 4 respectively).
