- Halogen-Lithium Exchange of Sensitive (Hetero)aromatic Halides under Barbier Conditions in a Continuous Flow Set-Up
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A halogen-lithium exchange reaction of (hetero)aromatic halides performed in the presence of various electrophiles such as aldehydes, ketones, Weinreb amides, and imines using BuLi as exchange reagent and a commercially available flow set-up is reported. The organolithiums generated in situ were instantaneously trapped with various electrophiles (Barbier conditions) resulting in the formation of polyfunctional (hetero)arenes. This method enables the functionalization of (hetero)arenes containing highly sensitive functional groups such as esters, which are not tolerated in batch conditions.
- Weidmann, Niels,Nishimura, Rodolfo H. V.,Harenberg, Johannes H.,Knochel, Paul
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supporting information
p. 557 - 568
(2020/09/18)
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- Electrophotochemical Ring-Opening Bromination oftert-Cycloalkanols
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An electrophotochemical ring-opening bromination of unstrainedtert-cycloalkanols has been developed. This electrophotochemical method enables the oxidative transformation of cycloalkanols with 5- to 7-membered rings into synthetically useful ω-bromoketones without the use of chemical oxidants or transition-metal catalysts. Alkoxy radical species would be key intermediates in the present transformation, which generate through homolysis of the O-Br bond in hypobromite intermediates under visible light irradiation.
- Yamamoto, Kosuke,Toguchi, Hiroyuki,Kuriyama, Masami,Watanabe, Shin,Iwasaki, Fumiaki,Onomura, Osamu
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p. 16177 - 16186
(2021/09/13)
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- Samarium-based Grignard-type addition of organohalides to carbonyl compounds under catalysis of CuI
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Grignard-type additions were readily achieved under the mediation of CuI (10 mol%) and samarium (2 equiv.) by employing various organohalides,e.g.benzyl, aryl, heterocyclic and aliphatic halides (Cl, Br or I), and diverse carbonyl compounds (e.g.carbonic esters, carboxylic esters, acid anhydrides, acyl chlorides, ketones, aldehydes, propylene epoxides and formamides) to afford alcohols, ketones and aldehydes, respectively, with high efficiency and chemoselectivity, in which the organosamarium intermediate might be involved.
- Liu, Chen,Liu, Yongjun,Qi, Yan,Song, Bin,Wang, Liang,Xiao, Shuhuan
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supporting information
p. 6169 - 6172
(2021/06/30)
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- Terminal Trifluoromethylation of Ketones via Selective C-C Cleavage of Cycloalkanols Enabled by Hypervalent Iodine Reagents
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We report the first terminal trifluoromethylation at aryl and alkyl ketones' ?, or more remote sites via the selective C-C bond cleavage of cycloalkanols. The noncovalent interactions between alcohols and hypervalent iodines(III) reagents were disclosed to activate both alcohols and the Togni I reagent in the dual photoredox/copper catalysis for the transformation. This reaction was scalable to the gram-scale synthesis, applicable to the structurally complex steroid trifluoromethylation, and extendable to the pentafluoroethylation.
- Wu, Shuang,Li, Junzhao,He, Ru,Jia, Kunfang,Chen, Yiyun
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supporting information
p. 9204 - 9209
(2021/11/30)
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- The Barbier-Grignard-Type Arylation of Ketones and Unexpected Cross-Coupling of Phenolic Ketones using Unactivated Aryl Bromides
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A novel, highly versatile and efficient method has been developed for the Barbier-Grignard-type arylation of ketones and an unexpected cross-coupling of phenolic ketones was observed using unactivated bromides and magnesium in tetrahydrofuran/toluene at 96°C promoted by multicatalysts of cupric bromide (15 mol%), bismuth chloride (5 mol%) and silver bromide (10 mol%). The substituent and electronic effects on the reaction have been discussed. High yields of arylation and cross-coupling have been attained under mild conditions. A novel reasonable mechanism involving a quinone intermediate is proposed. The high chemical selectivity in the cross-coupling to the hydroxy group of phenolic ketones should help ketones find new applications.
- Wen, Yunming,Chen, Guifang,Huang, Shiqiang,Tang, Yu,Yang, Jun,Zhang, Yuanming
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p. 947 - 957
(2016/04/05)
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- Enantioselective photoredox catalysis enabled by proton-coupled electron transfer: Development of an asymmetric aza-pinacol cyclization
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The first highly enantioselective catalytic protocol for the reductive coupling of ketones and hydrazones is reported. These reactions proceed through neutral ketyl radical intermediates generated via a concerted proton-coupled electron transfer (PCET) event jointly mediated by a chiral phosphoric acid catalyst and the photoredox catalyst Ir(ppy)2(dtbpy)PF6. Remarkably, these neutral ketyl radicals appear to remain H-bonded to the chiral conjugate base of the Bronsted acid during the course of a subsequent C-C bond-forming step, furnishing syn 1,2-amino alcohol derivatives with excellent levels of diastereo- and enantioselectivity. This work provides the first demonstration of the feasibility and potential benefits of concerted PCET activation in asymmetric catalysis.
- Rono, Lydia J.,Yayla, Hatice G.,Wang, David Y.,Armstrong, Michael F.,Knowles, Robert R.
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supporting information
p. 17735 - 17738
(2014/01/06)
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- Synthesis and antinociceptive behaviors of new methyl and hydroxyl derivatives of phencyclidine
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Phencyclidine (I) and its derivatives show such pharmacological behaviors as analgesic, anticonsulvant, anti-anxiety and antidepressant, while interacting with central nervous system. In this study, new methyl and hydroxyl derivatives of PCP were synthesized and their antinociceptive behaviors in animals were examined by measuring the number of writhing in a writhing test of visceral pain and the pain scores in Formalin test. Compared to control and PCP groups, findings in experimental groups indicated the new synthesized analogues (compounds II, III and V, 10 mg/kg) of PCP were able to produce more analgesic effects in formalin and writhing tests, especially for compound V. It was concluded that the new synthesized derivatives of PCP could substantially and respectively diminish acute and chronic pains.
- Ahmadi,Kermani,Naderi,Hajikhani,Rezaee,Javadi,Niknafs
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scheme or table
p. 763 - 769
(2012/06/30)
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- Synthesis and application of 2,6-bis(trifluoromethyl)-4-pyridyl phosphanes: The most electron-poor aryl phosphanes with moderate bulkiness
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The poor will be rich: BFPy phosphanes (see scheme) mimic the electronic and steric characters of P(C6F5)3 and PPh 3, respectively. These novel ligands showed a large ligand acceleration effect on Stille coupling, the Rh-catalyzed 1,2-addition of aryl boronic acid to unactivated ketones and the asymmetric arylation of N-tosylimine using phenylboronic acid. Copyright
- Korenaga, Toshinobu,Ko, Aram,Uotani, Kotaro,Tanaka, Yuki,Sakai, Takashi
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supporting information; experimental part
p. 10703 - 10707
(2012/01/04)
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- Broonsted acid-promoted hydrocyanation of arylalkenes
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Nonactivated arylalkenes are effectively converted to tertiary benzylic nitriles in the presence of triflic acid and trimethylsilyl cyanide. The hydrocyanation reactions result in good to excellent yield when electron-donating groups are substituted on the benzene ring. The reaction conditions are mild and relatively safe, notably without need for handling hazardous hydrogen cyanide gas, providing simple and easy access to tertiary benzylic nitriles. The reaction was applied to the preparation of a PDE4 inhibitor (3) as well as a series of analogues.
- Yanagisawa, Arata,Nezu, Tetsuya,Mohri, Shin-Ichiro
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supporting information; experimental part
p. 5286 - 5289
(2009/12/29)
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- Enantioselective protonation of silyl enol ethers and ketene disilyl acetals with Lewis acid-assisted chiral Bronsted acids: Reaction scope and mechanistic insights
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Enantioselective protonation is a potent and efficient way to construct chiral carbons. Here we report details of the reaction using Lewis acid-assisted chiral Bronsted acids (chiral LBAs). The 1:1 coordinate complex of tin tetrachloride and optically active binaphthol ((R)- or (S)-BINOL) can directly protonate various silyl enol ethers and ketene disilyl acetals to give the corresponding α-aryl ketones and α-arylcarboxylic acids, respectively, with high enantiomeric excesses (up to 98% ee). A catalytic version of enantioselective protonation has also been achieved using stoichiometric amounts of 2,6-dimethylphenol and catalytic amounts of monomethyl ether of optically active BINOL in the presence of tin tetrachloride. This protonation is also effective for producing α-halocarbonyl compounds (up to 91% ee). DFT calculations on the B3LYP/LANL2DZ level show that the conformational structure of the chiral LBA and the orientation of activated proton on (R)-BINOLs are important for understanding the absolute stereochemistry of the products.
- Nakamura, Shingo,Kaneeda, Masanobu,Ishihara, Kazuaki,Yamamoto, Hisashi
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p. 8120 - 8130
(2007/10/03)
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- Soluble highly reactive form of calcium and reagents thereof
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A soluble highly reactive form of calcium, prepared from Ca(II) salts and a reducing agent in ethereal, polyethereal, or hydrocarbon solvents, is presented. This form of calcium can be used in the preparation of organocalcium reagents. The organocalcium reagents resulting from the reaction of the soluble highly reactive calcium with organic compounds containing either halide, cyanide, a 1,3-diene, or a polyunsaturated functionality, are stable, useful reagents for organic synthesis. The organocalcium halide reagents undergo Grignard-type reactions. They also undergo reactions with Cu(I) salts to form organocalcium cuprate reagents. The organocalcium cuprate reagents undergo a variety of cross-coupling reactions. The soluble highly reactive calcium reacts with 1,3-dienes to yield the corresponding 2-butene-1,4-diylcalcium complexes. These bis-organocalcium reagents can undergo dialkylation reactions with α,ω-alkylene dihalides and dichlorosilanes to form the corresponding 3-, 5-, and 6-membered ring derivatives. The soluble highly reactive calcium also reacts with organic dihalides to form mono- or diorganocalcium compounds which can be converted into a wide variety of polymers.
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- Organocalcium Chemistry: Preparation and Reactions of Highly Reactive Calcium
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A highly reactive form of calcium was prepared by the reduction of Ca(II) salts with preformed lithium biphenylide.Remarkably, this activated calcium undergoes oxidative addition to organic bromides, chlorides, or even fluorides to form the organocalcium reagents under very mild conditions in high yields.The resulting organocalcium compounds undergo Grignard-type reactions.Transmetalation with Cu(I) salts forms calcium cuprate reagents which undergo a variety of cross-coupling reactions.The activated calcium reacts with 1,3-dienes to yield the corresponding 2-butene-1,4-diylcalcium complexes.These bis-organocalcium reagents can undergo dialkylation reactions with α,ω-alkylene dihalides and dichlorosilanes to form the corresponding 3-, 5-, and 6-membered ring derivatives.Significantly, these reactions are highly stereospecific and regioselective.
- Wu, Tse-Chong,Xiong, Heping,Rieke, R. D.
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p. 5045 - 5051
(2007/10/02)
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- Synthesis and Anticonvulsant Activity of 1-Phenylcyclohexylamine Analogues
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Thirty-eight analogues of 1-phenylcyclohexylamine (PCA), a phencyclidine (PCP) derivative, were examined for their activities in the mouse maximal electroshock (MES) seizure test and in a motor-toxicity assay.In addition, we determined the binding affinities of the compounds for PCP acceptor sites in rat brain membranes labeled with -1-piperidine.Many of the analogues were protective against MES seizures (ED50s of 4-41 mg/kg, ip) and all of these compounds caused motor toxicity.The potencies in the motor toxicity and MES seizure tests showed a moderate correlation with the affinities for PCP sites.Several analogues exhibited a greater separation of potencies in the motor toxicity and MES seizure tests than did the parent compound PCA.These were obtained by (i) 3-methylation of the cyclohexyl ring trans to the phenyl ring, (ii) methoxylation at the ortho position on the phenyl ring, and (iii) contraction of the cyclohexane ring to form the corresponding cyclopentane.
- Thurkauf, Andrew,Costa, Brian de,Yamaguchi, Shun-ichi,Mattson, Mariena V.,Jacobson, Arthur E.,et al.
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p. 1452 - 1458
(2007/10/02)
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- SYNTHESIS OF AROMATIC SESQUITERPENES, (+/-)-CUPARENE AND (+/-)-LAURENE BY MEANS OF AN INTRAMOLECULAR CARBENOID DISPLACEMENT (ICD) REACTION
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The synthesis of (+/-)-cuparene and (+/-)-laurene was accomplished by means of an intramolecular carbenoid displacement (ICD) reaction of the benzyl sulphide (12) as a key reaction.
- Kametani, Tetsuji,Kawamura, Kuniaki,Tsubuki, Masayoshi,Honda, Toshio
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p. 193 - 200
(2007/10/02)
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