The Ryu Research Group, Department of Chemistry, Graduate School of Science, Osaka Prefecture University

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Published in 2017

Transition‐Metal‐Catalyst‐Free Cross‐Coupling Reaction of Secondary Propargylic Acetates with Alkenyl‐ and Arylboronic Acids
Mitsuhiro Ueda, Daiki Nakakoji, Takahiro Morisaki, Ilhyong Ryu
Eur JOC, 2017, 2017, 47 pp. 7040 - 7045
A cross‐coupling reaction between secondary propargylic acetates and alkenylboronic acids proceeded to give 1,4‐enynes in good yields without addition of transition metal catalyst and base. This simple protocol was also applicable to arylboronic acids, which gave 3‐arylated alkynes in good yields. The observed induction period suggested that the reaction of propargylic acetates and organoboronic acids was affected by the in‐situ generated AcOH as a catalyst, which was confirmed by a separate experiment.

Continuous Flow Synthesis Using Recyclable Reaction Media
Takahide Fukuyama, Akihiro Furuta, Ilhyong Ryu
Sustainable Flow Chemistry, 2017, , pp. -
DOI: 10.1002/9783527689118.ch2
This chapter focuses on the recent progress of micro flow synthesis combined with two greener reaction media, ionic liqs. and fluorous solvents, and discusses their potential in flow synthesis.

Organic Letters
Photocatalyzed Site-Selective C(sp3)–H Functionalization of Alkylpyridines at Non-Benzylic Positions
Takahide Fukuyama, Tomohiro Nishikawa, Keiichi Yamada, Davide Ravelli, Maurizio Fagnoni, Ilhyong Ryu
Org. Lett., 2017, 19, 23 pp. 6436 - 6439
DOI: 10.1021/acs.orglett.7b03339
201714                                                                                                                                 Tetrabutylammonium decatungstate (TBADT)-photocatalyzed C–H functionalization of alkylpyridines was investigated. Unlike alkylbenzene counterparts, alkylation of α-C–H bonds did not proceed for the reaction of 2- and 4-alkylpyridines and reluctantly proceeded for 3-alkylpyridines, which allow site-selective C(sp3)–H functionalization at nonbenzylic positions. The observed nonbenzylic site selectivities are rationalized by the polar inductive effects of pyridyl groups in the SH2 transition states. Consecutive γ-functionalization and α-bromofunctionalization were successfully carried out in selected cases.

Scalable Flow Synthesis of [6,6]-Phenyl-C61-butyric Acid Methyl Ester (PCBM) using a Flow Photoreactor with a Sodium Lamp
Mitsuhiro Ueda, Naoyuki Imai, Shunsuke Yoshida, Hiroshi Yasuda, Takahide Fukuyama, Ilhyong Ryu
European Journal of Organic Chemistry, 2017, 2017, 44 pp. 6483 - 6485
DOI: 10.1002/ejoc.201700745
201713                                                       An efficient flow system was constructed for the synthesis of [6,6]-phenyl-C61-butyric acid methyl ester (PCBM); the process involved flow [2+1] addition of C60 and subsequent flow photoisomerization of the resulting fulleroid to PCBM by using a flow photoreactor in combination with an Na lamp. With the present flow system, a scalable synthesis of PCBM (0.79 g/3.3 h) was achieved by continuous operation for 3.3 h.

Organic Letters
Bromoallylation of Alkenes Leading to 4-Alkenyl Bromides Based on Trapping of β-Bromoalkyl Radicals
Takashi Kippo, kanako Hamaoka, Mitsuhiro Ueda, Takahide Fukuyama, Ilhyong Ryu
Org. Lett., 2017, 19, 19 pp. 5198 - 5200
DOI: 10.1021/acs.orglett.7b02471
201712               A radical-chain addition of allyl bromides to aryl alkenes, vinyl ester, and vinyl phthalimide was studied in which elusive β-bromoalkyl radicals were trapped efficiently to give 5-bromo-1-pentenes in good to high yields (16 examples). A subsequent carbonylative radical cyclization with AIBN/Bu3SnH/CO was successful in giving the corresponding 3,5-disubstituted cyclohexanone derivatives in moderate yields. Synthesis of a piperidine ring was also successful by subsequent reaction with primary amine.

Ammonium chiral borate salt catalyzed asymmetric Friedel-Crafts alkylation of indoles with α,β-disubstituted enals
Mitsuhiro Ueda, Yoshitaka Yagyu, Ilhyong Ryu
Tetrahedron: Asymmetry, 2017, 28, 8 pp. 1070 - 1077
DOI: 10.1016/j.tetasy.2017.06.003
201701 In the presence of a catalytic amount of ammonium chiral borate salt, asymmetric Friedel-Crafts alkylation of indoles with α,β-disubstituted enals proceeded to give the corresponding 1,4-addition products with moderate enantioselectivities.

Efficient Flow Fischer Esterification of Carboxylic Acids with Alcohols Using Sulfonic Acid-Functionalized Silica as Supported Catalyst
Akihiro Furuta, Takahide Fukuyama, Ilhyong Ryu
Bulletin of the Chemical Society of Japan, 2017, 90, 5 pp. 607 - 612
DOI: 10.1246/bcsj.20170025

Flow Fischer esterification of carboxylic acids using hydroxy-substituted sulfonic acid-functionalized silica (HO-SAS) packed into a stainless steel column reactor was investigated. HO-SAS well catalyzed flow esterification of long chain carboxylic acids with methanol within 3 min of residence time at 110 °C, and the methyl esters were quantitatively obtained. The flow esterification protocol was applied to the synthesis of a variety of esters (19 examples) and scalable synthesis was also successful.

Bromine-Radical-Mediated Synthesis of β-Functionalized β,γ- and δ,ε-Unsaturated Ketones via C–H Functionalization of Aldehydes
Takashi Kippo, Yuki Kimura, Mitsuhiro Ueda, Takahide Fukuyama, Ilhyong Ryu
Synlett, 2017, 28, 14 pp. 1733 - 1737
DOI: 10.1055/s-0036-1588494

The bromine-radical-mediated allylation reaction of aldehydes was studied. In the presence of V-65 as radical initiator, the reaction of aldehydes with allyl bromides gave β,γ-unsaturated ketones in good yields (13 examples, 45–84%). The reaction is triggered by hydrogen abstraction from the aldehyde by bromine radical to form an acyl radical, which undergoes an SH2′-type addition–elimination reaction with allyl bromides to give coupling products with liberation of bromine radical. Three-component coupling reactions comprising aldehydes, electron-deficient alkenes, and methallyl bromide also proceeded to give δ,ε-unsaturated ketones.

Cobalt-catalyzed regioselective [3+2] annulation of ortho-formyl and acetyl substituted phenylboronic acids with alkynes
Mitsuhiro Ueda, Tamami Ueno, Yuki Suyama, Ilhyong Ryu
Tetrahedron Letters, 2017, 58, 30 pp. 2972 - 2974
DOI: 10.1016/j.tetlet.2017.06.049

Treatment of alkynes with ortho-formyl and acetyl phenylboronic acids in the presence of a cobalt catalyst resulted in the formation of 2,3-disubstituted indenols in good yields. When aryl silyl alkynes were used, 2-aryl-3-silyl indenols were obtained regioselectively in good yields.

Ionic liquids are not innocent in Pd catalysis. C–H arylation of thiazolium and imidazolium ionic liquids with aryl halides
Takahide Fukuyama, Taifur Md. Rahman, Hiroshi Mashima, Hideo Takahashi, Ilhyong Ryu
Org. Chem. Front., 2017, 4, 9 pp. 1863 - 1866
DOI: 10.1039/C7QO00331E

The ionic liquids bearing an aromatic vinylic C–H moiety are not innocent during Pd-catalyzed cross-coupling reactions of aryl halides, since palladium-catalyzed direct C–H arylation of thiazolium and imidazolium ionic liquids competes.

Cooperative Polar/Steric Strategy in Achieving Site-Selective Photocatalyzed C(sp3)−H Functionalization
Keiichi Yamada, Takahide Fukuyama, Saki Fujii, Davide Ravelli, Maurizio Fagnoni, Ilhyong Ryu
ChemEurJ, 2017, 23, 36 pp. 8615 - 8618
DOI: 10.1002/chem.201701865

Synergistic control over the SH2 transition states of hydrogen abstraction exploiting polar and steric effects provides a promising cooperative strategy for site-selective C(sp3)−H functionalization using decatungstate anion photocatalysis. By using this photocatalytic approach, the C−H bonds of substituted lactones and cyclic ketones were functionalized selectively. In the remarkable case of 2-isoamyl 4-tert-butyl cyclohexanone (1 t) bearing five methyl, five methylene, and three methine C−H bonds, one methine C−H bond in the isoamyl tether was selectively functionalized.

Photoredox-Catalyzed Hydrodifluoroalkylation of Alkenes Using Difluorohaloalkyl Compounds and a Hantzsch Ester
Shuhei Sumino, Misae Uno, Takahide Fukuyama, Ilhyong Ryu, Makoto Matsuura, Akinori Yamamoto, Yosuke Kishikawa
J. Org. Chem, 2017, 82, 10 pp. 5469 - 5474
DOI: 10.1021/acs.joc.7b00609

 Photoredox-catalyzed hydrodifluoroalkylation of alkenes proceeded smoothly in the presence of a Hantzsch ester as a hydrogen source under visible light irradiation. The reaction was also applicable to the hydrodifluoroalkylation of alkynes, and a continuous photo flow reaction was also successful.

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A Palladium/Light System Combined with Hanztsch Ester: Radical Vinylation of Alkyl Iodides with Vinyl Bromides
Shuhei Sumino, Ilhyong Ryu
Asian Journal of Organic Chemistry, 2017, 6, 4 pp. 410 - 413
DOI: 10.1002/ajoc.201600547

 Radical vinylation of alkyl iodides with vinyl bromides proceeds smoothly with a combined Pd/light/Hanztsch ester system. In this reaction system, the Hanztsch ester acts as an effective reducing reagent of PdII to Pd0 that generates key alkyl radicals via single electron transfer (SET) with alkyl iodides upon photo-excitation.

J. Org. Chem
Formal Total Synthesis of l-Ossamine via Decarboxylative Functionalization Using Visible-Light-Mediated Photoredox Catalysis in a Flow System
Shinsuke Inuki, Keisuke Sato, Takahide Fukuyama, Ilhyong Ryu, Yukari Fujimoto
J. Org. Chem, 2017, 82, 2 pp. 1248 - 1253
DOI: 10.1021/acs.joc.6b02531
A formal total synthesis of l-ossamine was achieved. The key feature of the synthesis was the decarboxylative functionalization of a threonine derivative using visible-light-mediated photoredox catalysis. This reaction was implemented in a flow reactor, allowing for the efficient conversion to the desired product.

Flow Dehydration and Hydrogenation of Allylic Alcohols: Application to the Waste-Free Synthesis of Pristane
Akihiro Furuta, Yuki Hirobe, Takahide Fukuyama, Ilhyong Ryu, Yoshiyuki Manabe, Koichi Fukase
European Journal of Organic Chemistry, 2017, 10, pp. 1365 - 1368
DOI: 10.1002/ejoc.201700072
Hydroxy-substituted sulfonic acid functionalized silica (HO-SAS) in combination with THF containing a small amount of water as a solvent proved to be a reliable system for the dehydration of allylic alcohols. This process generally caused dehydration within 1 min through a column reactor charged with HO-SAS. The flow dehydration was sequenced by flow hydrogenation, which resulted in the synthesis of pristane. A scalable flow synthesis of pristane was successfully performed and afforded 10 g of pristane after an operation of 2 h. We also performed dehydration and hydrogenation by using a mixed column of HO-SAS and 10 % Pd/C.

Versatile cross-dehydrogenative coupling of heteroaromatics and hydrogen donors via decatungstate photocatalysis
Matteo C. Quattrini, Saki Fujii, Keiichi Yamada, Takahide Fukuyama, Davide Ravelli, Maurizio Fagnoni, Ilhyong Ryu
Chem. Commun., 2017, 53, 15 pp. 2335 - 2338
DOI: 10.1039/C6CC09725A
 A facile sunlight-induced derivatization of heteroaromatics via photocatalyzed C–H functionalization in amides, ethers, alkanes and aldehydes is described. Tetrabutylammonium decatungstate (TBADT) was used as the photocatalyst and allowed to carry out the process under mild conditions.



Laboratory for Advanced Organic Synthesis
Organization for Research Promotion Osaka Prefecture University
Sakai, Osaka 599-8531, JAPAN
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