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
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.
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
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
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.
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.
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.
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.