Ilhyong Ryu

Find an error

Name: Ilhyong Ryu

Organization: Osaka Prefecture University

Department: Department of Chemistry

Title:

Chemicals
References

Bromoallylation of Alkenes Leading to 4-Alkenyl Bromides Based on Trapping of β-Bromoalkyl Radicals

Co-reporter:Takashi Kippo, Kanako Hamaoka, Mitsuhiro Ueda, Takahide Fukuyama, and Ilhyong Ryu

Organic Letters October 6, 2017 Volume 19(Issue 19) pp:

Publication Date(Web):September 25, 2017

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.

Photoredox-Catalyzed Hydrodifluoroalkylation of Alkenes Using Difluorohaloalkyl Compounds and a Hantzsch Ester

Co-reporter:Shuhei Sumino, Misae Uno, Takahide Fukuyama, Ilhyong Ryu, Makoto Matsuura, Akinori Yamamoto, and Yosuke Kishikawa

The Journal of Organic Chemistry May 19, 2017 Volume 82(Issue 10) pp:5469-5469

Publication Date(Web):May 5, 2017

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.

Photocatalyzed Site-Selective C(sp3)–H Functionalization of Alkylpyridines at Non-Benzylic Positions

Co-reporter:Takahide Fukuyama, Tomohiro Nishikawa, Keiichi Yamada, Davide Ravelli, Maurizio Fagnoni, and Ilhyong Ryu

Organic Letters December 1, 2017 Volume 19(Issue 23) pp:6436-6436

Publication Date(Web):November 20, 2017

DOI:10.1021/acs.orglett.7b03339

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.

Versatile cross-dehydrogenative coupling of heteroaromatics and hydrogen donors via decatungstate photocatalysis

Co-reporter:Matteo C. Quattrini;Saki Fujii;Keiichi Yamada;Takahide Fukuyama;Davide Ravelli;Maurizio Fagnoni

Chemical Communications 2017 vol. 53(Issue 15) pp:2335-2338

Publication Date(Web):2017/02/16

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.

Ionic liquids are not innocent in Pd catalysis. C–H arylation of thiazolium and imidazolium ionic liquids with aryl halides

Co-reporter:Takahide Fukuyama;Md. Taifur Rahman;Hiroshi Mashima;Hideo Takahashi

Organic Chemistry Frontiers 2017 vol. 4(Issue 9) pp:1863-1866

Publication Date(Web):2017/08/22

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.

Flow Update for a Cossy Photocyclization

Co-reporter:Takahide Fukuyama, Yuki Fujita, Muhammad Abid Rashid, and Ilhyong Ryu

Organic Letters 2016 Volume 18(Issue 20) pp:5444-5446

Publication Date(Web):October 13, 2016

DOI:10.1021/acs.orglett.6b02727

A Cossy 5-exo-dig photocyclization of organohalides (X = Br, I) onto a C–C triple bond was studied using a flow photomicroreactor, which proceeded in a minute order of residence time. A deuterium labeling study supported the nonchain radical mechanism proposed by the Cossy group, in which a hydrogen source originates from a triethylamine cation radical. Scalable flow synthesis using a larger volume of flow reactor was also successful, providing 4 g of the product in high yield.

Hydroalkylation of Alkenes Using Alkyl Iodides and Hantzsch Ester under Palladium/Light System

Co-reporter:Shuhei Sumino and Ilhyong Ryu

Organic Letters 2016 Volume 18(Issue 1) pp:52-55

Publication Date(Web):December 21, 2015

DOI:10.1021/acs.orglett.5b03238

The hydroalkylation of alkenes using alkyl iodides with Hantzsch ester as a hydrogen source occurred smoothly under a Pd/light system, in a novel, tin-free Giese reaction. A chemoselective reaction at C(sp3)–I in the presence of a C(sp2)–X (X = Br or I) bond was attained, which allowed for the stepwise functionalization of two types of C–X bonds in a one-pot procedure.

Radical bromoallylation of alkynes leading to 1-bromo-1,4-dienes

Co-reporter:Takashi Kippo, Kanako Hamaoka, Mitsuhiro Ueda, Takahide Fukuyama, Ilhyong Ryu

Tetrahedron 2016 Volume 72(Issue 48) pp:7866-7874

Publication Date(Web):1 December 2016

DOI:10.1016/j.tet.2016.05.084

The full scope (30 examples) of the radical bromoallylation of alkynes using allyl bromides was studied. In this reaction, bromine radical adds to alkynes to form vinyl radicals, which then undergo an SH2′ reaction with allyl bromides to produce good yields of 1-bromo-1,4-dienes with the liberation of a bromine radical, which creates a radical chain. The sp2-carbon–bromine bond of the product dienes was further functionalized via cross-coupling and carbonylation reactions.

Carbonylative Mizoroki–Heck Reaction of Alkyl Iodides with Arylalkenes Using a Pd/Photoirradiation System

Co-reporter:Shuhei Sumino, Takahito Ui, Yuki Hamada, Takahide Fukuyama, and Ilhyong Ryu

Organic Letters 2015 Volume 17(Issue 20) pp:4952-4955

Publication Date(Web):October 6, 2015

DOI:10.1021/acs.orglett.5b02302

A carbonylative Mizoroki–Heck reaction using alkyl iodides was achieved with a Pd/photoirradiation system using DBU as a base. In this reaction, alkyl radicals were formed from alkyl iodides via single-electron transfer (SET) and then underwent a sequential addition to CO and alkenes to give β-keto radicals. It is proposed that DBU would abstract a proton α to carbonyl to form radical anions, giving α,β-unsaturated ketones via SET.

Photocatalyzed Site-Selective C–H to C–C Conversion of Aliphatic Nitriles

Co-reporter:Keiichi Yamada, Megumi Okada, Takahide Fukuyama, Davide Ravelli, Maurizio Fagnoni, and Ilhyong Ryu

Organic Letters 2015 Volume 17(Issue 5) pp:1292-1295

Publication Date(Web):February 18, 2015

DOI:10.1021/acs.orglett.5b00282

β- or γ-Site-selective C–H alkylation of aliphatic nitriles has been achieved using a decatungstate salt as the photocatalyst. The observed site selectivity was justified by a radical polar effect in transition states for hydrogen abstraction.

Photocatalytic One-Pot Synthesis of Homoallyl Ketones via a Norrish Type I Reaction of Cyclopentanones

Co-reporter:Megumi Okada, Keiichi Yamada, Takahide Fukuyama, Davide Ravelli, Maurizio Fagnoni, and Ilhyong Ryu

The Journal of Organic Chemistry 2015 Volume 80(Issue 18) pp:9365-9369

Publication Date(Web):August 28, 2015

DOI:10.1021/acs.joc.5b01850

A photocatalytic synthesis of homoallyl ketones was achieved via a one-pot procedure starting from a Norrish Type I reaction of cyclopentanones, followed by a decatungstate-catalyzed hydroacylation of electron-deficient olefins by the resulting 4-pentenals. The site-selective formyl H-abstraction in the second step can be explained by radical polar effects in the transition state.

Photoinduced Aminocarbonylation of Aryl Iodides

Co-reporter:Dr. Takuji Kawamoto;Aoi Sato ;Dr. Ilhyong Ryu

Chemistry - A European Journal 2015 Volume 21( Issue 42) pp:14764-14767

Publication Date(Web):

DOI:10.1002/chem.201503164

Abstract

Transition metal-catalyzed aminocarbonylation of aryl halides with CO and amines, pioneered by Heck and co-workers in the 1970s, is among the most commonly employed reactions to make aromatic amides. A catalyst-free aminocarbonylation of aryl iodides with CO and amines, which simply uses photoirradiation conditions by Xe-lamp, has now been developed. This methodology shows broad functional-group tolerance, including that of heteroaromatic amides. A hybrid radical/ionic chain mechanism, involving electron transfer from zwitterionic radical intermediates generated by nucleophilic attack of amines to aroyl radicals, is proposed.

Carbonylation Reactions of Alkyl Iodides through the Interplay of Carbon Radicals and Pd Catalysts

Co-reporter:Shuhei Sumino, Akira Fusano, Takahide Fukuyama, and Ilhyong Ryu

Accounts of Chemical Research 2014 Volume 47(Issue 5) pp:1563

Publication Date(Web):April 8, 2014

DOI:10.1021/ar500035q

Numerous methods for transition metal catalyzed carbonylation reactions have been established. Examples that start from aryl, vinyl, allyl, and benzyl halides to give the corresponding carboxylic acid derivatives have all been well documented. In contrast, the corresponding alkyl halides often encounter difficulty. This is inherent to the relatively slow oxidative addition step onto the metal center and subsequent β-hydride elimination which causes isomerization of the alkyl metal species. Radical carbonylation reactions can override such problems of reactivity; however, carbonylation coupled to iodine atom transfer (atom transfer carbonylation), though useful, often suffers from a slow iodine atom transfer step that affects the outcome of the reaction. We found that atom transfer carbonylation of primary, secondary, and tertiary alkyl iodides was efficiently accelerated by the addition of a palladium catalyst under light irradiation. Stereochemical studies support a mechanistic pathway based on the synergic interplay of radical and Pd-catalyzed reaction steps which ultimately lead to an acylpalladium species. The radical/Pd-combined reaction system has a wide range of applications, including the synthesis of carboxylic acid esters, lactones, amides, lactams, and unsymmetrical ketones such as alkyl alkynyl and alkyl aryl ketones. The design of unique multicomponent carbonylation reactions involving vicinal C-functionalization of alkenes, double and triple carbonylation reactions, in tandem with radical cyclization reactions, has also been achieved. Thus, the radical/Pd-combined strategy provides a solution to a longstanding problem of reactivity involving the carbonylation of alkyl halides. This novel methodology expands the breadth and utility of carbonylation chemistry over either the original radical carbonylation reactions or metal-catalyzed carbonylation reactions.

Carbonylation in microflow: close encounters of CO and reactive species

Co-reporter:Takahide Fukuyama, Takenori Totoki and Ilhyong Ryu

Green Chemistry 2014 vol. 16(Issue 4) pp:2042-2050

Publication Date(Web):13 Dec 2013

DOI:10.1039/C3GC41789A

Microreactors have brought significant improvements to chemical synthesis and production because of their advantageous characteristics over batch reactors, which include highly efficient mixing, efficient heat and mass transfer ability, precise control of the residence time, large surface area-to-volume ratio and high operational safety. Microreactor technology has been found to be beneficial for gas–liquid biphasic reactions, for which the large interfacial area between the two phases is ensured. Carbonylation reactions with carbon monoxide, by which a wide range of carbonyl compounds can be prepared, deal with a variety of reactive species, such as organo transition metals, radicals, cations and anions. These reactions have long been carried out using a glass batch flask or a stainless-steel made autoclave, however, carbonylation reactions using a flow microreactor are now rapidly increasing in popularity. This review focuses on a new greener wave of carbonylation reactions using a flow microreactor.

Sunlight photocatalyzed regioselective β-alkylation and acylation of cyclopentanones

Co-reporter:Megumi Okada, Takahide Fukuyama, Keiichi Yamada, Ilhyong Ryu, Davide Ravelli and Maurizio Fagnoni

Chemical Science 2014 vol. 5(Issue 7) pp:2893-2898

Publication Date(Web):08 May 2014

DOI:10.1039/C4SC01072H

Sunlight-induced direct regioselective β-alkylation of cyclopentanones with electron-deficient alkenes was accomplished by using tetrabutylammonium decatungstate (TBADT) as the catalyst. The regiochemistry can be rationalized by a polar transition state for an SH2 reaction. In the presence of CO, the reaction gave the three-component β-acylation product in good yield.

Flow Update for the Carbonylation of 1-Silyl-Substituted Organolithiums under CO Pressure

Co-reporter:Takahide Fukuyama, Takenori Totoki, and Ilhyong Ryu

Organic Letters 2014 Volume 16(Issue 21) pp:5632-5635

Publication Date(Web):October 16, 2014

DOI:10.1021/ol5026958

The generation of, and subsequent reactions with, 1-silyl-substituted organolithiums with CO was carried out using serially connected flow microreactors. The flow system proved to be quite useful for the carbonylation of silyl-substituted organolithiums under slightly pressurized conditions of CO, which was created conveniently by the use of a back-pressure regulator. This flow system, coupled with heating, accelerated the carbonylation reaction of 1-silyl-substituted organolithiums and allowed the stable silyl-substituted alkyllithium, 1,3-disilylallyllithium, which was not effective in a batch-flask reaction under a CO atmosphere, to participate in an efficient carbonylation reaction.

Synthesis of Fluorenones through Rhodium-Catalyzed Intramolecular Acylation of Biarylcarboxylic Acids

Co-reporter:Takahide Fukuyama, Shinji Maetani, Kazusa Miyagawa, and Ilhyong Ryu

Organic Letters 2014 Volume 16(Issue 12) pp:3216-3219

Publication Date(Web):June 9, 2014

DOI:10.1021/ol5012407

An efficient approach to the synthesis of fluorenones via the rhodium-catalyzed intramolecular acylation of biarylcarboxylic acids was developed. Using this procedure, fluorenones with various substituents can be synthesized in good to high yields. This work marks the first recorded use of catalytic intramolecular acylation to synthesize fluorenones.

Cyanoborohydride-Promoted Radical Arylation of Benzene

Co-reporter:Takuji Kawamoto, Aoi Sato, and Ilhyong Ryu

Organic Letters 2014 Volume 16(Issue 8) pp:2111-2113

Publication Date(Web):April 3, 2014

DOI:10.1021/ol500614q

Radical biaryl coupling of iodoarenes and benzene can be effectively promoted by tetrabutylammonium cyanoborohydride with air under photoirradiation conditions using a Xe lamp. The utility of this methodology is highlighted by its functional group tolerance and chemoselectivity.

A bromine-radical mediated three-component reaction comprising allenes, electron-deficient alkenes and allyl bromides: facile synthesis of 2-bromo-1,7-dienes

Co-reporter:Takashi Kippo and Ilhyong Ryu

Chemical Communications 2014 vol. 50(Issue 45) pp:5993-5996

Publication Date(Web):16 Apr 2014

DOI:10.1039/C4CC01597E

A bromine-radical mediated three-component coupling reaction was effectively achieved by the use of allenes, electron-deficient alkenes, and allyl bromides and led to the synthesis of 2-bromo-1,7-dienes in good to high yields. This protocol was extended to the three-component process using alkylidenecyclopropane, which gave 2-bromo-1,8-diene along with alkylidenecyclopentane.

Radical reactions of borohydrides

Co-reporter:Takuji Kawamoto and Ilhyong Ryu

Organic & Biomolecular Chemistry 2014 vol. 12(Issue 48) pp:9733-9742

Publication Date(Web):01 Oct 2014

DOI:10.1039/C4OB01784F

Borohydrides are an important class of reagents in both organic and inorganic chemistry. Though popular as hydride-transfer reagents for reduction, since earlier work from the 1970s, borohydride reagents have also been known to serve as hydrogen-transfer reagents. In pursuit of greener tin hydride substitutes, recent progress has been made to mediate radical C–C bond forming reactions, including Giese reactions, radical carbonylation and addition to HCHO reactions, with borohydride reagents. This review article focuses on state-of-the-art borohydride based radical reactions, also covering earlier work, kinetics and some DFT calculations with respect to the hydrogen transfer mechanism.

Revisiting the Bromination of CH Bonds with Molecular Bromine by Using a Photo-Microflow System

Co-reporter:Dr. Yoshiyuki Manabe;Yuriko Kitawaki;Masahiro Nagasaki; Koichi Fukase; Hiroshi Matsubara;Yoshiko Hino; Takahide Fukuyama; Ilhyong Ryu

Chemistry - A European Journal 2014 Volume 20( Issue 40) pp:12750-12753

Publication Date(Web):

DOI:10.1002/chem.201402303

Abstract

The photobromination of CH bonds by using molecular bromine was reinvestigated under microfluidic conditions. The continuous-flow method suppressed the production of dibrominated compounds and effectively produced the desired monobrominated products with high selectivity. Rapid bromination of benzylic substrates containing a photoaffinity azide group was achieved without any decomposition.

Borohydride-Mediated Radical Addition Reactions of Organic Iodides to Electron-Deficient Alkenes

Co-reporter:Takuji Kawamoto, Shohei Uehara, Hidefumi Hirao, Takahide Fukuyama, Hiroshi Matsubara, and Ilhyong Ryu

The Journal of Organic Chemistry 2014 Volume 79(Issue 9) pp:3999-4007

Publication Date(Web):April 9, 2014

DOI:10.1021/jo500464q

Cyanoborohydrides are efficient reagents in the reductive addition reactions of alkyl iodides and electron-deficient olefins. In contrast to using tin reagents, the reaction took place chemoselectively at the carbon–iodine bond but not at the carbon–bromine or carbon–chlorine bond. The reaction system was successfully applied to three-component reactions, including radical carbonylation. The rate constant for the hydrogen abstraction of a primary alkyl radical from tetrabutylammonium cyanoborohydride was estimated to be <1 × 104 M–1 s–1 at 25 °C by a kinetic competition method. This value is 3 orders of magnitude smaller than that of tributyltin hydride.

Free-Radical-Mediated [2 + 2 + 1] Cycloaddition of Acetylenes, Amidines, and CO Leading to Five-Membered α,β-Unsaturated Lactams

Co-reporter:Takahide Fukuyama ; Nao Nakashima ; Takuma Okada

Journal of the American Chemical Society 2013 Volume 135(Issue 3) pp:1006-1008

Publication Date(Web):January 11, 2013

DOI:10.1021/ja312654q

A free-radical-mediated [2 + 2 + 1] cycloaddition reaction comprising acetylenes, amidines, and CO was achieved by radical chain reaction to give five-membered α,β-unsaturated lactams in good yields. Both acyclic and cyclic amidines reacted with a variety of terminal acetylenes to afford monocyclic, bicyclic, and tricyclic lactams. We propose that vinyl radical carbonylation and nucleophilic addition of the amidine onto the resulting α-ketenyl radical give stable intermediates that are ready to undergo five-membered ring closure with elimination of tin radical.

Efficient C–H/C–N and C–H/C–CO–N Conversion via Decatungstate-Photoinduced Alkylation of Diisopropyl Azodicarboxylate

Co-reporter:Ilhyong Ryu, Akihiro Tani, Takahide Fukuyama, Davide Ravelli, Sara Montanaro, and Maurizio Fagnoni

Organic Letters 2013 Volume 15(Issue 10) pp:2554-2557

Publication Date(Web):May 7, 2013

DOI:10.1021/ol401061v

Tetrabutylammonium decatungstate (TBADT) accelerated the addition of C–H bonds to the N═N double bond of diisopropyl azodicarboxylate (DIAD) under irradiation conditions. The photoinduced three-component coupling between cyclic alkanes, CO, and DIAD was also achieved to give the corresponding acyl hydrazides.

Modernized Low Pressure Carbonylation Methods in Batch and Flow Employing Common Acids as a CO Source

Co-reporter:Célia Brancour, Takahide Fukuyama, Yu Mukai, Troels Skrydstrup, and Ilhyong Ryu

Organic Letters 2013 Volume 15(Issue 11) pp:2794-2797

Publication Date(Web):May 22, 2013

DOI:10.1021/ol401092a

Carbonylation reactions, such as Heck, Sonogashira, and radical carbonylations, were successfully carried out in a “two-chamber reactor” where carbon monoxide was produced ex situ by the Morgan reaction (dehydration of formic acid by sulfuric acid). By a subsequent application in a microflow system using a “tube-in-tube” reactor where gas-permeable Teflon AF2400 was used as the inner tube, it is demonstrated that formic acid/sulfuric acid can be employed concomitantly with an amine base such as triethylamine in the Heck aminocarbonylation of aryl iodide.

Rhodium-Catalyzed Decarbonylative C–H Arylation of 2-Aryloxybenzoic Acids Leading to Dibenzofuran Derivatives

Co-reporter:Shinji Maetani, Takahide Fukuyama, and Ilhyong Ryu

Organic Letters 2013 Volume 15(Issue 11) pp:2754-2757

Publication Date(Web):May 16, 2013

DOI:10.1021/ol4010905

Rhodium-catalyzed intramolecular C–H arylation of 2-aryloxybenzoic acids proceeded accompanied by decarbonylation to give dibenzofuran derivatives in high yields. The present reaction is widely applicable to substrates bearing various functionalities.

Synthesis of Alkyl Aryl Ketones by Pd/Light Induced Carbonylative Cross-Coupling of Alkyl Iodides and Arylboronic Acids

Co-reporter:Shuhei Sumino, Takahito Ui, and Ilhyong Ryu

Organic Letters 2013 Volume 15(Issue 12) pp:3142-3145

Publication Date(Web):June 3, 2013

DOI:10.1021/ol401363t

Alkyl aryl ketones were synthesized by the carbonylative cross-coupling reaction of alkyl iodides and arylboronic acids under combined Pd/light conditions. In this reaction, it is likely that an acylpalladium species would be formed via carbonylation of the alkyl radical, which would then undergo transmetalation of an arylboronic acid to give the corresponding acyl(aryl)palladium species, ready to undergo reductive elimination to yield the alkyl aryl ketone.

Reductive Bromine Atom-Transfer Reaction

Co-reporter:Shuhei Sumino, Akira Fusano, and Ilhyong Ryu

Organic Letters 2013 Volume 15(Issue 11) pp:2826-2829

Publication Date(Web):May 22, 2013

DOI:10.1021/ol4011536

Atom-transfer radical (ATR) reactions of alkenes with R–X usually give products having new C–C and C–X bonds at the adjacent carbons. However, when the reaction was carried out under irradiation using a low-pressure Hg lamp, addition/reduction products were obtained in good yield. Hydrogen bromide, formed by H-abstraction of a bromine radical from alkenes, is likely to play a key role in the reductive ATR reaction.

Ruthenium hydride/nitrogen tridentate ligand-catalyzed α-alkylation of acetamides with primary alcohols

Co-reporter:Takashi Kuwahara, Takahide Fukuyama and Ilhyong Ryu

RSC Advances 2013 vol. 3(Issue 33) pp:13702-13704

Publication Date(Web):24 Jun 2013

DOI:10.1039/C3RA42834F

The α-alkylation reaction of acetamides with primary alcohols to afford the corresponding amides was accomplished effectively using RuHCl(CO)(PPh3)3 as a catalyst, nitrogen tridentate ligand L1 as an additive, and KOtBu as a base. While the addition of bpy was effective only for benzylic alcohols, L1 affected the alkylation reaction when both benzylic and non-benzylic type alcohols were used.

Bromine Radical-Mediated Sequential Radical Rearrangement and Addition Reaction of Alkylidenecyclopropanes

Co-reporter:Takashi Kippo ; Kanako Hamaoka

Journal of the American Chemical Society 2012 Volume 135(Issue 2) pp:632-635

Publication Date(Web):December 26, 2012

DOI:10.1021/ja311821h

Bromine radical-mediated cyclopropylcarbinyl-homoallyl rearrangement of alkylidenecyclopropanes was effectively accomplished by C–C bond formation with allylic bromides, which led to the syntheses of 2-bromo-1,6-dienes. A three-component coupling reaction comprising alkylidenecyclopropanes, allylic bromides, and carbon monoxide also proceeded well to give 2-bromo-1,7-dien-5-ones in good yield.

RuHCl(CO)(PPh3)3-Catalyzed α-Alkylation of Ketones with Primary Alcohols

Co-reporter:Takashi Kuwahara, Takahide Fukuyama, and Ilhyong Ryu

Organic Letters 2012 Volume 14(Issue 18) pp:4703-4705

Publication Date(Web):August 29, 2012

DOI:10.1021/ol302145a

The α-alkylation reaction of ketones with primary alcohols to give α-alkylated ketones was achieved using RuHCl(CO)(PPh3)3 as a catalyst in the presence of Cs2CO3 as a base. This reaction proceeds via an aldol condensation of ketones with aldehydes, formed via transfer dehydrogenation of alcohols, to give α,β-unsaturated ketones, which then undergo transfer hydrogenation with primary alcohols to give α-alkylated ketones and aldehydes, the latter of which participate in the next catalytic cycle. While the reaction of aliphatic primary alcohols was sluggish compared with that of benzylic alcohols, a catalytic amount of 1,10-phenanthroline was found to promote the alkylation dramatically.

Iron-catalyzed decarbonylation reaction of aliphatic carboxylic acids leading to α-olefins

Co-reporter:Shinji Maetani, Takahide Fukuyama, Nobuyoshi Suzuki, Daisuke Ishihara and Ilhyong Ryu

Chemical Communications 2012 vol. 48(Issue 19) pp:2552-2554

Publication Date(Web):10 Jan 2012

DOI:10.1039/C2CC18093F

The catalytic decarbonylation reaction of aliphatic carboxylic acids can be carried out in the presence of an iron complex, and it proceeds smoothly to give α-olefins with high selectivity.

Rh-Catalyzed [5+1] and [4+1] Cycloaddition Reactions of 1,4-Enyne Esters with CO: A Shortcut to Functionalized Resorcinols and Cyclopentenones

Co-reporter: Takahide Fukuyama;Yuko Ohta;Dr. Célia Brancour;Kazusa Miyagawa; Ilhyong Ryu;Dr. Anne-Lise Dhimane; Louis Fensterbank; Max Malacria

Chemistry - A European Journal 2012 Volume 18( Issue 23) pp:7243-7247

Publication Date(Web):

DOI:10.1002/chem.201200045

Abstract

We have developed novel Rh-catalyzed [n+1]-type cycloadditions of 1,4-enyne esters, which involve an acyloxy migration as a key step. The efficient preparation of functionalized resorcinols, including biaryl derivatives, from readily available 1,4-enyne esters and CO was achieved by Rh-catalyzed [5+1] cycloaddition accompanied by 1,2-acyloxy migration. When enyne esters had an internal alkyne moiety, the reaction proceeded by a [4+1]-type cycloaddition involving 1,3-acyloxy migration, leading to cyclopentenones.

Pd/Light-Accelerated Atom-Transfer Carbonylation of Alkyl Iodides: Applications in Multicomponent Coupling Processes Leading to Functionalized Carboxylic Acid Derivatives

Co-reporter:Dr. Akira Fusano;Shuhei Sumino;Satoshi Nishitani;Takaya Inouye;Keisuke Morimoto;Dr. Takahide Fukuyama ; Ilhyong Ryu

Chemistry - A European Journal 2012 Volume 18( Issue 30) pp:9415-9422

Publication Date(Web):

DOI:10.1002/chem.201200752

Abstract

The atom-transfer carbonylation reaction of various alkyl iodides thereby leading to carboxylic acid esters was effectively accelerated by the addition of transition-metal catalysts under photoirradiation conditions. By using a combined Pd/hν reaction system, vicinal C-functionalization of alkenes was attained in which α-substituted iodoalkanes, alkenes, carbon monoxide, and alcohols were coupled to give functionalized esters. When alkenyl alcohols were used as acceptor alkenes, three-component coupling reactions, which were accompanied by intramolecular esterification, proceeded to give lactones. Pd-dimer complex [Pd₂(CNMe)₆][PF₆]₂, which is known to undergo homolysis under photoirradiation conditions, worked quite well as a catalyst in these three- or four-component coupling reactions. In this metal/radical hybrid system, both Pd radicals and acyl radicals are key players and a stereochemical study confirmed the carbonylation step proceeded through a radical carbonylation mechanism.

Radical Addition of Alkyl Halides to Formaldehyde in the Presence of Cyanoborohydride as a Radical Mediator. A New Protocol for Hydroxymethylation Reaction

Co-reporter:Takuji Kawamoto ; Takahide Fukuyama

Journal of the American Chemical Society 2011 Volume 134(Issue 2) pp:875-877

Publication Date(Web):December 20, 2011

DOI:10.1021/ja210585n

Hydroxymethylation of alkyl halides was achieved using paraformaldehyde as a radical C1 synthon in the presence of tetrabutylammonium cyanoborohydride as a hydrogen source. The reaction proceeds via a radical chain mechanism involving an alkyl radical addition to formaldehyde to form an alkoxy radical, which abstracts hydrogen from a hydroborate anion.

Radical carbonylation of ω-alkynylamines leading to α-methylene lactams. Synthetic scope and the mechanistic insights

Co-reporter:Ilhyong Ryu, Takahide Fukuyama, Mami Tojino, Yoshitaka Uenoyama, Yuka Yonamine, Nozomi Terasoma and Hiroshi Matsubara

Organic & Biomolecular Chemistry 2011 vol. 9(Issue 10) pp:3780-3786

Publication Date(Web):23 Mar 2011

DOI:10.1039/C1OB05145H

Tin hydride mediated radical carbonylation and cyclization reaction was investigated using a variety of ω-alkynyl amines as substrates. In this reaction α-methylene and α-stannylmethylene lactams having five to eight membered rings were obtained as principal products. In cases where the nitrogen has a substituent capable of giving stable radicals, such as an α-phenethyl group, the lactam ring formation again took place with extrusion of an α-phenethyl radical. Coupled with the subsequent protodestannylation procedure (TMSCl plus MeOH), these reactions provide a useful entry to α-methylene lactams with incorporation of CO as a lactam carbonyl group. In cases where the amines do not have a substituent acting as a radical leaving group, a reaction course involving a 1,4-H shift is chosen so as to liberate tin radicals ultimately. Thus the proposed mechanism involves (i) nucleophilic attack of amine nitrogen onto a carbonyl group of α,β-unsaturated acyl radicals/α-ketenyl radicals via lone pair–π* interaction, which leads to zwitterionic radical species, (ii) the subsequent proton shift from N to O to give hydroxyallyl radicals, (iii) 1,4-hydrogen shift from O to C, and (iv) β-scission to give lactams with liberation of tin radicals. DFT calculations reveal that the 1,4-hydrogen shifts, the key step of the reaction mechanism, can proceed under usual reaction conditions. On the other hand, an SHi type reaction to give lactams may be the result of the β-scission of the similar zwitterionic radical intermediates. DFT calculations also predict that an SHi type reaction would result when the intermediate has a good (radical) leaving group such as a phenethyl group.

Efficient Iridium-Catalyzed Decarbonylation Reaction of Aliphatic Carboxylic Acids Leading to Internal or Terminal Alkenes

Co-reporter:Shinji Maetani, Takahide Fukuyama, Nobuyoshi Suzuki, Daisuke Ishihara, and Ilhyong Ryu

Organometallics 2011 Volume 30(Issue 6) pp:1389-1394

Publication Date(Web):February 22, 2011

DOI:10.1021/om1009268

Vaska’s complex, IrCl(CO)(PPh3)2, when combined with KI as an additive, served as an excellent catalyst for the decarbonylation of long-chain aliphatic carboxylic acids to give internal alkenes with high selectivity. On combination with KI and Ac2O as additives under controlled temperatures, decarbonylation proceeded to give terminal alkenes with high selectivity.

Atom-Economical Synthesis of Unsymmetrical Ketones through Photocatalyzed CH Activation of Alkanes and Coupling with CO and Electrophilic Alkenes

Co-reporter: Ilhyong Ryu;Akihiro Tani;Dr. Takahide Fukuyama;Davide Ravelli; Maurizio Fagnoni; Angelo Albini

Angewandte Chemie 2011 Volume 123( Issue 8) pp:1909-1912

Publication Date(Web):

DOI:10.1002/ange.201004854

Atom-Economical Synthesis of Unsymmetrical Ketones through Photocatalyzed CH Activation of Alkanes and Coupling with CO and Electrophilic Alkenes

Co-reporter: Ilhyong Ryu;Akihiro Tani;Dr. Takahide Fukuyama;Davide Ravelli; Maurizio Fagnoni; Angelo Albini

Angewandte Chemie International Edition 2011 Volume 50( Issue 8) pp:1869-1872

Publication Date(Web):

DOI:10.1002/anie.201004854

Synthesis of Alkyl Alkynyl Ketones by Pd/Light-Induced Three-Component Coupling Reactions of Iodoalkanes, CO, and 1-Alkynes

Co-reporter:Akira Fusano, Takahide Fukuyama, Satoshi Nishitani, Takaya Inouye and Ilhyong Ryu

Organic Letters 2010 Volume 12(Issue 10) pp:2410-2413

Publication Date(Web):April 21, 2010

DOI:10.1021/ol1007668

Under photoirradiation conditions using xenon light, in the presence of a catalytic amount of PdCl2(PPh3)2 with triethylamine as a base, a three-component coupling reaction of iodoalkanes, carbon monoxide, and terminal alkynes proceeded to give alkyl alkynyl ketones in good yields.

Black-Light-Induced Radical/Ionic Hydroxymethylation of Alkyl Iodides with Atmospheric CO in the Presence of Tetrabutylammonium Borohydride

Co-reporter:Shoji Kobayashi, Takuji Kawamoto, Shohei Uehara, Takahide Fukuyama and Ilhyong Ryu

Organic Letters 2010 Volume 12(Issue 7) pp:1548-1551

Publication Date(Web):March 3, 2010

DOI:10.1021/ol1002847

Tin-free radical/ionic hydroxymethylation of secondary and tertiary alkyl iodides proceeded efficiently in the presence of tetrabutylammonium borohydride as the hydrogen source under atmospheric pressure of CO in conjunction with photoirradiation using black light. Two possible mechanisms were proposed, both of which involve hybrid radical/ionic processes.

Synthesis of 2-Hydroxymethyl Ketones by Ruthenium Hydride-Catalyzed Cross-Coupling Reaction of α,β-Unsaturated Aldehydes with Primary Alcohols

Co-reporter:Aurélien Denichoux, Takahide Fukuyama, Takashi Doi, Jiro Horiguchi and Ilhyong Ryu

Organic Letters 2010 Volume 12(Issue 1) pp:1-3

Publication Date(Web):November 25, 2009

DOI:10.1021/ol902289r

The cross-coupling reaction of α,β-unsaturated aldehydes with primary alcohols to give 2-hydroxymethyl ketones was achieved using RuHCl(CO)(PPh3)3 as a catalyst. This atom-economical reaction is likely to proceed via the hydroruthenation of α,β-unsaturated aldehydes followed by an aldol reaction of the resultant enolates with aldehydes to give α-formylated ketones, which undergo transfer hydrogenation with primary alcohols leading to α-hydroxymethyl ketones. The reduction step can generate aldehydes, participating in the next catalytic cycle.

Regioselective Synthesis of 1-Bromo-1,4-dienes by Free-Radical-Mediated Bromoallylation of Activated Acetylenes

Co-reporter:Takashi Kippo, Takahide Fukuyama, and Ilhyong Ryu

Organic Letters 2010 Volume 12(Issue 18) pp:4006-4009

Publication Date(Web):August 16, 2010

DOI:10.1021/ol1016096

The free-radical-mediated bromoallylation of acetylenes proceeded efficiently in the presence of V-65 (2,2-azobis(2,4-dimethylvaleronitrile)) as the radical initiator. The regioselective reaction, which yields 1-bromo-2-substituted 1,4-dienes, is complementary to the Pd-catalyzed bromoallylation reaction previously reported by Kaneda. The products of the free-radical-mediated bromoallylation of acetylenes could be converted into a variety of substituted dienes by subsequent Pd-catalyzed reactions.

Hydroruthenation triggered catalytic conversion of dialdehydes and keto aldehydes to lactones

Co-reporter:Sohei Omura, Takahide Fukuyama, Yuji Murakami, Hiromi Okamoto and Ilhyong Ryu

Chemical Communications 2009 (Issue 44) pp:6741-6743

Publication Date(Web):19 Oct 2009

DOI:10.1039/B912850F

Lactonization of dialdehydes and keto aldehydes was effectively catalyzed by RuHCl(CO)(PPh3)3. A cascade lactonization sequence accompanied by cross-coupling with enones was also attained.

Microflow Radical Carboaminoxylations with a Novel Alkoxyamine

Co-reporter:Inga C. Wienhöfer, Armido Studer, Md. Taifur Rahman, Takahide Fukuyama and Ilhyong Ryu

Organic Letters 2009 Volume 11(Issue 11) pp:2457-2460

Publication Date(Web):May 7, 2009

DOI:10.1021/ol900713d

Highly efficient thermal radical carboaminoxylations of various olefins by using the novel alkoxyamine A to give adducts of type B are described. It is reported that these radical addition reactions can be performed in a microflow reaction system. As compared to conventional batch reaction setup, significantly higher yields are obtained by running carboaminoxylations using the microflow system under analogous conditions.

Addition of allyl bromide to phenylacetylene catalyzed by palladium on alumina and its application to a continuous flow synthesis

Co-reporter:Takahide Fukuyama;Takashi Kippo

Research on Chemical Intermediates 2009 Volume 35( Issue 8-9) pp:

Publication Date(Web):2009 November

DOI:10.1007/s11164-009-0069-x

The reaction of allyl bromide with phenylacetylene catalyzed by Pd/Al2O3 pellets and Pd/C powder was investigated. Bromoallylation of phenylacetylene took place to give a regioisomeric mixture of 1-bromo-substituted 1,4-dienes. The bromoallylation of phenylacetylene was successfully applied to a continuous flow synthesis using a stainless steel made column packed with Pd/Al2O3 pellets.

Microflow photo-radical reaction using a compact light source: application to the Barton reaction leading to a key intermediate for myriceric acid A

Co-reporter:Atsushi Sugimoto, Takahide Fukuyama, Yukihito Sumino, Makoto Takagi, Ilhyong Ryu

Tetrahedron 2009 65(8) pp: 1593-1598

Publication Date(Web):

DOI:10.1016/j.tet.2008.12.063

Phase-vanishing methods based on fluorous phase screen: A simple way for efficient execution of organic synthesis

Co-reporter:Ilhyong Ryu;Hiroshi Matsubara;Hiroyuki Nakamura;Dennis P. Curran

The Chemical Record 2008 Volume 8( Issue 6) pp:351-363

Publication Date(Web):

DOI:10.1002/tcr.20161

Abstract

The phase-vanishing (PV) method is based on spontaneous reaction controlled by diffusion of reagents into fluorous media, such as perfluorohexanes (FC-72) and polyperfluoroethers. Thus, the original PV reaction utilizes a triphasic test tube method composed of a bottom reagent phase, a middle fluorous phase, and a top substrate phase. In such a triphasic system, the fluorous phase acts as a liquid membrane to transport the bottom reagents to the top organic phase containing substrates. In the end, the bottom layer disappears and two phases remain. Since the first demonstration of the PV method by bromination of alkenes with molecular bromine, a number of applications have been developed thus far. These include halogenation of alcohols with SOBr₂ and PBr₃, demethylation of methoxyarenes with BBr₃, cyclopropanation of alkenes by CH₂I₂-AlEt₃, and Friedel–Crafts acylation of aromatic compounds with SnCl₄. A fluorous triphasic U-tube method is effective for chlorination of alcohols based on lighter (less dense) reagents such as SOCl₂ and PCl₃. A system using a solution containing reagents as a bottom phase is useful for oxidation with m-CPBA, which may be defined as a new category for the “extractive PV” method. Recent advances include a “quadraphasic” PV method, in which an aqueous “scavenger” phase is added to the original triphasic PV method to remove acidic by-products. © 2008 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 8: 351–363; 2008: Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.20161

Ruthenium Hydride Catalyzed Regioselective Addition of Aldehydes to Enones To Give 1,3-Diketones

Co-reporter:Takahide Fukuyama Dr.;Takashi Doi Dr.;Satoshi Minamino;Sohei Omura Dr.

Angewandte Chemie 2007 Volume 119(Issue 29) pp:

Publication Date(Web):20 JUN 2007

DOI:10.1002/ange.200701005

Alles zusammen: Die durch den Rutheniumhydridkomplex [RuHCl(CO)(PPh₃)₃] katalysierte regioselektive Addition von Aldehyden an Enone eröffnet einen einfachen Zugang zu 2-Alkyl-substituierten 1,3-Diketonen (siehe Schema). Die Reaktion besteht aus der Hydrometallierung des Enons zu einem Metallenolat, einer gekreuzten Aldolreaktion, die eine Alkoxymetallspezies liefert, und einer β-Metallhydrideliminierung.

Ruthenium Hydride Catalyzed Regioselective Addition of Aldehydes to Enones To Give 1,3-Diketones

Co-reporter:Takahide Fukuyama Dr.;Takashi Doi Dr.;Satoshi Minamino;Sohei Omura Dr.

Angewandte Chemie International Edition 2007 Volume 46(Issue 29) pp:

Publication Date(Web):20 JUN 2007

DOI:10.1002/anie.200701005

It all adds up: Straightforward access to 2-alkyl-substituted 1,3-diketones is provided by a regioselective addition of aldehydes to enones catalyzed by the ruthenium hydride catalyst [RuHCl(CO)(PPh₃)₃] (see scheme). The reaction involves a hydrometalation of the enone to form a metal enolate, a cross-aldol reaction to form an alkoxymetal species, and a subsequent β-metal hydride elimination.

An unusual dimerization of primary unsaturated alcohols catalyzed by RuHCl(CO)(PPh3)3

Co-reporter:Takashi Doi, Takahide Fukuyama, Satoshi Minamino, Guillaume Husson and Ilhyong Ryu

Chemical Communications 2006 (Issue 17) pp:1875-1877

Publication Date(Web):21 Mar 2006

DOI:10.1039/B602103D

When primary unsaturated alcohols were treated with a catalytic amount of RuHCl(CO)(PPh3)3 in benzene under reflux, dimerization reactions took place to give α-hydroxymethyl ketones as major product.

Low pressure Pd-catalyzed carbonylation in an ionic liquid using a multiphase microflow system

Co-reporter:Md. Taifur Rahman, Takahide Fukuyama, Naoya Kamata, Masaaki Sato and Ilhyong Ryu

Chemical Communications 2006 (Issue 21) pp:2236-2238

Publication Date(Web):28 Apr 2006

DOI:10.1039/B600970K

A low pressure microflow system was developed for palladium-catalyzed multiphase carbonylation reactions in an ionic liquid. The microflow system resulted in superior selectivity and higher yields in carbonylative Sonogashira coupling and amidation reactions of aryl iodides compared to the conventional batch system.

Tin-Free Radical Carbonylation: Thiol Ester Synthesis Using Alkyl Allyl Sulfone Precursors, Phenyl Benzenethiosulfonate, and CO

Co-reporter:Sangmo Kim, Sunggak Kim, Noboru Otsuka,Ilhyong Ryu

Angewandte Chemie International Edition 2005 44(38) pp:6183-6186

Publication Date(Web):

DOI:10.1002/anie.200501606

Tin-Free Radical Carbonylation: Thiol Ester Synthesis Using Alkyl Allyl Sulfone Precursors, Phenyl Benzenethiosulfonate, and CO

Co-reporter:Sangmo Kim;Sunggak Kim Dr.;Noboru Otsuka Dr.

Angewandte Chemie 2005 Volume 117(Issue 38) pp:

Publication Date(Web):31 AUG 2005

DOI:10.1002/ange.200501606

Zinn, nein danke! Thiolester konnten mit der im Schema gezeigten zinnfreien Radikalcarbonylierung synthetisiert werden (V-40=Initiator). Dieser Ansatz lässt sich auf sequenzielle Radikalreaktionen ausdehnen, die Cyclisierung, Carbonylierung und das Abfangen von Acylradikalen durch Phenylbenzolthiosulfonat umfassen.

Hydroruthenation triggered catalytic conversion of dialdehydes and keto aldehydes to lactones

Co-reporter:Sohei Omura, Takahide Fukuyama, Yuji Murakami, Hiromi Okamoto and Ilhyong Ryu

Chemical Communications 2009(Issue 44) pp:NaN6743-6743

Publication Date(Web):2009/10/19

DOI:10.1039/B912850F

Lactonization of dialdehydes and keto aldehydes was effectively catalyzed by RuHCl(CO)(PPh3)3. A cascade lactonization sequence accompanied by cross-coupling with enones was also attained.

Versatile cross-dehydrogenative coupling of heteroaromatics and hydrogen donors via decatungstate photocatalysis

Co-reporter:Matteo C. Quattrini, Saki Fujii, Keiichi Yamada, Takahide Fukuyama, Davide Ravelli, Maurizio Fagnoni and Ilhyong Ryu

Chemical Communications 2017 - vol. 53(Issue 15) pp:NaN2338-2338

Publication Date(Web):2017/01/25

DOI:10.1039/C6CC09725A

Synthesis of aromatic β-keto esters via a carbonylative Suzuki–Miyaura coupling reaction of α-iodo esters with arylboronic acids

Co-reporter:Shuhei Sumino, Takahito Ui and Ilhyong Ryu

Inorganic Chemistry Frontiers 2015 - vol. 2(Issue 9) pp:NaN1087-1087

Publication Date(Web):2015/07/14

DOI:10.1039/C5QO00185D

Aromatic β-keto esters were synthesized via a carbonylative cross-coupling reaction of alkyl iodides and arylboronic acids in the presence of a catalytic amount of Pd catalyst. A cooperative radical and Pd-catalyzed mechanism is proposed.

Radical vinylation of dioxolanes and N-acylpyrrolidines using vinyl bromides

Co-reporter:Takashi Kippo, Yuki Kimura, Ayami Maeda, Hiroshi Matsubara, Takahide Fukuyama and Ilhyong Ryu

Inorganic Chemistry Frontiers 2014 - vol. 1(Issue 7) pp:

Publication Date(Web):

DOI:10.1039/C4QO00138A

A bromine-radical mediated three-component reaction comprising allenes, electron-deficient alkenes and allyl bromides: facile synthesis of 2-bromo-1,7-dienes

Co-reporter:Takashi Kippo and Ilhyong Ryu

Chemical Communications 2014 - vol. 50(Issue 45) pp:NaN5996-5996

Publication Date(Web):2014/04/16

DOI:10.1039/C4CC01597E

Iron-catalyzed decarbonylation reaction of aliphatic carboxylic acids leading to α-olefins

Co-reporter:Shinji Maetani, Takahide Fukuyama, Nobuyoshi Suzuki, Daisuke Ishihara and Ilhyong Ryu

Chemical Communications 2012 - vol. 48(Issue 19) pp:NaN2554-2554

Publication Date(Web):2012/01/10

DOI:10.1039/C2CC18093F

The catalytic decarbonylation reaction of aliphatic carboxylic acids can be carried out in the presence of an iron complex, and it proceeds smoothly to give α-olefins with high selectivity.

Sunlight photocatalyzed regioselective β-alkylation and acylation of cyclopentanones

Co-reporter:Megumi Okada, Takahide Fukuyama, Keiichi Yamada, Ilhyong Ryu, Davide Ravelli and Maurizio Fagnoni

Chemical Science (2010-Present) 2014 - vol. 5(Issue 7) pp:NaN2898-2898

Publication Date(Web):2014/05/08

DOI:10.1039/C4SC01072H

Radical reactions of borohydrides

Co-reporter:Takuji Kawamoto and Ilhyong Ryu

Organic & Biomolecular Chemistry 2014 - vol. 12(Issue 48) pp:NaN9742-9742

Publication Date(Web):2014/10/01

DOI:10.1039/C4OB01784F

Radical carbonylation of ω-alkynylamines leading to α-methylene lactams. Synthetic scope and the mechanistic insights

Co-reporter:Ilhyong Ryu, Takahide Fukuyama, Mami Tojino, Yoshitaka Uenoyama, Yuka Yonamine, Nozomi Terasoma and Hiroshi Matsubara