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

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Published in 2018

Theoretical calculations for the 1,​4-​hydrogen shift of 1-​hydroxyallyl radicals leading to α-​Keto radicals; prediction of facilitation by 1-​amino and 3-​Tin Substituents
Hiroshi Matsubara, Takuji Kawamoto, Takahide Fukuyama, Ilhyong Ryu
Chemistry Letters, 2018, 47, 9 pp. 1197 - 1199
DOI: 10.1246/cl.180522
DFT calcns. were carried out to elucidate the 1,​4-​hydrogen shift of 1-​hydroxyallyl radicals to give α-​keto radicals.  The 1,​4-​H shift is predicted to be exothermic with large energy barriers.  However, the energy barriers of 1,​4-​H shift were predicted to be lowered significantly by 1-​amino and 3-​tin substituents.  The results agreed well with the exptl. results shown by the stannylcarbonylation of alkynes in the presence of an amine, in which the 1,​4-​H shift of substituted 1-​hydroxyallyl radicals has been proposed as a key step.

A theoretical study on radical-​based aminocarbonylation of aryl iodides
Takuji Kawamoto , Hiroshi Matsubara, Takahide Fukuyama, Ilhyong Ryu
Chemistry Letters, 2018, 16, 41 pp. 1169 - 1171
DOI: 10.1246/cl.180599
Aminocarbonylation of aromatic iodides with CO and amines gives aromatic amides under photoirradiation conditions. DFT calculations predict that methylamine adds to benzoyl radical to give a zwitterionic radical, which would afford the product via two pathways: (a) an amine-assisted proton transfer followed by a single electron transfer reaction (SET) with iodobenzene or (b) complexation with iodobenzene and then the SET. Aminocarbonylation of aromatic iodides with CO and amines gives aromatic amides under photoirradiation. DFT calculations predict that methylamine adds to benzoyl radical to give a zwitterionic radical, which would afford the product via two pathways: (a) an amine-assisted proton transfer followed by a single electron transfer reaction (SET) with iodobenzene or (b) complexation with iodobenzene and then the SET.

Synthesis of perinaphthenones through rhodium-​catalyzed dehydrative annulation of 1-​naphthoic acids with alkynes
Takahide Fukuyama, Taiki Sugimori, Shinji Maetani, Ilhyong Ryu
Org. Biomol. Chem., 2018, 16, 41 pp. 7583 - 7587
DOI: 10.1039/C8OB01453A
ta An efficient approach to the synthesis of perinaphthenones via the rhodium-catalyzed dehydrative annulation of 1-naphthoic acids with internal alkynes was developed. Norbornadiene can act as an acetylene equivalent to give unsubstituted perinaphthenones at the 2- and 3-positions via dehydrative annulation followed by a retro Diels–Alder reaction.

Applications of Radical Carbonylation and Amine Addition Chemistry: 1,​4-​Hydrogen Transfer of 1-​Hydroxylallyl Radicals
Hiroshi Matsubara, Takuji Kawamoto, Takahide Fukuyama, Ilhyong Ryu
Acc. Chem. Res., 2018, 51, 9 pp. 2023 - 2035
DOI: 10.1021/acs.accounts.8b00278
ab 1,4-Hydrogen transfer from the 1-hydroxyallyl radical to give the enoxyl (α-keto) radical is an exothermic process with a high activation energy based on DFT calculations. The lack of experimental examples of such 1,4-H shift reactions lies in the difficulty of generating the 1-hydroxyallyl radical. We have shown that radical carbonylation of alkenyl radicals with CO followed by nucleophilic trapping of the carbonyl portion of the resulting radical by amines gives rise to 1-amino-substituted 1-hydroxyallyl radicals in situ. At the outset of this chemistry, we examined intramolecular trapping reactions via radical carbonylation of alkynylamines mediated by tributyltin hydride. Consequently, α-methylene lactams were obtained, for which the initially formed 1-amino-substituted 1-hydroxyallyl radical underwent a 1,4-H shift followed by subsequent β-scission, which led to the expulsion of a tributyltin radical. A competing pathway of the 1,4-H shift of 1-amino-substituted 1-hydroxyallyl radicals involving hydrogen abstraction was observed, which led to the formation of α-stannylmethylene lactams as a major byproduct. However, in contrast, when intermolecular trapping of α-ketenyl radicals by amines was carried out, the 1,4-H shift from the 1-amino-substituted 1-hydroxyallyl radical became the major pathway, which gave good yields of α,β-unsaturated amides. Thus, we were able to develop three-component reactions comprising terminal alkynes, CO, and amines that led to α,β-unsaturated amides via the 1,4-H shift reaction. DFT calculations support the observation that the 1,4-H shift is more facile when 1-hydroxyallyl radicals have both 1-amino and 3-tin substituents. The choice of substituents on the amine nitrogen is also important, since N–C bond cleavage via an SH2-type reaction can become a competing pathway. Such an unusual SH2-type reaction at the amine nitrogen is favored when the leaving alkyl radicals are stable, such as PhC(•)H(CH3) and t-Bu•. Interestingly, even nucleophilic attack of tertiary amines onto α-ketenyl radicals causes cleavage of the C–N bond. For this reaction, DFT calculations predict an indirect homolytic substitution mechanism involving expulsion of alkyl radicals through the zwitterionic radical intermediate arising from nucleophilic amine addition onto the α-ketenyl radical. In contrast, the carbonylation of aryl radicals, generated from aryl iodides, in the presence of amines gave aromatic carboxylic amides in good yields. It is proposed that radical anions originating from acyl radicals and amines undergo electron transfer to aryl iodides to give aminocarbonylation products.

Electron-​Transfer-​Induced Intramolecular Heck Carbonylation Reactions Leading to Benzolactones and Benzolactams
Takahide Fukuyama, Takanobu Bando, Ilhyong Ryu
Synthesis, 2018, 50, 15 pp. 3015 - 3021
DOI: 10.1055/s-0037-1609964
A metal-catalyst-free intramolecular Heck carbonylation reaction of benzyl alcohols and benzyl amines with carbon monoxide under heating at 250 °C affords the corresponding benzolactones and benzolactams in good to excellent yields. A hybrid radical/ionic chain mechanism, involving electron transfer from radical anions generated by nucleophilic attack of alcohols or amines on intermediate acyl radicals, is proposed.

Electron transfer-induced reduction of organic halides with amines
Takahide Fukuyama, Yuki Fujita, Hayato Miyoshi, Ilhyong Ryu, Shih-Chieh Kao, Yen-Ku Wu
Chem. Commun., 2018, 54, 44 pp. 5582 - 5585
DOI: 10.1039/C8CC02445F
3-2 Reduction of a variety of organo halides was examined by using amines as a sacrificial hydrogen source. UV light-induced reduction of vinyl and aryl halides with triethylamine proceeded smoothly to give the corresponding reduced products. High temperature heating also caused the reduction and DABCO (1,4-diazabicyclo[2.2.2]octane) also served as a good reducing reagent.

Palladium/Light Induced Radical Alkenylation and Allylation of Alkyl Iodides Using Alkenyl and Allylic Sulfones
Shuhei Sumino, Misae Uno, Hsin-Ju Huang, Yen-Ku Wu, Ilhyong Ryu
Org. Lett., 2018, 20, 4 pp. 1078 - 1081
DOI: 10.1021/acs.orglett.7b04050
Palladium   Alkenylation and allylation of alkyl iodides with alkenyl and allyl sulfones, respectively, took place under Pd/photoirradiation system. The initial alkyl radical, derived from a single electron transfer between Pd(0) and RI, underwent the title transformations. Pd(0) was regenerated through a reductive elimination of PhSO2PdI, which is formed by the combination of the sulfonyl radical and the palladium radical. The addition of water was effective, presumably by pushing the equilibrium through hydrolysis of PhSO2I.

Site-selectivity in TBADT-photocatalyzed C(sp3)–H Functionalization of Saturated Alcohols and Alkanes
Fukuyama, Takahide, Yamada, Keiichi, Nishikawa, Tomohiro, Ravelli, Davide, Fagnoni, Maurizio, Ryu, Illhyong
Chemistry Letters, 2018, 47, 2 pp. 207 - 209
DOI: 10.1246/cl.171068
Site-selectivity in C(sp3)–H functionalization of aliphatic alcohols and alkanes was studied using the decatungstate anion as a photocatalyst. In the case of aliphatic alcohols, C–H bond α to the hydroxy group was preferentially functionalized. The α-site-selectivity is rationalized by polar effects imparted by the hydroxy group in the SH2 transition states. In contrast, C–H functionalization of alkanes was largely affected by steric effects.

Site-Selective C–H Functionalization by Decatungstate Anion Photocatalysis: Synergistic Control by Polar and Steric Effects Expands the Reaction Scope
Davide Ravelli, Maurizio Fagnoni, Takahide Fukuyama, Tomohiro Nishikawa, Ilhyong Ryu
ACS Catal., 2018, 8, 1 pp. 701 - 713
DOI: 10.1021/acscatal.7b03354
1-1 The synergistic control of the SH2 transition states of hydrogen abstraction by polar and steric effects provides a promising strategy in achieving site-selective C(sp3)–H functionalization under decatungstate anion photocatalysis. By using this photocatalytic approach, the C–H bonds of alkanes, alcohols, ethers, ketones, amides, esters, nitriles, and pyridylalkanes were functionalized site-selectively. In the remarkable case of a 2,4-disubstituted cyclohexanone bearing five methyl, five methylene, and three methine C–H bonds, one methine C–H bond in the isoamyl tether was selectively functionalized.



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