Researcher Profile and Settings

Master

Affiliation (Master)

• Faculty of Engineering　Applied Chemistry　Industrial Organic Chemistry

Affiliation (Master)

• Faculty of Engineering　Applied Chemistry　Industrial Organic Chemistry

researchmap

Profile and Settings

Profile and Settings

• Contact Point

  n-araieng.hokudai.ac.jp

• Name (Japanese)

  Arai

• Name (Kana)

  Noriyoshi

• Name

  201201082475184696

Alternate Names

https://orgsynth.eng.hokudai.ac.jp

Achievement

Research Areas

• Life sciences / Bioorganic chemistry
• Nanotechnology/Materials / Structural/physical organic chemistry

Research Experience

• 2006/04 - Today Hokkaido University Faculty of Engineering
• 2005/04 - 2006/03 名古屋産業科学研究所中部TLO 博士研究員
• 2000/04 - 2005/03 科学技術振興機構戦略的基礎研究推進事業 分子複合系の構築と機能 博士研究員
• 1998/03 - 2000/03 日立化成工業株式会社総合研究所
• 1997/04 - 1998/03 東京大学 大学院・理学系研究科 助手

Education

• 1993/04 - 1996/03  東京大学大学院
• 1991/04 - 1993/03  東京大学大学院
• 1989/04 - 1991/03  The University of Tokyo  Faculty of Science  Department of Chemistry
• 1987/04 - 1989/03  The University of Tokyo  College of Arts and Sciences

Published Papers

• Asymmetric Hydrogenation of α-Alkyl-Substituted β-Keto Esters and Amides through Dynamic Kinetic Resolution

  Taiga Yurino, Ryo Nishihara, Toshihisa Yasuda, Shuangli Yang, Noriyuki Utsumi, Takeaki Katayama, Noriyoshi Arai, Takeshi Ohkuma

  Organic Letters 1523-7060 2024/01/11
• Asymmetric Hydrogenation of α-Amino Esters into Optically Active β-Amino Alcohols through Dynamic Kinetic Resolution Catalyzed by Ruthenabicyclic Complexes

  Hiroki Ishikawa, Taiga Yurino, Ryo Komatsu, Ming-Yuan Gao, Noriyoshi Arai, Taichiro Touge, Kazuhiko Matsumura, Takeshi Ohkuma

  Organic Letters 1523-7060 2023/03/24
• Intramolecular [2 + 2] Cycloaddition of Isocarbostyrils Catalyzed by an Iridium Visible-Light Photocatalyst

  Noriyoshi Arai

  The Journal of Organic Chemistry 88 (7) 4848 - 4853 0022-3263 2023/03/09 [Refereed][Not invited]
  
• Formation of anti‐Bredt‐type azabicyclo[4.2.0]octene frameworks through photochemical intramolecular [2+2] cycloaddition between indole and a distal double bond of allene

  Noriyoshi Arai

  Journal of Heterocyclic Chemistry 60 (2) 219 - 231 0022-152X 2023/02 [Refereed][Not invited]
   

  Abstract Irradiation of 1‐(penta‐3,4‐dienoyl)indole derivatives in the presence of an aromatic ketone by a high‐pressure mercury lamp through Pyrex glass gave two types of cyclized products stereoselectively in high combined yields. The major product was a tetracyclic indoline derivative containing anti‐Bredt‐type azabicyclo[4.2.0]octene moiety produced via photo [2+2] cycloaddition between indole and a distal double bond of allene, accompanied by a small amount of proximal [2+2] adduct. Among a range of aromatic ketones screened, 3′,4′‐methylenedioxyacetophenone was found to sensitize the substrate most effectively.
• Stereospecific Skeletal Rearrangement of Epoxides Derived from Methylenecyclobutane-Fused N-Heterocycles

  Noriyoshi Arai

  HETEROCYCLES 106 (7) 1198 - 1198 0385-5414 2023 [Refereed][Not invited]
  
• Stereoselective construction of cycloheptene-fused indoline frameworks through photosensitised formal [5+2] cycloaddition

  Noriyoshi Arai, Takeshi Ohkuma

  Tetrahedron Letters 88 153588 - 153588 0040-4039 2022/01 [Refereed][Not invited]
  
• Asymmetric (Transfer) Hydrogenation of Functionalized Ketones

  Noriyoshi Arai, Takeshi Ohkuma

  Asymmetric Hydrogenation and Transfer Hydrogenation 55 - 85 2021/04/26 [Refereed][Invited]
  
• Photosensitized Intramolecular [2+2] Cycloaddition of 1H-Pyrrolo[2,3-b]pyridines Enabled by the Assistance of Lewis Acids

  Noriyoshi Arai, Takeshi Ohkuma

  The Journal of Organic Chemistry 85 (23) 15717 - 15725 2020/11 [Refereed][Not invited]
  
• Isomerization‐Asymmetric Hydrogenation Sequence Converting Racemic β‐Ylidenecycloalkanols into Stereocontrolled β‐Substituted Cycloalkanols Using a Ru Catalytic System with Dual Roles

  Noriyoshi Arai, Yuki Okabe, Takeshi Ohkuma

  Advanced Synthesis & Catalysis 361 (24) 5540 - 5547 1615-4150 2019/12/17 [Refereed][Not invited]
  
• Stereoselective preparation of methylenecyclobutane-fused angular tetracyclic spiroindolines via photosensitized intramolecular [2+2] cycloaddition with allene

  Noriyoshi Arai, Takeshi Ohkuma

  Tetrahedron Letters 60 (46) 151252 - 151252 0040-4039 2019/11 [Refereed][Not invited]
  
• Stereoselective Construction of Methylenecyclobutane-Fused Indolines through Photosensitized [2+2] Cycloaddition of Allene-Tethered Indole Derivatives

  Noriyoshi Arai, Takeshi Ohkuma

  Organic Letters 21 (5) 1506 - 1510 1523-7060 2019/03 [Refereed][Not invited]
  
• Chemoselectivity Control in the Asymmetric Hydrogenation of γ- and δ-Keto Esters into Hydroxy Esters or Diols

  Noriyoshi Arai, Takanori Namba, Kei Kawaguchi, Yuki Matsumoto, Takeshi Ohkuma

  Angewandte Chemie - International Edition 57 (5) 1386 - 1389 1521-3773 2018/01/26 [Refereed][Not invited]
   

  The asymmetric hydrogenation of aromatic γ- and δ-keto esters into optically active hydroxy esters or diols under the catalysis of a novel DIPSkewphos/3-AMIQ–RuII complex was studied. Under the optimized conditions (8 atm H2, Ru complex/t-C4H9OK=1:3.5, 25 °C) the γ- and δ-hydroxy esters (including γ-lactones) were obtained quantitatively with 97–99 % ee. When the reaction was conducted under somewhat harsh conditions (20 atm H2, [t-C4H9OK]=50 mm, 40 °C), the 1,4- and 1,5-diols were obtained predominantly with 95–99 % ee. The reactivity of the ester group was notably dependent on the length of the carbon spacer between the two carbonyl moieties of the substrate. The reaction of β- and ϵ-keto esters selectively afforded the hydroxy esters regardless of the reaction conditions. This catalyst system was applied to the enantioselective and regioselective (for one of the two ester groups) hydrogenation of a γ-ϵ-diketo diester into a trihydroxy ester.
• Construction of Unique Heterocyclic Frameworks by Photochemical Reaction of 5- and 6-Membered Heteroaromatics

  Arai, Noriyoshi, Ohkuma, Takeshi

  Heterocycles 96 (6) 997 - 1035 2018 [Refereed][Invited]
  
• Asymmetric Hydrogenation of Polysubstituted Aromatic Ketones Catalyzed by the DIPSkewphos​/PICA Derivative-​Ruthenium(II) Complexes

  Utsumi, Noriyuki, Arai, Noriyoshi, Kawaguchi, Kei, Katayama, Takeaki, Yasuda, Toshihisa, Murata, Kunihiko, Ohkuma, Takeshi

  ChemCatChem 10 (18) 3955 - 3959 2018 [Refereed][Not invited]
  
• Photochemically Promoted Aza-Diels Alder-Type Reaction: High Catalytic Activity of the Cr(III)/Bipyridine Complex Enhanced by Visible Light Irradiation

  Noriyoshi Arai, Takeshi Ohkuma

  JOURNAL OF ORGANIC CHEMISTRY 82 (14) 7628 - 7636 0022-3263 2017/07 [Refereed][Not invited]
   

  Aza-Diels Alder-type cycloaddition reactions between a range of N-arylimines and functionalized alkenes were effectively catalyzed by the Cr(III)/bipyridine complex under irradiation of blue light, to give the corresponding 1,2,3,4tetrahydroquinoline derivatives in high yields with excellent diastereoselectivity. Typically, the reaction of benzylideneaniline with 1-vinyl-2-pyrrolidinone proceeded smoothly with a substrate-to catalyst molar ratio (S/C) of 1000 and completed within 4 h at room temperature (20-25 degrees C), affording the cycloaddition product in 97% yield.
• Double Asymmetric Hydrogenation of Linear beta,beta-Disubstituted alpha,beta-Unsaturated Ketones into gamma-Substituted Secondary Alcohols using a Dual Catalytic System

  Noriyoshi Arai, Hironori Satoh, Ryo Komatsu, Takeshi Ohkuma

  CHEMISTRY-A EUROPEAN JOURNAL 23 (37) 8806 - 8809 0947-6539 2017/07 [Refereed][Not invited]
   

  Double asymmetric hydrogenation of linear beta,beta-disubstituted alpha,beta-unsaturated ketones catalyzed by the DM-SEGPHOS/DMAPEN/Ru-II complex with t-C4H9OK afforded the gamma-substituted secondary alcohols in high diastereo-and enantioselectivities. Some mechanistic experiments suggested that two different reactive species, type (I) and (II), were reversibly formed in this catalytic system: Type (I) with the diamine ligand DMAPEN enantioselectively hydrogenated the enones into the chiral allylic alcohols, and type (II) without the diamine ligand diastereoselectively hydrogenated the allylic alcohols into the gamma-substituted secondary alcohols. This dual catalysis protocol was successfully applied to the reaction of a variety of aliphatic-and aromatic-substituted enone substrates.
• Advancement in Catalytic Asymmetric Hydrogenation of Ketones and Imines, and Development of Asymmetric Isomerization of Allylic Alcohols

  Takeshi Ohkuma, Noriyoshi Arai

  CHEMICAL RECORD 16 (6) 2801 - 2819 1527-8999 2016/12 [Refereed][Not invited]
   

  Catalytic asymmetric hydrogenation of ketones through the "metal-ligand cooperative mechanism" has been improved in terms of the efficiency, stereoselectivity, and scope of substrates by varying the arrangement of the catalyst structure and reaction conditions. Imino compounds are also smoothly converted to the optically active amines with appropriate catalysts. This type of catalyst exhibits excellent performance on the asymmetric isomerization of primary allylic alcohols into the optically active aldehydes. This personal account describes recent progress on these topics.
• Efficient chemoselective hydrogenation of organic azides catalyzed by palladium nanoparticles with alkyne-derived homogeneous supports

  Noriyoshi Arai, Nozomi Onodera, Takeshi Ohkuma

  TETRAHEDRON LETTERS 57 (37) 4183 - 4186 0040-4039 2016/09 [Refereed][Not invited]
   

  Catalytic chemoselective hydrogenation of organic azides using palladium nanoparticles stabilized by alkyne derivatives was studied. A broad range of aromatic and aliphatic azides were smoothly reduced to the corresponding amines in excellent yields with a quite small amount of the catalyst. Hydrogenation of 3-phenylpropylazide gave 3-phenylpropylamine almost quantitatively with a substrate-to-palladium molar ratio (S/Pd) of 12,900 under 8 atm of H-2. The reaction under 1 atm of H2 also proceeded smoothly with an S/Pd of 1000. Several reduction-sensitive functional groups, such as carbonyl, halide, benzylic OH, and aliphatic nitro were well tolerated under the reaction conditions. (C) 2016 Elsevier Ltd. All rights reserved.
• Development of Methods for Construction of Heterocyclic Frameworks by Photochemical Activation of Molecules

  Noriyoshi Arai, Takeshi Ohkuma

  JOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN 74 (4) 360 - 371 0037-9980 2016/04 [Refereed][Invited]
   

  Novel methods for the construction of molecular frameworks were developed by means of photochemical activation of 5-membered heteroaromatics, including furans, thiophenes, thiazoles, and oxazoles. Intramolecular Diels-Alder-type cycloaddition reactions between furan and an unactivated alkene moiety were found to proceed in high yields in the presence of 9,10-dicyanoanthracene under UV irradiation to afford oxabicyclo[2.2.1]heptane derivatives with high stereoselectivity. Photoirradiation onto alpha-arylthiophene derivatives linked with an alkene moiety through a three-atom spacer gave unprecedented cyclobutene-fused perhydrothiapentalene-type compounds in high yields with high stereoselectivity. A photo-ene type cyclization of 2-aryloxazole derivatives linked with an alkene moiety through a three-atom spacer at the 5-position gave a range of functionalized spiro[4.4] cyclic compounds that included cyclopentane, tetrahydrofuran, and pyrrolidine moieties in moderate to high yields with excellent diastereoselectivity.
• Hydrogenation of nitroarenes with palladium nanoparticles stabilized by alkyne derivatives in homogeneous phase

  Noriyoshi Arai, Nozomi Onodera, Atsushi Dekita, Junichi Hori, Takeshi Ohkuma

  TETRAHEDRON LETTERS 56 (25) 3913 - 3915 0040-4039 2015/06 [Refereed][Not invited]
   

  Palladium nanoparticles stabilized by alkyne derivatives catalyzed the hydrogenation of nitroarenes to the aryl amines in homogeneous phase. The reaction of nitrobenzene proceeded smoothly with a substrate-to-palladium molar ratio (S/Pd) of 51,000 under 8 atm of H-2. The reaction under 1 atm of H-2 with an S/Pd of 1030 was completed in 4 h. A series of substituted nitroarenes, including 4-acetyl- and 4-formylnitrobenzenes, were converted to the aryl amines with high chemoselectivity. (C) 2015 Elsevier Ltd. All rights reserved.
• NOVEL INTRAMOLECULAR CYCLIZATION-SKELETAL REORGANIZATION OF 2-ARYLTHIAZOLES UNDER PHOTOIRRADIATION

  Noriyoshi Arai, Moe Mizota, Takeshi Ohkuma

  HETEROCYCLES 90 (1) 607 - 616 0385-5414 2015/01 [Refereed][Not invited]
   

  Photoirradiation of 2-arylthiazoles derivatives linked with an alkene moiety through a three-atom spacer was investigated. The main products were unexpected tetrahydrofuran-fused thiazepine derivatives with concomitant formation of [2+2] cycloaddition products and regioisomeric thiazoles. The product distribution was little influenced by the reaction conditions and substituents of the substrates.
• Stereoselective Preparation of Spiro[4.4] Cyclic Compounds by the Photochemical Activation of Oxazoles

  Noriyoshi Arai, Moe Mizota, Takeshi Ohkuma

  ORGANIC LETTERS 17 (1) 86 - 89 1523-7060 2015/01 [Refereed][Not invited]
   

  A novel photocyclization of 2-aryloxazole derivatives linked with an alkene moiety through a three-atom spacer at the 5-position gave a range of functionalized spiro[4.4] cyclic compounds that included cyclopentane, tetrahydrofuran, and pyrrolidine moieties in moderate to high yields with excellent diastereoselectivity.
• Enantioselective Isomerization of Primary Allylic Alcohols into Chiral Aldehydes with the tol-binap/dbapen/Ruthenium(II) Catalyst

  Noriyoshi Arai, Keisuke Sato, Keita Azuma, Takeshi Ohkuma

  ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 52 (29) 7500 - 7504 1433-7851 2013/07 [Refereed][Not invited]
  
• Asymmetric Hydrogenation of Alkynyl Ketones with the eta(6)-Arene/TsDPEN-Ruthenium(II) Catalyst

  Noriyoshi Arai, Hironori Satoh, Noriyuki Utsumi, Kunihiko Murata, Kunihiko Tsutsumi, Takeshi Ohkuma

  ORGANIC LETTERS 15 (12) 3030 - 3033 1523-7060 2013/06 [Refereed][Not invited]
   

  Enantioselective hydrogenation of alkynyl ketones catalyzed by Ru(OTf)(TsDPEN)(eta(6)-p-cymene) (TsDPEN = N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine) affords the propargylic alcohols in up to 97% ee. The alkynyl moieties are left intact In most cases. The reaction can be conducted with a substrate-to-catalyst molar ratio as high as 5000 under 10 atm of H-2. The mode of enantioselection is elucidated with the transition state models directed by the CH/pi attractive interaction between the substrate and the catalytic species.
• Asymmetric hydrogenation of quinoxalines, benzoxazines, and a benzothiazine catalyzed by chiral ruthenabicyclic complexes

  Noriyoshi Arai, Yu Saruwatari, Kotaro Isobe, Takeshi Ohkuma

  Advanced Synthesis and Catalysis 355 (14-15) 2769 - 2774 1615-4169 2013 [Refereed][Not invited]
   

  The ruthenabicyclic complex RuCl[(R)-daipena][(R)-dm-segphos] with potassium tert-butoxide catalyzes the hydrogenation of 2-alkylquinoxalines and a 3-methyl-2H-1,4-benzoxazine in toluene under 20-100 atm of hydrogen at 40 °C to afford S-configured cyclic amino products in greater than 97% enantiomeric excess {DAIPENA=anion of DAIPEN at the 2-position of an anisyl group, DAIPEN=1,1-di (4-anisyl)-2-isopropyl-1,2-ethylenediamine, DM-SEGPHOS=(4,4′-bi-1,3-benzodioxole)-5,5′-diylbis[di(3,5-xylyl) phosphine]}. The high catalytic activity results in a turnover number as high as 9400. Hydrogenation of the benzoimine heterocycles with the RuCl[(R)-daipena][(R)-segphos]/ potassium tert-butoxide system yields the R-configured products in high enantiomeric excess [SEGPHOS=(4,4′-bi-1,3- benzodioxole)-5,5′-diylbis-(diphenylphosphine)]. The mode of enantioselection is discussed based on transition state models involving six-membered pericyclic structures. © 2013 Wiley-VCH Verlag GmbH& Co. KGaA, Weinheim.
• 5.11 Reduction - Hydrogenation: C=O; Chemoselective

  T. Ohkuma, N. Arai

  Comprehensive Chirality 5 270 - 300 2012/09 [Refereed][Not invited]
   

  In this chapter asymmetric hydrogenation of ketones by the use of chiral catalysts is described. In the first part, the asymmetric hydrogenation of functionalized ketones including β-keto esters, α-keto esters, and α-alkoxy or amino ketones is discussed mainly in homogeneous catalytic systems. In the second part, we describe the highly stereoselective manner of the reaction with nonfunctionalized (simple) ketones. The final part of this chapter deals with the highly diastereo- and enantioselective hydrogenation accompanied by dynamic kinetic resolution. © 2012 Elsevier Ltd. All rights reserved.
• Asymmetric Hydrogenation of N-Arylimines Catalyzed by the Xyl-Skewphos/DPEN-Ruthenium(II) Complex

  Noriyoshi Arai, Noriyuki Utsumi, Yuki Matsumoto, Kunihiko Murata, Kunihiko Tsutsumi, Takeshi Ohkuma

  ADVANCED SYNTHESIS & CATALYSIS 354 (11-12) 2089 - 2095 1615-4150 2012/08 [Refereed][Not invited]
   

  The new catalyst system of RuBr2[(S,S)-xyl-skewphos][(S,S)-dpen] and potassium tert-butoxide shows high reactivity and enantioselectivity in the hydrogenation of N-arylimines [Xyl-Skewphos=2,4-bis(di-3,5-xylylphosphino)pentane, DPEN=1,2-diphenylethylenediamine]. A range of imines derived from aromatic and heteroaromatic ketones as well as some ferrocenyl and vinylic imines are hydrogenated with a turnover number as high as 18,000 under 10-50 atm of hydrogen to afford the amine products in up to 99% enantiomeric excess. The reaction is applied to the synthesis of a chiral N-arylamine, which is the synthetic intermediate of a biologically active compound. The mode of enantioselection is interpreted by using transition-state models based on the X-ray structure of the Xyl-Skewphos/DPEN-RuBr2 complex.
• Design of molecular catalysts for achievement of high turnover number in homogeneous hydrogenation

  Noriyoshi Arai, Takeshi Ohkuma

  CHEMICAL RECORD 12 (2) 284 - 289 1527-8999 2012/04 [Refereed][Invited]
   

  Development of highly active catalysts has been an important research area in synthetic chemistry, especially from a practical point of view. Herein, we focus on the homogeneous catalytic hydrogenation using well-defined molecular catalysts and discuss recent advances in the field with regard to the turnover number for these catalysts. DOI 10.1002/tcr.201100019
• Novel Intramolecular Photocyclization of alpha-Arylthiophene Derivatives

  Noriyoshi Arai, Koichiro Tanaka, Takeshi Ohkuma

  ORGANIC LETTERS 14 (6) 1488 - 1491 1523-7060 2012/03 [Refereed][Not invited]
   

  Photoirradiation of alpha-arylthiophene derivatives linked with an alkene moiety through a three-atom spacer gave unprecedented cyclobutene-fused perhydrothiapentalene-type compounds in high yields, but neither [2 + 2] nor [4 + 2] cycloaddition products. The reaction afforded a single diastereomer in many cases. The chemical structure and relative configuration of a typical product were unambiguously determined by X-ray crystallographic analysis.
• Catalyst-Controlled Diastereoselection in the Hydrogenation of Heterocycloalkyl Ketones

  Masaya Akashi, Noriyoshi Arai, Tsutomu Inoue, Takeshi Ohkuma

  ADVANCED SYNTHESIS & CATALYSIS 353 (11-12) 1955 - 1960 1615-4150 2011/08 [Refereed][Not invited]
   

  alpha-Substituted chiral ketones that have small steric and electronic differences around the reaction sites are difficult substrates to reduce with high diastereoselectivity. Metal hydride reduction of 2-(4-benzoylmorpholinyl) phenyl ketone and 3-(1-tert-butoxycarbonylpiperidinyl) phenyl ketone using sodium borohydride, zinc borohydride, and potassium tri-sec-butylborohydride as reducing agents affords the syn- and anti-alcohols in a lower than 80:20 ratio. Hydrogenation of these ketones with a catalyst system of RuCl(2)(BIPHEP) (DMEN) and potassium tert-butoxide in 2-propanol results in the syn-alcohols with >= 99:1 selectivity [BIPHEP= 2,2'-bis(diphenylphosphino)biphenyl, DMEN= N,N-dimethylethylenediamine]. The marked difference in the diastereoselectivity suggests that the stereoselection in this hydrogenation is primarily regulated by the structure of the catalyst's reaction field ("catalyst-controlled diastereoselection") but not the internal stereocontrol of the substrates. This chemistry is applied to the asymmetric hydrogenation through dynamic kinetic resolution with a RuCl(2)[(S)-BINAP][(R)-DMAPEN]/potassium tert-butoxide catalyst [BINAP= 2,2'-bis(diphenylphosphino)- 1,1'-binaphthyl, DMAPEN = 2-dimethylamino-1-phenylethylamine]. A series of aryl heterocycloalkyl ketones has been converted to the alcohols in excellent diastereo- and enantioselectivities. The modes of catalyst-controlled diastereoselection and enantioselection are interpreted by using transition-state molecular models. (S,S)-Reboxetine, a selective norepinephrine uptake inhibitor, was synthesized from one of product alcohols.
• Chiral Ruthenabicyclic Complexes: Precatalysts for Rapid, Enantioselective, and Wide-Scope Hydrogenation of Ketones

  Kazuhiko Matsumura, Noriyoshi Arai, Kiyoto Hori, Takao Saito, Noboru Sayo, Takeshi Ohkuma

  JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 133 (28) 10696 - 10699 0002-7863 2011/07 [Refereed][Not invited]
   

  A novel ruthenabicyclic complex with base shows excellent catalytic activity in the asymmetric hydrogenation of ketones. The turnover frequency of the hydrogenation of acetophenone reaches about 35 000 min(-1) in the best case, affording 1-phenylethanol in >99% ee. Several aliphatic and base-labile ketones are smoothly converted to the corresponding alcohols in high enantioselectivity. The catalytic cycle for this hydrogenation, in which the ruthenabicyclic structure of the catalyst is maintained, is proposed on the basis of the deuteration experiment and spectroscopic analysis data.
• Intramolecular iminium ene reaction with Cu(I) catalysts: facile formation of 4-amino-3-methylenechromans from O-propargyl salicylaldehydes and dialkylamines

  Noriyoshi Arai, Takeshi Ohkuma

  TETRAHEDRON 67 (9) 1617 - 1622 0040-4020 2011/03 [Refereed][Not invited]
   

  Reaction of O-propargyl salicylaldehyde and related compounds with dialkylamines in the presence of copper(I) iodide gave 4-(alkylamino)-3-methylenechroman derivatives in good yields through the loss of one alkyl group of the dialkylamine. The reaction also worked well by employing 2-amino benzaldehyde derivatives to afford 4-(alkylamino)-3-methylene-1,2,3,4-tetrahydroquinolines. A deuterium-labeling experiment suggested that the a-hydrogen of the dialkylamine was transferred intramolecularly into the terminal methylene. This result indicated the reaction mechanism, which involved the formation of iminium ion between the aldehyde and the dialkylamine followed by ene-type C-C bond formation with inverse electron demand and hydrolysis. (C) 2011 Elsevier Ltd. All rights reserved.
• Asymmetric Hydrogenation of Bicyclic Ketones Catalyzed by BINAP/IPHAN-Ru(II) Complex

  Noriyoshi Arai, Masaya Akashi, Satoshi Sugizaki, Hirohito Ooka, Tsutomu Inoue, Takeshi Ohkuma

  ORGANIC LETTERS 12 (15) 3380 - 3383 1523-7060 2010/08 [Refereed][Not invited]
   

  Hydrogenation of 3-quinuclidinone and bicyclo[2.2.2]octan-2-one with a combined catalyst system of RuCl(2)[(S)-binap][(R)-iphan] and t-C(4)H(9)OK in 2-propanol afforded the chiral alcohols in 97-98% ee. 2-Diphenylmethyl-3-quinuclidinone was hydrogenated with the same catalyst to the cis alcohol with perfect diastereo- and enantioselectivity. The reaction of unsymmetrical ketones with a bicyclo[2.2.1] or -[2.2.2] skeleton gave the corresponding alcohols with high stereoselectivity.
• Photosensitized intramolecular cyclization of furan and non-activated alkene: pathway switching by the substituent on the furan ring

  Noriyoshi Arai, Koichiro Tanaka, Takeshi Ohkuma

  TETRAHEDRON LETTERS 51 (9) 1273 - 1275 0040-4039 2010/03 [Refereed][Not invited]
   

  A photosensitized reaction of furan with a non-activated simple alkene was investigated Intramolecular Diels-Alder-type cycloaddition reactions between furan and a trisubstituted alkene were found 10 proceed in high yield in the presence of 9,10-dicyanoanthracene under UV irradiation to afford oxabicyclo[2 2 1]heptane derivatives in high stereoselectivity when the furan was alkyl substituted. On the other hand, the aryl-substituted furan cyclized via a completely different pathway to give spirocyclic and tricyclic products. (C) 2009 Elsevier Ltd All rights reserved.
• ASYMMETRIC HYDROGENATION OF AROMATIC HETEROCYCLIC KETONES CATALYZED BY THE MsDPEN-Cp*Ir(III) COMPLEX

  Noriyuki Utsumi, Kunihiko Tsutsumi, Masahiko Watanabe, Kunihiko Murata, Noriyoshi Arai, Nobuhito Kurono, Takeshi Ohkume

  HETEROCYCLES 80 (1) 141 - 147 0385-5414 2010/01 [Refereed][Not invited]
   

  Asymmetric hydrogenation of aromatic heterocyclic ketones catalyzed by Cp*Ir(OTf)(Msdpen) (MsDPEN = N-(methanesulfonyl)-1,2-diphenylethylenediamine) affords the heterocyclic alcohols in 93% to >99% ee. The reaction is conducted in a methanolic solution with a substrate-to-catalyst molar ratio of 200-5000 under 15 atm of H-2. The heterocyclic rings of substrates are left intact.
• Highly Active and Selective Semihydrogenation of Alkynes with the Palladium Nanoparticles-Tetrabutylammonium Borohydride Catalyst System

  Junichi Hori, Kunihiko Murata, Toshiki Sugai, Hisanori Shinohara, Ryoji Noyori, Noriyoshi Arai, Nobuhito Kurono, Takeshi Ohkuma

  ADVANCED SYNTHESIS & CATALYSIS 351 (18) 3143 - 3149 1615-4150 2009/12 [Refereed][Not invited]
   

  Palladium nanoparticles are prepared from palladium(II) acetate and 2 equivalents of potassium tert-butoxide in the presence of 4-octyne. The palladium nanoparticles-tetrabutylammonium borohydride system shows excellent catalytic activity and selectivity in the semihydrogenation of alkynes to the [(Z)-]alkenes. The hydrogenation of 4-octyne is conducted with the catalyst system at a substrate-to-palladium molar ratio of 10,000-200,000 under 8 atm of hydrogen to give (Z)-4-octene in > 99% yield. Isomerization and over-reduction of the Z-alkene are very slow even after consumption of the alkyne.
• Practical Asymmetric Hydrogenation of 3-Quinuclidinone Catalyzed by the XylSkewphos/PICA-Ruthenium(II) Complex

  Kunihiko Tsutsumi, Takeaki Katayama, Noriyuki Utsumi, Kunihiko Murata, Noriyoshi Arai, Nobuhito Kurono, Takeshi Ohkuma

  ORGANIC PROCESS RESEARCH & DEVELOPMENT 13 (3) 625 - 628 1083-6160 2009/05 [Refereed][Not invited]
   

  Asymmetric hydrogenation of 3-quinuclidinone with RuBr(2)[(S,S)-xylskewphos](pica) in a base containing ethanol affords (R)-3-quinuclidinol in 88-90% ee (XylSkewphos = 2,4-bis(di-3,5-xylylphosphino)pentane, PICA = alpha-picolylamine). The optical purity of the product is readily increased to >99% by recrystallization. The hydrogenation of a 4.3-kg scale with a substrate-to-catalyst molar ratio of 100 000 under 15 atm of H(2) at 30-45 degrees C completes in 4 h. Use of methanol or 2-propanol as a solvent decreases the catalyst efficiency. RuCl(2)(skewphos)(pica), and RuCl(2)(tolbinap)(pica) which have similar structures, are less effective for this reaction.
• Asymmetric Hydrogenation of Aromatic Ketones Catalyzed by the TolBINAP/DMAPEN-Ruthenium(II) Complex: A Significant Effect of N-Substituents of Chiral 1,2-Diamine Ligands on Enantioselectivity

  Hirohito Ooka, Noriyoshi Arai, Keita Azuma, Nobuhito Kurono, Takeshi Ohkuma

  JOURNAL OF ORGANIC CHEMISTRY 73 (22) 9084 - 9093 0022-3263 2008/11 [Refereed][Not invited]
   

  Asymmetric hydrogenation of acetophenone in the presence of Ru(II) catalysts coordinated by TolBINAP and a series of chiral 1,2-diamines was studied. The sense and degree of enantioselectivity were highly dependent on the N-substituents of the diamine ligands. The N-substituent effect was discussed in detail. Among these catalysts, the (S)-TolBINAP/(R)DMAPEN-Ru(II) complex showed the highest enantioselectivity. The mode of enantioface selection was interpreted by using transition state models based on the X-ray structure of the catalyst precursor. The chiral catalyst effected the hydrogenation of alkyl aryl ketones and arylglyoxal dialkyl acetals to afford the chiral alcohol in >99% ee in the best cases. Hydrogenation of racemic benzoin methyl ether with the chiral catalyst through dynamic kinetic resolution gave the anti-alcohol (syn:anti = 3:97) in 98% ee, while the reaction of alpha-amidopropiophenones resulted in the syn-alcohols (syn:anti = 96:4 to >99:1) in >98% ee.
• Carbonyl Hydroboration

  Noriyoshi Arai, Takeshi Ohkuma

  Modern Reduction Methods 159 - 181 2008/04/04 [Refereed][Not invited]
  
• Highly enantioselective hydrogenation of aryl vinyl ketones to allylic alcohols catalyzed by the tol-binap/dmapen ruthenium(II) complex

  Noriyoshi Arai, Keita Azuma, Noriyuki Nii, Takeshi Ohkuma

  ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 47 (39) 7457 - 7460 1433-7851 2008 [Refereed][Not invited]
  
• Asymmetric hydrogenation of aromatic, aliphatic, and alpha,beta-unsaturated acyl silanes catalyzed by tol-binap/pica ruthenium(II) complexes: Practical synthesis of optically active alpha-hydroxysilanes

  Noriyoshi Arai, Ken Suzuki, Satoshi Sugizaki, Hiroko Sorimachi, Takeshi Ohkuma

  ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 47 (9) 1770 - 1773 1433-7851 2008 [Refereed][Not invited]
  
• Asymmetric hydrogenation of alpha-hydroxy ketones catalyzed by MsDPEN-Cp*Ir(III) complex

  Takeshi Ohkuma, Noriyuki Utsumi, Masahito Watanabe, Kunihiko Tsutsumi, Noriyoshi Arai, Kunihiko Murata

  ORGANIC LETTERS 9 (13) 2565 - 2567 1523-7060 2007/06 [Refereed][Not invited]
   

  Asymmetric hydrogenation of a series of alpha-hydroxy aromatic ketones in methanol catalyzed by Cp*Ir(OTf)(MsDPEN) (MsDPEN = N-(methanesulfonyl)-1,2-diphenylethylenediamine) affords the 1-aryl-1,2-ethanediols in up to 99% ee. The reaction can be conducted with a substrate-to-catalyst molar ratio as high as 6000 under 10 atm of H-2. 1-Hydroxy-2-propanone is also hydrogenated with high enantioselectivity.
• General asymmetric hydrogenation of alpha-branched aromatic ketones catalyzed by TolBINAP/DMAPEN-ruthenium(II) complex

  Noriyoshi Arai, Hirohito Ooka, Keita Azuma, Toshio Yabuuchi, Nobuhito Kurono, Tsutomu Inoue, Takeshi Ohkuma

  ORGANIC LETTERS 9 (5) 939 - 941 1523-7060 2007/03 [Refereed][Not invited]
   

  A catalyst system consisting of RuCl2[(S)-tolbinap][(R)-dmapen] and t-C4H9OK in 2-propanol effects asymmetric hydrogenation of arylglyoxal dialkylacetals to give the alpha-hydroxy acetals in up to 98% ee. Hydrogenation of racemic alpha-amidopropiophenones under dynamic kinetic resolution predominantly gives the syn alcohols in up to 99% ee and > 98% de, while the reaction of racemic bezoin methyl ether gives the anti alcohols in excellent stereoselectivity.
• Asymmetric hydrogenation of alpha-chloro aromatic ketones catalyzed by eta(6)-arene/TsDPEN-ruthenium(II) complexes

  Takeshi Ohkuma, Kunihiko Tsutsumi, Noriyuki Utsumi, Noriyoshi Arai, Ryoji Noyori, Kunihiko Murata

  ORGANIC LETTERS 9 (2) 255 - 257 1523-7060 2007/01 [Refereed][Not invited]
   

  Asymmetric hydrogenation of various alpha-chloro aromatic ketones with Ru(OTf)(TsDPEN)(eta(6)-arene) (TsDPEN = N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine) produces the chiral chlorohydrins in up to 98% ee. This reaction can be conducted even on a 206-g scale. The hydrogenation of an alpha-chloro ketone with a phenol moiety has been utilized for the synthesis of (R)-norphenylephrine without protection-deprotection operations.
• Generation of nitrile oxides from oxime derivatives by the oxidation with ammonium hexanitratocerate(IV)

  N Arai, M Iwakoshi, K Tanabe, K Narasaka

  BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN 72 (10) 2277 - 2285 0009-2673 1999/10 [Refereed][Not invited]
   

  Aromatic and aliphatic nitrile oxides are generated by the oxidation of alpha-hydroxyimino carboxylic acid with ammonium hexanitratocerate(IV). They react with olefinic and acetylenic dipolarophiles to give the corresponding cycloaddition products in good yield. The oxidation of alpha-oxo aldoximes also affords alpha-oxo carbonitrile oxides.
• Generation of radical species from cyclohexane-1,2-dione and the reaction with olefins: Preparation of 4,5-dihydro-7(6H)-benzofuranone derivatives

  M Miura, N Arai, K Narasaka

  BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN 71 (6) 1437 - 1441 0009-2673 1998/06 [Not refereed][Not invited]
   

  Oxidation of cyclohexane-l,2-dione with ammonium hexanitratocerate(Iv) (CAN) generates 2,3-dioxocyclohexyl radical, which reacts with electron-rich olefins to afford the corresponding addition products. The adducts thus generated are converted to 4,5-dihydro-7(6H)-benzofuranone by acid treatment. In addition to cydohexane-1,2-dione, radical species are also generated from cyclopentane-l,2-dione acid cycloheptane-1,2-dione.
• Oxidative generation of 1-nitroalkyl radicals and their addition reaction to olefins

  N Arai, K Narasaka

  BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN 70 (10) 2525 - 2534 0009-2673 1997/10 [Not refereed][Not invited]
   

  1-Nitroalkyl radicals are generated by oxidation of potassium salt of 1-aci-nitroalkanes with ammonium hexanitratocerate(IV). When the oxidation is carried out in the presence of electron-rich olefins, such as silyl enol ethers, intermolecular addition of the radicals onto the olefins proceeds to afford beta-nitro ketones, which are further converted to alpha,beta-unsaturated ketones in high yield. Stereoselective construction of fused ring systems is achieved by intramolecular addition of 1-nitroalkyl radicals.
• Generation of alpha-alkylthio radicals by photoinduced one-electron oxidation of alpha-stannyl sulfides and their use for carbon-carbon bond formation

  T Ikeno, M Harada, N Arai, K Narasaka

  CHEMISTRY LETTERS (2) 169 - 170 0366-7022 1997 [Not refereed][Not invited]
   

  Cation radicals, generated from alpha-stannyl sulfides by the photoinduced single electron transfer, cleave into alpha-alkylthio radical intermediates with the elimination of the stannyl group. The alpha-alkylthio radicals thus formed are utilized for carbon-carbon bond forming reactions.
• Development of new methods for generation of radical species by one-electron oxidation with metallic oxidants toward construction of carbon skeletons

  N Arai, K Narasaka

  JOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN 54 (11) 964 - 975 0037-9980 1996/11 [Refereed][Not invited]
   

  By oxidation of beta-keto acids, cyclopropanols, and acyl chromate complexes with tris(2-pyridinecarboxylato)manganese(III) (Mn(pic)(3)), alpha-keto, beta-keto, and alkyl radicals are generated respectively, which react with olefinic compounds to afford intermolecular addition products in good yield. On the other hand, the cation radicals can be generated from alpha-stannylalkyl sulfides, alpha-stannylalkyl amine derivatives, and alpha-stannyl carboxylic eaters by oxidation with ammonium hexanitratocerate(IV) (CAN). These cation radicals of stannyl compounds readily cleave into carbocation or radical species, which are utilized as reactive intermediates for carbon-carbon bond formation.
• GENERATION OF ALPHA-NITROALKYL RADICALS BY OXIDATION OF NITRONATE ANIONS WITH CERIUM(IV) AMMONIUM-NITRATE AND THEIR ADDITION-REACTION TO ELECTRON-RICH OLEFINS

  N ARAI, K NARASAKA

  CHEMISTRY LETTERS (11) 987 - 988 0366-7022 1995/11 [Not refereed][Not invited]
   

  alpha-Nitroalkyl radicals are generated by oxidation of nitronate anions with cerium(IV) ammonium nitrate. When the reactions are carried out in the presence of electron-rich olefins, such as silyl enol ethers, intermolecular addition of the radicals proceeds to afford beta-nitroketones, which are further converted to alpha,beta-unsaturated ketones in good yield.
• GENERATION OF ARYL RADICALS BY THE OXIDATION OF ALPHA-(ARYLAZO)TRIPHENYLMETHANES BY CERIUM(IV) AMMONIUM-NITRATE

  N ARAI, K NARASAKA

  BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN 68 (6) 1707 - 1714 0009-2673 1995 [Refereed][Not invited]
   

  The one-electron oxidation of alpha-(arylazo)triphenylmethanes by cerium(IV) ammonium nitrate (CAN) generated aryl radicals along with the triphenylmethyl cation. When the reaction was carried out in the presence of appropriate radical-trapping agents, such as arenes and olefins, the corresponding addition products were obtained in moderate yield. The oxidation of the arylazo compounds with CAN was accelerated by the addition of acids.
• OXIDATIVE GENERATION OF THIOALKYL CATIONS FROM 2-TRIBUTYLSTANNYL-1,3-DITHIANES AND 1-(TRIBUTYLSTANNYL)ALKYL SULFIDES AND THEIR REACTIONS WITH OLEFINIC NUCLEOPHILES

  K NARASAKA, N ARAI, T OKAUCHI

  BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN 66 (10) 2995 - 3003 0009-2673 1993/10 [Refereed][Not invited]
   

  2-'Tributylstannyl-1,3-dithianes and 1- (tributylstannyl)alkyl sulfides are oxidized with ammonium hexanitratocerate(IV) or ferrocenium hexafluorophosphate to generate their cation radicals, which dissociate into the carbocations and tributylstannyl radical. The carbocations thus generated react with olefinic nucleophiles to afford the corresponding addition products in good yield.
• GENERATION OF CATION RADICALS FROM 2-TRIBUTYLSTANNYL-1,3-DITHIANES AND THEIR REACTION WITH OLEFINS

  K NARASAKA, T OKAUCHI, N ARAI

  CHEMISTRY LETTERS (7) 1229 - 1232 0366-7022 1992/07 [Not refereed][Not invited]
   

  Oxidation of 2-tributylstannyl-1,3-dithianes with metallic oxidants generates reactive species such as 1,3-dithian-2-yl radical and/or cation by eliminating the stannyl group. Those intermediates react with olefins to give the intermolecular addition products.

MISC

• Investigation on the Stereoselective Construction of Fused─Ring Frameworks by Using Photochemical Properties of N─Heteroaromatic Compounds

  NoriyoshiArai  Journal of Synthetic Organic Chemistry Japan  82-  (3)  234  -245  2024/03  [Refereed][Not invited]
  
• Development of Asymmetric Reactions Catalyzed by Ruthenium Complexes with Two Kinds of Ligands

  Takeshi Ohkuma, Nobuhito Kurono, Noriyoshi Arai  Bulletin of the Chemical Society of Japan  92-  (3)  475  -504  2019  [Refereed][Not invited]
   

  Two types of chiral Ru(II) complexes, each with two kinds of ligands, have been designed and utilized as catalysts for several asymmetric reactions under appropriate conditions. The first type, the diphosphine/diamine-Ru(II)-type complexes, were found to catalyze the hydrogenation of a variety of simple and functionalized ketones as well as imino compounds with high activity and enantioselectivity. The double asymmetric hydrogenation of alpha,beta-unsaturated ketones into the chiral saturated alcohols was achieved by using the dual catalyst system, which reversibly forms two catalytic species. The asymmetric isomerization of primary allylic alcohols into the optically active aldehydes with almost perfect enantioselectivity was realized with this type of catalyst. The second type, the amino acid/diphosphine-Ru(II)-type complexes combined with Li compounds, exhibited excellent catalyst performance in the asymmetric cyanosilylation of aldehydes as well as simple and functionalized ketones. The isolated Ru.Li bimetallic complexes were suitable for the asymmetric hydrocyanation of aldehydes. This combined system was applicable to the asymmetric conjugate hydrocyanation of alpha,beta-unsaturated ketones and carboxylic acid derivatives, and the Strecker-type reaction of the pi-isoelectronic N-alkoxycarbonyl aldimines. This account describes the concept underlying the design of these catalysts, and the catalyst performance in the asymmetric reactions.
• 基礎講座：有機合成化学(2) あの身近な化合物はこうやって作られた

  新井則義, 大熊毅  現代化学  (561)  18  -23  2017/12  [Not refereed][Invited]
  
• 基礎講座：有機合成化学(1) 有機化合物の作り方事始め

  新井則義, 大熊毅  現代化学  (560)  17  -21  2017/11  [Not refereed][Invited]
  
• Design of molecular catalysts for achievement of high turnover number in homogeneous hydrogenation

  Noriyoshi Arai, Takeshi Ohkuma  CHEMICAL RECORD  12-  (2)  284  -289  2012/04  [Refereed][Not invited]
   

  Development of highly active catalysts has been an important research area in synthetic chemistry, especially from a practical point of view. Herein, we focus on the homogeneous catalytic hydrogenation using well-defined molecular catalysts and discuss recent advances in the field with regard to the turnover number for these catalysts. DOI 10.1002/tcr.201100019
• 4 Studies toward the Total Synthesis of Kazusamycin, an Antitumor Compound

  Arai Noriyoshi, Chikaraishi Noriko, Omura Satoshi, Kuwajima Isao  Symposium on the Chemistry of Natural Products, symposium papers  0-  (44)  19  -24  2002/09/01  [Not refereed][Not invited]
   

  Kazusamycin, which was isolated as a metabolite of actinomycete strain 81-484, attracts much attention due to its potent antitumor activity on P388 leukemia and sarcoma 180. It was also effective in completely preventing growth of HeLa cells at a concentration of 3.3ng/ml. On the other hand, from the structural point of view, only its planar structure was elucidated, and both its absolute configuration and complete relative configuration remain unknown. We are making an effort on the total synthesis of Kazusamycin in order to determine its absolute configuration and to establish a practical...
• スズヒドリドに代わる新規ラジカルメディエーター:シリルシクロヘキサジエン

  新井 則義  化学と工業 = Chemistry and chemical industry  54-  (4)  492  -492  2001/04/01  [Not refereed][Not invited]
  

Books etc

• 有機合成実験法ハンドブック

  大熊毅, 新井則義 (Joint work25.1.4 還元法―水素ガスを用いる―触媒の調製と反応例)
  丸善 2015
• e-EROS Encyclopedia of Reagents for Organic Synthesis

  Ohkuma, Takeshi, Arai, Noriyoshi (Joint workPhosphine, 1,1'-(1R)-[1,1'-binaphtharene]-2,2'-diylbis[bis(4-methylphenyl)-; Phosphine, 1,1'-(1S)-[1,1'-binaphtharene]-2,2'-diylbis[bis(4-methylphenyl)-)
  Wiley Online Library 2014
• Comprehensive Chirality

  Ohkuma, Takeshi, Arai, Noriyoshi (Joint workReduction–Hydrogenation: C=O; Chemoselective)
  Elsevier 2012
• Science of Synthesis, Stereoselective Synthesis 2

  Arai, Noriyoshi, Ohkuma, Takeshi (Joint workReduction of Carbonyl Groups: Hydrogenation)
  Thieme 2010
• 触媒便覧

  大熊毅, 新井則義 (Joint work17.6.2不斉水素化反応)
  講談社サイエンティフィク 2008
• Modern Reduction Methods

  Arai, Noriyoshi, Ohkuma, Takeshi (Joint workCarbonyl Hydroboration)
  Wiley-VCH 2008

Presentations

• Generation of Molecular Complexity by Photochemical Activation of 5-Membered Heteroaromatics  [Invited]

  Noriyoshi Arai

  18th Malaysian International Chemical Congress  2014/11
• Enantioselective 1,3-Hydrogen Migration of Primary Allylic Alcohols Catalyzed by Diphosphine–Ru(II) Complexes  [Not invited]

  Arai, Noriyoshi, Sato, Keisuke, Ohkuma, Takeshi

  26th International Conference on Organometallic Chemistry  2014/07

Association Memberships

• THE SOCIETY OF SYNTHETIC ORGANIC CHEMISTRY   THE CHEMICAL SOCIETY OF JAPAN   

Research Projects

• 光による分子活性化を活用した高立体選択的有機分子構築手法の開発

  日本学術振興会：科学研究費助成事業，基盤研究C

  Date (from‐to) : 2013/04 -2015/03 

  Author : 新井則義
• 高原子価金属化合物による酸化反応を利用した1、3−双極子発生手法の開発

  日本学術振興会：科学研究費助成事業

  Date (from‐to) : 1997 -1998 

  Author : 新井 則義

   

  筆者は,α-ヒドロキシイミノカルボン酸に対し,アルケン,またはアルキン類の存在下,硝酸アンモニウムセリウム(IV)(CAN)を作用させることによりニトリルオキシドを生成し,対応する付加生成物として4,5-ジヒドロイソオキサゾール,あるいはイソオキサゾール誘導体がそれぞれ得られることをすでに見出している。今年度の検討において,ニトリルオキシドの前駆体としてα-ヒドロキシイミノカルボン酸のみならず2-オキソアルドキシムも有効に活用でき,アシル(アロイル)ニトリルオキシドの発生に利用できることを見出した。たとえば,フェニルグリオキサール-1-オキシムに対しアクリル酸エチルの存在下CANを作用させると,生じたベンゾイルニトリルオキシドとアクリル酸エチルとの環状付加反応が進行し,3-ベンゾイル-4,5-ジヒドロイソオキサゾール-5-カルボン酸エチルが85%の収率で得られる。アシル(アロイル)ニトリルオキシドの効率の良い発生手法についてはわずかしか報告例がないが,本手法を用いることにより3-アシルイソオキサゾール誘導体を収率良く合成することができる。さらに,2-オキソアルドキシムに代え2-オキソアルデヒド-1-ヒドラゾンを用いれば,ニトリルオキシドと同様1,3-双極子の一種であるニトリルイミンを発生させることも可能なのではないかと考え,フェニルグリオキサール-1-アセチルヒドラゾンに対し,CANを作用させ反応を試みた。その結果,オレフィンとの付加生成物は得られなかったものの,自己環化生成物である1,3,4-オキサジアゾール誘導体が得られた。この化合物はニトリルイミンの発生を示唆するものと考えられる。