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Stereocomplementary reactions for preparing multi-substituted olefins and its application to distinctive molecules

Research Project

Project/Area Number 15K05508
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Synthetic chemistry
Research InstitutionKwansei Gakuin University

Principal Investigator

Yoo Tanabe  関西学院大学, 理工学部, 教授 (30236666)

Co-Investigator(Renkei-kenkyūsha) MISAKI Tomonori  兵庫県立大学, 大学院理学研究科, 助教 (00411786)
NISHII Yoshinori  信州大学, 繊維学部, 准教授 (40332259)
Research Collaborator NAKATSUJI Hidefumi  関西学院大学, 理工学部, 助教 (80751817)
ASHIDA Yuichiro  関西学院大学, 大学院理工学研究科, リサーチアシスタント
Project Period (FY) 2015-10-21 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords立体選択的合成 / 多置換オレフィン / プロセス化学 / 立体補完的合成 / パラレル合成 / 医薬 / トシル化 / クロスカップリング / 立体補完的 / 立体補的合成
Outline of Final Research Achievements

A divergent synthetic methodology producing E- and Z-stereodefined multi-substituted olefin scaffolds has been performed. The present protocols, which are directed for process chemistry, involve highly substrate-general E- and Z-stereocomplementary parallel syntheses. As distinctive applications, the first parallel syntheses of a couple of notable and useful pharmaceuticals were accomplished. That is (1) parallel synthesis of SSRI-drug, Zimelidine, without use of resolution method, and (2) parallel synthesis of cancer-treatment drug, Tamoxifen, a representative synthetic motif of all-carbon (fully)-substituted olefins. This methodology was highlighted in “Synform,” which is the journal introducing a notable synthetic chemistry.
During the course of study, we could propose two “Organic syntheses” procedures, which document practical methods with reproducibility for important synthetic building blocks.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (33 results)

All 2018 2017 2016 2015 Other

All Journal Article (17 results) (of which Peer Reviewed: 17 results,  Open Access: 6 results,  Acknowledgement Compliant: 9 results) Presentation (15 results) (of which Int'l Joint Research: 5 results) Remarks (1 results)

  • [Journal Article] Stereocomplementary Synthesis of cis- and trans-2-(p-Bromophenyl)-5-methylthiazolidin-4-ones: Useful Umpolung-type Suzuki-Miyaura Cross-coupling Partner2018

    • Author(s)
      Ryosuke Sasaki, Hidefumi Nakatsuji, Yoo Tanabe
    • Journal Title

      J. Heterocycl. Chem.

      Volume: 55

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chiral Syntheses of Methyl (R)-2-Sulfanylcarboxylic Esters and Acids with Optical Purity Determination using HPLC2018

    • Author(s)
      Ryosuke Sasaki, Yoo Tanabe
    • Journal Title

      Chirality

      Volume: 30 Issue: 6 Pages: 816-827

    • DOI

      10.1002/chir.22860

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Straightforward synthesis of N-methyl-4-(pin)B-2(3H)-benzothiazol-2-one: A promising cross-coupling reagent2018

    • Author(s)
      Shotaro Izawa, Hidefumi Nakatsuji, Yoo Tanabe
    • Journal Title

      Molbank

      Volume: - Issue: 1 Pages: M976-M976

    • DOI

      10.3390/m976

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dehydration-type Ti-Claisen Condensation (Carbonhomologation) of α-Heteroatom-substituted Acetates with Alkyl Formates: Utilization as (Z)-Stereodefined Cross-coupling Partners and Application to Concise Synthesis of Strobilurin A2017

    • Author(s)
      Hidefumi Nakatsuji, Risa Kamada, Hideya Kitaguchi, Yoo Tanabe
    • Journal Title

      Adv. Synth. Catal.

      Volume: 359 Issue: 21 Pages: 3865-3879

    • DOI

      10.1002/adsc.201700879

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] General and Robust Method for the Preparation of (E)- and (Z)-Stereodefined Fully-substituted Enol Tosylates: A Promising Cross-coupling Partner2017

    • Author(s)
      Yuichiro Ashida, Yuka Sato, Atsushi Honda, Hidefumi Nakatsuji, Yoo Tanabe
    • Journal Title

      Synform

      Volume: -

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Divergent Synthetic Access to (E)- and (Z)-Stereodefined All-Carbon (fully)-substituted Olefin Scaffolds: Application to Parallel Synthesis of Both (E)- and (Z)-Tamoxifens2017

    • Author(s)
      Yuichiro Ashida, Atsushi Honda, Yuka Sato, Hidefumi Nakatsuji, Yoo Tanabe
    • Journal Title

      ChemistryOpen

      Volume: 6 Issue: 1 Pages: 73-89

    • DOI

      10.1002/open.201600124

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Asymmetric total syntheses of two 3-acyl-5,6-dihydro-2H-pyrones: (R)-podoblastin-S and (R)-lachnelluloic acid with its verification of the absolute configuration2017

    • Author(s)
      Tetsuya Fujiwara, Takeshi Tsutsumi, Kohei Nakata, Hidefumi Nakatsuji, Yoo Tanabe
    • Journal Title

      Molecules (asymmetric syntheses 2016, invited)

      Volume: 22 Issue: 1 Pages: 69-77

    • DOI

      10.3390/molecules22010069

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] A Useful Cross-coupling for the Synthesis of Methyl (Z)-3-Phenyl (or Aryl)-2-butenoate2017

    • Author(s)
      Yuichiro Ashida, Hidefumi Nakatsuji, Yoo Tanabe
    • Journal Title

      Organic Syntheses

      Volume: 94 Pages: 93-108

    • DOI

      10.15227/orgsyn.094.0093

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A General and Robust Method for the Preparation of (E)- and (Z)-Stereodefined Fully Substituted Enol Tosylates: Promising Cross-Coupling Partners2017

    • Author(s)
      Yuichiro Ashida, Yuka Sato, Atsushi Honda, Hidefumi Nakatsuji, Yoo Tanabe
    • Journal Title

      Synform

      Volume: 3 Pages: 38-43

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] (Z)-Enol p-Tosylate Derived from Methyl Acetoacetate: A Useful Cross-coupling Partner for the Synthesis of Methyl (Z)-3-Phenyl (or Aryl)-2-butenoate2017

    • Author(s)
      Yuichiro Ashida, Hidefumi Nakatsuji, Yoo Tanabe
    • Journal Title

      Organic Syntheses

      Volume: 94

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Synthesis of Methyl 1-Formylcyclopropanecarboxylate utilizing Ti-Claisen Condensation2016

    • Author(s)
      Yuichiro Ashida, Satomi Kajimoto, Hidefumi Nakatsuji, Yoo Tanabe
    • Journal Title

      Organic Syntheses

      Volume: 93 Pages: 286-305

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] A General and Robust Method for the Preparation of (E)- and (Z)-Stereodefined Fully-substituted Enol Tosylates: A Promising Cross-coupling Partner2016

    • Author(s)
      Yuichiro Ashida, Yuka Sato, Atsushi Honda, Hidefumi Nakatsuji, Yoo Tanabe
    • Journal Title

      Synthesis

      Volume: 48 Issue: 23 Pages: 4072-4080

    • DOI

      10.1055/s-0035-1562482

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Acid-induced Favorskii-type Reaction: Regiocontrolled Elimination of Acyloin Mesylates Leading to α,β-Unsaturated Ketones and Application to Formal Total Synthesis of (R)-Muscone from Racemic Muscone2016

    • Author(s)
      Yuichiro Ashida, Akihiro Tanaka, Kohei Hosomi, Atsushi Nakamura, Tomonori Misaki, Hidefumi Nakatsuji, Yoo Tanabe
    • Journal Title

      ChemistrySelect

      Volume: 1 Pages: 3215-3218

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Asymmetric Total Synthesis of (-)-Azaspirene utilizing Ti-Claisen Condensation and Ti-Direct Aldol Reaction2016

    • Author(s)
      Mikiko Sugi, Ryohei Nagase, Tomonori Misaki, Hidefumi Nakatsuji, Yoo Tanabe
    • Journal Title

      Eur. J. Org. Chem.

      Volume: non Pages: 4834-4841

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Straightforward synthesis of 2(5H)-furanones as promising cross-coupling partners: Direct furanone annulation utilizing Ti-mediated aldol addition2016

    • Author(s)
      Yuki Ban, Yuichiro Ashida, Hidefumi Nakatsuji, Yoo Tanabe
    • Journal Title

      Molbank (The 1st communication issue, invited)

      Volume: non Issue: 4 Pages: M908-M908

    • DOI

      10.3390/m908

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] (E)-, (Z)-Parallel Preparative Methods for Stereodefined β,β-Diaryl- and α,β-Diaryl-α,β-unsaturated Esters: Application to Stereocomplementary Concise Synthesis of Zimelidine2015

    • Author(s)
      Yuichiro Ashida, Yuka Sato, Takeyuki Suzuki, Kanako Ueno, Ken-ichiro Kai, Hidefumi, Nakatsuji, Yoo Tanabe
    • Journal Title

      Chem. Eur. J.

      Volume: 21 Issue: 15 Pages: 5934-5945

    • DOI

      10.1002/chem.201405150

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] (E)- and (Z)-Stereodefined enol phosphonates derived from β-ketoesters: Stereocomplementary synthesis of fully-substituted α,β-unsaturated esters2015

    • Author(s)
      Hidefumi Nakatsuji, Yuichiro Ashida, Hiroshi Hori, Yuka Sato, Atsushi Honda, Mayu Taira, Yoo Tanabe
    • Journal Title

      Org. Biomol. Chem.

      Volume: 13 Issue: 30 Pages: 8205-8210

    • DOI

      10.1039/c5ob01097g

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] (E)- , (Z)-Tamoxifenの (E)-, (Z)-立体補完的パラレル簡便合成の開発2016

    • Author(s)
      ○本田惇,蘆田雄一郎,仲辻秀文, 田辺 陽
    • Organizer
      日本化学会第96春季年会
    • Place of Presentation
      同志社大学(京都府・京田辺市)
    • Year and Date
      2016-03-26
    • Related Report
      2015 Research-status Report
  • [Presentation] ZrCl4-amine 反応剤を用いるα-ハロホルミルエステルの効率的合成法2016

    • Author(s)
      ○坂雄生,梶本紗智美,蘆田雄一郎,仲辻秀文,田辺 陽
    • Organizer
      日本化学会第96春季年会
    • Place of Presentation
      同志社大学(京都府・京田辺市)
    • Year and Date
      2016-03-26
    • Related Report
      2015 Research-status Report
  • [Presentation] (R)-チオ乳酸およびエステルの実用的合成法とキラルHPLC 光学純度測定2016

    • Author(s)
      ○佐々木亮祐,今井康明,仲辻秀文,田辺 陽
    • Organizer
      日本化学会第96春季年会
    • Place of Presentation
      同志社大学(京都府・京田辺市)
    • Year and Date
      2016-03-26
    • Related Report
      2015 Research-status Report
  • [Presentation] 芳香族の位置選択的カチオン的チオシアノ化反応2016

    • Author(s)
      ○井澤 章太郎,蘆田 雄一郎,仲辻 秀文,田辺 陽
    • Organizer
      日本化学会第96春季年会
    • Place of Presentation
      同志社大学(京都府・京田辺市)
    • Year and Date
      2016-03-26
    • Related Report
      2015 Research-status Report
  • [Presentation] 不斉向山アルドール反応を利用するGibberellin 共力物質 (-)-Pestalotin の不斉全合成研究2016

    • Author(s)
      ○中田孝平,藤原哲也,仲辻秀文,田辺陽
    • Organizer
      日本化学会第96春季年会
    • Place of Presentation
      同志社大学(京都府・京田辺市)
    • Year and Date
      2016-03-26
    • Related Report
      2015 Research-status Report
  • [Presentation] 不斉Ti-Claisen-Aldol Domino反応を鍵とする鎖状四連続不斉中心形成2016

    • Author(s)
      ○依田崚平,増山義和,蘆田雄一郎,仲辻 秀文,田辺 陽
    • Organizer
      日本化学会第96春季年会
    • Place of Presentation
      同志社大学(京都府・京田辺市)
    • Year and Date
      2016-03-26
    • Related Report
      2015 Research-status Report
  • [Presentation] β-ケトアミドのエノールトシル化・クロスカップリングを利用する α,β-不飽和アミドの(E)-, (Z)-立体補完的合成法2016

    • Author(s)
      ○竹本太一, 蘆田雄一郎, 仲辻秀文, 田辺 陽
    • Organizer
      日本化学会第96春季年会
    • Place of Presentation
      同志社大学(京都府・京田辺市)
    • Year and Date
      2016-03-26
    • Related Report
      2015 Research-status Report
  • [Presentation] エノールトシラートを前駆体とする (E)-, (Z)-立体補完的パラレル反応によるフル置換アルケンの合成法の開発とその医薬品合成への応用2016

    • Author(s)
      ○蘆田雄一郎, 佐藤有華, 仲辻秀文, 田辺 陽
    • Organizer
      日本化学会第96春季年会
    • Place of Presentation
      同志社大学(京都府・京田辺市)
    • Year and Date
      2016-03-25
    • Related Report
      2015 Research-status Report
  • [Presentation] ニトリルの α-アニオンの特性を活かした (+)-Grandisol の短段階不斉全合成2016

    • Author(s)
      ○藤原哲也・仲辻秀文・田辺 陽
    • Organizer
      日本化学会第96春季年会
    • Place of Presentation
      同志社大学(京都府・京田辺市)
    • Year and Date
      2016-03-24
    • Related Report
      2015 Research-status Report
  • [Presentation] Parallel and (E)-and (Z)-stereocomplementary synthesis of multi-substituted α,β-unsaturated esters directed for process chemistry: Application to expeditious parallel syntheses of all four (E)-and (Z)-Zimelidine and Tamoxifen2015

    • Author(s)
      ○Yuichiro Ashida, Yuka Sato, Hidefumi Nakatsuji, Yoo Tanabe
    • Organizer
      Pacifichem 2015
    • Place of Presentation
      Hawaii Convention Center(ホノルル市・アメリカ)
    • Year and Date
      2015-12-19
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Practical preparation of α-formyl esters from simple esters and methyl formate utilizing Ti-Claisen condensation and its utilization for useful building blocks2015

    • Author(s)
      ○Satomi Kajimoto, Yuichiro Ashida, Hidefumi Nakatsuji, Yoo Tanabe
    • Organizer
      Pacifichem 2015
    • Place of Presentation
      Hawaii Convention Center(ホノルル市・アメリカ)
    • Year and Date
      2015-12-19
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Chiral cyclopropane and cyclobutane forming reactions using α-anion of nitriles; asymmetric synthetic study of (1R,3R)-Metofluthrin and (+)-Grandisol2015

    • Author(s)
      ○Tetsuya Fujiwara, Yuji Takahama, Yuichiro Ashida, Noritada Matsuo, Hidefumi Nakatsuji, Yoo Tanabe
    • Organizer
      Pacifichem 2015
    • Place of Presentation
      Hawaii Convention Center(ホノルル市・アメリカ)
    • Year and Date
      2015-12-19
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] (E)-, (Z)-Stereocomplementary parallel synthesis of (E)- and (Z)- Tamoxifens2015

    • Author(s)
      ○Atsushi Honda, Yuichiro Ashida, Yuka Sato, Hidefumi Nakatsuji, Yoo Tanabe,
    • Organizer
      Pacifichem 2015
    • Place of Presentation
      Hawaii Convention Center(ホノルル市・アメリカ)
    • Year and Date
      2015-12-19
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Parallel(E)- and (Z)-Stereocomplementary Synthesis of Di- or Tri-Substituted α,β-Unsaturated Esters: Application to Expeditious Parallel Syntheses of All Four (E)- and (Z)-Zimeridines and Tamoxifens2015

    • Author(s)
      ○Yuichiro Ashida, Yuka Sato, Atsushi Honda, Hidefumi Nakatsuji, Yoo Tanabe
    • Organizer
      13th International Kyoto Conference on New Aspects of Organic Chemistry (IKCOC-13)
    • Place of Presentation
      Rihga Royal Hotel KYOTO(京都府・京都市)
    • Year and Date
      2015-11-10
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] エノールトシラートを前駆体とするフル置換 α, β-不飽和エステルの (E), (Z)-立体補完的パラレル合成2015

    • Author(s)
      ○蘆田雄一郎,佐藤有華,仲辻秀文,田辺陽
    • Organizer
      第41回反応と合成の進歩シンポジウム
    • Place of Presentation
      近畿大学(大阪府・東大阪市)
    • Year and Date
      2015-10-27
    • Related Report
      2015 Research-status Report
  • [Remarks] 関西学院大学理工学部,田辺研究室ホームページ

    • URL

      http://sci-tech.ksc.kwansei.ac.jp/~tanabe/index.html

    • Related Report
      2016 Research-status Report

URL: 

Published: 2015-10-21   Modified: 2019-03-29  

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