Regiocontrol of heteroaryne reactions by redox change

• Project/Area Number: 23790017
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Chemical pharmacy
• Research Institution: University of Shizuoka
• Principal Investigator: IKAWA Takashi 静岡県立大学, 薬学部, 助教 (20453061)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2011: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: ピリダイン / イソキノリン / Diels-Alder 反応 / 位置選択性 / ケイ素官能基 / フラン / 複素環 / カップリング / Diels-Alder反応 / アライン / アライン前駆体 / シリル基 / スタニル基 / ヘテロ環合成 / フッ素アニオン

Research Abstract

A new synthetic route to isoquinoline derivatives consisting regioselective Diels-Alder reactions of 3,4-pyridynes with furans and following functional group transformations is reported. The key for the regioselectivity of the cycloaddition reactions is electropositive silicon atom of the 2-position of 3,4-pyridyne. This directing group can also be substituted with various functional groups.

Research Products

• [Journal Article] Generation of 3-Borylbenzynes, Their Regioselective Diels-Alder Reactions, and Theoretical Analysis (2013)
  • Author(s): Takashi Ikawa, Akira Takagi, Yurio Kurita, Kozumo Saito, Kenji Azechi, Masahiro Egi, Yuji Itoh, Hiroaki Tkiwa, Yasuyuki Kita, and Shuji Akai
  • Journal Title: Tetrahedron Volume: 69 Issue: 21 Pages: 4338-4352
  • DOI: 10.1016/j.tet.2013.03.016
  • Peer Reviewed
• [Journal Article] Regiocomplementary Cycloaddition Reactions of Boryl- and Silylbenzynes with 1, 3-Dipoles : Selective Synthesis of Benzo-Fused Azole Derivatives (2013)
  • Author(s): Akira Takagi, Takashi Ikawa, Alcira Takagi, Masahiko Goto, Yuya Aoyama, Yoshinobu Ishikawa, Yuji Itoh, Hiroaki Tokiwa, and Shuji Akai
  • Journal Title: The Journal of Organic Chemistry Volume: 78 Issue: 7 Pages: 2965-2983
  • DOI: 10.1021/jo302802b
  • Peer Reviewed
• [Journal Article] Discovery of Aromatic Components with Excellent Fragrance Properties and Biological Activities: β-Ionols with Antimelanogenetic Effects and Their Asymmetric Syntheses (2013)
  • Author(s): Komaki Ryoichi, Ikawa Takashi, Saito Kozumo, Hattori Kazuyo, Ishikawa Natsuyo, Fukawa Hidemichi, Egi Masahiro, Akai Shuji
  • Journal Title: Chemical and Pharmaceutical Bulletin Volume: 61 Issue: 3 Pages: 310-314
  • DOI: 10.1248/cpb.c12-00916
  • NAID: 130003360738
  • ISSN: 0009-2363, 1347-5223
  • Peer Reviewed
• [Journal Article] Palladium-Catalyzed One-Pot Cross-Coupling of Phenols Using Nonafluorobutanesulfonyl Fluoride (2012)
  • Author(s): Ikawa Takashi, Saito Kozumo, Akai Shuji
  • Journal Title: Synlett Volume: 23 Issue: 15 Pages: 2241-2246
  • DOI: 10.1055/s-0032-1317076
• [Journal Article] Selective N-Alkylation of Amines Using Nitriles under Hydrogenation Conditions: Facile Synthesis of Secondary and Tertiary Amines (2012)
  • Author(s): Ikawa Takashi, Fujita Yuki, Mizusaki Tomoteru, Betsuin Sae, Takamatsu Haruki, Maegawa Tomohiro, Monguchi Yasunari, Sajiki Hironao
  • Journal Title: Org. Biomol. Chem. Volume: 10 Issue: 2 Pages: 293-304
  • DOI: 10.1039/c1ob06303k
• [Journal Article] Ortho-selective nucleophilicaddition of primary amines tosilylbenzynes: Synthesis of 2-silylanilines (2011)
  • Author(s): Y . Kita et al.
  • Journal Title: Angew . Chem., Int. Ed. Volume: 50 Issue: 25 Pages: 5674-5677
  • DOI: 10.1002/anie.201100360
  • Peer Reviewed
• [Journal Article] A Domino Process for Benzyne Preparation: Dual Activation of o-(Trimethylsilyl)phenols by Nonafluorobutanesulfonyl Fluoride (2011)
  • Author(s): Ikawa Takashi, Nishiyama Tsuyoshi, Nosaki Toshifumi, Takagi Akira, Akai Shuji
  • Journal Title: Org. Lett. Volume: 13 Issue: 7 Pages: 1730-1733
  • DOI: 10.1021/ol200252c
• [Journal Article] Preparation and regioselective Diels- Alder reactions of borylbenzynes: synthesis of functionalized arylboronates (2010)
  • Author(s): Y. Kita et al.
  • Journal Title: Angew. Chem., Int. Ed. Volume: 49 Issue: 32 Pages: 5563-5566
  • DOI: 10.1002/anie.201002191
  • Peer Reviewed
• [Presentation] Experimental and Theoretical Study on Regioselective Reactions of 3-Silyl-and 3-Borylbenzyne (2013)
  • Author(s): Ikawa Takashi, Takagi Akira, Akai Shuji
  • Organizer: The 6th Heron Island Conference on Reactive Intermediates and Unusual Molecules: Synthesis and Mechanism (Heron 6)
  • Place of Presentation: Australia
• [Presentation] Regioselective Diels-Alder Reactions of 2-Silyl-3,4-pyridynes with Furans: Selective Synthesis of Isoquinolines (2013)
  • Author(s): Ikawa Takashi, Urata Hirohito, Nishiyama Tsuyoshi, Akai Shuji
  • Organizer: 23nd French-Japanese Symposium of Medicinal and Fine Chemistry
  • Place of Presentation: Nagasaki, Japan
• [Presentation] Experimental and Theoretical Study on Regioselective Reactions of 3-Silyl- and 3-Borylbenzyne (2013)
  • Author(s): Ikawa, Takashi
  • Organizer: The 6th Heron Island Conference on Reactive Intermediates and Unusual Molecules: Synthesis and Mechanism (Heron 6)
  • Place of Presentation: Heron Island, Australia
  • Invited
• [Presentation] フェノール類から多置換芳香族化合物の効率的合成 (2013)
  • Author(s): 井川貴詞
  • Organizer: 平成25年度日本薬学会東海支部会 奨励賞受賞講演
  • Place of Presentation: 名古屋
  • Invited
• [Presentation] Regioselective Diels–Alder Reactions of 2-Silyl-3,4-pyridynes with Furans: Selective Synthesis of Isoquinolines (2013)
  • Author(s): Ikawa, Takashi
  • Organizer: 23nd French-Japanese Symposium of Medicinal and Fine Chemistry
  • Place of Presentation: Nagasaki, Japan
• [Presentation] 初めての5,6-及び6,7-キノラインの調製と縮合キノリン誘導体合成への応用 (2013)
  • Author(s): 井川貴詞
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 横浜
• [Presentation] 段階的官能基導入を実現する新規1,3-benzdiyne等価体の開発 (2013)
  • Author(s): 井川貴詞
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 横浜
• [Presentation] 含ホウ素前駆体を用いる官能基化されたベンザイン発生法の開発 (2013)
  • Author(s): 井川貴詞
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 横浜
• [Presentation] 四成分を連結するaloinの収束的合成研究 (2013)
  • Author(s): 井川貴詞
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 横浜
• [Presentation] シリル置換ピリダインの位置選択的Diels-Alder反応:多置換イソキノリンの構築 (2012)
  • Author(s): 浦田博一,西山剛史,井川貴詞,赤井周司
  • Organizer: 第38回反応と合成の進歩シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2012-11-06
• [Presentation] 置換ベンザインの(3+2)環化付加反応による縮合芳香族複素環の位置選択的合成 (2012)
  • Author(s): 高木晃,井川貴詞,後藤雅彦,青山祐也,赤井周司
  • Organizer: 第29回有機合成化学セミナー
  • Place of Presentation: 静岡
  • Year and Date: 2012-09-06
• [Presentation] 置換基効果を用いる3,4-ピリダインの位置選択的環化付加反応 (2012)
  • Author(s): 井川貴詞,浦田博一,西山剛史,赤井周司
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌
  • Year and Date: 2012-03-30
• [Presentation] NfF-Mediated in-situ Activation of Phenols for Benzyne Generation and Coupling Reactions (2012)
  • Author(s): Ikawa Takashi, Saito Kozumo, Nishiyama Tsuyoshi, Nosaki Toshifumi, Takagi Akira, Akai Shuji
  • Organizer: The 6th Takeda Science Foundation Symposium on PharmaSciences
  • Place of Presentation: Osaka, Japan
• [Presentation] Regioselective Cycloaddition Reactions of Silyl-and Boryl-Benzynes: Regiocontrolled Synthesis of Multisubstituted Aromatic Compounds (2012)
  • Author(s): Takagi Akira, Ikawa Takashi, Takayanagi Sho-ichi, Goto Masahiko, Aoyama Yuya, Itoh Yuji, Tokiwa Hiroaki, Akai Shuji
  • Organizer: The 6th Takeda Science Foundation Symposium on PharmaSciences
  • Place of Presentation: Osaka, Japan
• [Presentation] NfFを用いるフェノール類の直接クロスカップリング反応 (2012)
  • Author(s): 井川貴詞
  • Organizer: 第58回日本薬学会東海支部大会
  • Place of Presentation: 静岡
• [Presentation] Regioselective Cycloaddition Reactions of Silyl- and Boryl-Benzynes: Regiocontrolled Synthesis of Multisubstituted Aromatic Compounds (2012)
  • Author(s): Ikawa, Takashi
  • Organizer: The 6th Takeda Science Foundation Symposium on PharmaSciences
  • Place of Presentation: Osaka, Japan
• [Presentation] シリル置換ピリダインの位置選択的Diels-Alder反応：多置換イソキノリンの構築 (2012)
  • Author(s): 井川貴詞
  • Organizer: 第38回反応と合成の進歩シンポジウム
  • Place of Presentation: 東京
• [Presentation] ベンザインの位置選択的環化付加反応：DFT計算による機構解析 (2012)
  • Author(s): 井川貴詞
  • Organizer: 第23回基礎有機化学討論会
  • Place of Presentation: 京都
• [Presentation] ベンザインを経る芳香環への求核的フッ素化法 (2012)
  • Author(s): 井川貴詞
  • Organizer: 第29回有機合成化学セミナー
  • Place of Presentation: 静岡
• [Presentation] ケイ素官能基によるベンザインの(3+2)環化反応の位置制御とその応用 (2012)
  • Author(s): 井川貴詞
  • Organizer: 第58回日本薬学会東海支部大会
  • Place of Presentation: 静岡
• [Presentation] ortho-ボリルフェニルトリフラートを前駆体とするベンザインの新規発生法の開発 (2012)
  • Author(s): 井川貴詞
  • Organizer: 第58回日本薬学会東海支部大会
  • Place of Presentation: 静岡
• [Presentation] 連続するベンザインの位置選択的Diels-Alder反応によるアンスロン骨格の構築：aloinの合成研究 (2012)
  • Author(s): 井川 貴詞、野崎 俊史、繁田 尭、守川 由起、赤井 周司
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌
• [Presentation] ベンザインを経る芳香族フッ素化合物の合成 (2012)
  • Author(s): 井川貴詞、増田茂明、西山剛史、赤井周司
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌
• [Presentation] TBDMS置換ベンザインの位置選択的挿入反応 (2012)
  • Author(s): 井川貴詞、戸塚善博、赤井周司
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌
• [Presentation] Regiocontrol of Cycloaddition Reactions of Benzynes by Bory and Silyl Substituents (2011)
  • Author(s): Akai Shuji, Ikawa Takashi, Takagi Akira, Takayanagi Sho-ichi
  • Organizer: 22nd French-Japanese Symposium of Medicinal and Fine Chemistry
  • Place of Presentation: Rouen, France
  • Year and Date: 2011-09-12
• [Presentation] Theoretical Study of Regioselectivities in the Diels-Alder Reactions between Substituted Benzynes and Furans (2011)
  • Author(s): Takagi Akira, Ikawa Takashi, Takayanagi Sho-ichi, Itoh Yuji, Tokiwa Hiroaki, Akai Shuji
  • Organizer: Ninth Triennial Congress of the World Association of Theoretical and Computational Chemists (WATOC) 2011
  • Place of Presentation: Santiago de Compostela, Spain
  • Year and Date: 2011-07-19
• [Presentation] Practical Benzyne Preparation from Phenol Derivatives Using NfF (2011)
  • Author(s): Ikawa Takashi, Nishiyama Tsuyoshi, Akai Shuji
  • Organizer: The 2nd International Symposium for Process Chemistry
  • Place of Presentation: Kyoto, Japan
• [Presentation] ベンザインの位置選択的[3+2]環化付加反応：多置換ヘテロ芳香族化合物の位置制御合成 (2011)
  • Author(s): 井川貴詞，高木 晃，後藤雅彦，青山祐也，西山剛史，伊東祐二，常盤広明，赤井周司
  • Organizer: 第8回次世代を担う有機化学シンポジウム
  • Place of Presentation: 東京
• [Presentation] ケイ素官能基を配向基とする位置選択的ベンザイン挿入反応の開発 (2011)
  • Author(s): 井川貴詞，戸塚善博，赤井周司
  • Organizer: 第57回日本薬学会東海支部大会
  • Place of Presentation: 名古屋
• [Presentation] フッ素アニオン存在下におけるホウ素置換ベンザイン発生法及びその位置選択的反応の開発 (2011)
  • Author(s): 井川貴詞，後藤雅彦，高木 晃，赤井周司
  • Organizer: 第57回日本薬学会東海支部大会
  • Place of Presentation: 名古屋
• [Presentation] Theoretical Study of Regioselectivities in the Diels-Alder Reactions between Substituted Benzynes and Furans (2011)
  • Author(s): 高木 晃, 井川貴詞, 高柳祥一, 伊東祐仁, 常盤広明, 赤井周司
  • Organizer: Ninth Triennial Congress of the WORLD ASSOCIATIONOF THEORETICAL AND COMPUTATIONAL CHEMISTS WATOC 2011
  • Place of Presentation: スペイン, Santiago de Compostela
• [Presentation] Practicalbenzyne Preparation from Phenol Derivatives Using NfF (2011)
  • Author(s): 井川貴詞，西山剛史，赤井周司
  • Organizer: The 2nd International Symposium on Process Chemistry
  • Place of Presentation: 京都
• [Presentation] Regiocontrol of Cycloaddition Reactions of Benzynes by Bory and Silyl Substituents (2011)
  • Author(s): 赤井周司，井川貴詞，高木 晃，高柳祥一
  • Organizer: 22nd French-Japanese Symposium of Medicinal and Fine Chemistry
  • Place of Presentation: フランス, Rouen
• [Presentation] ホウ素置換ベンザインの三成分連結反応：多置換芳香族ボロン酸誘導体の合成 (2011)
  • Author(s): 井川貴詞，後藤雅彦，高木 晃，赤井周司
  • Organizer: 基礎有機化学討論会
  • Place of Presentation: つくば
• [Presentation] 位置選択的ベンザインDiels-Alder反応の連続的利用：aloinの合成研究 (2011)
  • Author(s): 井川貴詞，野崎俊史，繁田 尭，守川由起，赤井周司
  • Organizer: 第42回中部化学関係学協会支部連合秋季大会
  • Place of Presentation: 信州
• [Presentation] ケイ素及びホウ素置換ベンザインの環化付加反応における位置選択性発現機構の計算化学的解析 (2011)
  • Author(s): 高木 晃，井川貴詞，後藤雅彦，青山祐也，赤井周司，伊東祐仁，常盤広明
  • Organizer: 第37回反応と合成の進歩シンポジウム
  • Place of Presentation: 徳島