Synthesis of highly substituted chiral arylcyclopropanes via directing group-mediated tertiary C(sp3)-H arylation

• Project/Area Number: 26860003
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Chemical pharmacy
• Research Institution: Kyoto Pharmaceutical University
• Principal Investigator: Hoshiya Naoyuki 京都薬科大学, 薬学部, 助教 (40566949)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: C-H活性化 / シクロプロパン / 芳香環導入 / C-H官能基化 / 不斉４級炭素 / 三次元的多様性 / 配座制御

Outline of Final Research Achievements

In this research, functionalization of tertiary C(sp3)-H via catalytic C-H activation was investigated and Pd-catalyzed arylation and alkylation of tertiary C(sp3)-H bond were successfully developed. This is the first report of functionalization of tertiary C(sp3)-H via Pd-catalyzed C-H activation. The novel Pd-catalyzed functionalization provided alternative routes to chiral arylcyclopropanes and alkylcyclopropanes which are attractive candidates for new medicinal compounds. Now transition metal-catalyzed amination and alkoxylation of tertiary C-H bond on chiral cyclopropanes are under investigation.

Research Products

• [Journal Article] Pd(II)-Catalyzed Alkylation of Tertiary Carbon via Directing Group-Mediated C(sp3)-H Activation: Synthesis of Chiral 1,1,2-Trialkylsubstituted Cyclopropane. (2016)
  • Author(s): N. Hoshiya, K. Takenaka, S. Shuto, J. Uenishi
  • Journal Title: Org. Lett Volume: 18 Issue: 1 Pages: 48-51
  • DOI: 10.1021/acs.orglett.5b03229
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Nickel-Catalyzed Suzuki-Miyaura Coupling of a Tertiary Iodocyclopropane with Wide Boronic Acid Substrate Scope: Coupling Reaction Outcome Depends on Radical Species Stability (2015)
  • Author(s): Keisuke Yotsuji, Naoyuki Hoshiya, Takaaki Kobayashi, Hayato Fukuda, Hiroshi Abe, Mitsuhiro Arisawa and Satoshi Shuto
  • Journal Title: Adv. Synth. Catal. Volume: 357 Issue: 5 Pages: 1022-1028
  • DOI: 10.1002/adsc.201401000
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Pd 触媒 C(sp 3 )-H 活性化を経る第三級炭素のアルキル化を利用した光学活性1,1,2-アルキルシクロプロパンの合成 (2016)
  • Author(s): 竹中慧 、星谷 尚亨、周東 智、上西潤一
  • Organizer: 日本薬学会第136年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-03-26
• [Presentation] Pd 触媒 C(sp 3 )-H 活性化を鍵反応とする光学活性 3 - および 4 - 置換アリールシクロプロパンの合成 (2015)
  • Author(s): 近藤 萌美、星谷 尚亨、福田 隼、有澤 光弘、周東 智
  • Organizer: 第45回複素環化学討論会
  • Place of Presentation: 東京
  • Year and Date: 2015-11-19
• [Presentation] Pd(II)-Catalyzed Directing Group-Mediated Arylation and Alkylation of Tertiary C(sp3)-H bond on Chiral Cyclopropanes (2015)
  • Author(s): N. Hoshiya, K. Takenaka, M. Arisawa, S. Shuto, J. Uenishi
  • Organizer: The 13th International Kyoto Conference on New Aspects of Organic Chemistry
  • Place of Presentation: 京都
  • Year and Date: 2015-11-09
  • Int'l Joint Research
• [Presentation] 三級C(sp3)-H結合の活性化を経る光学活性シクロプロパン環上へのアルキル鎖導入反応の開発 (2015)
  • Author(s): 竹中慧、星谷尚亨、周東 智、上西潤一
  • Organizer: 日本薬学会第135年会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-25 – 2015-03-28
• [Presentation] Pd触媒およびNi触媒によるシクロプロパン第三級炭素上への芳香環導入反応－効率的化学空間探索型創薬ライブラリーの構築を目指して― (2014)
  • Author(s): 星谷尚亨、四辻慶佑、小林嵩明、福田 隼、阿部 洋、有澤光弘、周東 智
  • Organizer: 第40回反応と合成の進歩シンポジウム
  • Place of Presentation: 仙台
  • Year and Date: 2014-11-10 – 2014-11-11
• [Presentation] 三級C-H結合の活性化を利用した光学活性アリールシクロプロパン化合物の合成 (2014)
  • Author(s): 星谷尚亨、上西潤一
  • Organizer: 第64回日本薬学会近畿支部総会・大会
  • Place of Presentation: 京都
  • Year and Date: 2014-10-11
• [Presentation] Palladium-Catalyzed Intermolecular Direct Arylation of Tertiary Carbon on Cyclopropanes (2014)
  • Author(s): 星谷尚亨
  • Organizer: XXVI International Conference on Organometallic Chemistry; Post-symposium
  • Place of Presentation: 大阪
  • Year and Date: 2014-07-19
  • Invited