Lithium Amide in Consecutive Aminolithiation-Carbolithiation

• Project/Area Number: 24590035
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Chemical pharmacy
• Research Institution: Doshisha Women's College of Liberal Arts
• Principal Investigator: Tomioka Kiyoshi 同志社女子大学, 薬学部, 教授 (50114575)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 有機化学 / 薬学 / カルバニオン / 合成化学 / 活性種

Outline of Final Research Achievements

An addition reaction of nitrogen nucleophiles to C=C double bonds is important for C-N bond formation. Addition of lithium amides to olefins affords alkyllithiums, which is powerful nucleophiles and useful for additional bond forming reactions. We developed consecutive aminolithiation-carbolithiation reactions, and asymmetric one-pot [N+2+n] cyclization reactions. Asymmetric total synthesis of some natural products was also achieved by using our developed reactions.

Research Products

• [Journal Article] Cyclic Model for the Asymmetric Conjugate Addition of Organolithiums with Enoates (2015)
  • Author(s): Yasutomo Yamamoto
  • Journal Title: Synthesis Volume: 47 Issue: 15 Pages: 2256-2264
  • DOI: 10.1055/s-0034-1380702
  • NAID: 120005674638
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Exploration of Dimethylzinc-Mediated Radical Reactions. (2015)
  • Author(s): K. Yamada
  • Journal Title: Chem. Rec. Volume: 15 Issue: 5 Pages: 854-871
  • DOI: 10.1002/tcr.201500017
  • NAID: 120005689178
  • Peer Reviewed
• [Journal Article] Contiguous radical pivaloyloxymethylation-directed C(sp3)-H iodination of N-tosyl cycloalkanecarbaldimine. (2015)
  • Author(s): Ｋｉｙｏｓｈｉ Ｔｏｍｉｏｋａ
  • Journal Title: Tetrahedron Lettｅｒｓ Volume: 56 Issue: 23 Pages: 3086-3089
  • DOI: 10.1016/j.tetlet.2014.11.105
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A Short Synthesis of (+)-β-Lycorane by Asymmetric Conjugate Addition Cascade. (2015)
  • Author(s): Ｋｉｙｏｓｈｉ Ｔｏｍｉｏｋａ
  • Journal Title: Ｔｅｔｒａｈｅｄｒｏｎ Volume: 71 Issue: 39 Pages: 7222-7226
  • DOI: 10.1016/j.tet.2015.03.014
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] One-pot synthesis of N-heterocycles by a tandem addition reaction of ω-alkenylmagnesium bromide with C=N double bond–oxidative bromolactamization (2014)
  • Author(s): Yasutomo Yamamoto
  • Journal Title: Tetrahedron Lett. Volume: 54 Issue: 32 Pages: 4313-4315
  • DOI: 10.1016/j.tetlet.2013.06.002
  • Peer Reviewed
• [Journal Article] Total Synthesis of 8-epi-Javaberine A and Javaberine A (2014)
  • Author(s): Yasutomo Yamamoto
  • Journal Title: Heterocycles Volume: 88 Issue: 2 Pages: 1311-1321
  • DOI: 10.3987/com-13-s(s)101
  • Peer Reviewed
• [Journal Article] Addition and in situ halo-cyclization of ω-alkenyl Grignard reagents with aldehydes, ketones, carbon dioxide, and azodicarboxylate (2013)
  • Author(s): Yasutomo Yamamoto
  • Journal Title: New J. Chem. Volume: 37 Issue: 12 Pages: 3873-3876
  • DOI: 10.1039/c3nj00765k
  • Peer Reviewed
• [Journal Article] Critical Profiles of Chiral Diether-Mediated Asymmetric Conjugate Aminolithiation of Enoate with Lithium Amide as a Key to the Total Synthesis of (-)-Kopsinine (2013)
  • Author(s): Yasutomo Yamamoto
  • Journal Title: Tetrahedron Volume: 69 Issue: 15 Pages: 3264-3273
  • DOI: 10.1016/j.tet.2013.02.035
  • NAID: 120005244223
  • Peer Reviewed
• [Journal Article] NMR studies on the structure of a lithium amide-chiral diether complex for an asymmetric reaction (2013)
  • Author(s): Yasutomo Yamamoto
  • Journal Title: Tetrahedron Volume: 69 Issue: 19 Pages: 3836-3840
  • DOI: 10.1016/j.tet.2013.03.036
  • Peer Reviewed
• [Journal Article] Total Synthesis of (-)-Kopsinine by the Asymmetric One-Pot [N+2+3] Cyclization (2012)
  • Author(s): Yasutomo Yamamoto
  • Journal Title: Chem. Asian J. Volume: 7 Issue: 10 Pages: 2196-2198
  • DOI: 10.1002/asia.201200575
  • Peer Reviewed
• [Journal Article] Catalytic Asymmetric Synthesis of (S)-Laudanosine by Hydroamination (2012)
  • Author(s): Yasutomo Yamamoto
  • Journal Title: Heterocycles Volume: 86 Issue: 1 Pages: 469-485
  • DOI: 10.3987/com-12-s(n)44
  • Peer Reviewed
• [Journal Article] General Entry to Asymmetric One-Pot [N+2+n] Cyclization for the Synthesis of 3- to 7-Membered Azacycloalkanes (2012)
  • Author(s): Yasutomo Yamamoto
  • Journal Title: J. Org. Chem. Volume: 77 Issue: 17 Pages: 7212-7222
  • DOI: 10.1021/jo301495a
  • Peer Reviewed
• [Journal Article] Total Synthesis of (+)-trans-Dihydronarciclasine Utilizing Asymmetric Conjugate Addition. (2012)
  • Author(s): Kiyoshi Tomioka
  • Journal Title: Org. Lett. Volume: 14 Issue: 23 Pages: 5868-5871
  • DOI: 10.1021/ol302757y
  • Peer Reviewed
• [Journal Article] Steric Influence of N-Phosphorus-arylimines on the Rhodium-Catalyzed Asymmetric Arylation (2011)
  • Author(s): Hao, X.; Chen, Q.; Yamada, K.; Yamamoto, Y.; Tomioka, K
  • Journal Title: Tetrahedron Volume: 67(35) Issue: 22 Pages: 6469-6473
  • DOI: 10.1016/j.tet.2012.03.107
  • Peer Reviewed
• [Presentation] Short step asymmetric synthesis of complex molecules (2015)
  • Author(s): 富岡清
  • Organizer: Pacifichem2015
  • Place of Presentation: ヒルトンハワイアンビレッジ（ホノルル）
  • Year and Date: 2015-12-15
  • Int'l Joint Research / Invited
• [Presentation] 並列直列水素結合の有機化学 (2015)
  • Author(s): 富岡清
  • Organizer: 岐阜大学特別講演会
  • Place of Presentation: 岐阜大学工学部（岐阜）
  • Year and Date: 2015-05-15
  • Invited
• [Presentation] 医薬プロセス化学の科学と生産技術 (2015)
  • Author(s): 富岡清
  • Organizer: CPhI Japan 2015
  • Place of Presentation: 東京ビッグサイト（東京）
  • Year and Date: 2015-04-22
  • Invited
• [Presentation] 力量あるプロセス化学 (2014)
  • Author(s): 富岡 清
  • Organizer: 日本プロセス化学会 2014ウィンターシンポジウム
  • Place of Presentation: 富山国際会議場（富山）
  • Year and Date: 2014-12-05
  • Invited
• [Presentation] Paradigm re-shift of medicinal chemistry in Japan (2014)
  • Author(s): 富岡 清
  • Organizer: ドイツ薬学会年会
  • Place of Presentation: ゲーテ大学（フランクフルト）
  • Year and Date: 2014-09-24 – 2014-09-26
  • Invited
• [Presentation] Ｒadicals by Ｃhance (2014)
  • Author(s): 富岡 清
  • Organizer: CBC-Symposium on Free Radical Chemistry
  • Place of Presentation: ナンヤン工科大学（シンガポール）
  • Year and Date: 2014-04-25
  • Invited
• [Presentation] 彼岸花科アルカロイド類の不斉全合成 (2013)
  • Author(s): 富岡 清
  • Organizer: 第48回天然物化学談話会
  • Place of Presentation: アヤハレークサイドホテル（滋賀）
  • Invited
• [Presentation] 生産性プラス法則性-医薬プロセス化学の展望 (2013)
  • Author(s): 富岡 清
  • Organizer: 合同シンポジウム- 日本プロセス化学会 2013 ウインターシンポジウム・新学術領域研究「有機分子触媒による未来型分子変換」第3回公開シンポジウム-
  • Place of Presentation: 仙台市民会館（宮城）
  • Invited
• [Presentation] ithium Amide in Consecutive Aminolithiation-Carbolithiation (2013)
  • Author(s): 富岡 清
  • Organizer: 14th Tetrahedron Symposium
  • Place of Presentation: Seoul (Korea)
  • Invited
• [Presentation] Lithium amide-Chiral Diether as A Powerful Asymmetric Aminating Reagent (2013)
  • Author(s): 富岡 清
  • Organizer: 11st International Symposium of Organic Reactions (ISOR11)
  • Place of Presentation: Taipei (Taiwan)
  • Invited
• [Presentation] リチウムアミドを駆使する合成化学
  • Author(s): 富岡 清
  • Organizer: 九州大学先導物質化学研究所講演会
  • Place of Presentation: 九州大学 先導物質化学研究所（福岡）
  • Invited
• [Presentation] 彼岸花科アルカロイドの不斉全合成
  • Author(s): 富岡清
  • Organizer: 浜理薬品特別講演会
  • Place of Presentation: 浜理薬品（大阪）
  • Invited
• [Presentation] アミノリチオ化と炭素リチオ化の直結化学
  • Author(s): 富岡清
  • Organizer: 富山大学理学部-有機合成化学協会共催特別講演会
  • Place of Presentation: 富山大学理学部（富山）
  • Invited
• [Presentation] 医薬品プロセス化学の展望
  • Author(s): 富岡清
  • Organizer: 「電磁波励起非平衡反応場の物理化学と産業応用」に関する先導的研究開発委員会
  • Place of Presentation: 東京工業大学蔵前会館（東京）
  • Invited
• [Book] Copper-Catalyzed Asymmetric Synthesis (2014)
  • Author(s): Kiyoshi Tomioka
  • Total Pages: 29
  • Publisher: Wiley-VCH
• [Book] Comprehensive Chirality, Volume 3 (2012)
  • Author(s): Kiyoshi Tomioka
  • Total Pages: 29
  • Publisher: Elsevier
• [Book] Comprehensive Chirality, Volume 4 (2012)
  • Author(s): Kiyoshi Tomioka
  • Total Pages: 10
  • Publisher: Elsevier
• [Remarks] 同志社女子大学 研究者データベース
  • URL: http://research-db.dwc.doshisha.ac.jp/rd/html/japanese/researchersHtml/3239/3239_Researcher.html