Preparation of a chiral organocatalyst and their application for asymmetric carbon-carbon bond construction

• Project/Area Number: 16550032
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Organic chemistry
• Research Institution: Shizuoka University
• Principal Investigator: TAKABE Kunihiko Shizuoka University, Department of Materials Science and Chemical Engineering, Professor, 工学部, 教授 (30022239)
• Co-Investigator(Kenkyū-buntansha): YODA Hidemi Shizuoka University, Department of Materials Science and Chemical Engineering, Professor, 工学部, 教授 (20201072) ; MASE Nouyuki Shizuoka University, Department of Materials Science and Chemical Engineering, Assistant professor, 工学部, 助手 (40313936)
• Project Period (FY): 2004 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥3,600,000 (Direct Cost: ¥3,600,000); Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000); Fiscal Year 2004: ¥2,400,000 (Direct Cost: ¥2,400,000)
• Keywords: Organocatalyst / Chiral phase-transfer catalyst / Pyrrolidine alkaloid / Asymmetric carbon-carbon bond construction / Environmentally friendly synthesis / Aldol reaction / Michael reaction / Proline derivatives / 不斉合成 / Michael反応 / キラルアミノアルコール / キラル相関移動触媒 / アミノシュガー

Research Abstract

We have developed a practical synthesis of the chiral lactam as a new chiral building block for a multitude of asymmetric induction. Excellent kinetic resolution of the lactam, followed by racemization of the resolved product provided the chiral lactam in good yield with >99% ee. Chemical transformation of the lactam furnished chiral (-)-epi-lentiginosin in 20% yield in 10 steps with no loss of enantiomeric excess.
Convenient synthesis of Pulchellalactam and its related compounds was also accomplished. Total yields of (Z)-Pulchellalactam and (E)-Pulchellalactam were 55% for 5 steps and 43% for 8 steps from commercially available and inexpensive citraconic anhydride, respectively
Chiral phase-transfer catalyzed enantioselective alkylations of tert-butyl glycinate-benzophenone Schiff base were investigated in aqueous media without any organic solvent. Reactions in aqueous media smoothly proceeded to give the desired product in higher yield than under standard liquid-liquid biphasic conditi ons. In aqueous media the formation of benzophenone, which was caused by in-situ hydrolysis of Schiff base, was depressed.
We have developed direct asymmetric cross-aldol reactions that can be performed in water without addition of organic solvents. A bifunctional catalyst with a long hydrophobic alkyl chain efficiently catalyzed the reactions and afforded the desired aldol products in excellent yield with high enantiomeric excess, even when only an equal molar ratio of the donor and acceptor was used. These results reveal an effective design strategy for the development of aqueous organocatalytic systems.
We have developed a direct, asymmetric Michael reaction that can be performed in brine or seawater without addition of organic solvents. A bifunctional catalyst with long hydrophobic alkyl chains efficiently catalyzed Michael reactions and afforded the desired products in excellent yield with high enantiomeric excess, even when only an equal molar ratio of the donor to acceptor was used.

Research Products

• [Journal Article] Organocatalytic Direct Asymmetric Aldol Reactions in Water (2006)
  • Author(s): Mase, N.
  • Journal Title: Journal of the American Chemical Society 128 Pages: 734-735
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Organocatalytic Direct Michael Reaction of Ketones and Aldehydes with β-Nitrostyrene in Brine (2006)
  • Author(s): Mase, N.
  • Journal Title: Journal of the American Chemical Society 128 Pages: 4966-4967
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Organocatalytic Direct Asymmetric Aldol Reactions in Water (2006)
  • Author(s): Mase, N., Nakai, Y, Ohara, N., Yoda, H., Takabe, K., Tanaka, F., Barbas, C.F., III
  • Journal Title: Journal of the American Chemical Society 128(3) Pages: 734-735
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Organocatalytic Direct Michael Reaction of Ketones and Aldehydes with β-Nitrostyrene in Brine (2006)
  • Author(s): Mase, N., Watanabe, K., Yoda, H., Takabe, K., Tanaka, F., Barbas, C.F., III
  • Journal Title: Journal of the American Chemical Society 128(15) Pages: 4966-4967
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Organocatalytic direct asymmetric aldol reaction in water (2006)
  • Author(s): N.Mase
  • Journal Title: Journal of the American Chemical Society 128(3) Pages: 734-735
• [Journal Article] Organocatalytic direct Michael reaction of ketones and aldehides with β-nitrostyrene in brine (2006)
  • Author(s): N.Mase
  • Journal Title: Journal of the American Chemical Society 128(in press)
• [Journal Article] SmI_2-promoted novel tandem elimination and coupling reactions of aliphatic imides with carbonyl compounds ; application to the synthesis of dl-isoretronecanol (2006)
  • Author(s): M.Kabata
  • Journal Title: Tetrahedron Letters 47 Pages: 1607-1611
• [Journal Article] Enantioselective reactions of tert-butyl glycinate-benzophenone Schiff base catalyzed by chiral phase-transfer catalyst in aqueous media without any organic solvent (2005)
  • Author(s): Mase, N.
  • Journal Title: Tetrahedron Letters 46 Pages: 3213-3216
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Highly regioselective lipase-catalyzed acetylation and hydrolysis of acyclic α,α'-alkenediols and their diacetates (2005)
  • Author(s): Hisano, T.
  • Journal Title: Tetrahedron Letters 46 Pages: 6293-6295
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Enantioselective reactions of tert-butyl glycinate-benzophenone Schiff base catalyzed by chiral phase-transfer catalyst in aqueous media without any organic solvent (2005)
  • Author(s): Mase, N., Ohno, T., Morimoto, H., Nitta, F., Yoda, H., Takabe, K.
  • Journal Title: Tetrahedron Letters 46(18) Pages: 3213-3216
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Highly regioselective lipase-catalyzed acetylation and hydrolysis of acyclic α,α'-alkenediols and their diacetates (2005)
  • Author(s): Hisano, T., Onodera, K., Toyabe, Y, Mase, N., Yoda, H., Takabe, K.
  • Journal Title: Tetrahedron Letters 46(37) Pages: 6293-6295
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Highly regioselective lipase-catalyzed acetylation and hydrolysis of acyclic α,α'-alkenediols and their diacetates (2005)
  • Author(s): T.Hisano
  • Journal Title: Tetrahedron Letters 46 Pages: 6293-6295
• [Journal Article] An efficient and straightforward synthetic process to an amino sugar analogue, furanodictine B. (2005)
  • Author(s): D.Matsuura
  • Journal Title: SYNLETT (2) Pages: 287-288
• [Journal Article] Enantioselective reactions of tert-butyl glycinate-benzophenone Schiff base catalyzed by chiral phase-transfer catalyst in aqueous media. (2005)
  • Author(s): N.Mase
  • Journal Title: TETRAHEDRON LETTERS (in press)
• [Journal Article] Convenient synthesis of pulchellalactam, a CD45 protein tyrosine phosphatase inhibitor from the marine fungus Corollospora pulchella, and its related compounds (2004)
  • Author(s): Bessho, J.-i.
  • Journal Title: Heterocycles 63 Pages: 1013-1016
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] First asymmetric synthesis of the marine furanosesterterpene natural product, (18S)-variabilin, employing enzymatic desymmetrization of propanediol derivatives (2004)
  • Author(s): Takabe, K.
  • Journal Title: Tetrahedron : Asymmetry 15 Pages: 909-912
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Novel and stereoselective asymmetric synthesis of an amino sugar analog, furanodictine A (2004)
  • Author(s): Yoda, H.
  • Journal Title: Tetrahedron Letters 45 Pages: 1599-1601
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Convenient synthesis of pulchellalactam, a CD45 protein tyrosine phosphatase inhibitor from the marine fungus Corollospora pulchella, and its related compounds (2004)
  • Author(s): Bessho, J.-i., Shimotsu, Y., Mizumoto, S., Mase, N., Yoda, H., Takabe, K.
  • Journal Title: Heterocycles 63(5) Pages: 1013-1016
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] First asymmetric synthesis of the marine furanosesterterpene natural product, (18S)-variabilin, employing enzymatic desymmetrization of propanediol derivatives (2004)
  • Author(s): Takabe, K., Hashimoto, H., Sugimoto, H., Nomoto, M., Yoda, H.
  • Journal Title: Tetrahedron : Asymmetry 15(6) Pages: 909-912
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Novel and stereoselective asymmetric synthesis of an amino sugar analog, furanodictine A (2004)
  • Author(s): Yoda, H., Suzuki, Y., Takabe, K.
  • Journal Title: Tetrahedron Letters 45(8) Pages: 1599-1601
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Convenient synthesis of pulchellalactam, a CD45 protein tyrosine phosphatases inhibitor from the marine fungus Corollospora pulchella. (2004)
  • Author(s): J.Bessho
  • Journal Title: HETROCYCLES 63(5) Pages: 1013-1016
• [Journal Article] Novel and stereoselective asymmetric synthesis of an amino sugar analog, furapodictine A. (2004)
  • Author(s): H.Yoda
  • Journal Title: TETRAHEDRON LETERS 45(8) Pages: 1599-1601