Critical profiles of chiral diether-mediated asymmetric conjugate aminolithiation of enoate with lithium amide as a key to the total synthesis of (−)-kopsinine

• 原田, 慎吾

• Sakai, Takeo

• Takasu, Kiyosei

• 山田, 健一

• 山本, 康友

• 富岡, 清

抄録

Chiral diether-mediated asymmetric aminolithiation of indolylpropenoate with lithium amide in toluene at -78 °C for 15 min gave, after aqueous ammonium chloride quench, the corresponding conjugate addition product with 97% ee in 89% yield. If hydrogen chloride in methanol was selected as a quencher, however, aminolithiation at -78 °C for 3 h gave the corresponding adduct with 97% ee in 54% yield, along with recovery of the starting enoate in 39% yield. Based on this finding of an incomplete and slow reaction at -78 °C, the aminolithiation conditions were optimized to be at -60 °C for 15 h and subsequent enolate trap with alkyl halide upon an addition of DMPU afforded the desired aminoalkylation product with 98% ee in 89% yield. Further approach toward total synthesis of (−)-kopsinine was carried out by examining asymmetric aminolithiation with N-hydroxyethylamine equivalent, one-pot piperidine formation, and Claisen condensation.

収録刊行物

• Tetrahedron

  Tetrahedron 69 (15), 3264-3273, 2013-04

  Elsevier Ltd.

キーワード

• Total synthesis
• One-pot
• Lithium
• Asymmetric reaction
• Heterocycles

詳細情報

• CRID: 1050001335767292544
• NII論文ID: 120005244223
• NII書誌ID: AA00861787
• ISSN: 00404020
• DOI: 10.1016/j.tet.2013.02.035
• HANDLE: 2433/173087
• Web Site: https://api.elsevier.com/content/article/PII:S0040402013002275?httpAccept=text/xml
• Web Site: https://api.elsevier.com/content/article/PII:S0040402013002275?httpAccept=text/plain
• 本文言語コード: en
• 資料種別: journal article
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