36 有機リチウムの不斉タンデム型共役付加-閉環反応の開発とLycorine類の不斉全合成への展開(口頭発表の部)
書誌事項
- タイトル別名
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- 36 Asymmetric Total Syntheses of Lycorine Related Compounds via Tandem Asymmetric Conjugate Addition-Cyclization Reaction of Organolithium Reagent
抄録
We have been involved in development of asymmetric reactions using diether 2 as a chiral chelating ligand and have succeeded in asymmetric addition of organolithium reagents to α,β-unsaturated carboxylates (Scheme 1). The addition of organolithium reagent to α,β-unsaturated carboxylate gives lithium enolate intermediate, whose intermolecular trapping with another α,β-unsaturated carboxylate moiety would produce highly functionalized chiral cyclohexane building blocks, such as 4 (Scheme 2). We planned asymmetric synthesis of Amaryllidaceae alkaloids, lycorine (1) and related compounds using 4 as a key intermediate. The investigation of the key tandem asymmetric conjugate addition-cyclization reaction using chiral ligand 2 revealed that the bulky ortho-substituent, TMS group of aryllithium 6b using important to achieve the first addition step in high enantioselectivity (Scheme 3). Besides, the ethylenedioxy group of α,β-unsaturated carboxylate 3 improves diastereoselectivity in the cyclization step probably because the replacement of H with O makes 1,3-diaxial interaction more unfavorable in the transition state that gives trans-cis isomers 8 (Figure 2). With enantiomerically enriched cyclohexane 9 in hand, we started the asymmetric synthesis of lycorines (Scheme 4). Treatment of 9 with ethanolic HCl gave carboxylic acid 10, whose Curtius rearrangement gave carbamate 11 in good yield. Formation of the tetracyclic core was achieved via lactam formation and Bishler-Napieralski reaction to give ketone 14. Formal synthesis of 1-deoxylycorine was accomplished via double bond formation by IBX oxidation of silyl enolate and reduction of the resulting enone 15. Introduction of 2-hydroxy functionality to ketone 14 was achieved stereoselectively by Magnus' chemistry (Scheme5). Formation of double bond followed by reduction gave 2-epi-lycorine diacetate (23) after acetylation of the resulting 2-epi-lycorine (22).
収録刊行物
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- 天然有機化合物討論会講演要旨集
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天然有機化合物討論会講演要旨集 49 (0), 211-216, 2007
天然有機化合物討論会実行委員会
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詳細情報 詳細情報について
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- CRID
- 1390282681054539904
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- NII論文ID
- 110006682766
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- ISSN
- 24331856
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- 本文言語コード
- ja
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- データソース種別
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- JaLC
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可