Development of Enantiselective Radical Reactions

对映选择性自由基反应的发展

• 批准号: 11650887
• 负责人: TOMOOKA Katsuhiko
• 金额: $ 2.3万
• 依托单位: Tokyo Institute of Technology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11650887/
• 关键词: Enantiocontrol; Radical reaction; Chiral Coordinating Agents; [1,2]-witting rearrangement; Stevens rearrangement

In view of the recent progress in the chiral coordinating agent-based asymmetric synthesis, we have been exploring the various radical reactions induced by the chiral coordinating agent-based protocol. Disclosed herein are the enantioselective[1,2]-Witting rearrangement via the asymmetric lithiation with RLi/chiral bisoxazoline and Stevens rearrangement with chiral alkoxides.Enantioselective[1,2]-Witting RearrangementThe carbanion-radical rearrangement of dibenzyl ether(1), when induced with t-BuLi in the presence of chiral bisoxazoline[(S,S)-Box-i-Pr(2)], was found to afford the [1,2]-rearrangement product, benzyl alcohol 3 in 63% ee. This represents the first example of an enantioselective[1,2]-Witting rearrangement. Next, we also examined the asymmetric catalytic version of the present rearrangement. Thus, the rearrangement of 1 was carried out using 10 mol% of(S,S)-2, and 2 equiv of t-BuLi under the same conditions. As anticipated , alcohol(S)-3 was obtained in comparably high %ee and chemical yield(60% ee, 86%). Furthermore, the synthetic potential of the enantioselective[1,2]-Witting rearrangement has been demonstrated by the enantioselective synthesis of tertiary alcohols(up to 65% ee)from racemic ethers.Enantioselective Stevens RearrangementBenzyldimethylamine derived ammonium salt(racemic)was treated with suger derived chiral alkoxide to afford the enantio-enriched rearrangement product in 38% ee. This is the first example of the enantioselective version of Stevens rearrangement.

鉴于近年来基于手性配位剂的不对称合成的研究进展，我们对基于手性配位剂的方案诱导的各种自由基反应进行了探索。本发明公开了与RLi/手性双恶唑啉通过不对称锂化进行的对映选择性[1,2]-Witting重排和与手性烷氧化物进行的Stevens重排。对映选择性[1,2]-Witting重排在手性双恶唑啉[(S，S)-Box-i-Pr(2)]存在下，用t-BuLi诱导二苯醚(1)的碳自由基重排，在63% ee中生成[1,2]-重排产物苯甲醇3。这是对映选择性[1,2]-Witting重排的第一个例子。接下来，我们还研究了目前重排的不对称催化版本。因此，在相同的条件下，用10 mol%的（S，S）-2和2等量的t-BuLi进行1的重排。正如预期的那样，以相当高的%ee和化学产率（60% ee和86% ee）得到醇(S)-3。此外，外消旋醚对映选择性合成叔醇（高达65% ee）也证明了对映选择性[1,2]-Witting重排的合成潜力。对映选择性史蒂文斯重排用糖源性手性醇氧酯对苯二甲胺衍生铵盐（外消旋）进行处理，得到了对映性富集的重排产物。这是史蒂文斯重排对映选择性的第一个例子。

项目成果

K.Tomooka: "Modified Cyclization of Enantio-Enriched α-Homoallyloxy-Alkyllithiums Generated by Sn-Li Transmetallation : Effects of Additives and Structural Requirement"Heterocycles. 52. 1071-1074 (2000)

K. Tomooka：“Sn-Li 金属转移生成的对映体富集 α-高烯丙氧基烷基锂的改进环化：添加剂的影响和结构要求”杂环。

友岡克彦: "Modified Cyclization of Enantio-Enriched α-Homoallyloxy-Alkyllithiums Generated by Sn-Li Transmetallation : Effects of Additives and Structural Requirement"Heterocycles. 52. 1071-1074 (2000)

Katsuhiko Tomooka：“Sn-Li 金属转移生成的对映体富集 α-高烯丙氧基烷基锂的改进环化：添加剂的影响和结构要求”杂环。

K.Tomooka: "External Chiral Ligand-Induced Enantioselective Versions of The [2,3]-Witting Sigmatropic Rearrangement"Chirality. 12. 505-509 (2000)

K.Tomooka：“[2,3]-Witting Sigmatropic 重排的外部手性配体诱导的对映选择性版本”手性。

K.Tomooka: "Stereochemistry and Mechanism of Vinyl-migrating[1,2]-Witting Rearrangement of α-Lithioalkyl Vinyl Ether"Chemistry Let. 418-41t (2000)

K. Tomooka：“α-锂硫烷基乙烯基醚的乙烯基迁移[1,2]-Witting 重排的立体化学和机制”Chemistry Let. 418-41t (2000)

K.Tomooka: "External Chiral Ligand-Induced Enantioselective Lithiation /S_E2 Reactions of Isochroman and Phthalan"Tetrahedron Lett. 41. 6121-6125 (2000)

K.Tomooka：“异色满和 Phthalan 的外部手性配体诱导的对映选择性锂化 /S_E2 反应”四面体莱特。