DEVELOPMENT OF ASYMMETRIC RADICAL REACTIONS AND APPLICATION TO THE SYNTHESIS OF BIO-ACTIVE COMPOUNDS

不对称自由基反应的发展及其在生物活性化合物合成中的应用

• 批准号: 08672441
• 负责人: NISHIDA Atsushi
• 金额: $ 1.47万
• 依托单位: CHIBA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08672441/
• 关键词: Radical Cyclization; Diastereoselectivity; Chiral Auxiliary; Lewis Acid; Alkoxy Radical; beta-Cleavage; Chiral Cyclopropane; Enantioselectivity; trans-2-アミノシクロヘキサノール; 2-シクロペンテニル酢酸; アルキルスタニルエステル; スズラジカル; アセタール

1. DIASTEREOSELECTIVE RADICAL CYCLIZATION1) New chiral auxiliaries, trans-2-(N-benzenesulfonyl-N-benzylamino)cyclohexanol and its derivatives were developed and used for diastereoselective radical cyclization. When trans-2-(N- benzenesulfonyl-N-benzylamino)cyclohexyl 7-iodo-2,6-heptadienoate was reacted with nBu_3SnH in the presence of Et_3B and bulky Lewis acid, such as MAD, a diastereo mixture of (2- cyclopentenyl)acetate was obtained in 92% yield. After standard hydrolysis, (2-cyclopentenyl)acetic acid was obtained (53% ee) and the chiral auxiliary was recovered. Optically active (2- cyclopentenyl)acetic acid is a starting material for many biologically active compounds, such as coriolin, hirsutic acid C, and alepraic acid (a member of cyclopentenyl fatty acids).Optically active (2-cyclohexenyl)acetic acid (38% ee) was also obtained using the same auxiliary.2) Diastereoselective addition of tri-n-butyltin radical to chiral alpha, beta-unsaturated esters, having 8- phenylmenthyl grou … More p as a chiral auxiliary, was achieved in the presence of Lewis acid. Thus obtained beta-stannylester was converted to a chiral cyclopropane derivative.3) Chiral hydroxythiols, which were prepared from (R)-(+)-pulegone, were converted to chiral acetals, When the chiral acetals were irradiated using UV lamp in the presence of benzophenone, carbon radicals were generated and cyclized to chiral cyclopentane derivatives. Although diastereoselectivity was low, the reaction is a new method for the synthesis of chiral 2-substituted cyclopentanones.2. ENANTIOSELECTIVE RADICAL CYCLIZATIONWhen cyclohexyl 8-iodonona-2,8-dienoate was reacted with nBu_3SnH and Et_3B in the presence of chiral aluminum reagent, chiral (2-methylenecyclohexyl)acetate was obtained in 46% ee, This is the first example of enantioselective radical cyclization.3. NEW RADICAL SKELETAL REARRANGEMENT VIA ALKOXY RADICALThe radical reaction of epoxydecalin thiocarbonylimidazolide afforded rearranged bicyclic cyclooctanes. The reaction proceeded via ten-membered ring carbon radicals, which was generated by beta-cleavage of alkoxy radicals. This reaction is useful for some terpene synthesis having a cyclooctane ring. Less

1.非对映选择性自由基环化反应1）开发了新的手性助剂反式-2-（N-苯磺酰基-N-苄氨基）环己醇及其衍生物，并用于非对映选择性自由基环化反应。反式-2-（N-苯磺酰基-N-苄氨基）环己基7-碘-2，6-庚二烯酸酯与nBu_3SnH在Et_3B和大体积刘易斯酸（如MAD）存在下反应，得到（2-环戊烯基）乙酸酯的非对映体混合物，产率92%。标准水解后，得到（2-环戊烯基）乙酸（53%ee），回收手性助剂。光学活性（2-环戊烯基）乙酸是许多生物活性化合物的起始原料，如马桑皮素、多毛酸C和alepraic acid（环戊烯基脂肪酸的成员）。（2-环己烯基）乙酸（38%ee）。2）三正丁基锡自由基与手性α，β-不饱和酯的非对映选择性加成，具有8-苯基薄荷基格鲁 ...更多信息 p作为手性助剂，在刘易斯酸存在下实现。3）以（R）-（+）-胡薄荷酮为原料合成的手性羟基硫醇，经紫外灯照射后，在二苯甲酮存在下，生成碳自由基，环化为手性环戊烷衍生物。虽然该反应的非对映选择性较低，但为合成手性2-取代环戊酮提供了一种新的方法. 8-碘壬-2，8-二烯酸环己酯与nBu_3SnH和Et_3B在手性铝试剂存在下反应，得到手性（2-亚甲基环己基）乙酸酯，ee值为46%，这是第一例不对称自由基环化反应.通过烷氧基自由基进行的新的自由基骨架重排环氧萘烷硫代羰基咪唑的自由基反应得到重排的双环环辛烷。反应通过烷氧基的β-裂解产生的十元环碳自由基进行。该反应可用于某些具有环辛烷环的萜烯合成。少

项目成果

西田 篤司: "新規ラジカル反応の開発-アルコキシラジカルを経る骨格変換反応及びルイス酸存在下における不斉ラジカル環化反応-" 有機合成化学協会誌. 54巻. 27-35 (1996)

Atsushi Nishida：“新自由基反应的发展 - 在路易斯酸存在下通过烷氧基自由基和不对称自由基环化反应进行骨架转化反应”，合成有机化学学会杂志，第 54 卷，27-35 (1996)

Atsushi Nishida: "Development of New Radical Reactions : Skeletal Rearrangement via Alkoxy Radical and Asymmetric Radical Cyclization" Reviews on Heteroatom Chemistry. 16巻. 287-311 (1997)

Atsushi Nishida：“新自由基反应的发展：通过烷氧基自由基和不对称自由基环化进行骨架重排”杂原子化学评论第 16 卷。287-311 (1997)

Atsushi Nishida, Mayumi Nishida: "Development of New Radical Reactions-Skeletal Rearrangement via Alkoxy Radical and Asymmetric Radical Cyclization in the Presence of Lewis Acid-" Journal of Synthetic Organic Chemistry, Japan. 54. 27-35 (1996)

Atsushi Nishida、Mayumi Nishida：“新自由基反应的发展 - 在路易斯酸存在下通过烷氧基自由基和不对称自由基环化进行骨架重排 -”合成有机化学杂志，日本。

Atsushi Nishida: "Skeletal Rearrangement via Alkoxy Radical:Conversion of Epoxydecalin Thiocarbonylimidazolide to Bicyclo[6.3.0]undecanone and Bicyclo[5.3.1]undecanone" Tetrahedron Letters. 38巻31号. 5519-5522 (1997)

Atsushi Nishida：“通过烷氧基自由基进行骨架重排：环氧十烷硫代羰基咪唑化物转化为双环[6.3.0]十一烷酮和双环[5.3.1]十一烷酮”Tetrahedron Letters，第 38 卷，第 31 期。5519-5522 (1997)

A.Nishida: "Radical Cyclization Using a Thioacetal Group for Radical Generation" Tetrahedron. 52巻11号. 9713-9734 (1996)

A.Nishida：“使用硫缩醛基团进行自由基生成的自由基环化”Tetrahedron，第 52 卷，第 11 期。9713-9734 (1996)