アミン-N-オキシドを触媒とする新規不斉合成反応の開発

使用胺-N-氧化物作为催化剂开发新型不对称合成反应

• 批准号: 10671978
• 负责人: NAKAJIMA Makoto
• 金额: $ 1.73万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671978/
• 关键词: Amine N-Oxide; Chiral Catalyst; Epoxidation; Enantioselective Allylation; Enantioselective Conjugate Addition; 不斉共役付加反応; アミンN-オキシド

Although it is well documented that amine N-oxides act as powerful electron-pair donors to form complexes with a variety of acceptor molecules, synthetic utility of amine N-oxides as ligands or catalysts still remains to be developed. We have developed the following N-oxide-induced organic reactions. (1) Bipyridine N,N'-dioxide was found to be a felicitous ligand for methyltrioxorhenium-catalyzed epoxidation of olefins with hydrogen peroxide. (2) A new catalytic, enantioselective allylation of aldehydes with allyltrichlorosilanes exploiting (S)-3,3'-dimethyl-2,2'-biquinoline N,N'-dioxide as a catalyst affords homoallylic alcohols in virtually complete diastereoselectivities and high enantioselectivities of up to 92% ee, wherein the use of diisopropylethylamine as an additive has proven to be crucial for the acceleration of the catalytic cycle. It is also noteworthy that the above finding represents the first successful example of asymmetric reactions utilizing amine N-oxide as a chiral catalyst. A one-pot, convenient method for the preparation of optically active homoallylic alcohols from allyl halides was developed based on the above allylation. Allyltrichlorosilanes were generated in situ from allyl halides and trichlorosilane in the presence of cuprous chloride and tertiary amine. Without isolation of the allyltrichlorosilanes, benzaldehyde and chiral biquinoline N,N'-dioxide were introduced into the same flask, producing the corresponding homoallylic alcohols in good to high enantioselectivities. (3) (S)-3,3'-dimethyl-2,2'-biquinoline N,N'-dioxide-cadmium chloride complex was proven to be a good catalyst for the asymmetric conjugate addition of thiols to enones with enantioselectivit of up to 79% ee.

虽然它是有据可查的，胺N-氧化物作为强大的电子对供体，形成与各种受体分子的配合物，胺N-氧化物作为配体或催化剂的合成效用仍然有待开发。我们已经开发了以下N-氧化物诱导的有机反应。(1)N，N ′-联吡啶二氧化物是一种适宜的配体，可用于甲基三氧化铼催化的烯烃与过氧化氢的环氧化反应。(2)利用（S）-3，3 ′-二甲基-2，2 ′-联喹啉N，N ′-二氧化物作为催化剂的醛与烯丙基三氯硅烷的新的催化的对映选择性烯丙基化反应以几乎完全的非对映选择性和高达92%ee的高对映选择性提供高烯丙醇，其中使用二异丙基乙胺作为添加剂已被证明对于加速催化循环是至关重要的。还值得注意的是，上述发现代表了利用胺N-氧化物作为手性催化剂的不对称反应的第一个成功实例。基于上述烯丙基化反应，发展了一种由烯丙基卤一锅法制备光学活性高烯丙醇的简便方法。在氯化亚铜和叔胺存在下，由烯丙基卤和三氯硅烷原位生成烯丙基三氯硅烷。在不分离烯丙基三氯硅烷的情况下，将苯甲醛和手性联喹啉N，N '-二氧化物引入同一烧瓶中，以良好至高的对映选择性产生相应的高烯丙醇。(3)（S）-3，3 '-二甲基-2，2'-联喹啉-N，N '-二氧化物-氯化镉配合物催化硫醇与烯酮的不对称共轭加成反应，对映选择性高达79%ee.

项目成果

Makoto Nakajima, Yuka Sasaki, Hatsue Iwamoto, Shunichi Hashimoto: "Bipyridine N,N'-Dioxide : A Felicitous Ligand for Methyltrioxorhenium-Catalyzed Epoxidation of Olefins with Hydrogen Peroxide."Tetrahedron Letter. 39. 87-88 (1998)

Makoto Nakajima、Yuka Sasaki、Hatsue Iwamoto、Shunichi Hashimoto：“联吡啶 N,N-二氧化物：用于甲基三氧铼催化过氧化氢烯烃环氧化的合适配体。”四面体字母。

Nakajima,M.et al.: "Bipyridine N,N′-Dioxide : A Felicitous Ligand for Methyltrioxorhenium-Catalyzed Epoxidation of Olefins with Hydrogen Peroxide." Tetrahedron Letters. 39. 87-88 (1998)

Nakajima, M. 等人：“联吡啶 N,N-二氧化物：用于甲基三氧铼催化的过氧化氢烯烃环氧化的合适配体。” 39. 87-88 (1998)。

Nkajima M. et al.: "One-pot Enantioselective Synthesis of Optically Active Homoallylic Alcohols from Allyl Halides and Aldehydes"Chemical and Pharmaceutical Bulletin. 48. 306-307 (2000)

Nkajima M.等人：“从烯丙基卤化物和醛中一锅对映选择性合成光学活性高烯丙醇”化学和制药通报。

Makoto Nakajima: "Synthesis and Applications of Novel Biaryl Compounds with Axial Chirality as Catalysts in Enantioselective Reactions."YUKAGAKU ZASSHI. 120. 68-75 (2000)

Makoto Nakajima：“具有轴向手性的新型联芳基化合物作为对映选择性反应催化剂的合成和应用。”YUKAGAKU ZASSHI。

Nakajima, M. et al.: "One-pot Enantioselective Synthesis of Optically Active Homoallylic Alcohols from Allyl Halides and Aldehydes"Chemical and Pharmaceutical Bulletin. 48. 306-307 (2000)

Nakajima，M.等人：“从烯丙基卤化物和醛中一锅对映选择性合成光学活性高烯丙醇”化学和制药通报。