Development of novel carbon-nitrogen bond forming reactions by means of [2,3] sigmatropic rearrangement

通过[2,3]σ重排开发新型碳氮键形成反应

• 批准号: 08455430
• 负责人: SAITO Seiki
• 金额: $ 4.61万
• 依托单位: Okayama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08455430/
• 关键词: [2,3] sigmatropic rearrangement; N-alkyl-O-allylic-hydroxylamines; allylic amines; aminopolyols; diastereoselective rearrangement; enantioselective rearrangement; [2,3]シグマトロピー転位; 2級アリリックアミン; エナンチオ選択的転位反応; ジアステレオ選択的転位反応; 光学活性2級アリリックアミン; 1,2-不斉誘導

This research has disclosed for the first time that N-alkyl-O-allylic-hydroxylamines (1) rearrange to furnish allylic amines when treated with base such as butyllithium (THF, 0ﾟC, 5min), or thermally without base (DMF, 60ﾟC) depending on the structure of 1. This is unprecedented [2,3]-Wittig type rearrangement in which a migration terminus is a negatively charged nitrogen atom. Taking advantage of hydroxylamine as an N,O-bifunctional nucleophile, we can prepare 1 through a series of routine reactions involving Mitsunobu reaction of allylic alcohols with N-hydroxyphthalimide (Phth-N-OH), generation of O-allylic hydroxylamine with hydrazine, and N-benzylation with benzyl bromide. Hence we have been studying the scope and limitations of this novel [2,3]sigmatropic rearrangement to find that it highly merits organic synthesis as a method for the preparation of stereo-defined allylic amines which are biologically important class of compounds. It also turned out that the reaction was able to be applied to the synthesis of chiral amino polyols relying on substrate-controlled 1,2- and 1,3-asymmetric induction to result in achieving >90%de. Another synthetic potential of this method has been also demonstrated which gives opportunities for the preparation of optically active allylic amines when the reaction is carried out in the presence of chiral diaza-ligand such as bisoxazolines, featuring the first example of reagent-controlled enantioselective [2,3]sigmatropic rearrangement.

本研究首次揭示了N-烷基-O-烯丙基-羟胺（1）在碱（如丁基锂）作用下（THF，0 ℃，5 min），或在无碱条件下（DMF，60 ℃），根据1的结构，重排生成烯丙基胺。这是前所未有的[2，3]-Wittig型重排，其中迁移末端是带负电荷的氮原子。利用羟胺作为N，O-双功能亲核试剂的优势，通过烯丙醇与N-羟基邻苯二甲酰亚胺（Phth-N-OH）的Mitsunobu反应，与肼反应生成O-烯丙基羟胺，再与苄基溴反应生成1。因此，我们一直在研究这种新的[2，3] σ迁移重排的范围和局限性，发现它非常值得有机合成作为一种方法，用于制备立体定向烯丙基胺，这是生物学上重要的一类化合物。结果表明，该反应可应用于手性氨基多元醇的合成，通过底物控制的1，2-和1，3-不对称诱导，可获得>90%de。该方法的另一个合成潜力也已被证明，当反应在手性二氮杂配体如双恶唑啉的存在下进行时，为制备光学活性烯丙基胺提供了机会，其特征在于试剂控制的对映选择性[2，3] σ迁移重排的第一个例子。

项目成果

T.Ishikawa,K.Nagai,M.Senzaki,A.Tatsukawa,and S.Saito: "Hemiaminal Generated by Hydration of Ketone-based Nitrone as an N,O-Centered Nuclephile in Organic Synthesis" Tetrahedron. 54. 2433-2448 (1998)

T.Ishikawa、K.Nagai、M.Senzaki、A.Tatsukawa 和 S.Saito：“有机合成中酮基硝酮水合生成的半胺醛作为 N,O 中心亲核试剂”四面体。

S.Saito and T.Ishikawa: "Asymmetric Bias Generated by Protcted Vicinal Diol Controller and Its Application to Asymmetric Nitrone-Olefin Cycloaddition Reactios" J.Syn.Org.Chem.Jpn.56. 86-95 (1998)

S.Saito 和 T.Ishikawa：“受保护的邻位二醇控制器产生的不对称偏压及其在不对称硝酮-烯烃环加成反应中的应用”J.Syn.Org.Chem.Jpn.56。

T.Ishikawa, K.Nagai, M.Senzaki, A.Tatsukawa, and S.Saito: "Hemiaminal Generated by Hydration of Ketone-based Nitrone as an N,O-Centered Nucleophile in Organic Synthesis" Tetrahedron. 54. 2433-2448 (1998)

T.Ishikawa、K.Nagai、M.Senzaki、A.Tatsukawa 和 S.Saito：“有机合成中酮基硝酮水合生成的半胺醛作为 N,O 中心亲核试剂”四面体。

S.Saito,E.Uedo,Y.Kato,Y.Murakami,and T.Ishikawa: "Lewis-acid Promoted Generation of an Iminium Ion from Ethyl 2-(N-Benzyloxy-carbonylamino)-methylene-3-oxobutanoate and Its Reaction with Ketene Silyl Acetals" Synlett-. 1103-1105 (1996)

S.Saito、E.Uedo、Y.Kato、Y.Murakami 和 T.Ishikawa：“路易斯酸促进 2-(N-苄氧基-羰基氨基)-亚甲基-3-氧代丁酸乙酯生成亚胺离子及其

Teruhiko Ishikawa, Keita Nagai, Takayuki Kudoh, Seiki Saito: "Chiral Lewis Acid-Hydroxylamine Hybrid Reagent for Enantioselective Michael Addition Reaction Directed toward beta-Amino Acides Synthesis" Synlett. 1291-1293 (1998)

Teruhiko Ishikawa、Keita Nagai、Takayuki Kudoh、Seiki Saito：“用于β-氨基酸合成的对映选择性迈克尔加成反应的手性路易斯酸-羟胺混合试剂”Synlett。