Newly Designed Asymmetric Reaction Sites Induced by Rotational Barrier around the Carbon-Sulfur Bond Axis and their Reactions

新设计的碳硫键轴周围旋转势垒诱导的不对称反应位点及其反应

• 批准号: 13450369
• 负责人: TORU Takeshi
• 金额: $ 9.47万
• 依托单位: Nagoya Institute of Technology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13450369/
• 关键词: chiral axis; atropisomer; sulfoxide; naphthalene; stereoselective reaction; Palladium; allylic substitution; ferrocene; 不斉合成反応; トリイソプロピルフェニルスルフィニル基; イミン; キラルアミノ化合物; 立体選択的反応; 遠隔不斉誘導; アルキル化反応; 還元反応; 光学活性アルコール

Nucleophilic addition reactions to the carbaldehyde or imino groups at the 2-position of 1-sullinylnaplithalene have been examined. The reactions examined are as follows : Grignard reactions, alkylation reactions with alkyllithiums, reductions with LiAlH_4 or diisobutylaluminum hydride and Mukaiyama aldol reactions. Stereoselectivity was found dependent on the substituents on the sulfinyl group. High stereoselectivity (>98:2) could be achieved in the reactions of suffinylnaphthaldehyde having a 2,4,6-triisopropylphenyl group. On the other hand, tert-butylsulfinyl-naphthaldehyde or -naphthylmethanimine showed lower stereoselectivities which, however, were in good accord to the ratio of the diastereomers caused by the rotational barrier around the carbon-sulfur bond axis evidenced by the nmr analyses. We have concluded that the high stereoselectivity in the reactions of 1-(2,4,6-triisopropylphenyl)sulfinyl-2-naphthaldehyde or -naphthylmethanimine is caused by the high rotational barrier … More around the carbon-sulfur bond axis, because all the reactions shown above proceeded with high stereoselectivities irrespective of the chelating or non-chelating transition states. Furthermore, 1-p-tolylsulfinyl-benzaldehyde or -phenylmethanimine, in which a free rotation around the carbon-sulfur bond axis is assumed, showed high stereoselectivity only in the reaction through chelating transition states. The sulfinyl group can be removed from the products. For example, optically active alcohols especially having two aromatic groups can be prepared very efficiently. Thus, the present reaction provides a new efficient preparative method for optically active methanol having two different aromatic groups, with a similar bulkiness such as phenyl-p-tolylmethanol which is mostly difficult to prepare by the asymmetric reduction.Reduction of β-ketosuklfoxides with Dibal was found to show complete stereoselectivity which was controlled by the silyl group at the β-position. In this study a new chiral ligand having a rotational barrier for enantioselective reactions was also successfully designed. Thus, a ferrocenyl compound having sulfinyl and diphenylphosfinyl groups at 1-and 1'-positions was found to be an afficient chiral ligand for the allylation of malonate with a Pd catalyst.Through these studies, we could develop new stereoselective reactions caused by rotational barriers which includes a new concept of stereoselective reactions using a rotational barrier around the carbon-sulfur bond axis. Less

对1-sullinylnaplithalene 2位上的乙醛或亚胺基的亲核加成反应进行了研究。研究的反应有：格氏反应、烷基锂的烷基化反应、LiAlH_4或二异丁基氢化铝的还原反应和Mukaiyama醛醇反应。立体选择性依赖于亚砜基上的取代基。具有2,4,6-三异丙基苯基的suffinylnaphthaldehyde的反应具有很高的立体选择性（bbb98:2）。另一方面，叔丁基亚砜-萘醛或-萘甲基亚胺具有较低的立体选择性，但这与核磁共振分析证明的碳硫键轴周围的旋转势垒引起的非对映体的比例是一致的。我们已经得出结论，1-（2,4,6-三异丙基苯基）亚砜-2-萘醛或-萘甲基亚胺反应的高立体选择性是由碳-硫键轴周围的高旋转势垒引起的，因为上述所有反应都具有高立体选择性，而不管螯合或非螯合过渡态。此外，假设围绕碳-硫键轴自由旋转的1-对亚砜基苯甲醛或-苯基甲基亚胺仅在螯合过渡态反应中表现出较高的立体选择性。亚砜基可以从产物中除去。例如，具有光学活性的醇，特别是具有两个芳香基团的醇，可以非常有效地制备。因此，本反应为具有两种不同芳香基团的光学活性甲醇提供了一种新的高效制备方法，这种方法与苯基-对甲基甲醇的不对称还原法制备的体积相似。用Dibal还原β-酮基亚砜具有完全的立体选择性，这是由β位置的硅基控制的。本研究还成功地设计了一种新的手性配体，该配体具有对映选择性反应的旋转屏障。因此，二茂铁基化合物在1′和1′位置上具有亚砜基和二苯基磷酰基，被发现是丙二酸烯丙基化与Pd催化剂的有效手性配体。通过这些研究，我们可以开发新的由旋转势垒引起的立体选择反应，其中包括利用碳硫键轴周围的旋转势垒进行立体选择反应的新概念。少

项目成果

Shuichi Nakamura: "New Asymmetric Reactions of 2-Formyl- and 2-Acyl-l-[(2,4,6-triisopropylphenyl)sulfinyl]naphthalenes via Diastereomeric Rotamers"J. Org. Chem.. 65. 8640-8650 (2000)

Shuichi Nakamura：“通过非对映异构旋转异构体进行 2-甲酰基-和 2-酰基-1-[(2,4,6-三异丙基苯基)亚磺酰基]萘的新不对称反应”J。

Shuichi Nakamura, Hiroki Yasuda, Yoshihiko Watanabe, Takeshi Toru: "Diastereoselective Reaction of 1-(Arylsulfinyl)-2-naphthaldehydes"Tetrahedron Letters. 41. 4157-4160 (2000)

Shuichi Nakamura、Hiroki Yasuda、Yoshihiko Watanabe、Takeshi Toru：“1-(芳基亚磺酰基)-2-萘醛的非对映选择性反应”四面体字母。

Shuichi Nakamura, Takeo Fukuzumi, Takeshi Toru: "Novel Chiral Sulfur-Containing Ferrocenyl Ligands for Palladium-Catlyzed Asymmetric Allylic Substitution"Chirality. 16巻・1号. 10-12 (2004)

Shuichi Nakamura、Takeo Fukuzumi、Takeshi Toru：“用于钯催化不对称烯丙基取代的新型手性含硫二茂铁基配体”手性，第 16 卷，第 1. 10-12 期（2004 年）。

Shuichi Nakamura, Masahiro Oda, Hiroki Yasuda, Takeshi Toru: "Highly stereoselective 1,4-asymmetric reactions of 2-(arylsuifinyl) benzaldehydes and 2-(arylsulfinyl) phenyl ketones"Tetrahedron. 57. 8469-8480 (2001)

Shuichi Nakamura、Masahiro Oda、Hiroki Yasuda、Takeshi Toru：“2-(芳基亚磺酰基)苯甲醛和2-(芳基亚磺酰基)苯基酮的高度立体选择性1,4-不对称反应”四面体。

Shuichi Nakamura: "1,4-Asymmetric Reduction of γ-Ketosulfoxides Bearing the 2,4,6-Triisopropylphenyl Group"J. Chem. Soc., Perkin Trans. 1. No. 18. 3143-3148 (2000)

Shuichi Nakamura：“带有 2,4,6-三异丙基苯基的 γ-酮亚砜的 1,4-不对称还原”J. Chem. Soc.，Perkin Trans. 1. No. 18. 3143-3148 (2000)