Catalytic Asymmetric Synthesis of Physiologically Active Related compounds Bearing Lactone or Lactam Ring

催化不对称合成带有内酯或内酰胺环的生理活性相关化合物

• 批准号: 16550103
• 负责人: OKADA Yoshiharu
• 金额: $ 2.05万
• 依托单位: Kinki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16550103/
• 关键词: Triethyl Phosphonoacetate; Phosphine-carboxylic Acid; Asymmetric Synthesis; Chiral Ligand; Thiazolidine Derivative; Isocyanate; 炭酸セシウム; メルカプト酢酸メチル; アントラセン; 光学活性ホスフィンカルボン酸; パラジウム錯体触媒; 不斉アリル位アルキル化反応; Diels-Alder反応

In the transition metal complex catalyzed asymmetric synthesis, one of the most important needs is the development of effective chiral ligands. We describe here the synthesis of a bulky type of 2-diphenylphosphino-9,10-dihydro-9,10-ethanoanthracene bearing carboxyl group. Reaction of 1 with methyl acrylate gave an isomer mixture of 2a-d in 94% yield. Recrystallization of the mixture from ethyl acetate-hexane gave a pure 2b as a first crystal. Recycling preparative HPLC of the filtrate with CHCl_3 was succeeded to separate 2a. Reduction of 2b with HSiCl_3 and subsequent alkaline hydrolysis gave (±)-2-diphenylphosphino-9,10-dihydro-9,10-ethanoanthracene-12(anti)-carboxylic acid (3b) in 43% yield. Resolution of (±)-3b with (-)-α-methylbenzyl-amine was succeeded to give an optically pure (-)-3b, [α]_D^<23>=-37.55 (c 0.39, CHCl_3). The reaction of triethyl sodiophosphonoacetate with 2-cyclohexenyl acetate in the presence of Pd(OAc)_2・(-)-3b (1.5 mol%) gave the allylic alkylation product in 96% (53%ee).On the other hand, many compounds containing thiazolidinedione moiety such as rosiglitazone and pioglitazone have been useful as the medicine. However, the convenient synthesis of thiazolidine derivatives having phosphorus functional group has been rarely reported, to our knowledge. We now report the synthesis and synthetic application of 5-(diethylphosphono)-1,3-thiazolidine derivatives. Treatment of triethyl phosphonoacetate with sodium hydride and powdered sulfur generated thiolate anion intermediate. And subsequent reaction with phenyl isocyanate (4a) gave thiocarbamate 5a in 40% yield. While similar reaction with benzyl isocyanate (4b) gave 3-benzyl-5-(diethylphosphono)-1,3-thiazolidinedione (6b) in 8% yield together with thiocarbamate 5b in 25% yield.

在过渡金属配合物催化的不对称合成中，最重要的需求之一是开发有效的手性配体。本文报道了一种带羧基的2-二苯基膦基-9，10-二氢-9，10-乙蒽的合成。1与丙烯酸甲酯反应，得到2a-d的异构体混合物，产率94%。将混合物从乙酸乙酯-己烷中重结晶，得到纯的2b作为第一晶体。滤液用二氯甲烷循环制备HPLC成功分离出2a。2b经HSiCl_3还原，碱解得（±）-2-二苯基膦基-9，10-二氢-9，10-乙蒽-12（反）-羧酸（3b），产率43%。用（-）-α-甲基苄胺拆分（±）-3b，得到光学纯的（-）-3b，[α]_D^<23>=-37.55（c0.39，CHCl_3）。在Pd（OAc）_2·（-）-3b（1.5mol%）存在下，三乙基钠二膦酰基乙酸酯与2-环己烯基乙酸酯反应，得到96%（53%ee）的烯丙基烷基化产物。然而，据我们所知，具有磷官能团的噻唑烷衍生物的方便合成很少报道。本文报道了5-（二乙基膦酰基）-1，3-噻唑烷衍生物的合成及其在合成中的应用。膦酰基乙酸三乙酯与氢化钠和硫磺粉反应生成硫醇盐阴离子中间体。然后与异氰酸苯酯（4a）反应得到硫代氨基甲酸酯5a，产率40%。与异氰酸苄酯（4 b）进行类似反应，得到3-苄基-5-（二乙基膦酰基）-1，3-噻唑烷二酮（6 b），产率为8%，硫代氨基甲酸酯（5 b）产率为25%。