Stereoselective Synthesis of Quaternary Amino Acids by Transition Metal Catalyzed Reaction

过渡金属催化反应立体选择性合成季氨基酸

基本信息

批准号：
17550108
负责人：
KAWATSURA Motoi
金额：
$ 2.24万
依托单位：
Tottori University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

In this project, I succeeded to control the regioselectivity and diastereoselectivity in the transition metal catalyzed allylic alkylation of allyl acetates, and achieved to construct chiral quaternary amino acid and its analogues.I discovered the regio- and diastereo-selectivity in the palladium-catalyzed allylic alkylation of (R)- or (S)-2-acetoxy-4-phenyl-3-butene with N-(diphenylmethylidene)glycinate and N-(diphenylmethylidene)alaninate was highly control by using 2-(diphenylphosphino)benzoic acid. For example, the reaction with N-(diphenylmethylidene)glycinate formed the chiral amino acid analogues which possessing vicinal two chiral tertiary carbon centers at the α and β positions with up to 99% reio- and diastereo-selectivities. The alkylation product was further converted to chiral aspartic acid analogues in 7 steps. I also succeeded to control the regio- and diastereo-selectivity in the reaction with N-(diphenylmethylidene)alaninate, and constructed the amino acid analogues wh … More ich possessing vicinal chiral quaternary and tertiary carbon centers at the α and β positions with up to 99% reioselectivity and up to 95% diastereoselectivity. The chiral alkylated product also converted chiral 2,3-dimethylaspartic acid in 7 steps.Furthermore, I examined the similar stereoselective allylic alkylation with azlactones, and I also succeeded to control the regioselectivity and diastereoselectivity. In the reaction of azlactones, I confirmed the 2-(diphenylphosphino)benzoic acid was again key ligand to control the desired stereoselectivities. For example, the reaction with 2-methyl substituted azlactone proceeded in perfect regioselecitity and 98% diastereoselectivity, and demonstrated to convert it to chiral quaternary aspartic acid analogues. Furthermore, I found the triphenylarsine also an effective ligand for this stereoselective allylic alkylations, and 2-(diphenylphosphino)benzoic acid and triphenylarsine gave different diastereoselectivity.Totally, I succeeded to control the regio- and diastereo-selectivities in the palladium-catalyzed allylic alkylation of (R)- or (S)-2-acetoxy-4-phenyl-3-butene with several amino acid analogues. The coupling product which possessing vicinal two chiral carbon centers or vicinal chiral quaternary and tertiary carbon centers at the α and β positions were converted chiral quaternary amino acids. Less

在这个项目中，我成功地控制了过渡金属中的调节选择性和诊断性，催化了种植酸的酸盐酸，并实现了构建手性季季氨基酸及其类似物的类似物。 N-（二苯基甲基甲基二烯）甘油酸酯和N-（二苯基甲基二基）苯甲酸烷酸烷基化产物通过使用2-（二苯基磷酸）苯甲酸高度控制。例如，与N-（二苯基甲基甲基二烯）甘油酸酯的反应形成了手性氨基酸类似物，该氨基酸类似物在α和β位置具有导型两种手性第三级碳中心，最高为99％的REIO reio-Reio和Niotareo-Selecteo-Selecteo-Selectivities。将烷基化产物进一步转化为7个步骤的手性天冬氨酸类似物。我还成功地控制了与n-（二苯基甲基甲基二烯）甲酸盐反应中的区域和非对映选择性，并构建了氨基酸类似物的氨基酸类似物，其具有替代性手性Quaternary和第三级碳中心的ICH位于α和β的位置，最高为99％Reioselectitivity和99％reioselectitivity和95％的位置。手性烷基化产物还在7个步骤中转化了手性2,3-二甲基天冬事酸。Furthermore，我用azlactones检查了相似的立体选择性烯丙基烷基化，我也成功地控制了调控性选择性和对映射性。在阿兹乳酮的反应中，我证实了2-（二苯基磷酸）苯甲酸再次是控制所需的立体选择性的关键配体。例如，与2-甲基取代的无偶氮酮的反应以完美的调节性和98％的映射性进行，并证明将其转化为手性季季天冬氨酸类似物。此外，我发现三苯基氨基也是这种立体选择的烯丙基醇的有效配体，2-（二苯基磷酸）苯甲酸和三苯基氨基氨酸给出了不同的非对未映选择性。我成功地控制了良性和未核酸 - 或对未核酸菌的毛 - 或核酸含量 - 或（或未）。（S）-2-乙酰氧基-4-苯基-3-丁烯，带有几种氨基酸类似物。具有替代性两个手性碳中心的耦合产物，或在α和β位置处的典型手性季季中心和第三级碳中心。较少的