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

在本项目中，我成功控制了过渡金属催化乙酸烯丙酯烯丙烷基化的区域选择性和非对映选择性，并实现了手性季铵氨基酸及其类似物的构建。我发现了钯催化烯丙烷基化的区域选择性和非对映选择性。 (R)-或(S)-2-乙酰氧基-4-苯基-3-丁烯的烷基化N-(二苯基亚甲基)甘氨酸盐和N-(二苯基亚甲基)丙氨酸盐通过使用2-(二苯基膦)苯甲酸得到高度控制，例如与N-(二苯基亚甲基)甘氨酸盐反应形成具有邻位两个手性叔手性的手性氨基酸类似物。碳中心位于 α 和 β 位，reio- 和高达 99%非对映选择性。通过 7 个步骤，烷基化产物进一步转化为手性天冬氨酸类似物，我还成功地控制了与 N-(二苯基亚甲基)丙氨酸酯反应中的区域选择性和非对映选择性，并构建了氨基酸类似物 ...更多 ich 在 α 和 β 位点具有邻位手性季碳和叔碳中心，其立体选择性高达 99% 及以上手性烷基化产物也通过7个步骤转化为手性2,3-二甲基天冬氨酸。此外，我研究了二氢唑酮的类似立体选择性烯丙基烷基化，并且我还成功地控制了二氢唑酮反应中的区域选择性和非对映选择性。，我确认 2-(二苯基膦)苯甲酸再次是关键配体例如，与 2-甲基取代的二氢唑酮的反应以完美的区域选择性和 98% 的非对映选择性进行，并证明将其转化为手性季天冬氨酸类似物。此外，我发现三苯胂也是一种有效的配体。立体选择性烯丙基烷基化，以及 2-(二苯基膦)苯甲酸和三苯胂给出了不同的非对映选择性。总的来说，我成功地控制了钯催化的(R)-或(S)-2-乙酰氧基-4-苯基-3-丁烯与几种氨基酸类似物的烯丙基烷基化反应中的区域选择性和非对映选择性α和β位具有邻位两个手性碳中心或邻位手性季碳中心和叔碳中心的偶联产物被转化。手性季氨基酸较少。