Stereoselective Synthesis of Quaternary Amino Acids by Transition Metal Catalyzed Reaction

在本项目中，我成功地控制了过渡金属催化乙酸烯丙酯烯丙基烷基化反应的区域选择性和非对映选择性，发现了钯催化的（R）-或（S）-2-乙酰氧基-4-苯基-3-丁烯与N-（2-甲氧基苯基）-3-丁烯烯丙基烷基化反应中的区域选择性和非对映选择性。通过使用2-（二苯基膦基）苯甲酸高度控制N-（二苯基亚甲基）甘氨酸和N-（二苯基亚甲基）丙氨酸。例如，与N-（二苯基亚甲基）甘氨酸酯反应生成的手性氨基酸类似物在α和β位具有两个手性叔碳中心，其对映体和非对映体选择性高达99%。烷基化产物经7步反应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）丙氨酸反应的区域选择性和非对映选择性，并构建了具有两种结构的氨基酸类似物， ...更多信息 其在α和β位具有邻位手性季碳和叔碳中心，具有高达99%的立体选择性和高达95%的非对映选择性。此外，我还考察了手性烯丙基与吖内酯的类似立体选择性烷基化反应，并成功地控制了区域选择性和非对映选择性。在吖内酯的反应中，我证实了2-（二苯基膦基）苯甲酸再次是控制所需立体选择性的关键配体。例如，与2-甲基取代的吖内酯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，我发现三苯基胂也是这种立体选择性烯丙基烷基化反应的有效配体，2-（二苯基膦基）苯甲酸和三苯基胂具有不同的非对映选择性，总之，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的区域选择性和非对映选择性。偶联产物在α位和β位分别具有两个手性碳中心或两个手性季碳中心和叔碳中心，可转化为手性季胺酸。少

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