Stereoselective Synthesis of Quaternary Amino Acids by Transition Metal Catalyzed Reaction

在这个项目中，我成功地控制了过渡金属催化的乙酸烯丙基烯丙基化反应的区域选择性和非对映选择性，并实现了手性四元氨基酸及其类似物的构筑。我发现在钯催化的(R)-或(S)-2-乙酰氧基-4-苯基-3-丁烯与N-(二苯亚甲基)甘氨酸和N-(二苯亚甲基)丙氨酸的烯丙基化反应中，区域选择性和非对映选择性是用2-(二苯基膦)苯甲酸高度控制的。例如，与N-(二苯亚甲基)甘氨酸酯反应生成的手性氨基酸类似物在α和β位置附近具有两个手性叔碳中心，具有高达99%的区域和非对映选择性。烷基化产物再分7步转化为手性天冬氨酸类似物。我还成功地控制了与N-二苯亚甲基丙氨酸酯反应的区域选择性和非对映选择性，并用…构建了氨基酸类似物更多的ICH在α和β位置上具有邻近的手性、季碳和叔碳中心，具有高达99%的重映选择性和高达95%的非对映选择性。手性烷基化产物还经过7步反应转化为手性2，3-二甲基天冬氨酸。此外，我还考察了类似的与氮内酯的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。在氮内酯的反应中，我再次确认了2-(二苯基膦)苯甲酸是控制所需立体选择性的关键配体。例如，与2-甲基取代氮内酯的反应具有很好的区域选择性和98%的非对映选择性，可以将其转化为手性四元天冬氨酸类似物。此外，我还发现三苯砷也是这种立体选择性烯丙基烷基化反应的有效配体，而2-(二苯基膦)苯甲酸和三苯砷具有不同的非对映选择性。最终，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区域和非对映选择性。在α和β位置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转化为手性四元氨基酸。较少

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