Stereoselective Synthesis of Quaternary Amino Acids by Transition Metal Catalyzed Reaction

在本项目中，我成功控制了过渡金属催化醋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，实现了手性季氨基酸及其类似物的构建。发现钯催化(R)-或(S)-2-乙酰氧基-4-苯基-3-丁烯与N-（二苯基亚甲基）甘氨酸和N-（二苯基亚甲基）丙氨酸的烯丙基烷基化反应的区域选择性和非对映选择性被2-（二苯基膦）苯甲酸高度控制。例如，与N-（二苯基甲基）甘氨酸反应形成手性氨基酸类似物，在α和β位置具有相邻的两个手性叔碳中心，具有高达99%的对映和非对映选择性。烷基化产物经7步转化为手性天冬氨酸类似物。在与N-二苯基甲基丙氨酸盐的反应中，成功地控制了区域选择性和非对映选择性，构建了在α和β位置具有更丰富的邻手性季碳中心和叔碳中心的氨基酸类似物，其对映选择性和非对映选择性分别高达99%和95%。手性烷基化产物经7步转化手性2,3-二甲基天冬氨酸。此外，我研究了类似的立体选择性烯丙基烷基化与唑内酯，我也成功地控制了区域选择性和非对映选择性。在苯内酯的反应中，我再次证实了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-甲基取代氮杂内酯的反应具有完美的区域选择性和98%的非对映选择性，并被证明可将其转化为手性季天冬氨酸类似物。此外，我发现三苯基larsin也是这种立体选择性烯丙基烷基化的有效配体，并且2-（二苯基膦）苯甲酸和三苯基larsin具有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的区域选择性和非对映选择性。偶联产物在相邻的两个手性碳中心或在相邻的α和β位置上具有手性季碳中心和叔碳中心，即转化为手性季氨基酸。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