Novel Synthetic Methods of -Amino Acids and -Hydroxy Acids Using Transition Metal Catalysts

最近我们发现，在催化量的钯络合物存在下，包括芳基和烯基卤化物的各种有机卤化物可以在与一氧化碳和亲核试剂（仲胺和醇）的反应中转化成α-酮酸衍生物，例如α-酮酰胺和α-酮酯。在这项研究中，新的α-氨基酸和α-羟基酸的合成利用这些双羰基化反应进行了研究。(1)对双羰基化反应的机理和应用范围进行了详细的研究。(2)α-烯烃的化学计量双羰基化反应得到β，γ-不饱和α-酮酰胺已通过氨基钯化反应进行。(3)已经开发了将芳族醛和烃转化为α-酮酰胺的新型合成反应。(4)通过芳基卤化物的双羰基化反应制备的α-酮酰胺的水解，可以以良好的产率合成各种芳香族α-酮酸。(5)通过用苯肼处理，然后对所得α-酮酸的苯腙进行钯催化氢化，将由此获得的α-酮酸以超过90%的产率转化为相应的α-氨基酸。(6)通过使用面包酵母（酿酒酵母）进行各种帕拉和间位取代的苯甲酰基甲酸酯的高选择性不对称还原以得到光学活性扁桃酸酯衍生物。(7)α-酮酸可以在含有甲醇或甲醛的碱性水溶液中还原为相应的α-羟基酸。

Recently we found that various organic halides including aryl and alkenyl halides can be converted into alpha-keto acid derivatives such as alpha-keto amides and alpha-keto esters on reactions with carbon monoxide and nucleophiles (secondary amines and alcohols) in the presence of catalytic amounts of palladium complexes. In this study novel alpha-amino acid and alpha-hydroxy acid syntheses utilizing these double carbonylation reactions have been examined.(1) Mechanisms and scope of applications of the double carbonylation reactions have been studied in detail.(2) Stoichiometric double carbonylation of alpha-olefins to afford beta,gamma-unsaturated alpha-keto amides has been performed by using an aminopalladation reaction.(3) Novel synthetic reactions which convert aromatic aldehydes and hydrocarbons into alpha-keto amides have been developed.(4) A variety of aromatic alpha-keto acids can be synthesized in good yields by hydrolysis of alpha-keto amides prepared by the double carbonylation reactions of aryl halides.(5) The alpha-keto acids thus obtained are converted into corresponding alpha-amino acids in over 90% yields by treatment with phenylhydrazine followed by palladium-catalyzed hydrogenation of resulting phenylhydrozones of the alpha-keto acids.(6) Highly selective asymmetric reduction of various para- and meta-substituted benzoylformic acid esters to give optically active mandelic acid ester derivatives is performed by using a baker's yeast (Saccharomyces cervisiae).(7) Alpha-keto acids can be reduced to corresponding alpha-hydroxy acids in aqueous alkaline solutions containing methanol or formaldehyde.