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

最近我们发现，在钯络合物的催化量存在下，各种有机卤化物，包括芳基卤化物和烯基卤化物，可以与一氧化碳和亲核试剂（仲胺和醇）反应，转化为α -酮酸衍生物，如α -酮酰胺和α -酮酯。在这项研究中，研究了利用这些双羰基化反应合成新的α -氨基酸和α -羟基酸。(1)详细研究了双羰基化反应的机理和应用范围。(2)通过氨基化反应，对α -烯烃进行了化学计量双羰基化反应，得到-、- -不饱和α -酮酰胺。(3)开发了将芳香族醛和碳氢化合物转化为α -酮酰胺的新合成反应。(4)芳基卤化物双羰基化反应制备的α -酮酰胺，经水解可得到多种芳香型α -酮酸，产率较高。(5)得到的α -酮酸经苯肼处理后，经钯催化的α -酮酸苯基氢化反应，产率可达90%以上，转化为α -氨基酸。(6)利用面包酵母（Saccharomyces cervisiae）对各种对和间取代苯甲酰甲酸酯进行高选择性不对称还原，得到具有光学活性的扁桃酸酯衍生物。(7) -酮酸在含甲醇或甲醛的碱性水溶液中可还原为相应的-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.