Tang Liang, Deng Li
Department of Chemistry, Brandeis University, Waltham, MA 02454-9110, USA.
J Am Chem Soc. 2002 Mar 27;124(12):2870-1. doi: 10.1021/ja0255047.
A highly enantioselective catalytic transformation of racemic alpha-hydroxy acids to optically active alpha-hydroxy acids is reported. A new procedure was developed for the condensation of racemic alpha-hydroxy acids with trichloromethyl chloroformate (diphosgene) at room temperature in the presence of activated charcoal to form 5-substituted-1,3-dioxolane-2,4-diones in 90-100% yield. An efficient dynamic kinetic resolution of 5-aryl dioxolanediones was realized via a modified cinchona alkaloid-catalyzed alcoholytic opening of the dioxolanedione ring, generating a variety of optically active alpha-hydroxy esters in 91-96% ee and 61-85% chemical yield. In this dynamic kinetic resolution, the modified cinchona alkaloid was found to serve dual catalytic roles, mediating both the rapid racemization of the 5-aryl dioxolanediones and the enantioselective alcoholytic ring opening of the 5-aryl dioxolanediones. Consequently, both enantiomers of the 5-aryl dioxolanediones were converted to highly enantiomerically enriched aromatic alpha-hydroxy esters in yields (61-85%), far exceeding the maximum of 50% for a normal kinetic resolution. This development not only represents an expansion of the scope of asymmetric acyl-transfer catalysis of synthetic catalysts but also provides a new approach for the development of efficient chemical dynamic kinetic resolutions promoted by a single catalyst. 5-Alkyl dioxolanediones were resolved by a conventional but highly enantioselective kinetic resolution to provide alpha-hydroxy acids and esters in high optical purity and good yields.
报道了一种将外消旋α-羟基酸高效对映选择性催化转化为光学活性α-羟基酸的方法。开发了一种新方法，在外消旋α-羟基酸与三氯甲基氯甲酸酯（双光气）在室温下于活性炭存在下缩合，以90 - 100%的产率形成5-取代-1,3-二氧戊环-2,4-二酮。通过改进的金鸡纳生物碱催化的二氧戊环二酮环的醇解开环，实现了5-芳基二氧戊环二酮的高效动态动力学拆分，生成了各种光学活性α-羟基酯，对映体过量值（ee）为91 - 96%，化学产率为61 - 85%。在这种动态动力学拆分中，发现改进的金鸡纳生物碱起到双重催化作用，介导5-芳基二氧戊环二酮的快速外消旋化以及5-芳基二氧戊环二酮的对映选择性醇解开环。因此，5-芳基二氧戊环二酮的两种对映体都转化为对映体高度富集的芳香族α-羟基酯，产率（61 - 85%）远远超过常规动力学拆分的最大产率50%。这一进展不仅代表了合成催化剂不对称酰基转移催化范围的扩展，还为开发由单一催化剂促进的高效化学动态动力学拆分提供了一种新方法。5-烷基二氧戊环二酮通过常规但高度对映选择性的动力学拆分进行拆分，以高光学纯度和良好产率提供α-羟基酸和酯。
