CHIRAL CATALYSTS FOR ENANTIOSELECTIVE SYNTHESES

本研究计划的目标是设计和开发高选择性和高效的催化过程，用于合成生物相关化合物。研究将建立在我们的最新发现与独特的催化用途的羧酸二钠。它们在化学氧化和手性路易斯酸方面的应用取得了突破，证明了这些催化剂的多功能性将得到进一步的探索。这些催化剂具有固定的立体结构，可以在重氮乙酸酯的金属碳反应中生成高度富集对映体的产物，同时它们的低氧化势也为高选择性路易斯酸催化反应和高效的化学氧化提供了能力。在所有目标中，我们寻求高流动率和高选择性。在此资助期内，我们将通过新工艺解决手性羧酰胺镝金属碳转化的局限性，初步结果表明目标将实现。我们将发展重氮化学用于催化立体选择转化，进一步提高催化金属碳化学在有机合成中的适用性。多功能b -酮-a-的新催化合成

The goal of this research program is the design and development of highly selective and efficient catalytic processes for the synthesis of biologically relevant compounds. Investigations will build upon our newest discoveries with unique catalytic uses of dirhodium carboxamidates. Breakthroughs in their applications for chemical oxidations and as chiral Lewis acids have demonstrated greatly enhanced versatility for these catalysts that will be further explored. The fixed stereodefined geometry of these catalysts provides access to highly enantioenriched products in metal carbene reactions of diazoacetates and, together with their low oxidation potentials, also provides capabilities for highly selective Lewis acid catalyzed reactions and efficient chemical oxidations. In all aims we seek high turnover numbers and high selectivities. In this funding period we will resolve limitations of chiral dirhodium carboxamidates for metal carbene transformations by novel processes for which preliminary results indicate that the aims will be achieved. We will develop diazo chemistry for catalytic stereoselective transformations to further enhance applicability of catalytic metal carbene chemistry in organic synthesis. New catalytic syntheses of multi-functional B-keto-a- diazoesters with subsequent catalytic metal carbene transformations provides highly efficient access to more complex carbon frameworks than previously possible through reactions with diazoacetates. We will use active Lewis acidic chiral dirhodium(ll,lll) carboxamidate catalysts to broaden the range of applicable carbon-carbon bond forming transformations. Reactivity and selectivity enhancement through chiral dirhodium(ll,lll) catalysts expands their utilization to Lewis acid catalyzed reactions for which chiral dirhodium(ll,ll) catalysts are ineffective, and initial focus will be given to those transformations for which preliminary results are most promising. We will develop and apply catalytic oxidative methodologies to compounds that are of biological significance. Newly discovered tert-butyl hydroperoxide oxidations catalyzed by dirhodium caprolactamate, based largely on its low oxidation potential and solubilities, offer a unique opportunity to develop a spectrum of oxidative transformations, compatible with water as a solvent, that are not easily achieved by other methods (especially allylic and benzylic oxidations). Applications encompass reactions with steroids, phenolic compounds, unsaturated fatty acids, amines, and other biologically relevant substrates.