CHIRAL CATALYSTS FOR ENANTIOSELECTIVE SYNTHESES

用于对映选择性合成的手性催化剂

• 批准号: 7928258
• 负责人: Michael PATRICK Doyle
• 金额: $ 29.7万
• 依托单位: UNIV OF MARYLAND, COLLEGE PARK
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7928258
• 关键词: 3-hydroxybutanal; Acetates; Acetone; Acidity; Acids; Age; Alcohols; Aldehydes; Alder plant; Alkenes; Amides; Amines; Area; Aromatic Amines; Aziridines; Benzodiazepines; Biological; Biological Factors; Books; Bromides; Carbon; Carbonates; Catalysis; Characteristics; Chemicals; Chemistry; Chromium; Cobalt; Collaborations; Complex; Copper; Coupled; Crystallization; Cyclization; Cyclopropanes; DNA Sequence Rearrangement; Data; Detection; Development; Diels Alder reaction; Discrimination; Dissociation; Doctor of Philosophy; Electron Transport; Electronics; Employee Strikes; Epoxy Compounds; Equilibrium; Esters; Ethers; Exclusion; Free Energy; Funding; Goals; Grant; Heterocyclic Compounds; High Pressure Liquid Chromatography; Hydrogen; Hydrogen Bonding; Hydrogen Peroxide; Hydrolysis; Hydroxide Ion; Hydroxides; Imines; Individual; Investigation; Ions; Isomerism; Isoquinolines; Isotopes; Ketones; Kinetics; Laboratories; Lactones; Lead; Ligands; Link; Manganese; Manuscripts; Mediating; Metals; Methodology; Methods; Modeling; Modification; Nitrogen; Organic Synthesis; Outcome; Oxygen; Palladium; Pathway interactions; Phenols; Physical condensation; Polymers; Positioning Attribute; Potassium; Preparation; Process; Proline; Publishing; Pyrazoles; Pyrroles; Pyrrolidines; Quinine; Reaction; Recovery; Relative (related person); Reporting; Research; Research Peer Review; Resort; Rhodium; Role; Route; Ruthenium; Scandium; Scheme; Site; Slide; Solubility; Solvents; Steroids; Sulfonamides; System; Temperature; Thermodynamics; Titanium; Toluene; Transfer RNA; United States National Institutes of Health; Unsaturated Fatty Acids; Variant; Vertebral column; Water; alkyl group; analog; azetidinone; base; carbene; carbonyl compound; carboxylate; catalyst; coping; cycloaddition; cyclopropane; decane; deprotonation; design; diazo compound; dirhodium tetraacetate; enol; hydronium ion; inhibitor/antagonist; insight; interest; novel; oxidation; peroxidation; pi bond; prevent; programs; pyridine; pyrrolidine; pyrroline; racemization; sodium ion; stereochemistry; tert-Butylhydroperoxide; tertiary amine; tetrahydrofuran; ylide

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.

该研究计划的目标是设计和开发用于合成生物相关化合物的高选择性和高效的催化工艺。调查将建立在我们的最新发现的基础上，具有独特的催化作用。它们在化学氧化和手性路易斯酸应用方面的突破表明，这些催化剂的通用性大大增强，有待进一步探索。这些催化剂的固定立体构型提供了在重氮乙酸酯的金属卡宾反应中获得高对映体富集物的途径，加上它们的低氧化电位，还提供了高选择性Lewis酸催化反应和有效的化学氧化的能力。在所有目标中，我们都追求高成交量和高选择性。在这一资助期间，我们将通过新的工艺来解决手性碳酰亚胺在金属卡宾转化中的局限性，初步结果表明这些新工艺将实现目标。我们将发展催化立体选择性转化的重氮化学，以进一步增强催化金属卡宾化学在有机合成中的适用性。多官能团B-酮-a-的催化合成新方法 重氮酯通过随后的催化金属卡宾转化提供了比以前通过与重氮乙酸酯反应更复杂的碳骨架的高效途径。我们将使用活性刘易斯酸性手性(11，11)碳酰胺酯催化剂来扩大适用的碳-碳键形成转化的范围。手性镝(ll，ll)催化剂的反应活性和选择性的提高使其在Lewis酸催化的反应中得到了广泛的应用，而对于那些对手性镝(ll，ll)催化剂无效的反应，我们将首先关注那些初步结果最多的转化。 很有希望。我们将开发和应用催化氧化方法来处理具有生物意义的化合物。新发现的叔丁基过氧化氢氧化反应主要基于己内酰胺酸二氢钠的低氧化电位和低溶解性，为开发与水作为溶剂的氧化转化光谱提供了独特的机会，而这些氧化转化是其他方法(特别是烯丙基和苄基氧化)不易实现的。应用包括与类固醇、酚类化合物、不饱和脂肪酸、胺和其他生物相关底物的反应。