Catalytic C-C Bond Forming Hydrogenations

催化 C-C 键形成氢化

• 批准号: 7516041
• 负责人: MICHAEL J KRISCHE
• 金额: $ 31.61万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-15 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7516041
• 关键词: 1-Propanol; 3-hydroxybutanal; Accounting; Acetylene; Acylation; Alcohols; Aldehydes; Alkenes; Alkylation; Alkynes; Amines; Anhydrides; Butadiene; Carbon Monoxide; Catalysis; Classification; Cods; Coupling; Development; Drug Industry; Ethylenes; Family; Felis catus; Funding; Generations; Goals; Hydrogen; Hydrogen Bonding; Hydrogenation; Imines; Iridium; Ketones; Laboratories; Ligands; Marketing; Mediating; Metals; Methodology; Methods; Oxidation-Reduction; Parents; Pharmaceutical Preparations; Process; Propanols; Propionates; Reaction; Reagent; Reducing Agents; Reporting; Research; Resolution; Rhodium; Sales; Scheme; Screening procedure; Staging; Technology; base; carbonyl compound; catalyst; design; drug market; enantiomer; news; oxidation; prenylation; propadiene; public health relevance

DESCRIPTION (provided by applicant): Enantioselective hydrogenation accounts for over half the chiral drugs produced industrially, withstanding physical or enzymatic resolution. Whereas conventional hydrogenation involves C-H bond formation, our research breaks dogma by establishing hydrogenation as a method for C-C bond formation. In the prior funding period, we demonstrated that hydrogenation could be used to couple diverse p-unsaturated reactants to carbonyl compounds and imines, constituting a byproduct-free alternative to stoichiometrically preformed organometallics in a range of classical C=X (X = O, NR) addition processes. In the proposed funding period, we seek to continue these first systematic efforts to exploit catalytic hydrogenation in C-C couplings beyond hydroformylation. PUBLIC HEALTH RELEVANCE: Over 50% of the world's top-selling drugs are single enantiomers and it is estimated that 80% of all drugs currently entering development are chiral and will be marketed as single-enantiomer entities. In 1994, the chiral drug market grossed over "45.2 billion US dollars worldwide, which corresponds to an increase of 27% in a single year!" In 1999, the chiral drug market topped 100 billion US dollars in sales. In 2002, world-wide sales of single enantiomer drugs reached more than 159 billion US dollars. Notably, enantioselective hydrogenation accounts for over half the chiral drugs produced industrially, withstanding physical or enzymatic resolution. The enormous impact of hydrogenation vis-¿-vis chiral drugs portends an equally powerful approach to reductive C-C bond formations mediated by hydrogen. However, since the discovery of alkene hydroformylation and the parent Fischer-Tropsch reaction, processes restricted to the use of carbon monoxide, the field of hydrogenative coupling has lain fallow. In this proposal, we report the first systematic efforts to exploit hydrogenation in C-C couplings beyond hydroformylation. Our efforts have led to the development of a broad new family "hydrogenative C-C couplings" - byproduct-free alternatives to stoichiometrically preformed organometallics in an ever-increasing range classical C=X (X = O, NR) addition processes.

描述（由应用提供）：尽管有物理或酶促分辨率，对映选择性氢化占工业生产的手性药物的一半以上。而常规的氢化涉及C-H键的形成，而我们的研究通过建立氢化作为C-C键形成的方法来打破教条。在上一期的资金期间，我们证明了氢化可用于将潜水员的P-P-未饱和反应物与羰基化合物和亚胺相结合，在一系列经典的C = x（x = o，nr）的一系列经典c = x（x = o，nr）中，构成了无副产物的无副产物替代品。在拟议的资金期间，我们试图继续进行这些第一个系统的努力，以利用除氢甲基甲基化的C-C伴侣中的催化氢化。公共卫生相关性：超过50％的全球最畅销的药物是单一的对映异构体，据估计，目前进入开发的所有药物中有80％都是手性的，并且将作为单一南型人实体销售。 1994年，手性药物市场在“全球452亿美元的452亿美元相对应，这相当于一年中增长27％！” 1999年，手性药物市场的销售额超过了1000亿美元。 2002年，单一对映异构体药物的全球销售额达到了159亿美元。值得注意的是，尽管有物理或酶促分辨率，对映选择性氢化占工业生产的手性药物的一半以上。氢化相对于手性药物的巨大影响预示着一种同样强大的方法，可以减少由氢介导的C-C键形成。但是，由于发现烯烃的烯烃加氢甲基化和母体fischer-tropsch反应，因此限于使用一氧化碳的过程，氢化偶联的领域令人感到遗憾。在此提案中，我们报告了第一个系统的努力，以利用氢甲基化以外的C-C耦合中的氢化。我们的努力导致了一个广泛的新家族“氢化C-C耦合” - 在不断增加的经典C = x（x = o，nr）的添加过程中，无副产物的无副产物替代品。