Catalytic C-C Bond Forming Hydrogenations

催化 C-C 键形成氢化

• 批准号: 7797744
• 负责人: MICHAEL J KRISCHE
• 金额: $ 4.36万
• 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 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7797744
• 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（由申请人提供）：对映选择性氢化占工业生产的手性药物的一半以上，常规氢化涉及C-H键形成，我们的研究通过建立氢化作为C-C键形成方法打破了教条。在之前的资助期间，我们证明了氢化可用于将各种对不饱和反应物与羰基化合物和亚胺偶联，构成一种无副产物的替代品在一系列经典的 C=X (X = O, NR) 加成过程中，我们寻求继续这些首次系统性的努力，以在加氢甲酰化之外探索 C-C 偶联中的催化氢化。全球最畅销药物中 50% 是单一对映体，预计目前进入开发的所有药物中 80% 是手性药物，并且将1994年，手性药物市场总额超过“452亿美元，相当于一年增长了27%！”1999年，手性药物市场突破了1000亿美元。 2002年，全球单一对映异构体药物的销售额超过1590亿美元。超过一半的手性药物是工业生产的，能够承受物理或酶解氢化的巨大影响。 -vis 手性药物预示着一种同样有效的由氢介导的还原 C-C 键形成的方法。然而，自从烯烃加氢甲酰化和母体费托反应的发现，限制了一氧化碳的使用过程，氢化偶联领域已经出现。在这项提案中，我们报告了在加氢甲酰化之外的 C-C 偶联中首次系统性的努力，我们的努力导致了一个广泛的新家族“氢化”的发展。 C-C 耦合”——在不断增加的经典 C=X (X = O, NR) 加成工艺中按化学计量预先形成的有机金属的无副产物替代品。