Catalytic C-C Bond Forming Hydrogenations

催化 C-C 键形成氢化

• 批准号: 8269204
• 负责人: MICHAEL J KRISCHE
• 金额: $ 5.07万
• 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/8269204
• 关键词: 1-Propanol; 3-hydroxybutanal; Accounting; Acetylene; Acylation; Alcohols; Aldehydes; Alkenes; Alkylation; Alkynes; Amines; Anhydrides; Butadiene; Carbon Monoxide; Catalysis; Cods; Coupling; Development; Drug Industry; Ethylenes; Family; Felis catus; Funding; Generations; Goals; Health; 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 development; drug market; enantiomer; news; oxidation; prenylation; propadiene

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（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，可耐受物理或酶促拆分。而传统的氢化涉及C-H键的形成，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。在之前的资助期间，我们证明了氢化可用于将不同的p-不饱和反应物偶联到羰基化合物和亚胺上，在一系列经典的C=X（X = O，NR）加成过程中，构成了化学计量预形成的有机金属化合物的无副产物替代品。在拟议的资助期内，我们寻求继续这些首次系统性的努力，以利用C-C偶联中的催化氢化，而不仅仅是加氢。 公共卫生关系：超过50%的世界上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%是手性的，并将作为单一对映异构体实体上市。1994年，手性药物市场在全球范围内的总收入超过452亿美元，相当于一年内增长了27%！“1999年，手性药物市场销售额超过1000亿美元。2002年，全球单一对映体药物的销售额超过1590亿美元。值得注意的是，对映选择性氢化占工业生产的手性药物的一半以上，耐受物理或酶促拆分。氢化维斯手性药物的巨大影响预示着一种同样强大的方法来还原氢介导的C-C键形成。然而，自从烯烃加氢反应和母体费-托反应的发现以来，加氢偶联的领域一直处于闲置状态，该方法仅限于使用一氧化碳。在这个建议中，我们报告了第一个系统的努力，利用氢化以外的加氢C-C耦合。我们的努力已经导致了一个广泛的新的家庭的发展“氢化C-C耦合”-副产物的替代品化学计量预形成的有机金属化合物在一个不断增加的范围内的经典C=X（X = O，NR）的加成过程。