Directed Arylation of Unprotected Anilines Enabled by Continuous Flow Technology
通过连续流技术实现未保护苯胺的定向芳基化
基本信息
- 批准号:9107901
- 负责人:
- 金额:$ 4.86万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-08-01 至 2017-06-03
- 项目状态:已结题
- 来源:
- 关键词:AddressAmidinesAnilineAromatic AminesBindingCarbamatesCarbonCarbon DioxideCarbonatesCellsChemicalsChemistryComplexCouplingDecarboxylationDevelopmentFutureGenerationsHealthHigh temperature of physical objectHydrogen BondingIn SituLeadLibrariesLigandsMaintenanceMetalsMethodsMonitorPalladiumPharmaceutical PreparationsPharmacologic SubstancePreparationProcessReactionReaction TimeReagentReportingResearchRouteSaltsSocietiesSodium ChlorideStructureSystemTechniquesTechnologyTemperatureTransition ElementsTubeamino groupbasecostcost effectiveflasksfunctional grouppressurepreventresidencescaffoldsuccesstoolwasting
项目摘要
DESCRIPTION (provided by applicant): The direct functionalization of arene C-H bonds can be a powerful way of constructing biaryl motifs found in a variety of medicinally relevant molecules. Despite the potential utility of direct C-H arylation, control of regioselectivity remais a difficulty that limits its synthetic utility. One approach to address this issue is the use of an
ortho directing group. Although many such directing groups are currently known, most are synthetically inflexible or require added protection/deprotection steps for their use. Due to the versatility of the amino group, an ortho-arylation using this functional group would be synthetically valuable, allowing access to diverse ortho-substituted biaryl derivatives. However, use of the amino group for ortho direction is challenging, the first example of which having been reported only very recently. The current proposal provides an approach to ortho-arylation of anilines and heteroarylamines utilizing continuous flow technology. Specifically, through the use of carbon dioxide as an abundant and inexpensive reagent, the amino group of an arylamine will be converted to the carbamate salt, which can serve as an in situ protecting and directing group for ortho-arylation. The use of continuous flow methods for this approach is uniquely advantageous, since 1) the thermally labile carbamate salts can be produced and immediately consumed, and 2) high carbon dioxide pressure can be conveniently and safely accessed, a condition necessary to prevent decarboxylation of the carbamate intermediates at the high temperatures required for C-H arylation. Taken together, these two features of continuous flow synthesis allow for an expedient ortho-arylation of anilines that eliminates the need for separate protection/deprotection steps. This advance could lead to more cost-effective syntheses of biaryl scaffolds that are ubiquitous in pharmaceutical agents.
描述(由申请人提供):芳烃C-H键的直接官能化可以是构建在各种医学相关分子中发现的联芳基基序的有效方法。尽管直接C-H芳基化有潜在的用途,但区域选择性的控制仍然是限制其合成用途的一个困难。解决此问题的一种方法是使用
Ortho导演组。虽然目前已知许多这样的导向基团,但大多数合成上不灵活,或者需要额外的保护/解除保护步骤才能使用。由于氨基的多功能性,使用这种官能团的邻位芳基化反应将具有合成价值,从而可以获得各种邻位取代的联芳基衍生物。然而,将氨基用于邻位方向是具有挑战性的,第一个例子直到最近才被报道。目前的建议提供了一种利用连续流动技术进行苯胺和杂芳胺的邻位芳基化反应的方法。具体地说,通过使用二氧化碳作为一种丰富而廉价的试剂,芳胺的氨基将被转化为氨基甲酸酯盐,它可以作为邻位芳基化的原位保护和导向基团。对于这种方法使用连续流动方法是独特的优势,因为1)可以生产热不稳定的氨基甲酸盐并立即消费,以及2)可以方便和安全地获得高二氧化碳压力,这是防止在C-H芳基化所需的高温下氨基甲酸酯中间体脱羧所必需的条件。总而言之,连续流动合成的这两个特点使得苯胺可以方便地进行邻位芳基化反应,从而不需要单独的保护/去保护步骤。这一进展可能导致更具成本效益的联芳基支架的合成,这种支架普遍存在于药物中。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Yiming Wang其他文献
Yiming Wang的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Yiming Wang', 18)}}的其他基金
New Strategies and Reactions for the α-C–H Functionalization and Hydrofunctionalization of Carbon–Carbon Multiple Bonds
碳-碳多重键α-C-H官能化和氢官能化的新策略和反应
- 批准号:
10436379 - 财政年份:2021
- 资助金额:
$ 4.86万 - 项目类别:
New Strategies and Reactions for the α-C–H Functionalization and Hydrofunctionalization of Carbon–Carbon Multiple Bonds
碳-碳多重键α-C-H官能化和氢官能化的新策略和反应
- 批准号:
10276217 - 财政年份:2021
- 资助金额:
$ 4.86万 - 项目类别:
New Strategies and Reactions for the α-C–H Functionalization and Hydrofunctionalization of Carbon–Carbon Multiple Bonds
碳-碳多重键α-C-H官能化和氢官能化的新策略和反应
- 批准号:
10651859 - 财政年份:2021
- 资助金额:
$ 4.86万 - 项目类别:
Directed Arylation of Unprotected Anilines Enabled by Continuous Flow Technology
通过连续流技术实现未保护苯胺的定向芳基化
- 批准号:
8778839 - 财政年份:2014
- 资助金额:
$ 4.86万 - 项目类别:
Directed Arylation of Unprotected Anilines Enabled by Continuous Flow Technology
通过连续流技术实现未保护苯胺的定向芳基化
- 批准号:
8912912 - 财政年份:2014
- 资助金额:
$ 4.86万 - 项目类别:
相似海外基金
Optical resolution of weak acids with chiral amidines
手性脒光学拆分弱酸
- 批准号:
20K05458 - 财政年份:2020
- 资助金额:
$ 4.86万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Method development for synthesis of substituted pyrimidines using amidines.
使用脒合成取代嘧啶的方法开发。
- 批准号:
508542-2017 - 财政年份:2017
- 资助金额:
$ 4.86万 - 项目类别:
Experience Awards (previously Industrial Undergraduate Student Research Awards)
Method development for synthesis of Substituted pyrimidines using amidines.
使用脒合成取代嘧啶的方法开发。
- 批准号:
478936-2015 - 财政年份:2015
- 资助金额:
$ 4.86万 - 项目类别:
Experience Awards (previously Industrial Undergraduate Student Research Awards)
Method development for synthesis of substituted pyrimidines using amidines
使用脒合成取代嘧啶的方法开发
- 批准号:
488500-2015 - 财政年份:2015
- 资助金额:
$ 4.86万 - 项目类别:
Experience Awards (previously Industrial Undergraduate Student Research Awards)
Construction of Soft Materials Utilizing Charge-Assisted Hydrogen Bonding between Amidines and Oxo Acids
利用脒和含氧酸之间的电荷辅助氢键构建软材料
- 批准号:
26410102 - 财政年份:2014
- 资助金额:
$ 4.86万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Les hydroxy-amidines et leurs complexes métalliques
羟基脒等金属复合物
- 批准号:
368927-2008 - 财政年份:2008
- 资助金额:
$ 4.86万 - 项目类别:
University Undergraduate Student Research Awards
DEVELOPMENT OF AMIDINES AS SELECTIVE MUSCARINIC AGONISTS
脒作为选择性毒蕈碱激动剂的开发
- 批准号:
6258840 - 财政年份:1997
- 资助金额:
$ 4.86万 - 项目类别:
DEVELOPMENT OF AMIDINES AS SELECTIVE MUSCARINIC AGONISTS
脒作为选择性毒蕈碱激动剂的开发
- 批准号:
2269099 - 财政年份:1994
- 资助金额:
$ 4.86万 - 项目类别:
DEVELOPMENT OF AMIDINES AS SELECTIVE MUSCARINIC AGONISTS
脒作为选择性毒蕈碱激动剂的开发
- 批准号:
2269098 - 财政年份:1994
- 资助金额:
$ 4.86万 - 项目类别:
DEVELOPMENT OF AMIDINES AS SELECTIVE MUSCARINIC AGONISTS
脒作为选择性毒蕈碱激动剂的开发
- 批准号:
2269100 - 财政年份:1994
- 资助金额:
$ 4.86万 - 项目类别: