Strategies for the Catalytic Synthesis of Nitrogen-Containing Molecules

含氮分子的催化合成策略

基本信息

  • 批准号:
    10698004
  • 负责人:
  • 金额:
    $ 38.4万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-09-10 至 2027-06-30
  • 项目状态:
    未结题

项目摘要

Project Abstract for NIH R35 (MIRA): The discovery and development of new methods for the efficient synthesis of N-containing and F-containing chemical building blocks is an important goal in organic synthesis as a large number of pharmaceuticals and other bioactive molecules contain these atoms within a diverse set of chemical functional groups. More rapid and/or selective assembly of known motifs, and moreover the preparation of new chemical landscapes, requires innovative approaches to drug-like scaffolds, including the discovery of new reagents and new catalysts/catalytic strategies. The current goals of this project fall under three main focus areas. 1) We will develop 2-azatrienes, a novel class of enamine umpolung reagents, for myriad catalytic enantioselective approaches towards chiral amines. Representative reactions that will be developed include 6,3-, 6,5- and 5,6-hydrofunctionalizations including reductive couplings with carbonyls and imines, hydroalkynylations, and hydroarylations. Azadienes generated from 6,5- and 5,6-hydrofunctionalizations of the azatriene reagents may be utilized in myriad downstream reactions, including other catalytic processes, thereby providing a diastereodivergent avenue towards highly complex chiral amines through sequential catalysis. 2) We will expand upon our prior work in enantioselective transformations of 2-azadienes, the first class of enamine umpolung reagents developed in our laboratory. Examples include reductive couplings with aromatic heterocycles, such as quinoline N-oxides, catalytic enantioselective fluorofunctionalizations with 4,4-difluoro-2-azadienes, cascade desymmetrization reactions, and reductive [3+2]-cycloadditions. 3) We will develop catalytic remote C–C and C–B coupling reactions that result in the loss of a halide from a trifluoromethyl group or H-atom abstraction from a difluoromethyl group to deliver difluorocarbons in a number of settings. In one case, we will carry out borylation or enantioselective alkylation of a 3-trifluoromethylpyridine scaffold to yield medicinally important and highly functionalized 3- (difluoromethyl)pyridines. In another area, we will execute a radical hydrogen atom abstraction of 4- difluoromethyl-2-azadienes to furnish a difluoro-2-azapentadienyl radical, which then may be engaged in catalytic cross-couplings to furnish chiral allylic amines bearing a difluoroalkene unit. Together, these undertakings will enable new chemical space for drug discovery to be obtained readily and with great diversity from simple reagents. We will access more established N-containing motifs more quickly and with greater levels of regio/stereocontrol compared to known approaches because of the invention of new reagents and the novel reactivity that they embody.
NIH R35(MIRA)项目摘要: 含氮、含氟化合物高效合成新方法的发现与发展 化学结构单元是有机合成中的重要目标,因为大量的药物, 其它生物活性分子在一组不同的化学官能团中含有这些原子。更快速 和/或已知基序的选择性组装,以及新化学景观的制备,需要 药物样支架的创新方法,包括发现新试剂和新催化剂/催化剂 战略布局 该项目目前的目标属于三个主要重点领域。1)我们将开发2-氮杂三烯, 的烯胺聚合试剂,无数的催化对映体选择性的方法对手性胺。 将要开发的代表性反应包括6,3-、6,5-和5,6-氢官能化,包括 与羰基和亚胺的还原偶联、氢化炔基化和氢化芳基化。生成的氮杂二烯 从氮杂三烯试剂的6,5-和5,6-氢官能化可以用于无数下游反应中, 反应,包括其他催化过程,从而提供了实现高度非对映异构化的途径。 通过顺序催化来络合手性胺。2)我们将扩展我们以前的工作,在对映选择性 2-氮杂二烯的转化,这是我们实验室开发的第一类烯胺聚合试剂。 实例包括与芳族杂环如喹啉N-氧化物的还原偶联,催化偶联,以及与芳族杂环如喹啉N-氧化物的还原偶联。 用4,4-二氟-2-氮杂二烯的对映选择性氟官能化,级联去对称化反应, 和还原性[3+2]-环加成。3)我们将开发催化远程C-C和C-B偶联反应, 导致从三氟甲基失去卤素或从二氟甲基夺取H原子, 在许多环境中提供二氟碳化合物。在一种情况下,我们将进行硼化或对映选择性 3-三氟甲基吡啶骨架的烷基化,得到医学上重要的和高度官能化的3- (二氟甲基)吡啶。在另一个领域,我们将执行4-甲基-N 二氟甲基-2-氮杂二烯以提供二氟-2-氮杂戊二烯基,其然后可以参与 催化交叉偶联以提供带有二氟烯烃单元的手性烯丙基胺。 总之,这些承诺将使新的化学空间的药物发现容易获得, 从简单的试剂中获得巨大的多样性。我们将更快地访问更多已建立的含N基序, 由于新试剂的发明,与已知方法相比,区域/立体控制水平更高 以及它们所体现的新颖反应性。

项目成果

期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Palladium-Catalyzed Regiodivergent Three-Component Alkenylamination of 1,3-Dienes with Alkyl and Aryl Amines.
  • DOI:
    10.1021/jacs.3c09873
  • 发表时间:
    2023-12
  • 期刊:
  • 影响因子:
    15
  • 作者:
    Xiaoxiao Ma;Steven J. Malcolmson
  • 通讯作者:
    Xiaoxiao Ma;Steven J. Malcolmson
{{ 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 }}

Steven Joseph Malcolmson其他文献

Steven Joseph Malcolmson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('Steven Joseph Malcolmson', 18)}}的其他基金

Strategies for the Catalytic Synthesis of Nitrogen-Containing Molecules
含氮分子的催化合成策略
  • 批准号:
    10405392
  • 财政年份:
    2022
  • 资助金额:
    $ 38.4万
  • 项目类别:
A Reverse Polarity Stereoselective C-C Bond-Forming Strategy for Preparing Chiral Amines
制备手性胺的反极性立体选择性 C-C 键形成策略
  • 批准号:
    9975183
  • 财政年份:
    2017
  • 资助金额:
    $ 38.4万
  • 项目类别:
A Reverse Polarity Stereoselective C-C Bond-Forming Strategy for Preparing Chiral Amines
制备手性胺的反极性立体选择性 C-C 键形成策略
  • 批准号:
    9367817
  • 财政年份:
    2017
  • 资助金额:
    $ 38.4万
  • 项目类别:
A Reverse Polarity Stereoselective C-C Bond-Forming Strategy for Preparing Chiral Amines
制备手性胺的反极性立体选择性 C-C 键形成策略
  • 批准号:
    10217180
  • 财政年份:
    2017
  • 资助金额:
    $ 38.4万
  • 项目类别:
Probing the Biosynthesis of Thiazolyl Peptide Antibiotic Berninamycin A
噻唑基肽类抗生素伯尼霉素A的生物合成探讨
  • 批准号:
    8249239
  • 财政年份:
    2012
  • 资助金额:
    $ 38.4万
  • 项目类别:
Probing the Biosynthesis of Thiazolyl Peptide Antibiotic Berninamycin A
噻唑基肽类抗生素伯尼霉素A的生物合成探讨
  • 批准号:
    8426295
  • 财政年份:
    2012
  • 资助金额:
    $ 38.4万
  • 项目类别:

相似海外基金

More sustainable biocatalytic imine reductions to chiral amines with hydrogen-driven NADPH recycling operated in batch and continuous flow
通过批量和连续流操作的氢驱动 NADPH 回收,更可持续地生物催化亚胺还原为手性胺
  • 批准号:
    2889869
  • 财政年份:
    2023
  • 资助金额:
    $ 38.4万
  • 项目类别:
    Studentship
Organoborane-catalysed approaches to biologically active amines
有机硼烷催化制备生物活性胺的方法
  • 批准号:
    EP/Y00146X/1
  • 财政年份:
    2023
  • 资助金额:
    $ 38.4万
  • 项目类别:
    Research Grant
Transforming Amines into Complex Polycyclic Molecules and Bioactive Natural Products
将胺转化为复杂的多环分子和生物活性天然产物
  • 批准号:
    2247651
  • 财政年份:
    2023
  • 资助金额:
    $ 38.4万
  • 项目类别:
    Standard Grant
Ti-catalyzed cascading hydroaminoalkylation as a route to complex functionalized amines
Ti 催化级联氢氨基烷基化作为制备复杂官能化胺的途径
  • 批准号:
    10750347
  • 财政年份:
    2023
  • 资助金额:
    $ 38.4万
  • 项目类别:
New Photocatalytic C-C Bond-Forming Reactivity of Unprotected Primary Amines
未受保护伯胺的新光催化 C-C 键形成反应
  • 批准号:
    EP/X026566/1
  • 财政年份:
    2023
  • 资助金额:
    $ 38.4万
  • 项目类别:
    Research Grant
Nickel Cross-Coupling Cascades with α-Heteroatom Radicals to Prepare Sterically Hindered Alcohols and Amines
镍与α-杂原子自由基交叉偶联级联制备位阻醇和胺
  • 批准号:
    10604535
  • 财政年份:
    2023
  • 资助金额:
    $ 38.4万
  • 项目类别:
Mining the air for amines
开采空气中的胺
  • 批准号:
    2752688
  • 财政年份:
    2022
  • 资助金额:
    $ 38.4万
  • 项目类别:
    Studentship
Towards a better understanding of the effect of the pentafluorosulfanyl group on the lipophilicity and acid/base properties of alcohols and amines
更好地了解五氟硫基对醇和胺的亲脂性和酸/碱性质的影响
  • 批准号:
    571856-2021
  • 财政年份:
    2022
  • 资助金额:
    $ 38.4万
  • 项目类别:
    Alliance Grants
Development of Strategies for the Enantioselective Synthesis of Heterocycles and Acyclic Amines
杂环和无环胺对映选择性合成策略的发展
  • 批准号:
    10656344
  • 财政年份:
    2022
  • 资助金额:
    $ 38.4万
  • 项目类别:
Pd-Catalyzed C(sp3)-H Functionalizations Directed by Free Alcohols and Boc-Protected Amines
由游离醇和 Boc 保护的胺引导的 Pd 催化 C(sp3)-H 官能化
  • 批准号:
    10606508
  • 财政年份:
    2022
  • 资助金额:
    $ 38.4万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了