Copper Catalyzed Fluorination of Aryl Halides

铜催化芳基卤化物的氟化

• 批准号: 10115518
• 负责人: Liam Shin Sharninghausen
• 金额: $ 6.64万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10115518
• 关键词: Address; Agrochemicals; Alzheimer' s Disease; Alzheimer' s disease diagnosis; Area; Complex; Copper; Development; Diagnosis; Disease; Electrons; Enzyme Inhibitor Drugs; Fluorides; Fluorine; High temperature of physical object; Imaging Device; Imaging Techniques; Label; Lead; Ligands; Mediating; Metals; Methods; Parkinson Disease; Periodicity; Pharmacologic Substance; Positron-Emission Tomography; Process; Property; Protocols documentation; Radioisotopes; Reaction; Reporting; Research; Salts; Series; Source; System; Tracer; Transition Elements; Work; analog; aryl halide; base; carbene; catalyst; cost; functional group; improved; in vivo imaging; metal complex; non-invasive imaging; novel; prevent; radiotracer; scaffold

Project Summary. The aryl fluoride motif is prevalent in a range of important compounds. >25% of agrochemicals and >20% of pharmaceuticals contain fluorine, often in the form of aryl fluoride. Additionally, 18F is the favored radioisotope in Positron Emission Tomography (PET), an in-vivo imaging technique used in the diagnosis and treatment of diseases such as Alzheimer's and Parkinson's. Despite the widespread use of aryl fluorides in these areas, there are currently very few robust and functional group tolerant methods for their synthesis. Developing more efficient methods to introduce fluorine into organic molecules is therefore a priority. One promising method is the transition metal catalyzed synthesis of aryl fluorides from readily available aryl halides. However, there are few reported systems for this transformation. The two prior Cu-based systems use simple Cu salts and pose significant drawbacks that need to be addressed, such as the requirement for high temperatures, an excess of expensive fluoride source (AgF), supersoichiometric Cu, or limitation to specific directing groups. Developing systems that overcome these limitations is therefore an extremely important unsolved problem in the field. In order to improve on these systems, we aim to address key challenges inherent to Cu: (i) the instability of most CuIF complexes to disproportionation to form inactive Cu0 and CuF2 and (ii) the difficulty of the oxidative addition step. To overcome these issues we will move from simple Cu salts to well-defined copper complexes supported by N-heterocyclic carbenes (NHCs), cyclic alkyl amino carbene (CAACs), or related ligands. We hypothesize that these ligands will stabilize CuI intermediates, as well as favor oxidative addition, leading to more efficient catalysts. Specifically, we aim to use carbene-supported Cu complexes to: (1) study the effects of ligand properties on stoichiometric fluorination of aryl halides, (2) develop catalytic fluorination of a range of pharmaceutically relevant aryl halide scaffolds (3) synthesize 18F labeled tracer molecules for use in PET imaging. Completion of these aims will result in improved systems for the fluorination of aryl halides that can be applied to synthesis of pharmaceuticals, agrochemicals and PET tracers. Preliminary results have been obtained that support the feasibility of each proposed aim.

项目总结。

项目成果

Copper-Mediated Radiocyanation of Unprotected Amino Acids and Peptides.

• DOI: 10.1021/jacs.2c01959
• 发表时间: 2022-04-27
• 期刊: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
• 影响因子: 15
• 作者: Sharninghausen, Liam S.;Preshlock, Sean;Joy, Stephen T.;Horikawa, Mami;Shao, Xia;Winton, Wade P.;Stauff, Jenelle;Kaur, Tanpreet;Koeppe, Robert A.;Mapp, Anna K.;Scott, Peter J. H.;Sanford, Melanie S.
• 通讯作者: Sanford, Melanie S.

Sequential Ir/Cu-Mediated Method for the Meta-Selective C-H Radiofluorination of (Hetero)Arenes.

（杂音）领域的元选择性C-H射荧光的顺序IR/CU介导的方法。

• DOI: 10.1021/jacs.1c00523
• 发表时间: 2021-05-12
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: Wright JS;Sharninghausen LS;Preshlock S;Brooks AF;Sanford MS;Scott PJH
• 通讯作者: Scott PJH

Tandem Iridium-Catalyzed C-H Borylation/Copper-Mediated Radiofluorination of Aromatic C-H Bonds with [18F]TBAF.

[18F]TBAF 串联铱催化 C-H 硼化/铜介导的芳香族 C-H 键放射性氟化。

• DOI: 10.1007/978-1-0716-3499-8_4
• 发表时间: 2024
• 期刊: Methods in molecular biology (Clifton, N.J.)
• 作者: Morales,Maria;Preshlock,Sean;Sharninghausen,LiamS;Wright,JayS;Brooks,AllenF;Sanford,MelanieS;Scott,PeterJH
• 通讯作者: Scott,PeterJH

Copper-Mediated Late-stage Radiofluorination: Five Years of Impact on Pre-clinical and Clinical PET Imaging.

• DOI: 10.1007/s40336-020-00368-y
• 发表时间: 2020-06
• 期刊: Clinical and translational imaging
• 影响因子: 2.1
• 作者: Wright JS;Kaur T;Preshlock S;Tanzey SS;Winton WP;Sharninghausen LS;Wiesner N;Brooks AF;Sanford MS;Scott PJH
• 通讯作者: Scott PJH

Strategies for the Production of [11C]LY2795050 for Clinical Use.

临床用[11C]LY2795050 的生产策略。

• DOI: 10.1021/acs.oprd.2c00388
• 发表时间: 2023
• 期刊: Organic process research & development
• 影响因子: 3.4
• 作者: Kaur,Tanpreet;Shao,Xia;Horikawa,Mami;Sharninghausen,LiamS;Preshlock,Sean;Brooks,AllenF;Henderson,BradfordD;Koeppe,RobertA;DaSilva,AlexandreF;Sanford,MelanieS;Scott,PeterJH
• 通讯作者: Scott,PeterJH