Controlling Reactivity and Selectivity in the Nondirected C–H Activation of Arenes with Palladium

反应性(心理学) 选择性 化学 催化作用 有机化学 医学 替代医学 病理
作者
Simon Kaltenberger,Manuel van Gemmeren
出处
期刊:Accounts of Chemical Research [American Chemical Society]
卷期号:56 (18): 2459-2472 被引量:21
标识
DOI:10.1021/acs.accounts.3c00354
摘要

ConspectusAromatic structures are widespread motifs throughout organic chemistry, and C-H activation has been recognized as a major tool for enabling their sustainable and efficient functionalization. Through C-H activation, arenes can be modified without the need for prefunctionalization, leading to inherent atom- and step-economic advantages over traditional methods. However, for the development of synthetically useful methods, several hurdles have to be overcome. The strength of C-H bonds necessitates the development of sufficiently reactive catalysts, while the presence of multiple C-H bonds within a substrate poses challenges in terms of site-selectivity. Traditionally these challenges have been addressed by substrate control. By attaching different directing groups (DGs), the reactivity of the respective arene was significantly enhanced and the DG guided the metal in close proximity to specific C-H bonds, resulting in high site-selectivity. However, the introduction and removal of the DG add additional steps to the synthetic sequence, and the scope of the reaction is limited to a specific substrate class. The development of complementary nondirected methods that can be applied to a broad range of arenes without the necessity to carry a specific functional group that coordinates to Pd (referred to as simple arenes) is therefore highly desirable. However, the intrinsically lower reactivity of such substrates and the absence of a selectivity-determining DG pose significant challenges that can be solved only by the development of highly efficient catalysts. Consequently, the field of nondirected C-H activation, especially with respect to Pd-catalyzed methods, remained comparatively underdeveloped when we initiated our research program in 2017. At that time, state-of-the-art methods required the arene to be used in large excess, precluding its use in late-stage functionalization. Since organopalladium species are among the most versatile synthetic intermediates, we realized that developing a system, which can effectively and selectively activate C-H bonds in simple arenes with the arene as the limiting reagent, would be a powerful tool in synthetic organic chemistry. This account summarizes our groups' research toward the development and application of catalytic systems offering this desired reactivity and focuses explicitly on Pd-catalyzed nondirected C-H functionalization reactions of arenes, where the arene is employed as a limiting reagent. After an introduction that summarizes the state of Pd-catalyzed C-H activation of arenes before 2017 and the associated challenges, experimental and mechanistic details about the development of the first arene-limited, nondirected C-H functionalization of simple arenes with palladium will be discussed. This reactivity was enabled by the identification and combination of two complementary ligands, an N-heterocycle and an amino acid-derived ligand. Afterward we will discuss the expansion of this dual-ligand approach to further arene-limited transformations. Finally, we describe two methodologies that originated from the observations we made during our studies, namely, the late-stage deuteration of simple arenes and a highly selective olefination method that uses noncovalent interactions to induce meta selectivity.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
1秒前
姜惠完成签到 ,获得积分10
1秒前
小脸红扑扑完成签到 ,获得积分10
2秒前
奋斗的凡完成签到 ,获得积分10
2秒前
3秒前
zhutier完成签到,获得积分10
4秒前
wrr完成签到,获得积分10
4秒前
WxChen完成签到,获得积分10
4秒前
开朗艳一完成签到,获得积分10
6秒前
Wonder完成签到,获得积分10
7秒前
yang完成签到,获得积分10
9秒前
123123完成签到 ,获得积分10
10秒前
温暖宛筠完成签到,获得积分10
10秒前
小欣6116完成签到,获得积分10
11秒前
请叫我风吹麦浪应助冬月采纳,获得10
11秒前
LIUYONG发布了新的文献求助10
12秒前
12秒前
肖雪依完成签到,获得积分10
12秒前
影子完成签到,获得积分10
13秒前
14秒前
晨珂完成签到,获得积分10
14秒前
Florencia发布了新的文献求助10
16秒前
xiezhuochun发布了新的文献求助10
17秒前
17秒前
同瓜不同命完成签到,获得积分10
19秒前
牛马哥发布了新的文献求助10
20秒前
温婉的松鼠完成签到,获得积分10
20秒前
21秒前
辛勤的寄瑶完成签到,获得积分10
21秒前
Lauren完成签到 ,获得积分10
22秒前
23秒前
忆枫完成签到,获得积分10
27秒前
炒鸡小将发布了新的文献求助10
27秒前
花壳在逃野猪完成签到 ,获得积分10
27秒前
27秒前
银子吃好的完成签到,获得积分10
28秒前
西瓜霜完成签到 ,获得积分10
28秒前
科研废物完成签到 ,获得积分10
30秒前
冬月完成签到,获得积分10
30秒前
30秒前
高分求助中
【提示信息,请勿应助】关于scihub 10000
Les Mantodea de Guyane: Insecta, Polyneoptera [The Mantids of French Guiana] 3000
徐淮辽南地区新元古代叠层石及生物地层 3000
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
Handbook of Industrial Diamonds.Vol2 1100
Global Eyelash Assessment scale (GEA) 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 550
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 4038303
求助须知:如何正确求助?哪些是违规求助? 3576013
关于积分的说明 11374210
捐赠科研通 3305780
什么是DOI,文献DOI怎么找? 1819322
邀请新用户注册赠送积分活动 892672
科研通“疑难数据库(出版商)”最低求助积分说明 815029