Catalytic coupling of arene C-H bonds and alkynes for the synthesis of coumarins: substrate scope and application to the development of neuroimaging agents.
Catalytic coupling of arene C-H bonds and alkynes for the synthesis of coumarins: substrate scope and application to the development of neuroimaging agents.
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DOI：
10.1021/jo3006842
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发表时间：
2012-09-21
期刊：
影响因子：
--
通讯作者：
Sames D
中科院分区：
文献类型：
--
作者：
Vadola PA;Sames D
C-H键官能化为复杂有机化合物提供了具有战略意义的新方法，然而许多C-H官能化反应与Lewis碱性官能团的相容性很差，特别是胺，它们通常是生物活性所必需的。本研究以复杂氨基香豆素的合成为背景，系统地考察了催化氢芳化反应的底物范围。底物的选择是由下一代荧光假神经递质(FFN)的设计和开发指导的；FFN是我们最近推出的用于大脑神经传递的光学成像的神经成像探针。用PtCl4或Au(PPh3)Cl/AgSbF6催化的两种温和方法的比较表明，每种方法都有广泛的互补底物范围。活性相对较低的铂体系的催化性能优于在C-3位缺乏取代吲哚底物的金催化剂，并且在咔唑基底物中提供了更高的区域选择性。另一方面，活性较高的金催化剂表现出良好的官能团耐受性，并能够催化形成高度应变的螺旋产物。这两个方案的开发提供了更大的底物范围，并提供了FFN神经成像探针结构活性检测以及合成复杂香豆素所需的多种合成工具。
C-H bond functionalization offers strategically novel approaches to complex organic compounds, however many C-H functionalization reactions suffer from poor compatibility with Lewis basic functional groups; especially amines, which are often essential for biological activity. This study describes a systematic examination of the substrate scope of catalytic hydroarylation in the context of complex amino coumarin synthesis. The choice of substrates was guided by the design and development of the next generation of Fluorescent False Neurotransmitters (FFNs); neuroimiaging probes we recently introduced for optical imaging of neurotransmission in the brain. Comparison of two mild protocols, using catalytic PtCl4 or Au(PPh3)Cl/AgSbF6, revealed that each method has a broad and mutually complementary substrate scope. The relatively less active platinum system out-performed the gold catalyst with indole substrates lacking substitution at the C-3 position and provided higher regioselectivity in the case of carbazole-based substrates. On the other hand, the more active gold catalyst demonstrated excellent functional group tolerance, and the ability to catalyze the formation of highly strained, helical products. The development of these two protocols offers enhanced substrate scope and provides versatile synthetic tools required for the structure-activity examination of FFN neuroimaging probes as well as for the synthesis of complex coumarins in general.
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影响因子：
5.2
作者：
Pastine, SJ;Youn, SW;Sames, D
通讯作者：
Sames, D
影响因子：
7.3
作者：
HUANG, ZY;MCGOWAN, EB;DETWILER, TC
通讯作者：
DETWILER, TC
影响因子：
2.4
作者：
SCHIMITSCHEK, EJ;TRIAS, JA;ATKINS, RL
通讯作者：
ATKINS, RL
影响因子：
5.2
作者：
Pastine, SJ;Sames, D
通讯作者：
Sames, D
影响因子：
3.6
作者：
Tuan Thanh Dang;Boeck, Florian;Hintermann, Lukas
通讯作者：
Hintermann, Lukas