Regio-controllable [2+2] benzannulation with two adjacent C(sp3)-H bonds

被引:26
作者
Yang, Ji-Min [1 ]
Lin, Yu-Kun [1 ]
Sheng, Tao [1 ]
Hu, Liang [1 ]
Cai, Xin-Pei [1 ]
Yu, Jin-Quan [1 ]
机构
[1] Scripps Res Inst, Dept Chem, 10550 North Torrey Pines Rd, La Jolla, CA 92037 USA
关键词
C-H ACTIVATION; DERIVATIVES;
D O I
10.1126/science.adg5282
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Regiocontrol in traditional cycloaddition reactions between unsaturated carbon compounds is often challenging. The increasing focus in modern medicinal chemistry on benzocyclobutene (BCB) scaffolds indicates the need for alternative, more selective routes to diverse rigid carbocycles rich in C(sp(3)) character. Here, we report a palladium-catalyzed double C-H activation of two adjacent methylene units in carboxylic acids, enabled by bidentate amide-pyridone ligands, to achieve a regio-controllable synthesis of BCBs through a formal [2+2] cycloaddition involving s bonds only (two C-H bonds and two aryl-halogen bonds). A wide range of cyclic and acyclic aliphatic acids, as well as dihaloheteroarenes, are compatible, generating diversely functionalized BCBs and hetero-BCBs present in drug molecules and bioactive natural products.
引用
收藏
页码:639 / 644
页数:6
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