Photoredox-catalysed amidyl radical insertion to bicyclo[1.1.0]butanes

被引:10
|
作者
Chintawar, Chetan C. [1 ]
Laskar, Ranjini [1 ]
Rana, Debanjan [1 ]
Schaefer, Felix [1 ]
Van Wyngaerden, Nele [1 ]
Dutta, Subhabrata [1 ]
Daniliuc, Constantin G. [1 ]
Glorius, Frank [1 ]
机构
[1] Univ Munster, Organ Chem Inst, Munster, Germany
来源
NATURE CATALYSIS | 2024年 / 7卷 / 11期
基金
欧洲研究理事会;
关键词
PHOTOCATALYSIS; ATOM;
D O I
10.1038/s41929-024-01239-9
中图分类号
O64 [物理化学(理论化学)、化学物理学];
学科分类号
070304 ; 081704 ;
摘要
Replacing planar aromatic rings in drug molecules with C(sp3)-rich isosteric mimetics, such as bicyclo[n.1.1]alkanes, can significantly alter their physicochemical and pharmacokinetic properties, often leading to higher clinical success rates. However, unlike a benzene ring, the structurally rigid C(sp3)-rich isosteric mimetics of heteroaromatic rings are rare. Heterobicyclo[n.1.1]alkanes are promising in this regard, but the lack of modular synthetic methods has currently hindered their exploration. We envisioned that the strategic and selective insertion of different heteroatomic units to bicyclo[1.1.0]butanes could offer a highly modular platform to access diverse heterobicyclo[n.1.1]alkanes. Herein we report a photoredox-catalysed highly regioselective and chemoselective insertion of amidyl radicals to bicyclo[1.1.0]butanes, providing direct access to 2-oxa-4-azabicyclo[3.1.1]hept-3-enes. The exit vector analysis shows a geometric resemblance of these C(sp3)-rich heterobicyclic motifs with pyridine and pyrimidine derivatives, suggesting their potential as isosteric mimetics of such medicinally important heterocycles. Additionally, various downstream transformations demonstrate their utility as versatile building blocks in synthetic chemistry. Heteroatom-substituted C(sp3)-rich polycyclic hydrocarbon rings, isosteric to heterocyclic rings, are not common due to the challenging synthesis. Now a photoredox-catalysed strategy to insert amidyl radicals into bicyclo[1.1.0]butanes is presented, providing direct access to 2-oxa-4-azabicyclo[3.1.1]hept-3-enes.
引用
收藏
页码:1232 / 1242
页数:11
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