Abstract
The regioselective ortho arylation of polyhalo-substituted (hetero)aryl tosylates has been investigated employing an integrated continuous flow/batch protocol. The regioselective ortho metalation of (hetero)aryl tosylates using n-BuLi and ZnCl2 was effectively achieved using continuous flow chemistry in a short residence time of 10.92 s, without removal of the tosyloxy group. The Pd-catalyzed Negishi coupling reactions of various (hetero)aryl iodides with the resulting arylzinc species proceeded readily at room temperature in 31% to 98% yields. Finally, the method was applied to the synthesis of perampanel in four linear steps, with an overall yield of 43%. (Figure presented.).
Original language | English |
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Pages (from-to) | 263-268 |
Number of pages | 6 |
Journal | Advanced Synthesis and Catalysis |
Volume | 365 |
Issue number | 2 |
DOIs | |
State | Published - 24 Jan 2023 |
Keywords
- (Hetero)aryl tosylates
- Continuous flow chemistry
- Ortho metalation
- Perampanel
- Regioselective Negishi coupling