| Full text | |
| Author(s): |
Sanjose-Orduna, Jesus
;
Silva, Rodrigo C.
;
Raymenants, Fabian
;
Reus, Bente
;
Thaens, Jannik
;
de Oliveira, Kleber T.
;
Noel, Timothy
Total Authors: 7
|
| Document type: | Journal article |
| Source: | CHEMICAL SCIENCE; v. 13, n. 42, p. 6-pg., 2022-10-10. |
| Abstract | |
The efficient C-4 selective modification of pyridines is a major challenge for the synthetic community. Current strategies are plagued with at least one drawback regarding functional group-tolerant electronic activation of the heteroarene, mild generation of the required alkyl radicals, regioselectivity, safety and/or scalability. Herein, we describe a fast, safe and scalable flow process which allows preparation of said C-4 alkylated pyridines. The process involves a photochemical hydrogen atom transfer (HAT) event to generate the carbon-centered radicals needed to alkylate the C-2 blocked pyridine. In a two-step streamlined flow process, this light-mediated alkylation step is combined with a nearly instantaneous inline removal of the blocking group. Notably, cheap benzophenone plays a dual role in the pyridine alkylation mechanism by activating the hydrocarbon feedstock reagents via a HAT mechanism, and by acting as a benign, terminal oxidant. The key role of benzophenone in the operative reaction mechanism has also been revealed through a combination of experimental and computational studies. (AU) | |
| FAPESP's process: | 21/09145-8 - Synthesis of Iminophosphoranes from nitroarenes by an electrochemical approach |
| Grantee: | Rodrigo Costa e Silva |
| Support Opportunities: | Scholarships abroad - Research Internship - Doctorate |