Synthesis of Tetra-ortho-Methoxylated Azobenzene Photoswitches via Sequential Catalytic C–H Activation and Methoxylation

• Published in: Journal of organic chemistry 2024-12, Vol.89 (23), p.17141-17146
• Main Authors: Ruiz-Soriano, Albert, Lamelza, Lara, Pizzamiglio, Elena, Just-Baringo, Xavier
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904; 1520-6904
• DOI: 10.1021/acs.joc.4c01554

Functionalized tetra-ortho-methoxyazobenzenes have been prepared in a two-step approach based on palladium-catalyzed C–H ortho bromination of azobenzenes, followed by copper-catalyzed methoxylation. The method has shown a broad tolerance to different functional groups that could not be incorporated by previous strategies. With this two-step transition metal-catalyzed strategy, we achieved overall yields that range from good to excellent and enable the exploitation of these highly coveted photoswitches. The superior robustness of this scaffold for solid phase peptide synthesis (SPPS) applications when compared to its chlorinated counterpart has been demonstrated after extensive treatments with piperidine while bound to a RinkAmide ChemMatrix resin, showcasing their potential for use in the synthesis of red-light-operated peptides.