Benzo[b]furans (pictured right) are organic building blocks found in a wide range of natural products and pharmaceutical agents. The most common synthesis routes for these ring systems involve palladium catalysis. However, due to its scarcity and high price, replacing palladium with cheaper, more abundant metals would be useful.
Andrew Sutherland and Martyn C. Henry, University of Glasgow, UK, have developed a benzo[b]furane synthesis that starts from 1-arylketones or 1-alkylketones and is catalyzed by the earth-abundant transition metals iron and copper. The starting material is first converted to a reactive iodide by N-iodosuccinimide in the presence of iron(III)triflimide as a catalyst. The iodide is then transformed to the corresponding benzo[b]furan via an O-arylation catalyzed by copper[I] iodide.
The team also investigated whether both reaction steps could be catalyzed by an iron salt. This proved challenging due to the presence of copper impurities in the iron precursors, which were sufficient to catalyze the cyclization. When ultrapure iron salts were used, it could be shown that, in principle, iron alone can catalyze both reaction steps. However, the reaction is more effective when copper is also used. For example, for less reactive amino-substituted substrates, the use of 10 mol% of CuI was required for efficient conversion.
The synthesis can be used with various electron-rich and electron-poor starting materials. The best results were achieved when electron-rich starting materials were used. Several natural products containing benzo[b]furan units were synthesized using this approach, including corsifuran C, caleprunin B, and the antifungal agent moracin F.
- Synthesis of Benzo[b]furans by Intramolecular C–O Bond Formation Using Iron and Copper Catalysis,
Martyn C. Henry, Andrew Sutherland,
Org. Lett. 2020.