3- Bromofuran, halogen-metal exchange

Simply treating furan in DMF with Br2 at 20-30°C results in 70% of 2-bromofuran and 8% of 2,5-dibromofuran. Further treatment of 2-bromofuran with another equivalent of Br, at 30-40 C produces 2,5-dibromofuran in 48% yield [6, 7], Alternatively, deprotonation of furan at the C(2) position using EtLi followed by quenching with Br2 provides 2-bromofuran [8]. Similarly, quenching 3-lithiofuran, derived from halogen-metal exchange between 3-bromofuran and EtLi, with hexachloroethane yields 3-chlorofuran [9]. 

The classical transformations of 18 with electrophilic reagents (e.g., carboxylation with CO2, alkylation with R-X, acylation with R-COX, halogenation with X2) allow the introduction of other functionalities at the furan system. The preference of a-metalation at furan is demonstrated by the fact, that 3-lithiofuran (19) - obtained by halogen-metal exchange of 3-bromofuran with RLi at — 78°C - equilibrates to the more stable 2-lithio furan (18) on raising the temperature to —40°C. 

Bromofuran undergoes metal-halogen exchange at -78 C in THF (tetrahydrofuran) to yield 3-lithiofuran, but when this product is warmed to about -40 °C it rearranges to 2-lithiofuran (Scheme 6.26b). 

Metallation with alkyllithiums proceeds selectively at an a-position, indeed metallation of furan is one of the earliest examples of the now familiar practice of aromatic ring-metallation. The preference for a-deprotonation is nicely illustrated by the demonstration that 3-lithiofuran, produced from 3-bromofuran by metal/ halogen exchange at —78°C, equilibrates to the more stable 2-lithiofuran if the temperature rises to > —40°C more forcing conditions can bring about 2,5-dilithiation of furan. ... 

---