Synthesis of 2-Deoxy-2-halo-L-ascorbic Acids.

2-Iodo- and 2-bromo-2-deoxy-L-ascorbic acids (2 and 3) were prepared by facile halogenation of 2-deoxy-L-ascorbic acid (6) with NIS and NBS, respectively. Likewise, chlorination with NCS produced 2-chloro-2-deoxy-L-ascorbic acid (4), but formation of 4 was accompanied by formation of the dichloro hemiketal 9. Direct fluorination of 6 with 1-chloro-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (F-TEDA-BF(4)) gave only the difluoro hemiketal 10. A convenient synthesis of 2-deoxy-2-fluoro-L-ascorbic acid (5) was achieved by an indirect route. Fluorination of 2-bromo-2-deoxy-L-ascorbic acid (3) with F-TEDA-BF(4) produced the bromofluoro hemiketal 16 as a mixture of diastereoisomers. Debromination with tributyltin hydride gave 5 in good yield.