Richard D. Chambers, Christopher W. Hall, John Hutchinson and Ross W. Millar
Reductive replacement of fluorine in 3,5-dichloro-2,4,6-trifluoropyridine 2a and pentafluoropyridine 2 using DIBAL and LAH leads to useful syntheses of fluoro and chlorofluoro pyridine derivatives. Replacement of fluorine by bromine using a mixture of HBr and AlBr3 is extremely efficient, giving excellent routes to 2,4,6-tribromo-3,5-difluoropyridine 3. Bromofluoro-pyrimidine and -quinoxaline derivatives have also been efficiently synthesised from perfluorinated precursors. Catalytic hydrogenation of bromofluoro heterocycles gives high yields of the corresponding fluorinated heterocycles.
Reactions of nucleophiles with 3 gives surprising results. Soft nucleophiles, e.g. PhSNa displace bromine whereas hard nucleophiles, e.g. MeONa, displace fluorine.