Mechanistic Studies

We also tried to synthesize "mixed" trihalo-thiophenes via halogen migration technology:

This target should be approached by quenching the corresponding migration intermediates with appropriate electrophiles:

However, upon work-up in all cases a complex mixture of various di- and tri-halogenated compounds was obtained (see alternative chemical syntheses of the targets).

We suspected that these problems arise from non-selective a-transhalogenation reactions between already formed tri-halo-target and metalated rearranged intermediate.

In order to prove these suggestions and to elucidate the by-products the rearranged lithium intermediate obtained after a HD on 2-bromo-3-chlorothiophene was reacted with the trihalo-thiophene prepared by an independent method. From this reaction a complex mixture of halo-thiophenes was obtained, all of them could be unambigously assigned by NMR spectroscopy (mainly by means of independent syntheses).
One of our mechanistic investigations is presented below: