Deprotonation-triggered heavy-halogen migrations as a key to the structural elaboration of 2,2-difluoro-1,3-benzodioxole

Although proton abstraction from the 4-position of 2,2-difluoro-1,3-benzodioxole occurs with exceptional ease, lithiation of the more-remote 5-position can only be brought about if no oxygen-adjacent site remains unoccupied. Thus, unlike 4-bromo-2,2-difluoro-1,3-benzodioxole (1), (7-bromo-2,2-difluoro-1,3-benzodioxol-4-yl)triethylsilane (5b) does react with lithium diisopropylamide to generate an intermediate that isomerizes instantaneously by heavy-halogen migration. Upon neutralization and carboxylation, 5-bromo-2,2-difluoro-1,3-benzodioxole (8) and 5-bromo-2,2-difluoro-1,3-benzodioxole-4-carboxylic acid (3) are formed nearly quantitatively. A similar basicity gradient-driven heavy-halogen migration can be accomplished starting from 2,2-difluoro-4,7-diiodo-1,3-benzodioxole (11). These results procure a deeper insight in the acidifying effects of fluoroalkoxy groups and their distance dependence. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004).