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Deprotonation‐Triggered Heavy‐Halogen Migrations as a Key to the Structural Elaboration of 2,2‐Difluoro‐1,3‐benzodioxole
Author(s) -
Gorecka Joanna,
Leroux Frédéric,
Schlosser Manfred
Publication year - 2004
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200300553
Subject(s) - chemistry , halogen , lithium diisopropylamide , deprotonation , stereochemistry , medicinal chemistry , organic chemistry , ion , alkyl
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. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)