Bromine migration in lithiated 4-bromo-2,2-difluoro-1,3-benzodioxoles was achieved by protecting the 7-position of the bicycle by trialkylsilyl group, thus giving access to 5-bromo-2,2-difluoro-1,3-benzodioxole 4-iodo- and 4-carboxy-derivs. after protodesilylation. 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 achieved if no oxygen-adjacent site remains unoccupied. Thus, unlike 4-bromo-2,2-difluoro-1,3-benzodioxole (1), 4-bromo-2,2-difluoro-7-SiR3-1,3-benzodioxoles (5a,b; R = Me, Et) were lithiated by LDA to generate the 5-lithio-intermediate that isomerizes instantaneously by bromine migration to give 5-bromo-2,2-difluoro-4-lithio-7-SiR3-1,3-benzodioxoles, which were iodinated or carboxylated in 4-position. 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 quant. A similar basicity gradient-driven heavy-halogen migration can be accomplished starting from 2,2-difluoro-4,7-diiodo-1,3-benzodioxole (11). [on SciFinder (R)]
Title
Deprotonation-triggered heavy-halogen migrations as a key to the structural elaboration of 2,2-difluoro-1,3-benzodioxole
Published in
European Journal of Organic Chemistry
Issue
1
Pages
64-68
Date
2004
Note
CAN 140:217700 29-6 Organometallic and Organometalloidal Compounds Institute de Chimie moleculaire et biologique,Ecole Polytechnique Federale, BCh,Lausanne,Switz. Journal 1434-193X written in English. 663934-13-2P (2,2-Difluoro-4,7-diiodo-1,3-benzodioxole) Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (carboxylation, rearrangement; prepn. of 1,3-benzodioxole iodo-, silyl- and carboxy-derivs. by lithiation with subsequent heavy-halogen migration); 663934-15-4P (2,2-Difluoro-4,6-diiodo-1,3-benzodioxole) Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (dehalogenation, carboxylation; prepn. of 1,3-benzodioxole iodo-, silyl- and carboxy-derivs. by lithiation with subsequent heavy-halogen migration); 663934-07-4P (5-Bromo-2,2-difluoro-7-(triethylsilyl)-1,3-benzodioxole-4-carboxylic acid); 663934-09-6P (6-Bromo-2,2-difluoro-4-(triethylsilyl)-1,3-benzodioxole) Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (deprotection, desilylation; prepn. of 1,3-benzodioxole iodo-, silyl- and carboxy-derivs. by lithiation with subsequent heavy-halogen migration); 663934-11-0P (2,2-Difluoro-4,7-bis(trimethylsilyl)-1,3-benzodioxole) Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (iododesilylation; prepn. of 1,3-benzodioxole iodo-, silyl- and carboxy-derivs. by lithiation with subsequent heavy-halogen migration); 663934-04-1P (4-Bromo-2,2-difluoro-7-(triethylsilyl)-1,3-benzodioxole) Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (lithiation, carboxylation, iodination, rearrangement; prepn. of 1,3-benzodioxole iodo-, silyl- and carboxy-derivs. by lithiation with subsequent heavy-halogen migration); 663934-02-9P (4-Bromo-2,2-difluoro-7-(trimethylsilyl)-1,3-benzodioxole) Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (lithiation, carboxylation, rearrangement; prepn. of 1,3-benzodioxole iodo-, silyl- and carboxy-derivs. by lithiation with subsequent heavy-halogen migration); 144584-66-7 Role: RCT (Reactant), RACT (Reactant or reagent) (lithiation, carboxylation; prepn. of 1,3-benzodioxole iodo-, silyl- and carboxy-derivs. by lithiation with subsequent heavy-halogen migration); 75-77-4 (Chlorotrimethylsilane); 994-30-9 (Chlorotriethylsilane) Role: RCT (Reactant), RACT (Reactant or reagent) (prepn. of 1,3-benzodioxole iodo-, silyl- and carboxy-derivs. by lithiation with subsequent heavy-halogen migration); 33070-32-5P (5-Bromo-2,2-difluoro-1,3-benzodioxole); 126120-90-9P (2,2-Difluoro-4-(trimethylsilyl)-1,3-benzodioxole); 334778-43-7P (5-Bromo-2,2-difluoro-1,3-benzodioxole-4-carboxylic acid); 663933-99-1P (7-Bromo-2,2-difluoro-1,3-benzodioxole-4-carboxylic acid); 663934-00-7P (2,2-Difluoro-4-(triethylsilyl)-1,3-benzodioxole); 663934-06-3P (5-Bromo-2,2-difluoro-7-trimethylsilyl-1,3-benzodioxole-4-carboxylic acid); 663934-08-5P (6-Bromo-2,2-difluoro-4-(trimethylsilyl)-1,3-benzodioxole); 663934-10-9P (5-Bromo-2,2-difluoro-4-iodo-7-(triethylsilyl)-1,3-benzodioxole); 663934-12-1P (2,2-Difluoro-4,7-bis(triethylsilyl)-1,3-benzodioxole); 663934-14-3P (2,2-Difluoro-7-iodo-1,3-benzodioxole-4-carboxylic acid); 663934-16-5P (2,2-Difluoro-5,7-diiodo-1,3-benzodioxole-4-carboxylic acid); 663934-17-6P (2,2-Difluoro-5-iodo-1,3-benzodioxole); 663934-18-7P (2,2-Difluoro-6-iodo-1,3-benzodioxole-4-carboxylic acid) Role: SPN (Synthetic preparation), PREP (Preparation) (prepn. of 1,3-benzodioxole iodo-, silyl- and carboxy-derivs. by lithiation with subsequent heavy-halogen migration); 1583-59-1 (2,2-Difluoro-1,3-benzodioxole) Role: RCT (Reactant), RACT (Reactant or reagent) (silylation; prepn. of 1,3-benzodioxole iodo-, silyl- and carboxy-derivs. by lithiation with subsequent heavy-halogen migration)
Record creation date
2006-03-03
