The influence of boronate groups on the selectivity of the Br-Li exchange in model dibromoaryl boronates

Abstract

The selectivity of the Br/Li exchange reaction of 6-butyl-2-(2,5- dibromophenyl)-1,3,6,2-dioxazaborocane (2,5-Br2C6H 3B(OCH2CH2)2NBu) and the analogous anionic derivatives, 2,5-Br2C6H3B(OiPr) 3Li and 2,5-Br2C6H3BF3K, was investigated using nBuLi as the lithiating reagent. In the case of the former compound there was a slight preference for lithiation at the 5-position. For 2,5-Br2C6H3B(OiPr)3Li, the lithiation occured exclusively at C5, but for 2,5-Br2C 6H3BF3K, 2-lithiation was preferred. Calculations performed for the lithiation of ortho- and meta-brominated phenyl boronates revealed that ortho-lithiated aryl boronates are thermodynamically more stable, but that the Br/Li exchange is generally dictated by kinetics, which accounts for the variation of selectivity depending on the type of boronate group. In addition, the successful generation of the 2,5-dilithiophenyl boronate species 2,5-Li2C6H3B(OCH 2CH2)2NBu by a double Br/Li interconversion is reported. The Br/Li exchange in the related 6-butyl-2-[3-(2,5-dibromothienyl)]- 1,3,6,2-dioxazaborocane, 2,5-Br2-3-ThB(OCH2CH 2)2NBu, occured preferentially at the 5-position, but the product was readily transformed into the more stable 2-lithiated isomer. The use of 2 equiv. of nBuLi resulted in the efficient formation of the dilithiated species, 2,5-Li2-3-ThB(OCH2CH2)2NBu. The obtained lithiated aryl boronates were converted into functionalized arylboronic acids by treatment with selected electrophiles. The selectivity of the Br/Li exchange in model dibromoaryl boronates was studied in the context of the directing effect of boron-based groups. Theoretical calculations revealed that ortho-lithiated aryl boronates are thermodynamically more stable, but the Br/Li exchange is generally dictated by kinetics. The lithiated aryl and thienyl boronates were converted into functionalized boronic acids. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.