dibromides involves tetrabromination of 2,2′-bithiophene to
yield 3,3′,5,5′-tetrabromo-2,2′-bithiophene,11 which is either
reduced by reaction with Zn in acetic acid12 to obtain 3,3′-
dibromo-2,2′-bithiophene or double lithiated followed by
trapping with trialkylsilyl chlorides to obtain 5,5′-bistrialkyl-
silyl-3,3′-dibromo-2,2′-bithiophenes.6,7,13,14 Decades ago Gro-
nowitz15 demonstrated that lithiated thiophene derivatives
undergo oxidative coupling in the reaction with CuCl2; e.g.,
2-lithio-3-bromothiophene, generated by the lithium-halogen
exchange from 2,3-dibromothiophene, produced 3,3′-di-
bromo-2,2′-bithiophene in 50-60% yield. It had also been
shown that this so-called base-catalyzed halogen dance
(BCHD)16 reaction can cleanly produce R-lithium-ꢀ-bro-
moarenes from R-bromoarenes; for example, 2-lithio-3,5-
dibromothiophene was generated from 2,5-dibromothiophene
by the reaction with LDA at -78 °C.17 A variety of
heteroaromatic aryl halides were successfully used in the
BCHD reaction, and the lithiated species were typically
trapped with alcohol to get rearranged aryl halides or with
various electrophiles to obtain functionalized materials.18
Here we report a convenient preparation of heteroaryl
dihalides 3 from 2-bromo-5-trialkylsilyl-heteroarenes 1 by
the sequence of the BCHD reaction and CuCl2-promoted
oxidative coupling of the in situ generated R-lithio-ꢀ-
bromoarenes 2 (Scheme 1).
Scheme 1. Sequence of the BCHD Reaction and CuCl2
Oxidative Coupling As a Convenient Approach to Aryl
Dihalides 3a-d
to form 2-lithio-3-bromo-5-TMS-thiophene 2a and -sele-
nophene 2b, respectively (GC/MS and/or 1H NMR analyses
of the aryl bromides 4a,b confirmed the clean BCHD
reaction). CuCl2-promoted oxidative coupling of 2a and 2b
produces corresponding dibromides 3a (60-84% purified
yield) and 3b (50-66% purified yield). This one-pot
preparation of 3a from commercially available 2-bro-
mothiophene is a convenient alternative to the three-step
synthesis reported in the literature,19,11,13 while preparation
of 3b in one pot from 2-bromoselenophene provides an easy
access to selenium-containing analogues of DTT, DTP, etc.
A different thiophene derivative, 2,5-dibromo-3-n-hexy-
lthiophene (1c), also underwent a clean BCHD reaction
In the case of 5,5′-bistrimethylsilyl-3,3′-dibromo-2,2′-
bithiophene (3a) and -selenophene (3b), the reaction se-
quence starts from the corresponding bromide, 2-bro-
mothiophene or 2-bromoselenophene. The first lithiation with
1 equiv of LDA and trapping with TMSCl cleanly produced
substrates 1a and 1b, which are suitable for the BCHD
reaction with halogen at the first R-position and with the
second R-position of the heterocycle protected from lithiation
by the TMS group. Addition of the second equivalent of
LDA to 1a and 1b results in a clean and fast rearrangement
(3) Liu, J. Y.; Zhang, R.; Sauve, G.; Kowalewski, T.; McCullough, R. D.
J. Am. Chem. Soc. 2008, 130, 13167–13176.
1
(confirmed by H NMR analysis) followed by oxidative
coupling, and tetrabromide 3c was obtained in 80-87%
yield.
(4) Steckler, T. T.; Zhang, X.; Hwang, J.; Honeyager, R.; Ohira, S.;
Zhang, X. H.; Grant, A.; Ellinger, S.; Odom, S. A.; Sweat, D.; Tanner,
D. B.; Rinzler, A. G.; Barlow, S.; Bredas, J. L.; Kippelen, B.; Marder, S. R.;
Reynolds, J. R. J. Am. Chem. Soc. 2009, 131, 2824–2826.
(5) Lee, K. H.; Ohshita, J.; Kunai, A. Organometallics 2004, 23, 5481–
5487.
2-Triisopropylsilyl-5-bromothiazole (1d), which was suc-
cessfully used in the BCHD reaction,20 produced dibromide
3d in 60-82% purified yield. Another thiazole bromide,
2-bromo-5-trimethylsilylthiazole (5), generated in situ from
2-bromothiazole using Corey’s conditions (addition of LDA
in the presence of TMSCl)21 produced 4,4′-dibromo-5,5′-
bis(trimethylsilyl)-2,2′-bithiazole (6) in 35-50% purified
yield, when treated with LDA to induce the BCHD reaction
followed by CuCl2 oxidative coupling (Scheme 2). This one-
pot preparation of 6 is a valuable alternative to the literature
preparation22 of 4,4′-dibromo-2,2′-bithiazole, which was
synthesized from expensive 2,4-dibromothiazole by the
monolithiation-oxidative coupling sequence.
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