1134
H. Bonin et al. / Tetrahedron Letters 52 (2011) 1132–1135
dioxazaborocanes in reactions with electron deficient bromoarenes
(entries 1–4).
Coupling with more electron rich aryl bromides proved less effi-
cient as shown by the results obtained in the coupling reaction of
4-(1,3,6,2-dioxazaboracan-2-yl)-benzonitrile with trans ethyl-
2-(3-bromophenyl)cyclopropanecarboxylate and trans ethyl-2-
In conclusion, we have demonstrated that aryl dioxazaboro-
canes represents good boronic acid surrogates for the Suzuki–
Miyaura cross-coupling reaction. From a practical point of view,
these compounds are easy to synthesize and isolate in a very pure
fashion. As previously highlighted, they are highly stable, exhibit-
ing a bench life time of many years without noticeable degrada-
tion. Because of their high stability, they do not require the use
of a large excess of the boron partner which represents a significant
advantage. Moreover the best reaction conditions require a catalyst
source that is easily accessible. We do consider that all these
practical features are of primary interest and will make these
compounds attractive to both the academic and industrial
communities.
(4-bromophenyl)cyclopropanecarboxylate (entries
5
and 6).
Expectedly, no epimerization of the 1,2-disubstituted cyclopro-
panes occurred under these reaction conditions. It is noticeable
that these examples represent a straightforward access to biologi-
cally-active cyclopropanated biaryls recently described in the
patent literature (Fig. 1).32–34
Introducing a methoxy group at the para position of the bromo-
benzene moiety proved to be deleterious, mainly yielding degrada-
tion of starting material (entry 7).
Acknowledgments
Finally, the cross-coupling of aryl dioxazaborocanes with het-
eroaryl bromides could also be achieved in moderate to very good
yields (Table 3).
Minakem (Ph.D. grant for H.B., research grant for B.M.), the
France Alzheimer Association (Ph.D. grant for R.L.Y.), the Region
Midi Pyrénées (APRTCN 09004783), the CNRS, and the University
Paul Sabatier are acknowledged for their supports.
This approach provides a fairly straightforward route to 2-
(4-aminophenyl)benzothiazole derivatives, which have been
described as antitumor agents.35–37 Moreover, there is a strong
interest for this type of substrate for early detection of Alzheimer’s
disease b-amyloid peptide deposits by mean of Positron Emission
Tomography (PET).38–40 The coupling of differently substituted
benzothiazoles with various N-protected anilines bearing a diox-
azaborocane moiety in the para position have been carried out.
Doubly benzylated anilines 1e always achieved lower yields in
cross-couplings (entries 1 and 2) compared to 1f (entries 3 and
4). This might be seen as the consequence of a higher enrichment
of the aromatic ring (bulk induced by two benzyl groups force the
nitrogen in a sp2 hybridization), which can lower the transmetalla-
tion step by increasing the carbon–boron bond strength. On the
other side, deactivation of the nitrogen lone pair by a Boc group
as in 1g does not appear to influence the reaction efficiency (en-
tries 6–8).
References and notes
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Zhou, Q. Macromolecules 2009, 42, 1037–1046.
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N
Figure 1. Patented cyclopropane-substituted biaryl.
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27. Typical experimental procedure for the synthesis of aryl dioxazaborocane: To
1 equiv of bromoaryl in THF (1 mmol/mL) under Argon at ꢀ78 °C is added
dropwisely 1 equiv of n-BuLi. After 10 min at ꢀ78 °C neat B(O-iPr)3 is
dropwisely added. The resulting mixture is stirred for 1 h while allowed to
Table 3
Scope of cross-coupling reactions using aryl dioxazaborocanes and heteroaryl
bromides under the optimized conditions
Entry Dioxazaborocane Heteroaryl bromide
Isolated yield
(%)
N
B
B
r
r
2f
1
2
1e
1e
52
S
F
N
2g
51
S
3
4
1f
1f
2f
2g
63
81
warm to room temperature. Diethyl ether and
a saturated solution of
ammonium chloride are then added, and the resulting mixture is stirred for
30 min. The organic and aqueous phases are separated, the aqueous phase is
then extracted with ether, and the organic phases are washed with brine. The
organic phase is dried over MgSO4 and filtered. The diethanolamine solution (i-
PrOH, 3 M, 1 equiv) is added under stirring. A solid precipitates instantly. The
mixture is filtered, and the solid is washed with ether and dried under vacuum.
Spectroscopic data for selected dioxazaborocanes:
N
S
5b
1f
50
Br
2h
NO
2
6
7
1g
1g
2f
2g
82
75
N
S
4,5,7,8-Tetrahydro-2-(40-methoxyphenyl)-6H-[1,3,6,2]dioxazaborocane: 1H NMR
(DMSO-d6, 300 MHz), d = 7.34 (d, J = 8.5 Hz, 2H), 6.76 (d, J = 8.5 Hz, 2H), 3.89–
3.81 (td, J = 9.2 Hz, J = 5.4 Hz, 2H), 3.79–3.73 (m, 2H), 3.70 (s, 3H), 3.12–3.00
(tdd, J = 11.7 Hz, J = 9.0 Hz, J = 6.9 Hz, 2H), 2.85–2.77 (m, 2H). 13C NMR (DMSO-
2i
Br
8
1g
71
OMe