Communications
type Ar2-X (3; X = Cl, Br, I, ONf,[14] OTs,[15] OTf[16]) as the
electrophile.
Thus, under typical reaction conditions, the sensitive Boc-
zonitrile (3a) gives the alkenes 7a,b in 71 and 95% yield,
respectively. The magnesium dialkenylboronate 6c was
prepared from 1-bromostyrene (5c), B(OBu)3 (0.5 equiv),
Mg (1.6 equiv), and LiCl (1.1 equiv). The palladium-catalyzed
cross-coupling with ethyl 4-bromobenzoate (3i) under stan-
dard conditions gives the diarylethylene 7c in 95% yield
(Scheme 3).
Both electron-rich and electron-poor heterocycles such as
8a and 8b, respectively, readily react with Mg (1.6 equiv) and
LiCl (1.1 equiv) in the presence of B(OBu)3 (0.5 equiv) in
THF (0 or 258C, 0.5–1 h) to produce the diheterocyclic
magnesium boronates 9a,b (> 85% yield). A subsequent
Suzuki–Miyaura cross-coupling reaction with the aryl bro-
protected bromophenol 1b reacted with B(OBu)3 (0.5 equiv),
Mg (1.6 equiv), and LiCl (1.1 equiv) in THF within 1 h at
258C to provide the magnesium diarylboronate 2b (> 85%
yield). Its Pd-catalyzed cross-coupling with the bromobenza-
mide 3b proceeds within 3 h at 658C in the presence of 4%
[Pd(dppf)Cl2] and Cs2CO3 (2 equiv) in a 4:4:1 THF/EtOH/
DMF mixture and leads to the functionalized biphenyl 4b in
91% yield. This result clearly demonstrates that both aryl
groups of 2b are available for the cross-coupling. This
behavior was general and a wide range of diarylboronates
of type 2 bearing various functional groups (ester, cyanide,
Boc, (thio)methoxy, amino, or silyl groups) were prepared
conveniently at 258C within 15 min to 1 h (Table 1). The
cross-coupling reaction of the magnesium diarylboronates
2c–p produces the desired products 4c–u in 70–92% yield
under standard conditions (Table 1, entries 1–19). Although
aryl bromides have been used mostly as electrophiles
(Table 1, entries 1, 2, 6–9, 12, 14–19), aryl chlorides (Table 1,
entries 5 and 13), a nonaflate[14] (Table 1, entry 3), a tosylate
(Table 1, entry 4), and a triflate (Table 1, entry 10) readily
undergo the cross-coupling without any further optimization.
In some cases, when the aryl bromide is sterically hindered
(such as in the precursor to 2d) or strongly electron-deficient
(such as in the precursor to 2h), the preparation of the
monoarylboronate (ArB(OBu)3MgBr) was preferable[17] and
led to a significant improvement in the yield of the subsequent
Suzuki–Miyaura cross-coupling reaction (Table 1, entries 2
and 7).
The method described above also proved to be suitable
for alkenyl halides. Suzuki–Miyaura cross-coupling reactions
with mono- and dialkenylboronic derivatives such as 6a–c
proceed in high yields (Scheme 3). Thus, the treatment of
cyclohexenyl iodide with B(OBu)3 (1 equiv), Mg (1.6 equiv),
and LiCl (1.1 equiv) in THF at 258C produces the corre-
sponding magnesium alkenylboronate 6a within 1 h (> 85%
yield). Similarly, the reaction of 2-iodostyrene furnishes the
desired alkenylboronate 6b under the same conditions
(> 85% yield). The cross-coupling of 6a,b with 4-bromoben-
Scheme 4. Synthesis of diheterocyclic boronates 9a,b and subsequent
Suzuki–Miyaura cross-coupling reactions.
mides 3s and 3t furnishes the corresponding
heterocyclic products 10a,b in 72 and 84%
yield, respectively (Scheme 4). The related
diheterocyclic magnesium boronates 9c–h
are obtained in a similar manner. Suzuki–
Miyaura cross-coupling reactions of 9c–h
with aryl chlorides and bromides furnish the
expected heterocycles 10c–j (Table 2,
entries 1–8).
In summary, we have reported a general
and low-cost one-step synthesis of new
polyfunctional magnesium diorganoboro-
nates that tolerate a wide range of func-
tional groups. This atom-economical syn-
thesis gives ready access to functionalized
diaryl- and diheteroaryl- as well as to
dialkenylboronates from their correspond-
Scheme 3. Magnesium alkenylboronates 6a–c and their subsequent Suzuki–Miyaura cross-
coupling reactions.
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2011, 50, 7290 –7294
Haag, Benjamin A.
