Flash Generation of a Highly Reactive Pd Catalyst
COMMUNICATION
Figure 5. Generation of [tBu3PPd0]2 (1) from [Pd
formation of palladacycle 2.
ACHTUNGTREN(UNGN OAc)2] and tBu3P and
1640 cmÀ1, which are very similar to those reported for [Pd-
(OAc)2Ph3P]2 (u˜ =1314, 1411, 1580, and 1629 cmÀ1) with
both bridged and monodentate carboxylate groups.[17] There-
fore, the formation of [Pd(OAc)2tBu3P]2 is strongly suggest-
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
ed (Figure 5). Further increase in tR caused a decrease in the
intensities of these bands and an increase in the intensity of
other bands at u˜ =1550–1600 cmÀ1, which seemed to indicate
the formation of palladacycle 2 (Figure 5). In fact, the spec-
trum of the complex obtained at longer tR at 508C looks
very similar to that of 2. The intensity of bands at u˜ =1720–
1750 and 1420 cmÀ1 also increased, indicating simultaneous
formation of AcOH.
Figure 6. Comparison of the yields of the coupling products by using 1
generated by the flash method and those by using [PdACTHUNTRGNE(UNG tBu3P)2] (conven-
tional method). The aryl or heteroaryl groups derived from the corre-
sponding boronic acids are indicated in bold line. The reactions were car-
ried out at 248C for 5 min.
we envisioned that the flash method would solve the prob-
lem. As shown in Figure 7, the coupling of 2-thienyl-, 2-
furyl-, 2-benzothienyl-, 2-benzofuryl-, and 2,6-difluorophe-
nylboronic acids with bromobenzene, p-methoxybromoben-
zene, and unprotected 5-bromoindole proceeded to give the
corresponding coupling products in good yields.
The present flash method enables the use of commercially
available, less expensive, and air-stable [Pd
ate a highly reactive catalyst precursor. As stated above, the
coordination of tBu3P to [Pd(OAc)2] takes place in the mi-
crotube reactor to give [Pd(OAc)2tBu3P]2 (1). Compound 1
ACHTUNGRTEN(NUNG OAc)2] to gener-
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
is quickly transferred to the reaction vessel before the for-
mation of palladacycle 2 and then is reduced in the reaction
vessel to give catalytically active monoligated palladium(0)
species, [PdACHTUNGTRENNUNG(tBu3P)]. However, prolonged residence time in
the microtube led to the formation of palladacycle 2,[15]
which is less catalytically active as shown in Figure 3e.
By using the optimized conditions for the flash generation
of 1, the Suzuki–Miyaura coupling reactions of several aryl
halides with arylboronic acids were examined. As shown in
Figure 6, the reactions were extremely fast even at room
temperature, and the corresponding coupling products were
obtained within 5 min in high yield. Notably, 1 was much
Figure 7. Coupling of aryl halides and arylboronic acids, which easily de-
compose under the standard conditions. The aryl or heteroaryl groups de-
rived from the corresponding boronic acids are indicated in bold line.
The reactions were complete within 5 min at 248C.
more reactive than [PdACHTNUGTRNEUGN(tBu3P)2] in all cases examined. The
reaction can be performed at low catalyst loading. For ex-
ample, the coupling of p-bromotoluene and phenylboronic
acid gave the product in 95% yield in 18 h at room tempera-
ture with 0.01 mol% of the catalyst.
In summary, we found that fast 1:1 micromixing of [Pd-
AHCTUNTGRENGUN(N OAc)2] and tBu3P, and its quick transfer to the reaction
Arylboronic acids that quickly undergo deboronation
under basic conditions are challenging coupling partners for
Suzuki–Miyaura reactions. For example, perfluorophenyl-,
2-furyl-, and 2-thienylboronic acids are known to decompose
easily by deboronation under the standard conditions of
Suzuki–Miyaura coupling.[18] Because the use of flash-gener-
ated 1 enables the reactions to proceed under much milder
conditions (lower temperatures and shorter reaction time),
vessel by using the flow system enabled the use of highly re-
active unstable species as a catalyst precursor for Suzuki–
Miyaura coupling. The coupling reactions could be complete
within 5 min even at room temperature. Aryl- or heteroaryl-
boronic acids, which quickly deboronate under basic condi-
tions, could be also used as coupling partners, because the
reactions can be conducted at lower temperatures and in a
short time. The present observations open a new possibility
Chem. Eur. J. 2012, 00, 0 – 0
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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