LETTER
Precursor of Pd-Catalyzed Suzuki–Miyaura Reactions
1329
Table 2 Suzuki–Miyaura Reactions at Room Temperature (continued)
Entry
19
Aryl halide
Boronic acid
Product
Time
(min)
Yields
(%)a
O
O
75
80
91
(HO)2B
Cl
20
93
N
Cl
(HO)2B
N
a Yields refer to isolated products characterized by spectroscopic data [1H NMR, 13C NMR, MS (EI), IR, CHN analyses].
As illustrated in Table 2, our catalytic system enables the ropyridine as coupling partners which all reacted at room
cross-coupling of electron-rich as well as electron-defi- temperature in 91% to 95% yield (entries 16–18). The
cient aryl bromides (entries 1–11) in very good to excel- preparation of 4-(trifluoromethyl)biphenyl (entry 17) as
lent yields at room temperature. Thus our method to presented here is by far the mildest method, except for the
prepare terphenyl (entry 2) competes with recent Suzuki– usage of in situ generated nanoparticles in PEG-400 under
Miyaura reactions under microwave irradiation in water aerobic conditions.17 To the best of our knowledge, no
(7 h, 83%),5 or a procedure starting from boronic esters in room-temperature Suzuki–Miyaura reactions of the chlo-
aqueous EtOH or i-PrOH (6–18 h, 90–95%).6 Alternative- rides presented in entries 18–20 have been published to
ly, this coupling can be carried out in the presence of an date. Noteworthy is the formation of the sterically hin-
encapsulated Pd catalyst under microwave irradiation (15 dered 1-(trimethylbiphenyl-2-yl)ethanone (entry 19)
min, >98%)7 or using hydrazones as catalyst precursors (3 which is a tri-ortho-substituted biaryl.
h, 88%).8 The synthesis of 4-trifluoromethylbiphenyl (en-
In summary we present a very efficient catalyst system for
try 4) proceeds in quantitative yield within only 1 hour ap-
Suzuki–Miyaura reactions which allows for room-
plying our catalyst system. As a comparison, a recent
temperature cross-couplings.18
literature procedure using cyclometallated cis-chelated bi-
dentate benzimidazolylidene palladium complexes gave
91% yield within 24 hours at room temperature.9 Essen-
tially, the same yield of 4-methyl-4¢-(trifluoromethyl)bi-
phenyl (Table 2, entry 5) was obtained either starting from
cyclic triol borates and JohnPhos as ligand of Pd(OAc)2 in
DMF–water within a period of 5 hours,10 or according to
our procedure within 60 minutes. Noteworthy are the
reactions of the very electron-rich 4-bromo-N,N-dimethyl-
aniline (entry 8) and 2-bromophenol (entry 10) which
gave 86% and 94% yield of the corresponding biaryls at
room temperature, respectively, in considerably shorter
reaction times than reported for other catalyst systems (24
h,11 18 h12). Aryl iodides usually are the most reactive ha-
lides in Suzuki–Miyaura reactions. All iodides tested here
reacted in excellent yields (entries 12–15). The 1,4-di-
iodobenzene (entry 15) was reacted with two equivalents
of phenyl boronic acids to give terphenyl in almost quan-
titative yield at room temperature. A literature survey re-
vealed that our cross-coupling requires the mildest
reaction conditions (entries 12, 13,13 and 1414), or the
shortest reaction time at room temperature (entry 1515).
The use of chlorides as coupling partners has been a chal-
lenge over a longer period of time, as they proved to be
less reactive under standard Suzuki–Miyaura conditions;
nevertheless efforts have been devoted to this class of
compounds due to its attractive cost and readily available
diversity.16 We tested 4-chlorotoluene, 1-chloro-4-trifluo-
romethylbenzene, 1-acetyl-2-chlorobenzene, and 4-chlo-
Acknowledgment
The Deutsche Forschungsgemeinschaft (DFG) is gratefully ac-
knowledged for financial support.
References and Notes
(1) (a) Heck, R. F. Palladium Reagents in Organic Synthesis;
Academic Press: New York, 1985. (b) Principles and
Applications of Organotransition Metal Chemistry;
Collman, J. P.; Hegedus, L. S.; Norton, J. R.; Finke, R. G.,
Eds.; University Science: Mill Valley CA, 1987. (c) Metal-
Catalyzed Cross-Coupling Reactions; Diederich, F.; Stang,
P. J., Eds.; Wiley-VCH: Weinheim, 1998.
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Synlett 2010, No. 9, 1327–1330 © Thieme Stuttgart · New York