DOI: 10.1002/chem.201600420
Communication
&
Catalysis |Hot Paper|
A General Palladium-Catalyzed Hiyama Cross-Coupling Reaction
of Aryl and Heteroaryl Chlorides
On Ying Yuen,[a, b] Chau Ming So,*[a, b] Ho Wing Man,[a] and Fuk Yee Kwong*[a, b]
coupling reactions instead of the relatively cheaper and com-
Abstract: A general palladium-catalyzed Hiyama cross-
mercially more available aryl chlorides.[10] Since the first at-
coupling reaction of aryl and heteroaryl chlorides with aryl
tempt to use 10 mol% [Pd2(dba)3]/John-phos system (dba=di-
and heteroaryl trialkoxysilanes by a Pd(OAc)2/L2 catalytic
benzylideneacetone) for the Hiyama coupling of PhSi(OMe)3
system is presented. A newly developed water addition
with 4-chloroacetophenone that gave a product yield of
protocol can dramatically improve the product yields. The
47%,[7c] the effectiveness of the Hiyama coupling of aryl chlor-
conjugation of the Pd/L2 system and the water addition
ides has not been significantly improved compared with other
protocol can efficiently catalyze a broad range of electron-
cross-coupling methods. Palladium catalytic systems, such
rich, -neutral, -deficient, and sterically hindered aryl chlor-
as
Pd/(o-tol)3P,[11]
Pd/iPr-DPE
phos,[12]Pd/(4-FC6H4)3P,[13]
ides and heteroaryl chlorides with excellent yields within
three hours and the catalyst loading can be down to
0.05 mol% Pd for the first time. Hiyama coupling of heter-
oaryl chlorides with heteroaryl silanes is also reported for
the first time. The reaction can be easily scaled up
200 times (100 mmol) without any degasification and
purification of reactants; this facilitates the practical
application in routine synthesis.
Pd/phosphite,[14] Pd/phosphonate,[15] Pd/carbene ligand,[7f,16]
Pd/diamine ligand,[17] Pd/diimine ligand,[18] Pd/thiourea
ligand,[19] Pd/MIDA ligand,[20] ligand free Pd/C systems,[21] and
SBA-15-supported Pd nanoparticles[22] for the Hiyama coupling
of aryl(alkoxy)silanes with aryl chlorides have been reported.
However, these reports in general have several limitations.
1) narrow substrate scope (unreactive/poor results for the elec-
tron-rich aryl chlorides and/or functionalized aryl chlorides).
2) Limited examples (only a few aryl chlorides are demonstrat-
ed in some reports). 3) High catalyst loading (3–5 mol% Pd cat-
alysts are commonly used). 4) Long reaction times (10–24 h for
conventional heating techniques). Moreover, in some cases,
increasing the reaction temperature is not an effective means
to improve the yields (Figure 1).[15,17]
Palladium-catalyzed cross-coupling reactions have become
versatile protocols in organic synthesis for the construction of
carbon–carbon or carbon–heteroatom bonds.[1] Suzuki,[2] Ne-
gishi,[3] Kumada,[4] and Stille[5] reactions are common methods
for the preparation of biaryls that have numerous applications
in pharmaceutical, material, and agricultural chemistry.[6] The
Hiyama[7] cross-coupling reaction is one of the most attractive
methods to produce biaryl compounds because organosilicon
reagents are of low cost, low toxicity, commercially available,
easy to prepare and handle and are highly stable to a variety
of reaction conditions. However, organosilicons are less
reactive electrophiles owing to their less-polarized carbon and
silicon bonds.
Aryl(alkoxy)silane is one of the most extensively studied
organosilicons[8] in Hiyama coupling since the first report by
Shibata and co-workers.[9] Reactive aryl iodides and bromides
have been predominantly used as electrophiles in the Hiyama
Figure 1. General limitations of the Hiyama-coupling of aryl chlorides by
conventional heating techniques.
[a] Dr. O. Y. Yuen, Dr. C. M. So, H. W. Man, Prof. F. Y. Kwong
State Key Laboratory of Chirosciences and Department of Applied Biology
and Chemical Technology, The Hong Kong Polytechnic University
Hung Hom, Kowloon, Hong Kong, (P. R. of China)
Recent breakthroughs such as lowering the catalyst loading
to 0.5 mol% Pd, shorter reaction time, wider substrate scope
(steric hindered aryl chlorides) have been achieved by Verkade
and co-workers’ Pd/tBu2PÀN=P(iBuNCH2CH2)3N catalyst,[23] Jin
and co-workers’ b-diketiminatophosphane Pd complex,[18b] and
Wang and coworkers’ dinuclear N-heterocyclic carbene
(NHC)/Pd complex.[16b] Yet, catalyst loading remains high and
[b] Dr. O. Y. Yuen, Dr. C. M. So, Prof. F. Y. Kwong
The Hong Kong Polytechnic University Shenzhen Research Institute (SZRI)
Shenzhen (P. R. of China)
Supporting information and the ORCID identification number(s) for the au-
Chem. Eur. J. 2016, 22, 6471 – 6476
6471
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim