Highly efficient suzuki-miyaura coupling of aryl tosylates and mesylates catalyzed by stable, cost-effective [1,3-bis(diphenylphosphino)propane] nickel(II) chloride [Ni(dppp)Cl2] with only 1amol% loading

Article abstract of DOI:10.1002/adsc.201000710

We present a highly active, inexpensive, universally applicable, and markedly stable [1,3-bis(diphenylphosphino)propane]nickel(II) chloride [Ni(dppp)Cl₂] catalyst that is capable of effecting the Suzuki-Miyaura cross-coupling of the inherently less reactive but readily available aryl tosylates and mesylates with only 1amol% loading and in the absence of extra supporting ligand. Under the optimized reaction conditions, cross-coupling of a wide range of activated, non-activated, and deactivated, as well as sterically hindered and heteroaromatic substrates (36 examples) could proceed efficiently to afford the coupled products in 53-99% yields. Consequently, the results presented in this work provide a significant advance in Suzuki-Miyaura cross-coupling in terms of generality, practicality, and cost which are key concerns in recent research regarding transition metal-catalyzed cross-couplings.

Full text of DOI:10.1002/adsc.201000710

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DOI: 10.1002/adsc.201000710
Highly Efficient Suzuki–Miyaura Coupling of Aryl Tosylates and
Mesylates Catalyzed by Stable, Cost-Effective [1,3-Bis(diphenyl-
phosphino)propane]nickel(II) Chloride [Ni
1 mol% Loading
N
Han Gao,a,b You Li,c Yi-Guo Zhou,a Fu-She Han,a,* and Ying-Jie Linb,*
a
Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, Jilin 130022,
Peopleꢀs Republic of China
Fax : (+86)-431-8526-2926; phone: (+86)-431-8526-2936; e-mail: fshan@ciac.jl.cn
Department of Chemistry, Jilin University, Changchun, Jilin 130012, Peopleꢀs Republic of China
b
Fax : (+86)-431-8516-8398; e-mail: linyj@jlu.edu.cn
Department of Chemistry, Northeast Normal University, Changchun, Jilin 130024, Peopleꢀs Republic of China
c
Received: September 18, 2010; Revised: November 11, 2010; Published online: January 19, 2011
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201000710.
Abstract: We present a highly active, inexpensive,
universally applicable, and markedly stable [1,3-
bis(diphenylphosphino)propane]nickel(II) chloride
als.[4] In this transformation, phenol derivatives such
as triflates,[5] tosylates[6] and mesylates[6d–g] have been
extensively studied, among which the aryl tosylates
and mesylates are the most appealing coupling part-
ners because of their wide availability, low cost, and
high stability. Unfortunately, these electrophiles are
generally less reactive which has therefore led to con-
siderable efforts towards the development of highly
active catalysts over the past years.
Recently, remarkable progress has been achieved
that allows the reaction to be carried out at room
temperature,[6c,7] and to handle sterically hindered
substrates.[8] However, extensive use of these catalyst
systems is somewhat restricted owing to the several
main concerns: First, the high cost of the frequently
used Pd catalysts both for the palladium source[9] and
the supporting ligands[10] limits their general use in
commercial synthesis, e.g., the antihypertensive drug
valsatan, and the fungicide boscalid.[11] Second, fol-
[NiACHTUNGTRENNUNG(dppp)Cl2] catalyst that is capable of effecting
the Suzuki–Miyaura cross-coupling of the inherent-
ly less reactive but readily available aryl tosylates
and mesylates with only 1 mol% loading and in the
absence of extra supporting ligand. Under the opti-
mized reaction conditions, cross-coupling of a wide
range of activated, non-activated, and deactivated,
as well as sterically hindered and heteroaromatic
substrates (36 examples) could proceed efficiently
to afford the coupled products in 53–99% yields.
Consequently, the results presented in this work
provide a significant advance in Suzuki–Miyaura
cross-coupling in terms of generality, practicality,
and cost which are key concerns in recent research
regarding transition metal-catalyzed cross-cou-
plings.
lowing the pioneering work on a NiCl2ACTHUNTGRENNG(U dppf)/Zn
Keywords: aryl sulfonates; biaryls; boronic acids;
nickel catalyst; Suzuki–Miyaura coupling
system-catalyzed Suzuki–Miyaura coupling of aryl sul-
fonates by Percec,[12] several nickel-based Zn-free cat-
alysts such as NiCl2ACHTNUGRTEN(NNGU dppe), NiCl2ACHUTNTRGEG(NUNN PCy3)2, NiACHTUNGTRENNUNG(cod)2,
and Ni-NHC complex have been developed to effect
the Suzuki–Miyaura coupling of aryl tosylates and
mesylates,[6] ethers,[13] esters,[14] carbamates,[15] carbo-
The Suzuki–Miyaura cross-coupling of aryl halides nates,[15a] and sulfamates.[15a] However, high catalyst
and pseudo-halides (OTf, OTs, OMs, etc.) with aryl- loading (typically 3–10 mol%) paired with the re-
boronic acids has been recognized as one of the most quirement of an extra addition of 1–5 equivalents of
powerful and straightforward methods for the con- phosphine ligands, which are even much more expen-
struction of biaryls and heterobiaryls[1] that constitute sive than the nickel source, made the Ni-based cata-
the main scaffolds in numerous polymers,[1c] bioactive lysts also costly.[16] Finally, many of the Pd- and Ni-
compounds,[2] ligands,[3] and other functional materi- based catalysts suffer from poor stability and sensitivi-
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309

Han Gao et al.
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ty to air and moisture, which strongly restricts their plasma atomic emission spectrometry (ICP-AES,
industrial application.[17]
Prodigy, LEEMAN). The results showed a very high
Due to the aforementioned shortcomings versus the purity, no other metal impurities such as palladium
rapid increase of Suzuki–Miyaura coupling in practi- and copper were detected. These results firmly con-
cality, new catalyst systems that combine a greater firmed that NiCl2ACTHNUTRGNEU(GN dppp) presented herein is a highly
degree of activity and stability, low cost, and general active catalyst that is capable of catalyzing the
applicability are highly desirable. Herein, we disclose Suzuki–Miyaura coupling of less reactive aryl sulfo-
that the NiCl
catalyst in Suzuki–Miyaura reaction, is not only a
(dppp) complex, as an unprecedented nates.
Thus, with the optimized reaction conditions avail-
stable and cheap, but also a highly active, catalyst to able, we first examined the feasibility of this transfor-
catalyze the cross-coupling of unreactive aryl tosylates mation by varying the boronic acids. The results are
and mesylates with only 1 mol% loading and, more shown in Table 1. In general, the cross-coupling of
importantly, in the absence of extra supporting li- both 1-naphthyl tosylate and mesylate (1a and 1b)
gands.
proceeded very smoothly with various boronic acids
As groundwork for this study, we had previously (2b–g) whose structures are modified by electron-rich
demonstrated that a simple combination of NiCl2 and NH2 (entries 4 and 5), neutral Me and H (entries 6–
dppp in a 1:2 molar ratio could catalyze the Suzuki– 11), and electron-deficient CO2Me and C(O)Me
Miyaura reaction of aryl phosphoramides.[18] Although groups (entries 12–15). In addition, a sterically hin-
a high catalyst loading (10 mol% of NiCl2, and dered boronic acid 2d was also a viable coupling part-
20 mol% of dppp) was required in that coupling reac- ner, affording the product in high yields (entries 8 and
tion, the important advantages that pertain to using 9). Of particularly note is that for the boronic acid
NiCl2 and dppp, i.e., the low cost and high stability of having an unprotected NH2 substituent (2b), the reac-
both NiCl2 metal source[9] and dppp ligand,[10] as well tion occurred exclusively at the boronic acid group
as the excellent functional group tolerance of the cat- with the naked NH2 functionality remaining unconta-
alyst system stimulated us to further develop an minated (entries 4 and 5). To the best of our knowl-
NiCl2-dppp-based new catalyst system that is capable edge, such a highly chemoselective cross-coupling has
of catalyzing the Suzuki–Miyaura reaction of the in- not been observed in the known protocols. Indeed,
herently less reactive aryl tosylates and mesylates. Ac- we have noted that a similar coupling catalyzed by
cordingly, extensive experiments were carried out Pd(0) was unsuccessful and required a prior protec-
using 1-naphthyl tosylate (1a) and 4-methoxylphenyl- tion of the amino group.[20] Thus, as one of the fore-
boronic acid (2a) as a reference reaction in order to seeable advantages of this discovery, the orthogonal
optimize the reaction conditions (Table 1). Much to use of the NiCl2ACTHNUTRGNEU(GN dppp)-catalyzed Suzuki–Miyaura
our delight, a systematic survey of various reaction protocol presented herein with the Buchwald–Hart-
parameters including the form of the NiCl2/dppp com- wig coupling[21] would provide a straightforward path-
2
2
2
À
À
plex [e.g., NiCl
(dppp)1/2], bases (e.g., K3PO4, K2CO3, Na2CO3, bond formation reaction via a proper control of the
KOAc), ligands (dppp, dppe, dppp, PCy3), solvent, catalysts and the reaction sequences.
and temperature eventually revealed that NiCl2 Next, we examined the general applicability of this
(dppp)[19] is a promising catalyst to catalyze the cross- technology for a broad range of phenols. As listed in
2ACHTGNURTEN(UNGN dppp)2, NiCl2ACHTUNREGTG(NNUN dppp), and NiCl2 way for the selective C C (sp -sp ) and CACHTUNGTREN(NUGN sp ) N
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
coupling of 1a and 2a even in the absence of extra Table 2, tosylate and mesylate derived from 2-naph-
phosphine ligands. For instance, the cross-coupling of thol underwent smooth coupling to afford the desired
1a and 2a could proceed very smoothly to afford the product in almost quatitative yields (entries 1 and 2).
desired biaryl in 91% yield (entry 1) under the opti- The reaction was also tolerant of naphthol analogues
mized conditions, that is, NiCl2ACTHUNTGRENNG(U dppp) (1 mol%) and either substituted by a strong electron-donating OMe
K3PO4 (4.0 equiv.) in dioxane at 1008C. Equal effi- group (entries 3 and 4) or a strong electron-withdraw-
ciently, the coupling of 1-naphthyl mesylate (1b) with ing CN group (entries 5 and 6). Moreover, the non-
boronic acid 2a afforded the desired product in 99% fused (i.e., less electron-deficient) aryl tosylate and
yield under identical reaction conditions (entry 2).
mesylate derivatives are also competent coupling
To confirm that the cross-coupling is veritably cata- partners, affording the cross-coupled products in good
lyzed by the Ni-based catalyst rather than trace to excellent yields for a range of substrates whose
amounts of other metal impurities since NiCl2 with structures are modified by electron-rich (entries 7 and
98% purity was used in our experiments,[19] a control 8), neutral (entries 9 and 10), and electron-deficient
experiment was carried out by using NiCl2 with groups (entries 11–18).[22] In addition, the heteroaro-
99.999% purity purchased from Acros. A high yield matic tosylate and mesylate derived from 3-hydroxy-
(95%) was obtained for the coupling of 1a and 2a pyridine were also highly effective, delivering the cor-
(entry 3). In addition, we also tested the purity of the responding heterobiaryls in 98% and 96% yields, re-
NiCl2ACHTUNGTRENNUNG(dppp) complex by using inductively coupled spectively (entries 19 and 20). Finally, coupling of the
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Highly Efficient Suzuki–Miyaura Coupling of Aryl Tosylates and Mesylates
Table 1. Suzuki–Miyaura cross-coupling of 1-naphthyl tosylates (1a) and mesy-
lates (1b) with various boronic acids.[a]
[a]
Reaction conditions: 1-naphthyl tosylate (1a) or mesylate (1b) (1.0 mmol), bor-
onic acid 2 (2.0 mmol), NiCl
(4 mL), 1008C, 2-20 h.
Isolated yield.
2ACHTUNGRTNE(NUNG dppp) (1.0 mol%), K3PO4 (4.0 equiv.), dioxane
[b]
[c]
[d]
NiCl2 with 99.999% purity was used.
1
Yield was determined by H NMR spectroscopy due to the contamination of a
small amount of hard-to-separate by-product derived from homo-coupling of
boronic acids.
A mixture of dioxane and DMF (v/v=8:1) was used as solvent.
[e]
sterically hindered aryl sulfonates was somewhat chal- sulfonates exhibits a greater effect on the coupling ef-
lenging, affording the corresponding cross-coupled ficiency than that on the boronic acids as shown by a
product in moderate yields (entries 21 and 22). These comparison of the results in entries 8 and 9 in Table 1
results indicate that the steric hindrance on the aryl with entries 21 and 22 in Table 2.
Adv. Synth. Catal. 2011, 353, 309 – 314
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Table 2. Suzuki–Miyaura Cross-coupling of various aryl tosylates and mesylates with bor-
onic acids.[a]
[a]
Reaction conditions: aryl tosylate or mesylate (1.0 mmol), boronic acid (2.0 mmol),
NiCl2A(dppp) (1.0 mol%), K3PO4 (4.0 equiv.), dioxane (4 mL), 100–1108C, 2–20 h.
Isolated yield.
CTHUNGTRENNUNG
[b]
Thus, we have evidence that NiCl2ACTHNUTRGNEUNG
(dppp) is a highly couplings of aryl tosylates[6c] and esters.[14a] Further-
active catalyst for the Suzuki–Miyaura cross-coupling more, as an added highlight of our catalyst over the
of aryl tosylates and mesylates although the reaction reported ones, we should mention that, in addition to
mechanism deserves further clarification. Interesting- the high chemoselectivity for the NH2-substituted bor-
ly, recent studies showed that, being a supporting onic acid (vide supra), the new catalyst also exhibits a
ligand, the electron-deficient bidentate phosphines better functional group compatibility. For instance,
such as dppp, dppe, and dppf were inefficient in <br/ the NiCl HCTUNGTREN(NGNU dppp)-catalyzed coupling of CN-substituted
2A
Ni
ACHTUNGTRENNUNG(cod)2- and NiACHTUNGTRENNUNG(PCy3)2Cl2-catalyzed Suzuki–Miyaura aryl tosylates and mesylates could be converted to the
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Highly Efficient Suzuki–Miyaura Coupling of Aryl Tosylates and Mesylates
presented in this work is one of the most practical cat-
alysts among a myriad of Suzuki–Muyaura catalysts
developed so far. Consequently, this catalyst paired
with the use of aryl sulfonates as substrates, which are
generally more affordable than aryl halides, would
provide a great advance in the transition metal-cata-
lyzed Suzuki–Miyaura cross-coupling toward industri-
al applications. Furthermore, the high activity of NiCl2
AHCTUNGTREG(NNUN dppp) as evidenced by the Suzuki–Miyaura reaction
suggested that this catalyst is also possibly a suitable
catalyst for other couplings such as Heck and Stille
reactions. Studies on these reactions along with the
large-scale application of NiCl2ACTHNUTRGNE(NUG dppp) in Suzuki–
Miyaura coupling are currently underway in our labo-
ratory.
Scheme 1. Competition reaction of 1-naphthyl tosylate vs.
mesylate.
corresponding CN-substituted biaryls in excellent Experimental Section
yields (Table 2, entries 5, 6, 15, and 16). In contrast, as
the available examples from literatures, efforts at re- General Procedure for Suzuki–Miyaura Cross-
alizing the similar cross-coupling catalyzed by the Coupling Reactions of Aryl Sulfonates with
NiCl2ACHTUNGTRENNUNG
(PCy3)2-PCy3·HBF4 system[15b] or by Ni-NHC[6g] Arylboronic Acids
afforded only low to moderate yields due to the com-
peting coupling of cyano group with boronic acid, or
the low catalytic efficiency.
Finally, to evaluate the reactivity between aryl tosy-
lates and mesylates in NiCl2ACTHNUTRGNEUGN(dppp)-catalyzed Suzuki–
Miyaura reactions, a competition experiment was per-
formed by employing a 1:1:1 molar equivalent of 1-
naphthyl tosylate and mesylate, and 4-methoxylphenyl
boronic acid (Scheme 1). The results showed that the
reactivity between 1-naphthyl tosylate and mesylate
was almost identical with approximately 50% vs. 50%
of the coupled product (as deduced from the recov-
ered starting materials) was formed from 1-naphthyl
tosylate and mesylate, respectively.
To a 25-mL Schlenk tube equipped with a magnetic bar
were added NiCl2A(dppp) (0.01 mmol, 5.4 mg), aryl sulfonate
CTHUNGTRENNUNG
(1.0 mmol), aryboronic acid (2.0 mmol), and anhydrous
K3PO4 (4.0 mmol). The tube was then evacuated (3ꢂ
10 min) under vacuum and backfilled with N2. Dried diox-
ane (4.0 mL) was injected via syringe, and the reaction mix-
ture was stirred at 100–1108C until the aryl sulfonates had
disappeared as monitored by TLC. The reaction mixture
was then poured into water (30 mL) and extracted with
CH2Cl2 (20 mLꢂ3). The combined organic layer was dried
over anhydrous Na2SO4, filtered and concentrated to dry-
ness. The crude material was purified by flash chromatogra-
phy on silica gel using a mixture of hexane and CH2Cl2 (or
hexane and ethyl acetate) as eluents to give the desired
cross-coupled products.
In summary, through an extensive study, we have
unambiguously demonstrated that NiCl2ACTHUNTGRENNG(U dppp) is a
reliable and practical catalyst for Suzuki–Miyaura
cross-couplings of the inherently less reactive aryl to-
sylates and mesylates. This protocol offers several ad-
vantages over the available methods in terms of: (i)
the highly catalytic efficacy that allows the coupling
reaction to proceed efficiently with only 1.0 mol%
catalyst loading as well as in the absence of extra sup-
porting ligand; (ii) the general applicability and good
functional group tolerance both for a rich range of
aryl sulfonates and boronic acids; (iii) the low cost
either compared with the frequently used palladium
catalysts attributed to the non-noble metal nature of
nickel, or in comparison with the several available
nickel catalysts (vide supra) due to the significantly
lowered catalyst loading, the use of more affordable
dppp ligand, and the absence of extra supporting li-
gands; (iv) the markedly enhanced stability toward
air and moisture due to the high stability of the dppp
Acknowledgements
The authors are grateful to CIAC for financial support.
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[22] It should be mentioned that, as an exceptional exam-
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dimethylphenol is somewhat sluggish, affording the
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[9] The approximate cost for PdCl2 (99%) is $91.20 per
gram; however, NiCl2 (98%) used in this work is $61.80
per 50 g (Aldrich catalogue, 2009–2010).
[10] The cost for the several frequently used phosphine li-
gands in conventional cross-coupling of aryl chlorides,
tosylates, and mesylates is 2-(di-tert-butylphosphino)bi-
phenyl (JohnPhos, 97%) is $99.10 per gram; 2-di-tert-
butylphosphino-2’-methylbiphenyl (t-BuMePhos, 97%)
is $213.50 per gram; 2-di-tert-butylphosphino-2’,4’,6’-
triisopropylbiphenyl (Xphos, 97%) is $99.10 per gram;
however, bis(diphenylphosphino)propane (dppp, 97%)
used in this work is ca. $20.10 per gram, which makes it
one of the cheapest phosphine ligands in the chemical
price list (Aldrich catalogue, 2009–2010).
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