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Nickel-Catalyzed Heteroarenes Cross Coupling via Tandem C–H/C#O Activation Ting-Hsuan Wang, Ram Ambre, Qing Wang, Wei-Chih Lee, Pen-Cheng Wang, yuhua liu, Lili Zhao, and Tiow-Gan Ong ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.8b03436 • Publication Date (Web): 25 Oct 2018 Downloaded from http://pubs.acs.org on October 25, 2018
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ACS Catalysis
Nickel-Catalyzed Heteroarenes Cross Coupling via Tandem C–H/C‒O Activation Ting-Hsuan Wang,†,‡,¶ Ram Ambre,†,¶ Qing Wang$, Wei-Chih Lee,£ Pen-Cheng Wang,‡ Yuhua Liu,§ Lili Zhao,*,$ and Tiow-Gan Ong*,† † Institute
of Chemistry, Academia Sinica, No. 128, Sec. 2, Academia Road, Nangang, Taipei, Taiwan, ROC.
$ Institute
of Advanced Synthesis, School of Chemistry and Molecular Engineering, Jiangsu National Synergetic Innovation Center for Advanced Materials, Nanjing Tech University, Nanjing 211816, China ‡ Department
of Engineering and System Science, National Tsing Hua University, Hsinchu, Taiwan, ROC.
£
Green Energy and Environment Research Laboratories, Industrial Technology Research Institute, Hsinchu, Taiwan, ROC.
§
School of Chemistry and Chemical Engineering, Guangzhou University, Guangzhou, 510006, China.
ABSTRACT: Inert aryl methyl ethers as coupling components via C‒O activation has been established with Ni catalyst for C‒H activation of heteroarene. The key to simultaneous C‒H/C‒O bond activation is the use of steric demanding o-tolylMgBr. The protocol is effective for a wide scope of substrates including naphthyl methyl ethers, anisoles and a variety of other heteroarene derivatives. Detailed mechanistic studies indicated that the C‒O cleavage is assisted via synergistic effect of nickel and Grignard reagent in this C‒H/C‒O reaction, which is supported by DFT calculation. At this stage, single electron transfer can be ruled out as a main operative process for this tandem strategy. Keywords: Tandem catalysis; C–H activation; C–O cleavage; nickel; carbodicarbene; cross-coupling. INTRODUCTION Since the 1970’s, metal-mediated cross-coupling reactions have emerged as a significant and versatile synthetic strategy to streamline a variety of biaryl skeletons. In common practice, aryl halides are frequently used as electrophilic synthons, which currently appear to be less environmentally benign. For that reason, O-derived electrophiles have been promoted as a potential surrogate.1 In 1979 Wenkert reported the pioneering work of nickel catalyzed cross-coupling of aryl ethers with Grignard reagent via C‒O bond cleavage,1e however this reaction remained overlooked for 30 years until late 2000s. Since then, several examples of halide-free coupling reactions have been reported for carbamates,2 carbonates,3 ethers,4 and some limited cases in phenols5 and alcohols. Nickel appears to be the superior catalyst for the process of activating the inert C(aryl)–O bond.1b,c Our group has a longstanding interest in nickel directed C‒H activation reactions,6 as these methods generate less chemical waste by circumventing additional steps associated with prefunctionalized substrates. Ultimately, a protocol relying on tandem C‒H/C‒O bond activation would not only fulfill the tenets of a “green” process, but also further empower the utility of the cross-coupling paradigm, as both C‒H and C‒O moieties are pervasively present in many molecules. To date, efforts for C‒H functionalization with Oderived electrophiles, namely phenol derivatives have found limited success. Itami and co-workers first reported the nickel-catalyzed reaction of aryl pivalates with azoles.7 Shi and co-workers recently demonstrated that the coupling reaction is viable based on Ni/Cu mediated dual catalysis for C‒H activation of perfluorinated arenes with C‒O activation of aryl carbamates.8 Similarly, Chatani, Tobisu and co-workers employed aryl carbamates as
coupling partners for the C‒H activation of arenes bearing a convertible directing group using a rhodium bis(Nheterocyclic carbene) catalyst.9 Other notable cases could also be found in seminal works by Ackermann and Song utilizing aryl carbamates via a cobalt catalyzed process.10 In spite of methoxy being a pervasive motif, it is surprising that cross coupling reaction of heteroarene using C‒O activation’s strategy of aryl methyl ethers as coupling is not reported, as C‒OMe has the highest energy dissociation and is generally considered as a poor leaving group (Scheme 1).1b Herein we report a proof-of-concept strategy to forge a coupling product derived from simultaneous cross coupling reaction manifolds based on C‒H cleavage of benzimidazole and heteroarene derivatives by Grignard reagent and nickel mediated C–O bond activation of aryl methyl ethers. The present work also performed detailed experimental and computational study of the reactions in this tandem process in an effort to understand what factors (Grignard reagent, ligand) govern these simultaneous bond cleavages C‒H/C‒O as well as the nature of mechanism. easy of C(Ar)-O bond breaking ester O O O Ar S O CF3
O O Ar S O p-tol
triflate
tosylate
Ar
O
R
carbamate O Ar O NR2
O Ar
O
OR
Ar
carbonate
O
O P
OR OR phosphate
good availability, low cost
Scheme 1. Ability of C‒O bond cleavage.1b
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Ar
O
Me
aryl methyl ether
ACS Catalysis
yield into practical range,11 though these conditions were still plagued by side reactions (25%). Next, we varied ligand selection with a series of ligands in method D. Interestingly, sterically demanding scaffolds like P(o-tolyl)3, IPr and 4,5Me2IMes consistently afforded high chemo-selectivity for 3aa. Furthermore, the use of bulky reagent o-tolylMgBr in method E reinforced the notion that high steric favored productive reaction for 3aa, as clearly reflected by the very low yield in 5 (~5%). Finally, we successfully attained 92% yield with no byproduct at a lower temperature of 90 °C using a slight excess of 1a in method F based on selecting best of the best from methods A to E. We additionally note that the carbodicarbene (CDC), electron-rich ligand is also effective for this catalytic C‒H/C‒O protocol.12
RESULTS AND DISCUSSION Reaction Evaluation on Simultaneous C‒H/C‒O Activation. To test our thought, we began with the coupling reaction of 2-methoxynaphthalene (1a) and 1methybenzimidazole (2a) (Scheme 2). In screening A, 10 mol% Ni(cod)2 and PPh3 ligand appeared as an optimal catalyst system to generate preferred product 3aa in 46% yield at 130 °C (blue column in Scheme 2). Inclusion of PhMgBr (1.0 equiv) in the reaction was necessary to facilitate C‒O cleavage of 1a, but it also generated 20% undesired 5aa and trace amount of Kumada byproduct 11 (red column represent all minor side-products shown in Scheme 2). Selecting m- or o-xylene solvent in method B (63%) or adding LiCl salt in method C (60%) pushed the N
1a
2a
Ni(cod)2, solvent, PPh3, PhMgBr, 130°C
20%
Ni(cod)2
15% 4% Ni(OAc)2
64%
27%
22%
25%
63%
21%
41%
33%
25%
20%
Ni(cod)2, m-xylene, iPr, p-tolylMgBr, Temp, LiCl
29%
92%
88%
75% 75% CsCl
LiCl
MgCl2
40%
Ni(cod)2, toluene, PPh3, RMgBr, 130°C
60% PPh2
N 58%
50%
PPh2 10%
6% 10% P(o-tolyl)3
37% 21%
20% 9%12%
o
Yield 50%
61%
N
25%
57%
E: grignard variation
N
N
F: The best optimized condition via A, B, C, D & E
60% 46%
None
Ni(cod)2, toluene, ligand, PhMgBr, 130°C
PCy3
51%
O O
D: ligand selection
18%15%
11
Ni(cod)2, toluene, PPh3, PhMgBr, 130°C, additive
13%
NiCl2(PPh3)2
5
C: additive
Yield 50%
Yield 50%
cat, toluene, PPh3, PhMgBr, 130°C
R
+
N 3aa
B: solvent variations
51%
R
+
N
A: catalyst selection
46%
N
N
Yield 50%
H
+
Yield 50%
A. [M] 10 mol% B. Solvent C. Additive 1 equiv D. Ligand 10 mol% E. R-MgX 1 equiv
N
O
Yield 50%
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
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8%
Et
Cy
12%
5%
90 (CDC)
1.5 equiv 2a
iPr
N
20%
90
70
90
N
31%
14% 7% 3% 3% 0% R= Me
N
60%
46%
C = 130
C
N N
iPr
carbodicarbene :CDC Benzyl
Ph
p-tolyl
o-tolyl
N
Scheme 2. Optimization procedure. Substrate Scope and Limitation. With the optimized conditions in hand, we examined the reaction scope with a series of methoxynaphthalene derivatives 1 and 1methylbenzimidazole 2a (Table 1). Excellent yield was attained for 1a to afford coupling product 3aa (92%). Variations at C6 of methoxynaphthalene were first examined. 1b bearing silyl group was used to afford product 3ba in moderate yield (50%). Pyridyl (1c) and diphenylamino (1d) derivatives were also effectively converted to the desired coupling product 3ca (79%) and 3da (82%), respectively by CDC as the supporting ligand. Encouragingly, 2-methoxy-6-phenylnaphthalene (1e) could also undergo C‒O activation to afford the corresponding coupling product 3ea in 60% yield. In addition, we performed several 2-methoxy-6-arylnaphthalenes (1f-j), which proved suitable for this protocol, affording moderate to good yields. It is worth mentioning that a synthetic strategy using naphthalenes containing aryl and polyaromatic rings would be useful for constructing organic photosensitizer materials, which are further exemplified by the formation of 3ka (carbazole),13 3la (pyrene),14 and 3ma (styryl).15 Regrettably, neighboring steric hindrance has adverse effect on the yield of 1s. Finally, representative
samples of naphthalene with electronic variation at C7 (1nr) and commercially available 1-methoxynapthalene (1t) are effective coupling partners. It is noted that substrates bearing withdrawing groups are not suitable in this catalytic protocol, as they would interact with the Grignard reagents.16 The Scope of Aryl Methyl Ethers. At present, nickelpromoted C‒OMe cleavage for carbon-carbon bond forming reactions remains largely confined to the naphthalene moieties as coupling partners. The existing catalytic state-of-the-art takes advantage of the π-extended backbones of naphthalene for a strong π-coordination to Ni complexes, prior to C‒O functionalization. 17 Such a C‒O transformation is less likely to occur in anisole because of higher energy penalty for the loss of ring aromaticity.18 To address this challenge, we sought to extend the catalytic utility to aryl methyl ethers 4x (Table 2). Under similar reaction conditions, we were pleased to discover that anisole 4a is an effective substrate to afford coupling product 5aa in 82% yield. The methyl substituents at meta (4c) and para (4d) positions are tolerated affording good y i e l d s ( 6 6 % a n d 5 5 % , r e s p e c -
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ACS Catalysis
Table 1. Scope of Methoxynaphthalene Derivatives O
Me
R1
Ni(cod)2, IPr o-tolylMgBr (1.5 equiv) LiCl (1 equiv)
N +
N
Ar N
90 o C, 16 hrs m-xylene 20 examples
2a
1x
a,b
N
3xa
variaiton at 6-position: OMe
OMe
OMe
OMe
OMe
N TMS
Ph2N
1a, 92%
1c, 66% (79%c,d)
1b, 50%
R
1d, 82%c,d OMe
N Ph 1k, 71%c,d
1l, 52%c,d
1m, 41% variation at 1-position:
variation at 7-position: Ph2N
OMe
R OMe
OMe 1n, 81%c,d O
60%c,d 57%c,d 60%c,d 45%c,d 45%c,d 61%c,d
1e, R=H 1f, R=2-Me 1g, R=3-Me 1h, R=4-Me 1i, R=4-tBu 1j, R=2-Mes
OMe
OMe
Electron-donating substrates like dimethyamino and diphenylamino at different positions relative to the methoxy group also afforded effective transformations (4m-p) (68-87%). Finally, other less conventional substrates like 1-methoxy-4-styrylbenzene (4q), pyrrole (4r) and carbozole (4s) proved equally effective in this method, reinforcing its broad-scope applicability. The demonstrated protocol of simultaneous C‒H activation was further extended for the C‒O cleavage of steroidal hormone -esterdiol methoxy derivative (4t) with 1methylbenzimidazole (2a) under general nickel catalyzed reaction conditions readily accomplished corresponding product (5ta) with 74% yield leaving aliphatic methoxy group intact (Scheme 3).
1p, R=H 1q, R=Me 1r, R=t-Bu
1o, 46%
85%c,d 83%c,d 76%c,d
CH3 OMe
CH3 OMe
OMe OMe
N
1t, 60%c,d
Condition: 1 (0.75 mmol), 2a (0.5 mmol), Ni(cod)2 (0.05 mmol), IPr (0.05 mmol), o-tolylMgBr (0.75 mmol) and LiCl (0.5 mmol) in m-xylene (0.7 mL) at 90 oC for 16 hours unless otherwise noted. b Isolated yield. c CDC is used instead of IPr. d w/o LiCl.
H
H
MeO
a
2a
H
Ni(cod)2, CDC o-tolylMgBr LiCl m-xylene o 90 C, 16 hrs
H
+
N
1s, 35%c,d
4t
H
N
H
N 5ta (74%)
Scheme 3. Simultaneous C‒H activation and C‒O cleavage of steroid hormone -Esterdiol derivative.
Table 2. Scope of Various Anisole Analogues a,b O R
N
OMe
OMe
OMe
Table 3. Scope of Heteroarenes a,b
R
N
5xa 1a : Naph-OMe 4a: Anisole
2x
OMe
4c 66%
4b 25%
4a 82%c,d
4e 76%c,d
4d 55%c,d
OMe
OMe
CH3
H 3C
CH3
+
HeteroAr
OMe
OMe
OMe
N
CH2CH3
tBu
4f 75%c,d
4g 40%
OMe
OMe
N
N
Ph
R
4h 62%c,d
4m 68%c,d
NMe2
NPh2 4n 75%c,d
NMe2
4o 78%c,d
2b, 81%
2a, 92%
OMe 4l 71%c,d
MeO
MeO
4q 33%
2e, 2f, 2g, 2h, 2i, 2j,
N
N
4r 50%c,d
MeO
R
4p 87%c,d
OMe N 4s 58%c,d
Condition: 1 (0.5 mmol), 2a (0.75 mmol), Ni(cod)2 (0.05 mmol), IPr (0.05 mmol), o-tolylMgBr (0.75 mmol) and LiCl (0.5 mmol) in m-xylene (0.7 mL) at 90 oC for 16 hours unless otherwise noted. b Isolated yield. c CDC is used instead of IPr. dw/o LiCl.
a
tively), but 4b bearing the ortho methyl group affords lower yields. We believed that the proximal steric influence was a contributing factor. In addition, the catalytic reaction could be performed with several anisoles possessing different alkyl substitutions (4e, 4f, and 4g), including a more bulky t-butyl group, albeit the latter resulted in lower yield. Next, we investigated 4-methoxy-1,1'-biphenyl (4h), 3-methoxy1,1'-biphenyl (4i) and other similar counterparts (4j and 4k) for coupling reactions which also afforded good yields. The success of constructing these end products (5ha, 5ia, 5ja and 5ka) represents a complementary method for polyaromatic compounds. Interestingly, 1,3dimethoxybenzene (4l) underwent only single-fold C–O cleavage, leaving the other methoxy functionality intact.
Imidazole derivatives
N
N
N
N
N
N
Ph
Bn
N
NPh2
6xa or 7xa
Benzimidazole derivatives N
c,d
4i R=H 83% 4j R=Me 65%c,d 4k R=tBu 68%c,d
HetroAr
22 examples
OMe
CH3 CH3
Ni(cod)2, IPr o-tolylMgBr (1.5 equiv) LiCl (1 equiv) 90 o C, 16 hrs m-xylene
O
N
90 o C, 16 hrs m-xylene 19 examples
2a
4x OMe
Ni(cod)2, IPr o-tolylMgBr (1.5 equiv) LiCl (1 equiv)
N Me +
R=H R=2-Me R=3-Me R=4-Me R=4-tBu R=4-OMe
2k, 53%
2d, 30%c
2c, 75%
N
N
N
N
N
N
Ph
2l, 30%e
2m, 35%
Mes 2n, 31%e
Other heteroarene derivatives
63%d N.D. 68%d 57%d 86%d 43%d
N
N 2p, 60%
2o, 60%
N
N
2q, 33%
Benzimidazole derivatives with anisole (4a) N
N
N
N
N
N
N
N
2a, 82%
e
2b, 65%
e
2c, 72%
2e, R=H 56%e 2i, R=4-tBu 60%e
e
R
a
Condition: 1a/4a (0.5 mmol), 2 (0.75 mmol), Ni(cod)2 (0.05 mmol), IPr (0.05 mmol), o-tolylMgBr (0.75 mmol) and LiCl (0.5 mmol) in m-xylene (0.7 mL) at 90 oC for 16 hours unless otherwise noted. b Isolated yield. c p-tolylMgBr is used instead of o-tolylMgBr. d P(o-tolyl) is used instead 3 of IPr w/o LiCl. e CDC is used instead of IPr w/o LiCl.
The Scope of Heteroarenes. As benzimidazole and its derivatives are inherent structures present in many biologically active natural products,19 pharmaceuticals,20 and optoelectronic materials,21 we next examined the scope of this reaction with its C–H manifold substrates (Table 3). Under similar reaction conditions, the electron-rich 1,5,6trimethyl-benzimidazole (2b) was coupled with 2methoxynapthalene (1a) to give 6ba in excellent yield (81%). Similarly, coupling with 1-ethylbenzimidazole (2c) afforded 75% yield, whereas coupling with 1benzylbenzimidazole (2d) afforded only 30% yield, likely due to the presence of its bulky dangling benzyl group. 1Phenylbenzimidazole (2e), 1-meta-tolylbenzimidazole (2g), 1-para-tolylbenzimidazole (2h), and more bulky 1-paratertiarybutyl phenyl benzimidazole (2i) generated coupling
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products with moderate to good yields (57-86%), whereas 1-ortho-tolylbenzimidazole (2f) did not provide the expected product due to steric hindrance. It is noteworthy that the electron donating 1-paramethoxyphenylbenzimidazole (2j) was successfully coupled with 2-methoxynaphthalene to construct 43% of 6ja, leaving the methoxy functional group intact. The reaction was not kept limited to the benzimidazole moiety but also extended to imidazole derivatives and other heteroarene compounds. Imidazole derivatives (2k-n) produced fused products in low to moderate yields. Other heteroarene compounds such as isoquinoline (2o), 3methylisoquinoline (2p), and imidazo[1,5-a]pyridine (2q) afforded coupling products 6oa (C–H activation at 1position), 6pa (C–H activation at 1-position), and 6qa (C–H activation at 3-position), respectively. The C–O cleavage of anisole 4a with representative benzimidazole derivatives (2a, 2b, 2c, 2e, and 2i) was also applied to produce their coupling products 5aa, 7ba, 7ca, 7ea, and 7ia respectively in good yields. Mechanistic Studies: The Nature of C‒H Bond Activation. Given the unique reactivity of the Ni-catalyzed tandem C‒H/C‒O activation, we are interested to gain further insight into the reaction mode. First, it is important to examine the nature of the CH functionalization in this catalytic reaction. A reaction of 2a in presence of otolylMgBr was stirred at 90 °C for 30 minutes followed by D2O treatment (Scheme 4.1), affording only deuterium substituted-2a in 1H NMR analysis. A similar outcome was observed with the reaction with PhMgBr (Scheme 4.2). These results indicate the possibility that the C‒H activation of 2a might occur via deprotonation process by Grignard reagent to generate Hetero-MgBr species (2a-MgBr). Nevertheless, the known nickel-mediated C‒H activation process could not be ruled out at this stage.22 Regardless to the nature of C‒H activation, the studies on kinetic isotope effect of 2a-D and 2a in Scheme 4.3 and 4.4 showed there are no significant intermolecular KIE value (kH/kD ≈ 1.1). in situ generation N
(1)
N
H
o-tolylMgBr 90 oC, 30 mins
2a
N
H
PhMgBr 90 oC, 30 mins
2a
N N
MgBr
N
N
N 2a-D
H/D
(H:D = 0:100) N
D 2O
N
H/D
(H:D = 0:100)
H + 1a 1.5 equiv
N
N
D 2O
OMe
2a
(4)
MgBr
2a-MgBr N
(3)
N
2a-MgBr N
(2)
N
Ni(cod)2 / IPr 10 mol% o-tolylMgBr 1.5 equiv m-xylene, 90 oC, 45 mins
OMe
D + 1a 1.5 equiv
N N 3aa KIE = 1.1
Scheme 4. Reaction studies pertaining C‒H activation.
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can be easily excluded because of the very high barrier of 33.4 kcal/mol (TS1’’, see Figure S2 for details), which is mainly due to the larger steric effects. Alternatively, the addition of 2a lead to the intermediate IM1’ (see Figure S2), with one ether ligand 1a released from the Mg-center. The C–H activation barrier is predicted to be 22.8 kcal/mol (IM1’ →TS1’, Figure S2), which is in the range for experimental realization under high temperature. This agrees with the experimental verification as shown in Scheme 4.
Figure 1. Computed energy profiles of C‒H activation with Ni-catalyst and Grignard reagent at the BP86/def2TZVPP(PCM, solvent=m-xylene)//BP86/def2-SVP level. Key bond distances are given in Å. Trivial hydrogen atoms have been omitted for clarity. Color code: Ni, purple; N, blue; O, orange; C, gray; H, white; Mg, yellow; Br, dark red.
Nonetheless, the addition of the nickel complex in the reaction system can further reduce the energy barrier. As shown in Figure 1, the addition of IPrNi(COD) in presence of [RMgX(1a)2] and 2a can firstly generate the intermediate IM1, with one 1a and COD ligand released. Subsequently, C– H activation can be easily achieved via a low barrier of 7.4 kcal/mol (IM1→TS1), leading to IM2, in which the activated H-atom is bonding to Ni-center. The Ni-H moiety in IM2 then slightly adjust position to transfer the H atom to the phenyl group by passing a barrier of 10.3 kcal/mol (TS2), leading to IM3 and PhCH3. The feasible kinetics and thermodynamics imply that the nickel complex indeed participates in C‒H bond activation or the deprotonation step. This calculation result is further confirmed by performing reactions with 2a at 35 °C and 60 °C in Scheme 5. No deprotonation was observed in presence of otolylMgBr (Scheme 5.1) at both temperatures, after reaction was quenched with excess of D2O in 45 minutes. Nevertheless, we witnessed 35 % and 42 % yield of deuterium substituted-2a when the reaction is conducted in the presence of Ni(cod)2 (10 mol %) and o-tolylMgBr (1 equiv) at 35 °C and 60 °C, respectively (Scheme 5.2). These outcomes obviously highlight the importance of both nickel and Grignard reagent in assisting the C‒H bond activation. N
To understand the nature of C‒H bond activation, DFT calculations were further performed to the study the role of nickel complex in the deprotonation process. Inspired by the previous study23, the structure of Grignard reagent could be calculated as the simplified model [RMgX(ether)2] (i.e., [RMgX(1a)2]). As shown in Figure 1, the reaction pathway for the C‒H activation mediated by [RMgX(1a)]2
H
(1)
N
o-tolylMgBr (1 equiv)
T = 35 T = 60
N H N 2a
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Ni(cod)2, IPr (10 mol%) o-tolylMgBr (1 equiv)
D +
N
2a
(2)
N
D 2O
T oC, 45 mins
0% 0%
N
D 2O
N
T oC, 45 min T = 35 T = 60
N H N 100 % 100 %
D +
35 % 42 %
N H N 65 % 58 %
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Scheme 5. Reaction studies about the synergistic roles of Ni-ArMgBr in assisting C‒H bond activation. The Role of Grignard Reagents in C‒O Cleavage. Undoubtedly, the Grignard reagent is essential for the coupling reaction with 1-benzimidazole 2a. Thus, it should make no difference in the reactivity topology of which type of Grignard reagents were used if the deprotonation process is a true operative mechanism. However, we were also puzzled by the necessity of employing an excess amount of Grignard reagent (~1.5 equiv) in this tandem catalytic manifold. In practice, only one equivalent of Grignard reagent is needed in this catalytic reaction to generate a HeteroMgBr 2a-MgBr, which would be, in theory capable of assisting C‒O bond cleavage. Interestingly, otolylMgBr, a sterically demanding reagent appeared much more effective than PhMgBr (see optimization process in Scheme 2). These observations hinted that ArMgBr had more roles other than a simple possible deprotonation. We elected to study this reaction by using one equivalent of Grignard reagent stirred with 2a for 30 minutes with Ni/IPr catalyst’s addition (Scheme 6). The reaction with one equivalent o-tolylMgBr yielded product 3aa (52%) and other unproductive couplings 5ba (4%), 11a (7%) and 12a (0%) (Scheme 6.1). Unproductive coupling of 5aa (27%), 11b (20%) and 12a (9%) increased even substantially in the expense of the productive 3aa’s formation (30%), when a catalytic reaction used a less bulky PhMgBr (Scheme 6.2). The alkyl Grignard reagent MeMgI have suffered an even lower yield of 3aa (11%) (Scheme 6.3) The outcome in Scheme 6 demonstrated the spatially crowded Grignard was critical to the success of the reaction, particularly in the aspect of assisting C‒OMe bond cleavage. It is plausible to infer that in-situ formation of Grignard adduct of 2a was not as effective as o-tolylMgBr in assisting C‒O/C‒H bond cleavage, resulting a non-productive formation of undesirable coupling product. To further verify the postulation, a reaction of anisole 4a in presence of otolylMgBr (1 equiv) was conducted (Scheme 6.4), and its high proportion of productive coupling is indeed consistent with our thought that the Grignard plays a secondary role in minimizing non-productive coupling and assisting C‒H/C‒O bond activation. The Scheme 6 also revealed the noticeable discrepancy of the yield for 3aa using different Grignard reagents, strongly suggesting that a simple deprotonation of 2a by Grignard might not be the key reaction in C‒H bond activation. It suggests that nickel complex is playing a significant role not only in C‒H bond activation with Grignard reagent (Figure 1 and Scheme 5), but also in C‒O bond cleavage process. This agrees well with the DFT calculations. The very high barrier (∆G ≠ =66.2 kcal/mol, Figure S3 in Supporting Information) excluded the possibility of the direct reaction of methoxyarenes with Grignard reagent. As expected, the inclusion of the Ni-complex can significantly promote the C‒O bond cleavage, with an activation barrier of 25.7 kcal/mol (IM9→TS5) (see Figure S3), which demonstrates the significant role of nickel catalyst and Grignard reagent in the C‒O cleavage process. Possibility of Radical Intermediate? The key to the successful catalytic reaction for simultaneous C‒H and C‒O
bond activation is rested upon the dual ability synergistic effect invoked by Grignard reagent and nickel to deprotonate 2a, and to hinder the reaction pathway favoring undesirable coupling products in the C‒O bond cleavage. The contemporary mechanistic argument hinged on Ni(0)-Ni(II) cycle should well explain about the side reaction for the formation of Kumada byproducts 11a-d, when less bulky Grignard reagent is used. However, it could not account for the formation of other side-products for 5aa, 5ab and 12a-b (homo-coupling byproducts) in Scheme 6. unproductive couplings O
MgBr
N N
O
MgBr
N 2a
O
Me MgI
MgBr
tol
Nap tol
Nap Nap
5ab
11a
12a
52%
4%
7%
0%
N
N
Nap
N
Ph
Nap Ph
Nap Nap
3aa
5aa
11b
12a
30%
27%
20%
9%
N N
O
N
3aa
N N
Nap
N
Nap
N N
3aa
10a
11%
trace
N N
Ph
N N
Me
Nap Me 11c
tol
Nap Nap
(1)
(2)
(3)
12a
35%
0%
Ph tol
Ph Ph
5aa
5ab
11d
12b
34%
5%
8%
trace
(4)
Scheme 6. Reaction studies pertaining the ArMgBr’s roles. We suspected that the single electron transfer process with Ni(I) intermediate species might come into play. The results of several studies involving Ni and Pd catalysts have provided evidence that radical pathways, including singleelectron-transfer processes, are involved in the crosscoupling reactions.24 A radical scavenger such as TEMPO was employed to probe this catalytic reaction.25 Under the exact catalytic conditions, the CDC-promoted reaction was partially inhibited by the addition of TEMPO (~10 mol%), as the catalytic efficiency has been diminished from its original of 88% to 26% (Scheme 7.1). Interestingly, we also found that increasing the amount of TEMPO up to 50 mol% did not completely impede the catalytic activity (22%). Similar trend of observation is also witnessed in the reaction using IPr ligand. Additional reaction was subsequently carried out under the standard reaction conditions with 1,1’-diphenylethylene treatment (1,1’-DPE, Scheme 7.2) in hope to recapture any the aryl or naphthyl radial species in the reaction to afford the corresponding coupling product of 21 and 22.26 Despite of slightly lower yield (~78%) than the normal condition, no any trace amount of 21 and 22 was detected by GC-MS. Notably, no EPR signal was detected in the reaction solution in ambient or low temperature (10K). With these results, we have some reasonable doubts about the main operative pathway involving a continued generation of the aryl or naphthyl radical. More importantly, the sheer volumes of literatures of the C‒O bond transformation reported mechanistic evidence involved 2-electron process so far.27 For example, a recent comprehensive theoretical and experimental study by Tobisu, Chatani and Mori indicated nickel-promoted cross-coupling of methoxyarenes via C‒O cleavage revolved around Ni(0)-Ni(II).27a
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The Ni(I) Complex in the Catalytic Cycle. Next, we turned our attention to postulate that the nickel(I) species might be responsible for the formation of side products in the catalytic reaction. To further confirm this postulation, a carbodicarbene Ni(I) complex 20 was prepared via comproportionation reaction of Ni(cod)2 and Ni(PPh3)2Cl2 in presence of CDC ligand and its structural identity was confirmed as a distorted trigonal Ni(I) chloride complex bearing both CDC and PPh3 ligands (see Scheme 8.1). N
+
2a
1a TEMPO
N 3aa
L = CDC 3aa yield
88%
26%
22%
19%
L = IPr 3aa yield
92%
23%
15%
14%
Ni(cod)2 10 mol% ligand 10 mol% o-tolylMgBr 1.5 equiv. X mol% 1,1'-DPE 90 oC, 16 hrs
O
N N
N
0 mol% 10 mol% 20 mol% 50 mol%
L
(2)
Ni(cod)2 10 mol% ligand 10 mol% o-tolylMgBr 1.5 equiv. X mol% TEMPO 90 oC, 16 hrs
O
N
(1)
+
2a
1a 1,1'-DPE
N
Nap
N
non-detected Ph
3aa
Nap
L L = CDC 3aa yield
88%
80%
80%
75%
L = IPr 3aa yield
92%
83%
81%
77%
Ph 21
0 mol% 10 mol% 20 mol% 50 mol%
Ph o-tolyl
Ph 22
Scheme 7. Reactions to probe possibility of radical reaction. Performing the catalytic reaction with 20 under similar reaction conditions furnished a good conversion of product 3aa in 72% yield, a sign that Ni(I) species was possible part of the intermediacy or resting state in this catalytic process (Scheme 8.2). Based on the recent seminal work on dinuclear system in the efficient nickel-catalyzed KumadaTamao-Corriu cross-coupling of aryl halide,28 we have reason to believe that the tentatively non-radical bimetallic mechanism could be the key for generating byproducts 5, 11 and 12 as illustrated in Scheme 9. Yet, Ni(0)-Ni(II) catalytic cycle cannot be rule out as a possibility at this stage. This minor amount of Ni(I) appeared in the catalytic reaction perhaps resulted from the comproportionation reaction between the mixture of Ni(0) and Ni(II) species.29 iPr N C (1)
Ni(PPh3)2Cl2
+
Ni(cod)2
N
iPr
N N
Ph3P Cl iPr Ni N C
N N iPr
N
90 %
20
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invoked between RMgBr and nickel is essential for not only lowering the activation energy barrier of the C‒O/C‒H cleavage but a more sterically demanding Grignard reagent is also important to suppressing the unproductive products in this reaction. Subsequently, the reductive elimination of complex V completes the catalytic cycle to deliver desired product 3aa. At this juncture, we also performed a series of intermolecular competition experiments with various aryl methyl ethers (Scheme 10). The results revealed that biphenyl 4h (36 %) was favorably functionalized, while the analogous 4p (6%) underwent low reactivity (Scheme 10.1). More importantly, we also observed similar result positively correlated with intermolecular competition reactions between 1a and 4a, in which the substrate bearing more π-conjugation reacted more favorably (Scheme 10.2). These results thus highlight that πcoordination of Ni complex with the assistance of Lewis acid is important to lower C‒O activation barrier. Moreover, Lewis acid promoted C‒O cleavage assisted by πcoordination with Ni complex has been well-documented in recent theoretical and experimental works by Chatani, Tobisu and Mori27 and many other related literatures.3e,4a,4e It should be noted that control experiments to test eletronic influnce arisen from substituents (Scheme 10.3) show no major difference between 4p and 4a in the yield of the reaction, indicating the slowest stage may not related to the oxidative addition of C‒O bond.17e Ln
(2)
N 2a
O + 1a
complex 20 10 mol% o-tolylMgBr 1.5 equiv 90 oC, 16 h 72 %
R
RMgBr(1a)2 I
I
Ni Ln
Ni Ln Ln
N H
R H
N
Mg 1a
N Ni N Ln III Mg 1a
Br
R
R
NiI
H II or III
R
Br
OMe
N N 2a
Ln Ni0 I
RMgBr(1a)2
1a
3aa
1a Ln
Ln Ni
N Ni
Mg
Me
N
V
N
O
N
Me O Mg
Br
1a
IV Br
1a
Scheme 9. Proposed mechanism of C‒H and C‒O activation. N OMe
OMe
N
N Ph
1.5 equiv 1.5 equiv
N
N
+
N
N
4p
4h
N
N 0.5 mmol Ni(cod)2 10 mol% C2-allene 10 mol% o-tolMgBr 1.5 equiv m-xylene, 90 oC, 45 mins
+
(1) Ph
N
1a
byproducts
II Ni
N 5ha
5pa
36%
6%
N
3aa
Scheme 8. CDC-Ni(I) complexes and the catalytic reaction. Taking into account of all mechanistic studies considerations, a general proposed mechanistic cycle is outlined in Scheme 9. The nickel-promoted deprotonation reaction of 1-methylbenzimidazole 2a with excess RMgBr affords the intermediate II, which undergoes C‒H activation step generating the complex III. The addition of 2methoxynaphthalene 1a to III would deliver a Ni(0) complex IV (see Figure S4 and Table S7 in SI for details),30 which can further be transformed to intermediate V via the oxidative addition step. Importantly, cooperative effect
OMe OMe (2)
+ 1a
4a
1.5 equiv
1.5 equiv
N
0.5 mmol
N
N
N
Ni(cod)2 10 mol% IPr 10 mol% o-tolMgBr 1.5 equiv m-xylene, 90 oC, 45 mins
+
N
N
3aa
5aa
34%
12%
0.5 mmol
N OMe
OMe (3)
+ H
N
4a
4p
Ni(cod)2 10 mol% C2-allene 10 mol% o-tolMgBr 1.5 equiv m-xylene, 90 oC, 45 mins
N H N
N N
+ N
5aa
5pa
24%
18%
1.5 equiv 1.5 equiv
Scheme 10. The intermolecular competition experiments.
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Finally, we also carried out an experiments, as illustrated in Scheme 11 to demostrate the high energy barrier in the reductive elimination step, which may required high temperature condition. In Scheme 11.1, we can witness a complete conversion of 2a to deuterium substituted-2a at slightly lower temperature 60 °C in presence of 1 equiv of Ni catalyst and ArMgBr for 45 minutes, a strong experimental evidence of a cooperative role of Ni and Grignard reagent in the C‒H and C‒O activation. At the same time, we also continued to heat the reaction at 90 °C for 45 minutes (see Scheme 11) to afford coupling product 3aa in 66% yield. With these results, it is no surprise to find out that the rate determining step of this catatytic reaction hinged on the C‒H/C‒O activtion is reductive elimination with high temperature. N H
(1)
N
Ni(cod)2, IPr (1 equiv) o-tolylMgBr (1 equiv)
N
D 2O
H 2a
N
100 %
N N
H
N
60 oC, 45 min
2a
(2)
N
D +
Ni(cod)2, IPr (1 equiv) o-tolylMgBr (1 equiv) LiCl (1 equiv) 60 oC, 45 min OMe (1 equiv)
90 oC 45 min
D 2O
0%
N D/H
+
3aa
N trace
66 %
Scheme 11. The experimental studies for establishing a possible rate determining step. CONCLUSION In summary, we have demonstrated nickel-catalyzed cross coupling reactions of inert methoxyarenes with heteroarene derivatives based on a tandem strategy of C– O/C–H activations. Mechanistic studies show that the Grignard reagent and nickel complex are responsible for not only the C‒H activation of heteroarene, but its critical role to minimize non-productive coupling in the C‒O bond transformation. Additionally, the single electron process is ruled out as main operative process for this tandem strategy, and Ni(I) is believed to be accountable for homo-coupling product via dimerization pathway. The influence of the catalyst/ligand and the mechanism and further scope of this prove-of-concept are the subject of ongoing studies in our group now.
ASSOCIATED CONTENT Supporting Information The Supporting Information is available free of charge via the Internet at http://pubs.acs.org. Detailed experimental procedures, characterization data, 1H and 13C NMR spectra of all compounds. Computational details, C‒H/C‒O activation mechanism, energies and coordinates of the optimized structures. The Supporting Information is available free of charge on the ACS Publications website.
AUTHOR INFORMATION Corresponding Author *
[email protected] *
[email protected] ORCID ID: Tiow-Gan Ong: 0000-0001-9817-6300
Author Contributions ¶These authors contributed equally to this work. All authors have given approval to the final version of the manuscript
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT This work was financially supported by the Ministry of Science & Technology of Taiwan (MOST-104-2628-M-001-005-MY4 grant) and Academia Sinica Career Development Award (104CDA-M08). L.Z is acknowledge the high performance center of Nanjing Tech University for supporting the computational resources, the financial support from Nanjing Tech University (grant number 39837123) and SICAM Fellowship from Jiangsu National Synergetic Innovation Center for Advanced Materials, Natural Science Foundation of Jiangsu Province for Youth (grant no: BK20170964), and National Natural Science Foundation of China (grant no. 21703099).
REFERENCES (1) (a) Tobisu, M.; Chatani, N. Cross-Couplings Using Aryl Ethers via C–O Bond Activation Enabled by Nickel Catalysts. Acc. Chem. Res. 2015, 48, 1717-1726. (b) Zeng, H.; Qiu, Z.; DomínguezHuerta, A.; Hearne, Z.; Chen, Z.; Li, C.-J. An Adventure in Sustainable Cross-Coupling of Phenols and Derivatives via Carbon–Oxygen Bond Cleavage. ACS Catal. 2017, 7, 510-519. (c) Yamaguchi, J.; Muto, K.; Itami, K. Nickel-Catalyzed Aromatic C– H Functionalization. Top. Curr. Chem. 2016, 374, 55. (d) Tasker, S. Z.; Standley, E. A.; Jamison, T. F. Recent Advances in Homogeneous Nickel Catalysis. Nature 2014, 509, 299-309. (e) Wenkert, E.; Michelotti, E. L.; Swindell, C. S., Nickel-Induced Conversion of Carbon-Oxygen into Carbon-Carbon Bonds. OneStep Transformations of Enol Ethers into Olefins and Aryl Ethers into Biaryls. J. Am. Chem. Soc. 1979, 101, 2246-2247. (2) (a) Antoft-Finch, A.; Blackburn, T.; Snieckus, V. N,N-Diethyl O-Carbamate: Directed Metalation Group and Orthogonal Suzuki−Miyaura Cross-Coupling Partner. J. Am. Chem. Soc. 2009, 131, 17750-17752. (b) Hie, L.; Ramgren, S. D.; Mesganaw, T.; Garg, N. K. Nickel-Catalyzed Amination of Aryl Sulfamates and Carbamates Using an Air-Stable Precatalyst. Org. Lett. 2012, 14, 4182-4185. (c) Huang, K.; Yu, D.-G.; Zheng, S.-F.; Wu, Z.-H.; Shi, Z.-J. Borylation of Aryl and Alkenyl Carbamates through Ni‐Catalyzed C–O Activation. Chem. Eur. J. 2011, 17, 786-791. (d) Mesganaw, T.; Silberstein, A. L.; Ramgren, S. D.; Nathel, N. F. F.; Hong, X.; Liu, P.; Garg, N. K. Nickel-Catalyzed Amination of Aryl Carbamates and Sequential Site-Selective Cross-Couplings. Chem. Sci. 2011, 2, 1766-1771. (e) Muto, K.; Hatakeyama, T.; Yamaguchi, J.; Itami, K. C–H Arylation and Alkenylation of Imidazoles by Nickel Catalysis: Solvent-Accelerated Imidazole C– H Activation. Chem. Sci. 2015, 6, 6792-6798. (f) Ohtsuki, A.; Yanagisawa, K.; Furukawa, T.; Tobisu, M.; Chatani, N. Nickel/NHeterocyclic Carbene-Catalyzed Suzuki–Miyaura Type CrossCoupling of Aryl Carbamates. J. Org. Chem. 2016, 81, 9409-9414. (g) Quasdorf, K. W.; Riener, M.; Petrova, K. V.; Garg, N. K.
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Suzuki−Miyaura Coupling of Aryl Carbamates, Carbonates, and Sulfamates. J. Am. Chem. Soc. 2009, 131, 17748-17749. (3) (a) Cornella, J.; Jackson, E. P.; Martin, R. Nickel-Catalyzed Enantioselective C‒C Bond Formation through Csp2‒O Cleavage in Aryl Esters. Angew. Chem., Int. Ed. 2015, 54, 4075-4078. (b) Guan, B.-T.; Wang, Y.; Li, B.-J.; Yu, D.-G.; Shi, Z.-J. Biaryl Construction via Ni-Catalyzed C−O Activation of Phenolic Carboxylates. J. Am. Chem. Soc. 2008, 130, 14468-14470. (c) Li, B.-J.; Xu, L.; Wu, Z.H.; Guan, B.-T.; Sun, C.-L.; Wang, B.-Q.; Shi, Z.-J. CrossCoupling of Alkenyl/Aryl Carboxylates with Grignard Reagent via Fe-Catalyzed C−O Bond Activation. J. Am. Chem. Soc. 2009, 131, 14656-14657. (d) Meng, L.; Kamada, Y.; Muto, K.; Yamaguchi, J.; Itami, K. C–H Alkenylation of Azoles with Enols and Esters by Nickel Catalysis. Angew. Chem., Int. Ed. 2013, 52, 10048-10051. (e) Quasdorf, K. W.; Tian, X.; Garg, N. K. Cross-Coupling Reactions of Aryl Pivalates with Boronic Acids. J. Am. Chem. Soc. 2008, 130, 14422-14423. (f) Takise, R.; Muto, K.; Yamaguchi, J.; Itami, K. Nickel-Catalyzed -Arylation of Ketones with Phenol Derivatives. Angew. Chem., Int. Ed. 2014, 53, 6791-6794. (4) (a) Dankwardt, J. W. Nickel‐Catalyzed Cross‐Coupling of Aryl Grignard Reagents with Aromatic Alkyl Ethers: An Efficient Synthesis of Unsymmetrical Biaryls. Angew. Chem., Int. Ed. 2004, 43, 2428-2432. (b) Guan, B.-T.; Xiang, S.-K.; Wu, T.; Sun, Z.-P.; Wang, B.-Q.; Zhao, K.-Q.; Shi, Z.-J. Methylation of Arenes via NiCatalyzed Aryl C–O/F Activation. Chem. Commun. 2008, 14371439. (c) Leiendecker, M.; Hsiao, C.-C.; Guo, L.; Alandini, N.; Rueping, M. Metal‐Catalyzed Dealkoxylative Caryl-Csp2 Cross‐Coupling—Replacement of Aromatic Methoxy Groups of Aryl Ethers by Employing a Functionalized Nucleophile. Angew. Chem., Int. Ed. 2014, 53, 12912-12915. (d) Liu, X.; Hsiao, C.-C.; Kalvet, I.; Leiendecker, M.; Guo, L.; Schoenebeck, F.; Rueping, M. Lewis Acid Assisted Nickel‐Catalyzed Cross‐Coupling of Aryl Methyl Ethers by C−O Bond‐Cleaving Alkylation: Prevention of Undesired ‐Hydride Elimination. Angew. Chem., Int. Ed. 2016, 55, 6093-6098. (e) Tobisu, M.; Shimasaki, T.; Chatani, N. NickelCatalyzed Cross-Coupling of Aryl Methyl Ethers with Aryl Boronic esters. Angew. Chem., Int. Ed. 2008, 47, 4866-4869. (f) Tobisu, M.; Takahira, T.; Chatani, N. Nickel-Catalyzed CrossCoupling of Anisoles with Alkyl Grignard Reagents via C–O Bond Cleavage. Org. Lett. 2015, 17, 4352-4352. (g) Tobisu, M.; Takahira, T.; Morioka, T.; Chatani, N. Nickel-Catalyzed Alkylative Cross-Coupling of Anisoles with Grignard Reagents via C–O Bond Activation. J. Am. Chem. Soc. 2016, 138, 6711-6714. (h) Tobisu, M.; Takahira, T.; Ohtsuki, A.; Chatani, N. Nickel-Catalyzed Alkynylation of Anisoles via C–O Bond Cleavage. Org. Lett. 2015, 17, 680-683. (i) Tobisu, M.; Yasutome, A.; Kinuta, H.; Nakamura, K.; Chatani, N. 1,3-Dicyclohexylimidazol-2-ylidene as a Superior Ligand for the Nickel-Catalyzed Cross-Couplings of Aryl and Benzyl Methyl Ethers with Organoboron Reagents. Org. Lett. 2014, 16, 5572-5575. (j) Tobisu, M.; Yasutome, A.; Yamakawa, K.; Shimasaki, T.; Chatani, N. Ni(0)/NHC-Catalyzed Amination of N-Heteroaryl Methyl Ethers Through the Cleavage of Carbon‒Oxygen Bonds. Tetrahedron 2012, 68, 5157-5161. (k) Wang, C.; Ozaki, T.; Takita, R.; Uchiyama, M. Aryl Ether as a Negishi Coupling Partner: An Approach for Constructing C–C Bonds under Mild Conditions. Chem. Eur. J. 2012, 18, 3482-3485. (l) Yang, Z.-K.; Wang, D.-Y.; Minami, H.; Ogawa, H.; Ozaki, T.; Saito, T.; Miyamoto, K.; Wang, C.; Uchiyama, M. Cross‐Coupling of Organolithium with Ethers or Aryl Ammonium Salts by C−O or C−N Bond Cleavage. Chem. Eur. J. 2016, 22, 15693-15699. (m) Yue, H.; Guo, L.; Liu, X.; Rueping, M. Nickel-Catalyzed Synthesis of Primary Aryl and Heteroaryl Amines via C–O Bond Cleavage. Org. Lett. 2017, 19, 1788-1791. (n) Zarate, C.; Manzano, R.; Martin, R. Ipso-Borylation of Aryl Ethers via Ni-Catalyzed C– OMe Cleavage. J. Am. Chem. Soc. 2015, 137, 6754-6757. (5) (a) Iranpoor, N.; Panahi, F. Direct Nickel‐Catalyzed Amination of Phenols via C–O Bond Activation using
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2,4,6‐Trichloro‐1,3,5‐triazine (TCT) as Reagent. Adv. Synth. Catal. 2014, 356, 3067-3073. (b) Yu, D.-G.; Li, B.-J.; Zheng, S.-F.; Guan, B.-T.; Wang, B.-Q.; Shi, Z.-J. Direct Application of Phenolic Salts to Nickel‐Catalyzed Cross‐Coupling Reactions with Aryl Grignard Reagent. Angew. Chem., Int. Ed. 2010, 49, 4566-4570. (c) Yu, D.G.; Shi, Z.-J. Mutual Activation: Suzuki-Miyaura Coupling through Direct Cleavage of the sp2 C–O Bond of Naphtholate. Angew. Chem., Int. Ed. 2011, 50, 7097-7100. (d) Zhang, S.-S.; Jiang, C.-Y.; Wu, J.-Q.; Liu, X.-G.; Li, Q.; Huang, Z.-S.; Li, D.; Wang, H. Cp*Rh(III) and Cp*Ir(III)-Catalysed Redox-Neutral C– H Arylation with Quinone Diazides: Quick and Facile Synthesis of Arylated Phenols. Chem. Commun. 2015, 51, 10240-10243. (6) (a) Yu, M.-S.; Lee, W.-C.; Chen, C.-H.; Tsai, F.-Y.; Ong, T.-G. Controlled Regiodivergent C–H Bond Activation of Imidazo[1,5a]pyridine via Synergistic Cooperation between Aluminum and Nickel. Org. Lett. 2014, 16, 4826-4829. (b) Shih, W.-C.; Chen, W.C.; Lai, Y.-C.; Yu, M.-S.; Ho, J.-J.; Yap, G. P. A.; Ong, T.-G. The Regioselective Switch for Amino-NHC Mediated C–H Activation of Benzimidazole via Ni–Al Synergistic Catalysis. Org. Lett. 2012, 14, 2046-2049. (c) Lee, W.-C.; Wang, C.-H.; Lin, Y.-H.; Shih, W.C.; Ong, T.-G. Tandem Isomerization and C–H Activation: Regioselective Hydroheteroarylation of Allylarenes. Org. Lett. 2013, 15, 5358-5361. (d) Huang, H.-J.; Lee, W.-C.; Yap, G. P. A.; Ong, T.-G. Synthesis and Characterization of Amino-NHC Coinage Metal Complexes and Application for C–H Activation of Caffeine. J. Organomet. Chem. 2014, 761, 64-73. (e) Chen, W.-C.; Lai, Y.-C.; Shih, W.-C.; Yu, M.-S.; Yap, G. P. A.; Ong, T.-G. Mechanistic Study of a Switch in the Regioselectivity of Hydroheteroarylation of Styrene Catalyzed by Bimetallic Ni–Al through C‒H Activation. Chem. Eur. J. 2014, 20, 8099-8105. (f) Lee, W.-C.; Chen, C.-H.; Liu, C.-Y.; Yu, M.-S.; Lin, Y.-H.; Ong, T.-G. Nickel-catalysed para-CH Activation of Pyridine with Switchable Regioselective Hydroheteroarylation of Allylarenes. Chem. Commun. 2015, 51, 17104-17107. (g) Chen, W.-C.; Hsu, Y.C.; Shih, W.-C.; Lee, C.-Y.; Chuang, W.-H.; Tsai, Y.-F.; Chen, P. P.-Y.; Ong, T.-G. Metal-Free Arylation of Benzene and Pyridine Promoted by Amino-Linked Nitrogen Heterocyclic Carbenes. Chem. Commun. 2012, 48, 6702-6704. (h) Wang, T.-H.; Lee, W.C.; Ong, T.-G. Ruthenium‐Mediated Dual Catalytic Reactions of Isoquinoline via C−H Activation and Dearomatization for Isoquinolone. Adv. Synth. Catal. 2016, 358, 2751-2758. (7) Muto, K.; Yamaguchi, J.; Itami, K. Nickel-Catalyzed C–H/C– O Coupling of Azoles with Phenol Derivatives. J. Am. Chem. Soc. 2012, 134, 169-172. (8) Wang, Y.; Wu, S.-B.; Shi, W.-J.; Shi, Z.-J. C–O/C–H Coupling of Polyfluoroarenes with Aryl Carbamates by Cooperative Ni/Cu Catalysis. Org. Lett. 2016, 18, 2548-2551. (9) Tobisu, M.; Yasui, K.; Aihara, Y.; Chatani, N. C−O Activation by a Rhodium Bis(N‐Heterocyclic Carbene) Catalyst: Aryl Carbamates as Arylating Reagents in Directed C−H Arylation. Angew. Chem., Int. Ed. 2017, 56, 1877-1880. (10) Song, W.; Ackermann, L. Cobalt‐Catalyzed Direct Arylation and Benzylation by C‒H/C‒O Cleavage with Sulfamates, Carbamates, and Phosphates. Angew. Chem., Int. Ed. 2012, 51, 8251-8254. (11) Krasovskiy, A.; Knochel, P. A LiCl‐Mediated Br/Mg Exchange Reaction for the Preparation of Functionalized Aryl‐ and Heteroarylmagnesium Compounds from Organic Bromides.. Angew. Chem., Int. Ed. 2004, 43, 3333-3336. (12) Chen, W.-C.; Shen, J.-S.; Jurca, T.; Peng, C.-J.; Lin, Y.-H.; Wang, Y.-P.; Shih, W.-C.; Yap, G. P. A.; Ong, T.-G. Expanding the Ligand Framework Diversity of Carbodicarbenes and Direct Detection of Boron Activation in the Methylation of Amines with CO2. Angew. Chem., Int. Ed. 2015, 54, 15207-15212. (13) Venkateswararao, A.; Thomas, K. R. J.; Lee, C.-P.; Li, C.-T.; Ho, K.-C. Organic Dyes Containing Carbazole as Donor and
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πLinker: Optical, Electrochemical, and Photovoltaic Properties. ACS Appl. Mater. Interfaces 2014, 6, 2528-2539. (14) (a) Baheti, A.; Lee, C.-P.; Thomas, K. R. J.; Ho, K.-C. Pyrenebased Organic Dyes with Thiophene Containing π-Linkers for DyeSensitized Solar Cells: Optical, Electrochemical and Theoretical Investigations. Phys. Chem. Chem. Phys. 2011, 13, 17210-17221. (b) Saritha, G.; Wu, J. J.; Anandan, S. Modified Pyrene based Organic Sensitizers with Thiophene-2-Acetonitrile as π-Spacer for Dye Sensitized Solar Cell Applications. Org. Electron. 2016, 37, 326-335. (15) Tang, Z.-M.; Lei, T.; Jiang, K.-J.; Song, Y.-L.; Pei, Benzothiadiazole Containing D‐π‐A Conjugated Compounds for Dye‐Sensitized Solar Cells: Synthesis, Properties, and Photovoltaic Performances. J. Chem. Asian J. 2010, 5, 1911-1917. (16) See supporting information for further information. (17) (a) Wisniewska, H. M.; Swift, E. C.; Jarvo, E. R. FunctionalGroup-Tolerant, Nickel-Catalyzed Cross-Coupling Reaction for Enantioselective Construction of Tertiary Methyl-Bearing Stereocenters. J. Am. Chem. Soc. 2013, 135, 9083-9090. (b) Zhou, Q.; Srinivas, H. D.; Dasgupta, S.; Watson, M. P. Nickel-Catalyzed Cross-Couplings of Benzylic Pivalates with Arylboroxines: Stereospecific Formation of Diarylalkanes and Triarylmethanes. J. Am. Chem. Soc. 2013, 135, 3307-3310. (c) Taylor, B. L.; Harris, M. R.; Jarvo, E. R. Synthesis of Enantioenriched Triarylmethanes by Stereospecific Cross‐Coupling Reactions. Angew. Chem., Int. Ed. 2012, 51, 7790-7793. (d) Yu, D.-G.; Shi, Z.-J. Mutual Activation: Suzuki-Miyaura Coupling through Direct Cleavage of the sp2 C–O Bond of Naphtholate. Angew. Chem., Int. Ed. 2011, 50, 7097-7100. (e)Tobisu, M.; Shimasaki, T.; Chatani, N. NickelCatalyzed Cross-Coupling of Aryl Methyl Ethers with ArylBoronic Esters. Angew. Chem., Int. Ed. 2008, 47, 4866-4869. (18) Bauer, D. J.; Krueger, C. Bonding of Aromatic Hydrocarbons to Nickel(0). Structure of bis(Tricyclohexylphosphine)(1,2-.eta.2anthracene)Nickel(0)-Toluene. Inorg. Chem. 1977, 16, 884-891. (19) Gellis, A.; Kovacic, H.; Boufatah, N.; Vanelle, P. Synthesis and Cytotoxicity Evaluation of Some Benzimidazole-4,7-Diones as Bioreductive Anticancer Agents. Eur. J. Med. Chem. 2008, 43, 1858-1864. (20) Shin, Y.; Suchomel, J.; Cardozo, M.; Duquette, J.; He, X.; Henne, K.; Hu, Y.-L.; Kelly, R. C.; McCarter, J.; McGee, L. R.; Medina, J. C.; Metz, D.; San Miguel, T.; Mohn, D.; Tran, T.; Vissinga, C.; Wong, S.; Wannberg, S.; Whittington, D. A.; Whoriskey, J.; Yu, G.; Zalameda, L.; Zhang, X.; Cushing, T. D. Discovery, Optimization, and in Vivo Evaluation of Benzimidazole Derivatives AM-8508 and AM-9635 as Potent and Selective PI3K δ Inhibitors. J. Med. Chem. 2016, 59, 431-447. (21) (a) Ge, Z.; Hayakawa, T.; Ando, S.; Ueda, M.; Akiike, T.; Miyamoto, H.; Kajita, T.; Kakimoto, M.-a. Solution-Processible Bipolar Triphenylamine-Benzimidazole Derivatives for Highly Efficient Single-Layer Organic Light-Emitting Diodes. Chem. Mater. 2008, 20, 2532-2537. (b) Han, Y.; Cao, H.-T.; Sun, H.-Z.; Wu, Y.; Shan, G.-G.; Su, Z.-M.; Hou, X.-G.; Liao, Y. Effect of Alkyl Chain Length on Piezochromic Luminescence of Iridium(III)-based Phosphors Adopting 2-Phenyl-1HBenzoimidazole Type Ligands. J. Mater. Chem. C 2014, 2, 76487655. (22) Muto, K.; Hatakeyama, T.; Yamaguchi, J.; Itami, K. C–H Arylation and Alkenylation of Imidazoles by Nickel Catalysis: Solvent-Accelerated iImidazole C–H a\Activation. Chem. Sci. 2015, 6, 6792-6798. (23) Wang, T.; Liang, Y.; Yu, Z.-X. Density Functional Theory Study of the Mechanism and Origins of Stereoselectivity in the Asymmetric Simmons–Smith Cyclopropanation with Charette Chiral Dioxaborolane Ligand. J. Am. Chem. Soc. 2011, 133, 93439353.
(24) (a) Manolikakes, G.; Knochel, P. Radical Catalysis of Kumada Cross‐Coupling Reactions Using Functionalized Grignard Reagents. Angew. Chem.,Int. Ed. 2009, 48, 205-209. (b) Ford, L.; Jahn, U. Radicals and Transition‐Metal Catalysis: An Alliance Par Excellence to Increase Reactivity and Selectivity in Organic Chemistry. Angew. Chem., Int. Ed. 2009, 48, 6386-6389. (c) Gao, C.-Y.; Cao, X.; Yang, L.-M. Nickel-Catalyzed Cross-Coupling of Diarylamines with Haloarenes. Org. Biomol. Chem. 2009, 7, 39223925. (d) Jones, G. D.; McFarland, C.; Anderson, T. J.; Vicic, D. A. Analysis of Key Steps in the Catalytic Cross-Coupling of Alkyl Electrophiles under Negishi-like Conditions. Chem. Commun. 2005, 4211-4213. (e) Jones, G. D.; Martin, J. L.; McFarland, C.; Allen, O. R.; Hall, R. E.; Haley, A. D.; Brandon, R. J.; Konovalova, T.; Desrochers, P. J.; Pulay, P.; Vicic, D. A. Ligand Redox Effects in the Synthesis, Electronic Structure, and Reactivity of an Alkyl−Alkyl Cross-Coupling Catalyst. J. Am. Chem. Soc. 2006, 128, 13175-13183. (f) Ren, P.; Vechorkin, O.; von Allmen, K.; Scopelliti, R.; Hu, X. A Structure–Activity Study of Ni-Catalyzed Alkyl–Alkyl Kumada Coupling. Improved Catalysts for Coupling of Secondary Alkyl Halides. J. Am. Chem. Soc. 2011, 133, 70847095. (g) Breitenfeld, J.; Ruiz, J.; Wodrich, M. D.; Hu, X. Bimetallic Oxidative Addition Involving Radical Intermediates in Nickel-Catalyzed Alkyl–Alkyl Kumada Coupling Reactions. J. Am. Chem. Soc. 2013, 135, 12004-12012. (25) The TEMPO generated homocoupling Ar-Ar product from ArMgBr has beeen reported by Studer grop. (a) Sudan, M. M.; Thorben, P.; Armido, S. Oxidative Homocoupling of Aryl, Alkenyl, and Alkynyl Grignard Reagents with TEMPO and Dioxygen.. Angew. Chem., Int. Ed. 2008, 47, 9547-9550. However, no anagalous homocoupling product derived from steric hinderance o-tolylMgBr has been not observed in this catalytic reaction with TEMPO addition. Similar result is obtained in Studer’s study. (b) Murarka, S.; Mobus, J.; Erker, G.; Muck-Lichtenfeld, C.; Studer, A. TEMPO-Mediated Homocoupling of Aryl Grignard Reagents: Mechanistic Studies. Org. Biomol. Chem. 2015, 13, 2762-2767. (26) Ni, S.; Zhang, W.; Mei, H.; Han, J.; Pan, Y. Ni-Catalyzed Reductive Cross-Coupling of Amides with Aryl Iodide Electrophiles via C–N Bond Activation. Org. Lett. 2017, 19, 25362539. (27) (a) Schwarzer, M. C.; Konno, R.; Hojo, T.; Ohtsuki, A.; Nakamura, K.; Yasutome, A.; Takahashi, H.; Shimasaki, T.; Tobisu, M.; Chatani, N.; Mori, S. Combined Theoretical and Experimental Studies of Nickel-Catalyzed Cross-Coupling of Methoxyarenes with Arylboronic Esters via C–O Bond Cleavage. J. Am. Chem. Soc. 2017, 139, 10347-10358. (b) Takise, R.; Itami, K.; Yamaguchi, J. Cyanation of Phenol Derivatives with Aminoacetonitriles by Nickel Catalysis. Org. Lett. 2016, 18, 44284431. (28) Matsubara, K.; Yamamoto, H.; Miyazaki, S.; Inatomi, T.; Nonaka, K.; Koga, Y.; Yamada, Y.; Veiros, L. F.; Kirchner, K. Dinuclear Systems in the Efficient Nickel-Catalyzed Kumada– Tamao–Corriu Cross-Coupling of Aryl Halides. Organometallics 2017, 36, 255-265. (29) Miyazaki, S.; Koga, Y.; Matsumoto, T.; Matsubara, K. A New Aspect of Nickel-Catalyzed Grignard Cross-Coupling Reactions: Selective Synthesis, Structure, and Catalytic Behavior of a T-shape Three-Coordinate Nickel(I) Chloride Bearing a Bulky NHC Ligand. Chem. Commun. 2010, 46, 1932-1934. (30) Ogawa, H.; Minami, H.; Ozaki, T.; Komagawa, S.; Wang, C.; Uchiyama, M. How and Why Does Ni(0) Promote Smooth Etheric C‒O Bond Cleavage and C‒C Bond Formation? A Theoretical Study. Chem. Eur. J. 2015, 21, 13904-13908.
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N H N +
O
Ni(cod)2 10 mol% IPr 10 mol% Ar-MgBr 1 equiv LiCl 1 equiv m-xylene
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N
N
+
N 92%
Ar N
Kumuda coupling product
60 examples
Not observed
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