Ni-Catalyzed Cross-Coupling of Dimethyl Aryl Amines with Arylboronic Esters under Reductive Conditions

Article abstract of DOI:10.1021/jacs.8b08779

Herein, we reported a successful Suzuki-Miyaura coupling of dimethyl aryl amines to forge biaryl skeleton via Ni catalysis in the absence of directing groups and preactivation. This transformation proceeded with high efficiency in the presence of magnesium. Preliminary mechanism studies demonstrated dual roles of magnesium: (i) a reductant that reduced Ni(II) species to active Ni(I) catalyst; (ii) a unique promoter that facilitated the Ni(I)/Ni(III) catalytic cycle.

Full text of DOI:10.1021/jacs.8b08779

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Communication
Ni-Catalyzed Cross-Coupling of Dimethyl Aryl Amines
with Aryl-boronic Esters under Reductive Conditions
Zhi-Chao Cao, Si-Jun Xie, Huayi Fang, and Zhang-Jie Shi
J. Am. Chem. Soc., Just Accepted Manuscript • Publication Date (Web): 05 Oct 2018
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Ni-Catalyzed Cross-Coupling of Dimethyl Aryl Amines with Aryl-
boronic Esters under Reductive Conditions
Zhi-Chao Caoa,b, Si-Jun Xiea, Huayi Fang*a, and Zhang-Jie Shi*a,b,c
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a Department of Chemistry, Fudan University, Shanghai 200433, b College of Chemistry and Molecular Engineering, Peking
University, Beijing 100871 and c State Key Laboratory of Organometallic Chemistry, Chinese Academy of Science, Shang-
hai 200032, China
Supporting Information Placeholder
of dimethyl aryl amines without directing group. Herein, we re-
ABSTRACT: Herein, we reported a successful Suzuki-Miyaura
ported the successful catalytic Suzuki-Miyaura coupling of unmod-
ified dimethyl aryl amines via Ni-catalysis under reductive condi-
tions (Scheme 1c).
coupling of dimethyl aryl amines to forge biaryl skeleton via Ni
catalysis in the absence of directing groups and preactivation. This
transformation proceeded with high efficiency in the presence of
magnesium. Preliminary mechanism studies demonstrated dual
roles of magnesium: i) a reductant that reduce Ni(II) species to ac-
tive Ni(I) catalyst; ii) an unique promoter that facilitate the
Ni(I)/Ni(III) catalytic cycle.
N,N-dialkyl aryl amine is an important structural motif in nat-
ural and synthetic world, and is found as core structural unit in
many natural products, pharmaceuticals and organic materials.1 At
current stage, although a myriad of methods, such as Ullmann cou-
pling reaction,2 Buchwald-Hartwig amination,3 and C-H amina-
tion,4 on aromatic C-N bond construction have been well developed
(Scheme 1a),5 the reactivity pattern of N,N-dialkyl aryl amine is
rarely investigated due to its thermodynamic and kinetic stability,
as well as strong coordinating ability of both substrates and in-situ
generated amides.6 For example, transition-metal catalyzed direct
carbon-carbon forming cross-coupling of N,N-dialkyl aryl amines
in the absence of directing group and preactivation has not been
achieved so far. Triggered by the easy availability and the interest
on widening the synthetic application of N,N-dimethyl aryl amines,
we intended to explore the new transformation of N,N-dimethyl
aryl amines through C-C bond forming cross-coupling reaction
based on transition-metal catalyzed direct aromatic C-N activation.
This research was also beneficial for understanding the intrinsic re-
activity of aromatic C-N bond of dialkyl aryl amines.
Scheme 1. Proposal for Ni-catalyzed Suzuki-Miyaura cou-
pling (SMC) reaction of dimethyl aryl amines
To initiate the designed Suzuki-Miyaura coupling reaction, N,N-
dimethyl-2-naphthalenamine (1) and phenylboronic acid neopen-
tylglycol ester (PhBnep) (2) were chosen as coupling partners to
optimize the reaction conditions (Table 1). After extensive exami-
nation of different reaction parameters, a cocktail containing NiBr2
(10 mol%) as the catalyst, IMesMe (35 mol%) as the ligand, and
magnesium (3.0 equivalent) as the additive in THF at 135 oC facil-
itated the desired cross-coupling and the product 3 was detected in
84% NMR yield (entry 1). Control experiments clearly demon-
strated the crucial roles of the catalyst, ligand, and magnesium for
keeping the coupling efficiency (entries 2-4). Interestingly,
Ni(cod)2 and NiBr2(DME), which were both proved active catalysts
in the reported works on inert C-O and C-N bond activation, pro-
vided the desired product 3 in much lower yields (entries 5 and
6).8b-e, 8g, 8h, 12 The effects of various ligands were also carefully in-
vestigated. Other ligands, including PCy3, IPr, IMes, and SIMes,
were submitted to the transformation to replace IMesMe, but all re-
sulted lower efficiency (entries 7-11).13 We also attempted to use
the combination of IMesMe(HCl) (35 mol%) and tBuOK (35 mol%)
as the ligand to replace prepared IMesMe, while no desired product
Given the commercial availability, stability, and non-toxicity
of organoboron reagents, transition-metal catalyzed Suzuki-
Miyaura coupling of dimethyl aryl amines would be a suitable start-
ing point for achieving the aforementioned goals.7 During the past
decades, the Suzuki-Miyaura coupling reaction has been used as a
powerful method to construct carbon-carbon bond from aryl hal-
ides and various O-based electrophiles.8 Some activated N-based
electrophiles were also successfully applied into Suzuki-Miyaura
coupling.9 For example, the cross-coupling reactions of quaternary
ammonium via transition-metal catalysis have been well docu-
mented.10 Recently, with the assistance of directing group, Kakiu-
chi and co-workers pioneered the research by using N,N-dimethyl
aryl amine to construct C-C bonds through Ru-catalyzed Suzuki-
Miyaura coupling. However, frequently encountered dimethyl
amino group containing substrates without ortho-directing group
remained untouched (Scheme 1b).11 To the best of our knowledge,
there was no reported protocol for direct Suzuki-Miyaura coupling
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was obtained, which might arise from the presence of tBuOH (en-
try 12). Different organoboron reagents were also examined, but
proved unsuitable coupling partners (entries 13-14). The examina-
tion of solvent effect indicated that non-polar solvents were unsuit-
able for this transformation (entry 15). CsF, which was frequently
used as an additive in Suzuki-Miyaura couplings, terminated this
transformation (entry 16).10a
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Table 1. Optimization of reaction conditions a
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Notes: a NMR yields were reported using CH2Br2 as the internal standard, iso-
lated yield in the parenthesis; b 35 mol% tBuOK was added; c (PhBO)3 0.83 mmol.
With the optimal conditions in hand, the substrate scope was in-
vestigated. Firstly, we tested the reactivity of different dimethyl
aryl amines (Figure 1). Arylation of substrates with different alkyl
substituents were conducted, and the targeted products were ob-
tained in good yields (3-6). Arylation of substrate bearing the
strained cyclopropyl ring was conducted, and the targeted product
was obtained in a good yield (7).14 A collection of functional
groups, such as ether and ketal, were found compatible (8-10). To
our delight, alkyl-boronyl was also well tolerated (10), providing
the potential for orthogonal functionalization to build up complex
molecules.7 The reactivity of other N,N-dimethyl amines were also
investigated. For example, the arylation of N,N-dimethyl-1-naph-
thylamine and N,N-dimethylphenanthren-9-amine were conducted
and furnished the desired products in moderate yields (11-13). Nev-
ertheless, the steric hindrance at ortho-position would decrease the
efficiency severely (12). The conversion of biphenyl derivatives
were also investigated, and the corresponding products were ob-
tained in satisfactory yields (14 and 15). Simple tertiary aniline was
also tested, but presented low conversion at current stage (16). In-
terestingly, the substrate 17, which presented high reactivity in the
reported borylation protocol, exhibited a relatively low effi-
ciency.12b
a isolated yields were reported; b NMR yield; c 46% phenanthrene was obtained;
d 48 h.
Table 2. Examination of different metals or reductants a
entry
metal or reductant
magnesium
zinc
Loading (equiv.)
yield
84%
0%
1
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3
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5
6
7
3.0
3.0
3.0
6.0
3.0
3.0
6.0
manganese
sodium
0%
0%
aluminum
tin
0%
0%
Cp2Co
0%
a 1H-NMR yields were reported using CH2Br2 as the internal standard.
Subsequently, the reactivity of different arylboronates were
investigated. In general, the arylboronates bearing different alkyl
substituents were proved suitable nucleophiles (18-21). Aryl-
boronates containing phenyl substituents were also successful in
the preparation of tri-aryl skeleton (22 and 25). Although a number
of para- and meta- substituted arylboronates were successfully
coupled (18-25), the ortho-substituted ones failed, probably caused
by their steric hindrance. It is worthy to note that, aromatic C-B
bond was superior to couple with substrate 1 than that of the aro-
matic C-Si bond (23). Moreover, the coupling of substrate 1 with
di-substituted arylboronates smoothly delivered the biaryl com-
pound in high yield (26). Unfortunately, at current stage, the effi-
cient transformation of vinylboronate was not viable (27).
On the basis of the optimization experiments, we found that mag-
nesium, which was usually used as a reductant in the transition-
metal catalyzed reductive cross-coupling reaction, was crucial to
promote such a Ni catalyzed transformation in high efficiency. To
our surprise, other metals with different reductive potentials, such
as zinc (Zn), manganese (Mn), sodium (Na), aluminum (Al), and
tin (Sn) were used as the alternatives to replace magnesium (Mg),
while no desired product 3 was observed and the substrate 1 were
recovered (Table 2, entries 2-6).15 Cobaltocene (Cp2Co),16 a com-
mon one-electron reducing agent, was also submitted to the cata-
lytic cycle, while failed to promote the conversion of substrate 1
(Table 2, entry 7).
Figure 1. Catalytic SMC reaction of dimethyl aryl amines a
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THF heated at 135 oC for 6 hours and the photo of the sample (in-
serted).
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Experiments to identify the Ni(I)/Ni(III) pathway was also con-
ducted. Electron paramagnetic resonance (EPR) measurement at 10
K of the sampled reaction mixture of Ni(II)Br2, IMesMe and mag-
nesium, which was allowed to react at 135 oC in THF for 6 h prior
to the EPR measurement, showed an axial type signal with clear
hyperfine coupling from bromide atom (Figure 2). The g-values (g
⊥=2.461 and g∥=2.010) and A values (A⊥=111.3 MHz and A∥
=253.9 MHz) were obtained by the simulation of the experimental
spectrum using Easyspin toolbox.19 Density functional theory cal-
culation of (IMesMe)2Ni(I)Br, which displayed a slightly distorted
T-shape coordination geometry, reproduced the axial pattern of g-
values (g1=2.264, g2=2.237 and g3=2.042), and the hyperfine split-
ting constants of bromide atom (A1=115.0 MHz, A2=117.0 MHz
and A3=249.1 MHz) were very comparable to that of the experi-
mental values. The DFT calculation of (IMesMe)Ni(I)Br, another
possible candidate for the key intermediate of the catalytic cycle,
was also conducted, the calculated g (featuring rhombic pattern as
g1=2.625, g2=2.381 and g3=2.175) and A (A1=0.8 MHz, A2=1.0
MHz and A3=8.7 MHz) values were quite different from the exper-
imental results. Therefore, the observed paramagnetic species was
assigned as (IMesMe)2Ni(I)Br. Mulliken population analysis re-
vealed that 88.4% of the total spin density was localized on the Ni
center in (IMesMe)2Ni(I)Br, while considerable amount unpaired
electron was found on Br atom (5.8%). In comparison, nearly all
spin density was localized on Ni center (105.0%) and negligible
amount of unpaired electron was found on Br atom (-0.5%) for
(IMesMe)Ni(I)Br, thus should result in a undistinguishable hyper-
fine splitting of Br atom. Furthermore, a identical but weaker EPR
signal was also detected for the sample of the standard reaction pro-
cess, providing the solid evidence for Ni(I)/Ni(III) catalytic cycle
(see SI for details).
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Preliminary mechanism studies were conducted to elucidate the
active species in this catalytic system. As Ni(0)/Ni(II) catalytic cy-
cles were previously proposed for a series of coupling reactions,17
both (IMesMe)2Ni(0) and (IMesMe)2Ni(II)Br2 were prepared and
tested as the catalysts in the coupling reaction, unfortunately, no
product 3 was detected (eq. 1). The addition of Mg could improve
the efficiency, for example, the product 3 was observed in 53%
NMR yield for (IMesMe)2Ni(0) and 83% NMR yield for
(IMesMe)2Ni(II)Br2. Since the yield of phenylation by using Ni(0)
catalyst was much lower than that for Ni(II) catalyst, the following
two possibilities were suggested: 1) the in-situ generated MgBr2
might facilitate the Ni(0)/Ni(II) catalytic cycle; 2) a Ni(I)/Ni(III)
catalytic cycle might be responsible for this transformation rather
than a Ni(0)/Ni(II) pathway.
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Thus, the role of MgBr2, which was in-situ generated during the
reduction of NiBr2 to form active Ni catalyst by magnesium, was
explored. As previously reported, MgBr2 can be used as an additive
to promote the efficiency of transition-metal catalyzed cross-cou-
pling.18 To explore the effect of MgBr2 in the transformation, cata-
lytic amount of MgBr2 was subjected as an additive to the catalytic
system based on Ni(IMesMe)2 (Scheme 2a). Unfortunately, MgBr2
was completely inactive to promote the efficiency. Moreover, the
efficiency of cross-coupling under standard conditions dramati-
cally decreased in the presence of stoichiometric amount of MgBr2
(scheme 2b). These results ruled out the possibility that MgBr2
could act as the promoter in this transformation.
On the basis of the DFT calculations and EPR analysis, the
Ni(IMesMe)2Br complex were prepared and submitted it to the cat-
alytic transformation, interestingly, no desired product was ob-
served without Mg, but 86% NMR yield was obtained when 3.0
equivalent Mg was added (eq. 2). These results indicated that Mg
has dual roles: i) acted as a sufficient reductant to reduce Ni(II) to
Ni(I) species, ii) played a pivotal role in some elementary steps of
the catalytic cycle.
Scheme 2. Effect of MgBr2 in the SMC reaction
Based on the aforementioned results and previously reported
works,18, 20 a plausible mechanism based on magnesium-facilitated
Ni(I)/Ni(III) catalytic cycle was depicted in Scheme 3. Firstly, the
Ni(I) species II was formed via the ligand exchange of active cata-
lyst I with substrate, which led to oxidative addition of aromatic C-
N to produce the Ni(III) species III. With the presence of organo-
boronate, the Ni(III) species IV was generated via the transmetal-
lation. Finally, the desired biaryl product was released through the
sp2-sp2 C-C forming reductive elimination on Ni(III) center to re-
generate Ni(I) catalyst, thus fulfilling the catalytic cycle.
Figure 2. X-band EPR spectrum of the sampled reaction mixture
of NiBr2 (1.0 equiv.), IMesMe (3.5 equiv.) and Mg (0.6 mmol) in
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4. (a) Shin, K.; Kim, H.; Chang, S. Acc. Chem. Res. 2015, 48, 1040; (b)
Romero, N. A.; Margrey, K. A.; Tay, N. E.; Nicewicz, D. A. Science 2015,
349, 1326.
5. Kurti, L.; Czakó, B., Strategic applications of named reactions in or-
ganic synthesis. Elsevier: 2005.
1
2
3
6. (a) Hartwig, J. F.; Collman, J. P., Organotransition metal chemistry:
from bonding to catalysis. University Science Books Sausalito, CA: 2010;
(b) Luo, Y.-R., Handbook of bond dissociation energies in organic com-
pounds. CRC press: 2002; (c) Crabtree, R. H., The organometallic chemis-
try of the transition metals. John Wiley & Sons: 2009.
4
5
6
7
8
9
7. Hall, D. G., Boronic acids: preparation, applications in organic syn-
thesis and medicine. John Wiley & Sons: 2006.
8. (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457; (b) Su, B.;
Cao, Z.-C.; Shi, Z.-J. Acc. Chem. Res. 2015, 48, 886; (c) Zarate, C.; van
Gemmeren, M.; Somerville, R. J.; Martin, R. Adv. Organomet. Chem. 2016,
66, 143; (d) Rosen, B. M.; Quasdorf, K. W.; Wilson, D. A.; Zhang, N.;
Resmerita, A.-M.; Garg, N. K.; Percec, V. Chem. Rev. 2011, 111, 1346; (e)
Tobisu, M.; Chatani, N. Acc. Chem. Res. 2015, 48, 1717; (f) Kakiuchi, F.;
Usui, M.; Ueno, S.; Chatani, N.; Murai, S. J. Am. Chem. Soc. 2004, 126,
2706; (g) Tollefson, E. J.; Hanna, L. E.; Jarvo, E. R. Acc. Chem. Res. 2015,
48, 2344; (h) Guo, L.; Liu, X.; Baumann, C.; Rueping, M. Angew. Chem.
Int. Ed. 2016, 55, 15415.
9. (a) Ouyang, K.; Hao, W.; Zhang, W.-X.; Xi, Z. Chem. Rev. 2015, 115,
12045; (b) Wang, Q.; Su, Y.; Li, L.; Huang, H. Chem. Soc. Rev. 2016, 45,
1257.
10. (a) Blakey, S. B.; MacMillan, D. W. J. Am. Chem. Soc. 2003, 125,
6046; (b) Wenkert, E.; Han, A.-L.; Jenny, C.-J. J. Chem. Soc., Chem. Com-
mun. 1988, 975; (c) Reeves, J. T.; Fandrick, D. R.; Tan, Z.; Song, J. J.; Lee,
H.; Yee, N. K.; Senanayake, C. H. Org. Lett. 2010, 12, 4388; (d) Xie, L.-
G.; Wang, Z.-X. Angew. Chem. Int. Ed. 2011, 50, 4901.
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Scheme 3. Plausible mechanism for the SMC reaction
In summary, we demonstrated the first Suzuki-Miyaura coupling
reaction of N,N-dialkyl aryl amines via nickel catalysis under re-
ductive conditions in the absence of any directing groups and pre-
activation. Magnesium was proved to play dual roles to facilitate
the reported cross-coupling reaction. Further experiments demon-
strated that the reaction was delivered via Ni(I)/Ni(III) catalytic cy-
cle. Efforts to investigate the detailed mechanism, to extend the
substrate scope and to improve the efficiency of this transformation
are undergoing.
ASSOCIATED CONTENT
Supporting Information
11. (a) Ueno, S.; Chatani, N.; Kakiuchi, F. J. Am. Chem. Soc. 2007, 129,
6098; (b) Koreeda, T.; Kochi, T.; Kakiuchi, F. J. Am. Chem. Soc. 2009, 131,
7238.
The Supporting Information is available free of charge on the ACS
Publications website.
12. (a) Tobisu, M.; Nakamura, K.; Chatani, N. J. Am. Chem. Soc. 2014,
136, 5587; (b) Cao, Z.-C.; Li, X.-L.; Luo, Q.-Y.; Fang, H.; Shi, Z.-J. Org.
Lett. 2018, 20, 1995.
Supporting Information (PDF);
Cif files of Ni(IMesMe)2Br2, Ni(IMesMe)2, and Ni(IMesMe)2Br
13. Compared to other ligands, such as IMes, IMesMe was more electron-
rich: Huynh, H. V. Chem. Rev. 2018.
AUTHOR INFORMATION
Corresponding Author
14. Jun, C.-H. Chem. Soc. Rev. 2004, 33, 610.
15. (a) Everson, D. A.; Weix, D. J. The Journal of Organic Chemistry
2014, 79, 4793; (b) Weix, D. J. Acc. Chem. Res. 2015, 48, 1767; (c) I., K.
C. E.; Sabine, G.; Dominik, G.; Martin, C.; Corinne, G.; Axel, J. v. W.
Chemistry – A European Journal 2014, 20, 6828; (d) Cao, Z.-C.; Luo, Q.-
Y.; Shi, Z.-J. Org. Lett. 2016, 18, 5978; (e) Cao, Z.-C.; Shi, Z.-J. J. Am.
Chem. Soc. 2017, 139, 6546.
Z.J.S.: zshi@pku.edu.cn, zjshi@fudan.edu.cn
H.F.: hfang@fudan.edu.cn
Notes
The authors declare no competing financial interests.
16. Chan, C. K.; Amy, F.; Zhang, Q.; Barlow, S.; Marder, S.; Kahn, A.
Chem. Phys. Lett. 2006, 431, 67.
ACKNOWLEDGMENT
17. (a) Cornella, J.; Zarate, C.; Martin, R. Chem. Soc. Rev. 2014, 43,
8081; (b) Yu, D.-G.; Li, B.-J.; Shi, Z.-J. Acc. Chem. Res. 2010, 43, 1486.
18. (a) Jun, T.; Hirohisa, T.; Hideyuki, W.; Aki, I.; Nobuaki, K. Angew.
Chem. Int. Ed. 2004, 43, 6180; (b) Hatakeyama, T.; Hashimoto, T.; Kondo,
Y.; Fujiwara, Y.; Seike, H.; Takaya, H.; Tamada, Y.; Ono, T.; Nakamura,
M. J. Am. Chem. Soc. 2010, 132, 10674; (c) Ito, S.; Fujiwara, Y.-i.; Naka-
mura, E.; Nakamura, M. Org. Lett. 2009, 11, 4306.
19. Stoll, S.; Schweiger, A. J. magn. reson. 2006, 178, 42.
20. (a) Macgregor, S. A.; Neave, G. W.; Smith, C. Faraday Discuss.
2003, 124, 111; (b) Lim, C.-H.; Kudisch, M.; Liu, B.; Miyake, G. M. J. Am.
Chem. Soc. 2018, 140, 7667; (c) Lin, B. L.; Clough, C. R.; Hillhouse, G. L.
J. Am. Chem. Soc. 2002, 124, 2890; (d) Corcoran, E. B.; Pirnot, M. T.; Lin,
S.; Dreher, S. D.; DiRocco, D. A.; Davies, I. W.; Buchwald, S. L.; MacMil-
lan, D. W. C. Science 2016, 353, 279.
Support of this work by the “973” Project from the MOST
(2015CB856600),
NSFC
(Nos.
21332001,
21431008,
21761132027, and 91645111), Shanghai city (18YF1401800 and
18JC1411300), and Fudan-SIMM Joint Research Fund are grate-
fully acknowledged. Kai Wang (Fudan University), Ying Liu (Fu-
dan University), and Zhen Wang (Fudan University) were
acknowledged for the purification and analysis of partial substrates.
REFERENCES
1. Ricci, A., Amino group chemistry: from synthesis to the life sciences.
John Wiley & Sons: 2008.
2. Monnier, F.; Taillefer, M. Angew. Chem. Int. Ed. 2009, 48, 6954.
3. (a) Hartwig, J. F. Handbook of organopalladium chemistry for organic
synthesis 2002, 1051; (b) Yang, B. H.; Buchwald, S. L. J. Organomet. Chem.
1999, 576, 125.
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