Synthesis of (diarylmethyl)amines using Ni-catalyzed arylation of C(sp3)-H bonds

Article abstract of DOI:10.1039/c5sc01589h

The first nickel catalyzed deprotonative cross coupling between C(sp³)-H bonds and aryl chlorides is reported, allowing the challenging arylation of benzylimines in the absence of directing group or stoichiometric metal activation. This methodo

Full text of DOI:10.1039/c5sc01589h

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Synthesis of (diarylmethyl)amines using Ni-
catalyzed arylation of C(sp3)–H bonds†
Cite this: DOI: 10.1039/c5sc01589h
a
a
ab
*
Jose A. Fernandez-Salas, Enrico Marelli and Steven P. Nolan
´
´
The first nickel catalyzed deprotonative cross coupling between C(sp3)–H bonds and aryl chlorides is
reported, allowing the challenging arylation of benzylimines in the absence of directing group or
stoichiometric metal activation. This methodology represents a convenient access to the (diarylmethyl)-
amine moiety, which is widespread in pharmaceutically relevant compounds.
Received 1st May 2015
Accepted 11th June 2015
DOI: 10.1039/c5sc01589h
www.rsc.org/chemicalscience
Cross-coupling catalysis holds a preferred position in the to date, these protocols are based on palladium catalysis (see
synthetic chemist's arsenal as it provides a myriad of options for Scheme 1). In recent years, attention has focused on the use of less
the efficient and user-friendly access to organic motifs that are expensive and more earth-abundant rst-row transition metals as
otherwise difficult or impossible to obtain.1 In this context catalysts.11 Amongst these, nickel has long been used in a number
efforts have been devoted to extend the use of cross-coupling to of industrial applications,12 and its utility as a powerful catalyst
the functionalization of C–H bonds, as this highly attractive has been revisited in several areas of homogenous catalysis,
strategy leads to an atom-economical formation of new bonds ranging from coupling reactions13 to C–H bond functionaliza-
while generating minimal waste.2 The use of directing groups tion14 and small molecules activation.15 However, deprotonative
and/or activated C–H bonds in this chemistry has been thor- functionalization of benzylic C–H bond under nickel catalysis is,
oughly studied.3–5 In contrast, the use of less acidic C(sp3)–H to date, unprecedented. As the (diarylmethyl)amine moiety is a
pro-nucleophiles in the absence of any directing group6,7 has well-known pharmacophore motif found in pharmaceuticals,16
proven more challenging, and such examples remain scarce.8
the development of more sustainable synthetic methodologies
towards its synthesis is of signicant interest.
We therefore envisioned the use of a Ni–NHC (NHC: N-
heterocyclic carbene) system, known to be highly active in cross-
coupling chemistry,13d,h,n in lieu of Pd-based catalysts in this
challenging transformation. Our initial hypothesis relied on the
existence, for nickel, of a mechanistically closely related process
to palladium (see Scheme 2).
Scheme 1 Context of the present work.
The arylation of benzylamines-derived imines belongs to this
reaction class. It was initially reported by Yorimitsu and Oshima9
in 2008 and more recently alternative protocols have been
described.10 As most of the deprotonative cross couplings reported
aEaStCHEM School of Chemistry, University of St Andrews, St Andrews, KY16 9ST, UK.
E-mail: stevenpnolan@gmail.com
bChemistry Department, College of Science, King Saud University, Riyadh 11451, Saudi
Arabia
† Electronic supplementary information (ESI) available: Full experimental and
optimization details, characterization of all the synthesized products. See DOI:
10.1039/c5sc01589h
Scheme 2 The mechanism of the deprotonative cross coupling of
benzylimines.
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Our study began with the examination of a model reaction yield (entry 10). The optimal metal/ligand ratio was found to be
involving 1a and chlorotoluene (Table 1). The role of the base 1 : 2 (entry 11). The use of a representative phosphine ligand,
was examined early on and full conversion and good NMR yields PCy3, resulted in no conversion. Similar results were obtained
of the product were obtained using a [Ni(COD)2](1)/IPr catalytic when other Ni sources, such as [Ni(acac)2] and [Ni(DME)Cl2]
system in toluene (see Fig. 1) when potassium hexamethyldisi- were employed. Interestingly, further increasing the amount of
lylamide (KHMDS) was used as base. All other bases tested gave ligand completely suppressed the reaction. This result suggests
no conversion to the desired product (for full solvent-base that a monoligated Ni species is possibly the catalytically active
system optimization, see the ESI†).17
species, and large excess of ligand moves the equilibrium
towards the more stable but inactive bis-ligated species. Grati-
fyingly, the relatively mild operating temperature does not lead
to the formation of isomeric mixtures. It is important to
underline that, contrarily to previous reports,10a,b slow addition
of the base is unnecessary, thus making our protocol opera-
tionally simple.
Table 1 Optimization of the reaction conditionsa
Entry [Ni] (5 mol%) L (mol%) Conc. (mol LÀ1
)
Conv.b (yield)c
1
2
3
4
5
6
[Ni(COD)2]
[Ni(COD)2]
[Ni(COD)2]
[Ni(COD)2]
[Ni(COD)2]
4
IPr (6)
IMes (6)
IDD (6)
SIPr (6)
IPr* (6)
—
0.10
0.10
0.10
0.10
0.10
0.10
0.10
0.10
0.17
0.25
0.17
0.17
0.17
0.17
0.17
>95 (81)
24
—
94 (65)
>95 (60)
70 (45)
>95 (70)
>95 (72)
>95 (85)
>95 (53)
>95 (93)
—
7
5
—
8d
9
[Ni(COD)2]
[Ni(COD)2]
[Ni(COD)2]
[Ni(COD)2]
[Ni(COD)2]
[Ni(acac)2]
[Ni(DME)Cl2]
[Ni(COD)2]
IPr (6)
IPr (6)
IPr (6)
IPr (10)
PCy3 (10)
IPr (10)
IPr (10)
IPr (15)
10
11
12
13
14
15
Traces
—
—
Fig. 1 Ligands and complexes tested.
a
Conditions: 4-chlorotoluene (0.25 mmol), imine 1a (2.0 equiv.),
KHMDS (2.0 equiv.), toluene (1.0–2.5 mL), Ni source (2.5–5 mol%),
We proceeded to examine the inuence of the ligand: the use
of smaller NHCs resulted in poor or no conversion (entries 2–3),
while SIPr (entry 4) gave only a moderate yield. The use of the
very bulky IPr* ligand, which usually provides the best outcome
when employed in cross coupling chemistry,18 resulted in a
lower yield (entry 5). As we identied IPr as the optimal ligand,
in our initial reaction, the IPr-bearing well-dened catalysts 4
b
ligand (3–10 mol%), 45 ꢀC, 16 hours. Calculated by G.C. analysis.
c
Yield calculated by NMR analysis using dimethyl malonate as an
internal standard. d Reaction performed at 60 ꢀC.
Once the optimal reaction conditions were established, we
and 5 (entries 6–7) were tested. In contrast to previous examples sought to explore the generality of the new protocol by varying
of Ni–NHC catalyzed reactions,13n,15d both pre-catalysts gave the nature of the aryl chloride coupled with 1a (see Scheme 3).
poorer results compared to the in situ prepared [Ni(COD)2]/IPr We were pleased to nd that both the electron-rich 4-chlor-
system. We suspect the lower efficiency shown by the preformed oanisole 2b and the electron-poor chlorides 2c and 2d led to
pre-catalysts is due to the inability of the 2-azaallyl anion to high yields of the desired products. The compatibility of func-
effectively activate the Ni(II) center. This is an issue we are tionalized aryl chlorides, bearing functional groups such as
currently addressing in the design and synthesis of novel nickel- amines (3e), benzodioxole (3g) and relatively sensitive ketone
based pre-catalysts. To complete the optimization, temperature and nitrile derivatives (3g and 3h) was then examined. In all
effects were examined and yields decreased with higher cases, good to very good yields were obtained. The use of
temperature (entry 8). The concentration could be increased to heterocyclic (3i) and hindered aryl-chlorides (3j and 3k) was also
0.17 M (entry 9), but further increase led to dramatic decrease in possible; in these cases, complete conversion required a catalyst
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loading of 7.5 mol%. Compound 3k was isolated aer hydro- the methodology was tested on the commercially available
lysis, as the reaction mixture contained a small impurity that imine 1d. As the deprotonation of 1a and 1d converge to the
was not possible to remove by column chromatography (see same intermediate Int-1, a unique nal product was expected
ESI†). The results obtained in the coupling of bulky aryl chlo- (see Scheme 2). Under the optimized reaction conditions, the
rides clearly improve on previous Pd-based reports. Imines 1b desired coupling products were indeed obtained and in very
and 1c, bearing respectively a 4-methoxyphenyl and a 4-uo- good yields (see Scheme 4).
rophenyl moiety on the benzylamine starting material afforded
In order to shed light on the exact role of the base in this
the coupling products with chlorobenzene in good yields (see reaction, we performed the alkylation of 1a using benzyl chlo-
entries 3b-2 and 3c-2). To highlight some of the limitations of ride under the catalytic arylation reaction conditions (toluene,
the method, heterocyclic substrates 6–10 proved unsuitable in 45 ꢀC) in the absence of the catalyst, using three different bases:
this transformation.
KOtBu, NaHMDS and the optimal KHMDS (Table 2). We found
Encouraged by these results and to further increase the that in the presence of a base weaker than the azaallyl anion,
scope and demonstrate the versatility of this catalytic system, such as a t-butoxide, lower amounts of alkylated product were
observed (entry 3), and the crude NMR analysis showed the
formation of signicant amounts of side-products, which were
absent in the reactions using HMDS containing-bases (entries 1
and 2). This observation led us to test NaHMDS and KHMDS in
the absence of any electrophile, nding that while the latter
leads only to the formation the expected starting material and
the isomerized form 1d (entry 4), the use of NaHMDS caused
Scheme 4 Reaction scope of the Ni-catalyzed arylation of C(sp3)–H
bonds. Reaction conditions: aryl chloride (2) (0.25 mmol), 1 (2.0 equiv.),
KHMDS (2.0 equiv.), toluene (1.5 mL), [Ni(COD)2] (5 mol%), IPr (10
mol%), 45 ꢀC, 16 h.
Table 2 The role of the basea
11
Entry Base (equiv.)
(equiv.) 12b (%) Notes
1
2
3
4
5
6c
KHMDS (2.0)
NaHMDS (2.0) 0.10
KOtBu (2.0)
KHMDS (0.5)
NaHMDS (0.5)
KHMDS (0.5)
2.0
81
80
60
—
24
—
—
—
0.10
—
—
Side-products observed
Only 1a and 1d observed
Side-products observed
Only 1a and 1d observed
—
Scheme 3 Reaction scope of the Ni-catalyzed arylation of C(sp3)–H
bonds. Reaction conditions: aryl chloride (2) (0.25 mmol), 1 (2.0 equiv.),
KHMDS (2.0 equiv.), toluene (1.5 mL), [Ni(COD)2] (5 mol%), IPr (10
mol%), 45 ꢀC, 16 h. [a] 4 (7.5 mol%), IPr (15 mol%). [b] Isolated yield of
the corresponding ammonium chloride salt.
a
Conditions: benzyl chloride (0.24 mmol, 1.2 equiv., or none), imine 1a
(0.2 mmol, 1.0 equiv.), base (0.4 mmol or 0.1 mmol, 2.0 equiv. or 0.5
b
equiv.), toluene (0.6 mmol), 45 ꢀC, 3 hours. Calculated by NMR
c
analysis using dimethyl malonate as an internal standard. Reaction
performed in the presence of 5% [Ni(COD)2]/10% IPr.
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¨
side-products to arise (entry 5). No side-products were observed
using KHMDS even when the catalytic Ni/IPr system was present
in the reaction medium (entry 6). Although further studies are
needed to elucidate the mechanism of this reaction, the fact
that KHMDS is the only base which cleanly affords the azaallyl
indicates that this could be a reasonable explanation for the
lack of reactivity of other bases in the catalytic arylation
reaction.
N. Kuhl, N. Schroder and F. Glorius, Adv. Synth. Catal.,
2014, 356, 1443–1460.
4 (a) D. A. Culkin and J. F. Hartwig, Acc. Chem. Res., 2003, 36,
234–245; (b) C. C. C. Johansson and T. J. Colacot, Angew.
Chem., Int. Ed., 2010, 49, 676–707; (c) T. Ankner,
C. C. Cosner and P. Helquist, Chem.–Eur. J., 2013, 19,
1858–1871; (d) S. T. Sivanandan, A. Shaji, I. Ibnusaud,
C. C. C. J. Seechurn and T. J. Colacot, Eur. J. Org. Chem.,
2015, 2015, 38–49; for recent reports, see: (e) E. Marelli,
M. Corpet, S. R. Davies and S. P. Nolan, Chem.–Eur. J.,
2014, 20, 17272–17276; (f) B. Zheng, T. Jia and P. J. Walsh,
Adv. Synth. Catal., 2014, 356, 165–178.
5 (a) F. Bellina and R. Rossi, Tetrahedron, 2009, 65, 10269–
10310; (b) L. Joucla and L. Djakovitch, Adv. Synth. Catal.,
2009, 351, 673–714; for recent examples, see: (c)
L. Ackermann and S. Fenner, Chem. Commun., 2011, 47,
430–432; (d) L. Ackermann, C. Kornhaass and Y. Zhu, Org.
Lett., 2012, 14, 1824–1826; (e) S. I. Kozhushkov,
H. K. Potukuchi and L. Ackermann, Catal. Sci. Technol.,
2013, 3, 562–571; (f) D.-T. D. Tang, K. D. Collins and
F. Glorius, J. Am. Chem. Soc., 2013, 135, 7450–7453.
Conclusions
In summary, we have developed a synthetic methodology to
access the (diarylmethyl)amine motif via a high yielding Ni-
catalyzed coupling between C(sp3)–H bonds of benzylimine pro-
nucleophiles and aryl chlorides. This work discloses the use of a
commercially available Ni-based catalytic system under mild
and operationally simple conditions. We hope to soon report on
related Ni-catalyzed processes, as well as on the details of the
reaction mechanism.
Acknowledgements
6 Directing group assisted CH activation at the benzylic
position: (a) L.-C. Campeau, D. J. Schipper and K. Fagnou,
J. Am. Chem. Soc., 2008, 130, 3266–3267; (b) J. J. Mousseau,
A. Larivee and A. B. Charette, Org. Lett., 2008, 10, 1641–
1643; (c) N. Dastbaravardeh, M. Schnurch and
We thank the ERC (Advanced Researcher award-FUNCAT), the
EPSRC (grant no EP/J011053/1) and King Saud University for
funding. We thank the EPSRC NMSSC in Swansea for mass
spectrometric analyses. SPN is a Royal Society Wolfson Research
Merit Award holder. We thank Dr Marcel Brill for useful
discussions during the assembly of this paper.
´
¨
M. D. Mihovilovic, Org. Lett., 2012, 14, 1930–1933; (d)
N. Dastbaravardeh, M. Schnurch and M. D. Mihovilovic,
¨
Eur. J. Org. Chem., 2013, 2013, 2878–2890.
7 Metal-mediated CH activation at the benzylic position: (a)
V. N. Kalinin, I. A. Cherepanov and S. K. Moiseev, J.
Organomet. Chem., 1997, 536–537, 437–455; (b)
G. I. McGrew, J. Temaismithi, P. J. Carroll and P. J. Walsh,
Angew. Chem., Int. Ed., 2010, 49, 5541–5544; (c)
G. I. McGrew, C. Stanciu, J. Zhang, P. J. Carroll,
S. D. Dreher and P. J. Walsh, Angew. Chem., Int. Ed., 2012,
51, 11510–11513.
8 (a) J.-I. Inoh, T. Satoh, S. Pivsa-Art, M. Miura and M. Nomura,
Tetrahedron Lett., 1998, 39, 4673–4676; (b) G. Dyker,
J. Heiermann, M. Miura, J.-I. Inoh, S. Pivsa-Art, T. Satoh
and M. Nomura, Chem.–Eur. J., 2000, 6, 3426–3433; (c)
T. Niwa, H. Yorimitsu and K. Oshima, Org. Lett., 2007, 9,
2373–2375; (d) J. Zhang, A. Bellomo, A. D. Creamer,
S. D. Dreher and P. J. Walsh, J. Am. Chem. Soc., 2012, 134,
13765–13772; (e) N. Hussain, G. Frensch, J. Zhang and
P. J. Walsh, Angew. Chem., Int. Ed., 2014, 53, 3693–3697.
9 (a) T. Niwa, H. Yorimitsu and K. Oshima, Org. Lett., 2008, 10,
4689–4691; (b) T. Niwa, T. Suehiro, H. Yorimitsu and
K. Oshima, Tetrahedron, 2009, 65, 5125–5131.
Notes and references
1 (a) N. Miyaura and A. Suzuki, Chem. Rev., 1995, 95, 2457–
2483; (b) K. Sonogashira, J. Organomet. Chem., 2002, 653,
46–49; (c) K. C. Nicolaou, P. G. Bulger and D. Sarlah,
Angew. Chem., Int. Ed., 2005, 44, 4442–4489; (d) G. Zeni and
R. C. Larock, Chem. Rev., 2006, 106, 4644–4680; (e)
J.-P. Corbet and G. Mignani, Chem. Rev., 2006, 106, 2651–
2710; (f) D. S. Surry and S. L. Buchwald, Angew. Chem., Int.
Ed., 2008, 47, 6338–6361; (g) J. G. De Vries, Top. Organomet.
Chem., 2012, 42, 1–34; (h) C. C. C. Johansson Seechurn,
M. O. Kitching, T. J. Colacot and V. Snieckus, Angew.
Chem., Int. Ed., 2012, 51, 5062–5085.
2 (a) C. Jia, T. Kitamura and Y. Fujiwara, Acc. Chem. Res., 2001,
34, 633–639; (b) J. A. Labinger and J. E. Bercaw, Nature, 2002,
417, 507–514; (c) L. Ackermann, R. Vicente and A. R. Kapdi,
Angew. Chem., Int. Ed., 2009, 48, 9792–9826; (d) X. Chen,
K. M. Engle, D.-H. Wang and J.-Q. Yu, Angew. Chem., Int.
Ed., 2009, 48, 5094–5115; (e) F. Bellina and R. Rossi, Chem.
Rev., 2009, 110, 1082–1146; (f) J. Wencel-Delord, T. Droge,
F. Liu and F. Glorius, Chem. Soc. Rev., 2011, 40, 4740–4761; 10 (a) Y. Zhu and S. L. Buchwald, J. Am. Chem. Soc., 2014, 136,
(g) H. Li, B.-J. Li and Z.-J. Shi, Catal. Sci. Technol., 2011, 1,
191–206; (h) J. Wencel-Delord and F. Glorius, Nat. Chem.,
2013, 5, 369–375; (i) R. Ferraccioli, Synthesis, 2013, 45, 581–
591.
4500–4503; (b) J. Zhang, A. Bellomo, A. D. Creamer,
S. D. Dreher and P. J. Walsh, J. Am. Chem. Soc., 2012, 134,
13765–13772; (c) M. Li, B. Yucel, J. Adrio, A. Bellomo and
P. J. Walsh, Chem. Sci., 2014, 5, 2383–2391.
3 (a) D. A. Colby, R. G. Bergman and J. A. Ellman, Chem. Rev., 11 (a) C. Gosmini, J.-M. Begouin and A. Moncomble, Chem.
2010, 110, 624–655; (b) D. A. Colby, A. S. Tsai, R. G. Bergman
and J. A. Ellman, Acc. Chem. Res., 2012, 45, 814–825; (c)
Commun., 2008, 3221–3233; (b) D. S. Surry and
S. L. Buchwald, Chem. Sci., 2010, 1, 13–31; (c) G. Evano,
Chem. Sci.
This journal is © The Royal Society of Chemistry 2015

View Article Online
Edge Article
C. Theunissen and A. Pradal, Nat. Prod. Rep., 2013, 30, 1467–
Chemical Science
and N. Chatani, Chem.–Asian J., 2012, 7, 1357–1365; (c)
X. Wu, Y. Zhao and H. Ge, J. Am. Chem. Soc., 2014, 136,
1789–1792; (d) M. Li, J. Dong, X. Huang, K. Li, Q. Wu,
F. Song and J. You, Chem. Commun., 2014, 50, 3944–3946;
(e) X. Wu, Y. Zhao and H. Ge, Chem.–Eur. J., 2014, 20,
9530–9533; (f) C. Lin, W. Yu, J. Yao, B. Wang, Z. Liu and
Y. Zhang, Org. Lett., 2015, 17, 1340–1343; (g) S.-Y. Yan,
Y.-J. Liu, B. Liu, Y.-H. Liu and B.-F. Shi, Chem. Commun.,
2015, 51, 4069–4072; (h) J. S. Bair, Y. Schramm,
A. G. Sergeev, E. Clot, O. Eisenstein and J. F. Hartwig, J.
Am. Chem. Soc., 2014, 136, 13098–13101; (i) L. Ackermann,
B. Punji and W. Song, Adv. Synth. Catal., 2011, 353, 3325–
3329; (j) W. Song, S. Lackner and L. Ackermann, Angew.
Chem., Int. Ed., 2014, 53, 2477–2480.
¨
1489; (d) B. D. Sherry and A. Furstner, Acc. Chem. Res., 2008,
ˇ
41, 1500–1511; (e) W. M. Czaplik, M. Mayer, J. Cvengros and
A. J. von Wangelin, ChemSusChem, 2009, 2, 396–417.
12 (a) W. Keim, Angew. Chem., Int. Ed., 1990, 29, 235–244; (b)
S. Z. Tasker, E. A. Standley and T. F. Jamison, Nature, 2014,
509, 299–309.
13 (a) F.-S. Han, Chem. Soc. Rev., 2013, 42, 5270–5298; (b)
B. M. Rosen, K. W. Quasdorf, D. A Wilson, N. Zhang,
A.-M. Resmerita, N. K. Garg and V. Percec, Chem. Rev.,
2011, 111, 1346–1416; (c) J. Cornella, C. Zarate and
R. Martin, Chem. Soc. Rev., 2014, 43, 8081–8097; (d)
M. Henrion, V. Ritleng and M. J. Chetcuti, ACS Catal.,
2015, 5, 1283–1302; (e) S. Son and G. C. Fu, J. Am. Chem.
Soc., 2008, 130, 2756–2757; (f) F. Glorius, Angew. Chem., Int. 15 (a) S. Yao and M. Driess, Acc. Chem. Res., 2011, 45, 276–287;
¨
Ed., 2008, 47, 8347–8349; (g) C. Lohre, T. Droge, C. Wang
(b) T. Fujihara, K. Nogi, T. Xu, J. Terao and Y. Tsuji, J. Am.
´
and F. Glorius, Chem.–Eur. J., 2011, 17, 6052–6055; (h)
A. R. Martin, D. J. Nelson, S. Meiries, A. M. Z. Slawin and
S. P. Nolan, Eur. J. Org. Chem., 2014, 3127–3131; (i)
S. Z. Tasker, A. C. Gutierrez and T. F. Jamison, Angew.
Chem., Int. Ed., 2014, 53, 1858–1861; (j) E. A. Standley,
Chem. Soc., 2012, 134, 9106–9109; (c) T. Leon, A. Correa
and R. Martin, J. Am. Chem. Soc., 2013, 135, 1221–1224; (d)
Y. Makida, E. Marelli, A. M. Z. Slawin and S. P. Nolan,
Chem. Commun., 2014, 50, 8010–8013; (e) C. S. Yeung and
V. M. Dong, J. Am. Chem. Soc., 2008, 130, 7826–7827; (f)
´
¨
S. J. Smith, P. Muller and T. F. Jamison, Organometallics,
A. Correa, T. Leon and R. Martin, J. Am. Chem. Soc., 2013,
2014, 33, 2012–2018; (k) K. Nakai, Y. Yoshida, T. Kurahashi
and S. Matsubara, J. Am. Chem. Soc., 2014, 136, 7797–7800;
(l) J. Cornella, E. P. Jackson and R. Martin, Angew. Chem.,
136, 1062–1069; (g) Y. Liu, J. Cornella and R. Martin, J. Am.
Chem. Soc., 2014, 136, 11212–11215; (h) T. Moragas,
J. Cornella and R. Martin, J. Am. Chem. Soc., 2014, 136,
17702–17705.
´
Int. Ed., 2015, 54, 4075–4078; (m) J. A. Fernandez-Salas,
E. Marelli, D. B. Cordes, A. M. Z. Slawin and S. P. Nolan, 16 (a) Y. Ko, D. C. Malone and E. P. Armstrong,
Chem.–Eur. J., 2015, 21, 3906–3909; (n) S. Ge, R. A. Green
and J. F. Hartwig, J. Am. Chem. Soc., 2014, 136, 1617–1627;
(o) S. Ge and J. F. Hartwig, J. Am. Chem. Soc., 2011, 133,
16330–16333; (p) S. Ge and J. F. Hartwig, Angew. Chem., Int.
Ed., 2012, 51, 12837–12841; (q) R. A. Green and
J. F. Hartwig, Angew. Chem., Int. Ed., 2015, 54, 3768–3772;
(r) A. Borzenko, N. L. Rotta-Loria, P. M. MacQueen,
C. M. Lavoie, R. McDonald and M. Stradiotto, Angew.
Chem., Int. Ed., 2015, 54, 3773–3777; (s) A. M. Whittaker
Pharmacotherapy: The Journal of Human Pharmacology and
Drug Therapy, 2006, 26, 1694–1702; (b) S. A. Doggrell and
L. C. Liang, Naunyn-Schmiedeberg's Arch. Pharmacol., 1998,
357, 126–132; (c) N. Plobeck, D. Delorme, Z.-Y. Wei,
H. Yang, F. Zhou, P. Schwarz, L. Gawell, H. Gagnon,
B. Pelcman, R. Schmidt, S. Y. Yue, C. Walpole, W. Brown,
E. Zhou, M. Labarre, K. Payza, S. St-Onge, A. Kamassah,
P.-E. Morin, D. Projean, J. Ducharme and E. Roberts, J.
Med. Chem., 2000, 43, 3878–3894.
and V. M. Dong, Angew. Chem., Int. Ed., 2015, 54, 1312– 17 Walsh also observed a need for a very strong base to permit
1315; (t) M. Grigalunas, T. Ankner, P.-O. Norrby, O. Wiest
and P. Helquist, J. Am. Chem. Soc., 2015, 137, 7019–7022.
14 (a) H. Shiota, Y. Ano, Y. Aihara, Y. Fukumoto and N. Chatani,
J. Am. Chem. Soc., 2011, 14952–14955; (b) I. Hyodo, M. Tobisu
deprotonative cross couplings (see ref. 8d).
18 F. Izquierdo, S. Manzini and S. P. Nolan, Chem. Commun.,
2014, 50, 14926–14937.
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