A Sn atom-economical approach toward arylstannanes: Ni-catalysed stannylation of aryl halides using Bu3SnOMe

Article abstract of DOI:10.1039/c5ob01096a

Stannylation of carbon-halogen bonds is one of the most promising and straightforward approaches for the preparation of organostannane compounds. Although a wide variety of methods are now available, all protocols require the use of highly nucleophilic organometals or wasteful stannyl sources like distannanes. Here, we report a new nickel-catalysed stannylation of aryl and alkenyl-halides using Bu₃SnOMe as a stannyl source to afford aryl and vinyl-stannanes, respectively. This method enables the stannylation of not only bromides, but also chlorides and triflates to furnish functionalized aryl- and alkenyl-stannanes without the release of wasteful and toxic stannyl byproducts.

Full text of DOI:10.1039/c5ob01096a

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A Sn atom-economical approach toward
arylstannanes: Ni-catalysed stannylation of aryl
Cite this: DOI: 10.1039/c5ob01096a
halides using Bu3SnOMe†
Kimihiro Komeyama,* Ryota Asakura and Ken Takaki
Stannylation of carbon–halogen bonds is one of the most promising and straightforward approaches for
the preparation of organostannane compounds. Although a wide variety of methods are now available, all
protocols require the use of highly nucleophilic organometals or wasteful stannyl sources like distan-
nanes. Here, we report a new nickel-catalysed stannylation of aryl and alkenyl-halides using Bu3SnOMe as
a stannyl source to afford aryl and vinyl-stannanes, respectively. This method enables the stannylation of
not only bromides, but also chlorides and triflates to furnish functionalized aryl- and alkenyl-stannanes
without the release of wasteful and toxic stannyl byproducts.
Received 1st June 2015,
Accepted 8th July 2015
DOI: 10.1039/c5ob01096a
www.rsc.org/obc
Arylstannanes are useful synthetic intermediates because of strated as alternative procedures. Although both of the above
their versatility in the construction of aryl-C,1 -NR2,2 -F,3 and methods are useful and powerful for functionalized arylstan-
4
-OCF3 bonds. The most promising route to afford arylstan- nane synthesis, the release of highly toxic stannyl byproducts
nanes relies on the trapping of arylmetal species (Mg, Li, and is unavoidable. These disadvantages drastically reduce the
Zn)3a,5 using trialkylstannyl electrophiles R3SnX′ (route a, efficiency of organostannane chemistry in both academia and
Scheme 1). However, these protocols have some drawbacks: industrial pursuits.
poor functional group tolerance and/or delicate conditions for
On the other hand, a few transition metal-catalysed reac-
the preparation of arylmetal species. In contrast, the Pd-cata- tions involve nucleophilic stannylation processes using trialkyl-
lysed stannylation of aryl halides (Scheme 1b)6 and the stannyl alkoxides ROSn(alkyl)3 as terminal electrophiles. For
recently proposed Sandmeyer-type reaction of anilines instance, the interception of alkynylzinc8 and alkenylcopper
(Scheme 1c)7 using hexaalkyl distannanes have been demon- intermediates9 generated in situ using stannyl alkoxides
quickly transforms into the corresponding alkynyl or alkenyl
stannane compounds, respectively.10 However, these catalytic
processes have never been applied to the stannylation of ubi-
quitous carbon (sp2)–halogen bonds because of their low reac-
tivity for zinc and copper complexes. In this paper, we report a
Ni-catalysed stannylation of aryl halides using Bu3SnOMe in
the presence of manganese powder (Scheme 1d). This stanny-
lation process could be an ideal and straightforward approach
to afford aryl or vinyl stannanes from both organohalides and
organotriflates. The proposed process possesses the following
advantages: (1) available substrates, (2) a broad scope of func-
tional groups, and (3) Sn atom-economy without the release of
wasteful toxic inorganic stannyl residues.
Initially, we explored the suitable reaction conditions for
the stannylation of aryl bromides 1a and 1b using stannyl elec-
Scheme 1 Representative synthetic method for arylstannanes.
trophile as model substrates based on the previous work by
Tsuji and Fujihara (Table 1).11 When 1a was treated with
Bu3SnOMe (1.2 equiv.) in the presence of NiBr2 (10 mol%),
2,2′-bipyridine (bpy, 10 mol%), and Mn powder (2.0 equiv.
treated with 20 mol% of chlorotrimethylsilane), arylstannane
Department of Applied Chemistry, Graduate School of Engineering, Hiroshima
University, 1-4-1 Kagamiyama, Higashi-Hiroshima City, Hiroshima 739-8527, Japan.
E-mail: kkome@hiroshima-u.ac.jp
†Electronic supplementary information (ESI) available: Additional data for the
screening of reaction conditions, experimental procedures and characterization
2a was afforded in 72% yield along with biaryl 3a in 14% yield
for new compounds. See DOI: 10.1039/c5ob01096a
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halides with Bu3SnOMe (Table 2). Aryl bromides containing
electron-donating (1d) and -withdrawing substituents (1e–1g)
at the para-position were well tolerated, giving rise to the
Table 1 Screening of the reaction conditions in the stannylation of
4-methoxy bromobenzene (1a) and 4-trifluoromethyl bromobenzene
(1b)
Table 2 Scope of aryl and vinyl halides
Yielda/%
Entry
1
[Ni]cat.
Ligand (x mol%)
2
3
1
2
3
4
5
6
1a
1a
1a
1a
1a
1a
1a
1a
1a
1b
1b
1b
1b
NiBr2
NiBr2(bpy)
NiBr2
NiBr2
NiBr2
NiBr2
—
NiBr2(bpy)
NiBr2(bpy)
NiBr2(bpy)
NiBr2
bpy (10)
—
—
PPh3 (20)
dppe (10)
tbpyb (10)
bpy (20)
—
72
91 (85)
0
21
0
10
0
23
60
22
75
86
96 (90)
14
9
0
7
0
70
0
60
39
68
12
6
7
8c
9d,e
10f
11f
12f
13f,g
—
—
PPh3 (20)
PPh3 (30)
PPh3 (30)
NiBr2
NiBr2
4
a Determined by GC yield with tridecane as the internal standard.
Parenthetical value indicates isolated yield. b tbpy = 4,4′-di-tert-butyl-
2,2′-bipyridine. c Zn was used instead of Mn. d 4-Iodoanisole was used
instead of bromide 1a. e 25 °C, 4 h. f 25 °C, 18 h. g Et4NI (20 mol%) was
added.
(entry 1).12 The preformed [NiBr2(bpy)] complex exhibited
higher catalytic performance to afford 2a in 91% yield (entry
2).13 The 2,2′-bipyridine ligand and Ni catalyst were crucial
(entries 3–7). The replacement of Mn or 1a with Zn or 4-iodo-
anisole, respectively, induced the homocoupling reaction
(entries 8 and 9). In contrast, the optimized conditions (entry
2) were not sufficient for the stannylation of electron-poor aryl
bromides like 1b; instead, the homocoupling mainly pro-
ceeded due to the high reactivity of low-valent Ni toward the
aryl halides14 and/or the poor nucleophilicity of the generated
aryl nickel.15 Fortunately, the low chemoselectivity was
improved by replacing the bpy ligand with electron-donating
PPh3 (entry 10). Further improvement was achieved by increas-
ing ligand loading (30 mol%) and by adding Et4NI11,16 (entries
11–13). In this stannylation, other stannyl electrophiles such
as Bu3SnCl, Bu3SnOtBu, and Bu3SnOAc also participated,
leading to 2a in 74%, 69%, and 54% yields, respectively
(Table S1 in the ESI†). Additionally, hexane, toluene, tetra-
hydrofuran, 1,4-dioxane, and acetonitrile were not suitable sol-
vents; most of the substrates remained unchanged.
a 10 mol% NiBr2(bpy), 50 °C. b 10 mol% NiBr2, 30 mol% PPh3, 20 mol%
Et4NI, 25 °C. c 1.5 equivalent of Bu3SnOMe was used. d 2.05 g of 2e was
obtained. e Xantophos (20 mol%) was used instead of PPh3 (30 mol%).
Reaction temperature: 40 °C.
With the optimized conditions in hand (entries 2 and 13,
Table 1), we next investigated the substrate scope in the Ni-
catalysed stannylation by employing various aryl or vinyl
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corresponding stannylated products (2c–2g) in good yields. In
addition, the stannylation was successfully carried out on a
gram-scale synthesis, giving rise to 2e in 2.05 g (89% yield). For
the efficient stannylation of 4-cyano bromobenzene (1h), biden-
tate phosphine ligands bearing large bite angles were effective
(Table S2 in the ESI†). ortho and meta-substituents (1i–1o) also
participated in the stannylation, leading to the corresponding
stannylated products (2i–2o). Heteroaryl bromides (1p–1r) also
underwent this transformation to afford the stannylation pro- Scheme 2 Stoichiometric reaction of NiBr2(bpy) with 1a (1.0 equiv.)
and Bu3SnOMe (1.2 equiv.) in the presence of Mn powder (x equiv.).
ducts in good-to-high yields. Slightly acidic N–H bonds did not
prevent the reaction and afforded 4-amino-2-fluorophenyl stan-
nane (2s), which is an intermediate in torezolid synthesis.17 In
addition, the stereochemistry of (E)- and (Z)-olefinic moieties
(1t) was maintained during the stannylations. Furthermore, the
present stannylation is active not only for bromides, but also for
chloride 1u and triflates 1o and 1v, yielding the corresponding
even if excess scavenger (2.0–3.0 equiv.) was present in the
reaction media.22 These findings imply that the primary path-
ways for oxidative addition of Ni into organohalides 1 do not
generate free organic radicals.
stannylated products 2u, 2o, and 2v, respectively.
The stoichiometric reaction of NiBr2(bpy) with 1a and
Bu3SnOMe in the presence of various amounts of Mn powder
(Scheme 2) provided some important information about the
mechanism. As the loading of Mn was increased, the yield of
ð1Þ
stannylated product 2a increased, while that of the homocou-
pling product 3a decreased. Particularly note that the lower
loading (0.9–1.1 equiv.) of Mn powder mainly produced the
homocoupling product 3a. A similar product distribution was
observed in the reaction of Ni(COD)2/bpy with 1a and
Bu3SnOMe in the absence of an Mn reductant (eqn (3)). These
results could indicate that monovalent Ni is an active inter-
mediate in the Ni-catalysed stannylation. Thus, the present
stannylation could be initiated by the generation of [Ni]0
ð2Þ
complex A from the reduction of the initial Ni(II) with Mn
powder (Scheme 3). The oxidative addition of aryl halides (Ar–
X: 1) to A afforded Ar–[Ni]II–X B. Although the divalent Ni inter-
mediate B might be slightly active in the interception of
Bu3SnOMe (Scheme 2 and eqn (3)), disproportionation of B
ð3Þ
A stereocontrol study was conducted using (Z)-1-(bromo-
vinyl)naphthalene (1w), as shown in eqn (1). The reaction of
1w with Bu3SnOMe exclusively yielded (Z)-vinyl stannane 2w
with complete retention of the stereo-integrity.18 In addition, it
is known that the aryl radical possessing a (dialkylamino)
methyl group at the ortho-position, derived from the halogen
atom abstraction of 1-(2-iodobenzyl)piperidine (1x), rapidly
undergoes 1,5-hydrogen atom transfer to afford an α-amino
alkyl radical.19 This radical might be converted to alkyl stan-
nane 4x through the formation of alkyl nickel species via
recombination between Ni and the alkyl radical.20 However,
the reaction of 1w provided simple arylstannane 2x (eqn (2)).
Furthermore, the addition of a hydrogen atom donor like 9,10-
dihydroanthracene21 into the reaction media did not fully
Scheme 3 Plausible reaction pathway for the Ni-catalysed stannylation
block the stannylation; 45–62% yields of 2a were obtained of aryl halides.
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would spontaneously occur to afford [Ni]IIX2 and [Ni]IIAr2
C,14a,23 which would lead to the homocoupling product 3 and
A via reductive elimination. In contrast, in the presence of
excess Mn, B could be preferentially reduced to [Ni]I–Ar D,
which would be more active than B for interception because of
8 K. Kiyokawa, N. Tachikake, M. Yasuda and A. Baba, Angew.
Chem., Int. Ed., 2011, 50, 10393.
9 (a) Y. Takemoto, H. Yoshida and K. Takaki, Chem. – Eur. J.,
2012, 18, 14841; (b) T. Wakamatsu, K. Nagao, H. Ohmiya
and M. Sawamura, Angew. Chem., Int. Ed., 2013, 52, 11620.
the higher nucleophilicity of monovalent Ni.15,16 This would 10 Interception of the carbon–silver bond using other stannyl
afford the stannylated product 2 as well as [Ni]I–OMe E, fol-
lowed by the regeneration of A with Mn.
electrophiles was reported. See: J. Liu, X. Xie and Y. Liu,
Chem. Commun., 2013, 49, 11794.
11 T. Fujihara, K. Nogi, T. Xu, J. Terao and Y. Tsuji, J. Am.
Chem. Soc., 2012, 134, 9106.
Conclusions
12 A possibility that the biaryl 3a was formed through the
Stille coupling of 1a with the generated 2a was completely
ruled out in the reaction of 1a with PhSnBu3 under the
identical conditions. D. A. Powell, T. Maki and G. C. Fu,
J. Am. Chem. Soc., 2005, 127, 510.
13 The reaction of 4-anisyl chloride under the identical con-
ditions (Table 1, entry 2) afforded 2a in 33% yield, along
with 3a in 32%.
14 (a) T. T. Tsou and J. K. Kochi, J. Am. Chem. Soc., 1979, 101,
6319; (b) V. P. Ananikov, ACS Catal., 2015, 5, 1964.
15 J.-X. Hu, H. Wu, C.-Y. Li, W.-J. Sheng, Y.-X. Jia and
J.-R. Gao, Chem. – Eur. J., 2011, 17, 5234.
In conclusion, we have demonstrated a simple and atom-econ-
omical stannylation using stannyl electrophiles catalysed by Ni
complexes in the presence of an Mn reductant. This stannyla-
tion can be tolerated by a diverse set of functional groups on
aryl halides and does not release wasteful stannyl residues.
Preliminary mechanistic studies suggest that aryl Ni(I) species
are intermediates in this transformation. Further mechanistic
studies and synthetic applications of this transmetalation
process of the C–Ni bond are underway.
16 (a) M. Zembayashi, K. Tamao, J.-I. Yoshida and
M. Kumada, Tetrahedron Lett., 1977, 18, 4089; (b) M. Iyoda,
H. Otsuka, K. Sato, N. Nisato and M. Oda, Bull. Chem. Soc.
Jpn., 1990, 63, 80; (c) V. Percec, J.-Y. Bae, M. Zhao and
D. H. Hill, J. Org. Chem., 1995, 60, 176.
Acknowledgements
This work was partially supported by a Grant-Aid for Scientific
Research (KAKENHI) from the Ministry of Education, Culture,
Sports, Science and Technology of Japan. K. K. acknowledges
financial support from the Electronic Technology Research
Foundation of Chugoku. We also acknowledge the Natural
Science Center for Basic Research and Development (N-BARD)
in Hiroshima University for HRMS analysis.
17 W. B. Im, S. H. Choi, J.-Y. Park, S. H. Choi, J. Finn and
S.-H. Yoon, Eur. J. Med. Chem., 2011, 46, 1027.
18 J. J. Hirner and S. A. Blum, Organometallics, 2011, 30, 1299.
19 (a) V. Snieckus, J. C. Cuevas, C. P. Sloan, H. Liu and
D. P. Curran, J. Am. Chem. Soc., 1990, 112, 896;
(b) M. Murakami, M. Hayashi and Y. Ito, J. Org. Chem.,
1992, 57, 793; (c) N. Yoshikai, A. Mieczkowski,
A. Matsumoto, L. Ilies and E. Nakamura, J. Am. Chem. Soc.,
2010, 132, 5568.
Notes and references
1 (a) J. K. Stille, Angew. Chem., Int. Ed. Engl., 1986, 25, 508;
(b) M. Kosugi and K. Fugami, Handbook of Organopalladium 20 (a) H. Yin, C. Zhao, H. You, K. Lin and H. Gong, Chem.
Chemistry for Organic Synthesis, ed. E. Negishi, Wiley,
New York, 2002, p. 263.
2 P. Y. S. Lam, G. Vincent, D. Bonne and C. G. Clark, Tetra-
hedron Lett., 2002, 43, 3091.
3 (a) T. Furuya, A. E. Strom and T. Ritter, J. Am. Chem. Soc.,
2009, 131, 1662; (b) Y. Ye and M. S. Sanford, J. Am. Chem.
Soc., 2013, 135, 4648.
4 C. Huang, T. Liang, S. Harada, E. Lee and T. Ritter, J. Am.
Chem. Soc., 2011, 133, 13308.
Commun., 2012, 48, 7034; (b) D. A. Everson, B. A. Jones and
D. J. Weix, J. Am. Chem. Soc., 2012, 134, 6146; (c) H. Xu,
C. Zhao, Q. Qian, W. Deng and H. Gong, Chem. Sci., 2013, 4,
4022; (d) Y. Peng, X.-B. Xu, J. Xiao and Y.-W. Wang, Chem.
Commun., 2013, 50, 472; (e) Z. Zuo, D. T. Ahneman, L. Chu,
J. A. Terrett, A. G. Doyle and D. W. C. MacMillan, Science,
2014, 345, 437; (f) L. K. G. Ackerman, L. L. Anka-Lufford,
M. Naodovic and D. J. Weix, Chem. Sci., 2014, 6, 1115.
21 (a) B. L. Tran, B. Li, M. Driess and J. F. Hartwig, J. Am.
Chem. Soc., 2014, 136, 2555; (b) S. K. Bose, K. Fucke, L. Liu,
P. G. Steel and T. B. Marder, Angew. Chem., Int. Ed., 2014,
53, 1799.
5 (a) L. Adam Shih-Yuan and D. Wen-Chin, Tetrahedron Lett.,
1996, 37, 495; (b) T. Hayashi and M. Ishigedani, Tetra-
hedron, 2001, 57, 2589; (c) P. Knochel and R. D. Singer,
Chem. Rev., 1993, 93, 2117; (d) C. Gosmini and J. Périchon, 22 Decreasing the solubility of Bu3SnOMe by the addition of
Org. Biomol. Chem., 2005, 3, 216.
9,10-dihydroanthracene would cause low yields. Indeed, as
the amount of the scavenger increases (1.0–3.0 equiv.), the
homocoupling reaction exclusively occurred to form 3a in
16–31% yields. See Table S3 in the ESI.†
6 (a) D. Azarian, S. S. Dua, C. Eaborn and D. R. Walton,
J. Organomet. Chem., 1976, 117, C55; (b) H. Azizian, C. Eaborn
and A. Pidcock, J. Organomet. Chem., 1981, 215, 49.
7 D. Qiu, L. Jin, S. Wang, S. Tang, X. Wang, F. Mo, Y. Zhang 23 A. Nakamura and S. Otsuka, Tetrahedron Lett., 1974, 15,
and J. Wang, Angew. Chem., Int. Ed., 2013, 52, 11581.
463.
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