electrophiles (e.g., aryl-esters,7 -ethers,8 -carbamates,9
-sulfamates10).11,12 Considering the promise of nickel-
catalyzed couplings and the need to make industrial pro-
cesses more environmentally friendly, we explored cou-
pling reactions in green solvents. Herein, we demonstrate
that a range of substrates, including heterocycles, partici-
pate in the nickel-catalyzed SuzukiÀMiyaura coupling
in solvents that are attractive for industrial applications
(Figure 1).
the commercially available NiCl2(PCy3)2 precatalyst
(Table 1). Although solvents such as 1,4-dioxane and N-
methyl-2-pyrrolidone (NMP), which have been deemed as
environmentally unfriendly solvents,2 are commonly used
in nickel-catalyzed cross-couplings, we were delighted to
find that many other solvents may be employed in the
coupling to give biaryl 3. Of the >30 solvents that were
surveyed, more than half gave quantititative yields of 3,
while many others also showed promise.13 A subset of our
findings are summarized in Table 1. The solvent used in
our previous studies,7c,9b,9d toluene, gave biaryl 3 in quan-
titative yield (entry 1). Acetone, ethyl acetate, and isopro-
pyl acetate (entries 2À4, respectively) also gave product in
comparable yields. In addition, alcohol solvents were
examined. Whereas the use of n-BuOH proved ineffective
(entry 5), tert-amyl alcohol was found to be an excellent
solvent for the cross-coupling (entry 6). Ethereal solvents
also provided biaryl 3 in quantitative yield (entries 7À8).
Mixed results were observed for highly coordinating sol-
vents; for example, the use of DMSO was unsuccessful
(entry 9), but the use of acetonitrile led to the desired
coupling. Although many solvents could be employed, we
opted to pursue tert-amyl alcohol and 2-Me-THF (entries
6 and 8, respectively) for further studies.3,14
Figure 1. SuzukiÀMiyaura cross-coupling of aryl halides and
phenol derivatives in green solvents.
We initiated our efforts by examining the cross-coupling
of naphthyl sulfamate 1 and phenylboronic acid (2) using
(7) For selected examples involving aryl esters, see: (a) Guan, B.-T.;
Wang, Y.; Li, B.-J.; Yu, D.-G.; Shi, Z.-J. J. Am. Chem. Soc. 2008, 130,
14468–14470. (b) Li, B.-J.; Li, Y.-Z.; Lu, X.-Y.; Liu, J.; Guan, B.-T.; Shi,
Z.-J. Angew. Chem., Int. Ed. 2008, 47, 10124–10127. (c) Quasdorf, K. W.;
Riener, M.; Petrova, K. V.; Garg, N. K. J. Am. Chem. Soc. 2009, 131,
17748–17749. (d) Zhou, Q.; Srinivas, H. D.; Dasgupta, S.; Watson, M. P.
J. Am. Chem. Soc. 2013, 135, 3307–3310.
Table 1. Survey of Solvents in the SuzukiÀMiyaura Couplinga
(8) For selected examples involving aryl ethers, see: (a) Tobisu, M.;
Shimasaki, T.; Chatani, N. Angew. Chem., Int. Ed. 2008, 47, 4866–4869.
(b) Shimasaki, T.; Konno, Y.; Tobisu, M.; Chatani, N. Org. Lett. 2009,
11, 4890–4892. (c) Shimasaki, T.; Tobisu, M.; Chatani, N. Angew.
Chem., Int. Ed. 2010, 49, 2929–2932. (d) Li, X.-J.; Zhang, J.-L.; Geng,
Y.; Jin, Z. J. Org. Chem. 2013, 78, 5078–5084. (e) Sergeev, A. G.; Webb,
J. D.; Hartwig, J. F. J. Am. Chem. Soc. 2012, 134, 20226–20229.
(9) For selected examples involving aryl carbamates, see: (a)
Sengupta, S.; Leite, M.; Raslan, D. S.; Quesnelle, C.; Snieckus, V.
J. Org. Chem. 1992, 57, 4066–4068. (b) Quasdorf, K. W.; Tian, X.; Garg,
N. K. J. Am. Chem. Soc. 2008, 130, 14422–14423. (c) Antoft-Finch, A.;
Blackburn, T.; Snieckus, V. J. Am. Chem. Soc. 2009, 131, 17750–17752.
(d) Quasdorf, K. W.; Antoft-Finch, A.; Liu, P.; Silberstein, A. L.;
Komaromi, A.; Blackburn, T.; Ramgren, S. D.; Houk, K. N.; Snieckus,
V.; Garg, N. K. J. Am. Chem. Soc. 2011, 133, 6352–6363. (e) Mesganaw,
T.; Silberstein, A. L.; Ramgren, S. D.; Fine Nathel, N. F.; Hong, X.;
Garg, N. K. Chem. Sci. 2011, 2, 1766–1771. (f) Hie, L.; Ramgren, S. D.;
Mesganaw, T.; Garg, N. K. Org. Lett. 2012, 14, 4182–4185.
(10) For selected examples involving aryl sulfamates, see: (a) Macklin,
T. K.; Snieckus, V. Org. Lett. 2005, 7, 2519–2522. (b) Baghbanzadeh, M.;
Pilger, C.; Kappe, C. O. J. Org. Chem. 2011, 76, 1507–1510. (c) Ramgren,
S. D.; Silberstein, A. L.; Yang, Y.; Garg, N. K. Angew. Chem., Int. Ed.
2011, 50, 2171–2173. (d) Ackerman, L.; Sandmann, R.; Song, W. Org.
Lett. 2011, 13, 1784–1786. (e) Zhang, N.; Hoffman, D. J.; Gutsche, N.;
Gupta, J.; Percec, V. J. Org. Chem. 2012, 77, 5956–5964. (f) Chen, G.-J.;
Han, F.-S. Eur. J. Org. Chem. 2012, 3575–3579. (g) Wehn, P. M.; Du
Bois, J. Org. Lett. 2005, 7, 4685–4688.
(11) For selected examples involving aryl sulfonates, see: (a) Wilson,
D. A.; Wilson, C. J.; Moldoveanu, C.; Resmerita, A.-M.; Corcoran, P.;
Hoang, L. M.; Rosen, B. M.; Percec, V. J. Am. Chem. Soc. 2010, 132,
1800–1801. (b) Percec, V.; Bae, J.-Y.; Hill, D. H. J. Org. Chem. 1995, 60,
1060–1065. (c) Percec, V.; Bae, J.-Y.; Zhao, M.; Hill, D. H.; Percec, V. J.
Org. Chem. 1995, 60, 1066–1069. (d) Percec, V.; Bae, J.-Y.; Zhao, M.;
Hill, D. H.; Percec, V. J. Org. Chem. 1995, 60, 176–185. (e) Fan, X.-H.;
Yang, L.-M. Eur. J. Org. Chem. 2011, 1467–1471. (f) Gao, C.-Y.; Yang,
L. M. J. Org. Chem. 2008, 73, 1624–1627. (g) Percec, V. J.; Golding, G.
M.; Smidrkal, J.; Weichold, O. J. Org. Chem. 2004, 69, 3447–3452. (h)
Tang, Z.-Y.; Fu, Q.-S. J. Am. Chem. Soc. 2004, 126, 3058–3059. (i) Zim,
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(12) For recent reviews, see: (a) Rosen, B. M.; Quasdorf, K. W.;
Wilson, D. A.; Zhang, N.; Resmerita, A.-M.; Garg, N. K.; Percec, V.
Chem. Rev. 2011, 111, 1346–1416. (b) Li, B.-J.; Yu, D.-G.; Sun, C.-L.;
Shi, Z.-J. Chem.;Eur. J. 2011, 17, 1728–1759. (c) Mesganaw, T.; Garg,
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entry solvent, temp yieldb entry
solvent, temp
yieldb
1
2
3
4
5
toluene, 110 °C 100%
acetone, 75 °C 96%
EtOAc, 100 °C 100%
i-PrOAc, 110 °C 100%
n-BuOH, 110 °C 0%
6
7
8
9
t-amyl alcohol, 100 °C 100%
MTBE, 80 °C
2-Me-THF, 80 °C
DMSO, 110 °C
100%
100%
0%
10 acetonitrile, 100 °C
99%
a Conditions: NiCl2(PCy3)2 complex (5 mol %), sulfamate substrate
1 (1.00 equiv), 2 (2.50 equiv), K3PO4 (4.50 equiv), hexamethylbenzene
(0.10 equiv), 12 h. b Yield of 3 determined by 1H NMR analysis of crude
reaction mixtures using hexamethylbenzene as an internal standard.
With promising results in hand, we tested the analogous
cross-coupling of several other electrophilic partners
(Table 2). In addition to the naphthyl sulfamate (entry 1),
the corresponding carbamate15 and pivalate ester were
deemed competent substrates (entries 2À3). Furthermore,
sulfonate derivatives of 1-naphthol also gave high yields
(13) Solvents were selected from the ACS Green Chemistry Institute
Roundtable Solvent Selection Guide. See Supporting Information for
details.
(14) tert-Amyl alcohol and 2-Me-THF were selected in consultation
with the ACS Green Chemistry Institute. tert-Amyl alcohol is attractive
due to its safety profile, low freezing point (in comparison to t-BuOH),
and ability to solubilize polar compounds. 2-Me-THF is advantageous
because it is obtained from renewable feedstocks and possesses many
process chemistry-related over THF. For a discussion of 2-Me-THF,
see: Aycock, D. F. Org. Process Res. Dev. 2007, 11, 156–159.
(15) Under standard conditions using 5% Ni, 50À60% yields of 3
were obtained, with the remaining mass being an unreacted carbamate
substrate.
B
Org. Lett., Vol. XX, No. XX, XXXX