Nickel-catalyzed amination of aryl sulfamates and carbamates using an air-stable precatalyst

Article abstract of DOI:10.1021/ol301847m

A facile nickel-catalyzed method to achieve the amination of synthetically useful aryl sulfamates and carbamates is reported. Contrary to most Ni-catalyzed amination reactions, this user-friendly approach relies on an air-stable Ni(II) precatalyst, which, when employed with a mild reducing agent, efficiently delivers aminated products in good to excellent yields. The scope of the method is broad with respect to both coupling partners and includes heterocyclic substrates.

Full text of DOI:10.1021/ol301847m

ORGANIC
LETTERS
XXXX
Vol. XX, No. XX
Nickel-Catalyzed Amination of Aryl
Sulfamates and Carbamates Using
an Air-Stable Precatalyst
000–000
Liana Hie, Stephen D. Ramgren, Tehetena Mesganaw, and Neil K. Garg*
Department of Chemistry and Biochemistry, University of California, Los Angeles,
Los Angeles, California 90095-1569, United States
neilgarg@chem.ucla.edu
Received July 5, 2012
ABSTRACT
A facile nickel-catalyzed method to achieve the amination of synthetically useful aryl sulfamates and carbamates is reported. Contrary to most Ni-
catalyzed amination reactions, this user-friendly approach relies on an air-stable Ni(II) precatalyst, which, when employed with a mild reducing
agent, efficiently delivers aminated products in good to excellent yields. The scope of the method is broad with respect to both coupling partners
and includes heterocyclic substrates.
Nickel-catalyzed cross-couplings of phenol-based elec-
trophiles have received considerable attention in recent
because of their pronounced stability and capacity todirect
the installation of functional groups onto an aromatic ring
1
years. Attractive aspects of such processes include the low
1À3
through directed ortho-metalation
2
or electrophilic aro-
matic substitution processes. Although carbonÀcarbon
d
cost of Ni and the many benefits that pertain to utilizing
phenol derivatives. Of the substrates widely explored, aryl
carbamates and sulfamates are particularly attractive
bond forming reactions using aryl sulfamates and carbamates
(
4) For the use of aryl carbamates in CÀC bond forming processes,
see: (a) Quasdorf, K. W.; Riener, M.; Petrova, K. V.; Garg, N. K. J. Am.
Chem. Soc. 2009, 131, 17748–17749. (b) Finch, A. A.; Blackburn, T.;
Snieckus, V. J. Am. Chem. Soc. 2009, 131, 17750–17752. (c) Xi, L.; Li,
B.-J.; Wu, Z.-H.; Lu, X.-Y.; Guan, B.-T.; Wang, B.-Q.; Zhao, K.-Q.;
Shi, Z.-J. Org. Lett. 2010, 12, 884–887. (d) Yoshikai, N.; Matsuda, H.;
Nakamura, E. J. Am. Chem. Soc. 2009, 131, 9590–9599. (e) 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. (f) Baghbanzadeh, M.; Pilger,
C.; Kappe, C. O. J. Org. Chem. 2011, 76, 1507–1510. (g) Dallaire, C.;
Kolber, I.; Gingras, M. Org. Synth. 2002, 78, 42. (h) Sengupta, S.; Leite,
M.; Raslan, D. S.; Quesnelle, C.; Snieckus, V. J. Org. Chem. 1992, 57,
4066–4068.
(5) For the use of aryl sulfamates in CÀC bond forming processes,
see: (a) Civicos, J. F.; Gholinejad, M.; Alonso, D. A.; Najera, C. Chem.
Lett. 2011, 40, 907–909. (b) Shirbin, S. J.; Boughton, B. A.; Zammit,
S. C.; Zanatta, S. D.; Marcuccio, S. M.; Hutton, C. A.; Williams, S. J.
Tetrahedron Lett. 2010, 51, 2971–2974. (c) Albaneze-Walker, J.; Raju,
R.; Vance, J. A.; Goodman, A. J.; Reeder, M. R.; Liao, J.; Maust, M. T.;
Irish, P. A.; Espino, P.; Andrews, D. R. Org. Lett. 2009, 11, 1463–1466.
(d) Ackermann, L.; Barf u€ sser, S.; Pospech, J. Org. Lett. 2010, 12, 724–
726. (e) Leowanawat, P.; Zhang, N.; Resmerita, A.-M.; Rosen, B. M.;
Percec, V. J. Org. Chem. 2011, 76, 9946–9955. (f) When, P. M.; Du Bois,
J. Org. Lett. 2005, 7, 4685–4688. (g) Chen, G.-J.; Han, F.-S. Eur. J. Org.
Chem. 2012, 3575–3579. (h) Zhang, N.; Hoffman, D. J.; Gutsche, N.;
Gupta, J.; Percec, V. J. Org. Chem. 2012, 77, 5956–5964; see also refs 2e,
4a, 4e, and 4f.
(1) For recent reviews regarding the cross-coupling of phenolic
derivatives, 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) Yu, D.-G.; Li, B.-J.; Shi, Z.-J. Acc.
Chem. Res. 2010, 43, 1486–1495. (d) Knappke, C. E. I.; Jacobi von
Wangelin, A. Angew. Chem., Int. Ed. 2010, 49, 3568–3570. (e) Goossen,
L. J.; Goossen, K.; Stanciu, C. Angew. Chem., Int. Ed. 2009, 48, 3569–
3571.
(
2) (a) Snieckus, V. Chem. Rev. 1990, 90, 879–933. (b) Hartung, C. G.;
Snieckus, V. In Modern Arene Chemistry; Astruc, D., Ed.; WileyÀVCH:
New York, 2002; pp 330À367. (c) Macklin, T.; Snieckus, V. In Handbook
of CÀH Transformations; Dyker, G., Ed.; WileyÀVCH: New York, 2005;
pp 106À119. (d) Smith, M. B.; March, J. In March’s Advanced Organic
Chemistry, 6th ed.; John Wiley & Sons, Inc.: Hoboken, NJ, 2007; p 670.
(e) Macklin, T. K.; Snieckus, V. Org. Lett. 2005, 7, 2519–2522.
(3) Aryl carbamates may also be ortho-functionalized through tran-
sition metal-catalyzed processes; see: (a) Bedford, R. B.; Webster, R. L.;
Mitchell, C. J. Org. Biomol. Chem. 2009, 7, 4853–4857. (b) Zhao, X.;
Yeung, C. S.; Dong, V. M. J. Am. Chem. Soc. 2010, 132, 5837–5844. (c)
Nishikata, T.; Abela, A. R.; Huang, S.; Lipshutz, B. H. J. Am. Chem.
Soc. 2010, 132, 4978–4979. (d) Yamazaki, K.; Kawamorita, K.; Ohmiya,
H.; Sawamura, M. Org. Lett. 2010, 12, 3978–3981. (e) Feng, C.; Loh,
T.-P. Chem. Commun. 2011, 47, 10458–10460. (f) Gong, T.-J.; Xiao, B.;
Liu, Z.-J.; Wan, J.; Xu, J.; Luo, D.-F.; Fu, Y.; Liu, L. Org. Lett. 2011, 13,
3235–3237.
1
0.1021/ol301847m r XXXX American Chemical Society

4
have been most widely studied, several reports of car-
,5
are only available for aryl halides and typically use Zn or
11
hydrides as reducing agents.
6À9
bonÀnitrogen bond formation are available.
Amina-
tions of aryl sulfamates and carbamates are facile and
proceed in synthetically useful yields; however, the air
sensitivity of the nickel precatalyst employed in all cases
We selected phenylcarbamate 1 and phenylsulfamate 2
as substrates for the desired amination and then surveyed
Ni(II) complexes in the presence of the NHC ligand
1
0
12
(
bond forming processes.
i.e., Ni(cod)2) limits the widespread use of these CÀN
SIPr•HCl (3) and various reducing agents. Key results
are summarized in Table 1, where piperidine was employed
as the amine coupling partner. Reaction conditions utiliz-
ing Zn dust proved ineffective (entries 1 and 2), while the
use of triethylsilane gave either poor or modest results
(entries 3 and 4). Inspired by SuzukiÀMiyaura coupling
methodologies of sulfamates and carbamates, where boro-
We report the development of sulfamate and carbamate
aminations using an inexpensive air-stable nickel(II) pre-
catalyst (Figure 1). When used in combination with
phenylboronic acid pinacol ester (PhÀB(pin)) as a mild
reducing agent, this procedure provides an efficient and
user-friendly means to achieve amination reactions
across a range of aryl substrates and amine coupling
partners.
4
aÀ4f
nic acids serve to reduce Ni(II) to Ni(0) in situ,
we
tested the use of PhÀB(OH) in the amination reaction.
2
Gratifyingly, good to excellent yields could be obtained
(
1
entries 5 and 6), and the NiCl (DME) complex was
3
2
identified as the optimal Ni precatalyst (entry 6). Although
these results were promising, we found that the corre-
sponding coupling of sulfamate 2 gave inconsistent results
(entry 7). Nonetheless, it was observed that boronic esters
could be used in place of PhÀB(OH) or boroxines to give
2
more consistent results (entries 8 and 9). By using PhÀB-
(pin) as the reducing agent with NiCl (DME) as the
2
precatalyst, a 94% yield of the desired aminated product
was obtained. These conditions were also found to be
useful for the coupling of carbamate 1 (entry 10).
4
Figure 1. Amination of aryl carbamates and sulfamates using
Ni(II) precatalyst.
a
A key challenge in developing the desired amination
reaction using a Ni(II) precatalyst is the difficulty in
reducing Ni(II) to Ni(0). Although Pd(II) precatalysts
readily undergo in situ reduction with amines or phos-
phines in Pd-catalyzed BuchwaldÀHartwig couplings, the
corresponding reduction of Ni(II) is less facile. Ni-cata-
lyzed amination methodologies that use Ni(II) precatalysts
Table 1. Optimization of Amination Using Ni(II) Precatalyst
b
entry
substrate
Ni source
reducing agent
yield
c
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
2
2
2
1
Ni(acac)
NiCl (DME)
Ni(acac)
NiCl (DME)
Ni(acac)
2
Zn dust
0%
(6) For examples of sulfamate and carbamate amination, see: (a)
Mesganaw, T.; Silberstein, A. L.; Ramgren, S. D.; Fine Nathel, N. F.;
Hong, X.; Liu, P.; Garg, N. K. Chem. Sci. 2011, 2, 1766–1771.
c
2
Zn dust
0%
c
2
HÀSiEt
3
0%
c
(b) Ramgren, S. D.; Silberstein, A. L.; Yang, Y.; Garg, N. K. Angew.
HÀSiEt
51%
57%
98%
2
3
Chem., Int. Ed. 2011, 50, 2171–2173. (c) Ackermann, L.; Sandmann, R.;
Song, W. Org. Lett. 2011, 13, 1784–1786.
2
PhÀB(OH)
PhÀB(OH)
PhÀB(OH)
2
2
2
NiCl
NiCl
NiCl
NiCl
NiCl
2
(DME)
2
(DME)
2
(DME)
2
(DME)
2
(DME)
(7) For examples of the amination of aryl sulfonates, see: (a)
variable
58%
Hamann, B. C.; Hartwig, J. F. J. Am. Chem. Soc. 1998, 120, 7369–
7370. (b) Roy, A. H.; Hartwig, J. F. J. Am. Chem. Soc. 2003, 125, 8704–
8705. (c) Ogata, T.; Hartwig, J. F. J. Am. Chem. Soc. 2008, 130, 13848–
13849. (d) Gao, C.-Y.; Yang, L.-M. J. Org. Chem. 2008, 73, 1624–1627.
(PhÀBO)
3
PhÀB(pin)
PhÀB(pin)
94%
10
92%
(e) Fors, B. P.; Watson, D. A.; Biscoe, M. R.; Buchwald, S. L. J. Am.
Chem. Soc. 2008, 130, 13552–13554. (f) So, C. M.; Zhou, Z.; Lau, C. P.;
Kwong, F. Y. Angew. Chem., Int. Ed. 2008, 47, 6402–6406.
a
Conditions: Ni(II) complex (5 mol %), 3 (10 mol %), sulfamate/
carbamate substrate (1 equiv), piperidine (1.2 equiv), reducing agent
(
8) Fortheaminationof arylmethylethers, see:Tobisu, M.;Shimasaki,
T.; Chatani, N. Chem. Lett. 2009, 38, 710–711.
9) For the amination of aryl pivalates, see: Shimasaki, T.; Tobisu,
M.; Chatani, N. Angew. Chem., Int. Ed. 2010, 49, 2929–2932.
10) Ni(cod) is commercially available from Strem Chemicals Inc. or
(
0.55 equiv), NaOtBu (1.85 equiv), hexamethylbenzene (0.1 equiv), 3 h.
Yield determined by H NMR analysis of the crude reaction mixtures
b
1
(
c
using hexamethylbenzene as an internal standard. Reducing agent
(
0.8 equiv) and NaOtBu (1.4 equiv).
(
2
Sigma-Aldrich (CAS # 1295-35-8). For more information on this
catalyst, see: Wender, P. A.; Smith, T. E.; Zuo, G.; Duong, H. A.; Louie,
J. Encyclopedia of Reagents for Organic Synthesis 2006, DOI: 10.1002/
0
47084289X.rb118.pub2.
11) (a) Fan, X.-H.; Li, G.; Yang, L. M. J. Organomet. Chem. 2011,
96, 2482–2484. (b) Gao, C.-Y.; Cao, X.; Yang, L.-M. Org. Biomol.
(12) NHC ligand 3 has been employed in the Ni-catalyzed amination
of sulfamates and carbamates; see refs 6a and 6b.
(13) NiCl (DME) is commercially available from Strem Chemicals
(
6
2
Chem. 2009, 7, 3922–3925. (c) Manolikakes, G.; Gavryushin, A.;
Knochel, P. J. Org. Chem. 2008, 73, 1429–1434. (d) Amrani, R. O.;
Thomas, A.; Brenner, E.; Schneider, R.; Fort, Y. Org. Lett. 2003, 5,
Inc. (CAS #29046-78-4) at an approximate cost of $13 USD/gram.
(14) Although the optimal reaction conditions shown in Table 1
(entries 9 and 10) are generally useful across a range of substrates,
further optimization of reaction conditions for individual substrates led
to improved yields. The optimized conditions and results are shown in
Figures 2 and 3.
2311–2314. (e) Desmarets, C.; Schneider, R.; Fort, Y. J. Org. Chem.
2002, 67, 3029–3036. (f) Gradel, B.; Brenner, E.; Schneider, R.; Fort, Y.
Tetrahedron Lett. 2001, 42, 5689–5692: see also ref 8.
B
Org. Lett., Vol. XX, No. XX, XXXX

Figure 3. Amination of various amines. Reaction conditions:
NiCl
2
(DME) (5À20 mol %), 3 (10À40 mol %), sulfamate/
carbamate substrate (1 equiv), amine (1.2À2.4 equiv), PhÀ
B(pin) (0.15À1.05 equiv), NaOtBu (1.4À3.75 equiv), 3 h. Unless
otherwise noted, yields reflect those of isolated product.
a
Table 2. Survey of Halide and Pseudohalide Substrates
Figure 2. Amination of aryl sulfamates and carbamates using
morpholine. Reaction conditions: NiCl
(DME) (5À20 mol %),
2
3
(10À40 mol %), sulfamate/carbamate substrate (1 equiv),
morpholine (1.2À2.4 equiv), PhÀB(pin) (0.15À1.4 equiv),
NaOtBu (1.4À3.75 equiv), 3 h. Unless otherwise noted, yields
a
1
reflect those of isolated product. Yield determined by H NMR
analysis with hexamethylbenzene as the internal standard.
b
entry
X
yield
1
2
3
4
5
6
7
OCO
2
tBu
15%
44%
63%
4%
OPiv
OTs
OTf
I
1
4
Having identified optimal reaction conditions, we
examined the scope of aryl sulfamates and carbamates,
using morpholine asthe amine coupling partner (Figure 2).
Fused arenes were tolerated, as demonstrated by the
smooth formation of 5 and 6. The ability to form 7À12
in good yields shows the methodology’s tolerance to
nonfused arenes with a variety of substituent patterns. It
should also be noted that ortho-substituted substrates,
which are readily accessible by ortho-functionalization
25%
33%
98%
Br
Cl
a
2
Conditions: NiCl (DME) (5 mol %), 3 (10 mol %), substrate
(
(
1 equiv), morpholine (1.8 equiv), PhÀB(pin) (0.35 equiv), NaOtBu
b
2.25 equiv), hexamethylbenzene (0.1 equiv), 3 h. Yield determined by
H NMR analysis with hexamethylbenzene as the internal standard.
1
2
,3
of phenyl sulfamates or carbamates, underwent the
desired coupling to give 12À15. Heterocycles such as
indoles and pyridines were also tolerated, as revealed
by the formation of products 16À18. In many cases,
sulfamates and carbamates perform equally well in this
amination methodology.
The scope with respect to the amine coupling partner is
provided in Figure 3. In addition to morpholine, the cyclic
amines piperidine and pyrrolidine underwent the desired
coupling tofurnish 4and 19. Acyclicsecondaryaminesand
anilines reacted successfully, as shown by the formation of
20À23. Finally, amines with appended heterocycles were
also tolerated, thus giving rise to 24À25.
Given that most Ni-catalyzed amination reactions em-
ploy Ni(0) precatalysts, we tested the generality of our
optimal reaction conditions on other electrophilic sub-
strate classes using morpholine as the coupling partner
(Table 2). Although modest results were obtained using
tert-butyl phenyl carbonate and phenyl pivalate (entries
Org. Lett., Vol. XX, No. XX, XXXX
C

1
and 2), the use of phenyl tosylate was more promising,
Ni(II)-based methodology is expected to find use in various
applications that require CÀN bond construction.
giving a 63% yield of product (entry 3). Phenyl triflate was
not a suitable coupling partner (entry 4), and low yields
were observed using iodobenzene or bromobenzene as
the substrate (entries 5 and 6). On the other hand, chloro-
benzene coupled smoothly under our reaction condi-
tions to furnish the desired aminated product in 98% yield
Acknowledgment. The authors are grateful to Boehringer
Ingelheim, DuPont, Eli Lilly, Amgen, AstraZeneca, Roche,
the A. P. Sloan Foundation, the Foote family (fellowship to
S.D.R.), and the University of California, Los Angeles for
financial support. We thank Qi Liu for experimental assis-
tance. These studies were supported by shared instrumenta-
tion grants from the NSF (CHE-1048804) and the National
Center for Research Resources (S10RR025631).
(
entry 7).
In summary, we have developed a facile Ni-catalyzed
method to achieve the amination of synthetically useful aryl
sulfamates and carbamates. Our user-friendy approach
employs NiCl (DME) as a bench-stable Ni(II) precatalyst,
in addition to the mild reducing agent PhÀB(pin), to
furnish aminated products in good to excellent yields.
Given the attractive features of aryl sulfamates and carba-
mates, coupled with the transformation’s broad scope, this
2
Supporting Information Available. Experimental details
and compound characterization data. This material is avail-
able free of charge via the Internet at http://pubs.acs.org.
The authors declare no competing financial interest.
D
Org. Lett., Vol. XX, No. XX, XXXX