Homogeneous gold catalysis has found wide applications
in organic synthesis.6 As soft and carbophilic Lewis acids,
they can coordinate and activate unsaturated C-C bonds
toward intramolecular nucleophilic attack. On the basis of
this catalytic mode, gold-catalyzed [3,3]-sigmatrophic rear-
rangement of propagylic esters to allenyl esters7 and allenyl
carbinol esters to 1,3-butadien-2-ol esters8 and the isomer-
ization of allylic acetates9 have been well studied. AuCl and
AuCl3 have also been used to catalyze aza-Claisen rear-
rangement of allylic trichloriacetimidates; however, only
limited substrate scope (i.e., C1-substituted substrates) and
poor to moderate yields were obtained.10 Herein we report
a highly efficient gold(I)-catalyzed, base-induced decarboxy-
lative aza-Claisen rearrangement of allylic N-tosylcarbamates.
This transformation provides a highly regio- and stereose-
lective method for the preparation of N-tosyl allylic amines
from readily available allylic alcohols instead of allenes or
1,3-dienes as reported in the literature.11
N-Substituted allylic carbamates are generally used for the
synthesis of allylic amines via low-valent transition metal
catalyzed decarboxylative allylic substitution.12 They are also
good candidates for decarboxylative aza-Claisen rearrangement
once the NH group is deprotonated with a base. Such trans-
formation has been achieved thermally in which allylic N-
phenylcarbamates were treated with NaH at elevated temper-
atures to give N-phenyl allylic amines.13 However, very few
metal catalysts have been introduced to this kind of transforma-
tion.14 We chose allylic N-tosylcarbamates as the starting point
because it is highly acidic (pKa ) 8.5) and can be completely
deprotonated with simple organic base. With 1 equiv of
diisopropylethylamine (DIPEA) and 1a in toluene, a series of
gold catalysts were examined. The best result was obtained
when 5 mol % AuCl/AgOTf was used, affording 2a in 60%
yield (Table 1, entries 1-6). Solvent screening revealed that
1,2-dichloroethane (DCE) was the best choice, leading to 90%
isolated yield of 2a within 3 h (Table 1, entry 7).15 Remarkably,
we discovered that the reaction run in water was as efficient as
that in DCE (Table 1, entry 8).
Control experiments revealed that both the Au(I) catalyst and
base are necessary for this transformation. In the presence of
DIPEA, the reaction did not proceed in water without AuCl/
AgOTf or with AgOTf alone, even at 100 °C for 12 h. In
contrast, in the absence of the base, complete decomposition
of 1a to p-toluenesulfonamide took place under the AuCl/
AgOTf catalysis condition in less than 3 h.16 By screening
various organic and inorganic bases,15 we found that a complete
deprotonation of 1a with a stoichiometric amount of DIPEA
was essential to prevent the undesired decomposition and
therefore ensure a high yield of 2a. Other N-substituted allylic
carbamates such as N-Cbz- and N-Boc-substituted substrates
were also investigated under the optimized conditions; however,
no corresponding allylic amines were produced. These results
indicated that the reactivity of the substrate is highly dependent
on the NH acidity of the carbamate.
With optimized conditions in hand, we further tested the
substrate scope of this decarboxylative allylic amination in
water. Monosubstituted olefinic substrates generally gave the
desired products in good yields (Table 2, entries 1-5). When
the allylic position (C3) was substituted with alkyl or aryl
groups, high stereoselectivities (88:12 to 97:3) were achieved
with E isomers as the main products (Table 2, entries 2-4, 6,
and 11). Conjugated N-tosyl dienylamine 2g was produced from
the 1,4-diene substrate 1g in a moderate yield with a 88:12 E/Z
ratio (Table 2, entry 6). 1,2-Disubstituted olefinic substrates were
also examined, and the steric effect seemed to be crucial. For
substrates with less hindered substitutuent at C1 position, the
corresponding products were obtained in good yields (Table 2,
entries 7 and 8), whereas only moderate yields for more
hindered sec-butyl- or benzyl-substituted substrates, even after
prolonged reaction time (Table 2, entries 9 and 10). Cyclohex-
2-enyl N-tosylcarbamate (1m) also afforded the desired product
2m in a 42% yield (Table 2, entry 12).
Table 1. Optimization of Reaction Conditionsa
(7) (a) Marion, N.; Nolan, S. P. Angew. Chem., Int. Ed. 2007, 46, 2750.
(b) Zhang, L. J. Am. Chem. Soc. 2005, 127, 16804. (c) Marion, N.; D´ıez-
Gonza´lez, S.; de Fre´mont, P.; Noble, A. R.; Nolan, S. P. Angew. Chem.,
Int. Ed. 2006, 45, 3647. (d) Zhang, L.; Wang, S. J. Am. Chem. Soc. 2006,
128, 1442. (e) Wang, S.; Zhang, L. J. Am. Chem. Soc. 2006, 128, 8414. (f)
Buzas, A.; Istrate, F.; Gagosz, F. Org. Lett. 2006, 8, 1957.
(8) Buzas, A. K.; Istrate, F. M.; Gagosz, F. Org. Lett. 2007, 9, 985.
(9) (a) Marion, N.; Gealageas, R.; Nolan, S. P. Org. Lett. 2007, 9, 2653.
(b) Gourlaouen, C.; Marion, N.; Nolan, S. P.; Maseras, F. Org. Lett. 2009,
11, 81.
,
entry
catalyst
AuCl
AuCl/AgOTf
Au(L1)CI/AgOTf
Au(L2)CI/AgOTf
AuCl3
AuCl3/AgOTf
AuCl/AgOTf
AuCl/AgOTf
solvent
time (h)
conv (%)b c
1
2
toluene
toluene
toluene
toluene
toluene
toluene
DCE
H2O
H2O
H2O
H2O
3
3
3
3
3
3
3
3
10
62 (60)
<5
<5
12
10
92 (90)
90 (89)
0
(10) (a) Jaunzeme, I.; Jirgensons, A. Synlett 2005, 2984. (b) Jamieson,
A. G.; Sutherland, A. Org. Biomol. Chem. 2006, 4, 2932. (c) Swift, M. D.;
Sutherland, A. Tetrahedron Lett. 2007, 48, 3771. (d) Jaunzeme, I.;
Jirgensons, A. Tetrahedron 2008, 64, 5794.
3d
4d
5
(11) (a) Kinder, R. E.; Zhang, Z.; Widenhoefer, R. A. Org. Lett. 2008,
10, 3157. (b) Brouwer, C.; He, C. Angew. Chem., Int. Ed. 2006, 45, 1744.
(c) Giner, X.; Najera, C. Org. Lett. 2008, 10, 2919.
6
7
8
(12) (a) Mellegaard-Waetzig, S. R.; Rayabarapu, D. K.; Tunge, J. A.
Synlett 2005, 2759. (b) Singh, O. V.; Han, H. J. Am. Chem. Soc. 2007,
129, 774. (c) Singh, O. V.; Han, H. Org. Lett. 2007, 9, 4801.
(13) Synerholm, M. E.; Gilman, N. W.; Morgan, J. W.; Hill, R. K. J.
Org. Chem. 1968, 33, 1111.
9e
10e
11f
12
12
3
AgOTf
AuCl/AgOTf
0
decomp
(14) For a similar transformation via Pd(II)-catalyzed ꢀ-heteroatom
elimination, see: Lei, A.; Lu, X. Org. Lett. 2000, 2, 2357.
(15) For details, see Supporting Information.
a Reaction condition: 0.3 mmol substrate in the indicated solvent.
b Conversion determined by 1H NMR with nitrobenzene as internal
standard. c Isolated yields shown in the parentheses. d L1 ) PPh3, L2 )
[P(t-Bu)2(o-Phenyl)Ph]. e At 100 °C. f Without DIPEA.
(16) Similar decomposition of allylic N-tosylcarbamates in Au(I)-
catalyzed condition has been observed. See: Liu, X. Y.; Li, C. H.; Che,
C. M. Org. Lett. 2006, 8, 2707.
Org. Lett., Vol. 12, No. 5, 2010
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