Intermolecular amination of allyl alcohols with sulfamates: Effective utilization of mercuric catalyst

Article abstract of DOI:10.1002/ejoc.201100054

Herein, we describe the intermolecular amination of allyl alcohols with sulfamates, which have been underutilized as nitrogen nucleophiles for allylic amination. Methyl sulfamate is a good nucleophile in the presence of mercuric triflate and efficiently generates monoallylation products in excellent yield at room temperature. Furthermore, the solid-supported mercuric catalyst silaphenyl mercuric triflate also showed remarkable catalytic activity for the allylic amination. Intermolecular amination of allyl alcohol with sulfamate as a modifiable nitrogen nucleophile is presented. Mercuric reagents act as highly efficient catalyst for the allylic amination, and the procedure was applied to the preparation of various amine derivatives. In many cases, the reaction can be carried out at room temperature and is applicable to a large range of allylic alcohols to give the monoallylated products in excellent yield. Copyright

Full text of DOI:10.1002/ejoc.201100054

SHORT COMMUNICATION
DOI: 10.1002/ejoc.201100054
Intermolecular Amination of Allyl Alcohols with Sulfamates:
Effective Utilization of Mercuric Catalyst
Hirofumi Yamamoto,*[a] Elisabeth Ho,[a] Ikuo Sasaki,[a] Mizuho Mitsutake,[a]
Yuichi Takagi,[a] Hiroshi Imagawa,[a] and Mugio Nishizawa[a][‡]
Keywords: Allylation / Amination / Sulfur / Mercury / Supported catalysts
Herein, we describe the intermolecular amination of allyl
alcohols with sulfamates, which have been underutilized as
nitrogen nucleophiles for allylic amination. Methyl sulfamate
is a good nucleophile in the presence of mercuric triflate and
efficiently generates monoallylation products in excellent
yield at room temperature. Furthermore, the solid-supported
mercuric catalyst silaphenyl mercuric triflate also showed re-
markable catalytic activity for the allylic amination.
monoallylated products. Considering that hydrolysis of the
tosyl group did not take place upon treatment with a su-
peracid such as TfOH, we decided to switch to sulfamate
as a more modifiable nitrogen nucleophile.[9] Although sulf-
amate is now a well-known structural unit in organic syn-
thesis,[10] it has almost never been used as a nucleophile for
intermolecular aminations of allylic alcohols.[10f]
Introduction
Carbon–nitrogen bond-forming reactions are an impor-
tant tool in the synthesis of biologically active com-
pounds.[1] Indeed, the reliable and well-established Tsuji–
Trost-type allylic amination of allylic halides, acetates, and
carbonates with amine nucleophiles using Pd catalysts has
been largely employed over the last four decades.[2] The de-
velopment of an efficient strategy for allylic aminations has
attracted a great deal of interest, especially for reactions
involving the direct use of allylic alcohols as the allylation
agent.[3,4] Oshima and co-workers reported the intermo-
lecular amination of allylic alcohols with amines by using a
combination of Pd(OAc)2 and the trisodium salt of tris(m-
sulfonatophenyl)phosphane (tppts).[4a] The Shibasaki group
also achieved direct substitution of the hydroxy group in
allylic alcohols with sulfonamides by using a catalytic
amount of Bi(OTf)3.[5]
Likewise, we have demonstrated that a catalytic amount
of Hg(OTf)2 effectively promoted the cyclization of N-tosyl-
anilinoallyl alcohols to afford 2-vinyl-substituted indolines
Results and Discussion
Initially, we examined the allylic amination of commer-
[Equation (1)].[6] Recently, we found that the cyclization ap- cially available 2-cyclohexen-1-ol (5) with methyl sulfamate
plied to intermolecular allylic amination proceeded under (7a) in the presence of Hg(OTf)2 to establish the ideal reac-
the Hg(OTf)2-catalytic system. The amination of allyl tion conditions (Table 1). The use of acetonitrile, nitrometh-
alcohol 3 with tosylamide occurred efficiently to provide ane, and aromatic solvents, such as benzene or toluene, af-
monoallylated sulfonamide 4 in excellent yield [Equa- forded the desired monoallylation product 8a in low yield
tion (2)].[7,8] A Tsuji–Trost-type allylic amination using after 12 h (Table 1, Entries 1–4). In contrast, dichlorometh-
amine generates a mixture of mono- and diallylation reac- ane showed remarkable reactivity, giving rise to 8a in 88%
tion products.[4a,4b] However, the method using a sulfon- yield (Table 1, Entry 5). We found that 1.5 equiv. of methyl
amide-type nucleophile is more useful in generating sulfamate was sufficient to promote the amination reaction
to give 8a in 90% yield within 4 h (Table 1, Entry 6).[11] The
known combination[5] of Bi(OTf)3 and KPF6, which pro-
[a] Faculty of Pharmaceutical Sciences, Tokushima Bunri
University
motes the amination of allylic alcohol with tosylamide, af-
Yamashiro-cho, Tokushima 770-8514, Japan
forded a trace amount of 8a along with dimerized 9 as a
byproduct (Table 1, Entry 9). In addition, combinations of
Pd(OAc)2 and additives such as Et3B[4b] or Et2Zn[3b] were
inefficient at inducing allylic amination (Table 1, Entries 10
Fax: +81-88-655-3051
E-mail: hirofumi@ph.bunri-u.ac.jp
[‡] Deceased May 1, 2010
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201100054.
Eur. J. Org. Chem. 2011, 2417–2420
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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H. Yamamoto et al.
SHORT COMMUNICATION
and 11). Even with allyl carbonate derivative 6 as the allylic Table 2. Hg(OTf)2-catalyzed amination of alcohol 5 with various
sulfamates.[a]
source, methyl sulfamate did not work under general reac-
tion conditions for allylic amination using a Pd catalyst
(Table 1, Entries 12 and 13). Moreover, the majority of allyl
carbonate was subject to decomposition under reflux condi-
tions. Next, the effect of some O-substituted sulfamate nu-
cleophiles was confirmed by submitting 5 to a variety of
Entry
R
7 [1.5 equiv.]
Time [h]
8 [%][b]
alkyl and aryl sulfamates 7b–i using Hg(OTf)2 (2 mol-%)
in dichloromethane (Table 2). When sulfamate with alkyl
substituents were used, the corresponding allylic sulfamates
were obtained in moderate yield (Table 2, Entries 1–5; 65–
86%). In the case of phenyl sulfamate (Table 2, Entry 6),
the reaction rate was decreased compared to that of alkyl
sulfamates, as 5 mol-% of Hg(OTf)2 was necessary to in-
duce the amination. Furthermore, the contribution from
substitution of the phenyl sulfamate was not particularly
marked (Table 2, Entries 7 and 8). Among the sulfamates
evaluated, methyl sulfamate (7a) showed the best reactivity
for the amination. Thus, 7a was chosen to ascertain the ver-
satility of the reaction.
1
2
3
4
5
6
7
8
nPr
CH2Cy
Cy
CH2C6F5
CH2CCl3
Ph
7b
7c
7d
7e
7f
7g
7h
7i
4
4
8
4
4
8
8
8
86
77
72
79
65
26/80[c]
34/80[c]
35/83[c]
4-FC6H4
4-OMeC6H4
[a] Reactions were conducted with 5 (1.0 mmol) and 7 (1.5 mmol).
[b] Isolated yield. [c] Reaction was carried out using 5 mol-% of
Hg(OTf)2.
possessing symmetrical substituents (Table 3, Entries 1–4).
In all cases, methyl sulfamate adducts were obtained in very
good yield even when using sterically hindered allylic
alcohol 10c, which afforded 11c in 91% yield within a rea-
sonable reaction time (Table 3, Entry 3). To elucidate the
regioselectivity of the allylic amination, various asymmetri-
cal substituted alcohols were subjected to reaction with
methyl sulfamate under the same conditions (Table 3, En-
tries 5–12).
Table 1. Optimization of Hg(OTf)2-catalyzed direct allylic amina-
tions using methyl sulfamate (7a).[a]
Entry
Catalyst
[mol-%]
Solvent
Sub-
7a
Yield 8a
strate [equiv.] [%][b]
The use of either structural isomer 10e or 10f led to a
mixture of 11e or 11f in the same 1.8:1 ratio (Table 3, En-
tries 5 and 6). These results suggest that an equilibrium be-
tween 11e and 11f exists under the given reaction condi-
tions.[12] As a consequence, formation of thermodynami-
cally more stable isomer 11e was slightly favored over for-
mation of 11f. This difference in thermodynamic stability
of reaction products was even more pronounced in the case
of tert-butyl-substituted allylic alcohols 10g and 10h, which
gave a mixture of 11g to 11h in a ratio of 19:1 (Table 3,
Entries 7 and 8). In the case of phenyl-substituted allylic
alcohols 10i and 10j complete regioselectivity was observed,
resulting in the formation of single isomer 11i in 74 and
69% yield, respectively (Table 3, Entries 9 and 10). Conju-
gated diene alcohol 10k and nonconjugated 10l also af-
forded the same conjugated dienyl sulfamate 11k (Table 3,
Entries 11 and 12). Indeed, no trace of isomer 11l was de-
tected by NMR spectroscopy, and only conjugated 11k was
isolated. The effect of some functional groups on 2-cy-
clohexen-1-ol was then investigated by using dia-
stereomerically pure cis-5-substituted derivatives. By com-
parison to naked 5, ethoxymethyl-substituted 10m pre-
sented similar reactivity, affording adduct 11m (syn/anti =
1:6) in 82% yield after 9 h at room temperature. Substitu-
tion with a ketone or ester group led to a decrease in reac-
tivity so that after 12 h 11n and 11o were obtained in only
1
2
3
4
5
6
7
8
Hg(OTf)2 [2]
Hg(OTf)2 [2]
Hg(OTf)2 [2]
Hg(OTf)2 [2]
Hg(OTf)2 [2]
Hg(OTf)2 [2]
Hg(OTf)2 [2]
Hg(OTf)2 [1]
Bi(OTf)3 [5]
CH3CN
CH3NO2
C6H6
C6H5CH3
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
dioxane
THF
5
5
5
5
5
5
5
5
5
5
5
6
6
2
2
2
2
2
1.5
1
1.5
43
69
69
70
88
90[c]
52
68
9[d]
10[f]
11[g]
12[h]
13[i]
1.5 trace/72[e]
Pd(OAc)2 [5]
Pd(OAc)2 [5]
Pd(PPh3)2Cl2 [5]
1.5
1.5
1.5
1.5
0/28[e]
0/38[e]
0
C6H5CH3
CH2Cl2
[Pd(C3H5)Cl]2 [5] CH2Cl2
0/10[j]
[a] Reactions were conducted with 5 (1.0 mmol) and 7a (1.0–
2.0 mmol). [b] Isolated yield. [c] Starting material 5 disappeared
within 4 h. [d] Reaction was carried out using KPF6 (2 mol-%) and
CuSO4 (10 equiv). [e] Homodimer 9 was obtained under the reac-
tion conditions after 12 h. [f] Reaction was carried out using nBu3P
(20 mol-%) and Et3B (30 mol-%). [g] Reaction was carried out
using nBu3P (40 mol-%) and Et2Zn (3.2 equiv.). [h] Reaction was
carried out using PPh3 (10 mol-%) and NEt3 (20 mol-%) at reflux.
[i] Reaction was carried out using PPh3 (10 mol-%) and NEt3
(20 mol-%) at reflux. [j] Reaction was carried out for 2 h.
Table 3 shows the reactivity of 7a towards a variety of 19 and 56% yield, respectively (Table 3, Entry 14 and 15).
allylic alcohol derivatives. Initially we examined the amin- However, after short exposure to reflux conditions the yield
ation of 2-cyclopenten-1-ol (10a) and acyclic allylic alcohols of 11n and 11o increased to 86 and 90%, respectively.
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Eur. J. Org. Chem. 2011, 2417–2420

Intermolecular Amination of Allyl Alcohols with Sulfamates
Table 3. Hg(OTf)2-catalyzed direct allylic amination of various all-
The availability of monoallylated methyl sulfamate was
demonstrated by the synthesis of compounds 12–16 from
11n (Scheme 1). Transformation into amine derivative 13
was easily achieved by using 1 n HCl at room temperature
from tert-butylcarbonyl derivative 12,[13] which was pre-
pared from 11n by treatment with Boc2O in the presence of
DMAP. The conversion into tert-butylcarbonyl derivative
14 also succeeded at 0 °C within 5 min under the same
acidic conditions. Furthermore, the formation of a quater-
nary carbon center from 12 was successfully carried out by
using KHMDS to afford single diastereoisomer 16 in good
yield.[14] Indeed the migration of the tert-butylcarbonyl
group took place under complete syn regioselectivity
through accessible conformational state 15. Thus, our meth-
odology offers a novel alternative strategy for the stereose-
lective construction of quaternary carbon centers that are
otherwise difficult to access by conventional procedures.
ylic alcohols with 7a.[a]
Scheme 1. Transformations of methyl sulfamate adduct 11n.
Development of reactions catalyzed by heterogeneous
reagents is attractive and a challenging subject in view of
green chemistry. Therefore, the utility of the solid-sup-
ported mercuric catalyst silaphenyl mercuric triflate (17)[15]
was also investigated by analyzing the reaction of 5 with 7a
to give methyl sulfamate adduct 8a (Scheme 2). When 17
(10 mol-%) was employed, the reaction afforded 8a in 90%
yield. The catalyst was recovered by simple filtration by
using a cotton wool plug and was reused[16] without signifi-
cant leaching of the metal.
Scheme 2. Application of solid-supported mercuric catalyst 17.
[a] Reactions were conducted with 10 (0.5–1.0 mmol) and 7a (0.75–
1.5 mmol). [b] Isolated yield. [c] A 1.8:1 mixture of 11e/11f was ob-
tained. [d] A 19:1 mixture of 11g/11h was obtained. [e] Product was
11i. [f] Product was 11k. [g] Reaction was carried out under reflux
conditions for 2 h. [h] Reaction was carried out under reflux condi-
tions for 0.3 h.
Conclusions
In many respects, intermolecular amination of allylic
alcohols with methyl sulfamate catalyzed by mercuric rea-
Eur. J. Org. Chem. 2011, 2417–2420
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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H. Yamamoto et al.
SHORT COMMUNICATION
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gents such as Hg(OTf)2 and silaphenyl mercuric triflate
constitutes a reasonable alternative for the preparation of
various amines. Indeed, in many cases the procedure can be
carried out at room temperature and is applicable to a large
range of allylic alcohols to give the monoalkylated products
in excellent yield. Furthermore, encouraged by our recent
success in inducing enantioselective cyclization of sulfon-
amide allylic alcohols,[6a] asymmetric intermolecular amin-
ation catalyzed by chiral Hg(OTf)2 complexes is now under [4] Recent reports on the direct allylic amination of allylic
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Chem. 2007, 119, 413; Angew. Chem. Int. Ed. 2007, 46, 409–
General Procedure for the Direct Allylic Amination of Allylic
Alcohols with Sulfamates: A 0.1-m CH3CN solution of Hg(OTf)2
(0.2 mL, 0.02 mmol) was added to a dried two-neck flask. After
evaporation of the solvent, Hg(OTf)2 was suspended in CH2Cl2
(5.0 mL). To the suspension was added 5 (98 mg, 1.0 mmol) and
7a (167 mg, 1.5 mmol) under an argon atmosphere. The mixture
was stirred at room temperature for 4 h and then directly subjected
to column chromatography (CH2Cl2/EtOAc, 20:1) to afford allyla-
mine 8a (88 mg, 90%; Table 1, Entry 6) as a colorless oil.
413.
[6] a) H. Yamamoto, E. Ho, K. Namba, H. Imagawa, M. Nishiz-
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[7] H. Yamamoto, E. Ho, I. Sasaki, M. Mitsutake, Y. Takagi, H.
Imagawa, M. Nishizawa, unpublished results (cf. Supporting
Information).
[8] M. Nishizawa, H. Imagawa, H. Yamamoto, Org. Biomol.
Chem. 2010, 8, 511–521.
The Formation of a Quaternary Carbon Center from 11n: To a solu-
tion of 11n (89 mg, 0.34 mmol) in CH2Cl2 (1.5 mL) was added suc-
cessively DMAP (4.1 mg, 0.03 mmol) and Boc2O (73 mg,
0.34 mmol) at 0 °C. The resulting mixture was stirred for 1 h at
the same temperature. Then CH2Cl2 was removed under reduced
pressure, and the mixture was dissolved in EtOAc and washed with
distilled H2O (10 mL), dried with anhydrous Na2SO4, filtered, and
concentrated. Crude residue 12 was dissolved in THF (1.0 mL),
and the solution was cooled to –78 °C. A 0.5-m solution of
KHMDS in toluene (1.8 mL, 0.9 mmol) was added dropwise to the
mixture, which was stirred for 30 min at the same temperature. The
reaction mixture was quenched by the addition of saturated NH4Cl
and diluted with EtOAc. The organic layer was washed with brine
(10 mL), and the collected organic phases were dried with Na2SO4
and filtered. After the solvents were removed under reduced pres-
sure, the residue was purified by column chromatography (CH2Cl2/
EtOAc, 20:1), providing 16 (99 mg, 80%, Ͼ95%de; Scheme 1) as a
yellow syrup.
[9] M. Okada, S. Iwashita, N. Koizumi, Tetrahedron Lett. 2000,
41, 7047–7051.
[10] Recent reports on the reaction using sulfamate derivatives: a)
A. H. Stoll, S. B. Blakey, J. Am. Chem. Soc. 2010, 132, 2108;
b) S. Beaumont, V. Pons, P. Retailleau, R. H. Dodd, P. Dauban,
Angew. Chem. 2010, 122, 1678; Angew. Chem. Int. Ed. 2010,
49, 1634; c) F. J. Wyszynski, A. L. Thompson, B. G. Davis, Org.
Biomol. Chem. 2010, 8, 4246; d) S. Hanessian, S. Guesné, E.
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[11] When optically active alcohol 5 (97%ee) and 7a were used,
racemic product 8a was obtained.
[12] Unpublished results of allylic amination with tosylamide also
suggested that an equilibrium between each regioisomer exists
under the Hg(OTf)2 catalytic conditions (cf. Supporting Infor-
mation, pilot study-3).
Supporting Information (see footnote on the first page of this arti-
cle): Experimental details and copies of the NMR spectra.
[13] Derivative 12 is unstable under acidic conditions. During col-
umn chromatography on silica gel 12 decomposed into 14.
[14] The relative stereochemistry of tert-butyl ester 16 was estab-
lished by NOESY experiments (cf. Supporting Information).
[15] H. Yamamoto, I. Sasaki, Y. Hirai, K. Namba, H. Imagawa,
M. Nishizawa, Angew. Chem. 2009, 121, 1270; Angew. Chem.
Int. Ed. 2009, 48, 1244–1247.
Acknowledgments
This study was financially supported by a Grant-in-Aid from the
Ministry of Education, Culture, Sports, Science, and Technology
of the Japanese Government and a MEXT (Ministry of Education,
Culture, Sports, Science and Technology) Senryaku.
[16] The catalytic activity of recovered 17 was investigated by ana-
lyzing the same reaction of 5 with 7a to give 8a. The recycled
catalyst displayed complete catalytic activity until the fourth
reaction. However, a longer reaction time was required for the
fifth reaction (cf. Supporting Information).
[1] a) B. M. Trost, M. L. Crawley, Chem. Rev. 2003, 103, 2921; b) J.
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VCH, Weinheim, 2000, pp. 593–650; d) T. E. Müller, K. C.
Received: January 14, 2011
Published Online: March 10, 2011
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Eur. J. Org. Chem. 2011, 2417–2420