Gold(I)- and bronsted acid-catalyzed ring-opening of unactivated vinylcyclopropanes with sulfonamides

Article abstract of DOI:10.1002/adsc.200700006

The gold(I)- or Bronsted acid-catalyzed reaction of unactivated vinylcyclopropanes (VCPs) with sulfonamides affords useful homoallylic amine derivatives. This ring-opening reaction occurs in a highly selective manner affording in the case of α-phenyl-subs

Full text of DOI:10.1002/adsc.200700006

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DOI: 10.1002/adsc.200700006
Gold(I)- and Brønsted Acid-Catalyzed Ring-Opening of
Unactivated Vinylcyclopropanes with Sulfonamides
Wen-Jian Shi,a Yanyun Liu,a Pietro Butti,a and Antonio Tognia,*
a
Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology, ETH Zürich,
8093 Zürich, Switzerland
Fax : (+41)-44-632-1310; e-mail: togni@inorg.chem.ethz.ch
Received: January 6, 2007
Supporting information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: The gold(I)- or Brønsted acid-catalyzed
reaction of unactivated vinylcyclopropanes (VCPs)
with sulfonamides affords useful homoallylicamine
derivatives. This ring-opening reaction occurs in a
highly selective manner affording in the case of a-
phenyl-substituted VCPs products with the E-con-
figuration exclusively.
As part of our continuing efforts in this area, we
describe herein the first gold(I)-catalyzed highly ste-
reoselective intermolecular ring-opening of unactivat-
ed VCPs with sulfonamides. This hydroamination re-
action provides an alternative approach for the prepa-
ration of useful derivatives of homoallylicamines that
are widely used in the synthesis of bioactive heterocy-
cles.[6,7]
Keywords: catalysis; gold; hydroamination; ring-
opening; vinylcyclopropanes
Initially, we chose VCP 1a and benzenesulfonamide
for a study of the corresponding hydroamination in
the presence of gold complexes. Thus, compound E-
2aa[8] was identified as the main product isolated from
the reaction mixtures.[9] Moreover, the E configura-
tion was confirmed by an X-ray crystallographic study
Unactivated vinylcyclopropanes (VCPs) are potential- of its analogue 2ab whose structure is shown in
ly best-suited substrates for transition metal-catalyzed Figure 1.[10]
reactions involving ring-opening processes. However,
Further optimizations of this reaction were carried
only a limited number of such transformations has out by screening various metal catalysts, solvents and
been reported so far. These include the classical rear- conditions (Table 1). We found that by using 10
rangement to cyclopentenes and related reactions,[1a–c] mol% AuCl
(PPh3)/AgOTf and 3 equivs. of 1a in tolu-
G
[5+2] cycloadditions,[1d,e] couplings with aldehydes,[1f] ene at 508C (entry 14), 2aa could be isolated in 73%
and a silaboration reaction.[1g] However, the ring- yield. Interestingly, the yield of 2aa did not drastically
opening of unactivated VCPs using nitrogen nucleo-
philes remains vastly unexplored, despite its great po-
tential as a new complementary carbon-nitrogen
bond-forming reaction.[2]
Transition metal-catalyzed hydroamination is an ex-
tremely attractive and challenging process for the syn-
thesis of amines, having witnessed an increasing aca-
demicand industrial interest, thus evolving to a
highly active research area in the past decade.[3,4]
Gold complexes have been shown very recently to ex-
hibit unique properties in the activation of unsaturat-
ed carbon-carbon bonds and have been used in the
catalytic hydroamination of a series of alkynes, al-
lenes, 1,3-dienes and simple alkenes, thus affording
1,2-addition products.[5] Despite these achievements,
an extension of the scope of possible substrates for
hydroamination reactions is still very desirable.
Figure 1. ORTEP representation of compund E-2ab (proba-
bility ellipsoids at the 50% level). Selected bond lengths
À
À
(Š) and angles (8): S(1) N(1), 1.609(4); N(1) C(1),
1.472(6); C(3) C(4), 1.320(7); C(1) N(1) S(1), 120.7(3).
À
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Table 1. Optimization of reaction conditions.[a]
Entry
Metal catalyst
Solvent
Yield [%] of 2aa/3aa[b]
1
2
3
4
-
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
THF
-
AuCl3/3 AgOTf
-/64
39/-
51/-
53/-
48/-
32/-
-/48
-/63
-
-/42
-
-/37
73/-
AuCl
AuCl
AuCl
ACHTREUNG
ACHTREUNG
5
ACHTREUNG
6
AuCl[P
ACHTREUNG
7[c]
8
AuCl[P
AuCl[P
ACHTREUNG
9
ACHTREUNG
10[d]
11
12[e]
13[f]
14[g]
AuCl
AuCl
AuCl
AuCl
AuCl
ACHTREUNG
A
Cl
A
A
toluene
toluene
toluene
A
AHCTREUNG
[a]
0.2 mmol PhSO2NH2, 0.3 mmol 1a, 0.02 mmol metal catalyst, 2.0 mL solvent, 508C, 24 h.
Isolated yield.
L=(2-biphenyl)-di-tert-butylphosphine.
Polymer formed.
Room temperature.
808C.
[b]
[c]
[d]
[e]
[f]
[g]
0.6 mmol 1a.
change when using gold(I) complexes containing elec- though in these cases both more elevated tempera-
tron-rich and/or more sterically demanding phosphine tures and a prolonged reaction time were necessary
ligands (entries 3, 4, 6, and 7 vs. 5). On the other (entries 14 and 16).
hand, catalysts with electron-deficient arylphosphines
To gain a first insight into the reaction mechanism,
led to the preferred formation of product 3aa, isolated we performed experiments with the deuterated sulfon-
in moderate yields (entries 8 and 9).[11] Moreover, amide TsND2, at a deuteration degree of 60%. As de-
metal salts such as AuCl3, AgOTf, and Pd
were found to be catalytically inactive.
ACHTREUNG
With the optimized conditions in hand, we exam- with a level of deuterium incorporation of 38% based
1
ined the scope of this gold(I)-catalyzed ring-opening on H (700 MHz), 13C NMR and 13C-1H HZQC spec-
with a variety of amines and unactivated VCPs troscopic analysis. The relatively low deuterium con-
(Table 2). Thus, for a series of nitrogen nucleophiles, tent may be attributed to D/H exchange of TsND2
including aniline, benzamide, a benzotriazole and sub- with adventitious proton sources in the reaction mix-
stituted sulfonamides, TsNHMe gave excellent yield ture[12] and/or to a weak kineticisotope effect. More-
of ring-opening product 2ae (entry 5), while aniline over, competition experiments using the VCPs 1a–f
and benzamide did not show any conversion in 24 h. allowed to establish a clean linear free energy rela-
The large reactivity differences of these nucleophiles tionship. The corresponding Hammett plot is shown
may be attributed to differences in basicity and solu- in Figure 2 and indicates that, for example, the methyl
bility.[3f] With TsNHMe as nucleophile, we were de- substituted substrate 1b reacts ca. 35 times faster than
lighted to find that a variety of VCPs, both bearing the analogous trifluoromethyl derivative 1f.
aryl or alkyl substitutents can be successfully hydro-
Further investigations revealed that the Brønsted
aminated to form ring-opened products in high yields. acid HOTf also can catalyze the ring-opening reaction
The electronic nature of the para-substituent on the
phenyl ring of substrates of type 1a has a significant
impact on their reactivity, with trifluoromethyl lead-
ing to a slow reaction and only a moderate yield, and
methoxy affording a complex mixture (entries 10 and
11, respectively). Furthermore, this ring-opening reac-
tion also could be extended to trisubstituted VCPs, al- Scheme 1. Deuterium labelling experiment.
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Table 2. Ring-opening of unactivated VCPs 1 with RR’NH.[a]
Entry
RR’NH
VCPs, 1: R1, R2, R3
Yield of 2[b] [%]
1
2
3
4
5
6
7
8
PhSO2NH2
pBr-C6H4SO2NH2
TsNH2
1,2,3-benzotriazole
TsNHMe
TsNHMe
TsNHMe
TsNHMe
TsNHMe
TsNHMe
TsNHMe
TsNHMe
TsNHMe
TsNHMe
TsNHMe
TsNHMe
TsNHMe
H, H, Ph (1a)
1a
1a
1a
73 (2aa)
30 (2ab)
33 (2ac)
10 (2ad)
97 (2ae)
99 (2ba)
90 (2ca)
96 (2da)
96 (2ea)
58 (2fa)
N.D. (2ga)
99 (2ha)
80 (2ia)
76 (2ja)
57 (2ka)
54 (2la)
99 (2ma)
1a
H, H, p-Me-C6H4 (1b)
H, H, p-(t-Bu)-C6H4 (1c)
H, H, p-Cl-C6H4 (1d)
H, H, p-F-C6H4 (1e)
H, H, p-CF3-C6H4 (1f)
H, H, p-MeO-C6H4 (1g)
H, H, 2-naphthyl (1h)
H, H, phenylethyl (1i)
H(Me), Me(H), Ph (1j)
Ph, H, H (1k)
9
10
11[c]
12
13[d]
14
15[e]
16[e]
17[f]
Ph(Me), Me(Ph), H (1l)
H, H, cyclohexyl (1m)
[a]
0.2 mmol amine, 0.6 mmol 1, 0.02 mmol AuPPh3OTf, 2.0 mL toluene, 508C, 24 h.
Isolated yield.
Complete conversion, unidentified mixture, room temperature.
dr=80:20.
808C, 1.0 mmol 1, 63 h.
dr=86:14.
[b]
[c]
[d]
[e]
[f]
Figure 2. Hammett plot for the ring-opening of 1a–f with
TsNHMe using PPh3/AuOTf as catalyst.
Figure 3. Hammett plot for the ring- opening of 1a–e with
TsNHMe using HOTf as catalyst.
affording very similar results when compared to the value of À1.8, comparable to the value of À2.1 found
PPh3/AuOTf catalyst under otherwise the same condi- when using the Au catalyt.
tions and at the same concentration level.[13] Thus,
Thus, the question arose, whether PPh3/AuOTf or
employing 10 mol% HOTf as catalyst, the ring-open- HOTf, possibly generated from the reaction of the
ing of 1a with TsNHMe gave 92% yield at 508C in gold(I) precursor with sulfonamide, is the only true
24 h. Furthermore, competition experiments using catalyst. However, based on Heꢁs recent results,[13a] it
HOTf as catalyst also established a clean linear free appears unlikely that the in situ reaction of PPh3/
energy relationship, shown in Figure 3, displaying a 1 AuOTf with TsNH2 may generate HOTf in a suffi-
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Wen-Jian Shi et al.
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HOTf-catalyzed ring-opening reaction: To the solution of
a-phenylvinylcyclopropane 1a (88 mg, 0.6 mmol) and
TsNHMe (39 mg, 0.2 mmol) in 2 mL toluene at 508C, HOTf
(3.0 mg, 0.02 mmol) was added using a micro-syringe. The
resulting solution was stirred for 24 h. Then, the reaction
mixture was cooled to room temperature, evaporated and
the residue was purified by silica gel column chromatogra-
phy (eluent: EtOAc/petroleum ether=1/3) to afford the
product 2ae as a colorless liquid; yield: 60 mg (92%).
Scheme 2. Plausible simplified reaction mechanism for the
Au(I)-catalyzed ring-opening of VCP 1a.
Acknowledgements
ciently large concentration to account for the activity
observed when operating with 10 mol% HOTf.
Therefore, after having verified that AgOTf alone is
not a catalyst, we assume that the cationic gold(I)
complex is the main catalytically active species gener-
ated in situ. Thus, it is reasonable to assume that the
activation of the VCP occurs via coordination of the
olefinic bond to the cationic Au(I) species, thus form-
ing an intermediate of type A (Scheme 2).[14] This
should be favored by electron-donating groups at the
para-position of the phenyl ring in derivatives of 1a
and could account for the strongly negative slope dis-
played by the Hammett plot. The regiospecific deute-
rium incorporation observed in the experiment with
TsND2 invokes the formation of an intermediate of
type B, an Au(I)-primary alkyl derivative. Its proto-
nolysis leads to product formation and regeneration
of the catalytically active species. However, it still re-
mains unclear how the crucial ring-opening step ex-
actly occurs.
Financial support by ETH Zurich is gratefully acknowledged.
We thank Dr. Heinz Rüegger and Serena Filipuzzi for their
valuable NMR assistance.
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Experimental Section
General Procedures for Gold(I)- or HOTf-Catalyzed
Ring-Opening of Unactivated VCPs with
Sulfonamides
Gold(I)-catalyzed ring-opening reaction: To a suspension of
AuPPh3OTf, prepared in situ from AuCl
A
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Visus, W. Frey, Eur. J. Org. Chem. 2006, 4905; for a
0.02 mmol) and AgOTf (5.6 mg, 0.02 mmol) in 2 mL of tolu-
ene, TsNHMe was added (39 mg, 0.2 mmol), followed by a-
phenylvinylcyclopropane 1a (88 mg, 0.6 mmol). The result-
ing mixture was stirred for 24 h at 508C. Then, the reaction
mixture was cooled to room temperature, evaporated under
vacuum, and the residue was purified by silica gel column
chromatography (eluent: EtOAc/petroleum ether=1/3) to
afford the product 2ae as a colorless liquid; yield: 63 mg
(97%).
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[9] A similar ring-opening reaction leading to homoallylic
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À
À
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