Gold- and silver-catalyzed tandem amination/ring expansion of cyclopropyl methanols with sulfonamides as an expedient route to pyrrolidines

Article abstract of DOI:10.1002/chem.200801242

An efficient synthetic route to pyrrolidines that relies on AuCl/ AgOTf-catalyzed tandem amination/ ring expansion of substituted cyclopropyl methanols with sulfonamides is reported herein. The reactions proceed rapidly at 100 °C with catalyst loadings as low as 2 mol % and produce the pyrrolidine products in yields of 30-95%. The method was shown to be applica ble to a broad range of cyclopropyl methanols, including unactivated ones, and sulfonamide substrates containing electron-withdrawing, electron-donating, and sterically-demanding substitu ents. The mechanism is suggested to involve activation of the alcohol substrate by the AuCl/AgOTf catalyst, followed by ionization of the starting material, which causes ring opening of the cyclopropane moiety and trapping by the sulfonamide nucleophile. The resultant aminated acyclic intermediate undergoes subsequent intramolecular hydroamination to give the pyrrolidine.

Full text of DOI:10.1002/chem.200801242

DOI: 10.1002/chem.200801242
Gold- and Silver-Catalyzed Tandem Amination/Ring Expansion of
Cyclopropyl Methanols with Sulfonamides as an Expedient Route to
Pyrrolidines
Weidong Rao and Philip Wai Hong Chan*[a]
Abstract: An efficient synthetic route
to pyrrolidines that relies on AuCl/
AgOTf-catalyzed tandem amination/
ring expansion of substituted cyclo-
propyl methanols with sulfonamides is
reported herein. The reactions proceed
rapidly at 1008C with catalyst loadings
as low as 2 mol% and produce the pyr-
rolidine products in yields of 30–95%.
The method was shown to be applica-
ble to a broad range of cyclopropyl
methanols, including unactivated ones,
and sulfonamide substrates containing
electron-withdrawing, electron-donat-
ing, and sterically-demanding substitu-
ents. The mechanism is suggested to in-
volve activation of the alcohol sub-
strate by the AuCl/AgOTf catalyst, fol-
lowed by ionization of the starting ma-
terial, which causes ring opening of the
cyclopropane moiety and trapping by
the sulfonamide nucleophile. The resul-
tant aminated acyclic intermediate un-
dergoes subsequent intramolecular hy-
droamination to give the pyrrolidine.
Keywords: gold · nitrogen hetero-
cycles · ring expansion · silver ·
synthetic methods
Introduction
catalyzed intramolecular cyclization of monoallylic diols
could be accomplished in good to excellent yields.[6]
A
Gold complexes have emerged as powerful and versatile
tandem amination/intramolecular hydroamination strategy
for the synthesis of pyrroles from 1-en-4-yn-3-ols mediated
by HAuCl4·4H2O and AuCl3-catalyzed allylic alkylation of
sulfonamides with allylic alcohols were recently communi-
cated by Liang et al.[7] and Liu et al.[8] In view of these
works and our ongoing program on carbon–nitrogen bond
formation,[9] we turned our attention to expanding the scope
of alcohols as pre-electrophiles in gold catalysis as the basis
for developing new strategies for constructing pyrrolidines.
The pyrrolidine ring motif is a common structural unit
found in a myriad of bioactive natural products and pharma-
ceutically interesting compounds.[10–15] These include anatox-
in,[11] hyacinthacine C1,[12] (À)-kainic acid,[13] oxazolomy-
À
Lewis acidic catalysts for stereoselective C X (X=C, N, O,
S) bond formation in recent years.[1–7] Generally, this type of
reaction relies on interaction of the gold catalyst with the p
bonds of alkenes, alkynes, and allenes. In this regard, the de-
velopment of new methods that explore the scope of other
functional groups in gold-catalyzed reactions has gained mo-
mentum. In a recent notable advance Campagne and co-
workers showed that propargylation of allylic silanes, arenes,
thiols, and alcohols by propargylic alcohols proceeds
smoothly in the presence of HAuCl4·2H2O as catalyst.[2] Fol-
lowing this seminal work, we,[3] Dyker et al.,[4] and Beller
et al.[5] reported similar efficient gold-catalyzed approaches
for Friedel–Crafts allylic alkylation, propargylation, and
benzylation of aromatic compounds with allylic, propargylic,
and benzylic alcohols. Aponick and co-workers recently
demonstrated that formation of tetrahydropyrans by gold-
AHCTUNGTRENNUNG
cin A,[14] and (+)-preussin (Scheme 1),[15] which are reported
to exhibit bioactivities ranging from antiviral to cytotoxic.
Hence, developing methods for efficient formation of this
saturated nitrogen-containing heterocycle is of immense im-
portance in organic synthesis. Recently, Krause et al.[16] and
He et al.[17] respectively described gold-catalyzed cycloiso-
merization of a-amino allenes and intra- and intermolecular
hydroamination of alkenes as mild, efficient, and atom-eco-
nomic strategies[18] for pyrrolidine ring synthesis. Following
these works, Shi et al.[19] and Togni et al.[20] independently re-
ported that tandem versions of gold-catalyzed hydroamina-
tions involving reactions of methylene cyclopropanes
(MCPs) or vinyl cyclopropanes (VCPs) with sulfonamides
[a] W. Rao, Prof. Dr. P. W. H. Chan
Division of Chemistry and Biological Chemistry
School of Physical and Mathematical Sciences
Nanyang Technological University
Singapore 637371 (Singapore)
Fax : (+65)6791-1961
E-mail: waihong@ntu.edu.sg
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200801242.
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FULL PAPER
study that delineates the possible mechanism of the AuCl/
AgOTf-catalyzed pyrrolidine formation process is also pre-
sented.
Results and Discussion
Catalyst screening: We chose cyclopropylACHTNUTRGNEUNG(phenyl)methanol
(1a) and toluene-4-sulfonamide (2a) as model substrates to
establish the reaction conditions (Table 1). The best result
was obtained by treatment of 1 equiv of 1a and 2 equiv of
2a with 5 mol% of AuCl and 5 mol% of AgOTf in toluene
at 1008C for 15 h, which furnished 3a as the sole product in
95% yield (Table 1, entry 1). The pyrrolidine product was
1
confirmed by H NMR analysis and X-ray crystal structure
determination of a closely related product (see below). No-
tably, a slightly lower yield of 91% could be obtained on
lowering the catalyst loading of both AuCl and AgOTf to
2 mol% (Table 1, entry 2). In contrast, performing the reac-
tion in other solvents gave 3a in markedly lower yields and
with a variety of side products. Use of chlorinated solvents
such as CHCl3 and 1,2-dichloroethane afforded either (E)-4-
methyl-N-(4-phenylbut-3-enyl)benzenesulfonamide (4a) as
the major product in 44% yield or 4-methyl-N,N-bis[(E)-4-
Scheme 1. Examples of bioactive compounds containing a pyrrolidine
moiety.
are also efficient preparative methods. A synthetic approach
that also relies on the exceptional activity and mild condi-
tions offered by homogenous gold catalysis but makes use
of substituted cyclopropyl methanols as starting materials,
on the other hand, is not known. Although Pd-catalyzed in-
tramolecular aminocyclization of amino-tethered allylic al-
cohols has been described,[21,22] the reactions usually require
relatively high catalyst loadings and additives. In addition,
limited examples demonstrating substrate scope and moder-
ate to good regio- and chemoselectivities have lessened
their utility in organic synthesis. In this regard, we envi-
sioned that a gold-catalyzed strategy involving the use of
substituted cyclopropyl methanols as pre-electrophiles
would be attractive from a synthetic standpoint, as the ease
of preparing the alcohol starting material provides the possi-
bility to introduce a wide variety of substituents and the po-
tential to form a quaternary carbon center by addition to a
tertiary alcohol. Moreover, H2O is potentially the only side
product. Herein we report a convenient synthetic route to
pyrrolidine derivatives that involves tandem amination/ring
expansion of substituted cyclopropyl methanols and sulfona-
mides catalyzed by AuCl in the presence of AgOTf (OTf=
trifluoromethanesulfonate) as cocatalyst (Scheme 2). The re-
action proceeds in good to excellent yields of up to 95% for
a wide variety of readily available starting materials. A
phenylbut-3-enyl]benzenesulfonamide (5a) in
a
trace
amount (Table 1, entries 3 and 4). On the other hand, when
Table 1. Optimization of reaction conditions.[a]
Entry
Catalyst
Solvent
Yield [%][b]
3a
4a
5a
6a
1
2[c]
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19[e]
20
21
22
AuCl/AgOTf
AuCl/AgOTf
AuCl/AgOTf
AuCl/AgOTf
AuCl/AgOTf
AuCl/AgOTf
Ph3PAuCl/AgOTf
Ph3PAuCl/AgSbF6
AuCl3/AgOTf
AuCl
PhMe
PhMe
CHCl3
95
91
40
67
–
–
–
44
–
–
-
–
3
–
–
–
–
–
33
–
–
–
–
[d]
A
–
MeCN
THF
–
–
2
–
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
80
42
72
–
–
–
–
–
83
–
–
–
[d]
40
10
–
–
–
–
22
–
–
–
66
–
–
28
–
–
[d]
–
–
–
–
–
–
–
AuCl3
AgOTf
FeCl3.6H2O
15
80
21
55
–
–
–
–
–
Yb
N
[d]
Cu(OTf)2
N
–
InCl3
ZnCl2
BF3·Et2O
TfOH
TfOH
–
–
3
2
–
–
–
–
[d]
71
87
–
–
–
29
p-TsOH·H2O
TFA
–
[a] All reactions were performed at 1008C for 15 h with catalyst:1a:2a
ratio of 1:20:40. [b] Yields of isolated products. [c] Reaction conducted
with a catalyst loading of 2 mol%. [d] Trace amount: <1% of compound
isolated after flash column chromatography. [e] Reaction conducted with
TfOH catalyst loading of 20 mol%.
Scheme 2. Gold- and silver-catalyzed tandem amination/ring expansion of
cyclopropyl methanols with sulfonamides.
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P. W. H. Chan et al.
the solvent was changed to MeCN, N-[cyclopropyl-
(phenyl)methyl]-4-methylbenzenesulfonamide (6a) was
Variation of the substituted cyclopropyl methanol electro-
phile: To investigate the scope of the AuCl/AgOTf-cata-
lyzed tandem amination/ring-expansion reaction, we applied
these conditions to a series of substituted cyclopropyl meth-
anols (Table 2). Reactions of substituted cyclopropyl metha-
nols containing a pendant electron-donating group with 2a
afforded the corresponding pyrrolidine compounds 3b,c and
3e in yields of 81–91% (Table 2, entries 1, 2, and 4). Similar-
ly, analogous reactions of 1 f,g containing electron-with-
drawing groups with 2a afforded the corresponding pyrroli-
dine products 3 f,g in comparable yields of 77–84%
(Table 2, entries 5 and 6). Substituted cyclopropyl methanols
1h,i bearing a sterically bulky naphthyl or 2,6-dimethylben-
zene group, respectively, were found to be good alcoholic
substrates affording good product yields (Table 2, entries 7
and 8). Similarly, tertiary substituted cyclopropyl methanols
1k,l gave the corresponding quaternary substituted pyrroli-
dines 3k,l in 60–68% yield (Table 2, entries 10 and 11).
More notably, 3m–o could be obtained in moderate to good
yields from the respective reactions of 1o–q with 2a
(Table 2, entries 14–16). Although a slightly higher catalyst
loading of 10 mol% was required, this demonstrated that
the present method is also suitable for unactivated alkyl-
substituted cyclopropyl methanols. On the other hand, ex-
treme steric effects of tertiary substituted cyclopropyl meth-
anols may play a role, since two bulky geminal groups, such
as two benzene rings, led to preferential provided acyclic
but-3-enylsulfonamide 4b in 81% yield (Table 2, entry 12).
Strongly electron donating pendant groups such as alkynyl
and methoxyphenyl on the alcohol substrate also detrimen-
tally influenced the carbon–nitrogen bond-forming process.
As shown in entries 3 and 9 in Table 2, both 3d and 3j,
which was also structurally characterized by X-ray crystal
analysis (Figure 1),[24] were obtained in comparable low
yields regardless of whether the electron-rich starting alco-
hol contained a sterically bulky group or not. Similarly, reac-
tion of alkyne 1n with 2a was found to result in formation
of acyclic enyne 4c as the sole product in 69% yield with a
cis:trans ratio of 1:1 (Table 2, entry 13).[25] Retardation of re-
action by a strongly electron-donating substituent on the
substrate has also been reported by Shi et al.[19] and Hartwig
et al.[26] in their approaches to pyrrolidines.
ACHTUNGTRENNUNG
preferentially obtained as the sole product in 33% yield,
while the use of THF as solvent resulted in a mixture of side
1
products that could not be identified by H NMR analysis
(Table 1, entries 5 and 6). The structure of 6a was confirmed
1
by H NMR analysis and X-ray crystal analysis of a closely
related product (see below).
Inspection of entries 7–22 in Table 1 reveals that tandem
amination/ring expansion of 1a with 2a in the presence of
other Lewis and Brønsted acids as catalyst are less effective.
When Ph3PAuCl was used in combination with AgOTf or
AgSbF6, or AuCl3 with AgOTf, lower product yields of 42–
80% were obtained (Table 1, entries 7–9). Moreover, in
these reactions the use of Ph3PAuCl and AgOTf resulted in
formation of 4a as a side product while those mediated by
Ph3PAuCl/AgSbF6 or AuCl3/AgOTf gave both 4a (10–40%)
and 5a (2% or less) as side products. A similar outcome
was found when reactions employing single Lewis acidic cat-
alysts such as AuCl, AuCl3, AgOTf, Cu
InCl3, Yb(OTf)3, and ZnCl2 were examined. In our hands,
reaction with Cu(OTf)2 as catalyst afforded 3a in a lower
ACHTUGNTRENN(NUG OTf)2, FeCl3·6H2O,
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
yield of 83% and a trace amount of 5a (Table 1, entry 15).
However, the analogous reactions mediated by AuCl3,
AgOTf, FeCl3·6H2O, and YbACHTNUTRGENNUG(OTf)3 were found to preferen-
tially furnished 6a in 15–80% yield along with a variety of
1
byproducts that could not be identified by H NMR meas-
urements; 4a was also afforded in 22% yield with YbACTHNUTRGNEUNG(OTf)3
as catalyst (Table 1, entries 11–14). A switch in chemoselec-
tivity was further observed on employing BF3·Et2O, which
afforded 4a and 5a in yields of 66 and 3%, respectively
(Table 1, entry 18). In marked contrast, no reaction was
found on changing the catalyst to AuCl, InCl3, or ZnCl2
(Table 1, entries 10, 16, and 17).
We also examined the Brønsted acid catalysts trifluorome-
thanesulfonic acid (TfOH), para-toluenesulfonic acid mono-
hydrate (p-TsOH·H2O), and trifluoroacetic acid (TFA)
(Table 1, entries 19–22). The reaction of 1a with 2a in the
presence of 5 mol% of TfOH as catalyst was the only case
in which the desired product 3a was furnished in 71% yield
along with a trace amount of 4a and 5a (2% yield, Table 1,
entry 19). Efficient transformation to the product in 87%
yield was only achieved when the reaction was repeated
with an increased catalyst loading of 20 mol% of TfOH cat-
alyst (Table 1, entry 20). Based on recent results of He et al.
and our earlier findings for the analogous AgOTf-catalyzed
reaction (entry 12 in Table 1), this and the significantly
lower concentration of TfOH in 5 mol% of AuCl/AgOTf
also provides evidence that the cationic gold(I) complex is
the active species.[23] In contrast to the activity exhibited by
TfOH, when p-TsOH·H2O was employed as catalyst, the re-
action was found to give 4a exclusively in 28% yield, while
6a was the only product in 29% yield on changing the cata-
lyst to TFA (Table 1, entries 21 and 22). In each of these re-
actions, a wide variety of side products was also obtained
which could not be separated by flash column chromatogra-
Variation of the nitrogen nucleophile: To further explore
the scope of the AuCl/AgOTf-catalyzed reactions, the
tandem amidation/ring expansion of 1a with a variety of dif-
ferent nitrogen nucleophiles was examined (Table 3). Under
the standard conditions, reaction of 1a with benzenesulfona-
mide (2b) gave 3p in 84% yield (Table 3, entry 1), and 4-
bromobenzenesulfonamide (2c) gave the corresponding pyr-
rolidine product 3q in 68% yield (Table 3, entry 2). In con-
trast, a markedly lower product yield was obtained when
para-nitro-substituted sulfonamide 2d was employed as nu-
cleophile, presumably due its significantly lower nucleophi-
licity (Table 3, entry 3). On the other hand, the use of a
more nucleophilic sulfonamide such as 2e, which contains a
para-methoxyphenyl group, was found to result in no reac-
1
phy or identified by H NMR analysis of the crude mixtures.
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Amination/Ring Expansion of Cyclopropyl Methanols
FULL PAPER
Table 2. AuCl/AgOTf-catalyzed tandem amination/ring expansion of 1b–q with 2a.[a]
and 6). In both cases, formation
of the desired pyrrolidine
adduct could not be detected
Entry
Alcohol
Product
Yield [%][b]
81
1
by H NMR analysis on increas-
1
1b
1c
1d
3b
3c
3d
ing the catalyst loading to
10 mol% or increasing the re-
action time to 36 h.
2
3
91
30
On the mechanism of the
tandem amidation/ring expan-
sion of substituted cyclopropyl
methanols with sulfonamides:
Competitive formation of 4a
and 6a under certain conditions
during the reactions of 1a with
2a outlined in Table 1 led us to
initially speculate on their pos-
sible involvement as intermedi-
ates in the present AuCl/
AgOTf-catalyzed procedure. To
support this hypothesis and
gain a better understanding of
the reaction mechanism, we
conducted the following experi-
ments using 1a and 2a as probe
substrates. Treatment of these
starting materials with 5 mol%
of AuCl and AgOTf in toluene
for 15 h at room temperature
cleanly gave 6a as the only
product in 95% yield (Table 4,
entry 1). Under these modified
conditions, reactions of 2a with
cyclopropyl methanols bearing
electron-withdrawing, electron-
donating, and sterically de-
manding substituents also pro-
ceeded in a similar manner at
room temperature to give the
corresponding substituted cy-
clopropyl sulfonamides 6d–h in
yields of 61–99% (Table 4, en-
tries 2–6). The structure of 6h
was established by X-ray crys-
tallography (Figure 2).[24] Devel-
opment of a convenient route
to compounds having both cy-
clopropane and sulfonamide
functionality is noteworthy, as
these pharmacophores may
have interesting bioactivity. On
4
1e
3e
89
5
6
7
1 f
1g
1h
3 f
3g
3h
84
77
80
8
1i
3i
70
9
10
11
12
1j
3j
34
60
68
81
1k
1l
3k
3l
1m
4b
13
1n
4c
69[d]
14[c]
15[c]
3m, n=7
3n, n=11
50
37
1o,p
16[c]
1q
3o
44
[a] All reactions were performed at 1008C in toluene for 15 h with AuCl/AgOTf: 1: 2a ratio=1: 20: 40.
[b] Yields of isolated products. [c] Reaction conducted with 10 mol% AuCl/AgOTf catalyst. [d] Isolated as a
mixture of trans and cis isomers in 1:1 ratio.
tion on the basis of both TLC and 1H NMR analysis
(Table 3, entry 4). In addition, the analogous reactions of 1a
with carbamates such as 2 f,g did not proceed as anticipated.
Under our experimental conditions, these reactions were
found to afford amidated cyclopropanes 6b,c as the sole ad-
ducts in 85 and 73% yield, respectively (Table 3, entries 5
the other hand, 4a was exclusively furnished in 93% yield
by the analogous AuCl/AgOTf-catalyzed reaction of 1a and
2a at 1008C for 1 h. In both instances, conversion to 3a
from 4a in 93% yield and from 6a in 70% yield was found
on re-treating these compounds under the standard condi-
tions of 5 mol% of AuCl and AgOTf in toluene at 1008C
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P. W. H. Chan et al.
Table 4. AuCl/AgOTf-catalyzed amination of 1a-j with 2a.[a]
Entry
Alcohol
Product
Yield [%][b]
1
2
3
1a
1d
1 f
6a, R=H
6d, R=OMe
6e, R=F
95
95
87
4
5
6
1h
1i
6 f
6g
6h
91
61
99
1j
[a] All reactions were performed at room temperature in toluene for 15 h
with AuCl/AgOTf:1a:2 ratio of 1:20:40. [b] Yields of isolated products.
Figure 1. ORTEP drawing of 3j with thermal ellipsoids at 50% probabili-
ty.[24]
Table 3. AuCl/AgOTf-catalyzed tandem amination/ring expansions of 1a
with 2b–g.[a]
Entry
Nucleophile
Product
Yield [%][b]
1
2
3
4
2b
2c
2d
2e
3p, R=H
3q, R=Br
3r, R=NO2
84
68
31
[c]
–
Figure 2. ORTEP drawing of 6h with thermal ellipsoids at 50% probabil-
ity.[24]
5
6
2 f
2g
6b, R=tBu
6c, R=Bn
85
73
[a] All reactions were performed at 1008C in toluene for 24 h with AuCl/
AgOTf:1a:2 ratio of 1:20:40. [b] Yields of isolated products. [c] No reac-
tion.
for 15 h.[27] In the latter case, monitoring the reaction by
1H NMR spectroscopy revealed complete conversion of 6a
to a mixture of 3a and 4a in a ratio of 1:2 after 1 h. This
suggested a pathway by which generation of an intermediate
that closely resembles 4 could precede product formation.
The possible involvement of such a species would also ac-
count for our findings on the reaction of enantiopure 1a
with 2a. Under our experimental conditions, pyrrolidine
adduct 3a was obtained as a racemic mixture in 93% yield,
as shown in Scheme 3.[28]
On the basis of the above results, we tentatively propose
the present AuCl/AgOTf-catalyzed pyrrolidine-forming re-
action to proceed by the mechanism outlined in Scheme 4,
although it is highly speculative. In a manner similar to that
put forward by us,[3] Campagne et al.[2] and Aponick et al.,[6]
Scheme 3. AuCl/AgOTf-catalyzed tandem amination/ring expansion of
enantiopure 1a with 2a.
we postulate that the gold/silver catalyst combination acti-
vates alcohol substrate 1 by coordinating to the oxygen
atom. This affords gold(I)-coordinated cyclopropyl methanol
7, which can undergo elimination to give carbocation inter-
mediate 8 and [Au]-OH, which releases the gold catalyst by
protodemetalation. It is possible that this newly formed cat-
ionic species could initially react with 2 to produce cyclo-
propyl sulfonamide 6 (route a in Scheme 4). However, as
the introduced sulfonamide functionality can also be activat-
À
ed by coordination to the catalyst, the C N bond-forming
step may be reversible, and the carbocation intermediate is
reformed as quickly as it is amidated. Alternatively, as
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Amination/Ring Expansion of Cyclopropyl Methanols
FULL PAPER
number of experiments examined in this work. First, the
role of AgOTf in producing a more electrophilic gold cata-
lyst that can participate in substrate coordination seems to
be crucial for the reaction to proceed smoothly, since nei-
ther AgOTf nor AuCl was found to be an effective catalyst.
Moreover, the outcome of the reaction is influenced by the
nature of the solvent: polar solvents such as CHCl3, 1,2-di-
chloroethane, MeCN, and THF have a detrimental effect on
both product yields and chemoselectivity. This also appears
to be operative when such interactions are presumably
weakened due to competitive coordination with a very elec-
tron rich neighbor on the alcohol substrate or nitrogen nu-
cleophile, such as a methoxyphenyl or alkyne moiety, as in
1d, 1j, 1n, and 2e. We found that in each of these cases,
either markedly lower product yields or the acyclic enyne
adduct were obtained or no reaction could be detected.
Indeed, this is further supported by the fact that when a so-
lution of toluene containing 6h was treated with 5 mol% of
AuCl/AgOTf at 1008C for 15 h, the expected pyrrolidine 3j
was obtained in a yield of 37%, comparable to those found
for the analogous reactions of 1d and 1j (Scheme 6).
Scheme 4. Tentative mechanism for AuCl/AgOTf-catalyzed tandem ami-
nation/ring expansion of substituted cyclopropyl methanols with sulfona-
mides.
shown in route b in Scheme 4, the amidation step could be
skipped altogether, and ring opening of the cyclopropane
moiety of 8 followed by trapping with 2 directly furnishes
acyclic sulfonamide 4. Subsequent coordination to the cata-
lyst might be expected to give the gold(I)-activated alkene
species 10, which is the active species that undergoes intra-
molecular hydroamination to afford the pyrrolidine product.
A similar cyclization step was proposed by Shi and co-work-
ers for the gold(I)-catalyzed tandem ring-opening/ring-clos-
ing hydroamination of MCPs.[19]
Scheme 6. AuCl/AgOTf-catalyzed ring expansion of 6h.
Although a number of pathways are conceivable, we sur-
mise that the mechanism of the present procedure to likely
to proceed via ring-opening of the cyclopropane moiety of 8
irrespective of whether the reaction follows routes a and b
or only route b in Scheme 4. This is supported by our isolat-
ing 3a and 3p in yields of 47 and 36%, respectively, from
the crossover reaction of 1 equiv of 6a with 1 equiv of 2b in
the presence of 5 mol% of AuCl/AgOTf under the condi-
tions described in Scheme 5. A similar outcome was also ob-
tained on repeating the reaction with 5 mol% of TfOH as
catalyst, which furnished 3a and 3p in yields of 42 and
31%, respectively. The origin of the N,N-substituted sulfo-
namide side product 5 could be due to the acyclic adduct 4
competing with 2 in trapping the species resulting from frag-
mentation of 8. More notably, the manner in which the cata-
lyst can efficiently coordinate to the alcohol substrate and
Conclusion
We have described an efficient AuCl/AgOTf-catalyzed strat-
egy for formation of pyrrolidine derivatives, including exam-
ples with quaternary centers, starting from substituted cyclo-
propyl methanols. The method is applicable to a wide range
of activated and unactivated substituted cyclopropyl metha-
nol and sulfonamide substrates containing electron-with-
drawing, electron-donating, and sterically-demanding sub-
stituents. In addition, the gold-catalyzed tandem reaction ex-
hibits excellent catalytic activity at low catalyst loadings.
When the reactions were conducted at room temperature,
N-cyclopropylmethyl sulfonamides with potentially interest-
ing bioactivity were formed chemoselectively. Our studies
suggest activation of the substituted cyclopropyl methanol
substrate by the gold catalyst, which leads to ionization of
the alcohol. This possibly triggers subsequent ring opening
of the cyclopropane moiety followed by trapping with the
sulfonamide nucleophile to give an acyclic aminated inter-
mediate that undergoes intramolecular hydroamination to
form the pyrrolidine product. Our studies revealed that
TfOH can also mediate the tandem amidation/ring expan-
sion process, but the lower product yields and selectivities
exhibited by TfOH along with the significantly milder condi-
tions of gold catalysis provides an attractive alternative syn-
thetic approach for the formation of pyrrolidines. While the
À
resultant intermediates formed during the tandem C N
bond-forming process proposed in Scheme 4 seems to be a
pivotal aspect of the present procedure. This is evident in a
Scheme 5. AuCl/AgOTf-catalyzed ring expansion of 6a with 2b.
Chem. Eur. J. 2008, 14, 10486 – 10495
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
10491

P. W. H. Chan et al.
J=7.6, 3.3 Hz), 7.21–7.30 (m, 7H), 7.67 ppm (d, 2H, J=8.2 Hz);
13C NMR (CDCl3, 100 MHz, TMS): d=21.5, 24.0, 35.8, 49.4, 63.3, 126.2,
127.0, 127.5, 128.3, 129.6, 135.2, 143.1, 143.3 ppm; MS (ESI): m/z: 324
[M+Na]+, 302 [M+H]+.
2-(4-Methylphenyl)-1-tosylpyrrolidine (3b):[19,26,30] White solid; 1H NMR
(CDCl3, 400 MHz, TMS): d=1.62–1.68 (m, 1H), 1.76–1.98 (m, 3H), 2.32
(s, 3H), 2.42 (s, 3H), 3.37–3.43 (m, 1H), 3.58–3.63 (m, 1H), 4.73 (dd, 1H,
J=7.5, 3.4 Hz), 7.10 (d, 2H, J=7.9 Hz), 7.20 (d, 2H, J=8.0 Hz), 7.28 (d,
2H, J=8.0 Hz), 7.67 ppm (d, 2H, J=8.1 Hz); 13C NMR (CDCl3,
100 MHz, TMS): d=21.1, 21.5, 24.0, 35.8, 49.4, 63.1, 126.1, 127.5, 129.0,
129.6, 135.2, 136.6, 140.1, 143.2 ppm; MS (ESI): m/z: 338 [M+Na]+, 316
[M+H]+.
findings of this study suggest it is unlikely that TfOH poten-
tially generated in situ is the true species promoting the re-
action, it also demonstrates the care required when inter-
preting such results, given the similar reactivities exhibited
by both gold and Brønsted acid catalysts.
Experimental Section
General remarks: All reactions were performed under an argon atmos-
phere. Unless otherwise specified, all reagents and starting materials
were purchased from commercial sources and used as received. All sub-
stituted cyclopropyl methanol substrates used in this work were prepared
by following literature procedures.[29] Solvents were purified by standard
literature procedures; CH2Cl2 was purified prior to use by passing
through a PURESOLV Solvent Purification System. Analytical TLC was
performed on Merck 60 F254 precoated silica gel plates. Visualization
was achieved with UV light (254 nm). Flash chromatography was per-
formed on Merck silica gel 60 with a solvent-gradient system (EtOAc:n-
hexane as eluent). 1H and 13C NMR spectra were measured on a Bruker
Avance 400 MHz spectrometer. Chemical shifts (ppm) were recorded
with tetramethylsilane (TMS) as internal reference. Infrared spectra were
recorded on Shimadzu IR Prestige-21 FTIR Spectrometer. Solid samples
were examined as a thin film between NaCl plates. Low-resolution mass
spectra were determined on a Finnigan LCQ XP MAX mass spectrome-
ter. High-resolution mass spectra (HRMS) were obtained on a Finnigan
MAT95XP LC/HRMS mass spectrometer.
2-(4-tert-Butylphenyl)-1-tosylpyrrolidine (3c): White solid; m.p. 96–988C;
1H NMR (CDCl3, 400 MHz, TMS): d=1.30 (s, 9H), 1.63–1.70 (m, 1H),
1.79–1.99 (m, 3H), 2.41 (s, 3H), 3.41–3.47 (m, 1H), 3.58–3.63 (m, 1H),
4.77 (dd, 1H, J=7.6, 3.4 Hz), 7.19–7.30 (m, 6H), 7.64 ppm (d, 2H, J=
8.2 Hz); 13C NMR (CDCl3, 100 MHz, TMS): d=21.5, 24.1, 31.4, 34.4,
35.7, 49.3, 63.0, 125.2, 125.9, 127.5, 129.5, 135.4, 139.8, 143.1, 149.8 ppm;
IR (KBr): n˜ =2961, 1341, 1335, 1152, 1105, 1005, 671, 586 cmÀ1; MS
(ESI): m/z: 380 [M+Na]+; HRMS (ESI) calcd for C21H27NO2SNa:
380.1655; found: 380.1786.
2-(4-Methoxyphenyl)-1-tosylpyrrolidine (3d):[26] White solid; 1H NMR
(CDCl3, 400 MHz, TMS): d=1.63–1.69 (m, 1H), 1.75–1.97 (m, 3H), 2.42
(s, 3H), 3.37–3.44 (m, 1H), 3.57–3.62 (m, 1H), 3.79 (s, 3H), 4.73 (dd, 1H,
J=7.4, 3.6 Hz), 6.83 (d, 2H, J=8.6 Hz), 7.21–7.28 (m, 4H), 7.66 ppm (d,
2H, J=8.2 Hz); 13C NMR (CDCl3, 100 MHz, TMS): d=21.5, 24.0, 35.8,
49.3, 55.3, 62.8, 113.7, 127.3, 127.5, 129.5, 135.2, 135.2, 143.2, 158.7 ppm;
MS (ESI): m/z: 354 [M+Na]+.
2-(3,5-Dimethylphenyl)-1-tosylpyrrolidine (3e): White solid; m.p. 77–
798C; 1H NMR (CDCl3, 400 MHz, TMS): d=1.60–1.67 (m, 1H), 1.76–
1.99 (m, 3H), 2.26 (s, 6H), 2.42 (s, 3H), 3.41–3.47 (m, 1H), 3.58–3.63 (m,
1H), 4.72 (dd, 1H, J=7.2, 3.2 Hz), 6.85 (s, 3H), 7.26 (d, 2H, J=7.8 Hz),
7.65 ppm (d, 2H, J=8.0 Hz); 13C NMR (CDCl3, 100 MHz, TMS): d=
21.4, 21.5, 24.0, 35.9, 49.4, 63.3, 124.0, 127.5, 128.7, 129.5, 135.4, 137.7,
142.9, 143.1 ppm; IR (KBr): n˜ =1605, 1342, 1157, 1094, 1003, 818,
586 cmÀ1; MS (ESI): m/z: 352 [M+Na]+, 330 [M+H]+; HRMS (ESI)
calcd for C19H23NO2SNa: 352.1342; found: 352.1316.
2-(4-Fluorophenyl)-1-tosylpyrrolidine (3 f):[31] White solid; 1H NMR
(CDCl3, 400 MHz, TMS): d=1.62–1.69 (m, 1H), 1.73–1.88 (m, 2H), 1.93–
2.04 (m, 1H), 2.42 (s, 3H), 3.37–3.43 (m, 1H), 3.58–3.63 (m, 1H), 4.74
(dd, 1H, J=7.6, 3.6 Hz), 6.97 (t, 2H, J=8.7 Hz), 7.26–7.29 (m, 4H),
7.66 ppm (d, 1H, J=8.2 Hz); 13C NMR (CDCl3, 100 MHz, TMS): d=
21.5, 23.9, 35.9, 49.4, 62.7, 115.1(d, J=21.4 Hz), 127.5, 127.8 (d, J=
8.0 Hz), 129.6, 134.9, 138.9 (d, J=2.9 Hz), 143.5, 162.6 ppm (d, J=
243.4 Hz); MS (ESI): m/z: 342 [M+Na]+.
2-(4-Chlorophenyl)-1-tosylpyrrolidine (3g):[26,31] White solid; 1H NMR
(CDCl3, 400 MHz, TMS): d=1.68–1.87 (m, 3H), 1.95–2.02 (m, 12H), 2.43
(s, 3H), 3.38–3.44 (m, 1H), 3.58–3.63 (m, 1H), 4.72 (dd, 1H, J=7.8,
3.7 Hz), 7.23–7.30 (m, 6H), 7.66 ppm (d, 1H, J=8.2 Hz); 13C NMR
(CDCl3, 100 MHz, TMS): d=21.5, 24.0, 35.8, 49.4, 62.7, 127.5, 127.6,
128.4, 129.7, 132.8, 134.8, 141.7, 143.5 ppm; MS (ESI): m/z: 358 [M+Na]+
, 336 [M+H]+.
2-(Naphthalen-1-yl)-1-tosylpyrrolidine (3h):[19] White solid; 1H NMR
(CDCl3, 400 MHz, TMS): d=1.71–1.90 (m, 3H), 2.06–2.15 (m, 1H), 2.44
(s, 3H), 3.42–3.49 (m, 1H), 3.77–3.82 (m, 1H), 5.57 (d, 1H, J=6.8 Hz),
7.32 (d, 2H, J=8.0 Hz), 7.43–7.54 (m, 3H), 7.66 (d, 1H, J=8.1 Hz), 7.75–
7.92 ppm (m, 5H); 13C NMR (CDCl3, 100 MHz, TMS): d=21.6, 23.9,
34.6, 49.4, 60.7, 122.8, 123.8, 125.4, 125.9, 127.6, 127.6, 129.0, 129.7, 129.9,
133.9, 134.9, 138.2, 143.4 ppm; MS (ESI): m/z: 374 [M+Na]+, 352
[M+H]+.
General procedure for optimizing the Lewis and Brønsted acid-catalyzed
tandem amination/ring expansion of 1a with 2a: For reactions with a
gold/silver catalyst combination, the gold (15 mmol) and silver (15 mmol)
catalysts were first stirred in toluene (1.5 mL) at room temperature for
1 h. In all other cases, the catalyst was added to a toluene solution prior
to adding the starting materials. Then a toluene solution (1.5 mL) con-
taining 1a (0.3 mmol) and 2a (0.6 mmol) was added, and the reaction
mixture stirred at 1008C and monitored to completion by TLC analysis.
The reaction mixture was then cooled and the solvent removed under re-
duced pressure. Purification by flash column chromatography on silica
gel (n-hexane/EtOAc 7:1 as eluent) gave 3a.
General procedure for the AuCl/AgOTf-catalyzed tandem amination/
ring expansion of 1 with 2: A solution of AuCl (15 mmol) and AgOTf
(15 mmol) was stirred in toluene (1.5 mL) under an Ar atmosphere at
room temperature for 1 h. Then a toluene solution (1.5 mL) containing 1
(0.3 mmol) and 2 (0.6 mmol) was added to the reaction mixture, which
was stirred at 1008C and monitored to completion by TLC analysis. The
reaction mixture was then cooled and the solvent removed under reduced
pressure. Purification by flash column chromatography on silica gel (n-
hexane/EtOAc 7:1 as eluent) gave 3.
Procedure for the AuCl/AgOTf-catalyzed ring expansion of 6a with 2b:
A solution of AuCl (15 mmol) and AgOTf (15 mmol) in toluene (1.5 mL)
was stirred at room temperature for 1 h. Then
a toluene solution
(1.5 mL) containing 6a (0.3 mmol) and 2b (0.3 mmol) was added to the
reaction mixture, which was stirred at 1008C for 15 h. The reaction mix-
ture then cooled and the solvent was removed under reduced pressure.
Purification by flash column chromatography on silica gel (n-hexane/
EtOAc=7:1 as eluent) gave 3a and 3p.
Procedure for AuCl/AgOTf-catalyzed ring expansion of 6h: A solution
of AuCl (15 mmol) and AgOTf (15 mmol) in toluene (1.5 mL) was stirred
under an Ar atmosphere at room temperature for 1 h. Then a toluene so-
lution (1.5 mL) containing 6h (0.3 mmol) was added to the reaction mix-
ture, which was stirred at 1008C for 15 h. The reaction mixture was then
cooled and the solvent removed under reduced pressure. Purification by
flash column chromatography on silica gel (n-hexane/EtOAc 7:1 as
eluent) gave 3j.
2-Phenyl-1-tosylpyrrolidine (3a):[19,26,30] White solid; 1H NMR (CDCl3,
400 MHz, TMS): d=1.62–1.70 (m, 1H), 1.78–1.90 (m, 2H), 1.94–2.04 (m,
1H), 2.42 (s, 3H), 3.39–3.45 (m, 1H), 3.59–3.64 (m, 1H), 4.79 (dd, 1H,
2-(2,6-Dimethylphenyl)-1-tosylpyrrolidine (3i): White solid; m.p. 154–
1558C; 1H NMR (CDCl3, 400 MHz, TMS): d=1.53–1.61 (m, 1H), 1.89–
1.99 (m, 2H), 2.16–2.22 (m, 1H), 2.35 (s, 6H), 2.40 (s, 3H), 3.50–3.57 (m,
1H), 3.82 (t, 1H, J=9.8 Hz), 5.01 (dd, 1H, J=9.4, 7.8 Hz), 6.92–7.03 (m,
3H), 7.20 (d, 2H, J=8.0 Hz), 7.54 ppm (d, 2H, J=8.1 Hz); 13C NMR
(CDCl3, 100 MHz, TMS): d=20.8, 21.5, 25.5, 32.7, 49.3, 60.4, 126.9, 127.4,
129.3, 135.6, 135.9, 136.9, 143.1 ppm; IR (KBr): n˜ =1341, 1157, 1086, 989,
10492
www.chemeurj.org
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2008, 14, 10486 – 10495

Amination/Ring Expansion of Cyclopropyl Methanols
FULL PAPER
696, 592 cmÀ1; MS (ESI): m/z: 352 [M+Na]+; HRMS (ESI) calcd for
C19H23NO2SNa: 352.1342; found: 352.1319.
1H), 3.58–3.67 (m, 1H), 4.87 (dd, 1H, J=7.8, 4.3 Hz), 7.16–7.26 (m, 5H),
7.79–7.81 (m, 2H), 8.22–8.24 ppm (m, 2H); 13C NMR (CDCl3, 100 MHz,
TMS): d=24.3, 36.0, 49.5, 63.7, 124.0, 126.4, 127.5, 128.3, 128.4, 141.8,
144.7, 149.8 ppm; MS (ESI): m/z: 355 [M+Na]+.
(E)-4-Methyl-N-(4-phenylbut-3-enyl)benzenesulfonamide (4a):[19,30] Col-
ourless oil; 1H NMR (CDCl3, 400 MHz, TMS): d=2.36 (q, 2H, J=
6.8 Hz), 2.41 (s, 3H), 3.09 (q, 2H, J=6.5 Hz), 4.63 (t, 1H, J=5.8 Hz),
5.94–6.01 (m, 1H), 6.35 (d, 1H, J=15.8 Hz), 7.20–7.31 (m, 7H), 7.75 ppm
(d, 2H, J=8.2 Hz); 13C NMR (CDCl3, 100 MHz, TMS): d=21.5, 33.0,
42.6, 125.6, 126.1, 127.2, 127.5, 128.6, 129.7, 133.2, 136.8, 137.0,
143.5 ppm; MS (ESI): m/z: 324 [M+Na]+.
2-(2-Methoxyphenyl)-1-tosylpyrrolidine (3j):[19,24] White solid; 1H NMR
(CDCl3, 400 MHz, TMS): d=1.60–1.66 (m, 1H), 1.70–1.92 (m, 3H), 2.43
(s, 3H), 3.31–3.37 (m, 1H), 3.62–3.67 (m, 1H), 3.80 (s, 3H), 5.10 (dd, 1H,
J=7.6, 2.4 Hz), 6.82 (d, 1H, J=8.2 Hz), 6.93 (t, 1H, J=7.4 Hz), 7.19–
7.31 (m, 3H), 7.43 (d, 1H, J=7.4 Hz), 7.72 ppm (d, 2H, J=8.1 Hz);
13C NMR (CDCl3, 100 MHz, TMS): d=21.5, 23.8, 34.0, 49.4, 55.2, 58.8,
110.1, 120.3, 127.3, 127.6, 128.0, 129.5, 131.3, 135.1, 143.1, 155.7 ppm; MS
(ESI): m/z: 354 [M+Na]+, 332 [M+H]+.
2-Methyl-2-phenyl-1-tosylpyrrolidine (3k):[19] White solid; 1H NMR
(CDCl3, 400 MHz, TMS): d=1.78–1.89 (m, 5H), 1.94–2.01 (m, 1H), 2.11–
2.17 (m, 1H), 2.41 (s, 3H), 3.52–3.58 (m, 1H), 3.68–3.73 (m, 1H), 7.20–
7.31 (m, 5H), 7.39 (d, 2H, J=7.4 Hz), 7.58 ppm (d, 2H, J=8.2 Hz);
13C NMR (CDCl3, 100 MHz, TMS): d=21.5, 22.5, 26.4, 45.8, 49.8, 69.9,
125.8, 126.6, 127.1, 128.0, 129.3, 138.5, 142.5, 146.5 ppm; MS (ESI): m/z:
338 [M+Na]+, 316 [M+H]+.
N-(4,4-Diphenylbut-3-enyl)-4-methylbenzenesulfonamide
(4b):[33,34]
Yellow oil; 1H NMR (CDCl3, 400 MHz, TMS): d=2.26 (q, 2H, J=
7.1 Hz), 2.40 (s, 3H), 3.03 (q, 2H, J=6.6 Hz), 4.59 (t, 3H, J=6.0 Hz),
5.90 (t, 1H, J=7.4 Hz), 7.08–7.36 (m, 12H), 7.69 ppm (d, 2H, J=8.2 Hz);
13C NMR (CDCl3, 100 MHz, TMS): d=21.6, 29.9, 43.1, 124.6, 127.1,
127.3, 127.3, 127.3, 128.2, 128.4, 129.7, 129.7, 136.9, 139.5, 142.0, 143.4,
144.7 ppm; MS (ESI): m/z: 400 [M+Na]+, 378 [M+H]+.
2-(4-Fluorophenyl)-2-methyl-1-tosylpyrrolidine 3l: White solid; m.p. 109–
1108C; 1H NMR (CDCl3, 400 MHz, TMS): d=1.77–1.90 (m, 5H), 1.94–
2.13 (m, 2H), 2.41 (s, 3H), 3.51–3.57 (m, 1H), 3.67–3.72 (m, 1H), 6.93–
6.99 (m, 2H), 7.23 (d, 1H, J=8.1 Hz), 7.32–7.38 (m, 2H), 7.58 ppm (d,
2H, J=8.2 Hz); 13C NMR (CDCl3, 100 MHz, TMS): d=21.5, 22.4, 26.5,
45.8, 49.8, 69.3, 114.7 (d, J=21.1 Hz), 127.1, 127.5 (d, J=7.9 Hz), 129.3,
138.3, 142.5 (d, J=40.5 Hz), 161.6 ppm (d, J=243.6 Hz); IR (KBr): n˜ =
2853, 1599, 1508, 1335, 1155, 1005, 814, 665, 550 cmÀ1; MS (ESI): m/z:
356 [M+Na]+; HRMS (ESI) calcd for C18H20NO2FSNa: 356.1091; found:
356.1473.
2-Octyl-1-tosylpyrrolidine (3m): Brown oil; 1H NMR (CDCl3, 400 MHz,
TMS): d=0.88 (t, 3H, J=6.6 Hz), 1.18–1.28 (m, 12H), 1.42–1.59 (m,
4H), 1.71–1.84 (m, 2H), 2.42 (s, 3H), 3.15–3.21 (m, 1H), 3.33–3.39 (m,
1H), 3.55–3.60 (m, 1H), 7.29 (d, 2H, J=8.0 Hz), 7.71 ppm (d, 2H, J=
8.2 Hz); 13C NMR (CDCl3, 100 MHz, TMS): d=14.1, 21.5, 22.7, 24.1,
26.2, 29.3, 29.6, 30.6, 31.9, 36.5, 48.9, 60.6, 127.5, 129.6, 135.1, 143.1 ppm;
IR (KBr): n˜ =2924, 1346, 1159, 1094, 8160, 664, 588 cmÀ1; MS (ESI): m/z:
360 [M+Na]+; HRMS (ESI) calcd for C19H31NO2SNa: 360.1968; found:
360.1846.
4-Methyl-N-(6-p-tolylhex-3-en-5-ynyl)benzenesulfonamide (4c): Yellow
1
oil; H NMR (CDCl3, 400 MHz, TMS): d=2.28–2.42 (m, 14H), 2.25–2.27
(q, 2H, J=6.4 Hz), 3.03–3.13 (m, 4H), 5.54–5.58 (m, 2H), 5.66–5.83 (m,
3 Hz), 5.94–6.01 (m, 1H), 7.10–7.14 (m, 4H), 7.24–7.32 (m, 8H), 7.73–
7.76 ppm (m, 4H); 13C NMR (CDCl3, 100 MHz, TMS): d=21.5, 21.5,
30.3, 33.2, 42.2, 42.2, 84.8, 86.7, 89.5, 95.0, 112.6, 113.3, 120.0, 120.0, 127.1,
129.1, 129.1, 129.7, 129.8, 131.4, 131.4, 136.9, 138.0, 138.4, 138.6, 138.9,
143.4, 143.6 ppm; IR (KBr): n˜ =3291, 2920, 2265, 1327, 1159, 1094, 816,
664 cmÀ1
;
MS (ESI): m/z: 362 [M+Na]+; HRMS (ESI) calcd for
C20H21NO2SNa: 362.1185; found: 362.1031.
4-Methyl-N,N-bis[(E)-4-phenylbut-3-enyl]benzenesulfonamide
(5a):[19]
Colorless oil; 1H NMR (CDCl3, 400 MHz, TMS): d=2.39 (s, 3H), 2.49
(q, 4H, J=7.2 Hz), 3.30 (t, 4H, J=7.2 Hz), 6.05–6.12 (m, 2H), 6.39 (d,
2H, J=15.8 Hz), 7.19–7.29 (m, 12H), 7.71 ppm (d, 2H, J=8.3 Hz);
13C NMR (CDCl3, 100 MHz, TMS): d=21.5, 32.7, 48.1, 126.1, 126.2,
127.2, 127.3, 128.5, 129.7, 132.3, 137.2, 143.2 ppm; MS (ESI): m/z: 454
[M+Na]+.
General procedure for AuCl/AgOTf-catalyzed amination of 1a, 1d, 1 f,
and 1h–j with 2a: A solution of AuCl (15 mmol) and AgOTf (15 mmol) in
toluene (1.5 mL) was stirred at room temperature for 1 h. Then a toluene
solution (1.5 mL) containing 1 (0.3 mmol) and 2a (0.6 mmol) was added
to the reaction mixture, which was stirred at room temperature and
monitored to completion by TLC analysis. The reaction mixture was then
cooled and the solvent removed under reduced pressure. Purification by
flash column chromatography on silica gel (n-hexane/EtOAc 7:1 as
eluent) gave 6.
2-Dodecyl-1-tosylpyrrolidine (3n): Yellow oil; 1H NMR (CDCl3,
400 MHz, TMS): d=0.88 (t, 3H, J=6.9 Hz), 1.27 (s, 20H), 1.53–1.62 (m,
4H), 1.72–1.83 (m, 2H), 2.43 (s, 3H), 3.16–3.22 (m, 1H), 3.34–3.40 (m,
1H), 3.56–3.62 (m, 1H), 7.30 (d, 2H, J=7.9 Hz), 7.71 ppm (d, 2H, J=
8.0 Hz); 13C NMR (CDCl3, 100 MHz, TMS): d=14.1, 21.5, 22.7, 24.1,
26.2, 29.4, 29.6, 29.6, 29.7, 30.7, 31.9, 36.5, 48.9, 60.6, 127.5, 129.6, 135.1,
143.1 ppm; IR (KBr): n˜ =2922, 2853, 1341, 1157, 1091, 806, 667 cmÀ1; MS
(ESI): m/z: 416 [M+Na]+; HRMS (ESI) calcd for C23H39NO2SNa:
416.2594; found: 416.3034.
2-Phenethyl-1-tosylpyrrolidine (3o):[32] Yellow oil; 1H NMR (CDCl3,
400 MHz, TMS): d=1.43–1.63 (m, 3H), 1.74–1.83 (m, 2H), 2.18–2.26 (m,
1H), 2.41 (s, 3H), 2.60–2.77 (m, 2H), 3.17–3.23 (m, 1H), 3.38–3.44 (m,
1H), 3.55–3.61 (m, 1H), 7.19–7.32 (m, 7H), 7.62 ppm (d, 2H, J=8.1 Hz);
13C NMR (CDCl3, 100 MHz, TMS): d=21.5, 24.1, 30.8, 32.4, 37.7, 49.1,
59.8, 125.9, 127.6, 128.4, 128.5, 129.6, 134.7, 141.6, 143.2 ppm; MS (ESI):
m/z: 352 [M+Na]+, 330 [M+H]+.
2-Phenyl-1-(phenylsulfonyl)pyrrolidine (3p):[19] White solid; 1H NMR
(CDCl3, 400 MHz, TMS): d=1.63–2.05 (m, 4H), 3.43–3.49 (m, 1H), 3.61–
3.66 (m, 1H), 4.82 (dd, 1H, J=7.7, 3.5 Hz), 7.20–7.30 (m, 5H), 7.46–7.58
(m, 3H), 7.77–7.79 ppm (m, 2H); 13C NMR (CDCl3, 100 MHz, TMS): d=
24.0, 35.8, 49.4, 63.4, 126.2, 127.1, 127.4, 128.3, 129.0, 132.6, 138.1,
142.9 ppm; MS (ESI): m/z: 310 [M+Na]+.
N-[Cyclopropyl
U
(6a):
White solid; m.p. 127–1288C; 1H NMR (CDCl3, 400 MHz, TMS): d=
0.20–0.30 (m, 2H), 0.43–0.53 (m, 2H), 1.05–1.14 (m, 1H), 2.37 (s, 3H),
3.70 (dd, 1H, J=8.4, 6.0 Hz), 5.16 (d, 1H, J=5.6 Hz), 7.13–7.18 (m, 7H),
7.56 ppm (d, 2H, J=8.1 Hz); 13C NMR (CDCl3, 100 MHz, TMS): d=3.8,
4.5, 18.1, 21.5, 62.5, 126.9, 127.1, 127.4, 128.3, 129.3, 137.8, 140.4,
143.0 ppm; IR (KBr): n˜ =3250, 2927, 14521, 1346, 1160, 1088, 1043, 822,
679 cmÀ1
C17H19NO2SNa: 324.1029; found: 324.0650.
tert-Butylcyclopropyl(phenyl)methylcarbamate (6b): White solid; m.p.
;
MS (ESI): m/z: 324 [M+Na]+; HRMS (ESI) calcd for
71–728C; 1H NMR (CDCl3, 400 MHz, TMS): d=0.33–0.60 (m, 4H),
1.05–1.13 (m, 1H), 1.41 (s, 9H), 4.12 (brs, 1H), 5.00 (brs, 1H), 7.22–
7.33 ppm (m, 5H); 13C NMR (CDCl3, 100 MHz, TMS): d=3.6, 17.3, 28.4,
58.4, 79.4, 126.5, 127.1, 128.1, 128.4, 142.7, 155.4 ppm; IR (KBr): n˜ =3383,
1680, 1522, 1177, 1017, 878, 754, 702 cmÀ1; MS (ESI): m/z: 270 [M+Na]+;
HRMS (ESI) calcd for C15H21NO2Na: 270.1465; found: 270.1363.
1-(4-Bromophenylsulfonyl)-2-phenylpyrrolidine (3q): Pale yellow oil;
1H NMR (CDCl3, 400 MHz, TMS): d=1.70–2.10 (m, 4H), 3.43–3.49 (m,
1H), 3.59–3.64 (m, 1H), 4.79 (dd, 1H, J=7.7, 3.6 Hz), 7.23–7.30 (m, 5H),
7.58 ppm (s, 4H); 13C NMR (CDCl3, 100 MHz, TMS): d=24.1, 35.9, 49.4,
63.5, 126.2, 127.2, 127.4, 128.4, 128.9, 132.2, 137.5, 142.5 ppm; IR (KBr):
n˜ =2973, 1347, 1342, 1155, 1114, 692 cmÀ1; MS (ESI): m/z: 388 [M+Na]+;
HRMS (ESI) calcd for C16H16NO2BrSNa: 387.9983; found: 387.9975.
BenzylcyclopropylACTHUNRGTNEUNG(phenyl)methylcarbamate (6c): White solid; m.p. 60–
618C; 1H NMR (CDCl3, 400 MHz, TMS): d=0.33–0.61 (m, 4H), 1.11–
1.13 (m, 1H), 4.16 (brs, 1H), 4.99–5.11 (m, 2H), 5.26 (brs, 1H), 7.23–
7.33 ppm (m, 10H); 13C NMR (CDCl3, 100 MHz, TMS): d=3.7, 3.8, 17.2,
59.2, 66.8, 126.5, 127.3, 128.1, 128.5, 136.5, 142.2, 155.9 ppm; IR (KBr):
n˜ =3337, 1682, 1528, 1265, 1040, 878, 756, 698 cmÀ1; MS (ESI): m/z: 304
1-(4-Nitrophenylsulfonyl)-2-phenylpyrrolidine (3r):[19, 26] White solid;
1H NMR (CDCl3, 400 MHz, TMS): d=1.80–2.22 (m, 4H), 3.43–3.49 (m,
Chem. Eur. J. 2008, 14, 10486 – 10495
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10493

P. W. H. Chan et al.
[M+Na]+; HRMS (ESI) calcd for C18H19NO2Na: 304.1308; found:
304.1348.
Hashmi, Chem. Rev. 2007, 107, 3180–3211; f) E. Jimꢁnez-NfflÇez,
A. M. Echavarren, Chem. Commun. 2007, 333–346; g) A. Fürstner,
P. W. Davies, Angew. Chem. 2007, 119, 3478–3519; Angew. Chem.
Int. Ed. 2007, 46, 3410–3449; h) N. Asao, Synlett 2006, 1645–1656;
i) A. Hoffmann-Rçder, N. Krause, Org. Biomol. Chem. 2005, 3,
387–391.
N-[Cyclopropyl(4-methoxyphenyl)methyl]-4-methylbenzenesulfonamide
(6d): White solid; m.p. 124–1258C; 1H NMR (CDCl3, 400 MHz, TMS):
d=0.17–0.26 (m, 2H), 0.38–0.51 (m, 2H), 1.04–1.12 (m, 1H), 2.37 (s,
3H), 3.66 (dd, 1H, J=8.3, 6.0 Hz), 3.75 (s, 3H), 5.28 (d, 1H, J=6.6 Hz),
6.69 (d, 2H, J=8.7 Hz), 7.03 (d, 2H, J=10.0 Hz), 7.14 (d, 1H, J=
8.0 Hz), 7.56 ppm (d, 1H, J=8.2 Hz); 13C NMR (CDCl3, 100 MHz,
TMS): d=3.6, 4.4, 18.0, 21.5, 55.2, 61.9, 113.6, 127.2, 128.0, 129.2, 132.7,
137.9, 142.9, 158.8 ppm; IR (KBr): n˜ =3237, 1612, 1514, 1437, 1323, 1242,
1155, 1049, 806, 669 cmÀ1; MS (ESI): m/z: 354 [M+Na]+; HRMS (ESI)
calcd for C18H21NO3SNa: 354.1134; found: 354.1085.
[2] M. Georgy, V. Boucard, J.-M. Campagne, J. Am. Chem. Soc. 2005,
127, 14180–14181.
[3] W. Rao, P. W. H. Chan, Org. Biomol. Chem. 2008, 6, 2426–2433.
[4] J. Liu, E. Muth, U. Florke, G. Henkel, K. Merz, J. Sauvageau, E.
Schwake, G. Dyker, Adv. Synth. Catal. 2006, 348, 456–462.
[5] K. Mertins, I. Lovel, J. Kischel, A. Zapf, M. Beller, Adv. Synth.
Catal. 2006, 348, 691–695.
[6] A. Aponick, C.-Y. Li, B. Biannic, Org. Lett. 2008, 10, 669–671.
[7] X.-Z. Shu, X.-Y. Liu, H.-Q. Xiao, K.-G. Ji, L.-N. Guo, Y.-M. Liang,
Adv. Synth. Catal. 2008, 350, 243–248.
N-[Cyclopropyl(4-fluorophenyl)methyl]-4-methylbenzenesulfonamide
(6e): White solid; m.p. 100–1028C; 1H NMR (CDCl3, 400 MHz, TMS):
d=0.16–0.27 (m, 2H), 0.43–0.52 (m, 2H), 1.03–1.09 (m, 1H), 2.38 (s,
3H), 3.66 (dd, 1H, J=8.4, 6.0 Hz), 5.41 (d, 1H, J=5.7 Hz), 6.82–6.86 (m,
2H), 7.07–7.16 (m, 4H), 7.55 ppm (d, 2H, J=8.1 Hz); 13C NMR (CDCl3,
100 MHz, TMS): d=3.7, 4.4, 18.1, 21.5, 61.9, 115.0 (d, J=21.2 Hz), 127.1,
128.5 (d, J=8.0 Hz), 129.3, 136.4 (d, J=3.2 Hz), 137.7, 143.2, 162.8 ppm
(d, J=244.3 Hz); IR (KBr): n˜ =3237, 1612, 1514, 1437, 1323, 1242, 1155,
1049, 806, 669, 544 cmÀ1; MS (ESI): m/z: 342 [M+Na]+; HRMS (ESI)
calcd for C17H18NO2FSNa: 342.0934; found: 342.1003.
[8] S. Guo, F. Song, Y. Liu, Synlett 2007, 964–968.
[9] a) W. Wu, W. Rao, Y. Q. Er, K. J. Loh, C. Y. Poh, P. W. H. Chan, Tet-
rahedron Lett. 2008, 49, 2620–2624; b) J. W. W. Chang, P. W. H.
Chan, Angew. Chem. 2008, 120, 1154–1156; Angew. Chem. Int. Ed.
2008, 47, 1138–1140; c) W. Rao, P. W. H. Chan, Tetrahedron Lett.
2007, 48, 3789–3792; d) J. W. W. Chang, X. Xu, P. W. H. Chan, Tetra-
hedron Lett. 2007, 48, 245–248.
N-[Cyclopropyl(naphthalen-1-yl)methyl]-4-methylbenzenesulfonamide
(6 f): White solid; m.p. 119–1208C; 1H NMR (CDCl3, 400 MHz, TMS):
d=0.20- 0.32 (m, 2H), 0.37–0.53 (m, 2H), 1.34–1.43 (m, 1H), 2.24 (s,
3H), 4.61 (t, 1H, J=7.2 Hz), 5.51 (d, 1H, J=6.0 Hz), 6.89 (d, 2H, J=
8.2 Hz), 7.24–7.45 (m, 6H), 7.65 (d, 1H, J=8.1 Hz), 7.44–7.77 (m, 1H),
8.01–8.02 ppm (m, 1H); 13C NMR (CDCl3, 100 MHz, TMS): d=3.5, 5.3,
17.4, 21.3, 58.8, 123.2, 125.1, 125.3, 125.5, 126.1, 127.0, 128.1, 128.7, 128.9,
130.7, 133.7, 135.5, 137.5, 142.7 ppm; IR (KBr): n˜ =3254, 1597, 1508,
1443, 1163, 773, 671, 570 cmÀ1; MS (ESI): m/z: 374 [M+Na]+; HRMS
(ESI) calcd for C21H21NO2SNa: 374.1191; found: 374.1369.
[10] For recent reviews, see: a) F. Bellina, R. Rossi, Tetrahedron 2006,
62, 7213–7256; b) I. Coldham, R. Hufton, Chem. Rev. 2005, 105,
2765–2810; c) I. Nakamura, Y. Yamamoto, Chem. Rev. 2004, 104,
2127–2198; d) M. Yus, F. Foubelo, J. Org. Chem. 2001, 66, 6207–
6208; e) S. Laschat, T. Dickner, Synthesis 2000, 1781–1813; f) D. O.
Hagan, Nat. Prod. Rep. 2000, 17, 435–446; g) P. D. Bailey, P. A. Mill-
wood, P. D. Smith, Chem. Commun. 1998, 633–640; h) P. M.
Dewick, Medicinal Natural Products, Wiley, Chichester, 1997,
Chap. 6; i) S. Laschat, Liebigs Ann. 1997, 1, 1–11; j) M. Pichon, B.
Figadere, Tetrahedron: Asymmetry 1996, 7, 927–964, and references
therein; k) C. J. J. Wang, M. A. Wuonola, Org. Prep. Proced. Int.
1992, 24, 583–621; l) V. Baliah, R. Jeyaraman, L. Chandrasekaran,
Chem. Rev. 1983, 83, 379–423; m) K. R. Hill, Chem. Alkaloids 1970,
385–429.
[11] a) J. P. Devlin, O. E. Edwards, P. R. Gorham, N. R. Hunter, R. K.
Pike, B. Stavric, Can. J. Chem. 1977, 55, 1367–1371; b) W. W. Carmi-
chael, D. F. Biggs, P. R. Gorham, Science 1975, 187, 542–544.
[12] a) N. Asano, H. Kuroi, K. Ikeda, H. Kizu, Y. Kameda, A. Kato, I.
Adachi, A. A. Watson, R. J. Nash, G. W. J. Fleet, Tetrahedron:
Asymmetry 2000, 11, 1–8; b) A. Kato, I. Adachi, M. Miyauchi, K.
Ikeda, T. Komae, H. Kizu, Y. Kameda, A. A. Watson, R. J. Nash,
M. R. Wormald, G. W. J. Fleet, N. Asano, Carbohydr. Res. 1999, 316,
95–103.
N-[Cyclopropyl(3,5-dimethylphenyl)methyl]-4-methylbenzenesulfona-
mide (6g): White solid; m.p. 104–1058C; 1H NMR (CDCl3, 400 MHz,
TMS): d=0.24–0.31 (m, 2H), 0.41–0.53 (m, 2H), 1.04–1.13 (m, 1H), 2.16
(s, 6H), 2.37 (s, 3H), 3.62 (dd, 1H, J=8.4, 6.1 Hz), 5.15 (d, 1H, J=
5.9 Hz), 6.64 (s, 2H), 6.77 (s, 1H), 7.13 (d, 2H, J=8.1 Hz), 7.54 ppm (d,
2H, J=8.2 Hz); 13C NMR (CDCl3, 100 MHz, TMS): d=3.7, 4.5, 18.0,
21.2, 21.4, 62.6, 124.7, 127.2, 129.0, 129.1, 137.7, 137.9, 140.2, 142.8 ppm;
IR (KBr): n˜ =3262, 3009, 2918, 1431, 1333, 1163, 1096, 1026, 812, 712,
662 cmÀ1
;
MS (ESI): m/z: 352 [M+Na]+; HRMS (ESI) calcd for
C19H23NO2SNa: 352.1342; found: 352.1355.
N-[Cyclopropyl(2-methoxyphenyl)methyl]-4-methylbenzenesulfonamide
1
(6h):[24] White solid; m.p. 136–1388C; H NMR (CDCl3, 400 MHz, TMS):
d=0.19–0.24 (m, 1H), 0.33–0.40 (m, 2H), 0.47–0.53 (m, 1H), 1.28–1.36
(m, 1H), 2.28 (s, 3H), 3.66–3.70 (m, 4H), 5.84 (d, 1H, J=9.1 Hz), 6.60
(d, 1H, J=8.2 Hz), 6.71 (t, 1H, J=7.4 Hz), 6.84–7.10 (m, 4H), 7.45 ppm
(d, 2H, J=8.2 Hz); 13C NMR (CDCl3, 100 MHz, TMS): d=4.2, 4.9, 16.8,
21.4, 55.1, 61.7, 110.6, 120.4, 126.8, 128.0, 128.4, 128.8, 129.0, 137.9, 142.4,
156.2 ppm; IR (KBr): n˜ =3281, 2928, 1601, 1497, 1423, 1325, 1159, 762,
[13] S. Murakami, T. Takemoto, Z. Shimizu, K. Daigo, J. Pharm. Soc.
Jpn. 1953, 73, 571–574.
[14] P. J. Trippier, M. G. Moloney, Z. Wang, M. Yaqoob, Curr. Drug Dis-
covery Technol. 2004, 1, 181–199.
[15] a) J. H. Johnson, D. W. Phillipson, A. D. Kahle, J. Antibiot. 1989, 42,
1184–1185; b) R. E. Schwartz, J. Liesch, O. Hensens, L. Zitano, S.
Honeycutt, G. Garrity, R. A. Fromtling, J. Onishi, R. Monaghan, J.
Antibiot. 1988, 41, 1774–1779.
679 cmÀ1
;
MS (ESI): m/z: 354 [M+Na]+; HRMS (ESI) calcd for
C18H21NO3SNa: 354.1134; found: 354.1089.
[16] N. Morita, N. Krause, Org. Lett. 2004, 6, 4121–4123.
[17] J. Zhang, C.-G. Yang, C. He, J. Am. Chem. Soc. 2006, 128, 1798–
1799.
[18] a) B. M. Trost, Acc. Chem. Res. 2002, 35, 695–705; b) B. M. Trost,
Science 1991, 254, 1471–1477.
[19] M. Shi, L.-P. Liu, J. Tang, Org. Lett. 2006, 8, 4043–4046.
[20] W.-J. Shi, Y. Liu, P. Butti, A. Togni, Adv. Synth. Catal. 2007, 349,
1619–1623.
Acknowledgements
This work is supported by a University Research Committee Grant
(RG55/06) and Supplementary Equipment Purchase Grant (RG134/06)
from Nanyang Technological University. We thank the reviewers for their
helpful comments and suggestions.
[21] For recent reviews, see: a) J. Muzart, Tetrahedron 2005, 61, 4179–
4212; b) Y. Tamaru, Eur. J. Org. Chem. 2005, 2647–2656; c) V.
Jäger, T. Gracza, E. Dubois, T. Hasençhrl, W. Hümmer, B. K.
Kautz, A. Lieberknecht, L. Remen, D. Shaw, U. Stahl, O. Stephan in
Organic Synthesis via Organometallics, OSM 5 (Eds.: G. Helmchen,
J. Dibo, D. Flubacher, B. Wiese), Vieweg, Braunschweig, 1997,
p. 331.
[1] Recent reviews on gold-catalyzed reactions: a) H. C. Shen, Tetrahe-
dron 2008, 64, 3885–3903; b) Y. Yamamoto, J. Org. Chem. 2007, 72,
7817–7831; c) D. J. Gorin, F. D. Toste, Nature 2007, 446, 395–403;
d) A. S. K. Hashmi, G. J. Hutchings, Angew. Chem. 2006, 118, 8064–
8105; Angew. Chem. Int. Ed. 2006, 45, 7896–7936; e) A. S. K.
10494
www.chemeurj.org
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Chem. Eur. J. 2008, 14, 10486 – 10495

Amination/Ring Expansion of Cyclopropyl Methanols
FULL PAPER
[22] a) P. Szolcsµnyi, T. Gracza, M. Koman, N. Prónayovµ, T. Liptaj,
Chem. Commun. 2000, 471–472; b) W. Hümmer, E. Dubois, T.
Gracza, V. Jäger, Synthesis 1997, 634–642; c) M. Kimura, H. Har-
ayama, S. Tanaka, Y. J. Tamaru, J. Chem. Soc. Chem. Commun.
1994, 2531–2533; d) S. Saito, T. Hara, N. Takahashi, M. Hirai, T.
Morikawe, Synlett 1992, 237–238; e) V. Jäger, W. Hümmer, Angew.
Chem. 1990, 102, 1182–1183; Angew. Chem. Int. Ed. Engl. 1990, 29,
1171–1173; f) Y. Tamaru, M. Hojo, Z. Yoshida, J. Org. Chem. 1988,
53, 5731–5741; g) Y. Tamaru, Z. Yoshida, J. Organomet. Chem.
1987, 334, 213–223; h) Y. Tamaru, T. Kobayashi, S. Kawamura, H.
Ochiai, Z. Yoshida, Tetrahedron Lett. 1985, 26, 4479–4482.
[23] For recent works comparing the catalytic activity of metal triflates
with TfOH, see refs. [1,3,18,19] and a) T. Jin, Y. Yamamoto, Org.
Lett. 2007, 9, 5259–5262; b) D. C. Rosenfeld, S. Shekhar, A. Take-
miya, M. Utsunomiya, J. F. Hartwig, Org. Lett. 2006, 8, 4179–4182.
For spectroscopic evidence in a closely related system showing
Ph3PAuNHTs and TfOH could not be formed from reaction of
Ph3PAuOTf with NH2Ts but Ph3PAuOTf and NH2Ts could be fur-
nished from reaction of Ph3PAuNHTs with TfOH, see c) Z. Li, J.
Zhang, C. Brouwer, C.-G. Yang, N. W. Reich, C. He, Org. Lett. 2006,
8, 4175–4178, and references therein. For recent works comparing
catalytic activity of metal triflates with other Brønsted acids, see
ref. [4] and d) A. S. K. Hashmi, L. Schwarz, P. Rubenbauer, M. C.
Blanco, Adv. Synth. Catal. 2006, 348, 705–708; e) G. Dyker, E.
Muth, A. S. K. Hashmi, L. Ding, Adv. Synth. Catal. 2003, 345, 1247–
1252.
[25] For recent works on the formation of conjugated enynes from 1-cy-
clopropylprop-2-yn-1-ols, see: a) Y. Yamauchi, G. Onodera, K.
Sakata, M. Yuki, Y. Miyake, S. Uemura, Y. Nishibayashi, J. Am.
Chem. Soc. 2007, 129, 5175–5179; b) H.-Q. Xiao, X.-Z. Shu, K.-G.
Ji, C.-Z. Qi, Y.-M. Liang, New J. Chem. 2007, 31, 2041–2043.
[26] B. Schlummer, J. F. Hartwig, Org. Lett. 2002, 4, 1471–1474.
[27] The analogous conversion of 6a to 3a catalyzed by TfOH (5 mol%)
under similar conditions gave a lower product yield of 48%.
[28] For recent leading works on enantioselective gold-catalyzed synthe-
sis of pyrrolidines, see a) Z. Zhang, C. F. Bender, R. A. Widenhoe-
fer, J. Am. Chem. Soc. 2007, 129, 14148–14149; b) R. L. LaLonde,
B. D. Sherry, E. J. Kang, F. D. Toste, J. Am. Chem. Soc. 2007, 129,
2452–2453; c) G. L. Hamilton, E. J. Kang, M. Mba, F. D. Toste, Sci-
ence 2007, 317, 496–499.
[29] a) C. Singh, S. Pandey, G. Saxena, N. Srivastava, M. Sharma, J. Org.
Chem. 2006, 71, 9057–9061; b) M. Bietti, G. Gente, M. Salamone, J.
Org. Chem. 2005, 70, 6820–6826; c) N. Dwivedi, N. Tewari, V. K.
Tiwari, V. Chaturvedi, Y. K. Manju, A. Srivastava, A. Giakwad, S.
Sinhac, R. P. Tripathia, Bioorg. Med. Chem. Lett. 2005, 15, 4526–
4530; d) M. Masui, T. Shioiri, Synlett 1997, 273–274.
[30] Y. Tamaru, M. Hojo, S. Kawamura, Z. Yoshida, J. Org. Chem. 1986,
51, 4089–4090.
[31] V. Mutel, E. Vieira, J. Wickmann, PCT Int. Appl.
WO2000058285 20000318 A1, 2000.
[32] J. M. Andrꢁs, I. Herrµiz-Sierra, R. Pedrosa, A. Pꢁrez-Encoba, Eur. J.
Org. Chem. 2000, 9, 1719–1726.
[33] Y. Chen, M. Shi, J. Org. Chem. 2004, 69, 426–431.
[24] CCDC-679923 and CCDC-679924 contain the supplementary crys-
tallographic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
[34] M. Shi, Y. Chen, B. Xu, J. Tang, Green Chem. 2003, 5, 85–88.
Received: June 23, 2008
Published online: September 22, 2008
Chem. Eur. J. 2008, 14, 10486 – 10495
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
10495