Retention of stereochemistry in gold-catalyzed formal [4+3] cycloaddition of epoxides with arenynamides

Article abstract of DOI:10.1002/anie.201203723

Golden opportunity: [4+3] Cycloaddition reactions of arenynamides and epoxides are enabled under gold catalysis and have a broad substrate scope (see scheme; Ms=methanesulfonyl). An S_N2-type front-side attack of phenyl at the oxiranyl ring is expected to cause the retention of stereochemistry. Copyright

Full text of DOI:10.1002/anie.201203723

Angewandte
Chemie
DOI: 10.1002/anie.201203723
Synthetic Methods
Retention of Stereochemistry in Gold-Catalyzed Formal
[4+3] Cycloaddition of Epoxides with Arenynamides**
Somnath Narayan Karad, Sabyasachi Bhunia, and Rai-Shung Liu*
Table 1: Tests of the [4+3] cycloaddition over gold catalysts.
Metal-mediated intermolecular cycloadditions are powerful
tools to access carbo- and heterocyclic frameworks.[1] Epox-
ides and aziridines serve as three-atom building units for
various metal-mediated [3 + n] cycloadditions (n = 2,3) with
small molecules.[2–7] The cycloadditions of epoxides and
aziridines with alkenes or alkynes exclusively proceeded
through [3+2] cycloadditions,[3,4] whereas [3+3] cycloaddi-
tions occurred for propargylmetal reagents.[5] Catalytic inter-
molecular [4+3] cycloadditions of epoxides or aziridines have
only one precedent.[8] Herein, we report a new synthesis of
seven-membered oxacycles through a gold-catalyzed inter-
molecular [4C+3] cycloaddition[9] of arenynamides with
epoxides (Scheme 1). Particularly notable is the observed
Entry
Catalyst[a]
Solvent
Time [h]
Yield [%]
1a
3a[b]
1
2
3
4
5
6
7
8
[PPh3AuCl]/AgNTf2
[LAuCl]/AgNTf2
[IPrAuCl]/AgNTf2
[IPrAuCl]/[AgSbF6]
[IPrAuCl]/AgOTf
AgNTf2
[AgSbF6]
HOTf
[IPrAuCl]/AgNTf2
[IPrAuCl]/AgNTf2
[IPrAuCl]/AgNTf2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
(CH2Cl)2
toluene
CH3CN
4.0
4.0
1.8
1.7
3.0
12
–
–
–
–
–
4
62
87
71
20
-
85
80
–
20
14
85
12
–
[c]
4.0
1.7
12
–
9
10
11
61
58
–
12
[a] [1a]=0.20m. [b] Determined after purification by column chroma-
tography on neutral alumina. [c] Ketone 1A was isolated in 76% yield.
Bn=benzyl, IPr=1,3-bis(diisopropyl phenyl imidazol-2-ylidene, L=(o-
biphenyl)(tBu)2P, Ms=methanesulfonyl, Tf=trifluoromethanesulfonyl.
Scheme 1. Cycloadditions of phenylalkynes with epoxides or aziridines.
EWG=electron-withdrawing group, Ts=4-toluenesulfonyl.
(tBu)2AuCl]/AgNTf2 gave cycloadduct 3a in a significant
proportion (62%, entry 2). [IPrAuCl]/AgNTf2 (IPr= 1,3-
bis(diisopropylphenyl)imidazol-2-ylidene) improved the
yield of desired 3a to 87% yield (entry 3). Variation of
silver salts as in [IPrAuCl]/AgX (X = SbF6 and OTf, entries 4
and 5) led to compound 3a in a decreased yield of 71% and
20%, respectively; weakly acidic [IPrAuOTf] appears to be
less efficient in this cycloaddition. We found no reactivity for
AgNTf2 or AgSbF6 catalysts (entries 6 and 7). HOTf gave
hydration product 1A in 76% yield (entry 8). For
[IPrAuNTf2], the yield of compound 3a depended on the
solvents: dichloroethane (61%), toluene (58%), and aceto-
nitrile (0%); unreacted 1a was recovered in 14–85%
(entries 9–11). Treatment of compound 3a with HOTf
(3 mol%) in wet CH2Cl2 (08C, 1 h) delivered lactone 3 A in
85% yield.
retention of stereochemistry in the gold-catalyzed ring open-
ing of epoxides during the attack of external arene nucleo-
philes (Scheme 1). This process contrasts sharply with a silver-
catalyzed [3+2] cycloaddition between 1-phenylalkynes and
aziridines, reported by Wender and Strand.[3]
We examined the cycloaddition reactions of arenynamide
1a with isobutylene oxide 2a over cationic gold complexes,
which are active catalysts for the intermolecular [4+2]
cycloadditions of arenynamide 1a with electron-rich
alkenes.[10] The reaction of arenynamide 1a with epoxide 2a
(4 equiv) using [PPh3AuCl]/AgNTf2 (5 mol%) in dichloro-
methane (288C, 4 h) gave a mixture of products, from which
we isolated [4+3] cycloadduct 3a in only 4% yield (Table 1,
entry 1). To our pleasure, the use of [P(o-biphenyl)-
The chemoselectivity for seven-membered oxacycle 3a is
unexpected, because similar reactions typically gave the [3+2]
cycloadduct.[3,4] Accordingly, we examined the scope of
arenynamides with alterable amides and aryl substituents.
Table 2 shows the results for the [4+3] cycloadditions of
arenynamides 1b–1m with epoxide 2a using [IPrAuCl]/
AgNTf2 (5 mol%) in CH2Cl2 (288C, 0.9–12 h). We obtained
only seven-membered oxacycles 3b–3m after workup; the
[*] S. N. Karad, Dr. S. Bhunia, Prof. Dr. R.-S. Liu
Department of Chemistry, National Tsing Hua University
Hsinchu, 30013 (Taiwan)
E-mail: rsliu@mx.nthu.edu.tw
[**] We thank the National Science Council, Taiwan, for financial support
of this work.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201203723.
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
These are not the final page numbers!

.
Angewandte
Communications
Table 2: [4+3] Cycloadditions on various arenynes.
Table 3: Cycloaddition reactions on various epoxides.
[a] [arenynamides]=0.20m, [IPrAuCl]/AgNTf2 (5 mol%), CH2Cl2. 288C.
[b] Determined after purification by column chromatography on neutral
alumina.
[a] [arenynamides]=0.20m. [b] Determined after purification by column
chromatography on neutral alumina.
1
absence of [3+2] cycloadducts was ascertained by H NMR
spectroscopy of their crude products. These cycloadditions
worked well for substrates 1b–1e, which bear various amido
substituents (EWG = tosyl and mesyl; R = methyl, n-butyl,
benzyl, and phenyl); the resulting cycloadducts 3b–3e were
obtained in 73–85% yield (entries 1–4). We tested the
reactions on arenynes 1 f and 1g, which bear 4-chloro and 4-
bromo substituents, giving desired cycloadducts 3 f and 3g in
71% and 64% yield, respectively (entries 5 and 6). We
studied the reactions on arenynamides 1h–1j, which bear
electron-rich benzenes; their resulting oxacycles 3h–3j were
obtained in 65–66% yield (entries 7–9). The scope of the
reactions was further expanded to arenynamides 1k–1m,
which bear 2- and 3-thienyl and 3-benzofuranyl and produced
cycloadducts 3k–3m in 45–74% yield (entries 10–12). A
protracted period (12 h) was observed for the formation of
benzofuranyl derivative 3m because of its bulky size, which is
unfavorable for an SN2-type front attack at the epoxide.
Various epoxides 2b–2j were subjected to gold-catalyzed
cycloadditions on arenynamide 1a (Table 3); except 4-
methoxyphenyloxirane 2e (entry 4), all these substrates
produced [4+3] cycloadducts. With styrene oxide 2b and its
4-fluoro- and 4-chlorophenyl derivatives 2c and 2d, respec-
tively, the corresponding [4+3] cycloadducts 4b–4d were
produced in 60–83% yield (entries 1–3). Notably, electron-
rich 4-methoxyphenyloxirane 2e gave [3+2] cycloadduct 5e
in 67% yield, however, the reaction took longer (6 h), thus
reflecting a significant electronic effect to alter reaction
chemoselectivity (entry 4). This [4+3] cycloaddition is exten-
sible to 1,1-disubstituted epoxides 2 f and 2g, which gave
desired products 4 f and 4g in 62% and 42% yield,
respectively (entries 5 and 6). We tested cis- or trans-1,2-
disubstituted epoxides 2h–2j to study the stereochemical
course of this [4+3] cycloaddition (entries 7–9). In the
reactions of cis-stilbene oxide 2h (R1 = R3 = Ph, R2 = R4 =
H), the resulting cycloadduct 4h was obtained in 70% yield.
X-ray diffraction study on compound 4h showed a cis-
configuration for its two phenyl substituents,[11] indicative of
the retention of stereochemistry. For cis-2-methylstyrene
oxide 2i (R1 = Ph, R3 = Me, R2 = R4 = H) and its trans ana-
logue 2j (R1 = Ph, R4 = Me, R2 = R3 = H), their correspond-
ing products 4i and 4j were produced stereoselectively with
75% and 65% yield, respectively (entries 8 and 9); we did not
obtain the other diastereomer. The cis configuration of
cycloadduct 4i was likewise determined by X-ray diffrac-
tion,[11] again showing the retention of stereochemistry.
This cycloaddition is applicable to the synthesis of
enantiopure oxacycle 4i (93% ee) using (2R,3S)-(À)-2-
methyl-3-phenyloxirane 2i (93% ee, Scheme 2). X-ray dif-
fraction of 4i confirmed the retention of stereochemistry.[11]
Hydrolysis of this cycloadduct afforded chiral lactone 4I in
93% ee. The use of enantiopure (2S,3S)-(À)-2-methyl-3-
phenyloxirane 2j (99% ee) efficiently delivered the corre-
sponding cycloadduct 4j (99% ee), and subsequently lactone
4 J (99% ee).
We examined the enantiospecificity of the [4+3] and
[3+2] cycloadditions using enantiopure aryl-substituted oxir-
anes (Table 4); this information may enable us to understand
the reaction chemoselectivity. For (R)-styrene oxide 2b (99%
2
www.angewandte.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
These are not the final page numbers!

Angewandte
Chemie
Scheme 3. Metal-assisted ligand migration in SN2-type retention.
Scheme 2. Synthesis of enantiopure seven-membered lactones.
Table 4: Enantiospecificity for [4+3] and [3+2] cycloadditions.
Entry
Epoxide[a]
Products
4/5 (ee [%])[b] Yield [%][c]
2 (Ar)
ee [%]
1
2
3
4
2b (C6H5)
99 (+)
99 (+)
99 (+)
99 (À)
(+)-4b (81)
(+)-4c (70)
(+)-4d (75)
(À)-4k (39),
rac-5k (0)
73
68
55
65
Scheme 4. Plausible mechanisms for [4+3] and [3+2] cycloadditions.
2c(4-FC6H4)
2d (4-ClC6H4)
2k (4-MeC6H4)
species A gives an oxonium species B, which still retains an
oxiranyl ring. Attack of the neighboring benzene at the
epoxide in an SN2-type inversion is unlikely because of its
front orientation. Instead, we envisage that species B has
a ground-state conformation that involves a parallel orienta-
tion between the benzene and oxiranyl rings. This conforma-
tion facilitates a front attack of benzene at the reacting
oxiranyl carbon atom because of their proximity. Formation
(4k/5k=1:4)
61
5
2e (4-MeOC6H4)
99 (À)
rac-5e (0)
[a] [1a]=0.20m, 4 h for entries 1–3, 10 h for entries 4 and 5. [b] ee values
were determined by HPLC analysis on a chiral stationary phase
(chiralpak AD-H). [c] Determined after separation by column chroma-
tography on neutral alumina.
À
À
ee), its gold-catalyzed cycloaddition with arenyne 1a afforded
[4+3] cycloadduct 4b with (+)-81% ee (entry 1). Its absolute
configuration was determined to be S by X-ray diffraction,[11]
again indicating a retention of stereochemistry. For (R)-4-
fluoro- and (R)-4-chlorophenyl oxirane 2c and 2d (99% ee),
their corresponding [4+3] cycloadducts (S)-4c and (S)-4d was
obtained with 70% and 75% ee, respectively (entries 2 and 3).
(R)-4-Methylphenyl oxirane 2k (99% ee) gave an inseparable
mixture of two the cycloadducts 4k/5k = 1:4 (entry 4); seven-
membered oxacycle 4k was obtained with 39% ee, whereas
five-membered species 5k was completely racemic. For (R)-4-
methoxyphenyl oxirane 2e, we obtained only the racemic
form of [3+2] cycloadduct 5e in 61% yield. Our results show
that formation of seven-membered oxacycle 4 occurs at the
early stage of oxirane cleavage to achieve an SN2-type
retention, whereas five-membered oxacycles 5 are produced
on a free benzylic cation after a complete oxirane cleavage.
SN2-type retention of stereochemistry was documented
for few stoichiometric reactions between epoxides and AlX3
(X = Cl, Me),[12] in which a coordinated ligand X attacks at
the reacting carbon center from the front side (Scheme 3).
This 1,4 ligand migration is in disagreement with the
mechanism of the retention chemistry in our system.
Scheme 4 shows a plausible mechanism for the [4+3] cyclo-
addition, Au-p-ynamide 1a is highly electrophilic, and also
represented by its ketenimine resonance structure A.[13,14] An
of the C C bond and C O bond cleavage might be concerted,
as shown in structure C (path a), subsequently forming
a cyclohexadienyl cation D, which bears an S-configuration.
This pathway is expected to give oxacyclic product (S)-4b. We
À
envisage that the oxiranyl PhC O bond of species B is rather
weak to allow a C C bond rotation. Accordingly, a small
À
portion of intermediate B undergoes an epimerization of
oxirane to form rac-B; this process rationalizes a small loss of
chirality for resulting cycloadduct 4b. The high stereospeci-
ficity for 1,2-disubstituted epoxides 2i and 2j is attributed to
their rigid conformation B, which has a barrier to rotate the
À
C O bond between the oxiranyl and alkenylgold moieties.
This postulated model also rationalizes the non-stereo-
specific [3+2] cycloaddition of (R)-4-methoxyphenyloxirane
2e and arenynamide 1a (Table 4, entry 5). In this instance, the
corresponding benzylic cation E is readily attained because of
the stabilization effect of 4-methoxyphenyl. This benzylic
cation moves freely toward gold alkenyl to deliver a [3+2]
oxacycle 5e with a complete loss of chirality.
We prepared [D5]-1a to confirm the intermediacy of
species D (Scheme 5); its resulting cycloadduct [D5]-3a has
a high deuterium content (X = 0.83 D) at its alkenyl position.
This result indicates the occurrence of a deauration process at
this alkenyl carbon atom.
Thus far, epoxides participated almost exclusively in
metal-catalyzed [3+2][3,4] or [3+3] cycloaddition[5] reactions.
We have now developed a gold-catalyzed [4+3] cycloaddition
=
attack of (R)-epoxide 2b at the C NMeMs carbon center of
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
3
These are not the final page numbers!

.
Angewandte
Communications
[7] a) B. M. Trost, A. R. Sudhakar, J. Am. Chem. Soc. 1987, 109,
3792 – 3794; b) B. M. Trost, A. R. Sudhakar, J. Am. Chem. Soc.
1988, 110, 7933 – 7935; c) C. Larksarp, H. Alper, J. Am. Chem.
Soc. 1997, 119, 3709 – 3715; d) G. Bez, C.-G. Zhao, Org. Lett.
2003, 5, 4991 – 4993.
[8] A BF3-mediated [4+3] cycloaddition was recently reported for
epoxides and aromatic unsaturated ketones, but no stereochem-
istry was involved. See: Y.-Q. Zhou, N.-X. Wang, S.-B. Zhou, Z.
Huang, L. Cao, J. Org. Chem. 2011, 76, 669 – 672.
Scheme 5. Deuterium labeling experiment.
[9] For gold-catalyzed [4+3] cycloadditions, reported examples
were performed exclusively in an intramolecular fashions. See
of epoxides with arenynamides with a broad substrate scope.
Of particular interest is the retention of stereochemistry[15,16]
for an intermolecular aryl attack at the epoxide. We used
various enantiopure aryl-substituted oxiranes to study the
chirality transfer in the [4+3] and [3+2] cycloadditions; their
mechanisms are thus elucidated. We postulate an SN2-type
front-side attack of phenyl at the oxiranyl ring for [4+3]
cycloadducts, whereas an attack at a free benzylic cation leads
to [3+2] products that contain benzoxepine frameworks
(represented by cycloadducts 3), which can be found in
several naturally occurring compounds;[17] their enantioselec-
tive synthesis is under current investigations.
´
a) F. Lꢀpez, J. L. Mascarenas, Beilstein, Beilstein J. Org. Chem.
´
2011, 7, 1075 – 1094; b) M. Gulꢁas, F. Lꢀpez, J. L. Mascarenas,
Pure Appl. Chem. 2011, 83, 495 – 506; c) P. Mauleꢀn, R. M.
Zeldin, A. Z. Gonzꢂlez, F. D. Toste, J. Am. Chem. Soc. 2009, 131,
6348 – 6349; d) B. Trillo, F. Lꢀpez, S. Montserrat, G. Ujaque, L.
´
Castedo, A. Lledꢀs, J. L. Mascarenas, Chem. Eur. J. 2009, 15,
3336 – 3339; e) I. Alonso, H. Faustino, F. Lꢀpez, J. L. Mascar-
´
enas, Angew. Chem. 2011, 123, 11698 – 11702; Angew. Chem. Int.
Ed. 2011, 50, 11496 – 11500; f) I. Alonso, B. Trillo, F. Lꢀpez, S.
´
Montserrat, G. Ujaque, L. Castedo, A. Lledꢀs, J. L. Mascarenas,
J. Am. Chem. Soc. 2009, 131, 13020 – 13030.
[10] R. B. Dateer, B. S. Shaibu, R.-S. Liu, Angew. Chem. 2012, 124,
117 – 121; Angew. Chem. Int. Ed. 2012, 51, 113 – 117.
[11] X-ray crystallographic data of [4+3] cycloadducts 4h, 4i, and
(S)-4b are provided in the Supporting Information.
Received: May 14, 2012
[12] a) J. H. Brewster, J. Am. Chem. Soc. 1956, 78, 4061 – 4064; b) M.
Inoue, T. Sugita, Y. Kiso, K. Ichikawa, Bull. Chem. Soc. Jpn.
1976, 49, 1063 – 1071; c) T. Nakajima, S. Suga, T. Sugita, K.
Ichikawa, Tetrahedron 1969, 25, 1807 – 1916.
[13] For chemistry of ynamides, see: a) K. A. DeKorver, H. Li, A. G.
Lohse, R. Hayashi, Z. Lu, Y. Zhang, R. P. Hsung, Chem. Rev.
2010, 110, 5064 – 5106; b) G. Evano, A. Coste, K. Jouvin, Angew.
Chem. 2010, 122, 2902 – 2921; Angew. Chem. Int. Ed. 2010, 49,
2840 – 2859; c) A. S. K. Hashmi, M. Rudolph, J. Huck, W. Frey,
Revised: June 26, 2012
Published online: && &&, &&&&
Keywords: [4+3] cycloaddition · arenynamide · epoxide ·
.
gold catalysis · retention
[1] For metal-catalyzed cycloaddition reactions, see selected
reviews: a) P. A. Wender, V. A. Verma, T. H. Paxton, Acc.
Chem. Res. 2008, 41, 40 – 49; b) M. Lautens, W. Klute, W. Tam,
Chem. Rev. 1996, 96, 49 – 92; c) P. A. Inglesby, P. A. Evans,
Chem. Soc. Rev. 2010, 39, 2791 – 2805; d) S. M. A. Sohel, R.-S.
Liu, Chem. Soc. Rev. 2009, 38, 2269 – 2281.
[2] For selected reviews for epoxides and aziridines, see: a) A. K.
Yudin in Aziridines and Epoxides in Organic Synthesis, Wiley-
VCH, Weinheim, 2006; b) K. V. Gothelf, K. A. Jørgensen,
Chem. Rev. 1998, 98, 863 – 910; c) W. Carruthers in Cyclo-
addition in Organic Synthesis, Pergamon, Oxford, 1990, p. 1.
[3] P. A. Wender, D. Strand, J. Am. Chem. Soc. 2009, 131, 7528 –
7529.
[4] a) I. Ungureanu, P. Klotz, A. Mann, Angew. Chem. 2000, 112,
4790 – 4792; Angew. Chem. Int. Ed. 2000, 39, 4615 – 4617; b) J.
Sisko, S. M. Weinreb, J. Org. Chem. 1991, 56, 3210 – 3211; c) R. J.
Madhushaw, C.-C. Hu, R.-S. Liu, Org. Lett. 2002, 4, 4151 – 4153;
d) S. C. Bergmeier, S. L. Fundy, P. P. Seth, Tetrahedron 1999, 55,
8025 – 8038; e) Y. Sugita, Y. Kimura, I. Yokoe, Tetrahedron Lett.
1999, 40, 5877 – 5880; f) M. Nakagawa, M. Kawahara, Org. Lett.
2000, 2, 953 – 955; g) J.-G. Shim, Y. Yamamoto, J. Org. Chem.
1998, 63, 3067 – 3071; h) J. S. Yadav, B. V. S. Reddy, S. K. Pandey,
P. P. Srihari, I. Prathap, Tetrahedron Lett. 2001, 42, 9089 – 9092;
i) J. Fan, L. Gao, Z. Wang, Chem. Commun. 2009, 5021 – 5023.
[5] a) R. J. Madhushaw, C.-L. Li, J.-C. Hu, R.-S. Liu, J. Am. Chem.
Soc. 2001, 123, 7427 – 7428; b) K.-H. Shen, S.-F. Lush, T.-L.
Chen, R.-S. Liu, J. Org. Chem. 2001, 66, 8106 – 8111; c) S. Hedley,
W. J. Moran, D. A. Price, J. P. A. Harrity, J. Org. Chem. 2003, 68,
4286 – 4292.
´
J. W. Bats, M. Hamzic, Angew. Chem. 2009, 121, 5962 – 5966;
Angew. Chem. Int. Ed. 2009, 48, 5848 – 5852.
[14] For gold-catalyzed electrophilic activation of ynamides, see
reference [13] and selected examples: a) C.-W. Li, K. Pati, G.-Y.
Lin, S. M. A. Sohel, H.-H. Hung, R.-S. Liu, Angew. Chem. 2010,
122, 10087 – 10090; Angew. Chem. Int. Ed. 2010, 49, 9891 – 9894;
b) P. W. Davies, A. Cremonesi, N. Martin, Chem. Commun.
2011, 47, 379 – 381; c) C. Li, L. Zhang, Org. Lett. 2011, 13, 1738 –
1741; d) D. Vasu, H. H. Hung, S. Bhunia, S. A. Gawade, A. Das,
R.-S. Liu, Angew. Chem. 2011, 123, 7043 – 7046; Angew. Chem.
Int. Ed. 2011, 50, 6911 – 6914; e) S. Kramer, Y. Odabachian, J.
Overgaard, M. Rottlꢃnder, F. Gagosz, T. Skrydstrup, Angew.
Chem. 2011, 123, 5196 – 5200; Angew. Chem. Int. Ed. 2011, 50,
˝
5090 – 5094; f) A. S. K. Hashmi, M. Bꢄhrle, M. Wolfle, M.
Rudolph, M. Wieteck, F. Rominger, W. Frey, Chem. Eur. J.
2010, 16, 9846 – 9854; g) P. W. Davies, A. Cremonesi, L. Dumi-
trescu, Angew. Chem. 2011, 123, 9093 – 9097; Angew. Chem. Int.
Ed. 2011, 50, 8931 – 8935; h) P. Garcia, Y. Harrak, L. Diab, P.
Cordier, C. Ollivier, V. Gandon, M. Malacria, L. Fensterbank, C.
Aubert, Org. Lett. 2011, 13, 2952.
[15] Complete retention of stereochemistry has been reported for the
reactions of epoxides or aziridines with CO[16] and CO2 using
[6a]
low-valent metals; their mechanisms are distinct from those
reactions that use Lewis acid to implement nucleophilic attack at
epoxides.
[16] a) J.-T. Lee, P. J. Thomas, H. Alper, J. Org. Chem. 2001, 66,
5424 – 5426; b) S. Calet, F. Urso, H. Alper, J. Am. Chem. Soc.
1989, 111, 931 – 934.
[6] a) K. Yamaguchi, K. Ebitani, T. Yoshida, H. Yoshida, K.
Kaneda, J. Am. Chem. Soc. 1999, 121, 4526 – 4527; b) C. M.
Miralda, E. E. Macias, M. Zhu, P. Ratnasamy, M. A. Carreon,
ACS Catal. 2012, 2, 180 – 183.
[17] a) J.-H. Liu, A. Steigel, E. Reininger, R. Bauer, J. Nat. Prod.
2000, 63, 403 – 405; b) F. MeriÅli, A. H. Mericli, H. Becker, A.
Ulubelen, Phytochemistry 1996, 42, 1257 – 1258; c) A. Ulubelen,
E. Tuzlaci, N. Atilan, Phytochemistry 1989, 28, 649 – 650.
4
www.angewandte.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
These are not the final page numbers!

Angewandte
Chemie
Communications
Synthetic Methods
S. N. Karad, S. Bhunia,
R.-S. Liu*
&&&& — &&&&
Retention of Stereochemistry in Gold-
Catalyzed Formal [4+3] Cycloaddition of
Epoxides with Arenynamides
Golden opportunity: [4+3] Cycloaddition
reactions of arenynamides and epoxides
with a broad substrate scope are enabled
under gold catalysis (see scheme; Ms=
methanesulfonyl). An SN2-type front-side
attack of phenyl at the oxiranyl ring is
expected to cause the retention of ste-
reochemistry.
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!