Effects of haloniums on gold-catalyzed ring expansion of 1-oxiranyl-1-alkynylcyclopropanes

Article abstract of DOI:10.1039/c0cc03309j

We observed distinct chemoselectivities for the gold-catalyzed transformation of cis-1-oxiranyl-1-alkynylcyclopropanes 1 into various halogenated products in the presence of suitable Au(iii) catalysts and N-halosuccinimide (halo = chloro, bromo and iodo).

Full text of DOI:10.1039/c0cc03309j

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Effects of haloniums on gold-catalyzed ring expansion of
-oxiranyl-1-alkynylcyclopropanesw
1
Hsuan-Hung Liao and Rai-Shung Liu*
Received 17th August 2010, Accepted 3rd November 2010
DOI: 10.1039/c0cc03309j
We observed distinct chemoselectivities for the gold-catalyzed
Table 1 Gold-catalyzed oxacyclization/ring expansions using NCS
transformation of cis-1-oxiranyl-1-alkynylcyclopropanes
1
into various halogenated products in the presence of suitable
Au(III) catalysts and N-halosuccinimide (halo = chloro, bromo
and iodo).
Formation of a carbo- or heterocyclic ring is an impor-
tant topic in organic synthesis. Among various ring sizes,
Additive/
a
Entry Catalyst /mol% Solvent t/h mol%
b
6a (yield [%])
1
,2
3
and medium ring sizes (seven to nine
four-membered
1
PPh
AgSbF
AuCl (10)
3
AuCl (5)/ DCM
7
—
Complex mixture
members) are particularly notable because many natural
products possess these structural units. However, few practical
methods are available for these cyclic rings; among them, ring
6
(5)
2
3
4
5
6
7
8
9
3
DCM 0.5
—
—
—
15%
AuBr
3
(10)
PtCl /CO (10) DCM
DCM
7
7
Complex mixture
Complex mixture
49%
4
2
closure metathesis is a powerful tool for medium-sized rings.
AuClPic (10)
AuCl Pic (10)
AuCl Pic (5)
DCM 0.16 —
DCM 0.16 PPh O (10) 61%
3
DCM 0.16 PPh O (10) 60%
3
We reported a gold-catalyzed hydrative ring-expansion of
2
cis-1-oxiranyl-1-alkynylcyclopropanes 1, giving 3-oxabicyclo-
2
AuCl
AuCl
2
Pic (5)
Pic (5)
MeCN 0.5 PPh
MeCN 0.5 PPh
3
O (10) 25%
O (10) 35%
[4.2.0]oct-4-en-6-ols 2 stereoselectively (dr 4 10 : 1) via a
5
hypothetic tertiary cation A. Notably, their trans analogues
2
3
a
b
Substrate] = 0.1 M. Yields are reported after elution from a silica
[
column.
failed to undergo stereoselective ring expansions because of a
staggered orientation between the alkyne and epoxide groups.
5
(5 mol%), alcohols 2 form
In the presence of PPh
3
AuSbF
6
1
-oxyallyl cations that undergo [4+2]-cycloaddition with
butadienes or enones to give polycyclic products 3 and 4 with
3
excellent diastereoselectivities. Alkenyl halides are important
functionalities for various metal-catalyzed carbon–carbon
6
coupling reactions. We sought to prepare halogen-containing
bicyclic derivatives 5 via this hydrative ring expansion, in
7
+
which X replaces the gold fragment in intermediate A.
Table 1 shows our catalyst screening using common
8
p-alkyne activators, with which starting cis-epoxide 1a was
completely consumed for all cases. In a standard operation,
3 6
cis-epoxide 1a was treated with PPh AuCl/AgSbF (5 mol%)
in wet CH Cl (DCM, 25 1C) for a short period (2–3 min),
followed by an addition of N-chlorosuccinimide (NCS, 1.0 equiv.),
2
2
Scheme 1 Reaction pathways for gold-catalyzed cyclizations.
7a
giving a complex mixture of products (entry 1). Although
that could inhibit the protodeauration. The yield of 6a was
kept at 60% even with a small loading (5 mol%) of AuCl Pic.
AuCl3 (10 mol%) enabled
a
hydrative cyclization of
2
intermediate A derived from 1a (Scheme 1), its subsequent
treatment with NCS (1 equiv.) gave 3-chloro-4,5-dihydro-2H-
oxocin-6(3H)-one 6a, an eight-membered ether bearing a
This catalysis is greatly affected by solvents in that THF
and nitromethane gave poor yields (25–35%) of the desired
ether 6a (entries 8 and 9). Interestingly, naturally occurring
3a–c
3d,e
cis-configuration, albeit in 15% yield (entry 2); the cis-geometry
1
was determined by H NOE spectra. PtCl
compounds such as laurencin
similar structural skeletons.
and laurenyne
have
2
/CO and AuBr
3
failed to give 6a in a tractable amount (entries 3 and 4). Stable
Au(III) species such as AuCl Pic (Pic = picolate, 10 mol%)
2
greatly improved the yield of the desired 6a to 49% (entry 5),
and further to 61% in the presence of PPh PO (10 mol%, entry 6)
3
Department of Chemistry, National Tsing-Hua University, Hsinchu,
Taiwan, ROC. E-mail: rsliu@mx.nthu.edu.tw
Stereoselective formation of the eight-membered ether 6a
from starting cis-epoxide 1a is mechanistically appealing
because this process involves two consecutive openings of a
starting cyclopropyl ring. We prepared cis-epoxides 1b–1j to
w Electronic supplementary information (ESI) available: Experimental
details and characterization data and H and C NMR spectra of new
compounds. See DOI: 10.1039/c0cc03309j
1
13
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Chem. Commun., 2011, 47, 1339–1341 1339

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Table 2 Scope for the synthesis of eight-membered ring ethers
Table 3 Gold-catalyzed cyclization using NBS
b
Entry
Catalyst
Time
Product (yield [%])
a
Entry Epoxide Ar
1
2
b
R
R
Product (yield [%])
1
2
3
AuCl
AuCl
AuBr
2
(Pic)
10 min
30 min
7 h
7 (45%)
5b (68%)
5b (24%)
1
2
3
4
5
1b
1c
1d
1e
1f
C
6
H
5
n-Pentyl H
n-Pentyl H
n-Pentyl H
n-Pentyl H
n-Pentyl H
6b (81%)
6c (56%)
6d (69%)
6e (58%)
6f (53%)
3
p-MeOC
p-CNC
p-FC
p-ClC
6 4
H
3
a
6
H
4
[
Epoxide] = 0.1 M, NCS = N-chlorosuccinimide, DCM = dichloro-
6
H
4
b
methane. Yields are reported after elution from a silica column.
6
H
4
6
7
1g
1h
n-Pentyl H
n-Pentyl H
6g (79%)
6h (77%)
Table 4 Product yields for ring expansions with NBS and NIS
8
1i
n-Pentyl H
n-Pentyl H
6i (82%)
9
1
1j
6j (47%)
6k (83%)
0
1k
C
C
6
6
H
5
5
Methyl
Methyl
H
H
a
Entry Epoxide Ar
1
R
2
R
b
Product (yield [%])
11
1l
6l (80%)
1
2
1a
1g
6
p-MeOC H
4
Pentyl
Pentyl
H
H
5a (X = Br, 56%)
12
1m
H
Methyl Methyl 6m (57%)
5g (X = Br, 63%)
a
[
Epoxide] = 0.1 M, NCS = N-chlorosuccinimide, DCM = dichloro-
b
methane. Yields are reported after elution from a silica column.
3
1i
Pentyl
H
5i (X = Br, 70%)
5k (X = Br, 63%)
Methyl Pethyl 5m (X = Br, 61%)
assess the generality of this catalysis. For 1,2-disubstituted
4
5
6
7
1k
1m
1a
1b
C
C
6
H
H
5
5
Methyl H
epoxides 1b–f bearing variable para-substituents at the
6
0
p-MeOC
C
6
H
4
Pentyl
Pentyl
H
H
5a (X = I, 60%)
5b (X = I, 75%)
alkynylphenyl (Ar = 4-XC
6
4
H ) positions, we obtained good
0
6
H
5
yields (469%) of compounds 62b (X = H) and 6d (X = CN)
and moderate yields (53–58%) of compounds 6c (X = MeO),
0
8
9
1g
1h
Pentyl
Pentyl
H
H
5g (X = I, 72%)
6
e (X = F) and 6f (X = Cl). This new catalysis is particularly
suitable for epoxides 1g–i bearing Ar = 2-, 3-thienyl and
5h0 (X = I, 70%)
2
-benzothienyl; resulting ether products 6g–i were obtained in
7
7–82% yields (entries 6–8) (Table 2). The same reaction
0
1
0
1i
Pentyl
H
5i (X = I, 73%)
appears to be less efficient for the 2-furanyl derivative 1j that
gave the expected product 6j in 47% yield (entry 9). This
ether synthesis is also applicable for distinct 1,2-disubstituted
0
1
1
1
2
1k
1m
C
C
6
H
H
5
5
Methyl H
Methyl Methyl 5m (X = I, 70%)
5k (X = I, 72%)
0
6
a
b
[Substrate] = 0.1 M, NIS = N-iodosuccinimide. Yields are
1
epoxides 1k and 1l bearing R = Me, giving resulting products
reported after elution from a silica column.
6
k and 6l in 80–83% yields (entries 10–11). We obtained a
similar ether 6m in 57% yield from the trisubstituted epoxide
substrate 1m (entry 12). Among these cases, low product yields
NIS (N-iodosuccinimide) for several cis-epoxides, as depicted
in Table 4. This synthesis is extensible for cis-epoxides 1a, 1g,
1i, and 1k bearing alterable alkynylaryl (Ar = 4MePh,
2-thienyl, 2-benzothienyl) and epoxyalkyl (R = n-pentyl,
methyl) groups; their resulting products 5a, 5g, 5i and 5k were
obtained in 56–70% yields (entries 1–4). The reaction works
also for the trisubstituted epoxide 1m that gave the expected
product 5m in 61% yield (entry 5). The use of NIS for the same
epoxides 1a,b, 1g–i, 1k and 1m not only gave products of
of ethers 6c and 6j, bearing an electron-rich 4-MeOC
-furanyl, respectively, were presumably due to the occurrence
of side products such as 2 and 5 (Scheme 1).
6 4
H and
2
We examined this gold catalysis using a brominum source,
N-bromosuccinimide (NBS); the results appear in Table 3. In a
standard operation, epoxide 1a was treated with a gold
catalyst, H
simultaneously. Among three Au(III) catalysts, AuCl
the best yield (68%) for the resulting 5-bromo-3-oxabicyclo-
4.2.0]oct-4-en-6-ol 5b whereas PicAuCl produced 2,2-dibromo-
-phenylethanone 7 in 45% yield (entry 1). Compound 5b was
2
O (2 equiv.) and NBS (1.2 equiv.) in DCM
3
gave
0
0
0
0
0
0
the same type, including 5a ,b , 5g –I , 5k and 5m with
high diastereoselectivity, but also produced them in yields
(60–75%, entries 6–12) greater than those cases from the
NBS sources.
[
2
1
the target in our original proposal (Scheme 1).
We find an intriguing observation that NCS and NBS
exhibited distinct behaviors in the ring expansions of the same
epoxide 1b. We examined the generality of the 3-oxabicyclo-
Shown in Scheme 2 are control experiments to clarify the
possible intermediacy of alcohol 2b in the gold-catalyzed
transformation of the starting epoxide 1b into desired halogenated
0
[
4.2.0]oct-4-en-6-ol synthesis using AuCl (5 mol%), NBS and
3
products 6b, 5b and 5b , as depicted in Tables 2–4. Treatment
1
340 Chem. Commun., 2011, 47, 1339–1341
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AuCl
2
(Pic) catalysts, we obtained 3-chloro-4,5-dihydro-2H-
oxocin-6(3H)-one 6, an eight-membered ether, via two
consecutive ring openings of a starting cyclopropane ring. In
the presence of NXS (X = Br and I) and AuCl catalysts,
3
0
we obtained 5-halo-3-oxabicyclo[4.2.0]oct-4-en-6-ols 5 and 5
efficiently, via a single cyclopropane opening. Both reactions
gave one diastereomeric product.
Notes and references
1
(a) D. I. Schuster, G. Lem and N. A. Kaprinidis, Chem. Rev., 1993,
93, 3; (b) J. D. Winkler, C. M. Bowen and F. Liotta, Chem. Rev.,
Scheme 2 Control experiments and the use of chiral epoxide.
2
of 2b with 5% AuCl (Pic) and NCS (1.2 equiv.) in CH Cl led
1
995, 95, 2003; (c) J. Iriondo-Alberdi and M. F. Greaney, Eur. J. Org.
Chem., 2007, 4801; (d) N. Hoffman, Chem. Rev., 2008, 108, 1052.
For total synthesis of naturally occurring compounds bearing a
cyclobutane ring, see selected examples: (a) P. S. Baran,
A. L. Zografos and D. P. O’Malley, J. Am. Chem. Soc., 2004,
126, 3726; (b) V. B. Birman and X.-T. Jiang, Org. Lett., 2004, 6,
2
2
2
only to its recovery; good recovery yields were also obtained
for treatment of 2b with AuCl with NBS or NIS. We also
3
2
369; (c) P. S. Baran, K. Li, D. P. O’Malley and C. Mitsos, Angew.
Chem., 2006, 118, 255 (Angew. Chem., Int. Ed., 2006, 45, 249);
d) P. S. Baran and J. M. Richter, J. Am. Chem. Soc., 2005, 127,
5394; (e) S. E. Reisman, J. M. Ready, A. Hasuoka, C. J. Smith
and J. L. Wood, J. Am. Chem. Soc., 2006, 128, 1448.
prepared chiral epoxide 1m with 67% ee, but its gold-catalyzed
reaction with NCS gave the resulting product 6m with a
complete loss of chirality.
(
1
As alcohol 2b is not the intermediate for the generation of
0
3 For total synthesis of natural products Laurencin and Laurenyne
bearing an eight-membered ether ring, see: (a) M. T. Crimmins and
K. A. Emmitte, Org. Lett., 1999, 1, 2029; (b) J. W. Burton,
J. S. Clark, S. Derrer, T. C. Stork, J. G. Bendall and
A. B. Holmes, J. Am. Chem. Soc., 1997, 119, 7483; (c) M. Bratz,
W. H. Bullock, L. E. Overman and T. Takemoto, J. Am. Chem.
Soc., 1995, 117, 5958; (d) R. K. Boeckman Jr, J. Zhang and
M. P. Reeder, Org. Lett., 2002, 4, 2002; (e) L. E. Overman and
A. S. Thompson, J. Am. Chem. Soc., 1988, 110, 2248.
halogenated products 6b, 5b and 5b using epoxide 1a, we
propose a mechanism involving metal-containing 3-oxabicyclo-
[
4.2.0]oct-4-en-6-ol B via hydrolysis of the initial carbocation A.
In the presence of PPh PO and NCS, we believe that proto-
deauration of cation A to form alcohol 2b appears to be slow
3
due to the presence of PPh O such that the gold fragment of
3
intermediate B activates the proximate hydroxyl group toward
the attack of NCS. This process causes the opening of a
cyclobutanol ring to give an eight-membered ether 6b; the
proton released from the hydrolysis of cation A, in the form of
4
(a) R. H. Grubbs, Adv. Synth. Catal., 2007, 349, 27;
b) T. M. Trnka and R. H. Grubbs, Acc. Chem. Res., 2001, 34, 18.
(
5
For the synthesis of starting epoxide 1a, see: C.-Y. Yang, M.-S. Lin,
H.-H. Liao and R.-S. Liu, Chem.–Eur. J., 2010, 16, 2696 with its ESI.
+
+
9,10
PPh
We observed a change in the chemoselectivity for NBS and
3
PO-H , assists the liberation of Cl from NCS.
6 (a) N. Miyaura and A. Suzuki, Chem. Rev., 1995, 95, 2457;
b) E. Negishi and L. Anastasia, Chem. Rev., 2003, 103, 1979.
For selected examples, see: (a) L. Ye and L. Zhang, Org. Lett.,
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(e) A. Buzas and F. Gagosz, Synlett, 2006, 17, 2727;
f) S. F. Kirsch, J. T. Binder, B. Crone, A. Duschek, T. T. Haug,
C. Liebert and H. Menz, Angew. Chem., Int. Ed., 2007, 46, 2310.
(
7
+
’’
+’’
NIS because soft ‘‘Br
and ‘‘I
have a high affinity
2
toward the gold fragment to produce a direct replacement
7
(
(
Scheme 3).
In summary, we observed distinct chemoselectivities for
1
1
(
the gold-catalyzed transformation of cis-1-epoxy-1-alkynyl-
cyclopropanes 1 into various halogenated products in the
presence of suitable Au(III) catalysts and N-halosuccinimide
8 Selected reviews for gold and platinum catalyses, see: (a) A. S. K.
Hashmi and M. Rudolph, Chem. Soc. Rev., 2008, 37, 1766;
(
1
1
b) D. J. Gorin, B. D. Sherry and F. D. Toste, Chem. Rev., 2008,
08, 3351; (c) N. T. Patil and Y. Yamamoto, Chem. Rev., 2008,
08, 3395; (d) A. Furstner and P. W. Davies, Angew. Chem., Int.
(
halo = chloro, bromo and iodo). In the presence of NCS and
¨
Ed., 2007, 46, 3410; (e) S. Md. Abu Sohel and R.-S. Liu, Chem.
Soc. Rev., 2009, 38, 2269.
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9
(
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1
0 F. Mo, J. M. Yan, D. Qiu, F. Li, Y. Zhang and J. Wang, Angew.
Chem., Int. Ed., 2010, 49, 2028 and references therein.
1 The two Au(I)-catalyzed halogenation reactions failed to work
with epoxide substrates bearing an alkyl-substituted alkyne.
Cycloaddition reactions described in Scheme 1 have similar
limitations.
1
Scheme 3 Proposed mechanisms for various haloniums.
This journal is c The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 1339–1341 1341