Gold-catalyzed ring expansions of 1-alkynylcyclobutanol derivatives via tandem hydration and α-ketol rearrangement

Article abstract of DOI:10.1016/j.tet.2012.03.018

We report herein the gold-catalyzed tandem hydration/α-ketol rearrangement of 1-alkynylcyclobutanol derivatives, leading to cyclopentanones bearing an α-hydroxy substituted quaternary center. In the presence of water, coordination of gold catalyst onto alkynyl moiety triggers hydration rather than a direct ring expansion, which followed by unprecedented Au-catalyzed α-ketol rearrangement. The details and the scope of this method are presented.

Full text of DOI:10.1016/j.tet.2012.03.018

Tetrahedron 68 (2012) 5241e5247
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Gold-catalyzed ring expansions of 1-alkynylcyclobutanol derivatives via tandem
hydration and a-ketol rearrangement
*
Ki-Dae Kim, Hyun-Suk Yeom, Sunwoong Shin, Seunghoon Shin
Department of Chemistry and Research Institute for Natural Sciences, Hanyang University, 133-791 Seoul, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
We report herein the gold-catalyzed tandem hydration/
a
-ketol rearrangement of 1-alkynylcyclobutanol
-hydroxy substituted quaternary center. In the
presence of water, coordination of gold catalyst onto alkynyl moiety triggers hydration rather than
Received 3 February 2012
Received in revised form 28 February 2012
Accepted 6 March 2012
derivatives, leading to cyclopentanones bearing an
a
a direct ring expansion, which followed by unprecedented Au-catalyzed
details and the scope of this method are presented.
a-ketol rearrangement. The
Available online 19 March 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Gold catalysis
a
-Ketol rearrangement
Ring expansion
Tandem reaction
a
-Hydroxycyclopentanone
1. Introduction
2. Results and discussion
2.1. Initial investigations
Ring expansions of cyclobutanol derivatives have drawn signif-
icant interest because they provide versatile approaches to elabo-
rate cyclopentanone scaffolds in terms of functionality and
stereochemistry.1 Among myriads of catalytic methods to trigger
ring expansion of cyclobutanes, some recent developments are
particularly notable, including organocatalytic approaches2 as well
as transition metal catalysis employing Pd, Fe, Ru, and Co.3 Recently,
gold catalysts are also known to be powerful activators for small
ring expansion.4 In 2005, Toste and co-workers reported 1-
alkynylcyclopropanols and 1-alkynylcyclobutanols undergo direct
In order to realize the tandem reaction sequences outlined
above, several challenges resulting from competing processes are
to be addressed. In addition to the direct ring expansion pathway
(formation of A), Au(I) complexes are also known to catalyze
MeyereSchuster rearrangement leading to C, as reported by Chung
and co-workers employing closely related substrates.7 Thus we
started with identification of conditions that rapidly hydrate the 1-
alkynylcyclobutaols, thereby ensuring selective formation of B
rather than these competing processes.
As in Eq. 1, we prepared 1b as a test substrate and examined its
reaction in the presence of Au(IPr)Cl (5 mol %, IPr¼N,N0-bis(2,6-
diisopropylphenyl)imidazole-2-ylidene) and AgBF4 (5 mol %) in
dioxane at 80 ꢀC. Experiments conducted under anhydrous con-
ring expansion, leading to
a-methylenecyclobutanones and a-
methylenecyclopentanones, respectively (Scheme 1).4b We envi-
sioned that incorporation of water in the reaction mixture would
divert the reaction pathway from direct ring expansion to initial
hydration followed by a-ketol rearrangement, based on the well-
known reactivity of gold complexes as hydration catalysts.5 This
sequential catalysis would allow for a facile incorporation of an
ditions afforded 38% of a-hydroxylcyclopentanone 2b in addition
to the direct expansion product 3b (48% based on the crude 1H
NMR spectra), the former of which formed presumably from hy-
dration by adventitious water. In contrast, when we added one
drop of water (w15 equiv) into the reaction mixture, a near
complete selectivity toward 2b could be achieved (>99% yield by
hydroxyl group at the
quire oxidation of the corresponding cyclopentanone derivatives.6
Herein, we disclose that both hydration and -ketol rearrange-
ment are catalyzed by Au(I) complexes and the scope of this new
tandem catalysis are presented.
a-quaternary center, which otherwise re-
a
NMR). To verify the possible intermediacy of
shown in Scheme 1, we then attempted to intercept the putative
-ketol intermediate utilizing substrate 1d having a weaker ring
strain due to Thorpe-Ingold effect and therefore lower propensity
a-ketol intermediate
a
* Corresponding author. E-mail address: sshin@hanyang.ac.kr (S. Shin).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.03.018

5242
K.-D. Kim et al. / Tetrahedron 68 (2012) 5241e5247
Scheme 1.
toward ring expansion.8 As expected, the reaction of 1d at rt under
otherwise identical conditions led to an isolation of 4d in 76%
isolated yield after chromatographic separation (Eq. 2). This ex-
periment undoubtedly confirmed the
a-ketol is as an initial
product of this tandem reaction and furthermore the isolated 4d
served as a probe for identifying the catalysts for the subsequent
a
-ketol rearrangement (Eq. 3). Simple heating 4d in dioxane at
80 ꢀC did not afford any product and 4d remained intact even after
€
14 h. On the other hand, in the presence of Bronsted acid, HBF4
(5 mol %) instead of Au(IPr)BF4, the ring-expansion product 2d
(46%) was accompanied by a Rupe rearrangement product 5d
(52%). Finally, treating 4d with Au(IPr)BF4 (5 mol %) in 1,4-dioxane
led to a clean formation of the desired product 2d in excellent
isolated yield (91%). These results confirmed that the hydration
occurs faster than the competing direct 1,2-alkyl shift and the
same Au(I) catalyst efficiently mediate both regioselective hydra-
2.2. Optimization studies
tion and chemoselective
which presumably initiated by chelation of Au-catalyst onto
ketols as in D (Scheme 2). To the best of our knowledge, the gold-
a-ketol rearrangement, the latter of
To finely tune the reaction conditions that are generally ap-
plicable for diverse substrates, we conducted several screening
studies using 1c as a test substrate (Tables 1e3). As shown in
Table 1, among the ligands tested, Buchwald-type ligands, that
are bulky and relatively electron-rich, performed well for the
desired transformation and JohnPhos ligand stood out as an op-
a
-
catalyzed
our work.
a-ketol rearrangement has not been reported prior to
timal ligand (entry 3, Table 1). On the other hand, the reaction
was also highly sensitive to the counter-anions. Among the silver
salts examined, AgSbF6 provided the best results in terms of
Scheme 2. A proposed tandem hydration/a-ketol rearrangement.

K.-D. Kim et al. / Tetrahedron 68 (2012) 5241e5247
5243
Table 1
Screening of ligands
Entry
Au(L)Cl
Conva (%)
4ca (%)
2ca (%)
1
2
3
4
5
Au(IPr)Cl
Au(IMes)Cl
Au(L1)Cl
Au(L2)Cl
Au(L3)Cl
41
12
100
66
0
0
0
0
0
38
0
100
65
72
74
a
The yields are based on the crude 1H NMR spectra (1,3,5-trimethoxybenzene as an internal reference).
.
Table 2
Screening of counter-anions
Entry
AgX
Conva (%)
4ca (%)
2ca (%)
1
2
3
4
5
6
AgBF4
16
36
100
100
100
24
13
21
69
85
0
0
14
19
9
100
0
AgOTs
AgNTf2
AgOTf
AgSbF6
AgClO4
15
a
The yields are based on the crude 1H NMR spectra (1,3,5-trimethoxybenzene as an internal reference).
Table 3
Screening of solvents
Entry
Solvent
Conva (%)
4ca (%)
2ca (%)
1
2
3
4
5
6
1,4-Dioxane
Benzene
CH2Cl2
CH3NO2
CH3CN
100
49
21
100
23
0
0
0
0
54
21
0
100
46
18
41
0
CHCl3
0
a
The yields are based on the crude 1H NMR spectra (1,3,5-trimethoxybenzene as an internal reference).

5244
K.-D. Kim et al. / Tetrahedron 68 (2012) 5241e5247
Table 5
selective formation of 2c (entry 5, Table 2). Also notable is the
reaction with triflate counter-anion (AgOTf) that gave a hydration
product exclusively (entry 4, Table 2). Finally, among the
solvents tested, 1,4-dioxane served best as a reaction medium
(Table 3).
Substrate scope of tandem hydration/ring-expansion reaction
To further eliminate the possibility that the current tandem
hydration/ring expansion proceeds with a cheaper and simpler
catalytic system, we screened other catalysts as summarized below.
Replacing Au(JohnPhos)Cl/AgSbF6 with In(OTf)3, InCl3, Sc(OTf)3,
[RuCl(p-cymene)]2, Zn(OTf)2, Cu(OTf)2, CuI, and FeCl3 led to no
conversion at all, and only unreacted 1c remained in the mixture
(5 mol % of each salts in 1,4-dioxane at 80 ꢀC for 20 h, results not
shown). On the other hand, use of silver salts (5 mol %) alone dis-
played only marginal conversion toward the formation of desired
2c (Table 4). However, the efficiency is far behind the cationic
Au(JohnPhos)SbF6 complex. From these screening data, it is obvious
that the cationic Au(I) complex is uniquely fit for catalyzing tandem
hydration/ring-expansion reaction.
h
h
Entry
Substrate
R1
R2
R3
2a (%)
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
Ph
Ph
Ph
Ph
BnOCH2
H
(CH2)5
(CH2)5
H
H
Ph
Ph
H
H
COOEt
H
COOEt
H
COOEt
H
72b
87b
94
98
84b
99
H
1g
1h
70
64
COOEt
a
Isolated yield after chromatography.
The product was isolated as a single diastereomer.
b
2.3. Substrate scope
hydroxycyclopentanones and instead gave a direct ring-expansion
product 3i and a MeyereSchuster rearrangement product 6j, re-
spectively (Eqs. 4 and 5).
With the above-optimized conditions in hand, we next exam-
ined the scope of this tandem hydration/ring-expansion protocol as
6
shown in Table 5. In the presence of 2 mol % of Au(JohnPhos)Cl and
2 mol % of AgSbF6 in 1,4-dioxane, a smooth conversion occurred in
2 h at 80 ꢀC for diverse substrates having substitutions in the
cyclobutanes and/or at alkynes and the corresponding products
were obtained in good to excellent yields. However, internal alkyne
Having developed an efficient tandem hydration/ring-expan-
sion protocol in hand, we further explored intramolecular alkox-
ylation/ring-expansion cascade that would provide a concise route
toward spirocyclic ethers (Table 6). A brief optimization study
revealed that the Au(JohnPhos)SbF6 catalyst works smoothly for
the intended alkoxylation/ring-expansion sequence. For example,
when diol 1k was treated with Au(JohnPhos)SbF (5 mol %) in 1,4-
dioxane, a clean conversion into the corresponding spiroether 2k
was observed in 1.5 h at rt (65% isolated yield).9 Interestingly, while
the diastereoselectivity was low for 1l having a substituent at
homopropargylic position, a single diastereomer was isolated in
the reaction of 1m having a cyclobutane substituent. The proposed
course of reaction starts with initial 5-endo-dig alkoxylation giving
a protonated enol ether derivative E, which undergoes 1,3-
prototropic shift to give F (M¼Au), triggering 1,2-alkyl shift to
give the observed spiroether diastereomer after proto-demetala-
tion (Scheme 3). At this point, however, we could not rule out
a possibility that the 1,2-alkyl shift is initiated by the formation of
substrates 1i and 1j failed to provide the corresponding
a-
Table 4
Examination of silver catalysts in the absence of Au(L)Cl
Entry
AgX
Conva (%)
2ca (%)
1
2
3
4
5
6
AgBF4
73
11
32
29
19
43
60
8
24
17
14
43
€
AgOTs
AgNTf2
AgOTf
AgSbF6
AgClO4
oxocarbenium ion F (M¼H) due to a Bronsted acid.
3. Conclusions
a
The yields are based on the crude 1H NMR spectra (1,3,5-trimethoxybenzene as
In summary, we report herein a tandem hydration/ring expan-
an internal reference).
sion catalyzed by gold complexes that give a concise route toward a-

K.-D. Kim et al. / Tetrahedron 68 (2012) 5241e5247
5245
Table 6
dropwise n-BuLi (0.60 mL of 2.5 M soln in n-hexane). After 30 min
Synthesis of spirocyclic ethers via tandem alkoxylation/ring-expansion reaction
at ꢁ78 ꢀC, cyclobutanone (75.0
mL, 1.0 mmol) was added to the
mixture slowly. The reaction mixture was allowed to warm to room
temperature and was further stirred for 1 h. A similar procedure as
those for 1c was followed to give 1f (135.3 mg, 80%).
Compound 1k: To a solution of 3-butyn-1-ol (0.11 mL, 1.5 mmol)
in anhydrous diethyl ether at rt was added EtMgBr (2.0 mL of 2.0 M
solution in ether) dropwise. The mixture was stirred under reflux
for 1 h and was cooled to room temperature under Ar atmosphere.
Cyclobutanone (75.0 mL, 1.0 mmol) was then added dropwise and
the mixture was further stirred for 1 h at rt. A similar procedure as
Entry
1
Substrate
Condition
rt, 1.5 h
Product
Yielda (%)
65
those for 1c was followed to give 1k (113.1 mg, 81%).
4.2.1. 1-Ethynyl-3-phenylcyclobutanol (1a). 1H NMR (400 MHz,
CDCl3):
d 7.35e7.27 (m, 2H), 7.27e7.17 (m, 3H), 3.33 (m, 1H),
2
rt, 1 h
rt, 1 h
32b
45c
2.93e2.85 (m, 2H), 2.58 (s, 1H), 2.49 (br s, 1H, OH), 2.44e2.36 (m,
2H); 13C NMR (100 MHz, CDCl3):
71.8, 63.9, 45.9, 30.3.
d 143.8, 128.4, 126.7, 126.3, 87.4,
4.2.2. Ethyl 3-(1-hydroxy-3-phenylcyclobutyl)propiolate (1b). 1H
NMR (400 MHz, CDCl3): 7.35e7.26 (m, 2H), 7.26e7.18 (m, 3H), 4.25
3
d
(q, J¼7.0 Hz, 2H), 3.37 (m, 1H), 3.00e2.92 (m, 2H), 2.45e2.39 (m,
2H), 2.40 (br s,1H),1.35 (t, J¼7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3):
a
Isolated yield after chromatography.
A 1:1 diastereomeric mixture.
A single diastereomer; the relative stereochemistry was not determined.
b
c
d
153.7,143.4,128.6,126.7,126.5, 90.1, 75.6, 63.8, 62.4, 45.4, 30.3,14.1.
4.2.3. 1-Ethynyl-3,3-diphenylcyclobutanol (1c). 1H NMR (400 MHz,
hydroxycyclopentanone derivatives. With the current catalytic sys-
tem, it is possible to induce a regioselective hydration in preference
CDCl3):
d
7.37e7.10 (m, 10H), 3.43 (dd, J¼2.7, 10.2 Hz, 2H), 3.12 (dd,
J¼2.7, 10.1 Hz, 2H), 2.42 (s, 1H), 2.18 (s, 1H); 13C NMR (100 MHz,
to a direct ring expansion and the following gold-catalyzed
a-ketol
CDCl3):
d 149.8, 147.8, 128.5, 128.3, 126.5, 126.0, 125.9, 125.8, 86.8,
rearrangement provides convenient route for -oxygenated
a
a
73.0, 63.6, 50.8, 43.3.
cyclopentanone scaffolds from readily available starting materials.
4.2.4. Ethyl 3-(1-hydroxy-3,3-diphenylcyclobutyl)propiolate (1d). 1H
NMR (400 MHz, CDCl3): d 7.34e7.23 (m, 8H), 7.18e7.10 (m, 2H), 4.15
4. Experimental section
4.1. General
(q, J¼7.1 Hz, 2H), 3.45 (dd, J¼3.2, 13.3 Hz, 2H), 3.15 (dd, J¼2.8,
13.3 Hz, 2H), 2.36 (s, 1H), 1.25 (t, J¼7.0 Hz, 3H); 13C NMR (100 MHz,
CDCl3):
d 153.3, 149.0, 147.3, 128.5, 128.4, 126.4, 125.9, 125.8, 88.8,
All commercially available reagents were used without further
purification and solvents were purified according to Perin and
Armarego.10 Chromatographic purification of products was per-
formed with Kieselgel 60 (230e400 mesh) silica gel. 1H and 13C
NMR spectra were recorded on Varian Mercury-400 MHz spec-
trometer and are internally referenced to residual proton signals.
76.4, 63.3, 62.0, 50.0, 43.6, 13.9.
4.2.5. 3-(Benzyloxymethyl)-1-ethynylcyclobutanol (1e). The title
compound was prepared from 3-(benzyloxymethyl)cyclobutanone.
1H NMR (400 MHz, CDCl3):
d 7.38e7.26 (m, 5H), 4.55 (s, 2H), 3.49 (d,
J¼5.1 Hz, 2H), 2.88 (s, 1H), 2.68e2.61 (m, 2H), 2.52 (s, 1H),
2.16e2.08 (m, 2H); 13C NMR (100 MHz, CDCl3):
d 138.0, 128.4, 127.7,
87.3, 73.2, 73.1, 71.5, 64.7, 41.4, 26.3.
4.2. General procedure for the synthesis of substrates
4.2.6. Ethyl 3-(1-hydroxycyclobutyl)propiolate (1f).11 1H NMR
The preparation of 1c, 1f, and 1k is representative.
(400 MHz, CDCl3):
d
4.25 (q, J¼7.0 Hz, 2H), 2.57e2.47 (m, 2H),
Compound1c: To
a solution of 3,3-diphenylcyclobutanone
2.36e2.26 (m, 2H), 1.94e1.82 (m, 2H), 1.32 (t, J¼7.0 Hz, 3H); 13C
(340 mg, 1.5 mmol) in anhydrous tetrahydrofuran (8 mL) was
added dropwise a solution of ethynylmagnesium bromide (9.2 mL
of 0.5 M soln in THF) at 0 ꢀC. The mixture was allowed to warm to
room temperature and stirred further for 1 h. The reaction was
quenched with aqueous NH4Cl and the aqueous layer was extracted
with EtOAc. The combined organic extracts were dried over MgSO4,
concentrated, and the residue was purified by flash chromatogra-
phy (EtOAc/Hex¼1:4) to give 1c (353.2 mg, 93%).
NMR (100 MHz, CDCl3): d 153.8, 90.3, 75.2, 67.2, 62.1, 37.6,13.9,12.8.
4.2.7. 2-Ethynylspiro[3.5]nonan-2-ol (1g). 1H NMR (400 MHz,
CDCl3):
d
2.56 (s, 1H), 2.33 (d, J¼13.2 Hz, 2H), 2.10 (s, 1H), 2.13 (d,
J¼13.3 Hz, 2H), 1.66e1.46 (m, 4H), 1.46e1.28 (m, 6H); 13C NMR
(100 MHz, CDCl3): d88.8, 71.5, 63.1, 48.5, 39.8, 37.7, 31.3, 25.6, 22.9, 22.6.
4.2.8. Ethyl 3-(2-hydroxyspiro[3.5]nonan-2-yl)propiolate (1h). 1H
NMR (400 MHz, CDCl3):
4.24 (q, J¼7.1 Hz, 2H), 2.38 (d, J¼13.2 Hz,
Compound 1f: To a solution of ethyl propiolate (0.15 mmol,
1.5 mmol) in anhydrous ether (5 mL) cooled at ꢁ78 ꢀC was added
d
Scheme 3. A proposed course of alkoxylation/ring-expansion sequence.

5246
K.-D. Kim et al. / Tetrahedron 68 (2012) 5241e5247
2H), 2.25 (s,1H), 2.06 (d, J¼13.3 Hz, 2H),1.68e1.50 (m, 4H),1.44e1.30
calculated for [MþH]þ (C18H19O2) requires m/z 267.1385, found m/z
(m, 6H), 1.32 (t, J¼7.0 Hz, 3H); 13C (100 MHz, CDCl3):
d
153.7, 122.1,
267.1386.
90.7, 75.5, 63.0, 62.1, 48.0, 37.6, 38.0, 31.8, 25.6, 22.9, 22.6, 14.0.
4.3.4. Ethyl
2-(1-hydroxy-2-oxo-4,4-diphenylcyclopentyl)acetate
7.40e7.18 (m, 10H), 4.13 (q,
4.2.9. 1-(4-Hydroxybut-1-ynyl)cyclobutanol(1k). 1H NMR (400 MHz,
(2d). 1H NMR (400 MHz, CDCl3):
d
CDCl3):
J¼6.2 Hz, 2H), 2.44e2.36 (m, 2H), 2.29e2.20 (m, 2H), 1.86e1.75 (m,
2H); 13C (100 MHz, CDCl3):
85.7, 80.4, 67.8, 60.9, 38.6, 23.0, 12.8.
d
3.73 (q, J¼6.3 Hz, 2H), 3.20 (br s, 1H), 2.54 (br s, 1H), 2.51 (t,
J¼7.4 Hz, 2H), 3.35 (s, 1H), 3.33 (d of ABq, J¼18.0 Hz, 1H), 3.28 (d of
ABq, J¼18.0 Hz, 1H), 3.07 (d of ABq, J¼14.1 Hz, 1H), 3.02 (d of ABq,
J¼14.1 Hz, 1H), 2.42 (d of ABq, J¼16.0 Hz, 1H), 2.32 (d of ABq,
d
J¼16.0 Hz, 1H), 1.24 (t, J¼7.1 Hz, 3H); 13C (100 MHz, CDCl3):
d 215.8,
4.2.10. 1-(4-Hydroxy-4-(4-methoxyphenyl)but-1-ynyl)cyclobutanol
(1l). 1H NMR (400 MHz, CDCl3):
171.8, 147.5, 129.4, 129.3, 127.4, 127.3, 127.3, 127.2, 76.5, 61.7, 50.3,
49.3, 48.7, 41.8, 14.7; HRMS (FABþ) exact mass calculated for
[MþH]þ (C21H23O4) requires m/z 339.1596, found m/z 339.1595.
d
7.29 (d, J¼7.5 Hz, 2H), 6.87 (d,
J¼7.8 Hz, 2H), 4.80 (br s, 1H), 3.80 (s, 3H), 2.68e2.56 (m, 2H),
2.40e2.28 (m, 2H), 2.28e2.18 (m, 2H), 2.17 (s, 1H), 1.82e1.65 (m,
2H); 13C (100 MHz, CDCl3):
d
159.2, 134.9, 127.0, 113.7, 86.4, 80.1,
4.3.5. 4-(Benzyloxymethyl)-2-hydroxy-2-methylcyclopentanone
72.2, 67.7, 55.3, 38.5, 29.7, 12.8.
(2e). The title compound was obtained as a diastereomeric mixture
(dr¼10:1). 1H NMR (400 MHz, CDCl3):
d 7.36e7.25 (m, 5H), 4.54 (s,
4.2.11. 1-(4-Hydroxybut-1-ynyl)-3-phenylcyclobutanol
(1m).
2H), 3.54e3.44 (m, 2H), 3.07 (s, 1H), 2.55 (dd, J¼8.6, 19.1 Hz, 1H),
2.50e2.39 (m, 1H), 2.24e2.15 (m, 2H), 1.80 (dd, J¼9.4, 12.9 Hz, 1H);
Characterized as a mixture of diastereomers, dr¼1:0.22. 1H NMR
(400 MHz, CDCl3):
d
7.37e7.28 (m, 2H), 7.28e7.18 (m, 3H), 3.81e3.75
13C (100 MHz, CDCl3):
d 219.0, 137.8, 128.5, 128.4, 127.8, 127.7, 127.6,
(m, 2H, major), 3.75e3.65 (m, 2H, minor), 3.30 (m, 1H, major),
2.89e2.80 (m, 2H, major), 2.74e2.64 (m, 2H, minor), 2.64e2.58 (m,
2H, minor),2.56 (t, J¼6.2 Hz, 2H, major), 2.49 (t, J¼6.2 Hz, 2H, minor),
2.42e2.35 (m, 2H, major and minor), 2.00 (br s, 1H), 1.60 (br s, 1H).
77.1, 73.5, 73.4, 73.1, 72.8, 40.6, 40.4, 39.7, 38.4, 32.5, 31.4, 23.5, 23.0;
HRMS (FABþ) exact mass calculated for [MþH]þ (C14H19O3) requires
m/z 235.1334, found m/z 235.1334.
4.3.6. Ethyl 2-(1-hydroxy-2-oxocyclopentyl)acetate (2f). 1H NMR
(400 MHz, CDCl3):
d 4.25e4.13 (m, 2H), 3.80 (s, 1H), 2.58 (s, 2H),
4.3. General procedure for the tandem
hydration(alkoxylation)/ring expansion
2.50e2.40 (m, 1H), 2.35e2.24 (m,1H), 2.14e2.04 (m, 2H), 2.04e1.84
(m, 2H), 1.29 (t, J¼7.0 Hz, 3H); 13C (100 MHz, CDCl3):
d 172.2, 76.8,
61.8, 39.9, 36.5, 35.7, 18.4, 14.8; HRMS (FABþ) exact mass calculated
The preparation of 2d and 2k is representative.
for [MþH]þ (C9H15O4) requires m/z 187.0970, found m/z 187.0968.
Compound 2d: To
a solution of Au(JohnPhos)Cl (2.6 mg,
0.0050 mmol) and AgSbF6 (1.7 mg, 0.0050 mmol) in 1,4-dioxane
(w1 mL) was added 1-alkynylcyclobutanol 1d (16.8 mg,
0.10 mmol) and one drop of water (w25 mg, from a tip of Pasteur
pipette). The reaction mixture was heated to 80 ꢀC while stirring for
2 h. The solvent was removed and the residue was purified by flash
chromatography (EtOAc/Hex¼1:4) to give 2d (33.1 mg, 98%).
4.3.7. 3-Hydroxy-3-methylspiro[4.5]decan-2-one (2g). 1H NMR
(400 MHz, CDCl3):
d
2.42e2.25 (m, 2H), 2.05 (d, J¼14.1 Hz, 1H), 1.84
(d, J¼14.5 Hz, 1H), 1.58e1.36 (m, 10H), 1.31 (s, 3H); 13C (100 MHz,
CDCl3):
d 219.9, 76.2, 49.2, 48.6, 39.3, 38.1, 36.2, 26.4, 25.6, 23.0,
22.6; HRMS (FABþ) exact mass calculated for [MþNa]þ
(C11H18NaO2) requires m/z 205.1204, found m/z 205.1203.
Compound 2k: To
a solution of Au(JohnPhos)Cl (2.6 mg,
0.0050 mmol) and AgSbF6 (1.7 mg, 0.0050 mmol) in 1,4-dioxane
(w1 mL) was added 1-alkynylcyclobutanol 1k (14.0 mg,
0.10 mmol). The reaction mixture was stirred at rt for 1 h. The
solvent was removed and the residue was purified by flash chro-
matography (EtOAc/Hex¼1:2) to give 2k (9.1 mg, 65%).
4.3.8. Ethyl 2-(2-hydroxy-3-oxospiro[4.5]decan-2-yl)acetate (2h).
1H NMR (400 MHz, CDCl3):
d
4.18 (dq, J¼2.3, 7.0 Hz, 2H), 3.65 (s,1H),
2.60 (d of ABq, J¼16.0 Hz, 1H), 2.56 (d of ABq, J¼16.0 Hz, 1H), 2.25
(d, J¼18.0 Hz, 1H), 2.11 (d, J¼14.5 Hz, 1H), 1.80 (d, J¼14.4 Hz, 1H),
1.68e1.34 (m, 10H), 1.28 (t, J¼7.1 Hz, 3H); 13C (100 MHz, CDCl3):
d
216.9, 171.7, 76.5, 61.1, 41.5, 39.8, 38.0, 36.8, 25.8, 23.3, 22.7, 14.2;
4.3.1. 2-Hydroxy-2-methyl-4-phenylcyclopentanone (2a). 1H NMR
(400 MHz, CDCl3): d 7.38e7.23 (m, 5H), 3.39e3.28 (m,1H), 2.88 (ddd,
HRMS (FABþ) exact mass calculated for [MþH]þ (C14H23O4) re-
quires m/z 255.1596, found m/z 255.1595.
J¼2.3, 8.6,19.9 Hz,1H), 2.62 (s, 1H), 2.47 (ddd, J¼1.9, 5.8,12.5 Hz,1H),
2.43 (dd, J¼10.9, 19.5 Hz, 1H), 2.14 (t, J¼12.5 Hz, 1H), 1.39 (s, 3H); 13C
4.3.9. 1-Oxaspiro[4.4]nonan-6-one (2k). 1H NMR (400 MHz, CDCl3):
(100 MHz, CDCl3):
d
218.89, 142.55, 128.79, 126.94, 126.81, 78.42,
d
3.95 (t, J¼7.0 Hz, 2H), 2.38e2.16 (m, 2H), 2.14e1.86 (m, 6H),
44.84, 42.52, 36.47, 23.82; HRMS (FABþ) exact mass calculated for
1.85e1.69 (m, 2H); 13C (100 MHz, CDCl3):
d 218.7, 86.5, 69.0, 67.1,
[MþH]þ (C12H15O2) requires m/z 191.1072, found m/z 191.1073.
35.8, 35.2, 32.4, 25.7, 18.1; HRMS (FABþ) exact mass calculated for
[MþH]þ (C8H13O2) requires m/z 141.0916, found m/z 141.0915.
4.3.2. Ethyl 2-(1-hydroxy-2-oxo-4-phenylcyclopentyl)acetate (2b).
1H NMR (400 MHz, CDCl3):
d
7.39e7.24 (m, 5H), 4.21 (q, J¼7.0 Hz,
4.3.10. 2-(4-Methoxyphenyl)-1-oxaspiro[4.4]nonan-6-one (2l). The
2H), 3.38e3.28 (m, 1H), 2.86 (ddd, J¼2.0, 8.2, 19.2 Hz, 1H), 2.67 (s,
2H), 2.64 (ddd, J¼2.0, 6.7, 13.3 Hz, 1H), 2.54 (dd, J¼11.3, 19.5 Hz, 1H),
2.20 (t, J¼12.5 Hz, 1H), 1.30 (t, J¼7.4 Hz, 3H); 13C (100 MHz, CDCl3):
title compound was obtained as a 1:1 diastereomeric mixture. 1H
NMR (400 MHz, CDCl3):
d
7.43 (d, J¼8.6 Hz, 2H), 7.26 (d, J¼8.6 Hz,
2H), 6.87 (m, 4H), 5.08 (dd, J¼6.2, 7.8 Hz, 1H), 4.98 (dd, J¼5.5, 9.4 Hz,
1H), 3.79 (s, 6H), 2.45e2.14 (m, 12H), 2.14e1.95 (m, 4H), 1.95e1.76
d
215.68, 170.60, 142.39, 128.82, 127.00, 126.83, 78.12, 61.32, 43.61,
43.16, 40.04, 36.22, 14.12; HRMS (FABþ) exact mass calculated for
(m, 4H); 13C (100 MHz, CDCl3):
d 218.2, 159.2, 159.1, 133.9, 128.0,
[MþH]þ (C15H19O4) requires m/z 263.1283, found m/z 263.1283.
127.3, 113.8, 113.7, 87.1, 86.8, 82.6, 81.6, 55.3, 36.5, 36.4, 35.4, 35.3,
35.2, 34.8, 34.4, 32.5, 18.2, 17.9; HRMS (FABþ) exact mass calculated
for [MþH]þ (C15H19O3) requires m/z 247.1334, found m/z 247.1336.
4.3.3. 2-Hydroxy-2-methyl-4,4-diphenylcyclopentanone
NMR (400 MHz, CDCl3):
(2c). 1H
d
7.32e7.15 (m, 10H), 3.32 (d, J¼17.6 Hz,
1H), 3.14 (d, J¼18.0 Hz, 1H), 3.04 (d, J¼13.7 Hz, 1H), 2.86 (d,
4.3.11. 8-Phenyl-1-oxaspiro[4.4]nonan-6-one
(2m). 1H
NMR
J¼13.5 Hz, 1H), 2.11 (s, 1H), 1.08 (s, 3H); 13C (100 MHz, CDCl3):
(400 MHz, CDCl3): 4.15e4.09 (m, 1H), 4.04e3.98 (m, 1H),
d
d
217.63, 147.20, 146.73, 128.70, 128.65, 126.63, 126.61, 126.59,
3.29e3.19 (m, 1H), 2.77 (ddd, J¼2.0, 7.4 Hz, 18.7 Hz, 1H), 2.40 (dd,
J¼12.1, 19.1 Hz, 1H), 2.35 (ddd, J¼2.5, 5.8, 12.9 Hz, 1H), 2.23 (t,
126.51, 75.85, 49.81, 49.33, 47.83, 25.35; HRMS (FABþ) exact mass

K.-D. Kim et al. / Tetrahedron 68 (2012) 5241e5247
5247
J¼12.5 Hz, 1H), 2.18e1.96 (m, 3H), 1.96e1.86 (m, 1H); 13C (100 MHz,
2. Some notable organocatalytic approaches, see: (a) Zhang, Q. W.; Fan, C. A.;
Zhang, H. J.; Tu, Y. Q.; Zhao, Y. M.; Gu, P.; Chen, Z. M. Angew. Chem., Int. Ed. 2009,
48, 8572; (b) Zhang, E.; Fan, C.-A.; Tu, Y.-Q.; Zhang, F.-M.; Song, Y.-L. J. Am. Chem.
Soc. 2009, 131, 14626.
3. (Pd): (a) Trost, B. M.; Xie, J.; Maulide, N. J. Am. Chem. Soc. 2008, 130, 17258; (Fe):
(b) Chen, A.; Lin, R.; Liu, Q.; Jiiao, N. Chem. Commun. 2009, 6842; (Ru): (c)
Yoshida, M.; Sugimoto, M.; Ihara, M. Tetrahedron Lett. 2011, 42, 3877; (d) Su-
gimoto, K.; Yoshida, M.; Ihara, M. Synlett 2006, 1923; (Co): (e) Iwasawa, N.;
Matsuo, T.; Iwanoto, M.; Ikeno, T. J. Am. Chem. Soc. 1998, 120, 3930.
CDCl3): d 218.3, 142.5, 128.8, 126.9, 126.7, 88.3, 69.7, 43.7, 43.5, 36.8,
34.8, 25.7; HRMS (FABþ) exact mass calculated for [MþH]þ
(C14H17O2) requires m/z 217.1229, found m/z 217.1229.
Acknowledgements
4. For recent examples of Au-catalyzed small ring expansions: (a) Garayalde, D.;
Nevado, C. Beilstein J. Org. Chem. 2011, 7, 767; (b) Markham, J. P.; Staben, S. T.; Toste,
F. D. J. Am. Chem. Soc. 2005,127, 9708; (c) Kleinbeck, F.; Toste, F. D. J. Am. Chem. Soc.
2009,131, 9178; (d) Li, C.-W.; Pati, K.; Lin, G.-Y.; Sohel, S. M. A.; Hung, H.-H.; Liu, R.-
S. Angew. Chem., Int. Ed. 2010, 49, 9891; (e) Ye, S.; Yu, Z.-X. Org. Lett. 2010, 12, 804;
(f) Yeom, H.-S.; Yoon, S.-J.; Shin, S. Tetrahedron Lett. 2007, 48, 4817; Fora review on
1,2-alkyl migration: (g) Crone, B.; Kirsch, S. F. Chem.dEur. J. 2008, 14, 3514.
5. (a) Fukuda, Y.; Utimoto, K. J. Org. Chem. 1991, 56, 3729; (b) Teles, J. H.; Brode, S.;
Chabanas, M. Angew. Chem., Int. Ed. 1998, 37, 1415; (c) Lein, M.; Rudolph, M.;
Hashmi, A. S. K. Organometallics 2010, 29, 2206; (d) Krauter, C. M.; Hashmi, A. S.
K.; Pernpointner, M. ChemCatChem 2010, 2, 1226; For a recent review: (e)
The current work was supported by the National Research
Foundation of Korea (NRF-2009-0080741 and NRF-2011-0023686).
K.-D.K, H.-S.Y., S.S. thank the BK21 program for a fellowship and H.-
S.Y. also thanks the Seoul Science Foundation for a fellowship.
HRMS analysis was conducted at Korea Basic Science Institute at
Korea University.
Supplementary data
ꢀ
Corma, A.; Leyva-Perez, A.; Sabater, M. J. Chem. Rev. 2011, 111, 1657.
6. Duschek, A.; Kirsch, S. F. Angew. Chem., Int. Ed. 2011, 50, 1524.
7. (a) Lee, S. I.; Baek, J. Y.; Sim, S. H.; Chung, Y. K. Synthesis 2007, 2107; For a review
of Au-catalyzed MeyereSchuster rearrangement: (b) Engel, D. A.; Dudley, G. B.
Org. Biomol. Chem. 2009, 7, 4149.
Copies of 1H and 13C NMR spectra for products. Supplementary
data associated with this article can be found in the online version,
at doi:10.1016/j.tet.2012.03.018.
8. Ringer, A. L.; Magers, D. H. J. Org. Chem. 2007, 72, 2533.
9. The obtained 2k had identical spectral properties to those in the literature. (a)
Paquette, L. A.; Owen, D. R.; Bibart, R. T.; Seekamp, C. K.; Kahane, A. L.; Lanter, J.
C.; Corral, M. A. J. Org. Chem. 2001, 66, 2828; (b) Paquette, L. A.; Kinney, M. J.;
Dullweber, U. J. Org. Chem. 1997, 62, 1713.
References and notes
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Butterworth-Heinemann: Oxford, 1996.
11. Trost, B. M.; Gunzner, J. L.; Yasukata, T. Tetrahedron Lett. 2001, 42, 3775.
1. For recent reviews: (a) Seiser, T.; Saget, T.; Tran, D. N.; Cramer, N. Angew. Chem.,
Int. Ed. 2011, 50, 7740; (b) Leemans, E.; D’hooghe, M.; De Kimpe, N. Chem. Rev.
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