Chemistry of allenic/propargylic anions generated by base treatment of sulfonylallenes: synthesis of 1-alkynyl-1-sulfonylcycloalkanes and cycloalkanols

Article abstract of DOI:10.1016/j.tet.2010.03.071

The intramolecular trapping of allenyl/propargyl anions, generated from sulfonylallenes with the proper base, by a haloalkyl group or an aldehyde functionality was investigated. The treatment of 1-(ω-iodoalkyl)-1-(phenylsulfonyl)allenes with TBAF or NaH i

Full text of DOI:10.1016/j.tet.2010.03.071

Tetrahedron 66 (2010) 3687–3694
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Chemistry of allenic/propargylic anions generated by base treatment of
sulfonylallenes: synthesis of 1-alkynyl-1-sulfonylcycloalkanes and cycloalkanols
*
Shinji Kitagaki, Satoshi Teramoto, Yuu Ohta, Harumi Kobayashi, Mika Takabe, Chisato Mukai
Division of Pharmaceutical Sciences, Graduate School of Natural Science and Technology, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 2 March 2010
Received in revised form 17 March 2010
Accepted 19 March 2010
Available online 27 March 2010
The intramolecular trapping of allenyl/propargyl anions, generated from sulfonylallenes with the proper
base, by a haloalkyl group or an aldehyde functionality was investigated. The treatment of 1-(u-iodoalkyl)-
1-(phenylsulfonyl)allenes with TBAF or NaH in DMF efficiently produced the 1-alkynyl-1-(phenylsulfonyl)-
substituted three- to seven-membered carbocycles. The allenyl/propargyl anions could also be
intramolecularly trapped using a terminal aldehyde to stereoselectively afford the 2-alkynyl-2-(phenyl-
sulfonyl)-substituted five- and six-membered cycloalkanols. The latter reaction could be performed using
a catalytic amount of TBAF or DBU.
Keywords:
Allenyl anion
Propargyl anion
Ring-closing reaction
Cycloalkane
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
( )
EWG
R'
EWG
R'
( )
( )
EWG
R'
n
n
base
n
Activated allenes with an electron-withdrawing group (EWG),
like the sulfonyl, sulfinyl, phosphono, phosphoryl, or alkoxy-
carbonyl group, have significantly higher electrophilicities com-
pared to the corresponding alkenes. As a result, the base-promoted
endo-mode ring-closing reaction of the 1-alkyl-1-EWG-allenes 1
having a nucleophilic moiety at the alkyl chain terminus smoothly
proceeds to produce five- to medium-sized heterocycles or carbo-
cycles 3 (Scheme 1).1–3 On the other hand, allenes with the EWG
would also be anticipated to easily produce allenic/propargylic
anions upon exposure to a weak base due to the high acidity of the
proton at the C-3 position of the 1-EWG-substituted allene spe-
cies4–7 in contrast to the non-activated allenes, the anion formation
of which requires a strong base exemplified by the butyl lithium.8
We have now investigated the generation of the allenyl/propargyl
anion species 5 from the 1,1-disubstituted and 1,1,3-trisubstituted
allenes 4 having an EWG at the C-1 position and their intra-
molecular trapping by the proper electrophilic functionality, such
as an alkyl halide or aldehyde, resulting in the formation of the
1-alkynyl-1-EWG-substituted carbocycles 6.9 The phenylsulfonyl
group-substituted allene was mainly selected as the substrate be-
cause of its intrinsic strong electron-withdrawing ability as well as
its ease for the preparation and further elaboration to various
functional groups.10
XH
•
X–
•
X
R
R
2
R
1
3
n = 1~4; R, R' = H, alkyl
EWG = SO2Ph, SOPh, PO(OEt)2, POPh2, CO2Bn
XH = alcohol, amide, active methine
( )
EWG
R
R
– EWG
( )
EWG
base
( )
n
n
n
EWG
( )
X
·
X
X
·
–
H
R
n
Y
R
4
5
6
R = H or alkyl
Y = H or OH
X = H, leaving group
or X = O
Scheme 1. Base-promoted ring-closing reactions of 1-alkyl-1-EWG-allenes.
2. Results and discussion
2.1. Intramolecular trapping by alkyl halides
At the departure of this investigation, we synthesized the
* Corresponding author. Tel.: þ81 76 234 4411; fax: þ81 76 234 4410; e-mail
address: cmukai@kenroku.kanazawa-u.ac.jp (C. Mukai).
1-(u-haloalkyl)-1-(phenylsulfonyl)allenes
9
with or without
0040-4020/$ – see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.03.071

3688
S. Kitagaki et al. / Tetrahedron 66 (2010) 3687–3694
a substituent (Me or Ph) at the allenic terminus for the allenyl/
propargyl anion generation and its intramolecular trapping leading
to the formation of carbocycles. The tosylate 8 was prepared from the
hydroxyallenes 71a under the conventional conditions (Scheme 2).
The conversion of the 1,1-disubstituted allenes 8H into 9H occurred
without contamination of 90H. However, iodination of the tosylates
8Me and 8Ph having a substituent at the allenic terminus was partly
accompanied by isomerization of the allene moiety to acetylene (10–
20%). We first screened various bases using the tosylate 8aH (n¼1,
R¼H in Scheme 2). No reaction occurred when 8aH was treated with
triethylamine. The three-membered ring product 10aH was obtained
in 71% yield upon exposure to two equivalents of K2CO3 in THF, al-
though a fairly prolonged reaction time was needed (46 h, 17% re-
covery of starting material). Treatment with NaH or TBAF at 0 ꢀC
resulted in the full consumption of the starting material and the
production of 10aH in excellent yield (Eq. 1). Four- and larger-
membered ring constructions were performed using a 0.1 M DMF
solution of iodide 9b–eH (Eq. 2). NaH or TBAF in DMF at 0 ꢀC was
effective for the conversion of 9b–eH into the four- to seven-
membered ring products 10b–eH,y although a diluted condition
(0.01 M) was required for the seven-membered ring formation. The
eight-membered carbocycles were not obtained under any
conditions.
PhO2S
PhO2S
10bH
10cH
NaH: 88%
NaH: quant
TBAF: 90%
SO2Ph
H
( )
base
n
TBAF: 87%
(2 equiv)
(2)
I
·
DMF (0.1 M)
0 °C, 0.5 h
PhO2S
PhO2S
H
9b-eH
b: n = 2
c: n = 3
d: n = 4
e: n = 5
10dH
10eH
NaH: 92%
NaH: 85%
TBAF: 91%
(0.01 M soln)
The effect of the C-3 substituents on the 1-alkyl-1-sulfonylallene
was studied. Upon exposure to the standard conditions (2 equiv of
NaH or TBAF in DMF at 0 ꢀC), a mixture of 9cMe and 90cMe (4:1)
having a methyl group at the allenic terminus produced the
cyclopentane 10cMe in high yield, which was comparable to that of
10cH (Table 1, entries 1 and 3). Decreasing the amount of NaH to
1 equiv obviously delayed the completion of the reaction (entry 2).
The phenyl-substituted allene 9cPh and its one- or two-carbon
homologated iodoallenes (9d or 9e) also gave excellent results as
shown in Table 1.
( )
SO2Ph
R
( )
SO2Ph
R
n
n
TsCl, Et3N
NaI, acetone
reflux
OH
·
OTs
H
·
CH2Cl2
0 °C → rt
Table 1
H
Reaction of 1-(
Ph) at the allenic terminus
u-haloalkyl)-1-(phenylsulfonyl)allenes 9 with a substituent (Me or
67 ~ 84% (2 steps)
7
8
a: n = 1, b: n = 2, c: n = 3
d: n = 4, e: n = 5
R
( )
( )
n
SO2Ph
SO2Ph
( )
( )
n
SO2Ph
SO2Ph
n
n
R = H, Me, Ph
base (2 equiv)
PhO2S
I
+
I
·
I
+
I
·
DMF (0.1 M)
0 °C
H
R
H
R
( )
R
9'c-eMe,Ph
n-2
R
9
9'
9c-eMe,Ph
10c-eMe,Ph
Scheme 2. Preparation of iodoallenes 9.
Entry
Substrate
Base
Time (h)
Yield (%)
n
R
9:90
1
9cMe
9cMe
9cMe
9cPh
9cPh
3
3
3
3
3
Me
Me
Me
Ph
4:1
4:1
4:1
8:1
8:1
NaH
1
24
0.5
0.25
0.25
quant
quant
87
79
91
2
3
4
5
NaHa
TBAF
NaH
SO2Ph
H
Ph
TBAF
NaH or TBAF (2 equiv)
THF (0.1 M), 0 °C, 0.5 h
PhO2S
6
7
9dMe
9dPh
4
4
Me
Ph
4:1
8:1
NaH
NaH
1
0.5
93
87
OTs
H
·
(1)
8b
9b
9eMe
9ePh
5
5
Me
Ph
10:1
9:1
NaH
TBAF
0.5
0.5
90
93
10aH
NaH: 94%
TBAF: 97%
8aH
a
One equiv of base was used.
Reaction was performed in 0.01 M solution.
b
The phenylsulfonyl group served as a favorable functionality.
Thus, some other substituents at the allenic position were exam-
ined to see if they met our requirements. While the behavior of the
benzoylallene 11a was in good accordance with those of the sul-
fonylallene 9cH, the methoxycarbonylallene 11b was found to
provide a rather low yield of the cyclopentane derivative 12b pre-
sumably due to the insufficient electron-withdrawing ability (Eq.
3). The elimination of hydrogen iodide mainly occurred when the
benzylallene 11c was treated with NaH. The use of TBAF instead of
NaH resulted in the formation of the olefin 13 and fluorinated
allene 14 (Eq. 4). In either event, no ring-closing product was
obtained from 11c at all. These results strongly suggest that the
y
Treatment of the tosyloxyallene 8dH with NaH in THF afforded the desired
product 10dH in low yield (21%). After extensive examination on six-membered
ring formation, we found that changing the leaving group from the tosyloxy
group to iodo group and the reaction solvent from THF to DMF brought about
a drastic improvement. Therefore, the four- to seven-membered ring formations
were performed using the iodoallenes 9 as the substrates and DMF as the solvent.
We have not tried any reactions using the iodoallene 9aH because the readily
available 8aH gave the satisfactory result.

S. Kitagaki et al. / Tetrahedron 66 (2010) 3687–3694
3689
electron-withdrawing ability of the substituent at the allenic
position must govern the reaction process, in particular, generation
of the allenyl/propargyl anion.
of products [Table 2, entry 3 (cis-16dH/trans-16dH¼37:63)] was
exposed to TBAF in DMF at 0 ꢀC that produced a mixture of cis-16dH
and trans-16dH in the ratio of 84:16, which is similar to the product
ratio observed in entry 5 (Eq. 6). Less polar solvents (THF, CH2Cl2,
toluene) provided rather low selectivities (entries 6–8). Un-
expectedly, the use of t-BuOK as the base in THF at ꢁ78 ꢀC pre-
dominantly afforded the cis-16dH (entry 9).z Treatment with other
bases, K2CO3 orDBU, for30 minprovided a modestselectivity(entries
10 and 11).
R
base
R
3
(3)
(4)
DMF, 0 °C, 0.5 h
I
•
11a: R = COPh
11b: R = COOMe
12a: 93% (TBAF); 97% (NaH)
12b: 47% (TBAF); trace (NaH)
( )
( )
n
SO2Ph
SO2Ph
Dess-Martin periodinane
CH2Cl2, 0 °C
n
OH
·
O
·
(5)
or IBX, EtOAc, 80 °C
H
R
H
R
3
base
DMF
2
Ph
3
Ph
Ph
+
7
15
a: n = 1, b: n = 2, c: n = 3, d: n = 4
F
•
•
I
•
R = H, Me
86% ~ quant
11c
13
14
conditions
38%
43%
NaH, 0 °C → 50 °C
TBAF, 0 °C → rt
PhO2S
+
PhO2S
TBAF (2 equiv)
45%
OH
OH
(6)
16dH
DMF, 0 °C
0.5 h
(cis:trans = 84:16)
(37:63)
trans-16dH
quant
cis-16dH
2.2. Intramolecular trapping by aldehydes
Our next efforts focused on the application of the aforementioned
method to the construction of cycloalkanol derivatives starting from
the sulfonylallenes having an aldehyde moiety as an electrophilic
counterpart. The aldehyde 15dH, prepared from 7dH by oxidation
with Dess–Martin periodinane or IBX (o-iodoxybenzoic acid) (Eq. 5),
was exposed to NaH (2 equiv) in DMF at 0 ꢀC expecting the pro-
duction of the cyclohexanol derivative 16dH. However, no ring-
closing product could be detected in the reaction mixture. Similar
conditions at a lower temperature (ꢁ78 ꢀC) for 30 min led to the
favorable result, which involved an 81% yield of 16dH in a 56:44 ratio
of cis and trans isomers (Table 2, entries 1 and 2). The reaction carried
out in the range of ꢁ60 to 0 ꢀC in the presence of TBAF produced the
16dH in good to high yields. The higher reaction temperature, the
better the yield and the higher cis selectivity were achieved (entries
3–5). Interestingly, the lower temperature (ꢁ60 ꢀC) gave rise to
a reverse stereoselectivity (entry 3). This temperature dependent
stereoselectivity with TBAF in DMF indicates that cis-16dH must be
the thermodynamic product under this condition. In fact, the mixture
The stereochemical assignments were based on a 1H NMR eval-
uation, which involves the analysis of the coupling constants be-
tween H-6 and H-1 of the cyclohexane ring of 16dH as described in
Scheme 3. Furthermore, an NOE experiment with 2-vinylcyclohexyl
acetate possessing a trans-relationship between the ethynyl group
and hydroxy functionality (trans-17), derived from the trans-16dH
by acetylation and Lindlar reduction, recorded an enhancement
between the vinyl protons and H-1 of the cyclohexane ring, while no
enhancement could be detected when these protons of the corre-
sponding vinyl derivative cis-17 were irradiated.
J = 11 Hz
NOE
H
0%
H
1) Ac2O, DMAP
pyridine
SO2Ph
OAc
SO2Ph
OH
dd
H
2) Lindlar catalyst
MeOH, H2
Table 2
H
H
Reaction of allenyl aldehyde 15dH with various bases
cis-17
J = 3.2 Hz
cis-16dH
( )
SO2Ph
4
base (2 equiv)
PhO2S
PhO2S
O
·
+
H
OH
OH
NOE
3.5%
solvent (0.1 M)
0.5 h
1) Ac2O, DMAP
pyridine
H
H
H
H
H
15dH
cis-16dH
trans-16dH
SO2Ph
SO2Ph
H
H
2) Lindlar catalyst
MeOH, H2
Temp (ꢀC)
% Yield (cis:trans)a
H
brs
Entry
Base
Solvent
NOE
3%
OH
trans-16dH
OAc
trans-17
1
2
3
4
5
6
7
8
NaH
NaH
DMF
DMF
DMF
DMF
DMF
THF
CH2Cl2
Toluene
THF
0
ꢁ78
ꢁ60
ꢁ40
0
0
0
0
d
81 (56:44)
73 (37:63)
85 (84:16)
92 (84:16)
90 (80:20)
90 (74:26)
92 (67:33)
80 (86:14)
85 (73:27)
85 (67:33)
TBAF
TBAF
TBAF
TBAF
TBAF
TBAF
t-BuOK
K2CO3
DBU
Scheme 3. Stereochemical assignments of 16dH.
Our interest then turned to the catalytic version of this reaction
using allenyl aldehydes with or without a substituent at the allenic
terminus. A catalytic amount of TBAF (0.1 equiv) was found to be
9
10
11
ꢁ78
DMF
DMF
0
0
a
The ratio was determined by 1H NMR analysis of the crude product.
z
Reaction of 15dH with t-BuOK at 0 ꢀC gave a complex mixture of products.

3690
S. Kitagaki et al. / Tetrahedron 66 (2010) 3687–3694
effective for the conversion of 15dH into 16dH at 0 ꢀC for 30 min in
both its yield and selectivity comparable to those for 2 equiv of
TBAF (Table 3, entry 1 vs 2). The reaction at room temperature
afforded a similar result (entry 3). In the case of the methyl-
substituted allene 15dMe, however, 0.1 equiv of TBAF at 0 ꢀC for
a prolonged reaction time (5 h) nonselectively afforded the cyclized
products as a mixture of two diastereoisomers in the ratio of 48:52
(entry 6). A stereoselectivity similar to that of the stoichiometric
reaction (TBAF, 1 equiv, 0 ꢀC, 0.5 h) was observed when treated at
room temperature for one day (entry 8 vs entry 4). The stereo-
chemistry of 16dMe was assigned by analogy to 16dH based on the
1H NMR analysis.
Table 4
TBAF-catalyzed reaction of 15c
R
+
R
( )
SO2Ph
base
SO2Ph
R
CHO
18cH,Me
3
PhO2S
PhO2S
+
OH
O
·
OH
DMF
H
15cH,Me
R
(0.1 M)
cis-16cH,Me trans-16cH,Me
Entry
R
Base (equiv)
Temp
Time (h)
% Yield (cis:trans)a
16c
18c
1
2
3
4
H
H
H
H
TBAF (0.1)
TBAF (0.2)
DBU (0.5)
DBU (0.5)
rt
1
8
1
d
d
d
d
d
ꢁ40 ꢀ
C
74 (97:3)
75 (85:15)
73 (96:4)
ꢁ40 ꢀC
ꢁ40 ꢀC
Table 3
24
TBAF-catalyzed reaction of 15d
5
6
7
Me
Me
Me
TBAF (0.1)
DBU (0.1)
DBU (0.1)
rt
rt
rt
0.5
0.5
5
67 (94:6)
80 (90:10)
72 (94:6)
4
1
1
R
R
( )
SO2Ph
4
TBAF
PhO2S
PhO2S
a
The ratio was determined by 1H NMR analysis of the crude product.
O
·
+
OH
OH
DMF
H
R
(0.1 M)
The stereochemical relationship between the alkynyl group and
hydroxy functionality of the major isomers of 16c was determined
to be cis as described in Scheme 4 based on the following facts. (1)
The major isomer of 16cH could successfully be transformed into
1-oxabicyclo[3.3.0]octane 20. (2) The 1H NMR spectrum of
a diastereomeric mixture of 16cMe was very similar to that of 16cH,
except for the peak due to the acetylenic terminus.
cis-16dH,Me
trans-16dH,Me
% Yield (cis:trans)
15dH,Me
Entry
R
TBAF (equiv)
Temp
Time (h)
1
2
3
H
H
H
2
0.1
0.1
0 ꢀ
0 ꢀ
rt
C
C
0.5
0.5
0.5
92 (84:16)a
88 (84:16)a
84 (84:16)a
4
5
6
7
8
Me
Me
Me
Me
Me
1
0 ꢀ
0 ꢀ
0 ꢀ
rt
C
C
C
0.5
0.5
5
5
24
79 (82:18)b
71 (45:55)b
69 (48:52)b
73 (78:22)b
74 (84:16)b
0.1
0.1
0.1
0.1
1) Ac2O, DMAP, pyridine
PhO2S
PhO2S
OH
OAc
2) Lindlar cat., MeOH, H2
85% (2 steps)
rt
The ratio was determined by 1H NMR analysis of the crude product.
The ratio was calculated from isolated yields of both isomers.
a
b
19
cis-16cH
The one-carbon shorter aldehyde 15c was found to show a dif-
1) BH3·SMe2, THF, 0 °C → rt
ferent behavior from 15d. Upon exposure to a catalytic amount of
TBAF at room temperature, 15cH produced an intractable mixture
from which the expected cyclopentanol 16cH was not detected
(Table 4, entry 1). Lowering the reaction temperature to ꢁ40 ꢀC
resulted in the production of 16cH in good yield with a high cis
selectivity (entry 2). Raising the temperature from ꢁ40 ꢀC to
ꢁ20 ꢀC caused the partial transformation of 16cH into cyclo-
pentenecarbaldehyde 18cH (by 1H NMR analysis of the crude
product) (Eq. 7). The formation of the aldehyde 18cH from 16cH
might be rationalized by the addition of an aldehyde enolate,
generated from 16cH, to the allene in an endo-mode ring-closing
manner. A good yield of 16cH was also recorded for the reaction
with DBU (0.5 equiv) in DMF at ꢁ40 ꢀC, although a prolonged re-
action time was required to attain a high selectivity (entry 4). In-
terestingly, in the case of the methyl-substituted allene 15cMe, the
use of TBAF (0.1 equiv) at room temperature highly stereo-
selectively afforded 16cMe in 67% yield in a 94:6 ratio of the cis and
trans isomer, along with 18cMe in 4% yield (entry 5).x The higher
product yield was obtained using DBU as the base (entries 6 and 7).
PhO2S
then, H2O2, NaOH, 36%
O
H
2) MsCl, Et3N, CH2Cl2, 58%
20
Scheme 4. Stereochemical consideration of cyclopentanol 16c.
The smaller ring formation via the allenyl/propargyl anion was
next examined. The treatment of 15bH and 15aH with a base at
ꢁ40 ꢀC or room temperature produced neither the corresponding
cycloalkanol 16bH nor 16aH, and the pyran 21 and furan 22 were
obtained as the only isolable products, respectively (Scheme 5).
SO2Ph
SO2Ph
SO2Ph
base (0.1 equiv)
DMF
·
O
O
O
OH
16bH
15bH
21
4%
23%
TBAF, –40 °C, 16 h
DBU, rt, 30 min
not detected
not detected
TBAF
16cH
15cH
16cH + 18cH
(7)
DMF
–20 °C
(1:2)
–40 °C
SO2Ph
SO2Ph
base (0.1 equiv)
DMF
PhO2S
·
O
OH
15aH
22
16aH
x
3%
While the reasonable yield (62%, cis only) of 16cH was obtained in the reaction
of 15cH with 2 equiv of TBAF at ꢁ40 ꢀC for 0.5 h, the reactions of 15cMe with TBAF
at that temperature afforded the desired product 16cMe in low yields (TBAF
2 equiv, 0.5 h: 24%; TBAF 0.5 equiv, 1 h: 35%) with high cis selectivities (>97:3).
TBAF, –40 °C, 16 h
TBAF, 0 °C, 40 min
not detected
not detected
19%
Scheme 5. Reaction of allenyl aldehydes 15bH and 15aH with TBAF or DBU.

S. Kitagaki et al. / Tetrahedron 66 (2010) 3687–3694
3691
R
R
PhO2S
O–
PhO2S
PhO2S
H+
H+
O–
cis-16
( )
SO2Ph
R
( )
SO2Ph
–
m
m
cis-C (m = 2)
cis-B (m = 3)
·
·
exo-trig
O
O
R
R
–
trans-16
R
A
PhO2S
O–
O–
Hb
O
SO2Ph
R
( )
m
trans-C (m = 2)
trans-B (m = 3)
SO2Ph
–
( )
SO2Ph
R
m
H+
Ha
·
18
–O
15
enolexo-
endo-dig
OHC
R
+ base
D
E (m = 2)
SO2Ph
–
SO2Ph
SO2Ph
R
( )
( )
SO2Ph
–
H+
endo-dig
–
m
m
21, 22
·
·
O–
O
O
O
R
Ha
R
R
G (m = 1)
H (m = 0)
F
‡
‡
R
R
δ–
δ–
trans-B (m = 3)
cis-B (m = 3)
SO2Ph
SO2Ph
O
H
δ–
δ–O
A1 (m = 3)
H
A2 (m = 3)
Scheme 6. Reaction pathway for treatment of 15 with TBAF.
The results so far obtained strongly indicate that there exists an
equilibrium under the stated reaction conditions (TBAF in DMF) as
depicted in Scheme 6. In the case of 15dH and 15dMe (m¼3), the
allenyl/propargyl anions A, generated by kinetic abstraction of Ha,
would attack the aldehyde carbonyl carbon to produce the cis- and
trans-cyclohexanols B. The nonchelation transition state A1 col-
lapsing to the trans-B might minimize the dipolar repulsion be-
tween the allene and aldehyde functionalities in comparison to
that of another nonchelation transition state A2 leading to cis-B.
The once preferentially formed trans-B would subsequently
isomerize again to the thermodynamically more stable cis-B via
the allenyl/propargyl anions A finally reaching equilibrium. In
contrast, the one-carbon shorter aldehyde 15cH (m¼2) might ki-
netically and/or thermodynamically produce the anion in-
termediate cis-C in the presence of TBAF at low temperature
presumably due to the five-membered framework. At higher
temperature, the intermediate C should isomerize to E via the
successive formation of anion A and abstraction of Hb leading to
the enolate anion (D and/or F). On the other hand, the methyl-
substituted allene 15cMe hardly produces E because the methyl
group inhibits the attack of the enolate anion on the central car-
bon of the allene; therefore, cyclopentanol 16cMe is produced in
good yield at room temperature. Neither cyclobutanol 16b nor
cyclopropanol 16a are obtained because of their high strain en-
ergies, and the lower energy intermediates G and H, leading to the
pyran 21 and furan 22, respectively, are formed based on attack of
the (Z)-enolate oxygens on the allene moieties.
3. Conclusions
We demonstrated that the 1,1-disubstituted or 1,1,3-tri-
substituted allenes possessing a sulfonyl group at the C-1 position
generated the corresponding allenyl/propargyl anions by treatment
with NaH or TBAF, and the anions were intramolecularly captured
by the haloalkyl group to produce the 1-alkynyl-1-sulfonyl-
substituted three- to seven-membered carbocycles in high yields.
The intramolecular reaction of the anions, generated by TBAF or
DBU treatment, with the aldehyde functionality afforded the
2-alkynyl-2-sulfonylcyclopentanols or cyclohexanols in good to
high yields with moderate to high diastereoselectivities. This aldol-
type reaction smoothly proceeded even by the catalytic use of the
base. Application of these newly developed cyclization methods for
the synthesis of natural products is now in progress.
4. Experimental
4.1. General
Melting points are uncorrected. IR spectra were measured in
CHCl3. 1H NMR spectra were taken in CDCl3 unless otherwise in-
dicated. CHCl3 (7.26 ppm) for silyl compounds and tetramethylsi-
lane (0.00 ppm) for compounds without a silyl group were used as
internal standards. 13C NMR spectra were recorded in CDCl3 with
CDCl3 (77.00 ppm) as an internal standard. All reactions were car-
ried out under a nitrogen atmosphere. Silica gel (silica gel 60,

3692
S. Kitagaki et al. / Tetrahedron 66 (2010) 3687–3694
230–400 mesh) was used for chromatography. Organic extracts
were dried over anhydrous Na2SO4.
the ratio of 8:1 from 7dPh (132 mg, 0.386 mmol). A yellow oil; IR
1948 cmꢁ1 1H NMR (270 MHz)
8.01–7.90 (m, 2H), 7.73–7.47 (m,
;
d
3H), 7.39–7.17 (m, 5H), 6.68 (t, 0.89H, J¼3.3 Hz), 4.05 (dd, 0.11H,
J¼10.6, 4.1 Hz), 3.18 (t, 0.11ꢂ2H, J¼6.9 Hz), 3.08 (t, 0.89ꢂ2H,
J¼6.9 Hz), 2.49–2.42 (m, 0.89ꢂ2H), 2.30–1.33 (m, 6.22H); 13C NMR
4.2. Typical procedure for preparation of
iodo(phenylsulfonyl)alkadienes
(67.8 MHz)
d 205.3, 140.2, 136.8, 134.1, 133.5, 131.7, 131.1, 129.6,
5-(Phenylsulfonyl)octa-5,6-dien-1-ol (7cMe) was prepared
according to literature procedures.1a To a solution of 7cMe (195 mg,
0.732 mmol) in CH2Cl2 (7 mL) were added Et3N (0.4 mL, 2.9 mmol)
and TsCl (282 mg, 1.47 mmol) at 0 ꢀC. After stirring for 22 h at room
temperature, the reaction mixture was quenched by addition of
saturated aqueous NaHCO3 and extracted with EtOAc. The extract
was washed with water and brine, dried, and concentrated to
dryness. Chromatography of the residue with hexane/EtOAc (2:1)
afforded the tosylate 8cMe (290 mg, 93%) as a yellow oil. To a so-
lution of 8cMe (280 mg, 0.666 mmol) in acetone (6.7 mL) was
added NaI (465 mg, 3.10 mmol). After being refluxed for 5.5 h, the
mixture was allowed to cool to room temperature, diluted with
water, and extracted with EtOAc. The extract was washed with
water and brine, dried, and concentrated to dryness. Chromatog-
raphy of the residue with hexane/EtOAc (4:1) afforded a mixture of
9cMe and 90cMe in the ratio of 4:1 (225 mg, 90%) as a yellow oil.
Characterization data for compounds 8aH and 9b–eH have been
shown in Supplementary data of Ref. 9.
129.0, 128.9, 128.8, 128.7, 128.3, 128.1, 127.5, 117.2, 103.8, 59.9, 33.0,
32.9, 29.8, 29.7, 28.2, 27.2, 26.5, 25.8, 6.5; MS m/z 452 (Mþ, 1.7);
HRMS calcd for C20H21O2IS 452.0307, found 452.0305.
4.2.5. 10-Iodo-4-(phenylsulfonyl)deca-2,3-diene (9eMe) and 10-
iodo-4-(phenylsulfonyl)dec-2-yne
(90eMe). Title
compounds
(319 mg, 84%) were obtained as an inseparable mixture in the ratio
of 10:1 from 7eMe (278 mg, 0.944 mmol). A yellow oil; IR
1960 cmꢁ1 1H NMR (270 MHz)
; d 7.96–7.87 (m, 2H), 7.68–7.51 (m,
3H), 5.72 (qt, 0.91H, J¼7.3, 3.1 Hz), 3.79–3.75 (m, 0.09H), 3.20–3.12
(m, 0.09ꢂ2H), 3.15 (t, 0.91ꢂ2H, J¼7.0 Hz), 2.28–2.22 (m, 0.91ꢂ2H),
1.74 (d, 0.91ꢂ3H, J¼7.3 Hz), 2.10–1.27 (m, 8.45H); 13C NMR
(67.8 MHz)
d 204.3, 140.3, 136.9, 133.9, 133.2, 129.5, 128.9, 128.7,
127.9, 112.7, 96.2, 84.9, 71.3, 59.5, 33.2, 30.1, 30.0, 28.4, 27.8, 27.5,
27.2, 26.6, 26.5, 13.4, 6.9, 3.7; MS m/z 404 (Mþ, 54.9); HRMS calcd
for C16H21O2IS 404.0307, found 404.0312.
4.2.6. 9-Iodo-1-phenyl-3-(phenylsulfonyl)nona-1,2-diene (9ePh) and
9-iodo-1-phenyl-3-(phenylsulfonyl)non-1-yne (90ePh). Title com-
pounds (223 mg, 67%) were obtained as an inseparable mixture in
the ratio of 9:1 from 7ePh (257 mg, 0.721 mmol). A yellow oil; IR
4.2.1. 8-Iodo-4-(phenylsulfonyl)octa-2,3-diene (9cMe) and 8-iodo-
4-(phenylsulfonyl)oct-2-yne (90cMe). IR 1960 cmꢁ1
;
1H NMR
(270 MHz)
d
7.92–7.86 (m, 2H), 7.65–7.53 (m, 3H), 5.74 (qt, 0.8H,
1948 cmꢁ1 1H NMR (270 MHz)
; d 8.02–7.90 (m, 2H), 7.72–7.47 (m,
J¼7.4, 3.1 Hz), 3.80–3.73 (m, 0.2H), 3.16 (td, 0.2ꢂ2H, J¼6.8, 1.3 Hz),
3H), 7.35–7.17 (m, 5H), 6.67 (t, 0.9H, J¼3.3 Hz), 4.05 (dd, 0.1H,
J¼10.9, 4.1 Hz), 3.18 (t, 0.1ꢂ2H, J¼6.9 Hz), 3.09 (t, 0.9ꢂ2H, J¼6.9 Hz),
2.47–2.40 (m, 0.9ꢂ2H), 2.30–1.29 (m, 8.2H); 13C NMR (67.8 MHz)
3.11 (t, 0.8ꢂ2H, J¼6.8 Hz), 2.28 (td, 0.8ꢂ2H, J¼7.7, 3.1 Hz), 1.74 (d,
0.8ꢂ3H, J¼7.4 Hz), 1.84–1.48 (m, 5H); 13C NMR (67.8 MHz)
d 204.2,
140.1, 136.8, 133.9, 133.3, 129.5, 129.0, 128.8, 128.0, 112.3, 96.6, 85.2,
71.1, 59.3, 32.7, 32.3, 28.3, 27.7, 27.5, 25.6, 13.5, 5.9, 5.8, 3.7; MS m/z
376 (Mþ, 16.6); HRMS calcd for C14H17O2IS 375.9994, found
375.9993.
d 205.4, 140.2, 134.0, 133.5, 131.7, 131.1, 129.6, 129.0, 128.9, 128.7,
128.3, 128.1, 127.5, 117.4, 103.7, 88.2, 81.5, 60.0, 33.2, 30.1, 30.0, 28.3,
27.9, 27.7, 27.3, 27.2, 26.6, 6.9; MS m/z 466 (Mþ, 1.3); HRMS calcd for
C21H23O2IS 466.0464, found 466.0458.
Procedure for the preparation of iodoalkadienes 11a–c and their
characterization data have been shown in Supplementary data of
Ref. 9.
4.2.2. 7-Iodo-1-phenyl-3-(phenylsulfonyl)hepta-1,2-diene
(9cPh)
and 7-iodo-1-phenyl-3-(phenylsulfonyl)hept-1-yne (90cPh). Title
compounds (318 mg, 77%) were obtained as an inseparable mixture
in the ratio of 8:1 from 7cPh (313 mg, 0.953 mmol). A yellow oil; IR
4.3. Typical procedure for preparation of
(phenylsulfonyl)alkadienals
1948 cmꢁ1 1H NMR (270 MHz)
; d 8.02–7.90 (m, 2H), 7.72–7.46 (m,
3H), 7.35–7.15 (m, 5H), 6.69 (t, 0.89H, J¼3.1 Hz), 4.06 (dd, 0.11H,
J¼10.7, 4.1 Hz), 3.20 (td, 0.11ꢂ2H, J¼6.6, 1.6 Hz), 3.09 (t, 0.89ꢂ2H,
J¼6.8 Hz), 2.51–2.43 (m, 0.89ꢂ2H), 2.31–2.19 (0.11H), 1.93–1.52 (m,
To a solution of 7cMe (42.3 mg, 0.160 mmol) in CH2Cl2 (1.6 mL)
was added Dess–Martin periodinane (210 mg, 0.495 mmol) at 0 ꢀC.
After stirring for 1.5 h at that temperature, saturated aqueous
NaHCO3 and aqueous Na2S2O3 were added to the reaction mixture,
which was stirred for 30 min at room temperature. The mixture
was extracted with EtOAc, and the extract was washed with water
and brine, dried, and concentrated to dryness. Chromatography of
the residue with hexane/Et2O (1:2) afforded 15cMe (39.2 mg, 93%)
as a colorless oil.
4.11H); 13C NMR (67.8 MHz)
d 205.2, 139.9, 136.6, 134.0, 133.5, 131.5,
130.8, 129.4, 129.0, 128.8, 128.7, 128.6, 128.2, 127.9, 127.4, 121.5,
116.8, 103.9, 95.9, 88.3, 59.6, 32.5, 32.3, 28.2, 27.6, 27.2, 26.2, 5.7; MS
m/z 438 (Mþ, 9.5); HRMS calcd for C19H19O2IS 438.0151, found
438.0151.
4.2.3. 9-Iodo-4-(phenylsulfonyl)nona-2,3-diene (9dMe) and 9-iodo-
4-(phenylsulfonyl)non-2-yne (90dMe). Title compounds (80.7 mg,
80%) were obtained as an inseparable mixture in the ratio of 4:1
Characterization data for compounds 15dH and 15cH have been
shown in Supplementary data of Ref. 9.
from 7dMe (74.5 mg, 0.266 mmol). A yellow oil; IR 1961 cmꢁ1 1H
;
NMR (270 MHz)
d
7.94–7.85 (m, 2H), 7.68–7.50 (m, 3H), 5.72 (qt,
4.3.1. 5-(Phenylsulfonyl)octa-5,6-dien-1-al
1724 cmꢁ1 1H NMR (270 MHz)
(15cMe). IR
9.72 (t, 1H, J¼1.3 Hz), 7.90–7.86
1961,
0.8H, J¼7.4, 3.1 Hz), 3.80–3.75 (m, 0.2H), 3.16 (t, 0.2ꢂ2H, J¼6.9 Hz),
;
d
3.11 (t, 0.8ꢂ2H, J¼6.9 Hz), 2.28–2.22 (m, 0.8ꢂ2H), 1.74 (d, 0.8ꢂ3H,
(m, 2H), 7.66–7.50 (m, 3H), 5.75 (qt, 1H, J¼7.4, 3.1 Hz), 2.45 (td, 2H,
J¼7.4, 1.3 Hz), 2.33–2.28 (m, 2H), 1.78 (quin, 2H, J¼7.4 Hz), 1.74 (d,
J¼7.4 Hz), 2.10–1.31 (m, 7H); 13C NMR (67.8 MHz)
d 204.3, 140.2,
136.8, 133.9, 133.2, 129.5, 128.9, 128.7, 127.9, 112.5, 96.3, 85.0, 71.2,
59.4, 33.0, 32.9, 29.8, 29.4, 28.4, 26.5, 26.4, 25.6, 13.5, 6.7, 6.6, 3.7;
MS m/z 390 (Mþ, 18.4); HRMS calcd for C15H19O2IS 390.0151, found
390.0153.
3H, J¼7.4 Hz); 13C NMR (100 MHz)
d 204.3, 201.4,140.0,133.4,129.0,
128.0, 112.1, 96.7, 42.7, 26.1, 20.0, 13.4; MS m/z 264 (Mþ, 2.0); HRMS
calcd for C14H16O3S 264.0820, found 264.0814.
4.3.2. 6-(Phenylsulfonyl)nona-6,7-dien-1-al (15dMe). Title com-
pound (201 mg, 93%) was obtained as a colorless oil from 7dMe
4.2.4. 8-Iodo-1-phenyl-3-(phenylsulfonyl)octa-1,2-diene (9dPh) and
8-iodo-1-phenyl-3-(phenylsulfonyl)oct-1-yne (90dPh). Title com-
pounds (124 mg, 73%) were obtained as an inseparable mixture in
(219 mg, 0.781 mmol). IR 1960, 1722 cmꢁ1 1H NMR (270 MHz)
;
d
9.68 (t, 1H, J¼1.5 Hz), 7.86–7.83 (m, 2H), 7.62–7.47 (m, 3H), 5.70

S. Kitagaki et al. / Tetrahedron 66 (2010) 3687–3694
3693
(qt, 1H, J¼7.4, 3.1 Hz), 2.45 (td, 2H, J¼7.3, 1.3 Hz), 2.24 (td, 2H, J¼7.4,
3.1 Hz), 1.69 (d, 3H, J¼7.4 Hz), 1.63–1.37 (m, 4H); 13C NMR
7.69–7.63 (m, 1H), 7.56–7.51 (m, 2H), 7.38–7.27 (m, 5H), 2.04–1.99
(m, 4H), 1.84–1.19 (m, 6H); 13C NMR (67.8 MHz)
135.2, 133.8, 131.6,
130.9, 128.7, 128.3, 128.3, 122.1, 88.9, 85.4, 65.3, 30.6, 24.9, 22.5; MS
m/z 324 (Mþ, 0.5); HRMS calcd for C20H20O2S 324.1184, found
324.1186.
d
(67.8 MHz)
d
204.2, 202.0, 140.1, 133.3, 128.9, 127.9, 112.3, 96.4, 43.3,
26.9, 26.4, 21.0, 13.4.
4.3.3. 4-(Phenylsulfonyl)hexa-4,5-dien-1-al (15bH). Title com-
pound (31.6 mg, quant.) was obtained as a colorless oil from 7bH
4.4.5. 1-(Phenylsulfonyl)-1-(1-propynyl)cycloheptane
yellow oil; 1H NMR (270 MHz)
7.97–7.94 (m, 2H), 7.68–7.61 (m,
1H), 7.55–7.50 (m, 2H), 2.14–1.98 (m, 4H), 1.83 (s, 3H), 1.78–1.53 (m,
(10eMe). A
(31.4 mg, 0.132 mmol). IR 1971, 1728 cmꢁ1
;
1H NMR (400 MHz)
d
d
9.71 (s, 1H), 7.95–7.89 (m, 2H), 7.70–7.55 (m, 3H), 5.43 (t, 2H,
J¼3.7 Hz), 2.68 (t, 2H, J¼7.3 Hz), 2.57 (tt, 2H, J¼7.3, 3.7 Hz); 13C NMR
8H); 13C NMR (67.8 MHz)
d 135.6, 133.6, 131.0, 128.2, 84.7, 76.6, 67.6,
(100 MHz)
d
207.4, 199.8, 139.6, 133.7, 129.1, 128.0, 111.9, 85.2, 41.2,
33.8, 27.6, 23.1, 3.8; MS m/z 276 (Mþ, 3.4); HRMS calcd for
C16H20O2S 276.1184, found 276.1180.
19.6; MS m/z 236 (Mþ, 6.2); HRMS calcd for C12H12O3S 236.0507,
found 236.0511.
4.4.6. 1-(Phenylethynyl)-1-(phenylsulfonyl)cycloheptane (10ePh). A
4.3.4. 3-(Phenylsulfonyl)penta-3,4-dien-1-al (15aH). To a solution
of 7aH (35.2 mg, 0.157 mmol) in EtOAc (1.6 mL) was added IBX
(132 mg, 0.471 mmol) at room temperature, and the mixture was
stirred for 2 h at 80 ꢀC. The reaction mixture was allowed to cool to
room temperature and filtered. The filtrate was concentrated to
dryness and the residue was chromatographed with hexane/EtOAc
(3:2) to afford 15aH (30.1 mg, 86%) as a colorless oil. IR 1969,
colorless oil; 1H NMR (270 MHz)
d
8.02 (d, 2H, J¼7.4 Hz), 7.66 (t, 1H,
J¼7.4 Hz), 7.53 (t, 2H, J¼7.4 Hz), 7.38–7.28 (m, 5H), 2.27–2.14 (m,
4H), 1.90–1.55 (m, 8H); 13C NMR (67.8 MHz)
135.5, 133.8, 131.6,
d
131.1, 128.7, 128.4, 128.3, 122.2, 88.3, 86.7, 67.9, 33.8, 27.6, 23.3; MS
m/z 338 (Mþ, 1.0); HRMS calcd for C21H22O2S 338.1341, found
338.1334.
1734 cmꢁ1
;
1H NMR (400 MHz)
d
9.60 (t, 1H, J¼1.8 Hz), 7.91–7.89
4.4.7. 3-Benzylhepta-1,2,6-triene (13). A
colorless
oil;
IR
(m, 2H), 7.69–7.65 (m, 1H), 7.59–7.55 (m, 2H), 5.50 (t, 2H, J¼2.3 Hz),
1958 cmꢁ1 1H NMR (600 MHz)
;
d 7.30–7.20 (m, 5H), 5.80 (ddt, 1H,
3.33 (td, 2H, J¼2.3,1.8 Hz); 13C NMR (100 MHz)
d
209.3, 195.5, 139.3,
J¼17.2, 10.3, 6.9 Hz), 4.99 (d, 1H, J¼17.2 Hz), 4.93 (d, 1H, J¼10.3 Hz),
134.0, 129.3, 128.2, 105.5, 84.9, 41.0; MS m/z 222 (Mþ, 43.3); HRMS
4.69 (t, 2H, J¼3.4 Hz), 3.31 (s, 2H), 2.17 (td, 2H, J¼7.2, 6.9 Hz), 1.97
calcd for C11H10O3S 222.0351, found 222.0351.
(tt, 2H, J¼7.2, 3.4 Hz); 13C NMR (151 MHz)
d 206.7, 139.5, 138.3,
128.9,128.2,126.2, 114.6,102.2, 75.7, 39.7, 31.6, 30.4; FABMS m/z 185
4.4. General procedure for ring-closing reaction
(Mþþ1, 12.8); FABHRMS calcd for C14H17 185.1330, found 185.1337.
To a solution of allene (0.1 mmol) in solvent (1 mL) was added
base (0.01–0.2 mmol) at the temperature shown in Eqs. 1–4, Tables
1–4 and Scheme 5, and the reaction mixture was stirred at that
temperature until the complete disappearance of the starting ma-
terial (monitored by TLC). The mixture was quenched by addition of
water and extracted with Et2O. The extract was washed with water
and brine, dried and concentrated to dryness. Chromatography of
the residue with hexane/EtOAc afforded the ring-closing products
in pure form. Characterization data for compounds 10a–eH, 12a,b,
cis-16cH, cis- and trans-16dH, and 18cH have been shown in Sup-
plementary data of Ref. 9.
4.4.8. 7-Fluoro-3-benzylhepta-1,2-diene (14). A colorless oil; IR
1958 cmꢁ1; 1H NMR (400 MHz)
d 7.30–7.20 (m, 5H), 4.69 (quin, 2H,
J¼2.7 Hz), 4.40 (dt, 2H, J¼47.2, 6.0 Hz), 3.30 (t, 2H, J¼2.3 Hz), 1.92
(tt, 2H, J¼7.3, 3.7 Hz), 1.74–1.49 (m, 4H); 13C NMR (151 MHz)
d
206.6, 139.5, 128.9, 128.2, 126.2, 102.2, 84.0 (d, J¼163.9 Hz), 75.6,
39.6, 30.5, 29.9 (d, J¼19.2 Hz), 23.0 (d, J¼5.8 Hz); FABMS m/z 205
(Mþþ1, 1.2); FABHRMS calcd for C14H18F 205.1393, found 205.1396.
4.4.9. (1R
*
,2S
*
)-2-(Phenylsulfonyl)-2-(1-propynyl)cyclohexanol (cis-
1H NMR (270 MHz)
7.96–
16dMe). A colorless oil; IR 3533 cmꢁ1
;
d
7.93 (m, 2H), 7.70–7.64 (m, 1H), 7.58–7.52 (m, 2H), 4.20 (dd, 1H,
J¼10.9, 4.5 Hz), 3.04 (br s, 1H), 1.87 (s, 3H), 1.99–1.21 (m, 8H); 13C
4.4.1. 1-(Phenylsulfonyl)-1-(1-propynyl)cyclopentane
yellow oil; IR 2253 cmꢁ1 1H NMR (500 MHz)
(10cMe). A
7.98 (d, 2H,
NMR (67.8 MHz) d 135.3, 134.1, 130.8, 128.4, 87.6, 71.9, 70.3, 70.2,
;
d
31.9, 31.6, 23.6, 21.8, 3.9; FABMS m/z 279 (Mþþ1, 30.9); FABHRMS
J¼8.1 Hz), 7.66 (dd, 1H, J¼7.6, 7.3 Hz), 7.55 (dd, 2H, J¼7.8, 7.6 Hz),
calcd for C15H19O3S 279.1055, found 279.1055.
2.49–2.44 (m, 2H), 1.95–1.78 (m, 6H), 1.78 (s, 3H); 13C NMR
(67.8 MHz)
d
136.8, 133.6, 130.2, 128.4, 83.1, 78.1, 68.3, 36.2, 25.1,
4.4.10. (1R
(trans-16dMe). A white solid; IR 3499, 2249 cmꢁ1
(270 MHz) 7.96–7.93 (m, 2H), 7.72–7.66 (m, 1H), 7.60–7.54 (m,
2H), 4.13 (br s, 1H), 2.37 (td, 1H, J¼12.0, 3.5 Hz), 1.78 (s, 3H), 1.86–
*
,2R
*
)-2-(Phenylsulfonyl)-2-(1-propynyl)cyclohexanol
3.7; FABMS m/z 249 (Mþþ1, 14.4); FABHRMS calcd for C14H17O2S
;
1H NMR
249.0949, found 249.0956.
d
4.4.2. 1-(Phenylethynyl)-1-(phenylsulfonyl)cyclopentane (10cPh). A
1.25 (m, 7H); 13C NMR (67.8 MHz)
d 134.8, 134.1, 130.6, 128.5, 87.5,
white solid; 1H NMR (270 MHz)
d
8.05–8.02 (m, 2H), 7.69–7.63 (m,
1H), 7.57–7.51 (m, 2H), 7.35–7.27 (m, 5H), 2.65–2.54 (m, 2H), 2.13–
2.04 (m, 2H), 1.98–1.87 (m, 4H); 13C NMR (67.8 MHz)
136.7, 133.8,
74.4, 68.4, 67.4, 29.6, 24.5, 22.0, 18.1, 3.8; MS m/z 278 (Mþ, 5.3);
HRMS calcd for C15H18O3S 278.0977, found 278.0977.
d
131.5, 130.3, 128.6, 128.5, 128.3, 122.1, 88.2, 86.4, 68.7, 36.3, 25.3; MS
m/z 310 (Mþ, 1.3); HRMS calcd for C19H18O2S 310.1028, found
310.1022.
4.4.11. (1R
16cH). A white solid; IR 3495, 3304 cmꢁ1
8.01 (d, 2H, J¼8.2 Hz), 7.70 (t, 1H, J¼7.6 Hz), 7.59 (t, 2H, J¼7.6 Hz),
4.42 (br s, 1H), 2.75 (dt, 1H, J¼11.7, 8.2 Hz), 2.48 (d, 1H, J¼1.4 Hz),
2.17–2.03 (m, 3H), 1.96–1.86 (m, 2H); 13C NMR (151 MHz)
136.6,
*
,2R
*
)-2-Ethynyl-2-(phenylsulfonyl)cyclopentanol (trans-
;
1H NMR (600 MHz)
d
4.4.3. 1-(Phenylsulfonyl)-1-(1-propynyl)cyclohexane
white solid; IR 2243 cmꢁ1; 1H NMR (270 MHz)
7.96–7.92 (m, 2H),
7.68–7.62 (m,1H), 7.57–7.51 (m, 2H),1.83 (s, 3H),1.90–1.10 (m,10H);
(10dMe). A
d
d
134.3, 130.0, 128.7, 80.0, 79.1, 77.8, 70.5, 33.3, 31.5, 20.6; MS m/z 250
(Mþ, 4.9); HRMS calcd for C13H14O3S 250.0664, found 250.0665.
13C NMR (67.8 MHz)
d 135.2, 133.6, 130.8, 128.2, 85.3, 75.2, 64.9,
30.6, 24.9, 22.3, 3.8; MS m/z 262 (Mþ, 1.0); HRMS calcd for
4.4.12. (1R
(cis-16cMe). A colorless oil; IR 3560, 2243 cmꢁ1
(270 MHz) 7.98–7.94 (m, 2H), 7.71–7.64 (m, 1H), 7.58–7.53 (m,
*
,2S
*
)-2-(Phenylsulfonyl)-2-(1-propynyl)cyclopentanol
C15H18O2S 262.1028, found 262.1033.
;
1H NMR
d
4.4.4. 1-(Phenylethynyl)-1-(phenylsulfonyl)cyclohexane (10dPh). A
2H), 4.75–4.69 (m, 1H), 2.54–2.44 (m, 1H), 2.30–2.12 (m, 2H), 2.04–
1.93 (m, 1H), 1.84 (s, 3H), 1.86–1.69 (m, 3H); 13C NMR (67.8 MHz)
white solid; IR 2228 cmꢁ1; 1H NMR (270 MHz)
d 8.02–7.99 (m, 2H),

3694
S. Kitagaki et al. / Tetrahedron 66 (2010) 3687–3694
d
136.4, 133.9, 130.1, 128.5, 87.8, 74.8, 73.1, 72.5, 34.3, 32.8, 19.7, 3.9;
was added dropwise BH3$SMe2 (71.6 m
L, 0.755 mmol) at 0 ꢀC, and
MS m/z 264 (Mþ, 1.1); HRMS calcd for C14H16O3S 264.0820, found
the mixture was stirred for 40 h at room temperature. A 3 M
aqueous solution of NaOH (0.85 mL, 2.6 mmol) and 30% aqueous
H2O2 were successively added to the mixture, which was stirred
for three days. The mixture was quenched by addition of saturated
aqueous NH4Cl and extracted with EtOAc. The extract was washed
with water and brine, dried, and concentrated to dryness. Chro-
matography of the residue with hexane/EtOAc (1:1) afforded the
diol (9.1 mg, 36%) as a white solid. To a solution of the diol (2.3 mg,
8.5ꢂ10ꢁ3 mmol) in CH2Cl2 (0.5 mL) were added Et3N (0.1 mL,
0.7 mmol) and a solution of MsCl in CH2Cl2 (0.13 M, 0.13 mL,
1.7ꢂ10ꢁ2 mmol) at ꢁ78 ꢀC. After stirring for 22 h at room tem-
perature, the reaction mixture was quenched by addition of sat-
urated aqueous NH4Cl and extracted with EtOAc. The extract was
washed with water and brine, dried, and concentrated to dryness.
Chromatography of the residue with hexane/EtOAc (1:1) afforded
264.0819.
4.4.13. (1R
(trans-16cMe). A colorless oil; IR 3482, 2245 cmꢁ1
(600 MHz)
*
,2R
*
)-2-(Phenylsulfonyl)-2-(1-propynyl)cyclopentanol
;
1H NMR
d
7.98 (d, 2H, J¼8.2 Hz), 7.69 (dd, 1H, J¼8.2, 7.6 Hz), 7.58
(t, 2H, J¼7.6 Hz), 4.31 (d, 1H, J¼3.4 Hz), 2.71 (dt, 1H, J¼11.7, 8.9 Hz),
2.12–2.00 (m, 3H), 1.91–1.80 (m, 2H), 1.72 (s, 3H); 13C NMR
(151 MHz)
d 137.0, 134.0, 129.8, 128.6, 85.9, 79.0, 75.3, 70.9, 33.2,
31.2, 20.6, 3.8; MS m/z 264 (Mþ, 6.7); HRMS calcd for C14H16O3S
264.0820, found 264.0820.
4.4.14. 2-Ethyl-3-(phenylsulfonyl)cyclohex-2-ene-1-carbaldehyde
(18cMe). A colorless oil; IR 1670 cmꢁ1; 1H NMR (270 MHz)
d 10.0 (s,
1H), 7.89–7.85 (m, 2H), 7.70–7.64 (m, 1H), 7.58–7.52 (m, 2H), 4.48–
4.43 (m, 1H), 3.10 (dq, 1H, J¼14.5, 7.4 Hz), 2.88–2.73 (m, 1H), 2.51–
2.25 (m, 2H), 2.17–1.93 (m, 2H), 1.25 (t, 3H, J¼7.4 Hz); 13C NMR
20 (2.5 mg, 58%) as a colorless oil. 1H NMR (270 MHz)
d 7.97–7.94
(m, 2H), 7.71–7.66 (m, 1H), 7.61–7.55 (m, 2H), 4.89 (d, 1H,
J¼5.3 Hz), 3.90 (td, 1H, J¼7.9, 2.6 Hz), 3.59 (ddd, 1H, J¼9.4, 9.3,
5.9 Hz), 2.69 (ddd, 1H, J¼13.5, 5.9, 2.6 Hz), 2.33–2.23 (m, 1H), 1.95–
(67.8 MHz) d 187.6, 156.5, 144.0, 137.2, 134.2, 129.2, 128.9, 74.1, 28.4,
25.2, 20.6, 13.7; MS m/z 264 (Mþ, 22.2); HRMS calcd for C14H16O3S
264.0820, found 264.0817.
1.88 (m, 1H), 1.81–1.57 (m, 5H); 13C NMR (67.8 MHz)
d 137.3, 133.9,
129.8, 129.2, 85.7, 78.8, 68.4, 37.7, 35.9, 33.7, 24.0; FABMS m/z 253
(Mþþ1, 13.6); FABHRMS calcd for C13H17O3S 253.0899, found
253.0904.
4.4.15. 2-Methyl-3-(phenylsulfonyl)-4H-pyran (21). A red oil; 1H
NMR (270 MHz, C6D6)
d 7.79–7.74 (m, 2H), 6.95–6.86 (m, 3H), 5.66
(dt, 1H, J¼6.2, 2.0 Hz), 4.28 (dt, 1H, J¼6.2, 3.6 Hz), 2.77–2.74 (m, 2H),
Procedure for the preparation of cis- and trans-17 and their
characterization data have been shown in Supplementary data of
Ref. 9.
2.18 (t, 3H, J¼1.3 Hz); 13C NMR (100 MHz, C6D6)
d 158.3, 142.1, 139.1,
132.7, 129.0, 127.3, 111.5, 102.5, 21.5, 17.8; MS m/z 236 (Mþ, 100);
HRMS calcd for C12H12O3S 236.0507, found 236.058.
References and notes
4.4.16. 2-Methyl-3-(phenylsulfonyl)furan (22)11. A red oil; 1H NMR
1. For the reactions with oxygen nucleophiles, see: (a) Mukai, C.; Yamashita, H.;
Hanaoka, M. Org. Lett. 2001, 3, 3385–3387; (b) Mukai, C.; Ohta, M.; Yamashita,
H.; Kitagaki, S. J. Org. Chem. 2004, 69, 6867–6873; (c) Miyakoshi, N.; Ohgaki, Y.;
Masui, K.; Mukai, C. Heterocycles 2007, 74, 185–189; (d) Kitagaki, S.; Shibata, D.;
Mukai, C. Tetrahedron Lett. 2007, 48, 1735–1738; (e) Kitagaki, S.; Kawamura, T.;
Shibata, D.; Mukai, C. Tetrahedron 2008, 64, 11086–11095; (f) Pravia, K.; White,
R.; Fodda, R.; Maynard, D. F. J. Org. Chem. 1996, 61, 6031–6032; (g) Nagao, Y.;
Kim, K.; Sano, S.; Kakegawa, H.; Lee, W. S.; Shimizu, H.; Shiro, M.; Katunuma, N.
Tetrahedron Lett. 1996, 37, 861–864.
(400 MHz)
d 7.94–7.92 (m, 2H), 7.61–7.51 (m, 3H), 7.26 (s, 1H), 6.59
(d, 1H, J¼1.8 Hz), 2.59 (s, 3H); 13C NMR (100 MHz)
d 156.7, 142.4,
141.2, 133.1, 129.2, 126.8, 122.7, 110.0, 12.9; MS m/z 222 (Mþ, 50.2);
HRMS calcd for C11H10O3S 222.0351, found 222.0354.
4.5. Derivatization of ring-closing products
2. For the reactions with carbon nucleophiles, see: (a) Mukai, C.; Ukon, R.; Kuroda,
N. Tetrahedron Lett. 2003, 44, 1583–1586; (b) Mukai, C.; Kuroda, N.; Ukon, R.;
Itoh, R. J. Org. Chem. 2005, 70, 6282–6290.
3. For the reactions with nitrogen nucleophiles, see: (a) Mukai, C.; Kobayashi,
M.; Kubota, S.; Takahashi, Y.; Kitagaki, S. J. Org. Chem. 2004, 69, 2128–
2136; (b) Evans, C. A.; Cowen, B. J.; Miller, S. J. Tetrahedron 2005, 61, 6309–
6314.
4. For the anions generated from allenyl sulfones, see: Padwa, A.; Yeske, P. E. J. Org.
Chem. 1991, 56, 6386–6390; See also Back, T. G. Tetrahedron 2001, 57, 5263–
5301.
5. For the anions generated from propargyl sulfones, see: (a) Yoshimoto, M.;
Kishida, Y. Chem. Pharm. Bull. 1970, 18, 2518–2527; (b) Yoshimoto, M.; Kishida,
Y. Chem. Pharm. Bull. 1970, 18, 2528–2534.
6. For the anions generated from allenyl sulfoxides, see: (a) Bridges, A. J.; Fischer,
J. W. J. Chem. Soc. Chem. Commun. 1982, 665–666; (b) Baudin, J. B.; Julia, S. A.;
Lorne, R. Bull. Soc. Chim., Fr. 1992, 129, 440–456.
7. For the anions generated from allenoates, see: (a) Xu, B.; Hammond, G. B.
Angew. Chem., Int. Ed. 2008, 47, 689–692; (b) Wang, W.; Xu, B.; Hammond, G. B.
Org. Lett. 2008, 10, 3713–3716; (c) Liu, L.-P.; Xu, B.; Hammond, G. B. Org. Lett.
2008, 10, 3887–3890; (d) Yang, H.; Xu, B.; Hammond, G. B. Org. Lett. 2008, 10,
5589–5591 and references cited therein.
4.5.1. (1R
*
,2S )-2-Ethenyl-2-(phenylsulfonyl)cyclopent-1-yl acetate
*
(19). To a solution of cis-16cH (23.8 mg, 9.51ꢂ10ꢁ2 mmol) in pyri-
dine (1 mL) was added Ac2O (45 mL, 0.48 mmol) and DMAP (12 mg,
9.8ꢂ10ꢁ2 mmol) at room temperature. After stirring for 19 h, the
reaction mixture was quenched by addition of water and extracted
with EtOAc. The extract was washed with water and brine, dried,
and concentrated to dryness. Chromatography of the residue with
hexane/EtOAc (3:1) afforded the acetate (26.3 mg, 95%) as a color-
less oil. To a solution of the acetate (22.8 mg, 7.80ꢂ10ꢁ2 mmol) in
MeOH (1 mL) was added Lindlar catalyst (33 mg, 1.6ꢂ10ꢁ2 mmol)
at room temperature. After stirring under H2 atmosphere for 1 h,
the reaction mixture was filtered through a pad of Celite. The fil-
trate was concentrated to dryness, and the residue was chroma-
tographed with hexane/EtOAc (3:2) to afford 19 (20.5 mg, 89%) as
a colorless oil. IR 1738 cmꢁ1 1H NMR (270 MHz)
; d 7.83–7.79 (m,
2H), 7.67–7.61 (m, 1H), 7.55–7.49 (m, 2H), 6.04 (dd, 1H, J¼17.6,
10.9 Hz), 5.73 (t, 1H, J¼7.7 Hz), 5.51 (d, 1H, J¼10.9 Hz), 5.38 (d, 1H,
J¼17.6 Hz), 2.48–2.27 (m, 2H), 2.17–2.05 (m, 1H), 1.87 (s, 3H), 1.84–
8. (a) Marshall, J. A.; Gung, B. W.; Grachan, M. L. In Modern Allene Chemistry;
Krause, N., Hashmi, A. S. K., Eds.; Wiley-VCH: Weinheim, 2004; Vol.
1
Chapter 9; (b) Pasto, D. J. Tetrahedron 1984, 40, 2805–2827; (c) Allenes in
Organic Syntheses; Schuster, H. F., Coppola, G. M., Eds.; Wiley: New York, NY,
1984; (d) Epsztein, R. In Studies in Organic Chemistry 5, Comprehensive
Carbanion Chemistry, Part B; Buncel, E., Durst, T., Eds.; Elsevier: Amsterdam,
1984 Chapter 3.
1.44 (m, 3H); 13C NMR (67.8 MHz)
d 169.6, 136.7, 133.7, 130.3, 130.2,
128.5, 121.8, 75.5, 75.0, 30.4, 28.0, 20.8, 19.3; FABMS m/z 295
(Mþþ1, 35.4); FABHRMS calcd for C15H19O4S 295.1004, found
295.1004.
9. Part of this work was published as a preliminary communication: Kitagaki, S.;
Teramoto, S.; Mukai, C. Org. Lett. 2007, 9, 2549–2552.
10. (a) Najera, C.; Yus, M. Tetrahedron 1999, 55, 10547–10658; (b) Simpkins, N. S.
Sulphones in Organic Synthesis; Pergamon: Oxford, 1993.
11. Braverman, S.; Globerman, T. Tetrahedron 1974, 30, 3873–3881.
4.5.2. (1R
*
,5S )-5-(Phenylsulfonyl)-2-oxabicyclo[3.3.0]octane
*
(20). To a solution of 19 (27.8 mg, 9.44ꢂ10ꢁ2 mmol) in THF (1 mL)