Consecutive Aminolithiation-Carbolithiation of a Linear Aminoalkene Bearing Terminal Vinyl Sulfide Moiety to Give Hydro-indolizine

Article abstract of DOI:10.1055/s-0036-1588522

Aminolithiation-carbolithiation tandem cyclization of an aminoalkene bearing vinyl sulfide moiety proceeded smoothly using stoichiometric amounts of BuLi. Both aminolithiation and carbo-lithiation were in equilibrium at room temperature, and the stereoche

Full text of DOI:10.1055/s-0036-1588522

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© Georg Thieme Verlag Stuttgart · New York
2017, 28, A–E
letter
A
en
Y. Yamamoto et al.
Letter
Synlett
Consecutive Aminolithiation–Carbolithiation of a Linear Amino-
alkene Bearing Terminal Vinyl Sulfide Moiety to Give Hydro-
indolizine
Yasutomo Yamamoto*a
N
BuLi
N
H
SPh
Tatsuya Yamaguchib
Atsunori Kaneshigeb
Aiko Hashimotoa
Sachiho Kaibea
SPh
SPh
THF
88%
SPh
Li
Akari Miyawakia
Ken-ichi Yamadab
Kiyoshi Tomioka*a,b
N
SPh
N
SPh
N
Li
SPh
SPh
amino-
carbo-
lithiation
SPh
lithiation
SPh
Li
stable alkyllithium intermediates
a Faculty of Pharmaceutical Sciences, Doshisha Women’s
College of Liberal Arts, Kodo, Kyotanabe 610-0395,
Japan
ktomioka@dwc.doshisha.ac.jp
b Graduate School of Pharmaceutical Sciences, Kyoto
University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan
This paper is dedicated to Professor Victor Snieckus on
the occasion of his 80th birthday
Received: 08.06.2017
Accepted after revision: 04.07.2017
Published online: 08.08.2017
fords substituted indolizines 3,5 the reaction has limited
substrate scope. Aminolithiation of intramolecular styrene
(R1 = Ph) proceeds smoothly, whereas a competitive inter-
molecular addition reaction is observed in the reaction of
terminal olefin (R1 = H).3 The carbolithiation reaction oc-
curs only with terminal olefin (R2 = H) and not with inter-
nal olefin (R2 = alkyl).4 We postulated that stabilization of
alkyllithium intermediates 2-Li and 3-Li by adjacent sub-
stituents R1 and R2 accelerates the aminolithiation–carbo-
lithiation process. An alkylthio group stabilizes the neigh-
boring carbanion,6 and thus we planned a double cycliza-
tion with vinyl sulfide (R1 = R2 = SPh).7,8 Herein, we describe
the aminolithiation–carbolithiation of vinyl sulfides for
double cyclization of aminoalkenes.
DOI: 10.1055/s-0036-1588522; Art ID: st-2017-r0445-l
Abstract Aminolithiation–carbolithiation tandem cyclization of an
aminoalkene bearing vinyl sulfide moiety proceeded smoothly using
stoichiometric amounts of BuLi. Both aminolithiation and carbo-
lithiation were in equilibrium at room temperature, and the stereo-
chemistry of the cyclization was thermodynamically controlled. At
–78 °C the reaction was kinetically controlled and the cyclized product,
1,2-disubstituted octahydroindolizine, was obtained with good dia-
stereoselectivity.
Key words aminolithiation, carbolithiation, vinyl sulfide, N-hetero-
cycles, domino reaction
The addition of nitrogen nucleophiles to olefins is an
important C–N bond-forming reaction.1 We previously re-
ported an asymmetric conjugate addition of lithium amides
to α,β-unsaturated esters in the presence of a chiral diether
ligand.2 In the course of our studies on asymmetric amina-
tion, we found that intramolecular styrene moieties also act
as good acceptors of lithium amide in catalytic asymmetric
intramolecular hydroamination of aminoalkene (Scheme
1).3 Lithium amide 1-Li, generated from aminoalkene 1
with BuLi, reacts with intramolecular alkene to give 2-Li,
and subsequent protonation yields cyclized product 2. The
intermediate alkyllithium 2-Li can be further utilized for a
bond-forming reaction; 2-Li reacts with the intramolecular
olefin of the N-allyl group to give 3-Li, the protonation of
which furnishes the double-cyclized product 3.4 Although
this double cyclization process through aminolithiation (1-
Li to 2-Li) and carbolithiation (2-Li to 3-Li) efficiently af-
N
H
R2
N
R2
N
R1
R1
R2
R1
1
2
3
BuLi
H+
H+
Li
N
Li
R2
N
R2
N
R1
R1
R2
R1
Li
1-Li
2-Li
3-Li
Scheme 1 Consecutive aminolithiation–carbolithiation of N-allylami-
noalkenes
We first prepared aminoalkenes 1a–d to verify the ef-
fect of a phenylthio group on aminolithiation and carbo-
lithiation (Scheme 2). First, substrate 1a was synthesized
from commercially available hex-5-yn-1-ol (4). Radical
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–E

B
Y. Yamamoto et al.
Letter
Synlett
hydrothiolation9 of alkyne 4 gave vinyl sulfide 5 with an E/Z
ratio of 1:1. Then, o-nitrobenzenesulfonamide (o-NsNH2)
was coupled with alcohols 5 and 7 under Mitsunobu condi-
tions to give 8a, and subsequent removal of the Ns group
yielded 1a. Substrates 1b and 1d were prepared by Mitsu-
nobu condensation of N-allyl-o-nosylamide 1310 with alco-
hols 5 and 14, respectively, and subsequent removal of the
Ns group. Aminoalkene 1c was synthesized from commer-
cially available N-Boc propargylamine (9) in three steps:
radical hydrothiolation of alkene 9, N-alkylation of Boc
amide 10 with 1-bromo-5-hexene (11), and removal of the
Boc group of 12 with trifluoroacetic acid (TFA).
monocyclized product 2a (Table 1, entry 1).11 In contrast,
the reaction of 1b (R1 = SPh, R2 = H) gave monocyclized
product 2b in 57% yield and double-cyclized product 3b in
only 1% yield after 2 h (Table 1, entry 2). Increasing the tem-
perature to 40 °C and the reaction time to 24 hours some-
what enhanced the double cyclization: 2b (34%) and 3b
(13%) were obtained (Table 1, entry 3). Thus, carbolithiation
(2-Li to 3-Li in Scheme 1) of a vinyl sulfide proceeded
smoothly compared with that of a terminal olefin. Amino-
alkenes 1c (R1 = H, R2 = SPh) and 1d (R1 = R2 = H) did not
cyclize at all, and resulted in the recovery of starting mate-
rial 1 or the isomerization of olefin (Table 1, entries 4 and
5). These results indicated that aminolithiation (1-Li to 2-Li
in Scheme 1) of a vinyl sulfide was much more efficient
than that of a terminal olefin.
o-NsNH2
DEAD
PPh3
PhSH
AIBN
SPh
HO
HO
HO
benzene
reflux, 1 h
93%
toluene–THF
r.t., 3 h
4
5
Table 1 Cyclization of Aminoalkene 1 with n-BuLia
77%
SPh
7
Ns
N
H
R2
N
DEAD
PPh3
n-BuLi
R2
N
N
SPh
+
R1
R1
Ns
SPh
R2
N
THF
temp
time
SPh
H
benzene
1
2
R1
6
3
r.t., 2.5 h
8a
PhSH
K2CO3
N
H
SPh
Entry
1
R1
R2
n-BuLi
(equiv) (°C)
Temp Time
(h)
2
(%)
3
(%)
DMF
r.t., 7 h
60%
SPh
1
1ab
1bd
1bd
1cg
1d
SPh
SPh
SPh
H
SPh
1.5
1.1
1.1
1.1
1.1
r.t.
r.t.
40
r.t.
r.t.
2
0
60c
1a
PhSH
(2 steps)
Br
2
H
2
24
5
57
34
0
1e
13e
0
11
AIBN
NaH
3
H
BocHN
BocHN
SPh
benzene
reflux, 1.5 h
82%
DMF
r.t., 18 h
21%
4f
5h
SPh
H
9
10
H
23
0
0
a The reaction was performed with 1 (1 equiv) and n-BuLi (1.1–1.5 equiv) in
THF.
Boc
N
TFA
CH2Cl2
r.t., 20 min
31%
SPh
N
SPh
b E/Z ratios were 57:43 (regarding R1) and 55:45 (regarding R2).
c The dr was 23:50:27 (tc/tt/ct).
H
d The E/Z ratio was 1:1.
12
1c
e Only tc-3b was obtained.
f 1c (30%) was recovered.
Ns
N
g The E/Z ratio was 1:1.
H
13
h Compound 1d was recovered quantitatively.
Ns
N
DIAD
PPh3
PhSH
K2CO3
OH
N
H
SPh
SPh
SPh
DMF
THF
r.t., 1 h
The high efficiency of 1a for double cyclization was also
highlighted by comparison with 1e, the cyclization reaction
of which was reported in our previous study.4 Treatment of
1e with 0.2 equiv of lithium diisopropylamide (LDA) in THF
afforded 2e in 95% yield and 3e in 1% yield (Table 2, entry 1).
On the other hand, the reaction of 1a with 0.2 equivalents
of LDA increased the yield of 3a (26%) and 2a (46%) (Table 2,
entry 2). These results clearly revealed the higher efficiency
of 1a than of 1e for double cyclization. Using 1.5 equiva-
lents of base in the reaction of 1e, the yield of bicyclic
amine 3e was highly dependent on the base; the yield of 3e
was only 33% with n-BuLi, 74% with LDA, and 88%
with bulky t-Bu(Tr)NLi (Table 2, entries 2–4). The bulky
t-Bu(Tr)NH, generated in situ after deprotonation of 1e by
t-Bu(Tr)NLi, preferentially protonated less hindered 3-Li
rather than 2-Li to reach 3e (Scheme 1). On the other hand,
in the reaction of 1a, the alkyllithium 3a-Li was stabilized by
r.t., 23 h
72% (2 steps)
5
8b
1b
Ns
N
H
13
DEAD
PPh3
Ns
PhSH
K2CO3
OH
N
N
H
THF
r.t., 1 h
quant
DMF
r.t., 2 h
quant
14
8d
1d
Scheme 2 Synthesis of aminoalkenes 1a–d
With aminoalkenes 1a–d in hand, we examined the se-
quential aminolithiation–carbolithiation reaction using
stoichiometric amounts of n-BuLi in tetrahydrofuran (THF)
at room temperature (Table 1). As expected, aminoalkene
1a with two vinylsulfide moieties (R1 = R2 = SPh) afforded
double-cyclized product 3a in 60% yield after 2 h with no
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–E

C
Y. Yamamoto et al.
Letter
Synlett
the adjacent phenylthio group, and therefore bicyclic prod-
uct 3a was obtained in moderate (60%) yield with n-BuLi
(Table 2, entry 6).
N-Boc propargylamine 9 was alkylated by mesylate 15
to give diyne 16, and the following phenylthiolation afford-
ed alkynyl sulfide 17.12 Reduction of diyne 17 with LiAlH4
gave diene 18 with an E,E-configuration.13 Finally, Boc
deprotection by ZnBr2 gave the desired E,E-1a (Scheme 3).14
Table 2 Cyclization of Aminoalkene 1e and 1a
OMs
N
H
N
N
H
base
Me
+
Ph
Ph
n-BuLi
PhSSPh
MeI
Boc
N
Boc
N
THF
r.t.
15
NaH
Ph
1e
2e
3e
9
SPh
SPh
THF
r.t., 2 h
66%
DMF
r.t., 20 h
74%
SPh
16
17
N
SPh
base
H
2a
+
3a
Boc
SPh
THF
r.t.
LiAlH4
N
SPh ZnBr2
N
H
1a
SPh
SPh
THF
40 °C, 1 h
80%
CH2Cl2
r.t., 7 h
70%
Entry
1
Base (equiv)
Time (h) 2 (%)
3 (%)
18
E,E only
1a
1a
2
1e
LDA (0.2)
2
95
46
5
1
Scheme 3 E-Selective preparation of 1a
1a
1e
1e
1e
1a
1a
LDA (0.2)
1
26b
33c
74d
88e
60g
82h
3a
4a
5a
6f
7
n-BuLi (1.5)
LDA (1.5)
2
Treatment of E,E-1a with n-BuLi (1.05 equiv) in THF at
room temperature afforded 3a in 88% yield with a diaste-
reomeric ratio of 23:49:28 (Table 3, entry 1). The improved
yield of 3a compared with the previous experiment (Table
1, entry 1) was attributed to the suppression of competitive
isomerization of olefin by decreasing the amount of n-BuLi.
On the other hand, an E,Z-mixture of 1a and E,E-1a afforded
3a with almost the same diastereoselectivity, indicating the
presence of an equilibrium and that these diastereomeric
ratios reflect the thermodynamic stability of each diaste-
reomer. The reaction was relatively slow at –78 °C in THF;
3a was obtained in 18% yield after four hours and 37% yield
after 24 hours, and the major diastereomer was tc-3a,
which would be the kinetically favored product. An equilib-
rium still seemed to exist at –78 °C because the diastereo-
selectivity varied greatly according to the reaction time (Ta-
ble 3, entries 2 and 3). In toluene, the reaction did not oc-
3
15
0
t-Bu(Tr)NLi (1.5)
n-BuLi (1.5)
t-Bu(Tr)NLi (1.5)
2
2
0
0.5
0
a Quoted from ref.4
b The dr was 32:43:25 (tc/tt/ct).
c The dr was 25:75 (tc/tt).
d The dr was 86:14 (tc/tt).
e The dr was 60:30:10 (tc/tt/ct).
f From Table 1, entry 1.
g The dr was 23:50:27 (tc/tt/ct).
h The dr was 26:52:22 (tc/tt/ct).
The relative stereochemistry of 3a was unequivocally
determined by 1H-NOESY correlation, as shown in Figure 1.
Three diastereomers, trans-cis (tc), trans-trans (tt), and cis-
trans (ct) isomers were obtained in the cyclization of 1a
with a diastereomeric ratio of 23:50:27, whereas the cis-cis
isomer was not observed (Table 1, entry 1). Because the ge-
ometry of the olefin of 1a should affect the diastereomeric
ratio of product 3a, we planned an E-selective preparation
of 1a and its cyclization reaction to explore the nature of
the diastereoselectivity.
cur, whereas adding
3 equivalents of hexamethyl-
phosphoramide (HMPA) effectively gave 3a in 47% yield
with a diastereomeric ratio of 66:19:15 (Table 3, entries 4
and 5). Under these conditions, however, we observed a bu-
tyl addition product, and therefore we examined less nucleo-
philic bases: s-BuLi, t-BuLi, and LDA (Table 3, entries 6–8).
As a result, 3a was obtained in 73% yield with a diastereo-
meric ratio of 80:8:12 by using LDA and HMPA in THF. The
combination of n-BuLi and HMPA in THF also effectively
gave 3a in 69% yield with a diastereomeric ratio of 89:11
(Table 3, entry 9).
N
N
N
SPh
SPh
SPh
H
H
H
SPh
SPh
SPh
trans-cis (tc-3a)
trans-trans (tt-3a)
cis-trans (ct-3a)
H
H
A plausible stereochemical pathway is shown in Scheme
4. Based on Cohen’s report,15 aminolithiation of 1a-Li, gen-
erated from 1a by lithiation, should proceed through paral-
lel arrangement of N–Li and C=C, directed to an equatorial
position, to give 2a-Li. The following carbolithiation via
conformer A, in which C-Li and C=C had a pseudoequatorial
arrangement, afforded tc-3a-Li, whereas conformer B of
pseudoaxial C-Li and C=C yielded tt-3a-Li. Epimerization of
α-thioalkyllithium 2a-Li to give 2a′-Li was also possible,
H
H
H
PhS
N
H
H
H
H
SPh
H
N
N
H
SPh
H
H
H
H
H
H
PhS
PhS
H
H
H
SPh
H
H
Figure 1 Determination of the relative configuration of 3a by 1H-NOESY
correlation (red arrows)
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–E

D
Y. Yamamoto et al.
Letter
Synlett
Table 3 Cyclization of E,E-1a with n-BuLi
base
(1.05 equiv)
additive
N
SPh
N
H
SPh
solvent
temp
time
SPh
SPh
1a
E,E only
3a
Entry
Base
Additive
Solvent
Temp (°C)
Time (h)
3a (%)
dr
tc
tt
49
ct
1
2
3
4
5
6
7
8
9
n-BuLi
–
THF
r.t.
2
24
4
88
37
18
0
23
28
17
0
n-BuLi
n-BuLi
n-BuLi
n-BuLi
s-BuLi
t-BuLi
LDA
–
THF
–78
–78
–78
–78
–78
–78
–78
–78
50
73
–
33
27
–
–
THF
–
toluene
toluene
toluene
toluene
THF
4
–
HMPA
HMPA
HMPA
HMPA
HMPA
4
47
58
62
73
69
66
90
84
80
89
19
7
15
3
2
2
8
8
2
8
12
0
n-BuLi
THF
2
11
and the following carbolithiation produced ct-3a-Li via con-
former C and cc-3a-Li via conformer D, respectively. At –78 °C,
the major diastereomer was tc-3a, which appeared to be a
kinetically favored product. On the other hand, the reaction
at room temperature afforded tt-3a as a major product, in-
dicating the presence of an equilibrium in the carbolithia-
tion step, and tt-3a was the thermodynamically favored
product. Moreover, epimerization of alkyllithium 2a-Li to
2a′-Li is likely involved because there was little difference
in diastereoselectivity between the cyclization of E,E-1a
and the E/Z-mixture of 1a (Table 1, entry 1 and Table 3, en-
try 1).
α-proton of the phenylthio group, epimerization of α-thio-
alkyllithium tc-3a-Li′ to ct-3a-Li′, and subsequent protona-
tion (Scheme 5). In fact, treatment of tc-3a with n-BuLi at
–78 °C for 24 h caused partial isomerization to ct-3a. More
noteworthy was that retro-carbolithiation (3a-Li to 2a-Li)
did not occur at –78 °C because tt-3a was not obtained at
all under the conditions shown in Scheme 5.
In conclusion, vinyl sulfide was a highly efficient accep-
tor for the sequential aminolithiation–carbolithiation reac-
tion. This double-cyclization process was mediated by a
stoichiometric amount of BuLi, probably because a phen-
ylthio group would be able to stabilize the lithiated inter-
mediates. The cyclization reaction of E,E-vinylsulfide sug-
gested the existence of equilibrium in both aminolithiation
Another possible stereodetermining pathway is isomer-
ization between tc-3a and ct-3a by deprotonation of the
H
H
Li
H
H
N
SPh
N
SPh
Li
SPh
SPh
R
r.t.
Li
H
Li
H
H
H
N
N
SPh
N
tc-3a-Li
R
A
Li
SPh
SPh
SPh
SPh
Li
H
SPh
H
H
Li
H
2a-Li
E,E-1a-Li
N
N
N
N
H
H
SPh
SPh
H
H
tt-3a-Li
B
epimerization
H
H
H
Li
PhS
PhS
SPh
SPh
Li
H
H
H
H
N
SPh
ct-3a-Li
N
SPh
H
Li
C
R
SPh
Li
SPh
Li
H
SPh
E,Z-1a-Li
Li
PhS
N
N
2a'-Li
H
H
H
H
SPh
H
cc-3a-Li
D
Scheme 4 Plausible stereochemical pathway of aminolithiation–carbolithiation
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–E

E
Y. Yamamoto et al.
Letter
Synlett
and carbolithiation at room temperature, whereas at –78 °C
the reaction was kinetically controlled and the trans,cis-
isomer was preferentially obtained.
A.; Kenda, B.; Remacle, B. Tetrahedron 1996, 52, 7435. (d) Chen,
F.; Mudryk, B.; Cohen, T. Tetrahedron 1999, 55, 3291.
(e) Hoffmann, R. W.; Koberstein, R.; Harms, K. J. Chem. Soc.,
Perkin Trans. 2 1999, 183. (f) Ashweek, N. J.; Coldham, I.;
Snowden, D. J.; Vennall, G. P. Chem. Eur. J. 2002, 8, 195.
n-BuLi
tc-3a / tt-3a / ct-3a
= 9/0/1
tc-3a
(9) Miyake, H.; Yamamura, K. Bull. Chem. Soc. Jpn. 1988, 61, 3752.
(10) Beckwith, A. L. J.; Meijs, G. F. J. Org. Chem. 1987, 52, 1922.
(11) Typical procedure (Table 1, entry 1): Under Ar atmosphere, to
a solution of n-BuLi (1.62 M in hexane, 0.19 mL, 0.3 mmol) in
THF (1.5 mL) was added a solution of 1a (71 mg, 0.2 mmol) in
THF (0.5 mL) dropwise at –20 °C. The mixture was stirred for 2
h at room temperature, then the reaction was quenched with
water (5 mL). The mixture was extracted with Et2O (20 + 10 + 10
mL), and the combined organic layers were washed with brine
(20 mL), dried over K2CO3 and concentrated. Column chroma-
tography (hexane/EtOAc, 5:1 to 0:1, then EtOAc/Et3N 1:1) gave
3a (42 mg, 60%). The diastereomers of 3a were partially sepa-
rated by column chromatography to give tc-3a, tt-3a and ct-3a.
tt-3a: 1H NMR (CDCl3): δ = 1.09–1.21 (m, 2 H), 1.50 (m, 1 H),
1.59 (m, 1 H), 1.76 (m, 1 H), 1.81 (m, 1 H), 1.88 (m, 1 H), 1.93
(ddd, J = 3.0, 11.5, 11.5 Hz, 1 H), 2.21 (m, 1 H), 2.32 (dd, J = 9.0,
9.0 Hz, 1 H), 2.84 (dd, J = 6.0, 9.4 Hz, 1 H), 2.87 (dd, J = 10.3,
12.6 Hz, 1 H), 2.97 (br d, J = 10.5 Hz, 1 H), 3.01 (dd, J = 2.0,
9.4 Hz, 1 H), 3.15 (dd, J = 4.3, 12.6 Hz, 1 H), 7.17 (m, 1 H), 7.23–
7.28 (m, 7 H), 7.38–7.42 (m, 2 H). 13C NMR (CDCl3): δ = 24.0
(CH2), 25.1 (CH2), 29.7 (CH2), 38.7 (CH2), 43.2 (CH), 53.0 (CH2),
57.2 (CH), 57.8 (CH2), 70.8 (CH), 125.9 (CH), 127.4 (CH), 128.9
(CH x 2), 129.3 (CH), 133.0 (CH), 134.4 (C), 136.0 (C). IR, MS and
elemental analysis data were taken as a mixture of diastereo-
mers. IR (neat): 2932, 1582, 1481 cm–1. EIMS: m/z = 355 [M]+.
Anal. Calcd for C21H25NS2: C, 70.94; H, 7.09; N, 3.94. Found: C,
71.12; H, 7.23; N, 3.70.
THF
–78 °C, 24 h
(NMR ratio)
N
N
H
tc-3a
ct-3a
Li
Li
SPh
SPh
SPh
H
SPh
tc-3a-Li'
ct-3a-Li'
Scheme 5 Epimerization between tc-3a and ct-3a
Acknowledgment
We thank JSPS for financial support.
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0036-1588522.
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p
ortiInfogrmoaitn
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References and Notes
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tc-3a: 1H NMR (CDCl3): δ = 1.20–1.27 (m, 2 H), 1.53 (m, 1 H),
1.66 (m, 1 H), 1.78–1.84 (m, 2 H), 1.98–2.04 (m, 2 H), 2.07 (dd, J
= 9.0, 9.0 Hz, 1 H), 2.71 (m, 1 H), 2.83 (dd, J = 12.0, 12.0 Hz, 1 H),
3.08 (br d, J = 10.9 Hz, 1 H), 3.31 (dd, J = 4.0, 12.0 Hz, 1 H), 3.45
(dd, J = 10.0, 10.0 Hz, 1 H), 3.47 (dd, J = 7.2, 9.4 Hz, 1 H), 7.14–
7.18 (m, 2 H), 7.21–7.28 (m, 8 H). 13C NMR (CDCl3): δ = 24.1
(CH2), 25.3 (CH2), 30.1 (CH2), 36.6 (CH2), 37.4 (CH), 53.2 (CH2),
53.5 (CH), 61.3 (CH2), 68.2 (CH), 125.5 (CH), 126.1 (CH), 127.8
(CH), 128.8 (CH), 129.0 (CH), 129.5 (CH), 135.9 (C), 137.4 (C).
ct-3a: 1H NMR (CDCl3): δ = 1.14–1.24 (m, 2 H), 1.49–1.69 (m,
3 H), 1.78 (m, 1 H), 1.90–1.97 (m, 2 H), 2.24 (m, 1 H), 2.49 (m,
1 H), 2.79 (dd, J = 9.2, 12.9 Hz, 1 H), 3.07 (dd, J = 5.5, 12.9 Hz,
1 H), 3.14 (br d, J = 11.2 Hz, 1 H), 3.34 (dd, J = 7.7, 9.2 Hz, 1 H),
3.55 (dd, J = 4.0, 6.3 Hz, 1 H), 7.14–7.29 (m, 8 H), 7.38–7.41 (m,
2 H). 13C NMR (CDCl3): δ = 24.1 (CH2), 24.8 (CH2), 27.8 (CH2),
38.3 (CH2), 44.5 (CH), 53.7 (CH2), 55.2 (CH), 60.4 (CH2), 67.4
(CH), 126.1 (CH), 126.5 (CH), 128.8 (CH), 128.9 (CH), 129.5 (CH),
131.1 (CH), 135.6 (C), 136.3 (C).
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Commun. 1989, 19, 3139. (b) Murray, A. J.; Parsons, P. J.;
Hitchcock, P. Tetrahedron 2007, 63, 6485.
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Rossi, K.; Thiel, Y.; Wiberg, K. B. J. Am. Chem. Soc. 1991, 113,
5720. (b) Liu, H.; Deng, K.; Cohen, T.; Jordan, K. D. Org. Lett.
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