Synthesis of 1-Acyl-2-vinylcyclopropanes: Utilizing Copper-Carbenoid versus Sulfur Ylide Methodology

Article abstract of DOI:10.1055/s-0036-1591554

The synthesis of a range of racemic 1-acyl-2-vinylcyclopropanes by using two different methodologies is studied. We have developed a copper-catalyzed process for converting diazoketones into 1-acyl-2-vinylcyclopropanes and a sulfur-ylide-mediated procedur

Full text of DOI:10.1055/s-0036-1591554

SYNTHESIS
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
© Georg Thieme Verlag Stuttgart · New York
2018, 50, A–R
paper
A
en
A. Zens et al.
Paper
Synthesis
Synthesis of 1-Acyl-2-vinylcyclopropanes: Utilizing Copper-
Carbenoid versus Sulfur Ylide Methodology
Anna Zensa
H
H
R2
H
S
R2
R3
O
O
Philipp Seuberta
Benedikt Kolba
Marius Wurstera
Marcel Holzwartha
Fabian Mannchena
Robert Forschnera
Birgit Claasena
Doris Kunzb
for n = 1
[Cu]
for n = 1,2
S ylide
H
O
R3
+
R3
R2
N2
[2+1] cyclo-
addition
total 6 steps
conjugate
addition
total 2 steps
H
n
n
X
R2, R3 = H, Me, Et,
Ph, -(CH2)3-, -(CH2)4-
H
14 examples
Sabine Laschat*a
a Institut für Organische Chemie, Universität Stuttgart,
Pfaffenwaldring 55, 70569 Stuttgart, Germany
sabine.laschat@oc.uni-stuttgart.de
b Institut für Anorganische Chemie, Eberhard Karls
Universität Tübingen, Auf der Morgenstelle 18, 72076
Tübingen, Germany
Received: 18.12.2017
O
Accepted after revision: 22.02.2018
Published online: 27.03.2018
DOI: 10.1055/s-0036-1591554; Art ID: ss-2017-z0818-op
R3
N2
R1
R2
3
Abstract The synthesis of a range of racemic 1-acyl-2-vinylcyclo-
propanes by using two different methodologies is studied. We have
developed a copper-catalyzed process for converting diazoketones
into 1-acyl-2-vinylcyclopropanes and a sulfur-ylide-mediated procedure
which allows, in only two steps, a simplified access to 1-acyl-2-vinyl-
cyclopropanes with alkyl or aryl substituents on the alkene moiety.
route a
[Cu]
[2+1]
R1
O
R2
R3
n
Key words vinylcyclopropanes, cyclopropanation, cyclic enones, sulfur
ylides, copper catalysis, [2+1] annulations, diazoketones
1 n = 1
2 n = 2
route b
conjugate addition
S ylide
O
R1
There is a growing interest in vinylcyclopropanes (VCPs)
because they serve as valuable precursors for a variety of
transition-metal-catalyzed and nucleophilic ring-opening
processes leading to molecular scaffolds with high structur-
al diversity.1 In addition, vinylcyclopropanes have been suc-
cessfully employed for vinylcyclopropane–cyclopentene
S
R2
R3
n
X
4 n = 1
5 n = 2
ylide 6·X
Scheme 1 Studied routes to 1-acyl-2-vinylcyclopropanes 1 and 2
and
divinylcyclopropene–cycloheptatriene
rearrange-
ments,2 as well as for cycloadditions3 and polymerizations.4
Apart from this synthetic point of view, vinylcyclopropanes
are important structural subunits of biologically active
compounds, e.g., terpenoid natural products as well as
pharmaceutical and agrochemical compounds.5 Several
synthetic strategies have been developed toward
vinylcyclopropanes2a–c including sulfur ylide additions to
electron-poor alkenes,6 zinc-mediated Simmons–Smith re-
actions,7 Fischer carbene [2+1] cycloadditions,8 metal-me-
diated additions of diazo compounds to alkenes9 and metal-
catalyzed cycloisomerizations.10 Much work has been de-
voted to sulfur ylides11 including theoretical calculations.12
Particular breakthroughs have been achieved for chiral-
auxiliary-derived sulfur ylides13 and organocatalytic ver-
sions.14 More recently, Ni-catalyzed ring contractions of tet-
rahydrofurans and tetrahydropyrans15 and tandem hy-
droalumination/Cu-catalyzed asymmetric vinylmetalation
were reported.16 However, limited precedent is available
for the synthesis of 1-acyl-2-vinylcyclopropanes with sim-
ple alkyl or aryl substituents on the alkene moiety.17 In par-
ticular, vinylcyclopropanes with an anellated cyclic ketone
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–R

B
A. Zens et al.
Paper
Synthesis
unit such as 1 and 2 are desirable. We therefore initiated a
study to prepare such target compounds 1 and 2 by two dif-
ferent approaches, i.e., Cu-catalyzed [2+1] cycloaddition of
carbenoids derived from diazoketones 3 and conjugate ad-
dition of semi-stabilized sulfur ylides 6 to cyclic enones 4
and 5 (Scheme 1).
should be noted that a large excess of diazomethane (≥10
equiv) was required in order to achieve complete conver-
sion. As studied for diene 10b, addition of CaO19 was not
successful and only starting material could be recovered.
Diazoketones 3 were then submitted to catalytic cyclo-
propanation in the presence of Cu(acac)2 (10 mol%) (Table
1, entries 1 and 2) or CuSO4 (Table 1, entries 3–6) in toluene
under reflux following a procedure reported by Hudlicky.20
Vinylcyclopropanes 1a–c,e were isolated after chromato-
graphy in 81–85% yield, whereas VCPs 1d and 1f were ob-
tained in yields of 57% and 68%, respectively (Table 1, en-
tries 4 and 6). When considering the overall efficiency of
this sequence, it seems that the initial Wittig reaction is the
limiting step giving acceptable yields only for 10b and 10c
(Table 1, entries 2 and 3). In agreement with the litera-
ture,21 the cis diastereomer was formed as the major prod-
uct in all cases.
In order to examine the ylide route (Scheme 1, route b)
we prepared the starting tetrahydrothiophenium salts 6·X
according to a protocol reported by Chigboh.11 The results
are listed in Table 2. First, the respective allylic bromide 11
was treated with tetrahydrothiophene 13 (1 equiv) in
CH2Cl2 and the reaction mixture was stirred at room tem-
perature for the given time. After removal of the solvent,
the allylic sulfonium bromide 6a·Br was isolated after 6
days in 86% yield, being comparable to the literature (91%)
(Table 2, entry 1).11 In order to shorten the reaction time,
The aim was to test the scope and limitations of these
methods with respect to racemic 1-acyl-2-vinylcyclo-
propanes. Due to the fact that vinylcyclopropanes are
known for their propensity to undergo rearrangements, an-
other aim was to investigate the stereochemical integrity of
the cyclopropane ring toward cis/trans isomerization.
We first examined the Cu-catalyzed carbenoid route
(Scheme 1, route a). The results are summarized in Table 1.
The synthesis commenced with conversion of ethyl 4-bromo-
butyrate (7) into the known phosphonium salt 8,18 followed
by Z-selective Wittig reaction with enals 9 to give the Z,E-
dienes 10. It should be noted that Wittig reaction of acrole-
in (9a) required the use of NaHMDS in THF at –78 °C to r.t.
giving the dienylester 10a in a disappointingly low yield of
16% (Table 1, entry 1), whereas all other enals 9b–f were
converted in the presence of K2CO3 in toluene to afford the
esters 10b–f in moderate to good yields (30–85%) (Table 1,
entries 2–6). Saponification of esters 10 followed by se-
quential treatment with oxalyl chloride and diazomethane
according to a modified procedure by De Kimpe19 gave di-
azoketones 3 in moderate to good yields of 36–90%. It
Table 1 Synthesis of Vinylcyclopropanes 1 via Cu-Catalyzed [2+1] Annulation of Diazoketones 3
R3
R2
O
O
O
O
O
CuSO4 or
Cu(acac)2
H
H
H
H
R1
R1
1) NaOH, MeOH
reflux, 3 h
R1
H
9
H
H
OEt
+
Y
CO2Et
R2
R2
R3
R2
R3
R2
N2
toluene
reflux, 24 h
K2CO3, toluene
Temp., 2.5–18 h
2) (COCl)2, toluene
R3
R3
reflux, 24 h
3) CH2N2·Et2O
trans-1
cis-1
7 Y = Br
R1
R1
3
PPh3, 120 °C
16 h, quant.
10
8 Y = PPh3 Br
1,3,9,10
a
b
c
d
e
f
R1
R2
R3
H
H
H
H
H
H
H
H
Me
H
Me Ph
H
-(CH2)3-
H
Me Et
Entry
Temp (°C)
10
ad
Yield (%) E/Za
3
Yield (%)b E/Za
1
Yield (%)
E/Z
cis/trans
Yield (%)c
1
2
3
4
5
6
–78 to r.t.
16
85
65
55
34
30
n.d.e
20:80
a
b
c
d
e
f
36
90
71
64
80
37
14:86
n.d.e
af
bf
c
81
82
82
57
85
68
–
80:20
80:20
67:33
100:0g
80:20
50:50
<5
64
38
20
23
8
75
65
b
c
d
e
f
100:0
100:0
–
17:83
20:80
20:80
13:87
18:82
10:90
19:81
21:79
120
65
d
e
f
100:0
–
65
a E/Z ratios refer to the configuration of C4=C5 and were determined by 1H NMR.
b Overall yield over three steps starting from 10.
c Overall yield starting from 8.
d Prepared using NaHMDS in THF.
e Due to overlapping signals in the 1H NMR spectra, determination of E/Z ratios was not possible. However, in analogy to the derivatives with known E/Z ratios, we
assume that in the case of 10a and 3b the Z-isomer was formed predominantly.
f Cu(acac)2.
g No trace of the second diastereomer could be detected in the 1H NMR spectrum of the crude product.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–R

C
A. Zens et al.
Paper
Synthesis
the amount of 13 was increased to 11 equivalents following
a method described by Rousseau.22 However, the yield of
6a·Br decreased to 43% (Table 2, entry 2). When the respec-
tive allylic bromide 11a was treated with 3 equivalents of
13 in acetone instead of CH2Cl2, based on a protocol report-
ed by La Rochelle,23 the reaction indeed was complete after
24 hours affording 6a·Br in 92% yield (Table 2, entry 3). In
the case of sulfonium bromides 6b,d·Br, the replacement of
CH2Cl2 by acetone as the solvent also led to reduced reac-
tion times, albeit with lower yields in the range of 42–55%
(Table 2, entries 4, 5, 8 and 9). However, for cinnamyl bro-
mide (11c) and 2-phenylprop-2-enyl bromide (11h), the
use of acetone instead of CH2Cl2 provided similar high
yields of 86% and 97%, respectively, as compared to 97% and
91%, while simultaneously reducing the reaction time (Ta-
ble 2, entries 6, 7, 11 and 12).
In order to investigate the influence of the counterion of
6 on the subsequent cyclopropanation (Scheme 1, route b),
the preparation of the corresponding sulfonium tetrafluoro-
borates 6·BF4 was examined. First, the counterion exchange
was attempted by reaction of the generated sulfonium bro-
mide 6a·Br with 3 equivalents of NaBF4 in a solvent mixture
of CH2Cl2/acetone to give the desired 6a·BF4 in 35% yield
(Table 2, entry 13). Reducing the amount of NaBF4 to 1
equivalent significantly increased the yield of 6a·BF4 to 68%
(Table 2, entry 14). To gain access to 6a·BF4 by a one-pot re-
action, the allylic bromide 11a was treated with 13 and
subsequently NaBF4 (3 equiv) in CH2Cl2/H2O following the
procedure of Aggarwal.24 Disappointingly, after 2 days,
tetrahydrothiophenium tetrafluoroborate 6a·BF4 could be
isolated only in a low yield of 12% (Table 2, entry 15). How-
ever, this method proved to be efficient in the case of
Table 2 Synthesis of Sulfonium Salts 6·X from Allylic Compounds 11 and 12
R1
for 11
S
R2
R1
R3
S
13
Br
Y
R2
solvent
6a−d,g,h·Br
6a,d,f,i·BF4
NaBF4, CH2Cl2
solvent, 2 d
R3
HBF4·OEt2
Y = Br
Y = OH
11a−d,g,h
12a,d,f,i
for 12
Entry
Alkene
R1
R2
R3
13 (equiv)
Solvent
Time (d)
6·X
6a·Br
Yield (%)
1
2
11a
11a
11a
11b
11b
11c
11c
11d
11d
11g
11h
11h
6a·Br
6a·Br
11a
11c
12a
12a
12d
12f
H
H
H
1
11
3
CH2Cl2
CH2Cl2
acetone
CH2Cl2
acetone
CH2Cl2
acetone
CH2Cl2
acetone
acetone
CH2Cl2
acetone
acetone
acetone
H2O
6
1
1
7
2
9
2
6
2
1
7
2
2
2
2
2
2
2
9
12
7
86
43
92
89
55
97
86
98
42
46
91
97
35a
68b
12a
93
54
70
75
73
79
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
6a·Br
6a·Br
6b·Br
6b·Br
6c·Br
3
H
H
4
Me
Me
Ph
Ph
H
H
1
5
H
3
6
H
1
7
H
3
6c·Br
8
Me
Me
1
6d·Br
6d·Br
6g·Br
6h·Br
6h·Br
6a·BF4
6a·BF4
6a·BF4
6c·BF4
6a·BF4
6a·BF4
6d·BF4
6f·BF4
6i·BF4
9
H
3
10
11
12
13
14
15
16
17
18
19
20
21
–(CH2)4–
5
H
H
H
H
H
Ph
H
H
H
Ph
Ph
H
1
3
–
H
–
H
3
H
3
H2O
H
1
acetone
acetone
acetone
acetone
acetone
H
3
Me
–(CH2)3–
Et
3
3
12i
Me
a NaBF4 (3 equiv).
b NaBF4 (1 equiv).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–R

D
A. Zens et al.
Paper
Synthesis
6c·BF4, which was obtained in a good yield of 93% (Table 2,
entry 16). Based on an alternative procedure reported by
Rousseau,22 the allylic alcohol 12a was directly converted
into tetrafluoroborate 6a·BF4 in 54% yield in a one-pot fash-
ion by treatment with HBF4·OEt2 and 1 equivalent of 13 in
acetone for 2 days (Table 2, entry 17). By increasing the
amount of tetrahydrothiophene 13 from 1 to 3 equivalents,
the yield of 6a·BF4 could also be improved up to 70% (Table
2, entry 18). Following this protocol, sulfonium tetrafluo-
roborates 6d,f,i·BF4 were prepared in yields of 75%, 73% and
79%, respectively (Table 2, entries 19–21).
With tetrahydrothiophenium bromides 6·Br in hand, we
next studied the conjugate 1,4-addition to cyclopentenone
(4) based on the protocol of Chigboh.11 The results are sum-
marized in Table 3. Deprotonation of allylsulfonium bro-
mide 6a·Br with LiOtBu in DMSO at room temperature gave
the corresponding ylide, which reacted with 4 to afford a
47% yield of vinylcyclopropane 1a as a diastereomeric mix-
ture (50:50), which could not be separated by chromatogra-
phy (Table 3, entry 1). Analogously, 1-(but-2-enyl)- and 1-
(2-phenylprop-2-enyl)tetrathiophenium bromides 6b,c·Br
and LiOtBu provided VCPs 1b and 1c in yields of 55% and
62% as inseparable mixtures of cis/trans isomers (Table 3,
entries 2 and 3). Vinylcyclopropanes 1d and 1g with an α-
substituent on the allylic moiety were isolated in low yields
as equimolar mixtures of cis/trans isomers (Table 3, entries
4 and 5). Due to the high volatility of the vinylcyclopro-
panes, solvent evaporation over prolonged times was avoid-
ed, which in some cases resulted in residual solvent peaks
in the NMR spectra. The overall yields of the sulfur ylide
route (Table 3) were indeed similar to those of the copper-
catalyzed procedure (Table 1), but the number of synthetic
steps was reduced.
The reactions of sulfonium salts 6·X with cyclohexenone
(5) proceeded more sluggishly compared to those with
cyclopentenone (4). As can be seen from Table 4, treatment
of allylsulfonium bromide 6a·Br with LiOtBu (method A)
and subsequent addition of the resulting ylide to cyclohexe-
none (5) gave VCP 2a in a diastereomeric ratio (cis/trans) of
35:65. In contrast to the cyclopentenone-derived VCPs 1,
the diastereomers could be separated by flash chromatog-
raphy to afford cis-2a and trans-2a in 9% and 17% isolated
yields, respectively (Table 4, entry 1). The addition of 1-
(but-2-enyl)tetrahydrothiophenium bromide (6b·Br) to 5 in
the presence of LiOtBu gave 19% of cis-2b and 14% of trans-
2b (Table 4, entry 2).
When 1-(3-phenylprop-2-enyl)tetrahydrothiophenium
bromide (6c·Br) was treated with LiOtBu and cyclohexen-
one (5) in DMSO, 40% of cis-2c and 15% of trans-2c were
isolated (Table 4, entry 3). In the case of 6d·Br, 9% of cis-2d,
10% of trans-2d and 11% of the unexpected by-product 16
were obtained (Table 4, entry 4). The structure of 16 was
determined by NMR spectroscopy (see the Supporting In-
formation). Treatment of 6h·Br (Table 4, entry 5) with LiOt-
Bu and subsequent addition of the resulting ylide to cyclo-
hexenone (5) gave, apart from 6% of cis-2h and 12% of
trans-2h, 12% of the substituted tetrahydrothiophene 15,
obviously arising from a [2,3]-sigmatropic rearrangement
(Scheme 2). Under the used conditions, a vicinal substitu-
ent at the 2-position of the allylic moiety (i.e., R3 ≠ H), e.g.,
in bromides 6d,h, decreased the yields and favored by-
product formation (Table 4, entries 4 and 5).
Table 3 Vinylcyclopropanes 1 from Sulfonium Bromides 6·Br and Cy-
clopentenone (4)
In a further experiment, we anticipated that a positive
effect on the yield of the vicinal substituted VCP 2d might
arise from counterion exchange. However, the reaction of
6d·BF4 with 5 in the presence of LiOtBu gave only 3% of cis-
2d (Table 4, entry 6). Also, the yields of both VCPs 2i,f de-
rived from disubstituted sulfonium salts 6i·BF4 and 6f·BF4
(Table 4, entries 7 and 8) were much lower than those of cy-
clopropanes 2a–c with R3 = H. When allylsulfonium tetra-
fluoroborate 6a·BF4 was employed, 22% of cis-2a and 14% of
trans-2a could be isolated (Table 4, entry 9). Consequently,
the counterion in the unsubstituted allylsulfonium tetra-
fluoroborate 6a·BF4 improved the yield of VCP 2a. In con-
trast, no beneficial effect was observed for sulfonium salt
6c·BF4 as compared to 6c·Br (Table 4, entries 3 and 10).
As the cyclopropanation of cyclohexenone (5) with 1-
(3-phenylprop-2-enyl)tetrahydrothiophenium bromide (6c·Br)
(Table 4, entry 3) gave the best results, further investiga-
tions on the reaction were carried out with this system. An
excess of KOtBu was reported to improve generally the yield
of cyclopropanes.13d Initially, the sulfonium salt 6c·Br was
treated with 3.4 equivalents of KOtBu in THF (Table 4, entry
11), but the desired product 2c was obtained only in trace
R1
13
S
R2
11a−d,g
(see Table 2)
R3
6·Br
1, 6 R1 R2 R3
Br
a
b
c
d
g
H
H
H
H
H
H
H
O
Me
Ph
H
−(CH2)4−
H
H
LiOtBu, DMSO
Me
r.t., 1 h
4
O
O
H
H
H
R1
R1
H
H
+
R2
R2
R3
R3
H
cis-1
trans-1
Entry
6·Br
1
Yield (%) cis/trans
Overall yield (%)a
1
2
3
4
5
6a·Br
6b·Br
6c·Br
6d·Br
6g·Br
1a
47
55
62
20
17
50:50
80:20
67:33
50:50
50:50
43
49
58
19
8b
1b
1c
1d
1g
a Yield over two steps starting from bromides 11.
b Complete conversion (by GC), however, numerous unidentified by-prod-
ucts were formed.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–R

E
A. Zens et al.
Paper
Synthesis
Table 4 Vinylcyclopropanes 2 from Sulfonium Salts 6·X and Cyclohexenone (5)
R1
O
O
O
LiOtBu (A)
or KOtBu (B)
DMSO, r.t.
H
H
H
R1
R1
S
R2
H
H
+
+
+ by products
14−17
R3
6·X
R1 R2 R3
R2
R2
X
R3
R3
H
cis-2
5
trans-2
O
O
Ph
2, 6
a
b
c
d
f
h
i
H
H
H
H
H
H
H
H
H
Me
Ph
H
H
*
H
Me
S
S
Ph
O
*
Ph
−(CH2)3−
Ph
Et Me
14
15
16
17
*
H
Entry
6·X
6a·Br
Method
Time (h)
2
cis/trans
Yield cis-2 (%)
Yield trans-2 (%)
By-product
1
2
A
A
A
A
A
A
A
A
A
A
Ba
B
24
48
0.5
19
48
48
48
48
21
48
24
1
2a
2b
2c
2d
2h
2d
2i
35:65
56:44
73:27
47:53
31:69
>99:1
67:33
35:65
61:39
71:29
–
9
19
40
9
17
14
15
10
12
–
–
6b·Br
6c·Br
–
3
–
4
6d·Br
6h·Br
6d·BF4
6i·BF4
6f·BF4
6a·BF4
6c·BF4
6c·Br
16 (11%)
5
6
15 (12%)
6
3
–
7
2
1
–
8
2f
6
11
14
15
–
–
9
2a
2c
2c
2c
22
36
–
–
10
11
12
–
14 (100%)b
17 (76%)
6c·Br
–
–
15
a In THF, KOtBu (3.4 equiv).
b Determined by GC.
amounts, and sulfide 14 was generated instead, obviously
via [2,3]-sigmatropic rearrangement of ylide 18 (Scheme 2).
To suppress the formation of 18, the amount of KOtBu was
decreased, and THF was replaced by DMSO (Table 4, entry
12). The formation of 14 could indeed be avoided, but the
reaction led to trans-2c in only 15% yield, and an unexpect-
ed tricyclic compound 17 was isolated as the major product
(76%).
the Cu-bisoxazoline-catalyzed reaction of Cu-diazoester
with styrene as reported by Rasmussen26 (Scheme 3). Pre-
sumably, the strongly bent geometry of the tether between
the ketone and the Z-alkene unit in B leading to the trans-
cyclopropane trans-1 is disfavored as long as R3 carries only
small substituents. Such geometric constraints might ex-
plain a kinetic preference for A providing cis-1, while the
A proposed mechanistic rationale for the formation of
by-products 14, 15, and 17 is shown in Scheme 2.
R2 R1
R3
R3
1'
[2,3]-sigmatropic
rearrangement
In the presence of a base, deprotonation of 6c,h·Br at
C-1′ instead of C-1 should lead to ylide 18, which undergoes
a [2,3]-sigmatropic rearrangement13d,25 to give sulfides 14
and 15. This effect even dominated with an excess of base
(Table 4, entry 11). In the case of tricycle 17, presumably
the vinylcyclopropane 2c undergoes base-induced keto–
enol tautomerism toward enolate 19. Cyclization of enolate
19 followed by reprotonation should lead to the formation
of the tricyclic product 17, the structure of which could be
determined by NMR spectroscopy (see the Supporting In-
formation).
base
S
R2
S
R2
1
S
R3
14 R2 = Ph
15 R3 = Ph
R1
R1
Br
6c,h·Br
18
O
O
H
H
H
H
base
keto–enol
tautomerism
2c
19
H
H
cyclization
O
O
O
H
In order to rationalize the preferred formation of the cis-
configured cyclopropanes 1 obtained via the Cu-catalyzed
reaction, we propose two possible transition states A and B
in agreement with calculated transition-state structures for
17
Scheme 2 By-products in the cyclopropanation of sulfonium salts 6
with cyclohexenone (5)
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–R

F
A. Zens et al.
Paper
Synthesis
diastereomer trans-1 should be favored from a thermo-
dynamic point of view based on DFT calculations of prod-
ucts 1a–d,g and 2c at the BP86/def2-TZVP27–32 level of theo-
ry using TURBOMOLE33–40 (for details see the Supporting In-
formation).
ficiency of this sequence, it seems that the initial Wittig re-
action is the limiting step giving only acceptable yields in
two cases. Alternatively, we have described a second short
route to 1-acyl-2-vinylcyclopropanes 1 and 2 with simple
alkyl or aryl substituents on the alkene moiety. The yields
of vinylcyclopropanes 1 from semi-stabilized sulfur ylides
6·X and cyclopentenone (4) range from 17% up to 62%. It
was found that substitution at the terminal position of the
alkenes (R2 ≠ H) has a positive effect on the yield of the re-
action compared to the unsubstituted vinylcyclopropanes.
In contrast, a vicinal R3 substituent in the allylsulfonium
salt exerts unfavorable steric hindrance resulting in a lower
yield. Further investigations have shown that the reaction
of sulfonium salts 6·X with cyclohexenone (5) proceeded
less straightforwardly as compared to the corresponding re-
actions with cyclopentenone, resulting in the formation of
[2,3]-sigmatropic rearrangement products 14 and 15 and a
unique tricyclic ketone 17 among others. While the experi-
mentally observed prevalence of the Cu-catalyzed cyclopro-
panation toward the diastereomers cis-1 is in good agree-
ment with results from the literature,21 the diastereoselec-
tivity of the sulfur-ylide-mediated cyclopropanation
requires a more detailed future theoretical investigation.
R2
R1
R2
R1
H
H
O
O
R3
R3
H
H
H
H
Cu
Cu
A
B
cis-1
trans-1
favorable due to a
π–π interaction between
the carbonyl unit and the C=C bond
Scheme 3 Proposed possible transition states A and B in the Cu-cata-
lyzed cyclopropanation of diazoketones on the basis of Ref. 27
In the case of the semi-stabilized sulfur-ylide-promoted
cyclopropanations, a mechanistic rationale to explain the
experimentally observed diastereoselectivities is less clear-
cut. As shown in Scheme 4, the nucleophilic conjugate addi-
tion of ylide 6·X at C-β of cyclopentenone (4) [or cyclohexe-
none (5)] results in two different betaine intermediates 20
and 21. These betaines can directly undergo intramolecular
attack of the enolate and displacement of the tetrahydro-
thiophene to give cis- and trans-cyclopropanes cis-1 and
trans-1, respectively. Whereas steric interactions between
the terminal alkene substituents R1 and R2 and the enolate
moiety seem to disfavor betaine intermediate 20, a base-
promoted epimerization between 20 and 21 according to
previous reports by Aggarwal13a,41 as well as counterion ef-
All chemicals were received from commercial suppliers and used
without further purification unless otherwise noted. All solvents
were distilled using standard procedures. Oxygen- and moisture-sen-
sitive substances and reactions were handled and carried out under a
nitrogen atmosphere with dried solvents. Flash chromatography was
performed on Fluka silica gel 60 (40–63 μm) using the indicated sol-
vents. Infrared spectra were recorded on a Bruker ALPHA FT-IR spec-
trophotometer. 1H and 13C NMR spectra were recorded in CDCl3, un-
less otherwise noted, on Bruker AV300, 400, 500 and 700 instru-
ments, referenced to the residual solvent resonance as the internal
standard. The reaction progress of the cyclopropanation via the sulfur
ylide methodology was monitored by gas chromatography (GC) on a
Hewlett Packard HP6890 gas chromatograph, equipped with a HP-5
column (30 m × 0.32 mm), using the following program: H2 carrier
gas, start temperature 80 °C, heating rate 10 °C/min, end temperature
300 °C. HRMS was carried out on a Finnigan MAT95 mass spectrome-
ter with a Bruker Daltonics micro-TOF-Q analyzer (ESI, EI). See the
Supporting Information for the structure determination of by-prod-
ucts 16 and 17. CAUTION! Due to its explosive nature, full safety pre-
cautions should be taken when handling diazomethane.
–
fects (Br– vs BF4 and Li+ vs K+) have to be taken into ac-
count.
O
O
H
R1
H
H
H
O
H
R1
R2
S
R3
H
X
R3
20
R3
R2
trans-1
S
R2
4
base-promoted
epimerization
+
DMSO
R1
X
O
O
H
R1
R1
ylide 6·X
H
H
S
R2
R2
H
(Z)-Ethyl Hepta-4,6-dienoate (10a)42
R3
R3
H
H
Phosphonium salt 8 (10.0 g, 21.9 mmol) was suspended in abs THF
(40 mL) at –78 °C under an N2 atmosphere and a solution of NaHMDS
(20 mL, 2 M in THF, 40.0 mmol) was added. After stirring for 30 min,
freshly distilled acrolein (9a) (7.31 mL, 6.16 g, 110 mmol) was added
at room temperature. After additional stirring for 2 h, the reaction
was quenched with H2O (150 mL), the layers were separated, and the
aq layer was extracted with Et2O (3 × 100 mL). The combined organic
layers were dried (MgSO4) and concentrated. The residue was puri-
fied by flash chromatography on SiO2 (hexanes/EtOAc, 50:1, Rf = 0.35)
cis-1
X
21
Scheme 4 Proposed possible pathway to cis- and trans-cyclopropanes
via sulfur ylide 6·X
In conclusion, we first examined a Cu2+-catalyzed car-
benoid route, which allows access to a set of different race-
mic 1-acyl-2-vinylcyclopropanes 1 in 6 steps with overall
yields from <5% up to 64%. When considering the overall ef-
Yield: 532 mg, 2.60 mmol (16%); pale yellow oil.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–R

G
A. Zens et al.
Paper
Synthesis
1H NMR (300 MHz, CDCl3): δ = 1.25 (t, J = 7.2 Hz, 3 H, -CH2CH3), 2.35–
2.40 (m, 2 H, 2-H), 2.48–2.65 (m, 2 H, 1-H), 4.12 (q, J = 7.2 Hz, 2 H, -
CH2CH3), 5.08–5.24 (m, 2 H, 6-H), 5.29–5.49 (m, 1 H, 3-H), 5.99–6.07
(m, 1 H, 4-H), 6.58–6.71 (m, 1 H, 5-H).
13C NMR (75 MHz, CDCl3): δ = 14.4 (-CH2CH3), 23.4 (C-2), 34.3 (C-1),
60.5 (-CH2CH3), 117.9 (C-6), 130.2 (C-4), 130.6 (C-5), 131.9 (C-3),
173.1 (C=O).
Yield: 807 mg, 4.79 mmol (55%); pale yellow oil.
FT-IR (ATR): 3082 (w), 2980 (w), 1735 (s), 1639 (w), 1445 (w), 1372
(w), 1349 (w), 1248 (w), 1158 (m), 1097 (w), 1096 (w), 1064 (w),
1037 (w), 967 (w), 893 (w), 767 (w), 721 (w), 696 (w), 591 (w) cm–1
.
1H NMR (300 MHz, CDCl3): δ = 1.26 (t, J = 7.2 Hz, 3 H, CH2-CH3), 1.88
(s, 3 H, 7-H), 2.35–2.42 (m, 2 H, 2-H), 2.56–2.64 (m, 2 H, 1-H), 4.13 (q,
J = 7.2 Hz, 2 H, CH2CH3), 4.85 (s, 1 H, 6-Ha), 4.97 (s, 1 H, 6-Hb), 5.36 (dt,
J = 11.9, 7.2 Hz, 1 H, 3-H), 5.88 (d, J = 11.9 Hz, 1 H, 4-H).
(4Z,6E)-Ethyl Octa-4,6-dienoate (10b)
13C NMR (75 MHz, CDCl3): δ = 14.4 (-CH2CH3), 23.4 (C-2), 24.3 (C-7),
34.8 (C-1), 60.5 (CH2CH3), 115.8 (C-6), 129.2 (C-3), 132.2 (C-4), 141.6
(C-5), 173.2 (C=O).
A suspension of crotonaldehyde (9b) (10.0 g, 21.9 mmol), 8 (10.0 g,
21.9 mmol) and K2CO3 (12.1 g, 87.5 mmol) in toluene (40 mL) was
heated at 75 °C for 16 h. The reaction was quenched with H2O, the
layers were separated, and the aq layer was extracted with CH2Cl2
(3 × 20 mL). The combined organic layers were dried (MgSO4) and
concentrated. The residue was purified by distillation (88 °C, 20
mbar).
MS (EI): m/z (%) = 168.1 (45), 153.1 (1), 139.1 (2), 123.1 (20), 111.1
(1), 95.1 (100), 79.0 (24), 67.0 (9), 61.6 (1), 55.0 (7), 41.1 (7).
HRMS (EI): m/z [M]+ calcd for C10H16O2: 168.1150; found: 168.1142.
(4Z,6E)-Ethyl 6-Ethylocta-4,6-dienoate (10e)
Yield: 3.12 g, 18.6 mmol (85%); colorless oil.
A suspension of 9e (8.59 g, 87.5 mmol), 8 (10.0 g, 21.9 mmol) and K2-
CO3 (12.1 g, 87.5 mmol) in toluene (80 mL) was heated at 65 °C for 18
h. The reaction work-up was as described for 10b. The residue was puri-
fied by flash chromatography on SiO2 (hexanes/EtOAc, 100:1, Rf = 0.36).
FT-IR (ATR): 3021 (w), 2981 (w), 2914 (m), 1711 (s), 1655 (w), 1448
(w), 1371 (w), 1348 (w), 1225 (w), 1164 (m), 1097 (w), 1040 (w), 984
(w), 946 (w), 925 (w), 858 (w), 821 (w), 791 (w), 733 (w), 591 (w) cm–1
.
1H NMR (500 MHz, CDCl3): δ = 1.25 (t, J = 6.9 Hz, 3 H, CH2-CH3), 1.77
(d, J = 6.3 Hz, 3 H, 7-H), 2.34–2.39 (m, 2 H, 2-H), 2.44–2.51 (m, 2 H, 1-H),
4.12 (q, J = 6.9 Hz, 2 H, CH2CH3), 5.24 (dt, J = 10.7, 8.2 Hz, 1 H, 3-H), 5.49–
5.74 (m, 1 H, 6-H), 5.92–6.06 (m, 1 H, 4-H), 6.28–6.37 (m, 1 H, 5-H).
13C NMR (125 MHz, CDCl3): δ = 14.4 (-CH2CH3), 18.4 (C-7), 23.3 (C-2),
34.5 (C-1), 60.5 (CH2CH3), 126.8 (C-5), 127.0 (C-3), 130.0 (C-4), 130.2
(C-6), 173.2 (C=O).
Yield: 1.47 g, 7.49 mmol (34%); pale yellow oil.
FT-IR (ATR): 2964 (m), 2929 (m), 2874 (w), 1736 (vs), 1455 (w), 1371
(m), 1348 (w), 1259 (m), 1156 (s), 1097 (m), 1022 (m), 966 (m), 940
(w), 849 (w), 802 (m), 742 (w), 579 (w) cm–1
.
1H NMR (300 MHz, CDCl3): δ = 0.94 (t, J = 7.6 Hz, 3 H, 7′-H), 1.26 (t, J =
7.2 Hz, 3 H, -CH2CH3), 1.68 (d, J = 6.8 Hz, 3 H, 7-H), 2.02–2.25 (m, 2 H,
H-2), 2.32–2.56 (m, 4 H, 1-H, 6′-H), 4.13 (q, J = 6.8 Hz, 2 H, -CH2CH3),
5.24–5.71 (m, 2 H, 3-H, 6-H), 5.81 (d, J = 11.7 Hz, 1 H, 4-H).
13C NMR (75 MHz, CDCl3): δ = 13.0 (C-7′), 13.3 (C-7), 14.4 (-CH2CH3),
23.5 (C-6′), 24.2 (C-2), 35.0 (C-1), 60.5 (-CH2CH3), 123.1 (C-6), 128.0
(C-3), 132.8 (C-4), 139.0 (C-5), 173.4 (C=O).
MS (EI): m/z (%) = 168.1 (81), 139.1 (2), 123.1 (24), 111.1 (1), 94.1
(100), 81.0 (78), 67.0 (11), 60.0 (2), 53.0 (10), 41.1 (13).
HRMS (ESI): m/z [M + Na]+ calcd for C10H16O2Na: 191.1043; found:
191.1052.
MS (ESI): m/z = 219.13 [M + Na]+, 151.09.
HRMS (ESI): m/z [M + Na]+ calcd for C12H20O2Na: 219.1356; found:
(4Z,6E)-Ethyl 7-Phenylhepta-4,6-dienoate (10c)
A suspension of 9c (13.3 g, 101 mmol), 8 (9.30 g, 20.3 mmol) and K2-
CO3 (14.0 g, 101 mmol) in toluene (60 mL) was heated at 65 °C for 18
h. The reaction work-up was as described for 10b. The residue was puri-
fied by flash chromatography on SiO2 (hexanes/EtOAc, 100:1, Rf = 0.23).
219.1345.
(Z)-Ethyl 5-(Cyclopent-1-en-1-yl)pent-4-enoate (10f)
A suspension of 9f (1.00 g, 10.4 mmol), 8 (19.0 g, 41.6 mmol) and K2-
CO3 (5.74 g, 41.6 mmol) in toluene (100 mL) was heated at 65 °C for
16 h. The reaction work-up was as described for 10b. The residue was pu-
rified by flash chromatography on SiO2 (hexanes/EtOAc, 100:1, Rf = 0.24).
Yield: 3.06 g, 13.3 mmol (65%); pale yellow oil.
1H NMR (300 MHz, CDCl3): δ = 1.26 (t, J = 7.2 Hz, 3 H, -CH2CH3), 2.41–
2.46 (m, 2 H, 2-H), 2.63 (q, J = 7.4 Hz, 2 H, 1-H), 4.14 (q, J = 7.2 Hz, 2 H,
-CH2CH3), 5.49 (dt, J = 10.8, 7.6 Hz, 1 H, 3-H), 6.20 (dd, J = 10.9, 10.8
Hz, 1 Hz, 4-H), 6.44–6.58 (m, 1 H, 5-H), 7.00–7.13 (m, 1 H, 6-H), 7.18–
7.25 (m, 1 H, p-ArH), 7.27–7.44 (m, 4 H, o-ArH, m-ArH).
13C NMR (75 MHz, CDCl3): δ = 14.4 (-CH2CH3), 23.7 (C-2), 34.4 (C-1),
60.6 (CH2CH3), 124.1 (p-Ar), 126.6 (o-Ar), 127.7 (C-4), 128.8 (m-Ar),
130.1 (C-5), 130.3 (C-6), 133.1 (C-3), 137.6 (i-Ar), 173.1 (C=O).
Yield: 607 mg, 3.12 mmol (30%); E/Z = 1:7; pale yellow oil.
FT-IR (ATR): 2952 (w), 2844 (w), 1733 (vs), 1444 (w), 1371 (w), 1348
(w), 1297 (w), 1159 (s), 1097 (w), 1036 (w), 959 (w), 820 (w), 745
(w), 502 (w) cm–1
.
1H NMR (300 MHz, CDCl3): δ = 1.25 (t, J = 7.2 Hz, 3 H, -CH2CH3), 1.87–
1.97 (m, 2 H, 8-H), 2.32–2.63 (m, 8 H, 1-H, 2-H, 7-H, 9-H), 4.13 (q, J =
7.2 Hz, 2 H, -CH2CH3), 5.29 (dt, J = 11.5, 7.5 Hz, 1 H, 3-H), 5.62–5.70
(m, 1 H, 6-H), 6.05 (d, J = 11.5 Hz, 1 H, 4-H).
13C NMR (75 MHz, CDCl3): δ = 14.4 (-CH2CH3), 24.1 (C-2), 24.6 (C-8),
32.3 (C-7), 34.9 (C-1), 35.1 (C-9), 60.5 (-CH2CH3), 126.7 (C-6), 128.3
(C-3), 132.2 (C-4), 141.4 (C-5), 173.2 (C=O).
MS (EI): m/z (%) = 194.1 (76) [M]+, 165.1 (5), 149.1 (24), 131.1 (13),
120.1 (68), 106.1 (100), 91.0 (59), 79.0 (50), 67.0 (20), 60.0 (2), 55.0
(7), 41.0 (13), 29.0 (11).
MS (ESI): m/z (%) = 253.12 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C15H18O2Na: 253.1199; found:
253.1198.
(Z)-Ethyl 6-Methylhepta-4,6-dienoate (10d)
A suspension of 9d (4.00 g, 8.76 mmol), 8 (4.84 g, 35.1 mmol) and K2-
CO3 (4.84 g, 35.1 mmol) in toluene (40 mL) was heated at 120 °C for 16 h.
The reaction work-up was as described for 10b. The residue was purified
by flash chromatography on SiO2 (hexanes/EtOAc, 100:1, Rf = 0.40).
HRMS (EI): m/z [M]+ calcd for C12H18O2: 194.1307; found: 194.1310.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–R

H
A. Zens et al.
Paper
Synthesis
Saponification; General Procedure
(Z)-6-Methylhepta-4,6-dienoic Acid
To a solution of ester 10a–f in methanol (1 mL/mmol) was added aq
NaOH (10% in H2O, 1 mL/mmol) and the reaction was heated under
reflux for 3 h. After cooling to room temperature, the solution was
acidified with aq HCl (3 M), and the layers were separated. The aq lay-
er was extracted with CH2Cl2. The combined organic layers were
dried (MgSO4) and concentrated. The residue was purified by flash
chromatography on SiO2 (hexanes/EtOAc, 10:1).
Prepared from 10d (790 mg, 4.69 mmol).
Yield: 587 mg, 4.19 mmol (89%); colorless oil; Rf = 0.18 (hexanes/EtO-
Ac, 10:1).
FT-IR (ATR): 2969 (m), 2918 (m), 1704 (vs), 1641 (w), 1412 (m), 1373
(m), 1337 (w), 1279 (m), 1247 (m), 1208 (m), 1159 (w), 1007 (w), 890
(s), 838 (w), 769 (m), 676 (w), 530 (w) cm–1
.
1H NMR (300 MHz, CDCl3): δ = 1.88 (s, 3 H, 7-H), 2.41–2.47 (m, 2 H, 2-
H), 2.57–2.65 (m, 2 H, 1-H), 4.85 (s, 1 H, 6-Ha), 4.98 (s, 1 H, 6-Hb), 5.37
(dt, J = 11.7, 7.2 Hz, 1 H, 3-H), 5.89 (d, J = 11.7 Hz, 1 H, 4-H).
13C NMR (75 MHz, CDCl3): δ = 23.4 (C-2), 23.9 (C-7), 34.5 (C-1), 115.9
(C-6), 128.7 (C-3), 132.5 (C-4), 141.5 (C-5); quaternary carbon not ob-
served.
(Z)-Hepta-4,6-dienoic Acid43
Prepared from 10a (640 mg, 4.15 mmol).
Yield: 417 mg, 3.32 mmol (80%); colorless oil; Rf = 0.14 (hexanes/EtO-
Ac, 10:1).
1H NMR (300 MHz, CDCl3): δ = 2.35–2.60 (m, 4 H, 1-H, 2-H), 5.14 (d,
J = 9.8 Hz, 1 H, 6-Ha), 5.22 (d, J = 16.6 Hz, 1 H, 6-Hb), 5.35–5.49 (dt,
J = 10.9, 7.1 Hz, 1 H, 3-H), 6.05 (dd, J = 10.9, 10.9 Hz, 1 H, 4-H), 6.56–
6.72 (m, 1 H, 5-H).
MS (ESI): m/z = 463.21, 441.23, 371.18, 301.14, 209.12, 139.08
[M – H]+.
HRMS (ESI): m/z [M – H]+ calcd for C8H11O2: 139.0765; found:
139.0758.
13C NMR (75 MHz, CDCl3): δ = 23.3 (C-2), 34.1 (C-1), 118.2 (C-6), 129.8
(C-4), 130.9 (C-5), 131.8 (C-3), 179.3 (C=O).
(4Z,6E)-6-Ethylocta-4,6-dienoic Acid
Prepared from 10e (430 mg, 2.19 mmol).
(4Z,6E)-Octa-4,6-dienoic Acid
Yield: 341 mg, 2.03 mmol (97%); colorless oil; Rf = 0.24 (hexanes/EtO-
Ac, 5:1).
Prepared from 10b (900 mg, 5.35 mmol).
Yield: 689 mg, 4.92 mmol (92%); colorless oil; Rf = 0.11 (hexanes/EtO-
Ac, 10:1).
FT-IR (ATR): 2965 (m), 2932 (m), 2874 (m), 1707 (vs), 1412 (m), 1376
(m), 1278 (m), 1248 (m), 1208 (m), 1158 (m), 1061 (w), 939 (m), 851
FT-IR (ATR): 2970 (m), 2930 (m), 2152 (w), 1709 (vs), 1417 (m), 1376
(m), 742 (w), 592 (w) cm–1
.
(m), 1174 (s), 1056 (s), 972 (s), 922 (m), 821 (m), 655 (w) cm–1
.
1H NMR (700 MHz, CDCl3): δ = 0.94 (t, J = 7.4 Hz, 3 H, 7′-H), 1.68 (d,
J = 7.1 Hz, 3 H, 7-H), 2.08–2.17 (m, 2 H, 2-H), 2.38–2.54 (m, 4 H, 1-H,
6′-H), 5.30–5.43 (m, 2 H, 3-H, 6-H), 5.81 (d, J = 11.5 Hz, 1 H, 4-H).
13C NMR (175 MHz, CDCl3): δ = 12.9 (C-7), 13.2 (C-7′), 23.4 (C-6′), 23.9
(C-2), 34.7 (C-1), 123.1 (C-6), 127.6 (C-3), 133.1 (C-4), 138.8 (C-5),
179.7 (C=O).
1H NMR (300 MHz, CDCl3): δ = 1.78 (d, J = 6.8 Hz, 3 H, 7-H), 2.37–2.55
(m, 4 H, 1-H, 2-H), 5.21–5.30 (m, 1 H, 3-H), 5.51–5.78 (m, 1 H, 6-H),
5.96–6.04 (m, 1 H, 4-H), 6.28–6.38 (m, 1 H, 5-H).
13C NMR (75 MHz, CDCl3): δ = 18.5 (C-7), 23.0 (C-2), 34.2 (C-1), 126.5
(C-5), 126.6 (C-3), 130.2 (C-4), 130.6 (C-6), 179.2 (C=O).
MS (ESI): m/z = 139.08 [M – H]+, 135.04.
HRMS (ESI): m/z [M – H]+ calcd for C8H11O2: 139.0765; found:
MS (ESI): m/z = 235.10, 167.11 [M – H]+.
HRMS (ESI): m/z [M – H]+ calcd for C10H15O2: 167.1078; found:
139.0758.
167.1081.
(4Z,6E)-7-Phenylhepta-4,6-dienoic Acid
Prepared from 10c (2.00 g, 8.70 mmol).
(Z)-5-(Cyclopent-1-en-1-yl)pent-4-enoic Acid
Prepared from 10f (250 mg, 1.29 mmol).
Yield: 1.56 g, 7.71 mmol (89%); colorless oil; Rf = 0.18 (hexanes/EtOAc,
10:1).
Yield: 176 mg, 1.06 mmol (82%); colorless oil; Rf = 0.20 (hexanes/EtO-
Ac, 5:1).
FT-IR (ATR): 3025 (m), 1741 (m), 1703 (vs), 1595 (w), 1573 (w), 1492
(w), 1449 (m), 1410 (m), 1335 (w), 1282 (w), 1241 (w), 1210 (m),
1156 (w), 1119 (w), 1072 (w), 1028 (w), 988 (m), 945 (m), 911 (w),
1H NMR (300 MHz, CDCl3): δ = 1.86–1.97 (m, 2 H, 8-H), 2.33–2.65 (m,
8 H, 1-H, 2-H, 7-H, 9-H), 5.29 (dt, J = 11.7, 7.2 Hz, 1 H, 3-H), 5.63–5.71
(m, 1 H, 6-H), 6.05 (d, J = 11.7 Hz, 1 H, 4-H).
13C NMR (75 MHz, CDCl3): δ = 24.1 (C-2), 24.3 (C-8), 32.6 (C-7), 34.7
(C-1), 35.1 (C-9), 127.0 (C-6), 127.8 (C-3), 132.4 (C-4), 141.3 (C-5),
179.8 (C=O).
858 (w), 737 (m), 692 (m) cm–1
.
1H NMR (300 MHz, CDCl3): δ = 2.46–2.52 (m, 2 H, 2-H), 2.62 (q, J = 7.4
Hz, 2 H, 1-H), 5.48 (dt, J = 10.6, 7.5 Hz, 1 H, 3-H), 6.20 (dd, J = 10.9,
10.8 Hz, 1 Hz, 4-H), 6.43–6.60 (m, 1 H, 5-H), 6.99–7.12 (m, 1 H, 6-H),
7.19–7.26 (m, 1 H, p-ArH), 7.27–7.47 (m, 4 H, o-ArH, m-ArH).
13C NMR (75 MHz, CDCl3): δ = 23.3 (C-2), 34.1 (C-1), 123.9 (p-Ar),
126.6 (o-Ar), 127.8 (C-4), 128.8 (m-Ar), 129.8 (C-5), 130.4 (C-6), 133.3
(C-3), 137.5 (i-Ar), 179.0 (C=O).
HRMS (ESI): m/z [M – H]+ calcd for C10H13O2: 165.0921; found:
165.0913.
(Z)-1-Diazoocta-5,7-dien-2-one (3a)20
The acid (600 mg, 4.76 mmol) was dissolved in pentane (10 mL) un-
der an N2 atmosphere and oxalyl chloride (1.63 mL, 2.42 g, 19.0
mmol) was added. After 2 h of stirring at room temperature, the sol-
vent was removed, and the resulting acid chloride was added to a dia-
zomethane solution (100 mL, 0.50 M, 50.0 mmol) at 0 °C. After 30
min, the solution was allowed to warm to room temperature and stir-
MS (ESI): m/z = 235.10 [M + Na]+, 217.09, 201.09 [M – H]+, 157.10,
101.02.
HRMS (ESI): m/z [M – H]+ calcd for C13H13O2: 201.0910; found:
201.0912.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–R

I
A. Zens et al.
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Synthesis
ring was continued for 3 h. The mixture was concentrated to remove
excess diazomethane and solvent. The residue was purified by flash
chromatography on SiO2 (hexanes/EtOAc, 10:1, Rf = 0.24).
(Z)-1-Diazo-7-methylocta-5,7-dien-2-one (3d)
The acid (580 mg, 4.14 mmol) was dissolved in toluene (10 mL) under
an N2 atmosphere and oxalyl chloride (1.42 mL, 2.10 g, 16.6 mmol)
was added. After 2 h of stirring at room temperature, the solvent was
removed, and the resulting acid chloride was added to a diazometh-
ane solution (75 mL, 0.55 M, 41.2 mmol) at 0 °C. After 30 min, the
solution was allowed to warm to room temperature and stirring was
continued for 3 h. The mixture was concentrated to remove excess di-
azomethane and solvent. The residue was purified by flash chroma-
tography on SiO2 (hexanes/EtOAc, 10:1, Rf = 0.24).
Yield: 324 g, 2.16 mmol (45%); yellow oil.
1H NMR (300 MHz, CDCl3): δ = 2.33–2.46 (m, 2 H, 2-H), 2.47–2.58 (m, 2
H, 1-H), 5.05–5.30 (m, 3 H, CH, CHNN, 6-H), 5.41 (dt, J = 10.5, 7.5 Hz, 1
H, 3-H), 6.02 (dd, J = 10.5, 10.5 Hz, 1 H, 4-H), 6.55–6.70 (m, 1 H, 5-H).
(5Z,7E)-1-Diazonona-5,7-dien-2-one (3b)
The acid (600 mg, 4.28 mmol) was dissolved in toluene (10 mL) under
an N2 atmosphere and oxalyl chloride (1.60 mL, 2.37 g, 18.7 mmol)
was added. After 2 h of stirring at room temperature, the solvent was
removed, and the resulting acid chloride was added to a diazometh-
ane solution (100 mL, 0.24 M, 9.44 mmol) at 0 °C. After 30 min, the
solution was allowed to warm to room temperature and stirring was
continued for 3 h. The mixture was concentrated to remove excess di-
azomethane and solvent. The residue was purified by flash chroma-
tography on SiO2 (hexanes/EtOAc, 10:1, Rf = 0.28).
Yield: 508 mg, 3.09 mmol (72%); yellow oil.
FT-IR (ATR): 3083 (w), 2926 (m), 2102 (vs), 1726 (m), 1638 (s), 1444
(m), 1371 (vs), 1325 (s), 1243 (m), 1143 (m), 1041 (m), 893 (m), 770
(m), 531 (w) cm–1
.
1H NMR (300 MHz, CDCl3): δ = 1.87 (s, 3 H, 7-H), 2.31–2.50 (m, 2 H, 2-
H), 2.53–2.65 (m, 2 H, 1-H), 4.85 (s, 1 H, 6-Ha), 4.97 (s, 1 H, 6-Hb), 5.24
(br s, 1 H, CHNN), 5.36 (dt, J = 11.7, 7.4 Hz, 1 H, 3-H), 5.87 (d, J = 11.7
Hz, 1 H, 4-H).
13C NMR (75 MHz, CDCl3): δ = 23.4 (C-2), 24.3 (C-7), 116.0 (C-6), 129.2
Yield: 700 mg, 4.28 mmol (quant.); yellow oil.
(C-3), 132.3 (C-4), 141.6 (C-5), 194.3 (C=O).
HRMS (ESI): m/z [M + Na]+ calcd for C9H12N2ONa: 187.0842; found:
187.0846.
FT-IR (ATR): 3088 (w), 3020 (w), 2931 (w), 2100 (vs), 1638 (s), 1449
(w), 1370 (s), 1326 (s), 1146 (w), 1096 (w), 985 (w), 947 (w), 821 (w),
736 (w) cm–1
.
1H NMR (500 MHz, CDCl3): δ = 1.78 (d, J = 6.9 Hz, 3 H, 7-H), 2.30–2.44
(m, 2 H, 2-H), 2.49 (q, J = 7.4 Hz, 2 H, 1-H), 5.18–5.29 (m, 2 H, 3-H,
CHNN), 5.65–5.75 (m, 1 H, 6-H), 5.92–6.06 (m, 1 H, 4-H), 6.25–6.37
(m, 1 H, 5-H).
13C NMR (125 MHz, CDCl3): δ = 18.6 (C-7), 23.5 (C-2), 40.9 (C-1), 126.6
(C-5), 126.9 (C-3), 130.0 (C-4), 130.5 (C-6), 194.4 (C=O).
(5Z,7E)-1-Diazo-7-ethylnona-5,7-dien-2-one (3e)
The acid (350 mg, 2.08 mmol) was dissolved in toluene (10 mL) under
an N2 atmosphere and oxalyl chloride (0.71 mL, 1.05 g, 8.32 mmol)
was added. After 2 h of stirring at room temperature, the solvent was
removed, and the resulting acid chloride was added to a diazometh-
ane solution (35 mL, 0.55 M, 19.3 mmol) at 0 °C. After 30 min, the
solution was allowed to warm to room temperature and stirring was
continued for 3 h. The mixture was concentrated to remove excess di-
azomethane and solvent. The residue was purified by flash chroma-
tography on SiO2 (hexanes/EtOAc, 10:1, Rf = 0.24).
MS (ESI): m/z = 329.17, 311.16, 295.16, 267.17, 232.17, 219.09,
203.08, 187.08 [M + Na]+, 175.05, 137.10.
(5Z,7E)-1-Diazo-8-phenylocta-5,7-dien-2-one (3c)
The acid (1.56 g, 7.69 mmol) was dissolved in hexane (16 mL) under
an N2 atmosphere and oxalyl chloride (3.28 mL, 4.85 g, 38.5 mmol)
was added. After 2 h of stirring at room temperature, the solvent was
removed, and the resulting acid chloride was added to a diazometh-
ane solution (150 mL, 0.50 M, 75.0 mmol) at 0 °C. After 30 min, the
solution was allowed to warm to room temperature and stirring was
continued for 3 h. The mixture was concentrated to remove excess di-
azomethane and solvent. The residue was purified by flash chroma-
tography on SiO2 (hexanes/EtOAc, 10:1, Rf = 0.13).
Yield: 332 mg, 1.73 mmol (83%); yellow oil.
1H NMR (300 MHz, CDCl3): δ = 0.94 (t, J = 7.6 Hz, 3 H, 7′-H), 1.68 (d, J =
6.8 Hz, 3 H, 7-H), 2.01–2.18 (m, 2 H, H-2), 2.32–2.58 (m, 4 H, 1-H, 6′-
H), 5.23 (br s, 1 H, CHNN), 5.26–5.38 (m, 2 H, 3-H, 6-H), 5.81 (d, J =
11.4 Hz, 1 H, 4-H).
13C NMR (75 MHz, CDCl3): δ = 13.0 (C-7′), 13.4 (C-7), 23.5 (C-6′), 24.3
(C-2), 123.3 (C-6), 128.0 (C-3), 133.0 (C-4), 139.0 (C-5), 194.7 (C=O).
Yield: 1.39 g, 6.14 mmol (80%); yellow oil.
(Z)-6-(Cyclopent-1-en-1-yl)-1-diazohex-5-en-2-one (3f)
The acid (280 mg, 1.68 mmol) was dissolved in toluene (10 mL) under
an N2 atmosphere and oxalyl chloride (1.02 mL, 1.52 g, 12.0 mmol)
was added. After 2 h of stirring at room temperature, the solvent was
removed, and the resulting acid chloride was added to a diazometh-
ane solution (60 mL, 0.48 M, 28.8 mmol) at 0 °C. After 30 min, the
solution was allowed to warm to room temperature and stirring was
continued for 3 h. The mixture was concentrated to remove excess di-
azomethane and solvent. The residue was purified by flash chroma-
tography on SiO2 (hexanes/EtOAc, 10:1, Rf = 0.24).
FT-IR (ATR): 3103 (w), 3025 (w), 2098 (vs), 1646 (s), 1639 (s), 1631
(s), 1594 (w), 1573 (w), 1492 (w), 1449 (w), 1412 (w), 1375 (m), 1318
(m), 1327 (m), 1144 (m), 1089 (w), 1028 (w), 988 (m), 945 (w), 858
(w), 739 (m), 692 (m) cm–1
.
1H NMR (300 MHz, CDCl3): δ = 2.38–2.54 (m, 2 H, 2-H), 2.63 (q, J = 7.5
Hz, 2 H, 1-H), 5.26 (br s, 1 H, CHNN), 5.48 (dt, J = 10.5, 7.5 Hz, 1 H, 3-
H), 6.14–6.24 (m, 1 H, 4-H), 6.41–6.60 (m, 1 H, 5-H), 6.99–7.12 (m, 1
H, 6-H), 7.17–7.26 (m, 1 H, p-ArH), 7.27–7.48 (m, 4 H, o-ArH, m-ArH).
13C NMR (75 MHz, CDCl3): δ = 23.9 (C-2), 124.1 (p-Ar), 126.7 (o-Ar),
127.8 (C-4), 128.8 (m-Ar), 130.2 (C-5), 130.3 (C-6), 133.2 (C-3), 137.5
(i-Ar), 194.2 (C=O).
Yield: 142 mg, 0.75 mmol (45%), yellow oil.
FT-IR (ATR): 3014 (w), 2955 (w), 2924 (w), 2843 (w), 2095 (vs), 1647
(s), 1630 (s), 1442 (w), 1372 (s), 1317 (s), 1260 (w), 1141 (m), 1095 (m),
MS (ESI): m/z = 265.09, 249.10 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C14H14N2ONa: 249.0998; found:
1035 (m), 1011 (m), 960 (m), 895 (w), 820 (m), 798 (m), 702 (w) cm–1
.
1H NMR (300 MHz, CDCl3): δ = 1.84–1.99 (m, 2 H, 8-H), 2.30–2.66 (m,
8 H, 1-H, 2-H, 7-H, 9-H), 5.12–5.38 (m, 2 H, CH, 3-H), 5.66–5.73 (m, 1
H, 6-H), 6.05 (d, J = 11.7 Hz, 1 H, 4-H).
249.0993.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–R

J
A. Zens et al.
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Synthesis
13C NMR (75 MHz, CDCl3): δ = 24.1 (C-2), 24.1 (C-8), 32.3 (C-7), 32.9
(C-1), 35.2 (C-9), 126.9 (C-6), 128.3 (C-3), 132.5 (C-4), 141.4 (C-5),
194.5 (C=O).
1H NMR (500 MHz, CDCl3): δ = 1.92–2.35 (m, 12 H, 1-H, 2-H, 3-H, 4-H,
5-H, 1-H*, 2-H*, 3-H*, 4-H*, 5-H*), 5.70 (dd, J = 8.8, 15.6 Hz, 0.48 H, 6-
H*), 6.03 (dd, J = 6.4 Hz, 15.7 Hz, 1 H, 6-H), 6.51 (d, J = 15.6 Hz, 0.5 H,
7-H*), 6.70 (d, J = 15.7 Hz, 1 H, 7-H), 7.21–7.30 (m, 9 H, ArH, ArH*); *
denotes signals of trans-1c.
13C NMR (125 MHz, CDCl3): δ = 19.9 (C-3), 22.0 (C-3)*, 27.4, 29.0 (C-2,
C-5), 29.6, 30.5 (C-2, C-5)*, 32.5 (C-1/C-4)*, 35.2 (C-1/C-4), 36.4 (C-
4/C-1), 36.7 (C-4/C-1)*, 123.1 (C-p), 126.0 (C-m)*, 126.1 (C-m), 127.5
(C-7)*, 127.7 (C-7), 128.1 (C-o)*, 128.7 (C-o), 130.3 (C-i), 135.3 (C-6),
137.0 (C-6)*, 213.1 (C=O)*, 214.6 (C=O); * denotes signals of trans-1c.
Vinylcyclopropanes 1a–f via Cu-Catalysis; General Procedure 1
(GP1)
α-Diazo ketone 3a–f was suspended with Cu(acac)2 or CuSO4 (10
wt%) in toluene and refluxed for at least 16 h. After filtration over
Celite, the solvent was removed, and the residue was purified by flash
chromatography on SiO2 (hexanes/EtOAc).
MS (ESI): m/z = 221.09 [M + Na]+, 199.11.
6-Vinylbicyclo[3.1.0]hexan-2-one (1a)
HRMS (ESI): m/z [M + Na]+ calcd for C14H14ONa: 221.0937; found:
Following GP1, 3a (310 mg, 2.06 mmol) was treated with Cu(acac)2 in
221.0943.
toluene (15 mL) for 16 h.
Yield: 204 mg, 1.66 mmol (81%); colorless oil; Rf = 0.26 (hexanes/EtO-
Ac, 10:1); dr (cis-1a/trans-1a) = 80:20.
6-(Prop-1-en-2-yl)bicyclo[3.1.0]hexan-2-one (1d)
Following GP1, 3d (500 mg, 3.05 mmol) was treated with CuSO4 in
1H NMR (300 MHz, CDCl3): δ = 1.81–2.30 (m, 9 H, 1-H, 2-H, 3-H, 4-H,
5-H, 1-H*, 2-H*, 3-H*, 4-H*, 5-H*), 5.07 (m, 0.5 H, 7-H*), 5.24–5.41 (m,
2.2 H, 7-H, 6-H*), 5.61–5.72 (m, 1 H, 6-H); * denotes signals of trans-
1a.
13C NMR (75 MHz, CDCl3): δ = 19.8 (C-2), 22. 9 (C-2)*, 27.9 (C-3), 28.6
(C-5), 29.2 (C-3)*, 30.6 (C-5)*, 32.5 (C-1)*, 35.0 (C-1), 36.3 (C-4)*, 36.5
(C-4), 114.9 (C-7)*, 120.3 (C-7), 131.6 (C-6), 136.20 (C-6)*, 214.7
(C=O); * denotes signals of trans-1a.
toluene (10 mL) for 16 h.
Yield: 238 mg, 1.75 mmol (57%); colorless oil; Rf = 0.14 (hexanes/EtO-
Ac, 20:1); dr (cis-1d/trans-1d) = 100:0.
FT-IR (ATR): 2941 (m), 1719 (vs), 1647 (m), 1447 (m), 1407 (m), 1376
(m), 1306 (m), 1252 (w), 1187 (m), 1152 (m), 1013 (w), 965 (w), 902
(m), 831 (w), 597 (w) cm–1
.
1H NMR (700 MHz, CDCl3): δ = 1.80 (s, 3 H, 8-H), 1.88–2.25 (m, 7 H, 1-
H, 2-H, 3-H, 4-H, 5-H), 4.92–4.93 (m, 1 H, 7-Ha), 4.98–4.99 (m, 1 H, 7-
Hb).
13C NMR (175 MHz, CDCl3): δ = 20.4 (C-2), 22.8 (C-8), 28.6 (C-3), 31.2
(C-1), 34.0 (C-4), 36.3 (C-5), 114.5 (C-7), 139.7 (C-6), 215.6 (C=O).
MS (ESI): m/z = 159.08 [M + Na]+, 137.10, 109.07.
HRMS (ESI): m/z [M + Na]+ calcd for C9H12ONa: 159.0780; found:
(E)-6-(Prop-1-en-1-yl)bicyclo[3.1.0]hexan-2-one (1b)
Following GP1, 3b (252 mg, 1.54 mmol) was treated with Cu(acac)2 in
toluene (15 mL) for 24 h.
Yield: 171 mg, 1.26 mmol (82%); colorless oil; Rf = 0.35 (hexanes/EtO-
Ac, 10:1); dr (cis-1b/trans-1b) = 80:20.
159.0764.
FT-IR (ATR): 2939 (w), 2886 (w), 1715 (vs), 1455 (w), 1413 (w), 1377
(m), 1301 (w), 1185 (m), 1148 (w), 1066 (w), 1041 (w), 986 (m), 963
(E)-6-(Pent-2-en-3-yl)bicyclo[3.1.0]hexan-2-one (1e)
(m), 904 (m), 878 (m), 832 (w), 783 (m), 747 (w), 606 (w) cm–1
.
Following GP1, 3e (320 mg, 1.66 mmol) was treated with CuSO4 in
toluene (10 mL) for 16 h.
1H NMR (250 MHz, CDCl3): δ = 1.63–1.67 (m, 0.8 H, 8-H*), 1.70 (d, J =
6.5 Hz, 3.2 H, 8-H), 1.75–2.33 (m, 8.4 H, 1-H, 2-H, 3-H, 4-H, 5-H, 1-H*,
2-H*, 3-H*, 4-H*, 5-H*), 4.93–5.04 (m, 0.2 H, 6-H*), 5.26–5.35 (m, 1 H,
6-H), 5.53–5.64 (m, 0.3 H, 7-H*), 5.72–5.86 (m, 1 H, 7-H); * denotes
signals of trans-1b.
13C NMR (63 MHz, CDCl3): δ = 17.8 (C-8)*, 18.3 (C-8), 19.6 (C-3), 22.8
(C-3)*, 26.8, 28.2 (C-2, C-5), 28.9, 29.9 (C-2, C-5)*, 32.4 (C-1)*, 34.6 (C-
1), 36.2 (C-4)*, 36.4 (C-4), 123.7 (C-7), 126.0 (C-7)*, 128.9 (C-6)*,
131.2 (C-6), 215.0 (C=O)*; * denotes signals of trans-1b.
Yield: 231 mg, 1.41 mmol (85%); colorless oil; Rf = 0.18 (hexanes/EtO-
Ac, 20:1); dr (cis-1e/trans-1e) = 80:20.
FT-IR (ATR): 2965 (m), 2934 (m), 2877 (m), 1717 (vs), 1460 (m), 1406
(m), 1377 (m), 1308 (m), 1188 (s), 1151 (m), 1012 (m), 976 (m), 923
(m), 845 (m), 759 (m), 616 (w), 513 (w) cm–1
.
1H NMR (700 MHz, CDCl3): δ = 1.01 (t, J = 7.8 Hz, 0.8 H, 8′-H*), 1.05 (t,
J = 7.8 Hz, 3 H, 8′-H), 1.59 (d, J = 6.9 Hz, 0.9 H, 8-H*), 1.62 (d, J = 6.9 Hz,
3 H, 8-H), 1.75–2.25 (m, 14 H, 1-H, 2-H, 3-H, 4-H, 5-H, 7′-H, 1-H*, 2-
H*, 3-H*, 4-H*, 5-H*, 7′-H*), 5.20 (q, J = 7.2 Hz, 0.2 H, 7-H*), 5.44 (q, J =
7.2 Hz, 1 H, 7-H); * denotes signals of trans-1e.
13C NMR (175 MHz, CDCl3): δ = 12.6 (C-8′), 13.0 (C-8′)*, 13.2 (C-8)*,
13.2 (C-8), 20.4, 23.4, 28.6 (C-2, C-3, C-7′), 22.9, 23.0, 27.6 (C-2, C-3, C-
7′)*, 30.6, 33.8, 36.1 (C-1, C-4, C-5), 32.5, 32.7, 35.6 (C-1, C-4, C-5)*,
119.0 (C-7)*, 122.8 (C-7), 135.5 (C-6), 137.9 (C-6)*, 214.4 (C=O)*,
215.8 (C=O); * denotes signals of trans-1e.
MS (ESI): m/z = 159.08 [M + Na]+, 137.09.
HRMS (ESI): m/z [M + Na]+ calcd for C9H12ONa: 159.0780; found:
159.0772.
(E)-6-Styrylbicyclo[3.1.0]hexan-2-one (1c)
Following GP1, 3c (1.38 g, 6.10 mmol) was treated with CuSO4 in tolu-
ene (10 mL) for 20 h.
Yield: 995 mg, 5.02 mmol (82%); yellow oil; Rf = 0.09 (hexanes/EtOAc,
20:1); dr (cis-1c/trans-1c) = 67:33.
MS (ESI): m/z = 187.11 [M + Na]+, 165.13.
HRMS (ESI): m/z [M + Na]+ calcd for C11H16ONa: 187.1093; found:
FT-IR (ATR): 3415 (w), 3028 (w), 2925 (w), 1717 (vs), 1598 (w), 1494
(w), 1451 (w), 1411 (w), 1305 (m), 1184 (m), 1148 (w), 1120 (w),
1071 (w), 1042 (w), 964 (m), 882 (w), 853 (w), 830 (w), 752 (m), 696
187.1062.
6-(Cyclopent-1-en-1-yl)bicyclo[3.1.0]hexan-2-one (1f)
(m), 620 (w), 542 (w) cm–1
.
Following GP1, 3f (130 mg, 0.68 mmol) was treated with CuSO4 in tol-
uene (10 mL) for 22 h.
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A. Zens et al.
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Synthesis
Yield: 76 mg, 0.47 mmol (68%); colorless oil; Rf = 0.29 (hexanes/EtO-
Ac, 30:1); dr (cis-1f/trans-1f) = 50:50.
1H NMR (250 MHz, CDCl3): δ = 2.20 (m, 4 H, 2-H, 3-H), 3.71 (m, 4 H, 1-
H, 4-H), 4.45 (d, J = 7.23 Hz, 2 H, 1′-H), 5.66 (m, 2 H, 3′-H), 5.98 (m, 1
H, 2′-H).
13C NMR (63 MHz, CDCl3): δ = 31.1 (C-2, C-3), 32.9 (C-1, C-4), 43.5 (C-
1′), 119.1 (C-2′), 134.2 (C-3′).
FT-IR (ATR): 3046 (w), 2945 (m), 2848 (m), 1720 (vs), 1458 (w), 1406
(w), 1306 (w), 1187 (m), 1047 (w), 988 (w), 962 (w), 923 (w), 879 (w),
834 (w), 619 (w), 506 (w) cm–1
.
1H NMR (500 MHz, CDCl3): δ = 1.76–2.39 (m, 26 H, 1-H, 2-H, 3-H, 4-H,
5-H, 8-H, 9-H, 10-H, 1-H*, 2-H*, 3-H*, 4-H*, 5-H*, 8-H*, 9-H*, 10-H*),
5.46–5.47 (m, 1 H, 7-H*), 5.59–5.61 (m, 1 H, 7-H); * denotes signals of
trans-1f.
13C NMR (125 MHz, CDCl3): δ = 20.5, 23.0, 23.2, 23.3, 25.4 (C-2, C-3, C-
9, C-2*, C-3*,C-9*), 27.9, 28.3, 32.4, 32.5, 32.8, 32.8, 33.9, 35.4, 35.7,
36.3 (C-1, C-4, C-5, C-8, C-10, C-1*, C-4*, C-5*, C-8*, C-10*), 125.3 (C-
7*), 128.5 (C-7), 138.3 (C-6), 140.7 (C-6*), 214.0 (C=O)*, 215.5 (C=O); *
denotes signals of trans-1f.
1-[(2E)-But-2-enyl]tetrahydrothiophenium Bromide (6b·Br)11
Following general procedure A, 11b (2.57 g, 19.1 mmol) was dissolved
in CH2Cl2 (10 mL) and reacted with 13 (1.68 g, 1.69 mL, 19.1 mmol)
for 7 d at room temperature.
Yield: 3.77 g, 16.9 mmol (89%); amorphous brown solid.
1H NMR (500 MHz, CDCl3): δ = 1.64–1.69 (m, 3 H, 4′-H), 1.83–1.91 (m,
4 H, 2-H, 3-H), 2.74–2.79 (m, 4 H, 1-H, 4-H), 3.85–3.97 (m, 2 H, 1′-H),
5.62–5.80 (m, 2 H, 2′-H, 3′-H).
13C NMR (125 MHz, CDCl3): δ = 17.7 (C-4′), 31.1 (C-2, C-3), 31.8 (C-1,
C-4), 33.5 (C-1′), 127.6 (C-2′), 131.4 (C-3′).
MS (ESI): m/z = 185.10 [M + Na]+, 163.11.
HRMS (ESI): m/z [M + Na]+ calcd for C11H14ONa: 185.0937; found:
185.0953.
1-[(2E)-3-Phenylprop-2-enyl]tetrahydrothiophenium Bromide
(6c·Br)11
Tetrahydrothiophenium Salts; General Procedures A, B and C
(A) The respective commercially available substituted allyl bromide
11 (1 equiv) was dissolved in CH2Cl2. Tetrahydrothiophene (13) (1
equiv) was added to the solution, and the reaction mixture was
stirred at room temperature for several days. The solvent was re-
moved under reduced pressure, and the resulting salt was obtained as
a solid.
Following general procedure A, 11c (4.37 g, 22.2 mmol) was dissolved
in CH2Cl2 (15 mL) and reacted with 13 (1.96 g, 1.96 mL, 22.2 mmol)
for 9 d at room temperature.
Yield: 4.93 g, 17.3 mmol (97%); amorphous brown solid.
1H NMR (300 MHz, CDCl3): δ = 1.86–1.97 (m, 4 H, 2-H, 3-H), 2.83 (m, 4
H, 1-H, 4-H), 4.16 (d, J = 7.9 Hz, 2 H, 1′-H), 6.40 (m, 1 H, 2′-H), 6.65 (d,
J = 15.6 Hz, 1 H, 3′-H), 7.23–7.41 (m, 5 H, o-H, m-H, p-H).
13C NMR (75 MHz, CDCl3): δ = 31.1 (C-2, C-3), 31.8 (C-1, C-4), 33.5 (C-
1′), 116.8 (C-o), 125.2 (C-2′), 128.4 (C-p), 128.7 (C-m), 134.6 (C-3′),
135.8 (C-i).
(B) The respective substituted allyl bromide 11 (1 equiv) was dis-
solved in acetone, tetrahydrothiophene (13) (3 equiv) was added to
the solution, and the reaction mixture was stirred at room tempera-
ture for several days. After removing the solvent and the excess of 13,
the salt was obtained.
(C) A solution of the respective allyl alcohol 12 (1 equiv), tetrahydro-
thiophene (13) (3 equiv) and HBF4·Et2O (51–57 wt% in Et2O, 1 equiv)
in acetone was stirred for several days at room temperature. Then the
mixture was concentrated under reduced pressure and the pure sul-
fonium salt was obtained.
1-[(2E)-3-Phenylprop-2-enyl]tetrahydrothiophenium Tetrafluo-
roborate (6c·BF4)44
According to Ref. 24, 11c (2.50 g, 17 mmol) was dissolved in CH2Cl2 (8
mL). After addition of 13 (3.36 g, 3.36 mL, 38.1 mmol) and a sat. solu-
tion of NaBF4 (4.18 g, 38.1 mmol), the reaction mixture was stirred at
room temperature for 24 h. The aq layer was extracted with CH2Cl2
(3 × 75 mL), and the combined organic layers were dried (MgSO4) and
concentrated under reduced pressure. The desired product 6c·BF4 was
obtained by adding Et2O (2 mL).
1-Allyltetrahydrothiophenium Tetrafluoroborate (6a·BF4)
Following general procedure C, 12a (1.35 mL, 34.4 mmol) was treated
with 13 (9.11 mL, 9.11 mg, 103 mmol) and HBF4·Et2O (51–57 wt% in
Et2O, 3.20 mL, 3.78 g, 34.4 mmol) in acetone (16 mL) for 2 d at room
temperature.
Yield: 3.44 g, 1.77 mmol (93%); amorphous brown solid.
1H NMR (400 MHz, DMSO-d6): δ = 2.08–2.26 (m, 4 H, 2-H, 3-H), 3.37–
3.54 (m, 4 H, 1-H, 4-H), 4.14 (d, J = 8.2 Hz, 2 H, 1′-H), 6.35–6.45 (m, 1 H,
2′-H), 6.93 (d, J = 6.6 Hz, 1 H, 3′-H), 7.32–7.56 (m, 5 H, o-H, m-H, p-H).
13C NMR (100 MHz, DMSO-d6): δ = 28.3 (C-2, C-3), 41.7 (C-1, C-4),
43.7 (C-1′), 116.6 (C-2′), 126.8 (C-m), 128.7 (C-o), 128.8 (C-p), 135.2
(C-i), 139.5 (C-3′).
Yield: 5.10 g, 24.0 mmol (70%); brown amorphous solid.
FT-IR (ATR): 3412 (w, br), 2251 (w), 2126 (w), 1052 (s), 1023 (vs), 821
(s), 759 (s), 623 (m), 520 (w) cm–1
.
1H NMR (400 MHz, DMSO-d6): δ = 2.12–2.24 (m, 4 H, 2-H, 3-H), 3.29–
3.37 (m, 2 H, 1-Ha, 4-Ha), 3.43–3.50 (m, 2 H, 1-Hb, 4-Hb), 3.94 (d, J = 7.4
Hz, 2 H, 1′-H), 5.51–5.65 (m, 2 H, 3′-H), 5.86–5.96 (m, 1 H, 2′-H).
13C NMR (125 MHz, DMSO-d6): δ = 28.7 (C-2, C-3), 42.4 (C-1, C-4),
44.0 (C-1′), 126.6 (C-2′), 126.7 (C-3′).
MS (ESI): m/z = 169.01 [M + 2 Na]+.
1-(2-Methylprop-2-enyl)tetrahydrothiophenium Bromide
(6d·Br)11
Following general procedure A, 11d (7.00 g, 49.6 mmol) was dissolved
in CH2Cl2 (20 mL) and reacted with 13 (4.20 g, 4.20 mL, 49.6 mmol)
for 6 d at room temperature.
HRMS (ESI): m/z [M]+ calcd for C7H13S: 129.0732; found: 129.0716.
1-Allyltetrahydrothiophenium Bromide (6a·Br)11
Yield: 7.00 g, 31.4 mmol (98%); hygroscopic colorless solid.
1H NMR (400 MHz, CDCl3): δ = 1.87–1.99 (m, 3 H, 3′-H), 2.45–2.87 (m,
4 H, 3-H, 2-H), 3.58–4.03 (m, 4 H, 4-H, 1-H), 4.40 (s, 2 H, 1′-H), 4.93–
5.38 (m, 2 H, 4′-H).
Following general procedure A, 11a (5.09 g, 3.63 mL, 42 mmol) was
dissolved in CH2Cl2 (30 mL) and reacted with 13 (3.71 g, 3.71 mL, 42
mmol) for 7 d at room temperature.
Yield: 7.55 g, 36 mmol (86%); amorphous brown solid.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–R

L
A. Zens et al.
Paper
Synthesis
13C NMR (100 MHz, CDCl3): δ = 20.2 (C-4′), 31.1 (C-2, C-3), 31.8 (C-1,
C-4), 38.2 (C-1′), 115.8 (C-3′), 141.6 (C-2′).
1-(Cyclohex-1-en-1-ylmethyl)tetrahydrothiophenium Bromide
(6g·Br)
Following general procedure B, 11g (2.60 g, 14.9 mmol) was treated
with 13 (6.55 mL, 6.55 g, 74.3 mmol) in acetone (10 mL) for 1 d at
room temperature.
1-(2-Methylprop-2-enyl)tetrahydrothiophenium Tetrafluorobo-
rate (6d·BF4)
Following general procedure C, 12d (860 mg, 11.9 mmol) was treated
with 13 (3.14 mL, 3.14 g, 35.6 mmol) and HBF4·Et2O (51–57 wt% in
Et2O, 1.10 mL, 1.30 g, 11.9 mmol) in acetone (15 mL) for 9 d at room
temperature.
Yield: 1.92 g, 7.29 mmol (46%); amorphous brown solid.
FT-IR (ATR): 3359 (m), 2924 (vs), 2851 (s), 2201 (w), 2190 (w), 2148
(m), 2101 (w), 2062 (w), 2021 (w), 1996 (w), 1967 (w), 1647 (w),
1450 (m), 1260 (m), 1023 (s), 801 (m), 641 (w), 554 (w), 508 (w), 479
(w), 419 (w) cm–1
.
Yield: 2.05 g, 8.92 mmol (75%); amorphous brown solid.
FT-IR (ATR): 1052 (vs), 1025 (vs), 820 (s), 757 (vs), 623 (m) cm–1
.
1H NMR (300 MHz, CDCl3): δ = 1.63 (m, 4 H, 2-H, 3-H), 1.94 (m, 4 H,
5′-H, 6′-H), 2.08 (m, 4 H, 1-H, 4-H), 2.84 (m, 4 H, 4′-H, 7′-H), 3.94 (s, 2
H, 1′-H), 5.89 (s, 1 H, 3′-H).
13C NMR (75 MHz, CDCl3): δ = 21.9 (C-6′), 22.4 (C-5′), 25.4 (C-4′), 26.4
(C-2, C-3), 31.1 (C-7′), 31.8 (C-1, C-4), 39.9 (C-1′), 128.2 (C-3′), 134.8
(C-2′).
1H NMR (400 MHz, DMSO-d6): δ = 1.86 (s, 3 H, 4′-H), 2.11–2.35 (m, 4
H, 2-H, 3-H), 3.26–3.55 (m, 4 H, 1-H, 4-H), 3.93 (s, 2 H, 1′-H), 5.21–
5.32 (m, 2 H, 3′-H).
13C NMR (125 MHz, DMSO-d6): δ = 20.4 (C-4′), 27.5 (C-2, C-3), 42.1 (C-
1, C-4), 47.8 (C-1′), 120.2 (C-3′), 134.2 (C-2′).
MS (ESI): m/z = 169.01 [M + Na]+.
1-(2-Phenylprop-2-enyl)tetrahydrothiophenium Bromide (6h·Br)
Following general procedure B, 11h (1.00 g, 5.10 mmol) was dissolved
in acetone (10 mL) and treated with 13 (1.34 mL, 1.34 g, 15.2 mmol)
for 2 d at room temperature.
1-[(2E)-2-Methylpent-2-enyl]tetrahydrothiophenium Tetrafluo-
roborate (6i·BF4)
Following general procedure C, 12i (2.50 g, 25.0 mmol) was treated
with 13 (6.60 mL, 6.60 g, 74.9 mmol) and HBF4·Et2O (51–57 wt% in
Et2O, 2.30 mL, 2.76 g, 25.0 mmol) in acetone (15 mL) for 7 d at room
temperature.
Yield: 1.40 g, 4.90 mmol (97%); hygroscopic colorless solid.
FT-IR (ATR): 3046 (w), 3028 (w), 2969 (w), 2935 (m), 2883 (w), 2812
(w), 2164 (w), 2148 (w), 2053 (w), 2015 (w), 1978 (w), 1916 (w),
1837 (w), 1678 (w), 1628 (w), 1598 (w), 1495 (m), 1445 (w), 1426
(w), 1399 (m), 1332 (w), 1306 (m), 1281 (w), 1255 (s), 1211 (w), 1163
(w), 1138 (w), 1098 (w), 1078 (w), 1028 (m), 993 (w), 934 (w), 920
(s), 890 (w), 873 (w), 782 (vs), 747 (m), 736 (w), 708 (vs), 655 (m),
Yield: 5.07 g, 25.0 mmol (79%); amorphous brown solid.
FT-IR (ATR): 3633 (w), 2965 (w), 2877 (w), 1664 (w), 1452 (w), 1422
(w), 1395 (w), 1312 (w), 1285 (w), 1263 (w), 1206 (w), 1021 (vs), 952
(w), 882 (w), 197 (w), 764 (w), 689 (w), 647 (w), 520 (s), 425 (w) cm–1
.
580 (m), 521 (w), 500 (m), 407 (w) cm–1
.
1H NMR (400 MHz, CDCl3): δ = 0.99 (t, J = 7.6, 7.7, 15.3 Hz, 3 H, 5′-H),
1.76 (s, 3 H, 6′-H), 2.10 (q, J = 7.6, 7.7, 14.7 Hz, 2 H, 4′-H), 2.29–2.48
(m, 4 H, 2-H, 3-H), 3.24–3.64 (m, 4 H, 1-H, 4-H), 3.85 (s, 2 H, 1′-H),
5.74 (t, J = 7.0, 7.9, 14.3 Hz, 1 H, 3′-H).
13C NMR (125 MHz, CDCl3): δ = 13.5 (C-5′), 15.2 (C-6′), 21.8 (C-4′),
28.4 (C-2, C-3), 42.2 (C-1, C-4), 52.4 (C-1′), 123.3 (C-2′), 140.0 (C-3′).
1H NMR (400 MHz, DMSO-d6): δ = 2.09–2.38 (m, 4 H, 3-H, 2-H), 3.28–
3.54 (m, 4 H, 4-H, 1-H), 4.52 (s, 2 H, 1′-H), 5.73 (s, 1 H, 3′-Ha or 3′-Hb),
5.92 (s, 1 H, 3′-Hb or 3′-Ha), 7.38–7.69 (5 H, o-H, m-H, p-H).
13C NMR (125 MHz, DMSO-d6): δ = 28.6 (C-2, C-3), 43.3 (C-1, C-4),
45.8 (C-1′), 122.7 (C-3′), 126.8 (C-o), 129.3 (C-m), 129.5 (C-p), 136.5
(C-i or C-2′), 137.3 (C-2′ or C-i).
MS (ESI): m/z = 171.12 [M]+.
HRMS (ESI): m/z [M]+ calcd for C10H19S: 171.1201; found: 171.1202.
MS (ESI): m/z = 205.10 [M]+.
HRMS (ESI): m/z [M]+ calcd for C13H17S: 205.1045; found: 205.1047.
1-(Cyclopent-1-en-1-ylmethyl)tetrahydrothiophenium Tetrafluo-
roborate (6f·BF4)
Cyclopropanation of 4 and 5 with Sulfonium Salts 6·X; General
Procedure 2 (GP2)
Following general procedure C, 12f (2.32 g, 23.7 mmol) was treated
with 13 (6.26 mL, 6.26 g, 71.0 mmol) and HBF4·Et2O (51–57 wt% in
Et2O, 2.18 mL, 2.60 g, 23.7 mmol) in acetone (15 mL) for 12 d at room
temperature.
The vacuum-dried sulfonium salt 6 (2 equiv) was dissolved in anhy-
drous DMSO and stirred under nitrogen. Cyclopentenone (4) or cyclo-
hexenone (5) (1 equiv) was added, followed by LiOtBu or KOtBu (1
equiv) and n-dodecane (internal standard for monitoring the reaction
progress by GC). After the reaction had finished, the solution was
quenched with ice-cold brine, and filtered through a pad of Celite
rinsing with Et2O. The aq solution was extracted with Et2O, and the
combined organic layers were dried (MgSO4) and concentrated under
reduced pressure. The product mixture was separated by column
chromatography.
Yield: 3.23 g, 12.6 mmol (73%); amorphous brown solid.
FT-IR (ATR): 2950 (m), 1715 (w), 1420 (w), 1366 (w), 1262 (w), 1049
(vs), 883 (s), 764 (w), 693 (w), 579 (w), 520 (s) cm–1
.
1H NMR (500 MHz, DMSO-d6): δ = 1.88–1.95 (m, 2 H, 5′-H), 2.13–2.30
(m, 4 H, 2-H, 3-H), 2.34–2.40 (m, 4 H, 4′-H, 6′-H), 3.23–3.53 (m, 4 H, 1-
H, 4-H), 4.05 (s, 2 H, 1′-H), 6.04–6.07 (m, 1 H, 3′-H).
13C NMR (125 MHz, DMSO-d6): δ = 22.8 (C-5′), 28.1 (C-2, C-3), 32.4 (C-
4′/C-6′), 33.7 (C-6′/C-4′), 42.5 (C-1′), 42.6 (C-1, C-4), 132.7 (C-2′),
135.5 (C-3′).
MS (ESI): m/z = 169.10 [M]+.
HRMS (ESI): m/z [M]+ calcd for C10H17S: 169.1045; found: 169.1044.
6-Vinylbicyclo[3.1.0]hexan-2-one (1a)
Following GP2 using 6a·Br (2.00 g, 9.56 mmol), 4 (0.40 mL, 0.39 g, 4.78
mmol) and LiOtBu (0.77 g, 9.56 mmol) in dried DMSO (20 mL) for 1 h.
Yield: 0.23 g, 1.91 mmol (47%); colorless oil; Rf = 0.27 (hexanes/EtOAc,
10:1), tR (cis-1a) = 4.73 min, tR (trans-1a) = 4.91 min; dr = 50:50
(cis/trans). Spectroscopic data see above.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–R

M
A. Zens et al.
Paper
Synthesis
6-[(1E)-Prop-1-enyl]bicyclo[3.1.0]hexan-2-one (1b)
1H NMR (400 MHz, CDCl3): δ = 1.67–1.84 (m, 2 H, 4-Ha, 5-Ha), 1.84–1.94
(m, 3 H, 3-H, 2-H, 4-Hb), 1.95–2.18 (m, 3 H, 6-Ha, 5-Hb, 7-H), 2.24–2.39
(m, 1 H, 6-Hb), 5.19–5.35 (m, 2 H, 9-H), 5.67–5.82 (m, 1 H, 8-H).
13C NMR (100 MHz, CDCl3): δ = 18.4 (C-5), 23.4 (C-3), 24.6 (C-4), 28.5
(C-2), 29.3 (C-7), 40.1 (C-6), 119.7 (C-9), 132.2 (C-8), 209.1 (C-1).
Following GP2 using 6b·Br (0.66 g, 2.94 mmol), 4 (0.12 mL, 0.12 g, 4.78
mmol) and LiOtBu (0.33 g, 2.94 mmol) in dried DMSO (20 mL) for 1 h.
Yield: 93.6 mg, 0.69 mmol (55%): colorless oil; Rf = 0.28 (hexanes/EtO-
Ac, 10:1), tR (cis-1b) = 5.16 min; dr = 80:20 (cis/trans). Spectroscopic
data see above.
MS (EI): m/z (%) = 136.1 [M]+ (30), 121.1 (15), 118.1 (7), 108.1 (17),
93.1 (28), 79.1 (100), 67.1 (21), 53.0 (13), 39.0 (26), 27.0 (13).
HRMS (ESI): m/z [M + Na]+ calcd for C9H12ONa: 159.0780; found:
(E)-6-Styrylbicyclo[3.1.0]hexan-2-one (1c)
Following GP2 using 6c·Br (3.46 g, 12.1 mmol), 4 (0.48 mL, 0.48 g, 6.05
mmol) and LiOtBu (0.97 g, 12.1 mmol) in dried DMSO (20 mL) for 1 h.
159.0780.
trans-2a
Yield: 60.5 mg, 3.05 mmol (62%); yellow oil; Rf = 0.20 (hexanes/EtOAc,
10:1), tR (cis-1c) = 14.31 min, tR (trans-1c) = 14.99 min; dr = 67:33
(cis/trans). Spectroscopic data see above.
FT-IR (ATR): 3499 (br), 3082 (w), 2929 (s), 2860 (w), 1686 (vs), 1636
(m), 1448 (m), 1398 (w), 1334 (m), 1241 (m), 1193 (w), 1172 (w),
1130 (w), 1065 (w), 986 (s), 897 (vs), 794 (w), 731 (s), 650 (w), 475
(w), 433 (w) cm–1
.
6-(Prop-1-en-2-yl)bicyclo[3.1.0]hexan-2-one (1d)
Following GP2 using 6d·Br (4.56 g, 20.6 mmol), 4 (0.85 mL, 0.84 g, 10.3
mmol) and LiOtBu (1.64 g, 20.6 mmol) in dried DMSO (20 mL) for 1 h.
1H NMR (400 MHz, CDCl3): δ = 1.58–1.72 (m, 2 H, 5-H), 1.70–1.75 (m,
1 H, 3-H), 1.75–1.80 (m, 1 H, 2-H), 1.83–2.03 (m, 2 H, 4-H), 1.99–2.11
(m, 1 H, 6-Ha), 2.17–2.26 (m, 1 H, 7-H), 2.26–2.37 (m, 1 H, 6-Hb), 4.96–
5.20 (m, 2 H, 9-H), 5.30–5.45 (m, 1 H, 8-H).
Yield: 0.24 g, 1.75 mmol (20%); yellow oil; Rf = 0.30 (hexanes/EtOAc,
10:1), tR (cis-1d) = 4.51 min, tR (trans-1d) = 4.95 min; dr = 50:50
(cis/trans). Spectroscopic data see above.
13C NMR (100 MHz, CDCl3): δ = 18.6 (C-5), 20.9 (C-4), 25.1 (C-3), 27.5
(C-7), 34.4 (C-2), 36.9 (C-6), 114.6 (C-9), 137.7 (C-8), 206.9 (C-1).
6-(Cyclohex-1-en-1-yl)bicyclo[3.1.0]hexan-2-one (1g)
MS (EI): m/z (%) = 136.1 [M] (30), 121.1 (15), 118.1 (7), 108.1 (17),
93.1 (28), 79.1 (100), 67.1 (21), 53.0 (13), 39.0 (26), 27.0 (13).
HRMS (ESI): m/z [M + Na]+ calcd for C9H12O: 159.0780; found:
Following GP2 using 6g·Br (1.00 g, 3.60 mmol), 4 (0.15 mL, 0.15 g, 1.80
mmol) and LiOtBu (0.29 g, 3.60 mmol) in dried DMSO (20 mL) for 1 h.
159.0780.
Yield: 0.26 g, 1.49 mmol (17%); colorless amorphous solid; Rf = 0.26
(hexanes/EtOAc, 10:1), tR (cis-1g) = 8.75 min, tR (trans-1g) = 9.19 min;
dr = 50:50 (cis/trans).
7-[(1E)-Prop-1-enyl]bicyclo[4.1.0]heptan-2-one (2b)
FT-IR (ATR): 3350 (w), 2933 (m), 2251 (w), 1711 (s), 1438 (w), 1407
(w), 1308 (w), 1261 (w), 1189 (m), 1045 (w), 907 (vs), 838 (w), 802
Following GP2 using 6b·Br (4.80 g, 21.5 mmol), 5 (1.04 mL, 1.03 g,
10.8 mmol) and LiOtBu (1.72 g, 21.5 mmol) in dried DMSO (20 mL) for
48 h.
(w), 725 (vs), 647 (m), 461 (w) cm–1
.
1H NMR (300 MHz, CDCl3): δ = 1.48–1.67 (m, 8 H, 9-H, 10-H, 9-H*, 10-
H*), 1.75–2.22 (m, 22 H, 1-H, 2-H, 3-H, 4-H, 5-H, 8-H, 11-H, 1-H*, 2-
H*, 3-H*, 4-H*, 5-H*, 8-H*, 11-H*), 5.48–5.51 (m, 1 H, 7-H*), 5.65–5.69
(m, 1 H, 8-H); * denotes signals of trans-1g.
Yield: cis-2b: 0.30 g, 2.02 mmol (19%); colorless oil; Rf = 0.4 (hex-
anes/EtOAc, 5:1), tR = 6.97 min); trans-2b: 0.22 g, 1.46 mmol (14%);
yellow oil; Rf = 0.3 (hexanes/EtOAc, 5:1), tR = 7.26 min); chromatogra-
phy with hexanes/EtOAc (15:1).
13C NMR (75 MHz, CDCl3): δ = 20.5 (C-2), 22.2 (C-2)*, 22.3 (C-9), 22.6
(C-9)*, 22.8 (C-10), 23.0 (C-10)*, 25.2 (C-3), 25.3 (C-3)*, 26.5 (C-8),
26.7 (C-8)*, 28.2 (C-11), 28.7 (C-11)*, 29.7 (C-1), 31.1 (C-1)*, 32.6 (C-
5), 33.5 (C-5)*, 34.8 (C-4), 36.2 (C-4)*, 122.7 (C-7), 125.8 (C-7)*, 131.9
(C-6), 133.7 (C-6)*, 214.4 (C=O), 215.7 (C=O)*; * denotes signals of
trans-1g.
cis-2b
FT-IR (ATR): 3021 (w), 2934 (m), 2858 (w), 1864 (vs), 1449 (m), 1405
(w), 1377 (w), 1333 (m), 1241 (s), 1192 (w), 1129 (m), 1063 (m), 1004
(w), 960 (s), 921 (w), 894 (s), 876 (m), 799 (w), 745 (w), 704 (w), 601
(w), 478 (m), 443 (w), 412 (w) cm–1
.
MS (ESI): m/z = 199.11 [M + Na]+, 177.13 [M]+, 149.10.
1H NMR (700 MHz, CDCl3): δ = 1.72 (m, 3 H, Me), 1.72–1.80 (m, 2 H, 4-
Ha, 5-Ha), 1.81–1.91 (m, 3 H, 2-H, 3-H, 5-H), 1.95–2.01 (m, 1 H, 6-Ha),
2.01–2.06 (m, 1 H, 4-Hb), 2.06–2.11 (m, 1 H, 7-H), 2.25–2.30 (m, 1 H,
6-Hb), 5.37–5.43 (m, 1 H, 8-H), 5.68–5.78 (ddd, J = 15.1, 6.5, 1.2 Hz, 1
H, 9-H).
13C NMR (100 MHz, CDCl3): δ = 18.3 (Me or C-4), 18.5 (C-4 or Me),
23.1 (C-3), 24.7 (C-5), 28.3 (C-2), 28.4 (C-7), 40.1 (C-6), 124.6 (C-8),
131.0 (C-9), 209.7 (C-1).
7-Vinylbicyclo[4.1.0]heptan-2-one (2a)
Following GP2 using 6a·BF4 (4.10 g, 7.80 mmol), 5 (0.37 mL, 0.38 g,
3.90 mmol) and LiOtBu (0.63 g, 7.80 mmol) in dried DMSO (20 mL) for
21 h.
Yield: cis-2a: 116 mg, 0.85 mmol (22%); colorless oil; Rf = 0.5 (hex-
anes/EtOAc, 5:1), tR = 4.69 min); trans-2a: 76 mg, 0.56 mmol (14%);
yellow oil; Rf = 0.4 (hexanes/EtOAc, 5:1), tR = 5.35 min; chromatogra-
phy with n-pentane/Et2O (15:1).
MS (EI): m/z (%) = 150.1 [M]+ (60), 135.1 (20), 132.1 (3), 121.1 (22),
117.1 (4), 107.1 (21), 94.1 (56), 79.0 (100), 73.1 (3), 67.0 (10), 59.0 (1),
53.0 (8), 39.0 (16), 27.0 (7).
HRMS (EI): m/z [M]+ calcd for C10H14O: 150.1045; found: 150.1044.
cis-2a
FT-IR (ATR): 3505 (br), 3081 (w), 2934 (s), 2865 (m), 1686 (vs), 1633
(m), 1449 (w), 1423 (w), 1346 (m), 1246 (w), 1224 (w), 1181 (w),
1116 (w), 1081 (w), 985 (m), 900 (vs), 883 (s), 825 (w), 789 (w), 753
(w), 731 (w), 710 (w), 647 (w), 590 (w), 482 (w), 409 (w) cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–R

N
A. Zens et al.
Paper
Synthesis
trans-2b
MS (ESI): m/z = 235.11 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C15H16ONa: 235.1093; found:
235.1088.
FT-IR (ATR): 3021 (w), 2934 (m), 2858 (w), 1864 (vs), 1449 (m), 1405
(w), 1377 (w), 1333 (m), 1241 (s), 1192 (w), 1129 (m), 1063 (m), 1004
(w), 960 (s), 921 (w), 894 (s), 876 (m), 799 (w), 745 (w), 704 (w), 601
(w), 478 (m), 443 (w), 412 (w) cm–1
.
(5R,7R,8S)-8-Benzyltricyclo[3.2.1.02,7]octan-6-one (17)
1H NMR (400 MHz, CDCl3): δ = 1.54–1.70 (m, 7 H, Me, 5-H, 3-H, 2-H),
1.78–1.96 (m, 2 H, 4-H), 1.96–2.05 (m, 1 H, 6-Ha), 2.05–2.11 (m, 1 H,
7-H), 2.17–2.30 (m, 1 H, 6-Hb), 4.91–5.00 (m, 1 H, 9-H), 5.47–5.56 (m,
1 H, 8-H).
13C NMR (100 MHz, CDCl3): δ = 17.7 (Me), 18.7 (C-5), 21.1 (C-4), 25.1
(C-3), 26.9 (C-7), 34.5 (C-2), 36.9 (C-6), 125.9 (C-8), 130.5 (C-9), 207.1
(C-1).
Following GP2 using 6c·Br (1.11 g, 3.91 mmol), 5 (0.19 mL, 0.19 g, 1.95
mmol) and KOtBu (0.44 g, 3.91 mmol) in dried DMSO (35 mL) for 24 h.
Yield: trans-2c: 61 mg, 0.29 mmol (15%); yellow oil; Rf = 0.20 (hex-
anes/EtOAc, 10:1), tR = 16.62 min); 17: 31 mg, 1.46 mmol (76%); yel-
low oil; Rf = 0.25 (hexanes/EtOAc, 10:1), tR = 15.16 min; chromatogra-
phy with hexanes/EtOAc (15:1 → 10:1 → 5:1).
MS (EI): m/z (%) = 150.1 [M] (60), 135.1 (20), 132.1 (3), 121.1 (22),
117.1 (4), 107.1 (21), 94.1 (56), 79.0 (100), 73.1 (3), 67.0 (10), 59.0 (1),
53.0 (8), 39.0 (16), 27.0 (7).
HRMS (EI): m/z [M]+ calcd for C10H14O: 150.1045; found: 150.1044.
17
FT-IR (ATR): 3429 (br), 3060 (w), 3026 (w), 2941 (w), 2873 (w), 1720
(vs), 1602 (w), 1495 (w), 1470 (w), 1453 (s), 1309 (w), 1237 (w), 1195
(w), 1135 (w), 1081 (w), 1029 (w), 967 (w), 951 (w), 908 (w), 877 (w),
850 (w), 826 (w), 800 (w), 748 (m), 700 (s), 619 (m), 554 (w), 528 (w),
494 (w), 469 (w) cm–1
.
(1S,6S,7R)-7-[(E)-2-phenylvinyl]bicyclo[4.1.0]heptan-2-one (2c)
1H NMR (700 MHz, C6D6): δ = 1.18–1.22 (m, 1 H, 3-H), 1.50–1.54 (m, 1
H, 7-H), 1.55–1.58 (m, 1 H, 5-Ha), 1.57–1.61 (m, 1 H, 4-Ha), 1.61–1.64
(m, 1 H, 4-Hb), 1.64–1.66 (m, 1 H, 2-H), 1.66–1.70 (m, 1 H, 5-Hb),
1.79–1.83 (m, 1 H, 6-H), 2.25–2.30 (m, 1 H, 8-H), 2.49 (d, J = 7.9 Hz, 2
H, 9-H), 6.99 (d, J = 7.3 Hz, 2 H, o-ArH), 7.10–7.14 (m, 1 H, p-ArH),
7.17–7.20 (m, 2 H, m-ArH).
13C NMR (125 MHz, CDCl3): δ = 16.3 (C-4), 24.7 (C-5), 28.6, 28.9 (C-7,
C-3), 31.4 (C-2), 36.7 (C-9), 38.6 (C-8), 44.0 (C-6), 126.2 (C-p), 128.5
(C-m), 128.7 (C-o), 139.6 (C-i), 215.0 (C-1).
Following GP2 using 6c·Br (1.36 g, 4.71 mmol), 5 (0.23 mL, 0.23 g,
2.36 mmol) and LiOtBu (0.38 g, 4.71 mmol) in dried DMSO (30 mL) for
30 min.
Yield: cis-2c: 0.16 g, 0.92 mmol (40%); yellow oil; Rf = 0.45 (hex-
anes/EtOAc, 5:1), tR = 15.76 min; trans-2c: 75 mg, 0.35 mmol (15%);
yellow oil; Rf = 0.20 (hexanes/EtOAc, 10:1), tR = 16.62 min; chroma-
tography with hexanes/EtOAc (15:1).
cis-2c
MS (ESI): m/z = 235.1 [M + Na]+, 447.2 [2 M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C15H16ONa: 235.1093; found:
FT-IR (ATR): 3476 (w), 3025 (w), 2942 (w), 2866 (w), 1682 (vs), 1599
(w), 1494 (w), 1449 (w), 1346 (w), 1245 (w), 1179 (w), 1152 (w),
1074 (w), 1029 (w), 961 (s), 907 (s), 728 (vs), 692 (vs), 645 (w), 560
235.1098.
(w), 480 (w), 407 (w) cm–1
.
1H NMR (700 MHz, CDCl3): δ = 1.77–1.84 (m, 2 H, 5-Ha, 6-Ha), 1.85–
1.92 (m, 1 H, 5-Hb), 1.93–2.02 (m, 2 H, 1-H, 2-H), 2.02–2.13 (m, 2 H, 4-
Ha, 6-Hb), 2.25–2.36 (m, 2 H, 7-H, 4-Hb), 6.13 (dd, J = 7.6, 15.8 Hz, 1 H,
8-H), 6.63 (d, J = 15.8 Hz, 1 H, 9-H), 7.12–7.24 (m, 1 H, p-ArH), 7.26–
7.36 (m, 4 H, o-ArH, p-ArH).
13C NMR (175 MHz, CDCl3): δ = 18.6 (C-6), 23.8 (C-1), 24.5 (C-5), 28.8
(C-2 or C-7), 29.0 (C-2 or C-7), 40.1 (C-4), 123.8 (C-8), 125.9 (C-o or C-
m), 127.5 (C-p), 128.6 (C-o or C-m), 134.7 (C-9), 137.0 (C-i), 209.1 (C-3).
2-(1-Phenylprop-2-enyl)tetrahydrothiophene (14)
Following GP2 using 6c·Br (0.12 g, 0.42 mmol), 5 (0.05 mL, 0.05 g,
0.51 mmol) and KOtBu (0.16 g, 1.44 mmol) in dried THF (20 mL) for
24 h.
Yield: 19 mg, 0.09 mmol (22%); yellow oil; Rf = 0.78 (hexanes/EtOAc,
10:1), tR = 11.35 min; chromatography with hexanes/EtOAc (50:1).
FT-IR (ATR): 3060 (w), 3026 (w), 2944 (m), 2860 (w), 1712 (w), 1636
(w), 1600 (w), 1492 (m), 1441 (m), 1413 (w), 1263 (w), 1182 (w), 991
MS (ESI): m/z = 235.11 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C15H16ONa: 235.1093; found:
(m), 917 (m), 850 (w), 756 (m), 699 (s), 588 (w), 518 (m) cm–1
.
1H NMR (500 MHz, CDCl3): δ = 1.62–1.71 (m, 1 H, 3-Ha), 1.84–1.96 (m,
1 H, 1-Ha), 2.02–2.21 (m, 2 H, 3-Hb, 1-Hb), 2.76–2.86 (m, 2 H, 2-H),
3.26–3.33 (m, 1 H, 4-H), 3.74–3.81 (m, 1 H, 1′-H), 5.01–5.10 (m, 2 H,
3′-H), 5.91–6.27 (m, 1 H, 2′-H), 7.17–7.24 (m, 3 H, m-ArH, p-ArH),
7.27–7.32 (m, 2 H, o-ArH).
13C NMR (125 MHz, CDCl3): δ = 30.6 (C-1), 32.4 (C-2), 35.9 (C-3), 53.4
(C-4), 57.8 (C-1′), 115.4 (C-3′), 126.6 (C-p), 127.8 (C-m), 128.5 (C-o),
140.7 (C-2′), 143.3 (C-i).
235.1102.
trans-2c
FT-IR (ATR): 3476 (w), 3025 (w), 2935 (w), 1681 (vs), 1598 (w), 1493
(w), 1468 (w), 1405 (w), 1340 (m), 1287 (m), 1240 (m), 1124 (w),
1065 (m), 960 (s), 875 (s), 808 (s), 774 (m), 743 (s), 693 (vs), 607 (w),
519 (w), 477 (m) cm–1
.
1H NMR (500 MHz, CDCl3): δ = 1.62–1.78 (m, 2 H, 5-H), 1.80–1.88 (m,
1 H, 1-H), 1.88–1.97 (m, 2 H, 2-H, 6-Ha), 1.99–2.15 (m, 2 H, 4-Ha, 6-
Hb), 2.28–2.37 (m, 2 H, 7-H, 4-Hb), 5.71 (dd, J = 8.5, 15.7 Hz, 1 H, 8-H),
6.51 (d, J = 15.7 Hz, 1 H, 9-H), 7.16–7.21 (m, 1 H, p-ArH), 7.24–7.30
(m, 4 H, o-ArH, m-ArH).
13C NMR (125 MHz, CDCl3): δ = 18.6 (C-5), 21.0 (C-6), 25.5 (C-1), 27.2
(C-7), 34.8 (C-2), 36.8 (C-4), 125.9 (C-o), 126.9 (C-p), 128.4 (C-m),
129.7 (C-8), 130.1 (C-9), 136.9 (C-i), 206.6 (C-3).
MS (ESI): m/z = 227 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C13H16ONa: 227.0865; found:
227.0859.
7-Isopropenylbicyclo[4.1.0]heptan-2-one (2d)
Following GP2 using 6d·Br (7.00 g, 31.6 mmol), 5 (1.46 mL, 1.46 g,
15.1 mmol) and LiOtBu (2.42 g, 30.2 mmol) in dried DMSO (25 mL) for
19 h.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–R

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A. Zens et al.
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Synthesis
Yield: cis-2d: 0.20 g, 1.30 mmol (9%); colorless oil; Rf = 0.34 (hexanes/
EtOAc, 10:1), tR = 6.27 min); trans-2d: 0.22 g, 1.53 mmol (10%); yel-
low oil; Rf = 0.25 (hexanes/EtOAc, 10:1), tR = 6.46 min); 3-(2-isoprope-
nyl-1-oxaspiro[2.5]oct-5-yl)cyclohex-2-en-1-one (16): 230 mg, 0.93
mmol (11%); yellow oil; Rf = 0.34 (hexanes/EtOAc, 10:1), tR = 15.25
min (diastereomer 1), Rf = 0.25, tR = 15.97 min (diastereomer 2); col-
umn chromatography with hexanes/EtOAc (15:1).
13C NMR (175 MHz, CDCl3): δ = 19.9 (C-16), 22.8 (C-5), 23.7 (C-10),
26.1 (C-4), 27.0 (C-9), 31.7 (C-8), 35.4 (C-7), 39.0 (C-6), 39.7 (C-12),
64.0 (C-11), 65.3 (C-13), 111.5 (C-12), 139.0 (C-14), 143.3 (C-3), 143.5
(C-2), 198.7 (C-1).
MS (EI): m/z (%) = 246.1 [M]+ (20), 228.1 (5), 213.1 (3), 200.1 (1), 185.1
(4), 176.1 (100), 161.1 (12), 148.1 (14), 133.1 (14), 118.1 (14), 105.1
(7), 91.0 (12), 79.0 (8), 67.0 (5), 55.0 (7), 41.0 (8), 27.0 (2).
HRMS (EI): m/z [M]+ calcd for C16H22O2: 246.1620; found: 246.1622.
cis-2d
FT-IR (ATR): 3487 (br), 3084 (w), 2936 (s), 2863 (w), 1685 (vs), 1448
(m), 1375 (w), 1347 (m), 1335 (m), 1256 (w), 1235 (m), 1206 (w),
1164 (w), 1140 (w), 1092 (w), 1061 (w), 1019 (w), 940 (w), 917 (vs),
898 (vs), 857 (w), 776 (w), 755 (w), 731 (s), 645 (w), 614 (w), 585 (w),
7-[(1E)-1-methylbut-1-enyl]bicyclo[4.1.0]heptan-2-one (2i)
Following GP2 using 6i·BF4 (2.23 g, 8.60 mmol), 5 (0.42 mL, 0.42 g,
4.30 mmol) and LiOtBu (0.69 g, 8.60 mmol) in dried DMSO (20 mL) for
48 h.
546 (w), 520 (w), 482 (w), 456 (m), 425 (w), 411 (w) cm–1
.
Yield: cis-2i: 15.0 mg, 0.08 mmol (2%); yellow oil; Rf = 0.5 (hex-
anes/EtOAc, 10:1), tR = 5.87 min; trans-2i: 8.00 mg, 0.04 mmol (1%),
yellow oil; Rf = 0.4 (hexanes/EtOAc, 10:1), tR = 6.08 min; chromatogra-
phy with hexanes/EtOAc (15:1).
1H NMR (700 MHz, CDCl3): δ = 1.62–1.71 (m, 1 H, 5-Ha), 1.72–1.81 (m,
3 H, 5-Hb, 4-Ha, 3-H), 1.83 (s, 3 H, 10-H), 1.85–1.91 (m, 1 H, 7-H),
1.97–2.10 (m, 2 H, 2-H, 4-Hb), 2.11–2.23 (m, 2 H, 6-H), 4.77–4.96 (m,
2 H, 9-H).
13C NMR (175 MHz, CDCl3): δ = 19.7 (C-4), 21.7 (C-3), 22.2 (C-5), 23.4
(C-7), 28.0 (C-10), 31.8 (C-2), 39.5 (C-6), 115.3 (C-9), 140.7 (C-8),
210.7 (C-1).
MS (EI): m/z (%) = 150.1 [M]+ (13), 135.1 (100), 122.1 (15), 117.1 (6),
107.1 (25), 93.1 (50), 79.1 (90), 67.1 (8), 53.0 (7), 39.0 (16), 27.0 (8).
cis-2i
FT-IR (ATR): 2959 (s), 2932 (s), 2869 (m), 1685 (vs), 1457 (m), 1379
(w), 1347 (w), 1248 (w), 1228 (w), 1140 (w), 1061 (w), 932 (w), 905
(m), 881 (w), 755 (w), 710 (w), 656 (w), 481 (w), 420 (w) cm–1
.
1H NMR (500 MHz, CDCl3): δ = 0.89 (t, J = 7.6, 3 H, 11-H), 1.58–1.70
(m, 2 H, 4-H), 1.72 (s, 3 H, 12-H), 1.70–1.73 (m, 1 H, 3-H), 1.74–1.80
(m, 1 H, 5-Ha), 1.81–1.88 (m, 1 H, 7-H), 1.93–2.03 (m, 3 H, 10-H, 5-Hb),
2.03–2.10 (m, 2 H, 2-H, 6-Ha), 2.15–2.21 (m, 1 H, 6-Hb), 5.23–5.25 (m,
1 H, 9-H).
13C NMR (125 MHz, CDCl3): δ = 13.7 (C-11), 17.0 (C-12), 19.9 (C-5),
21.3 (C-10), 21.8 (C-3), 22.2 (C-4), 28.3 (C-7), 33.5 (C-2), 33.4 (C-2),
39.6 (C-6), 129.4 (C-8), 131.4 (C-9), 211.0 (C-1).
MS (EI): m/z (%) = 178.1 [M]+ (20), 163.1 (17), 149.1 (100), 135.1 (10),
121.1 (23), 107.1 (30), 93.1 (80), 79.0 (25), 67.0 (6), 55.0 (7), 41.0 (13),
27.0 (5).
HRMS (ESI): m/z [M + H]+ calcd for C12H19O: 179.1430; found:
179.1430.
HRMS (EI): m/z [M]+ calcd for C10H14O: 150.1045; found: 150.1039.
trans-2d
FT-IR (ATR): 3499 (br), 3084 (w), 2936 (s), 2863 (w), 1685 (vs), 1448
(m), 1375 (w), 1347 (m), 1335 (m), 1256 (w), 1235 (m), 1206 (w),
1164 (w), 1140 (w), 1092 (w), 1061 (w), 1019 (w), 940 (w), 917 (vs),
898 (vs), 857 (w), 776 (w), 755 (w), 731 (s), 645 (w), 614 (w), 585 (w),
546 (w), 520 (w), 482 (w), 456 (m), 425 (w), 411 (w) cm–1
.
1H NMR (700 MHz, CDCl3): δ =1.65 (s, 3 H, 10-H), 1.67–1.76 (m, 2 H,
5-H), 1.85–1.88 (m, 2 H, 2-H, 3-H), 1.90–2.01 (m, 2 H, 4-H), 2.09–2.13
(m, 1 H, 6-Ha), 2.18–2.20 (m, 1 H, 7-H), 2.29–2.34 (m, 1 H, 6-Hb), 4.77–
4.81 (m, 2 H, 9-H).
13C NMR (100 MHz, CDCl3): δ = 18.8 (C-5), 20.2 (C-10), 21.2 (C-4), 23.4
(C-3), 30.2 (C-7), 33.2 (C-2), 37.0 (C-6), 111.0 (C-9), 142.5 (C-8), 207.2
(C-1).
MS (EI): m/z (%) = 150.1 [M]+ (55), 135.1 (95), 121.1 (15), 117.1 (6),
107.1 (30), 93.1 (47), 79.1 (97), 71.1 (2), 67.1 (10), 53.0 (10), 39.0 (18),
27.0 (10).
trans-2i
FT-IR (ATR): 2959 (s), 2932 (s), 2869 (m), 1685 (vs), 1457 (m), 1379
(w), 1347 (w), 1248 (w), 1228 (w), 1140 (w), 1061 (w), 932 (w), 905
(m), 881 (w), 755 (w), 710 (w), 656 (w), 481 (w), 420 (w) cm–1
.
1H NMR (500 MHz, CDCl3): δ = 0.93 (t, J = 7.5, 3 H, 11-H), 1.49 (s, 3 H,
12-H), 1.67–1.73 (m, 2 H, 5-H), 1.77–1.82 (m, 1 H, 7-H), 1.82–1.86 (m,
1 H, 3-H), 1.87–1.93 (m, 1 H, 4-Ha), 1.94–2.02 (m, 3 H, 4-Hb, 10-H),
2.04–2.11 (m, 1 H, 6-Ha), 2.14-2.18 (m, 1 H, 2-H), 2.25–2.93 (m, 1 H,
6-Hb), 5.28 (t, J = 7.1, 1 H, 9-H).
HRMS (EI): m/z [M]+ calcd for C10H14O: 150.1045; found: 150.1049.
3-(2-Isopropenyl-1-oxaspiro[2.5]oct-5-yl)cyclohex-2-en-1-one
(16)
FT-IR (ATR): 3481 (br), 2932 (s), 2861 (m), 1709 (m), 1671 (vs), 1445
(m), 1388 (w), 1375 (w), 1345 (w), 1320 (w), 1278 (w), 1248 (w),
1171 (w), 1133 (w), 1116 (w), 1100 (w), 1055 (w), 1007 (w), 994 (w),
978 (w), 966 (w), 901 (vs), 868 (m), 840 (w), 795 (w), 730 (vs), 700
13C NMR (125 MHz, CDCl3): δ = 13.8 (C-12), 14.1 (C-11), 19.0 (C-5),
21.2 (C-10), 21.3 (C-5), 22.8 (C-3), 32.0 (C-2), 32.7 (C-7), 36.9 (C-6),
128.2 (C-9), 131.2 (C.8), 208.2 (C-1).
MS (EI): m/z (%) = 178.1 [M]+ (20), 163.1 (17), 149.1 (100), 135.1 (10),
121.1 (23), 107.1 (30), 93.1 (80), 79.0 (25), 67.0 (6), 55.0 (7), 41.0 (13),
27.0 (5).
(w), 647 (w), 609 (w), 547 (m), 504 (w), 427 (m) cm–1
.
1H NMR (700 MHz, CDCl3): δ = 1.21–1.31 (m, 2 H, 8-Ha, 12-Ha), 1.42–
1.46 (m, 2 H, 9-H), 1.64–1.67 (m, 1 H, 10-Ha), 1.74–1.75 (m, 3 H, 16-
H), 1.76–1.82 (m, 2 H, 8-Hb, 10-Hb), 1.91–1.98 (m, 3 H, 5-H, 12-H),
2.34–2.37 (m, 2 H, 4-H), 2.40–2.43 (m, 2 H, 6-H), 2.86–2.91 (m, 1 H, 7-
H), 3.14 (s, 1 H, 13-H), 4.90–5.00 (m, 2 H, 15-H), 6.64 (t, J = 4.3 Hz, 1 H,
2-H).
HRMS (ESI): m/z [M + H]+ calcd for C12H19O: 179.1430; found:
179.1430.
7-Cyclopent-1-en-1-ylbicyclo[4.1.0]heptan-2-one (2f)
Following GP2 using 6f·BF4 (3.00 g, 11.7 mmol), 5 (0.57 mL, 0.57 g,
5.90 mmol) and LiOtBu (0.94 g, 11.7 mmol) in dried DMSO (20 mL) for
24 h.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–R

P
A. Zens et al.
Paper
Synthesis
Yield: cis-2f: 0.06 g, 0.35 mmol (6%); yellow oil; Rf = 0.5 (hexanes/EtO-
Ac, 5:1), tR = 7.46 min); trans-2f: 0.108 g, 0.35 mmol (11%); yellow oil;
Rf = 0.4 (hexanes/EtOAc, 5:1), tR = 7.69 min); chromatography with
hexanes/EtOAc (15:1).
0.27 H, 9-Hb*), 7.28–7.29 (m, 0.37 H, p-ArH*), 7.30–7.39 (m, 0.95 H,
m-ArH* or o-ArH*), 7.31–7.33 (m, 1 H, p-ArH), 7.35–7.40 (m, 2 H, m-
ArH or o-ArH), 7.48–7.50 (m, 2 H, o-ArH or m-ArH), 7.61–7.63 (m,
0.54 H, o-ArH* or m-ArH*); * denotes signals of cis-2h.
13C NMR (175 MHz, CDCl3): δ = 18.9 (C-5), 19.7 (C-5*), 21.2 (C-4), 21.8
(C-4* or C-3*), 22.3 (C-3* or C-4*), 24.5 (C-3), 27.9 (C-7), 28.0 (C-2* or
C-6*), 29.7 (C-7*), 34.6 (C-2), 37.0 (C-6), 39.5 (C-6* or C-2*), 111.5 (C-
9), 116.3 (C-9*), 125.6 (C-o* or C-m*), 126.1 (C-o or C-m), 127.9 (C-p),
128.0 (C-p*), 128.4 (C-m or C-p), 128.5 (C-m* or C-o*), 139.5 (C-i*),
140.4 (C-i), 142.1 (C-8*), 146.0 (C-8), 207.8 (C-1), 210.4 (C-1*); * de-
notes signals of cis-2h.
MS (EI): m/z (%) = 212.1 [M]+ (33), 197.1 (39), 184.1 (20), 169.1 (13),
155.1 (57), 141.1 (41), 128.1 (100), 115.1 (27), 103.1 (11), 91.1 (22),
84.0 (11), 77.0 (17), 65.0 (4), 51.0 (6), 39.0 (4), 27.0 (2).
cis-2f
FT-IR (ATR): 2937 (s), 2845 (m), 1687 (vs), 1446 (w), 1347 (m), 1242
(w), 1177 (w), 1150 (w), 1042 (w), 956 (w), 920 (w), 903 (w), 835 (w),
755 (w), 479 (w) cm–1
.
1H NMR (300 MHz, CDCl3): δ = 1.64–1.74 (m, 2 H, 5-H), 1.75–1.83 (m,
2 H, 4-Ha, 3-H), 1.84–1.97 (m, 4 H, 11-H, 7-H, 2-H), 1.96–2.09 (m, 2 H,
6-Ha, 4-Hb), 2.15–2.18 (m, 1 H, 6-Hb), 2.24–2.39 (m, 4 H, 12-H, 10-H),
5.46–5.49 (m, 1 H, 9-H).
13C NMR (175 MHz, CDCl3): δ = 19.6 (C-4), 22.0 (C-3), 22.7 (C-5), 23.3
(C-11), 26.2 (C-7), 27.8 (C-2), 32.7 (C-12), 36.1 (C-10), 39.6 (C-6),
129.3 (C-9), 139.1 (C-8), 210.8 (C-1).
HRMS (EI): m/z [M]+ calcd for C15H16O: 212.1198; found: 212.1201.
MS (EI): m/z (%) = 176.1 [M]+ (78), 158.1 (24), 147.1 (45), 133.1 (16),
120.1 (68), 105.1 (45), 91.1 (100), 87.0 (10), 79.1 (37), 67.1 (20), 55.0
(18), 55.0 (18), 41.0 (24), 27.0 (12).
2-(2-Phenylprop-2-enyl)tetrahydrothiophene (15)
FT-IR (ATR): 3079 (w), 3054 (w), 3023 (w), 2941 (s), 2958 (w), 1802
(w), 1626 (w), 1599 (w), 1574 (w), 1493 (s), 1441 (s), 1303 (w), 1260
(w), 1184 (w), 1158 (w), 1074 (w), 1028 (m), 968 (w), 896 (s), 845
HRMS (EI): m/z [M]+ calcd for C12H16O: 176.1201; found: 176.1202.
(w), 777 (vs), 699 (vs), 594 (w), 551 (w), 510 (w) cm–1
.
1H NMR (700 MHz, CDCl3): δ = 1.58–1.66 (m, 1 H, 1-Ha), 1.77–1.90 (m,
1 H, 3-Ha), 1.97–2.13 (m, 2 H, 1-Hb, 3-Hb), 2.77–2.86 (m, 3 H, 1′-H, 2-
Ha), 2.86–2.95 (m, 1 H, 4-H), 3.43 (m, 1 H, 2-Hb), 5.10–5.32 (m, 2 H, 3′-
H), 7.22–7.43 (m, 5 H, o-ArH, p-ArH, m-ArH).
13C NMR (175 MHz, CDCl3): δ = 30.2 (C-3), 32.4 (C-2), 36.8 (C-1), 43.5
(C-1′), 47.0 (C-4), 114.0 (C-3′), 126.3 (C-m), 127.5 (C-p), 128.3 (C-o),
140.8 (C-i), 147.1 (C-2′).
trans-2f
FT-IR (ATR): 2937 (s), 2845 (m), 1687 (vs), 1446 (w), 1347 (m), 1242
(w), 1177 (w), 1150 (w), 1042 (w), 956 (w), 920 (w), 903 (w), 835 (w),
755 (w), 479 (w) cm–1
.
1H NMR (300 MHz, CDCl3): δ = 1.64–1.74 (m, 2 H, 5-H), 1.75–1.83 (m,
2 H, 4-Ha, 3-H), 1.84–1.97 (m, 4 H, 11-H, 7-H, 2-H), 2.00–2.09 (m, 2 H,
6-Ha, 4-Hb), 2.15–2.21 (m, 1 H, 6-Hb), 2.24–2.39 (m, 4 H, 12-H, 10-H),
5.46–5.49 (m, 1 H, 9-H).
MS (EI): m/z (%) = 204.1 [M]+ (37), 87.0 (100).
HRMS (EI): m/z [M]+ calcd for C13H16S: 204.0975; found: 204.0973.
13C NMR (175 MHz, CDCl3): δ = 18.7 (C-5), 21.2 (C-3), 23.1 (C-11), 23.8
(C-4), 25.4 (C-10), 32.3 (C-12), 32.5 (C-7), 33.3 (C-2), 36.9 (C-6), 125.5
(C-9), 141.6 (C-8), 207.7 (C-1).
MS (EI): m/z (%) = 176.1 [M]+ (78), 158.1 (24), 147.1 (45), 133.1 (16),
120.1 (68), 105.1 (45), 91.1 (100), 87.0 (10), 79.1 (37), 67.1 (20), 55.0
(18), 55.0 (18), 41.0 (24), 27.0 (12).
Funding Information
Generous financial support from the Ministerium für Wissenschaft,
Forschung und Kunst des Landes Baden-Württemberg, the Deutsche
Forschungsgemeinschaft (shared instrumentation grants for 700 MHz
NMR) and the Fonds der Chemischen Industrie is gratefully acknowl-
edged.
HRMS (EI): m/z [M]+ calcd for C12H16O: 176.1201; found: 176.1202.
7-(1-Phenylvinyl)bicyclo[4.1.0]heptan-2-one (2h)
)(
Following GP2 using 6h·Br (1.92 g, 6.70 mmol), 5 (0.33 mL, 0.32 g,
3.40 mmol) and LiOtBu (0.54 g, 6.70 mmol) in dried DMSO (20 mL) for
48 h.
Supporting Information
Yield: cis-2h/trans-2h: 0.12 g, 0.92 mmol (18%); yellow oil; Rf = 0.7
(hexanes/EtOAc, 5:1), tR = 14.59 min (cis-2h), tR = 15.08 (trans-2h); dr
Supporting information for this article is available online at
https://doi.org/10.1055/s-0036-1591554.
S
u
p
p
o
nrtogI
f
rmoaitn
S
u
p
p
ortiInfogrmoaitn
(cis/trans)
= 31:69; 2-(2-phenylprop-2-enyl)tetrahydrothiophene
(15): 0.08 g, 0.40 mmol (12%); yellow oil; Rf = 0.8 (hexanes/EtOAc,
10:1), tR = 12.16 min; column chromatography with hexanes/EtOAc
(15:1).
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