Synthesis of cyclopropenes via 1,2-elimination of bromocyclopropanes catalyzed by crown ether

Article abstract of DOI:10.1055/s-0028-1088122

A new synthetic protocol for the preparation of 3,3-disubstituted cyclopropenes from the corresponding bromocyclopropanes via a base-assisted 1,2-elimination has been developed. Employment of catalytic amounts of 18-crown-6 in ethereal solvents allowed for improved yields, as compared to the classical procedure employing dimethyl sulfoxide, making this protocol applicable to the synthesis of hydrophilic cyclopropenes. The application of this new method for the efficient synthesis of cyclopropene-3-carboxamides, an important class of functionalized 3,3-disubstituted cyclopropenes, is demonstrated. Scope and limitation studies are discussed. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0028-1088122

PAPER
1477
Synthesis of Cyclopropenes via 1,2-Elimination of Bromocyclopropanes
Catalyzed by Crown Ether
C
yclopropenes via 1,2-E
i
limina
l
tion of
l
Bromo
i
cyclopr
a
opanes m M. Sherrill, Ryan Kim, Michael Rubin*
Department of Chemistry, University of Kansas, 1251 Wescoe Hall Drive, Lawrence, KS 66045-758, USA
Fax +1(785)8645396; E-mail: mrubin@ku.edu
Received 12 November 2008; revised 17 December 2008
significant development in the decades8 since the first re-
port on the synthesis of 3,3-disubstituted cyclopropenes
via the 1,2-elimination of a hydrogen halide in the pres-
ence of sodium tert-butoxide and dimethyl sulfoxide.9 At
Abstract: A new synthetic protocol for the preparation of 3,3-di-
substituted cyclopropenes from the corresponding bromocyclopro-
panes via a base-assisted 1,2-elimination has been developed.
Employment of catalytic amounts of 18-crown-6 in ethereal sol-
vents allowed for improved yields, as compared to the classical pro- the same time, the requisite use of dimethyl sulfoxide as
cedure employing dimethyl sulfoxide, making this protocol
reaction medium significantly limits the potential of the
applicable to the synthesis of hydrophilic cyclopropenes. The appli-
method for scale-up and its appeal for process develop-
cation of this new method for the efficient synthesis of cyclopro-
ment. Furthermore, it becomes a major liability when the
pene-3-carboxamides, an important class of functionalized 3,3-
target cyclopropene is relatively hydrophilic. In this case,
disubstituted cyclopropenes, is demonstrated. Scope and limitation
repetitive washing of the organic phase with water, neces-
sary for complete removal of dimethyl sulfoxide,8 leads to
substantial loss of the product. Alternative approaches in-
volving removal of dimethyl sulfoxide by distillation or
column chromatography usually do not provide satisfac-
tory results, particularly in multigram-scale syntheses.
studies are discussed.
Key words: amides, cyclopropenes, crown ether, eliminations,
phase-transfer catalysis
Recent impressive advances in the development of novel,
highly selective additions to cyclopropenes1 have signifi-
cantly broadened the application of these building blocks
in organic chemistry.2,3 Accordingly, recent efforts have
focused on the development of efficient synthetic ap-
proaches for the preparation of diversely substituted cy-
clopropenes. To date, two general methods have mainly
been used for the synthesis of cyclopropenes 1; they in-
clude the transition-metal-catalyzed addition of car-
benoids 2 to alkynes 3 (Scheme 1, path A)4 and a protocol
involving 1,2-elimination of H–Hal5 or Hal–Hal6 (Hal =
halogen) entities from cyclopropyl halide precursors 4
(Scheme 1, path B).
In an attempt to overcome this problem, we considered the
possibility of replacing dimethyl sulfoxide with alterna-
tive, more practical solvents. We rationalized that em-
ployment of chelating agents, such as crown ethers,10
could potentially help enhance the basicity of potassium
tert-butoxide and enable an efficient elimination reaction
in less polar media. It should be mentioned that prepara-
tive methods for 1,2-dehydrohalogenation in nonpolar
media employing 18-crown-6 as phase-transfer catalyst
have been reported previously;10 however, they have nev-
er been used for the preparation of strained olefins. Herein
we wish to report a new protocol for the synthesis of cy-
clopropenes via a base-assisted 1,2-elimination in ethereal
solvents in the presence of catalytic amounts of 18-crown-
6. We also demonstrate the application of the new method
for the efficient synthesis of cyclopropene-3-carbox-
amides, an important class of functionalized cyclopro-
penes.11
The former method has been receiving much attention
from the synthetic community, resulting in substantial ex-
pansion of its scope, thereby making available a range of
cyclopropenes,7 including optically active compounds.4d–g
In contrast, the second approach has not undergone any
R2
R3
First, we tested the dehydrobromination of 2-bromo-1-
methyl-1-phenylcyclopropane (5a) with potassium tert-
butoxide in tetrahydrofuran in the presence of various
amounts of 18-crown-6 (Table 1, entries 1–3). It was
found that the addition of stoichiometric amounts of
crown ether facilitated a rapid dehydrohalogenation; how-
ever, notable decomposition of product 6a led to moderate
overall yields. Decreasing the amount of crown ether was
beneficial for the reaction yield (Table 1, entries 2 and 3),
and with additional optimization we discovered yields can
be further improved by lowering the reaction temperature
to 30 °C (Table 1, entry 4). Screening of various ethereal
solvents demonstrated that tetrahydrofuran and diethyl
ether appeared to be the most suitable media for this trans-
path A
path B
2
+
formal [2+1]
cycloaddition
R1
R2
R1
R3
3
1
R2
R1
R3
1,2-elimination
X
4
Y
Scheme 1 The two most important retrosynthetic approaches to the
cyclopropene core
SYNTHESIS 2009, No. 9, pp 1477–1484
Advanced online publication: 14.04.2009
DOI: 10.1055/s-0028-1088122; Art ID: M07008SS
x
x
.
x
x
.2
0
0
9
© Georg Thieme Verlag Stuttgart · New York

1478
W. M. Sherrill et al.
PAPER
formation. In contrast, reactions in dibutyl ether and di-
glyme did not produce any product at all (Table 1, entries
6 and 9), while other ethers resulted in a much slower and
less efficient reaction. Although both tetrahydrofuran and
diethyl ether provided essentially the same results, we
chose tetrahydrofuran as the more practical solvent.
Table 2 Preparative Syntheses of Cyclopropenes
t-BuOK (1.2 equiv)
R
R
18-crown-6 (10 mol%)
THF
Br
5
6
Entry R
Time Temp Yielda
(h)
18
18
18
3
(°C)
30
30
40
30
30
30
30
30
30
30
40
30
30
(%)
Table 1 Optimization of 1,2-Elimination Reaction
1
2
Ph (5a, 6a)
85b (79)
84
Ph
Ph
t-BuOK (1.2 equiv)
Naph (5b, 6b)
18-crown-6
solvent
Br
5a
6a
3
2-FC6H4 (5c, 6c)
75
Entry
18-Crown-6 Solvent
(equiv)
Time
(h)
Temp
(°C)
Yielda
(%)
4
C(O)NEt2 (5d, 6d)
90c (60)
85 (69)
81 (30)
85 (61)
75 (50)
95
5
C(O)N(i-Pr)2 (5e, 6e)
C(O)N(CH2CH2)2O (5f, 6f)
C(O)N(CH2CH2)2CH2 (5g, 6g)
C(O)N(CH2CH2)2NMe (5h, 6h)
C(O)N[(CH2)5Me]Me (5i, 6i)
C(O)NPh2 (5j, 6j)
2
1
2
1.2
0.3
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
THF
1
3
50
50
50
30
30
30
30
30
30
30
40
65
70
93
86
0
6
1
THF
7
1
3
THF
3
8
1
4
THF
14
48
48
48
48
48
14
9
2
5
1,4-dioxane
Bu2O
10
11
12
13
2
0
6
C(O)N(4-O2NC6H4)Et (5k, 6k)
C(O)N(Ph)Et (5l, 6l)
C(O)N(PMP)Et (5m, 6m)
18
2
0
7
TBDME
DME
76
21
0
30
8
24
53
9
diglyme
Et2O
a Isolated yields (250 mg scale); isolated yields obtained for reactions
in DMSO are provided in parentheses.
10
84
b The reaction was performed on a 10.0 g scale.
a Yield determined by GC.
c The reaction performed on a 15.0 g scale afforded 6d in 89% yield.
more sensitive toward nucleophilic substitution by an
alkoxide. To prove this rationale, we tested the dehydro-
bromination reaction on a series of N-ethyl-N-arylamides
5k–m (Table 2, entries 11–13). As expected, the reaction
of amide 5k possessing an electron-poor 4-nitrophenyl
group resulted in rapid alcoholysis, affording N-ethyl-4-
nitroaniline as the sole reaction product (entry 11). It
should be mentioned that formation of tert-butyl ester 9
(Scheme 2) was observed at early stages of the reaction in
this case.13 Similar results were obtained with phenyl-
substituted amide 5l; however, product decomposition
proceeded much slower, permitting isolation of the corre-
sponding cyclopropene 6l in poor yield (entry 12). Final-
ly, more-electron-rich anisidine-derived amide 5m
afforded cyclopropene 6m in moderate yield (entry 13).
Overall, these results demonstrated a clear-cut correlation
between the electronic nature of the carboxamide and the
stability of the corresponding product toward nucleophilic
attack under the described reaction conditions.
Preparative-scale synthesis under the optimized condi-
tions provided 3-methyl-3-phenylcyclopropene (6a) in
high yield, which slightly exceeded that obtained in di-
methyl sulfoxide (Table 2, entry 1).8 Similarly, other 3-
methyl-3-arylcyclopropenes 6b,c were efficiently synthe-
sized by the tetrahydrofuran protocol (entries 2 and 3).
The major advantage of the new method was revealed in
the synthesis of significantly more polar cyclopropenecar-
boxamides 6d–i,l,m (Table 2, entries 4–9, 12, and 13).
Thus, in contrast to the reactions performed in dimethyl
sulfoxide, which suffered from substantial product loss
due to the high hydrophilicity of the compounds, the new
conditions allowed for high isolated yields for all alkyl-
substituted amides tested.
On the other hand, an attempted reaction employing N,N-
diphenylcyclopropenecarboxamide 5j did not lead to the
formation of a cyclopropene (Table 2, entry 10). The only
product detected by GC-MS analysis of the crude reaction
mixture was diphenylamine; this suggests that this type of
substrate has increased carbonyl activity.12 Apparently,
the less-electron-rich nitrogen in diphenylamide 6j, as
compared to dialkylamide analogs (Scheme 2), results in
a greater positive charge on the carbon atom of carbonyl
group. Furthermore, diphenylamide species 8j (R = Ph)
(Scheme 2) makes a much better nucleofuge than dialkyl-
amide equivalents, altogether making arylamides much
In conclusion, a convenient, general protocol for the syn-
thesis of cyclopropenes via dehydrobromination of bro-
mocyclopropanes has been developed. The new
optimized conditions significantly improved the scale-up
compatibility of the method and allowed for expanding
the scope of available cyclopropenes, particularly those
possessing polar functionalities. Application of the new
Synthesis 2009, No. 9, 1477–1484 © Thieme Stuttgart · New York

PAPER
Cyclopropenes via 1,2-Elimination of Bromocyclopropanes
1479
1H NMR (400 MHz, CDCl3): d = 7.35–7.29 (m, 2 H), 7.16–7.11 (m,
2 H), 2.14 (br d, J = 7.6 Hz, 1 H), 1.84 (br s, 1 H), 1.72 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 160.2 (d, 1JCF = 250.3 Hz), 130.0
(br), 129.7 (br), 129.2 (d, J = 8.0 Hz), 124.2, 115.8 (d, 2JCF = 21.2
Hz), 35.5 (br), 33.8 (br), 25.1 (br), 14.1 (br).
O
O
Ot-Bu
NR2
Ot-Bu
NR2
6
7
O
19F NMR (376.5 MHz, CDCl3): d = –113.6.
– NR2 (8)
ESI-HRMS (TOF): m/z [M – Br]+ calcd for C10H10F: 149.0767;
Ot-Bu
found: 149.0767.
9
Bromocyclopropanes 5b and 5c
Scheme 2 Decomposition of cyclopropene-3-carboxamides upon
nucleophilic attack by tert-butoxide species
Bromocyclopropanes 5b and 5c were prepared by partial reduction
of the corresponding dibromocyclopropanes 10b and 10c with
EtMgBr in the presence of Ti(Oi-Pr)4 (cat.) (Scheme 4) according
to the published general protocol.8
protocol for the efficient preparation of cyclopropene-3-
carboxamides has been demonstrated.14
Ar
Ar
Ti(Oi-Pr)4 (cat.)
EtMgBr, Et2O
Br
Br
NMR spectra were recorded on a Bruker Avance DPX-400 instru-
ment, equipped with a quadruple-band gradient probe (H/C/P/F
QNP). 13C NMR spectra were registered with broad-band decou-
pling. Column chromatography was carried out on silica gel (Selec-
to Scientific, 63–200 mm). Precoated silica gel plates (Merck
Kieselgel 60 F-254) were used for TLC. IR spectra were recorded
on a Shimadzu FT-IR 8400S instrument. HRMS was carried out on
an LCT Premier (Micromass Technologies) instrument; ESI and
TOF detection techniques were used. The abbreviation ‘ps t’ is used
to describe pseudo-triplets in the 1H NMR spectra. When the prod-
uct was characterized as a mixture of diastereomers, the chemical
shifts of the multiplets corresponding to both of the diastereomeric
groups are listed, followed by a summation sign (S) to indicate that
the sum of both integrals is given. No special notation is used to de-
scribe equivalent carbons in 13C NMR spectra.
Br
10b: Ar = 2-naphthyl
10c: Ar = 2-FC6H4
5b: Ar = 2-naphthyl
5c: Ar = 2-FC6H4
Scheme 4
2-Bromo-1-methyl-1-(2-naphthyl)cyclopropane (5b)
Bromocyclopropane 5b was obtained as a mixture of diastereomers
(ca. 2:1, by 1H NMR). It was isolated and purified by short column
chromatography (silica gel, hexanes); this afforded an opaque,
slowly crystallizing oil. Yield: 5.19 g (73%).
IR (film): 3053, 2959, 2926, 1599, 1504, 1443, 1209, 1153, 856,
818, 746, 505, 476 cm–1.
1H NMR (400 MHz, CDCl3): d = [7.90–7.79 (m), S4 H], [7.72 (s),
S1 H], [7.54–7.42 (m), S2 H], [3.35 (dd, J = 8.1 Hz, 4.5 Hz), 3.19
(dd, J = 7.3 Hz, 4.3 Hz), S1 H], [1.81 (ps t, J = 6.6 Hz), 1.57 (m),
S1 H], [1.74 (s), 1.57 (s), S3 H], [1.49 (ps t, J = 7.3 Hz), 1.02 (ps t,
J = 6.1 Hz), S1 H], [1.19 (dd, J = 6.3 Hz, 4.6 Hz), 0.85 (dd, J = 5.8
Hz, 4.0 Hz), S1 H].
Dibromocyclopropanes 10b and 10c
The dibromocyclopropane starting materials 10b and 10c were pre-
pared from 2-acetonaphthone and 2-fluoroacetophenone, respec-
tively (Scheme 3), according to general procedures for the synthesis
of dibromocyclopropanes described in our recent report.8
13C NMR (100 MHz, CDCl3): d = 141.9, 140.0, 139.9, 133.4, 132.5,
132.2, 128.4, 128.0, 127.9, 127.8, 127.7, 127.6, 126.3, 125.9, 125.7,
125.6, 125.5, 30.4, 28.3, 27.9, 26.9, 26.3, 24.1, 23.3, 22.3.
ESI-HRMS (TOF): m/z [M – Br]+ calcd for C14H13: 181.1017;
found: 181.1022.
Ph3PMeBr
Ar
Me
Ar
Me
t-BuOK, THF
O
Ar
Me
Br
Br
CHBr3
50% aq NaOH
2-Bromo-1-(2-fluorophenyl)-1-methylcyclopropane (5c)
Bromocyclopropane 5c was purified by flash chromatography (sil-
ica gel, hexanes) to afford a mixture of diastereomers (ca. 2:1) as a
colorless oil. Yield: 6.89 g (91%).
n-C16H33NMe3Br (cat.)
10b: Ar = 2-naphthyl
10c: Ar = 2-FC6H4
Scheme 3
IR (film): 3041, 2962, 2926, 1493, 1447, 1207, 1153, 1032, 756,
621, 505 cm–1.
1H NMR (400 MHz, CDCl3): d = [7.32–7.21 (m), S 2 H], [7.17–
7.02 (m), S 2 H], [3.27 (dd, J = 8.3, 4.8 Hz), 3.15 (dd, J = 7.6, 4.6
Hz), S1 H], [1.58 (s), 1.43 (s), S3 H], [1.58 (m), 1.43 (ps t, J = 6.6
Hz), S1 H], [1.35 (m), 1.10 (dd, J = 6.3, 4.8 Hz), S1 H].
13C NMR (100 MHz, CDCl3): d = 163.4 (d, 1JCF = 248.1 Hz), 163.0
(d, 1JCF = 248.8 Hz), 131.6, 131.4 (d, J = 4.3 Hz), 130.0 (d, J = 4.0
Hz), 129.6, 128.8 (d, J = 8.3 Hz), 128.6 (d, J = 7.9 Hz), 124.1 (d,
J = 3.7 Hz), 123.9 (d, J = 3.7 Hz), 115.7 (d, J = 21.2 Hz), 115.6 (d,
J = 22.0 Hz), 29.2, 27.3, 24.9, 24.4, 23.4, 22.5, 22.4, 22.3.
2,2-Dibromo-1-methyl-1-(2-naphthyl)cyclopropane (10b)
Flash column chromatography (silica gel, hexanes) gave a clear oil.
Yield: 10.31 g (66%).
1H NMR (400 MHz, CDCl3): d = 7.94–7.88 (m, 4 H), 7.76 (s, 1 H),
7.58–7.53 (m, 2 H), 2.36 (d, J = 7.6 Hz, 1 H), 1.91 (d, J = 7.6 Hz, 1
H), 1.85 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 140.0, 133.3, 132.6, 128.2, 127.9,
127.8, 127.0, 126.9, 126.3, 126.1, 36.7, 36.0, 33.9, 27.7.
ESI-HRMS (TOF): m/z [M – Br]+ calcd for C14H12Br: 259.0122;
found: 259.0125.
19F NMR (376.5 MHz, CDCl3): d = –114.9, –115.8.
ESI-HRMS (TOF): m/z [M – Br]+ calcd for C10H10F: 149.0767;
found: 149.0767.
2,2-Dibromo-1-(2-fluorophenyl)-1-methylcyclopropane (10c)
Quick filtration through a short plug of silica gel (hexanes) afforded
a clear oil. Yield: 10.14 g (88%).
Synthesis 2009, No. 9, 1477–1484 © Thieme Stuttgart · New York

1480
W. M. Sherrill et al.
PAPER
4-[(2-Bromo-1-methylcyclopropyl)carbonyl]morpholine (5f)
Cyclopropanecarboxamide 5f was prepared according to the typical
procedure (as described for 5d) from acyl chloride 12 (5.00 g, 25.3
mmol) and freshly distilled morpholine (6.60 mL, 6.62 g, 76 mmol).
Kugelrohr vacuum distillation (oven temperature 133 °C/0.6 Torr)
of the resulting residue afforded a mixture of trans- and cis-isomers
of 5f (1:1) as a colorless oil. Yield: 5.52 g (88%).
2-Bromo-1-methylcyclopropanecarbonyl Chloride (12)
A mixture of carboxylic acid 1115 (1:1 diastereomeric mixture; 25.9
g, 200 mmol) and freshly distilled SOCl2 (50 mL) was stirred over-
night at r.t (Scheme 5). The excess SOCl2 was removed by distilla-
tion at ambient pressure. Distillation of the residue in vacuo (bp 50–
53 °C/10 Torr) gave a diastereomeric mixture of acyl chlorides 12
(1:1) as a colorless oil. This material was used as is in further acy-
lations of primary and secondary amines as described below. Yield:
37.9 g (96%).
IR (film): 2962, 2922, 2854, 2897, 1643, 1460, 1429, 1281, 1207,
1153, 1115, 1032, 851, 623, 505 cm–1.
1H NMR (400 MHz, CDCl3): d = 3.67–3.64 (m, 8 H), [3.15 (dd,
J = 8.3 Hz, 5.1 Hz), 2.98 (dd, J = 7.6 Hz, 4.8 Hz), S1 H], [1.70 (ps
t, J = 8.1), 1.58 (dd, J = 6.8 Hz, 4.8 Hz), S1 H], [1.45 (s), 1.37 (s),
S3 H], [1.20 (ps t, J = 7.3 Hz), 0.91 (dd, J = 6.6 Hz, 4.8 Hz), S1 H].
CO2H
Br
COCl
Br
SOCl2
11
12
13C NMR (100 MHz, CDCl3): d = 170.6, 168.9, 67.1 (–), 66.9 (–),
66.7 (–, 2C), 46.4 (–), 42.6 (–), 27.5 (+), 27.1, 25.6, 25.4 (+), 21.6
(–), 21.4 (+), 21.2 (–), 19.4 (+).
CONR1R2
R1R2NH
anhyd THF, Et3N
ESI-HRMS (TOF): m/z [M – Br]+ calcd for C9H14NO2: 168.1025;
Br
found: 168.1026.
5d–h,j–m, 13
5d: R1 = R2 = Et
5e: R1 = R2 = i-Pr
5j: R1 = R2 = Ph
1-[(2-Bromo-1-methylcyclopropyl)carbonyl]piperidine (5g)
Cyclopropanecarboxamide 5g was prepared according to the typical
procedure (as described for 5d) from acyl chloride 12 (5.10 g, 25.8
mmol) and freshly distilled piperidine (7.7 mL, 6.6 g, 85 mmol).
Kugelrohr vacuum distillation (oven temperature 150 °C/0.4 Torr)
of the resulting residue afforded a mixture of trans- and cis-isomers
of 5g (1:1) as a colorless oil. Yield: 6.26 g (98%).
5k: R1 = 4-O2NC6H4, R2 = Et
5l: R1 = Ph, R2 = Et
5f: R1R2 = (CH2CH2)2O
5g: R1R2 = (CH2CH2)2CH2
5h: R1R2 = (CH2CH2)2NMe
5m: R1 = 4-MeOC6H4, R2 = Et
13: R1 = n-Hexyl, R2 = H
Scheme 5
IR (film): 2934, 2854, 1641, 1431, 1207, 1151, 1014, 854 cm–1.
2-Bromo-N,N-diethyl-1-methylcyclopropanecarboxamide(5d);
Typical Procedure
1H NMR (400 MHz, CDCl3): d = [3.70–3.57 (m), 3.49–3.35 (m), S4
H], [3.11 (dd, J = 8.1 Hz, 4.8 Hz), 2.94 (dd, J = 8.1 Hz, 4.8 Hz), S1
H], 1.65–1.45 (m, 7 H), [1.38 (s), 1.30 (s), S3 H], [1.10 (ps t, J = 8.6
Hz, 5.3 Hz), 0.82 (ps t, J = 6.8 Hz, 4.8 Hz), S1 H].
13C NMR (100 MHz, CDCl3): d = 170.1, 168.8, 46.9, 43.2, 27.9,
27.5, 26.5, 26.1, 26.0, 25.7, 25.6, 24.6, 24.5, 21.9, 21.7, 21.3, 19.5.
Acid chloride 12 (5.00 g, 25.3 mmol) in anhyd THF (35 mL) was
added dropwise to a stirred soln of freshly distilled Et2NH (5.56 g,
7.94 mL, 76.0 mmol) in anhyd THF (20 mL) under a N2 atmosphere
(Scheme 5). After the mixture had stirred at r.t. for ca. 1 h, the start-
ing materials were consumed (GC-MS). The precipitate formed in
the reaction mixture was removed by suction filtration and the filter
cake was rinsed with THF (2 × 20 mL). Then the precipitate was
dissolved in H2O (20 mL) and extracted with EtOAc (2 × 20 mL).
The combined organic phases were washed with brine (20 mL),
dried (MgSO4), combined with the THF filtrate, and evaporated in
vacuo. Kugelrohr vacuum distillation (90 °C/0.6 Torr) gave a dias-
tereomeric mixture of products (1:1) as a pale-yellow oil. Yield
(overall): 5.64 g (95%).
ESI-HRMS (TOF): m/z [M – Br]+ calcd for C10H16NO: 166.1232;
found: 166.1233.
1-[(2-Bromo-1-methylcyclopropyl)carbonyl]-4-methylpipera-
zine (5h)
Cyclopropanecarboxamide 5h was prepared according to the typi-
cal procedure (as described for 5d) from acyl chloride 12 (5.00 g,
25.3 mmol) and freshly distilled 1-methylpiperazine (8.5 mL, 7.61
g, 76 mmol). Purification by Kugelrohr vacuum distillation (oven
temperature 150 °C/0.6 Torr) afforded a mixture of trans- and cis-
isomers of 5h (1:1) as a colorless oil. Yield: 5.72 g (87%).
IR (film): 2970, 2934, 1637, 1425, 1209, 1153, 636, 503 cm–1.
1H NMR (400 MHz, CDCl3): d = [3.73–3.69 (m), 3.61–3.55 (m),
3.35–3.30 (m), 3.21–3.17 (m), S4 H], [3.13 (dd, J = 7.3 Hz, 4.6 Hz),
2.96 (dd, J = 7.3 Hz, 4.6 Hz), S1 H], [1.67 (dd, J = 6.7 Hz, 4.8 Hz),
1.59 (dd, J = 6.7 Hz, 4.8 Hz), S1 H], [1.25 (t, J = 14.3 Hz, 7.1 Hz),
1.10 (t, J = 14.0 Hz, 7.0 Hz), S3 H], [1.43 (s), 1.35 (s), S3 H], [1.11–
1.06 (m), 0.86 (dd, J = 6.7 Hz, 5.0 Hz), S4 H].
13C NMR (125 MHz, CDCl3): d = 171.1, 169.6, 41.2, 41.1, 39.0,
38.9, 27.9, 27.4, 25.9, 22.2, 22.0, 21.6, 21.4, 20.6, 13.9, 13.7, 12.4,
12.2.
IR (film): 2935, 2791, 1643, 1431, 1207, 1151, 1040, 1003 cm–1.
1H NMR (400 MHz, CDCl3): d = 3.75–3.45 (m, 4 H), [3.09 (dd,
J = 4.89 Hz, 4.12 Hz), 2.92 (dd, J = 4.89 Hz, 4.12 Hz), S1 H], 2.55–
2.27 (m, 4 H), [2.25 (s), 2.24 (s), S3 H], [1.60 (ps t, J = 8.1 Hz, 7.1
Hz), 1.48 (ps t, J = 8.1 Hz, 7.1 Hz), S1 H], [1.38 (s), 1.30 (s), S3 H],
[1.11 (ps t, J = 7.7 Hz, 6.8 Hz), 0.82 (ps t, J = 7.7 Hz, 6.8 Hz), S1
H].
ESI-HRMS (TOF): m/z [M + H]+ calcd for C9H17BrNO: 234.0493;
found: 234.0490.
13C NMR (100 MHz, CDCl3): d = 170.2, 168.8, 55.4, 54.6, 46.1,
46.0, 45.8, 42.1, 28.3, 27.7, 27.3, 25.6, 25.5, 21.7, 21.6, 19.5.
ESI-HRMS (TOF): m/z [M + H]+ calcd for C10H18BrN2O:
261.0603; found: 261.0603.
2-Bromo-N,N-diisopropyl-1-methylcyclopropanecarboxamide
(5e)
Cyclopropanecarboxamide 5e was prepared according to the typical
procedure (as described for 5d) from acyl chloride 12 (2.00 g, 10.1
mmol) and freshly distilled i-Pr2NH (4.50 mL, 3.13 g, 30.3 mmol).
Yield: 2.31 g (87%).
2-Bromo-1-methyl-N,N-diphenylcyclopropanecarboxamide
(5j)
Acid chloride 12 (4.94 g, 25.0 mmol, 1equiv) was added to a stirred
soln of Ph2NH (4.23 g, 25.1 mmol, 1equiv), DMAP (100 mg), and
Et3N (5 mL) in THF (30 mL), and the mixture was allowed to reflux
overnight. It was worked up according to the above procedure and
isolated by column chromatography (silica gel, hexanes–EtOAc,
The physical and spectral properties of this substance were identical
to those reported in the literature.16
Synthesis 2009, No. 9, 1477–1484 © Thieme Stuttgart · New York

PAPER
Cyclopropenes via 1,2-Elimination of Bromocyclopropanes
1481
5:1, Rf = 0.40 and 0.23). A diastereomeric mixture (1:1) of 5j was
obtained as an off-white solid. Yield: 6.76 g (82%).
ESI-HRMS (TOF): m/z [M + H]+ calcd for C13H16BrN2O3:
327.0344; found: 327.0345.
IR (film): 3061, 2980, 2932, 2872, 1659, 1591, 1494, 1339, 1151,
756, 696 cm–1.
2-Bromo-N-ethyl-N-(4-methoxyphenyl)-1-methylcyclopro-
panecarboxamide (5m)
1H NMR (400 MHz, CDCl3): d = [7.38–7.24 (m), S10 H], [3.42 (dd,
J = 8.5 Hz, 5.3 Hz), 2.90 (dd, J = 7.6 Hz, 5.0 Hz), S1 H], [2.07 (dd,
J = 8.5 Hz, 6.4 Hz), 1.53 (dd, J = 7.0 Hz, 5.0 Hz), S1 H], [1.17 (s),
1.09 (s), S3 H], [1.26 (ps t, J = 7.0 Hz), 0.86 (dd, J = 6.4 Hz, 5.3
Hz), S1 H].
13C NMR (100 MHz, CDCl3): d = 173.0, 171.2, 144.0, 143.5, 129.8,
129.7, 128.0, 127.8, 127.4, 127.3, 30.9, 29.0, 28.4, 26.8, 25.2, 24.5,
22.8, 19.8.
Cyclopropanecarboxamide 5m was prepared according to the pro-
tocol described above for amide 5l, from acyl chloride 12 (1.24 g,
6.29 mmol), N-ethylanisidine (0.99 g, 6.47 mmol), and Et3N (1.68
g, 14.9 mmol). Acid–base extraction followed by Kugelrohr vacu-
um distillation (oven temperature 200 °C/0.1 Torr) afforded a dia-
stereomeric mixture of amides 5m (1:1). Yield: 1.96 g (99%).
IR (film): 3051, 2970, 2934, 2872, 2835, 1641, 1510, 1396, 1205,
1151, 1032, 837 cm–1.
ESI-HRMS (TOF): m/z [M + H]+ calcd for C17H17BrNO: 330.0493;
found: 330.0485.
1H NMR (400 MHz, CDCl3): d = [7.33 (d, J = 8.8 Hz), 6.95 (d,
J = 8.8 Hz), S2 H], [7.07 (d, J = 8.8 Hz), 6.97 (d, J = 9.1 Hz), S2 H],
[4.21–4.15 (m), 3.81–3.76 (m), S1 H], [3.87 (s), 3.85 (s), S3 H],
[3.63–3.57 (m), 3.41–3.35 (m), S1 H], [3.22 (dd, J = 8.3 Hz, 5.1
Hz), 2.75 (dd, J = 7.1 Hz, 4.8 Hz), S1 H], [1.85 (dd, J = 8.1 Hz, 6.6
Hz), 1.66 (dd, J = 6.3 Hz, 5.1 Hz), S1 H], [1.14 (t, J = 7.1 Hz), 1.08
(t, J = 7.1 Hz), S3 H], [1.05 (br s), 0.89 (br s), S3 H], [0.95 (ps t,
J = 7.1 Hz), 0.72 (br s), S1 H].
13C NMR (100 MHz, CDCl3): d = 171.4, 169.2, 158.7, 135.3, 129.6,
129.2, 114.6, 114.5, 55.5, 55.4, 46.5, 45.9, 29.7, 28.2, 27.1, 26.2,
24.1, 23.4, 22.1, 20.0, 12.9, 12.7.
ESI-HRMS (TOF): m/z [M + H]+ calcd for C14H19BrNO2:
312.0599; found: 312.0593,
2-Bromo-N-ethyl-1-methyl-N-phenylcyclopropanecarbox-
amide (5l)
Cyclopropanecarboxamide 5l was prepared according to the typical
procedure (as described for 5d) from acyl chloride 12 (2.0 g, 10.1
mmol) and N-ethylaniline (3.81 mL, 3.68 g, 30.3 mmol). Purifica-
tion involved partitioning between a sat. aq soln of citric acid (75
mL) and EtOAc (2 × 50 mL). The combined organic phase was
washed with brine (50 mL), dried (MgSO4), filtered, and concen-
trated in vacuo. The residue was distilled twice in a Kugelrohr ap-
paratus (oven temperature 155 °C/0.2 Torr); this gave a diaste-
reomeric mixture (1:1) of 5l as a colorless oil. Yield: 1.45 g (51%).
IR (film): 3090, 3061, 2974, 2932, 1645, 1595, 1495, 1394, 1207,
1153, 1130, 700, 623, 505 cm–1.
2-Bromo-N-hexyl-1-methylcyclopropanecarboxamide (13)
A soln of hexylamine (4.01 mL, 30.4 mmol, 3.00 equiv) in THF (10
mL) was added dropwise to a soln of acid chloride 12 (2.00 g, 10.1
mmol) in THF (7 mL). After the amine addition was complete, the
mixture was allowed to stir at r.t. until GC-MS analysis showed no
remaining starting materials (1 h). The precipitate was removed by
filtration through a fritted funnel, and the filtrate was washed with
EtOAc (15 mL), then dissolved in H2O (10 mL), and extracted with
EtOAc (2 × 15 mL). The combined organic layers were washed
with brine (20 mL) and dried (MgSO4). All the organic phases were
combined and evaporated under vacuum. The residue was purified
by Kugelrohr vacuum distillation (oven temperature 175 °C/0.6
Torr); this afforded a diastereomeric mixture of 13 (ca. 1:1) as a
clear oil. Yield: 2.16 g (81%).
1H NMR (400 MHz, CDCl3): d = [7.46–7.15 (m), S5 H], [4.22–4.16
(m), 3.44 (br s), S1 H], [3.85–3.76 (m), 3.70–3.61 (m), S1 H], [3.21
(dd, J = 8.3 Hz, 5.1 Hz), 2.75 (br s), S1 H], [1.85 (ps t, J = 6.6 Hz),
1.61 (ps t, J = 5.6 Hz), S1 H], [1.13 (t, J = 7.1 Hz), 1.08 (t, J = 7.3
Hz), S3 H], [1.03 (br s), 0.88 (br s), S3 H], [0.88 (br s), 0.71 (ps t,
J = 5.6 Hz), S1 H].
13C NMR (100 MHz, CDCl3): d = 171.2, 169.1, 142.6, 141.6, 129.5,
129.4, 128.4, 127.9, 127.6, 127.5, 46.6, 45.9, 29.8, 28.2, 27.2, 24.4,
24.2, 23.4, 19.9, 12.8.
ESI-HRMS (TOF): m/z [M – Br]+ calcd for C13H16NO: 202.1232;
found: 202.1234.
IR (film): 3319, 2957, 2934, 2856, 1634, 1537, 1462, 1321, 1205,
1153 cm–1.
2-Bromo-N-ethyl-1-methyl-N-(4-nitrophenyl)cyclopropane-
carboxamide (5k)
1H NMR (500 MHz, CDCl3): d = [5.99 (s), 5.87 (s), S1 H], [3.59
(dd, J = 8.2 Hz, 5.4 Hz), 2.98 (dd, J = 7.6 Hz, 5.0 Hz), S1 H], [3.44–
3.31 (m), 3.11–3.06 (m), S2 H], [1.95 (dd, J = 7.6 Hz, 5.7 Hz), 1.75
(ps t, J = 5.7 Hz), S1 H], 1.62 (m, 2 H), [1.58 (s), 1.48 (s), S3 H],
1.42–1.35 (m, 6 H), 1.27 (ps t, J = 6.9 Hz, 1 H), 0.98 (br t, J = 5.7
Hz, 3 H).
13C NMR (125 MHz, CDCl3): d = 172.1, 169.9, 40.3, 40.2, 31.5,
31.2, 29.7, 29.6, 29.2, 27.9, 27.6, 26.7, 26.3, 25.3, 24.3, 24.0, 22.6,
22.5, 21.6, 21.1, 17.3, 14.1.
Cyclopropanecarboxamide 5k was prepared according to the proto-
col described above for amide 5l, from acyl chloride 12 (1.24 g, 6.25
mmol), N-ethyl-4-nitroaniline (0.99 g, 5.96 mmol), and Et3N (1.68
g, 14.9 mmol). The crude material was purified by short column
chromatography (silica gel, hexanes–EtOAc, 3:1, Rf = 0.39 and
0.32); this gave a diastereomeric mixture (1:1) of 5k. Yield: 1.67 g
(86%).
IR (film): 3080, 2974, 2934, 1651, 1591, 1520, 1344, 1205, 1151,
1109, 854 cm–1.
1H NMR (400 MHz, CDCl3): d = [8.34 (d, J = 8.8 Hz), 8.31 (d,
J = 8.8 Hz), S2 H], [7.55 (d, J = 8.8 Hz), 7.37 (d, J = 8.8 Hz), S2 H],
[4.22 (sext, J = 7.1 Hz), 3.93 (sext, J = 7.1 Hz), S1 H], [3.74 (sext,
J = 7.1 Hz), 3.66 (sext, J = 7.1 Hz), S1 H], [3.26 (dd, J = 8.3 Hz, 5.1
Hz), 2.94 (dd, J = 7.3 Hz, 4.8 Hz), S1 H], [1.96 (dd, J = 8.3 Hz, 6.6
Hz), 1.80 (ps t, J = 6.3 Hz), S1 H], [1.30 (dd, J = 7.6 Hz, 6.6 Hz),
0.83 (dd, J = 6.6 Hz, 5.3 Hz), S1 H], [1.18 (t, J = 7.1 Hz), 1.12 (t,
J = 7.1 Hz), S3 H], 1.10 (s, 3 H).
ESI-HRMS (TOF): m/z [M + H]+ calcd for C11H21BrNO: 262.0807;
found: 262.0809.
2-Bromo-N-hexyl-N,1-dimethylcyclopropanecarboxamide (5i)
A flame-dried flask was charged with NaH (60 wt% suspension in
mineral oil; 183 mg, 4.77 mmol, 2.5 equiv) under a N2 atmosphere.
This was suspended in anhyd THF (25 mL), and amide 13 (500 mg,
1.91 mmol) was added. The mixture was stirred at 50 °C for 10 min
before MeI (325 mg, 143 mL, 2.29 mmol, 1.2 equiv) was added. The
reaction was complete after 4 h at 50 °C, as shown by the disappear-
ance of the starting material. The reaction was quenched by pouring
of the mixture into brine (20 mL), and extracting with EtOAc
13C NMR (100 MHz, CDCl3): d = 178.9, 171.4, 147.5, 146.2, 128.4,
128.1, 125.0, 124.8, 46.0, 45.9, 29.3, 28.9, 26.8, 25.9, 23.6, 23.2,
21.6, 19.6, 13.4, 13.0;
Synthesis 2009, No. 9, 1477–1484 © Thieme Stuttgart · New York

1482
W. M. Sherrill et al.
PAPER
(3 × 15 mL). The combined organic layers were washed with brine
(ca. 15 mL) and condensed under vacuum. The crude product was
purified by column chromatography [silica gel, hexanes (to remove
the mineral oil), then hexanes–EtOAc, 3:1]; this gave a diastereo-
meric mixture of 5i (ca. 2:1, Rf = 0.34 and 0.27) as a colorless oil.
Yield: 329 mg (62%).
1H NMR (400 MHz, CDCl3): d = 7.83–7.77 (m, 3 H), 7.49–7.43 (m,
3 H), 7.38 (s, 2 H), 7.35 (dd, J = 8.6, 1.7 Hz, 1 H), 1.78 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 147.4, 133.4, 131.5, 127.6, 127.5,
127.2, 125.9, 125.0, 124.7, 124.5, 115.8, 25.6, 22.2.
ESI-HRMS (TOF): m/z [M – H]+ calcd for C14H11: 179.0861; found:
179.0859.
IR (film): 2955, 2828, 2856, 1641, 1485, 1460, 1404, 1209, 1153,
1086 cm–1.
3-(2-Fluorophenyl)-3-methylcyclopropene (6c)
1H NMR (500 MHz, CDCl3): d = [3.46–3.40 (m), 3.33–3.27 (m), S2
H], [3.18 (dd, J = 8.2 Hz, 5.0 Hz), 2.99 (dd, J = 7.6 Hz, 4.7 Hz), S1
H], [3.15 (s), 2.94 (s), S3 H], 1.71 (ps t, J = 7.3 Hz), 1.61–1.58 (m),
S1 H], [1.60–1.57 (m), 1.17 (dd, J = 14.9 Hz, 7.3 Hz), S1 H], [1.47
(s), 1.39 (s), S3 H], [1.30–0.88 m, 11 H].
13C NMR (125 MHz, CDCl3): d = 169.8, 169.7, 49.8, 48.2, 47.8,
47.7, 35.6, 35.3, 32.8, 31.6, 31.5, 28.6, 27.9, 26.7, 26.5, 25.9, 22.6,
22.5, 21.8, 20.9, 19.8, 18.9, 14.0, 13.9.
Cyclopropene 6c was prepared according to the typical procedure
(as described for 6d) from bromocyclopropane 5c (250 mg, 1.09
mmol), and purified by Kugelrohr vacuum distillation (oven tem-
perature 75 °C/10 Torr) to afford a clear oil. Yield: 121 mg (75%).
Final assay of this product showed approximately 5% of 1-(2-fluo-
rophenyl)-1-methylcyclopropane resulting from exhaustive reduc-
tion of dibromide 10c.
IR (film): 3053, 2964, 1637, 1627, 1597, 1209, 1153, 993, 889, 856,
818, 743, 621, 598 cm–1.
ESI-HRMS (TOF): m/z [M + H]+ calcd for C12H23BrNO: 276.0963;
found: 276.0960.
1H NMR (400 MHz, CDCl3): d = 7.63 (s, 2 H), 7.12–7.06 (m, 4 H),
1.59 (s, 3 H).
N,N-Diethyl-1-methylcycloprop-2-enecarboxamide (6d); Typi-
cal Procedure
13C NMR (100 MHz, CDCl3): d = 162.9 (d, 1JCF = 245.9 Hz), 136.1
2
3
3
(d, JCF = 15.4 Hz), 129.1 (d, JCF = 5.1 Hz), 127.4 (d, JCF = 8.1
Hz), 123.9 (d, 4JCF = 3.7 Hz), 119.8, 115.8 (d, 2JCF = 22.7 Hz), 27.6
(d, 3JCF = 2.2 Hz), 20.2.
An oven-dried 10-mL Wheaton vial equipped with a Mininert cap
was charged with t-BuOK (160 mg, 1.43 mmol, 1.50 equiv), 18-
crown-6 (25 mg, 0.095 mmol, 0.10 equiv), and anhyd THF (5 mL).
Carboxamide 5d (250 mg, 0.954 mmol) was added to this soln, and
the reaction mixture was stirred at 30 °C until GC-MS showed the
disappearance of the starting materials (3 h). Then the reaction was
quenched by pouring the mixture into brine (50 mL). The aqueous
layer was extracted with EtOAc (2 × 25 mL). The combined organ-
ic phases were washed with brine (25 mL), dried (MgSO4), and con-
centrated under vacuum. The residue was purified by Kugelrohr
vacuum distillation (oven temperature of 60 °C/0.2 Torr); this gave
6d as a colorless liquid. Yield: 146.7 mg (90%).
19F NMR (376.5 MHz, CDCl3): d = –117.5.
ESI-HRMS (TOF): m/z [M – F]+ calcd for C10H9: 129.0704; found:
129.0707.
N,N-Diisopropyl-1-methylcycloprop-2-enecarboxamide (6e)
Cyclopropene 6e was prepared according to the typical procedure
(as described for 6d) from bromocyclopropane 5e (250 mg, 0.96
mmol) and was purified by Kugelrohr distillation (oven temperature
of 55 °C/0.2 Torr) to afford a colorless liquid. Yield: 148 mg (85%).
A scale-up synthesis was performed according to the same proce-
dure, starting from 5d (15.0 g, 61.7 mmol), t-BuOK (10.4 g, 92.5
mmol), and 18-crown-6 (1.63 g, 6.17 mmol, 10 mol%) in THF (290
mL). Yield: 8.74 g (89%).
IR (film): 3082, 3001, 2964, 2932, 1639, 1616, 1437, 1369, 1331,
1215, 1155, 1040, 609 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.31 (s, 2 H), 4.57 (br s, 1 H), 3.30
(br s, 1 H), 1.38 (br s, 6 H), 1.31 (s, 3 H), 1.24 (br s, 6 H).
13C NMR (100 MHz, CDCl3): d = 175.2, 115.6, 48.9, 45.3, 28.0,
23.7, 20.9, 20.6.
ESI-HRMS (TOF): m/z [M + H]+ calcd for C11H20NO: 182.1545;
IR (film): 3082, 2972, 2935, 2874, 1616, 1460, 1427, 1381, 1283,
1211, 1153, 1103, 621 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.28 (s, 2 H), 3.54 (br s, 2 H), 3.29
(br s, 2 H), 1.31 (s, 3 H), 1.18 (br s, 3 H), 1.06 (br s, 3 H).
found: 182.1543.
13C NMR (100 MHz, CDCl3): d = 175.5, 115.8, 41.3, 38.7, 23.9,
23.2, 14.3, 12.6.
4-[(1-Methylcycloprop-2-enyl)carbonyl]morpholine (6f)
Cyclopropene 6f was prepared according to the typical procedure
(as described for 6d) from cyclopropane 5f (250 mg, 1.01 mmol).
The reaction mixture was quenched by pouring into brine (30 mL)
and extracting the aqueous layer with THF (2 × 25 mL). The com-
bined organic layers were washed once with brine (15 mL), dried
(MgSO4), and concentrated in vacuo. The residue was purified by
Kugelrohr vacuum distillation (oven temperature 95 °C/0.2 Torr) to
afford a clear liquid. Yield: 137 mg (81%).
ESI-HRMS (TOF): m/z [M + H]+ calcd for C9H16NO: 154.1232;
found: 154.1231.
3-Methyl-3-phenylcyclopropene (6a)
Cyclopropene 6a was prepared according to the typical procedure
(as described for 6d) from bromocyclopropane 5a (10.00 g, 47.18
mmol). The crude material was purified by Kugelrohr vacuum dis-
tillation (oven temperature 75 °C/5 Torr) to afford a clear oil. Yield:
5.22 g (85%).
IR (film): 2964, 2920, 2856, 1618, 1431, 1275, 1207, 1151, 1113,
1030 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.32 (s, 2 H), 3.62 (br s, 8 H), 1.35
(s, 3 H).
13C NMR (100 MHz, CDCl3): d = 174.8, 115.4, 66.9, 23.6, 22.49
(due to the restricted rotation about the amide bond, the CH2 groups
a to N are not observed).
ESI-HRMS (TOF): m/z [M + H]+ calcd for C9H14NO2: 168.1025;
found: 168.1024.
All physical and spectral properties of this material were identical
to those described in the literature.17
3-Methyl-3-(2-naphthyl)cyclopropene (6b)
Cyclopropene 6b was prepared according to the typical procedure
(as described for 6d) from bromocyclopropane 5b (250 mg, 0.95
mmol). Purification by Kugelrohr vacuum distillation (oven tem-
perature of 120 °C/0.2 Torr) afforded a colorless oil. Yield: 144.1
mg (84%).
IR (film): 3053, 2964, 1628, 1597, 1504, 1209, 1153, 993, 889, 856,
818, 743, 650, 621, 598 cm–1.
Synthesis 2009, No. 9, 1477–1484 © Thieme Stuttgart · New York

PAPER
Cyclopropenes via 1,2-Elimination of Bromocyclopropanes
1483
1-[(1-Methylcycloprop-2-enyl)carbonyl]piperidine (6g)
N-Ethyl-N-(4-methoxyphenyl)-1-methylcycloprop-2-enecar-
boxamide (6m)
Cyclopropene 6m was prepared according to the typical procedure
(as described for 6d) from bromocyclopropane 5m (110 mg, 0.353
mmol). Purification by column chromatography (silica gel, hex-
anes–EtOAc, 2:1, Rf = 0.32) afforded a yellow oil. Yield: 37.6 mg
(53%).
Cyclopropene 6g was prepared according to the typical procedure
(as described for 6d) from cyclopropane 5g (250 mg, 1.02 mmol).
The product was isolated by Kugelrohr vacuum distillation (oven
temperature 75 °C/0.2 Torr) as a colorless oil. Yield: 143 mg (85%).
IR (film): 2934, 2854, 1614, 1435, 1207, 1153, 1113, 1011 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.28 (s, 2 H), 3.61 (br s, 2 H), 3.46
(br s, 2 H), 1.61 (br s 2 H), 1.53 (br s 4 H), 1.31 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 174.5, 115.7, 46.7, 42.5, 26.6,
25.6, 24.6, 23.7, 22.9.
ESI-HRMS (TOF): m/z [M – Me]+ calcd for C9H12NO: 150.0919;
found: 150.0917.
IR (film): 3065, 2966, 2932, 1647, 1628, 1510, 1458, 1442, 1391,
1290, 1204, 1151, 1117, 1043, 1030, 833 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.05 (d, J = 8.8 Hz, 2 H), 6.94 (d,
J = 8.8 Hz, 2 H), 6.62 (s, 2 H), 3.85 (s, 3 H), 3.65 (q, J = 7.3 Hz, 2
H), 1.15 (s, 3 H), 1.07 (t, J = 6.9 Hz, 3 H).
13C NMR (125 MHz, CDCl3): d = 176.3, 158.5, 134.8, 129.2, 114.5,
114.2, 55.5, 44.9, 24.1, 23.7, 12.8.
1-Methyl-4-[(1-methylcycloprop-2-enyl)carbonyl]piperazine
(6h)
ESI-HRMS (TOF): m/z [M – H]+ calcd for C14H16NO2: 230.1181;
Cyclopropene 6h was prepared according to the typical procedure
(as described for 6d) from bromocyclopropane 5h (250 mg, 0.96
mmol). The product was isolated by Kugelrohr vacuum distillation
(oven temperature 85 °C/0.2 Torr) as a colorless oil. Yield: 128 mg
(75%).
found: 230.1180.
Acknowledgment
Financial support from the University of Kansas and the National
Science Foundation (EEC-0310689) is gratefully acknowledged.
IR (film): 2922, 2793, 1621, 1462, 1433, 1292, 1142, 1128, 1030,
1001 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.28 (s, 2 H), 3.70 (br s, 2 H), 3.56
(br s 2 H), 2.39 (br s, 4 H), 2.29 (s, 3 H), 1.31 (s, 3 H).
References
13C NMR (100 MHz, CDCl3): d = 174.6, 115.5, 55.3, 54.6, 46.0,
(1) For recent reviews, see: (a) Marek, I.; Simaan, S.; Masarwa,
A. Angew. Chem. Int. Ed. 2007, 46, 7364. (b) Rubin, M.;
Rubina, M.; Gevorgyan, V. Chem. Rev. 2007, 107, 3117.
(c) Rubin, M.; Rubina, M.; Gevorgyan, V. Synthesis 2006,
1221. (d) Fox, J. M.; Yan, N. Curr. Org. Chem. 2005, 9, 719.
(2) For recent reports on selective carbometalations, see:
(a) Yang, Y.; Fordyce, E. A. F.; Chen, F. Y.; Lam, H. W.
Angew. Chem. Int. Ed. 2008, 47, 7350. (b) Yan, N.; Liu, X.;
Fox, J. M. J. Org. Chem. 2008, 73, 563. (c) Hirashita, T.;
Shiraki, F.; Onishi, K.; Ogura, M.; Araki, S. Org. Biomol.
Chem. 2007, 5, 2154. (d) Simaan, S.; Marek, I. Org. Lett.
2007, 9, 2569. (e) Smith, M. A.; Richey, H. G. Jr.
45.5, 41.3, 23.7, 22.7.
ESI-HRMS (TOF): m/z [M + H]+calcd for C10H17N2O: 181.1341;
found: 181.1343.
N-Hexyl-N,1-dimethylcycloprop-2-enecarboxamide (6i)
Cyclopropene 6i was prepared according to the typical procedure
(as described for 6d) from bromocyclopropane 5i (250 mg, 0.911
mmol); purification by column chromatography (silica gel, hex-
anes–EtOAc, 3:1, Rf = 0.31) provided a colorless oil. Yield: 169 mg
(95%).
Organometallics 2007, 26, 609. (f) Yang, Z.; Xie, X.; Fox,
J. M. Angew. Chem. Int. Ed. 2006, 45, 3960. (g) Liu, X.;
Fox, J. M. J. Am. Chem. Soc. 2006, 128, 5600. (h) Liao, L.;
Fox, J. M. J. Am. Chem. Soc. 2002, 124, 14322. For hydro-
and dimetalations, see: (i) Trofimov, A.; Rubina, M.; Rubin,
M.; Gevorgyan, V. J. Org. Chem. 2007, 72, 8910.
IR (film): 2955, 2928, 2858, 1620, 1487, 1456, 1402, 1377, 1204,
1153, 1111, 1080, 1009, 617 cm–1.
1H NMR (500 MHz, C6D6): d = 7.27 (s, 2 H), 3.35–3.25 (br s, 2 H),
2.76 (br s, 3 H), 1.37 (s, 3 H), 1.47–1.16 (m, 8 H), 0.97 (t, J = 7.3
Hz, 3 H).
13C NMR (125.67 MHz, C6D6): d = 174.8, 116.1, 53.4, 47.1, 34.2,
31.9, 26.7, 23.2, 22.9, 14.2.
(j) Rubina, M.; Rubin, M.; Gevorgyan, V. J. Am. Chem. Soc.
2004, 126, 3688. (k) Rubina, M.; Rubin, M.; Gevorgyan, V.
J. Am. Chem. Soc. 2003, 125, 7198. (l) Rubina, M.; Rubin,
M.; Gevorgyan, V. J. Am. Chem. Soc. 2002, 124, 11566.
For hydrophosphorylation, see: (m) Alnasleh, B. K.;
Sherrill, W. M.; Rubin, M. Org. Lett. 2008, 10, 3231. For
additions of C–H entities, see: (n) Sherrill, W. M.; Rubin,
M. J. Am. Chem. Soc. 2008, 130, 13804. (o) Yin, J.;
Chisholm, J. D. Chem. Commun. 2006, 632. For other
transformations, see: (p) Rubina, M.; Woodward, E. W.;
Rubin, M. Org. Lett. 2007, 9, 5501. (q) Masarwa, A.;
Stanger, A.; Marek, I. Angew. Chem. Int. Ed. 2007, 46,
8039. (r) Chuprakov, S.; Malyshev, D. A.; Trofimov, A.;
Gevorgyan, V. J. Am. Chem. Soc. 2007, 129, 14868.
(s) Giudici, R. E.; Hoveyda, A. H. J. Am. Chem. Soc. 2007,
129, 3824. (t) Ashirov, R. V.; Balandina, A. A.; Kharlamov,
S. V.; Appolonova, S. A.; Figadere, B.; Latypov, S. K.;
Plemenkov, V. V. Lett. Org. Chem. 2006, 3, 670.
ESI-HRMS (TOF): m/z [M – Me]+ calcd for C11H18NO: 180.1388;
found: 180.1388.
N-Ethyl-1-methyl-N-phenylcycloprop-2-enecarboxamide (6l)
Cyclopropene 6l was prepared according to the typical procedure
(as described for 6d) from bromocyclopropane 5l (250 mg, 0.891
mmol). The product was isolated as a yellow oil by column chroma-
tography (silica gel, hexanes–EtOAc, 2:1, Rf = 0.35). Yield: 51.9
mg (30%).
IR (film): 3063, 2970, 2930, 2870, 1649, 1632, 1593, 1495, 1452,
1387, 1300, 1281, 1117, 766, 700, 629, 586 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.46–7.37 (m, 2 H), 7.32 (m, 1 H),
7.19–7.11 (m, 2 H), 6.56 (s, 2 H) 3.70 (q, J = 14.1 Hz, 7.1 Hz, 2 H),
1.14 (s, 3 H), 1.08 (t, J = 7.3 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 176.4, 142.1, 129.1, 128.1, 127.2,
114.37, 44.9, 24.0, 23.9, 12.9.
(u) Ashirov, R. V.; Appolonova, S. A.; Plemenkov, V. V.
Chem. Nat. Compd. 2006, 42, 434. (v) Simaan, S.;
Masarwa, A.; Bertus, P.; Marek, I. Angew. Chem. Int. Ed.
ESI-HRMS (TOF): m/z [M + H]+ calcd for C13H16NO: 202.1232;
found: 202.1231.
2006, 45, 3963. (w) Weatherhead-Kloster, R. A.; Corey, E.
Synthesis 2009, No. 9, 1477–1484 © Thieme Stuttgart · New York

1484
W. M. Sherrill et al.
PAPER
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group at C3, there is no indication that the presented
synthetic method is limited to this particular type of
substrate. Those reported here were chosen for these studies
because they were the most readily available model
compounds.
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Synthesis 2009, No. 9, 1477–1484 © Thieme Stuttgart · New York