Ring-retentive deprotonation of cyclopropene-3-carboxamides

Article abstract of DOI:10.1016/j.tet.2010.04.123

A remarkable stability of anionic species generated from cyclopropene-3-carboxamides toward ring-opening is demonstrated. The resulting cyclopropenyllithium species can be reacted with a range of electrophiles, which allows for efficient introduction of additional substituents at C1 of the strained ring.

Full text of DOI:10.1016/j.tet.2010.04.123

Tetrahedron 66 (2010) 4947e4953
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Ring-retentive deprotonation of cyclopropene-3-carboxamides
*
Ryan Kim, William M. Sherrill, Michael Rubin
Department of Chemistry, University of Kansas, 1251 Wescoe Hall Drive, Lawrence, KS 66045-758, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
A remarkable stability of anionic species generated from cyclopropene-3-carboxamides toward ring-
opening is demonstrated. The resulting cyclopropenyllithium species can be reacted with a range
of electrophiles, which allows for efficient introduction of additional substituents at C1 of the strained
ring.
Received 10 December 2009
Received in revised form 27 April 2010
Accepted 28 April 2010
Available online 4 May 2010
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
process. Thus, Eckert-Maksic demonstrated that cyclic anion 2,
generated from cyclopropene 1 by slow addition of a non-nucleo-
Cyclopropene-3-carboxamides and closely related N-acyl
derivatives are attractive pharmacophores1 and practical versatile
synthons,2,3 which have lately become a focus of attention,
primarily owing to the increasing interest in highly selective
transformations of cyclopropenes.4 The most recent advance-
ments in this area include the employment of optically active
cyclopropene-3-carboxamides and related imides in diaster-
eoselective addition reactions;5 synthesis of enantiomerically
enriched cyclopropenes via the diastereomeric chromatographic
separation,6 parallel kinetic resolution,7 and enantioselective
desymmetrization.8 It was also demonstrated that certain steri-
cally hindered imide substituents can significantly stabilize the
structure of otherwise very fragile mono-substituted cyclo-
propenes.9 Our group has recently demonstrated that the amide
function at C3 of cyclopropene can be used to efficiently control
the facial selectivity in additions of OeH and PeH entities to the
cyclopropene double bond.10 A practical synthetic approach to
cyclopropene-3-carboxamides was also disclosed,11 which
allowed for efficient and scalable synthesis of these substrates.
However, this methodology is limited to preparation of
1,2-unsubstituted cyclopropenes only. Accordingly, we sought
complementary synthetic methods to further expand the scope of
available cyclopropenylcarboxamides.
philic base, can be efficiently intercepted with silyl- or germyl-
chlorides.13 This strategy was also employed by Fox14 and
Gevorgyan15 to install a silyl protection at the double bond of
cyclopropene-3-carboxylates.
EWG
R
EWG
R
EWG
base
R
1
2
3
(1)
E
R
EWG
E
4
This protocol, however, cannot be used for selective installation
of a single silyl group at the double bond of 1,2-unsubstituted
cyclopropenes, and is inapplicable to reactions with carbon-based
electrophiles. Recently, Fox disclosed a useful method for gener-
ation of a dianionic carboxylate species 2 (EWG¼COꢀ2 ), which
permitted efficient trapping of the cyclopropenyl anion with
a wide range of electrophiles.16 This dianionic species, however,
required the presence of a stabilizing additive, an amine N-oxide,
for efficient coupling with certain less reactive electrophiles.16b
Alternative methods for ring-retentive derivatization of cyclo-
propene-3-carboxylic acids include Pd-catalyzed electrophilic
arylation17 and MoritaeBayliseHillman reaction15 reported by
Gevorgyan, as well as Lam’s Cu-catalyzed silylation18 and fluoride-
assisted stannylation19 reactions. Herein, we demonstrate an effi-
cient and chemoselective method for synthesis of trisubstituted
Due to relatively high acidity of the C(sp2)eH bonds in cyclo-
propenes, their deprotonation usually proceeds routinely providing
a convenient tool for further functionalization of the double bond.
However, electron-withdrawing substituents at C-3 are well known
to promote facile ring-opening and rearrangement into a thermo-
dynamically more stable propargyl anion 3 (Eq. 1).12 Several ap-
proaches have been developed to circumvent this unwanted
cyclopropene-3-carboxamides (4, EWG¼CONR2) via
a ring-
retentive deprotonation of cyclopropene-3-carboxamides (1),
followed by trapping of the cyclopropenylmetal species with
electrophilic reagents.
* Corresponding author. Tel.: þ1 785 864 5071; fax: þ1 785 864 5396; e-mail
address: mrubin@ku.edu (M. Rubin).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.04.123

4948
R. Kim et al. / Tetrahedron 66 (2010) 4947e4953
2. Results and discussion
allyl iodide afforded dienynes 7c,d as the only isolable products in
low yield (Scheme 4). When we doubled the amount of both base
and allyl iodide, compounds 7c and 7d were obtained in good
yields as sole products. It should be mentioned that complemen-
tary experiments involving the quenching of 2c,d with a proton
source returned unchanged starting materials, indicating the
electrophile plays a crucial role in the observed ring-opening
(Scheme 4). We speculated that the Lewis acidity of lithium iodide
The reasoning behind our trial experiments was the antici-
pated increased stability of our cyclopropenylcarboxamide an-
ions, bearing a relatively electron-rich amide function, toward
ring-opening. Analogously to the cyclopropenylcarboxylate
dianions, which were successfully employed in ring-retentive
deprotonation,16 the amide group was expected to impart addi-
tional stabilization to the strained anionic species. Accordingly,
we exposed N,N-diethyl-1-methylcycloprop-2-enecarboxamide
(1a) to a range of different bases, while trapping the resulting
O
O
Me
Me
1. LiHMDS
NR2
NR2
(2)
2. E+ (5)
cyclopropenyllithium species with
a
suitable electrophile
1
E
4
(Table 1). The initial experiments involving quenching reaction
mixtures with methyl iodide were discouraging, providing
complex mixtures containing both cyclopropenes and ring-
opening products. In contrast, deprotonation of 1a followed by
trapping with dimethyl sulfate (5a) occurred with retention of
the three-membered ring, affording inseparable mixtures of
mono- (4aa) and dimethylation (6a) products.
1a: R = Et; 1b: R = i-Pr;
5b: BnBr; 5c: Me2CO; 5d: Et2CO
5e 5f 5i
1c
: R2 = -(CH2)4-
: cyclohexanone; : Ph2CO; : allyl bromide
1d: R2 = -(CH2)2O(CH2)2-
produced in this reaction, as well as in the reaction with MeI
described above (Scheme 1), promotes cleavage of the three-
membered ring.21 To obtain experimental evidences in support of
this idea we examined electrophilic trapping of the cyclo-
propenyllithium species generated from cyclopropene 1d in the
presence of allyl bromide (5i). Remarkably, no ring cleavage was
observed in this case, and 1-allylcyclopropene 4di was obtained in
high yield (Scheme 5), suggesting that the much less Lewis acidic
lithium bromide byproduct does not cause the ring cleavage under
the reported conditions. Similarly to the electrophilic benzylation
demonstrated above, no migration of the cyclopropene double
bond into the exocyclic position took place in the allylated prod-
uct. At the same time, carrying out the same reaction in the
presence of 1.5 equiv of lithium iodide enabled ring cleavage to
give 7c as the only isolable product. It should be mentioned that
non-activated electrophiles, such as n-butylbromide, did not react
with cyclopropenyllithium species 2c, and lead to recovery of the
starting material 1c.
Table 1
Optimization of the ring-retentive lithiationa
#
Base
Electrophile (equiv)
1a/4aa/6ab
1
2
3
4
5
6
7
8
MeLi
MeI (1.05)
MeI (1.05)
MeI (1.05)
MeI (1.05)
MeI (1.05)
MeI (1.05)
DMS (1.05)
DMS (1.05)
DMS (1.05)
DMS (1.05)
DMS (1.05)
DMS (1.05)
DMS (3.00)
20:43:14
17:52:16
20:37:11
18:39:12
40:12:15
15:18:14
31:59:9
14:72:12
32:60:10
29:57:11
50:17:13
15:75:5
MeLiþNMO
n-BuLi
t-BuLi
LDA
LiHDMS
MeLi
MeLiþNMO
n-BuLi
t-BuLi
9
10
11
12
13
LDA
LiHDMS
LiHDMSc
0:12:82
a
All reactions shown in this table were performed at ꢀ30 ꢁC in THF.
b
GC yields are provided, obtained from quantitative analysis employing n-octane
as internal standard. The rest of material balance should account for unidentified
O
ring-opening products.
c
Base (3.00 equiv) was used.
Me
1. Base
2. MeI
NEt2
4aa 6a
+
+ ring
opening products
After substantial optimization (Table 1), it was found that
selective mono-deprotonation can be carried out in the presence
of 1.5 equiv of LiHMDS20 in THF at ꢀ30 ꢁC. Upon addition of
1.05 equiv dimethyl sulfate to the resulting anion, the corre-
sponding trisubstituted cyclopropene 4aa was obtained as a major
product in good yield (Scheme 2, Conditions A). Employment of
excess base and electrophile allowed for predominant formation
of bis-methylated product 6a (Scheme 2, Conditions B).
Remarkably, no stabilizing additives were necessary to preserve
the strained cyclic anion. Next, we tested other electrophiles in the
reaction with cyclopropenyl species generated under conditions
A. Thus, reaction of 1a with benzyl bromide (5b) afforded
trisubstituted cyclopropene 4ab as a sole product in high isolated
yield (Scheme 2). The analogous reaction of a more sterically
hindered diisopropyl amide 1b also proceeded uneventfully, pro-
viding product 4bb in excellent yield. Interestingly, in contrast to
the methylation reaction described above, all our attempts to
effect double alkylation of 1a,b with benzyl bromide failed,
providing only monobenzylated products 4ab and 4bb, re-
spectively. Remarkably, under these very mild reaction conditions
no base assisted migration of the strained double bond into
exocyclic position was observed. We rationalized that the bulky
base employed in this transformation makes deprotonation at the
benzylic position inefficient under our reaction conditions. In
striking contrast to the above examples (Scheme 2), treatment of
the cyclopropenyl anions 2c and 2d with equimolar amounts of
1a
O
O
1. Base
2. Me2SO4
Me
Me
NEt2
Me
NEt2
Me
+
5a
(
)
Me
4aa
6a
Scheme 1. Base: MeLi, n-BuLi, MeLiþNMO, t-BuLi, LDA, LiHMDS.
O
O
O
1. LiHMDS
Me
Me
Me
Me
NR2
NEt2
NEt2
Me
+
2. Me2SO4
Me
Cond. A or B
1a
: R = Et
4aa
A 4aa 6a
6a
1b: R = i-Pr
4aa
Cond.
:
:
= 5:1; yield of
= 1:7; yield of
68%
B 4aa 6a
6a
Cond.
:
:
73%
O
Me
1. LiHMDS
NR2
2. BnBr (5b)
Cond. A or B
4ab: R = Et; yield 71% (Cond. A)
4bb: R = i-Pr; yield 85% (Cond. A)
Scheme 2. Conditions A: LiHMDS (1.50 equiv; electrophile 1.05 equiv). Conditions
B: LiHMDS (3.00 equiv; electrophile 2.10 equiv).

R. Kim et al. / Tetrahedron 66 (2010) 4947e4953
4949
O
O
O
O
Me
Me
Me
Me
Me
i
NEt2
N(Pr )2
N
NEt2
HO
Me
O
4ab
4bb
4ac
, 71%
, 85%
4di
, 85%
, 90%
O
O
O
O
Me
Me
Me
Et
Me
Me
Ph
i
i
i
i
N(Pr )2
N(Pr )2
N(Pr )2
N(Pr )2
HO
Me
HO
Et
HO
HO
Ph
4bd
4be, 83%
4bf
4bc
, 78%
, 79%
, 71%
O
N
O
O
O
N
Me
Me
Me
Me
Me
N
N
HO
Et
HO
Me
HO
Me
HO
O
Et
Me
4cc
, 77%
4cd
4ce
4dc
, 79%
, 74%
, 83%
Scheme 3. Synthesis of trisubstituted cyclopropenes via ring-retentive mono-deprotonation of cyclopropene-3-carboxamides.
with bulky benzophenone (5f) to afford 4bf required prolonged
heating at 65 ꢁC to achieve complete conversion (Scheme 3).
Nonetheless, even under such harsh condition, no ring-opening
products were detected.
In conclusion, it was demonstrated that anionic species gener-
ated from cyclopropene-3-carboxamides possess remarkable sta-
bility toward ring-opening, even at elevated temperatures, without
employment of stabilizing additives. This feature sets them apart
from all the previously described carbonyl derivatives of cyclo-
propenes. The resulting cyclopropenyllithium species can be reac-
ted with a range of electrophiles, which allows for efficient
introduction of additional substituents at C1 of the strained ring.
O
O
Me
Me
LiHMDS (1.05 equiv)
THF
N
N
X
X
H2O
1c, X =CH2
1d, X = O
2c, X =CH2
2d, X = O
Me
1. LiHMDS
(2.50 equiv)
O
N
2.
I
X
(2.10 equiv)
O
O
7c: X = CH2, 66%
7d: X = O, 56%
Me
OH
Me
1. LiHMDS
N
N
2. PhCHO
Ph
Scheme 4. Ring-opening of cyclopropenyl anion upon electrophilic trapping with allyl
O
O
5g
(
)
iodide.
1d
4dg
: 75%, dr 2:1
O
Me
O
O
N
1. LiHMDS
Me
LiHMDS/THF
Br
Me
Ph
Me
O
N
N
2. PhCOMe
O
O
OH
4dh: 62%, dr 1:1
(5h)
1d
4di
Scheme 6.
LiHMDS/THF; LiI
Br
7c
Unusual reactivity of allyl iodide in the electrophilic trapping of
cyclopropenyllithium species was observed, which resulted in
Scheme 5.
a
rapid ring-opening promoted by lithium iodide, affording
(diallylpropargyl)carboxamides.
Next, a series of carbonyl electrophiles were examined in order
to access cyclopropenylcarbinols, which are useful synthons for
organic chemistry.22 The reactions proceeded smoothly with
benzaldehyde and acetophenone, providing inseparable mixtures
of diastereomeric mono-adducts 4dg and 4dh (Scheme 6).
Symmetric aliphatic ketones 5cee reacted effortlessly at ꢀ30 ꢁC,
providing the corresponding strained allylic alcohols 4ac, 4bc, 4bd,
4be, 4cc, 4cd, 4ce, and 4dc in high yields (Scheme 3). Reaction of 1b
3. Experimental part
3.1. General
NMR spectra were recorded on a Bruker Avance DPX-400
instrument, equipped with a quadruple-band gradient probe (H/C/
P/F QNP) or a Bruker Avance DRX-500 with a dual carbon/proton

4950
R. Kim et al. / Tetrahedron 66 (2010) 4947e4953
cryoprobe (CPDUL). The abbreviation ‘app. t’ is used to describe
apparent triplets (i.e., double doublets with unresolved central line,
or unresolved higher order multiplets in a shape of a triplet) in 1H
NMR spectra. 13C NMR spectra were registered with broad-band
decoupling. The (þ) and (ꢀ) designations represent positive and
negative intensities of signals in 13C DEPT-135 experiments. IR
spectra were recorded on a Shimadzu FT-IR 8400S instrument.
HRMS was carried out on LCT Premier (Micromass Technologies)
instrument, ESI TOF detection techniques were used. GC analyses
were performed on a Shimadzu GC-2010 gas chromatograph with
FID detector and equipped with an AOC-20i auto-injector and an
3.3. N,N-Diethyl-1,2-dimethylcycloprop-2-enecarboxamide
(4aa)
The reaction was performed according to a typical procedure,
employing cyclopropene 1a (274 mg, 1.64 mmol) and dimethyl
sulfate (163
title compound as colorless oil, Rf 0.49 (CH2Cl2/THF, 5:1). Yield
187 mg (1.12 mmol, 68%); 1H NMR (400.13 MHz, CDCl3)
6.67
mL, 217 mg, 1.72 mmol) as an electrophile to afford the
d
(s, 1H), 3.57e3.27 (br m, 4H), 2.18 (s, 3H), 1.26 (s, 3H), 1.22e1.15
(br m, 3H), 1.14e1.06 (br m, 3H); 13C NMR (100.67 MHz, CDCl3)
d
176.2, 123.6, 105.2 (þ), 41.3 (br, ꢀ), 38.3 (br, ꢀ), 24.8, 22.3 (þ), 14.3
AOC-20S auto-sampler tray (150 vials); 30 mꢂ0.25 mmꢂ0.25
mm
(br, þ), 12.6 (br, þ), 9.8 (þ); IR (film, cmꢀ1): 2968, 2933, 2920, 2872,
1772, 1624, 1458, 1421, 1379, 1364, 1281, 1207, 1151, 1101, 845, 795,
764, 750, 694; HRMS (TOF ES): found 166.1234, calculated for
C10H16NO (MꢀH) 166.1232 (1.2 ppm).
capillary column, SHR5XLB, polydimethylsiloxane; 5% Ph was
employed. Helium (99.96%), additionally purified by passing
consecutively through a CRS oxygen/ moisture/hydrocarbon trap
(#202839) and VICI oxygen/ moisture trap (P100-1), was used as
a carrier gas. Carrier gas flow rate (1 mL/min) was stabilized using
constant linear velocity algorithm. Hydrogen gas was used as FID
fuel; zero-grade air and zero-grade nitrogen were used as an
oxidant and make-up gas, respectively, for the FID. All these gases
were purified by passing through CRS #202839 traps. The following
GC parameters were used for all analyses: carrier gas flow rate
0.68 mL/min with constant linear velocity 29.9 sm/s; oven
temperature program: 50 ꢁC (2 min)e20 ꢁC/mine275 ꢁC (6 min),
injector temperature 275 ꢁC. Glassware employed in moisture-free
syntheses was flame-dried in vacuum prior to use. A combination
of glovebox and standard Schlenk technique was used to handle
moisture sensitive materials. Column chromatography was carried
3.4. N,N-Diethyl-1,2,3-trimethylcycloprop-2-enecarboxamide
(6a)
The reaction was performed according to a typical procedure,
employing cyclopropene 1a (274 mg, 1.64 mmol), lithium hexam-
ethyldisilazide (823 mg, 492 mmol, 3.00 equiv), and dimethyl
sulfate (467
title compound as colorless oil, Rf 0.56 (CH2Cl2/THF, 5:1). Yield
217 mg (1.20 mmol, 73%); 1H NMR (400.13 MHz, CDCl3)
3.52 (br s,
2H), 3.33 (br s, 2H), 2.06 (s, 6H),1.27 (br s, 3H), 1.20 (s, 3H), 1.11 (br s,
3H); 13C NMR (100.67 MHz, CDCl3)
mL, 620 mg, 4.92 mmol) as an electrophile to afford the
d
d
177.2, 112.5 (2C), 41.3 (br, ꢀ),
38.1 (br, ꢀ), 26.0, 20.3 (þ), 14.4 (br, þ), 12.9 (br, þ), 8.6 (þ, 2C); IR
(film, cmꢀ1): 2968, 2918, 1626, 1460, 1435, 1421, 1379, 1362, 1279,
1209, 1151, 1101, 793, 750, 638; HRMS (TOF ES): found 181.1466,
calculated for C11H19NO (Mþ) 181.1467 (0.6 ppm).
out on silica gel (Selecto Scientific, 63e200 mm). Pre-coated silica
gel plates (Merck Kiezelgel 60 F-254) were used for TLC analyses.
Anhydrous tetrahydrofuran was obtained by passing degassed
commercially available stabilizer-free solvent consecutively
through two columns filled with activated alumina (Innovative
Technology). Cyclopropenes 1aed were obtained according to the
procedure, described in our recent report.20 All other reagents were
purchased from SigmaeAldrich, Alpha-Aesar or Acros Organics and
used as received.
3.5. 2-Benzyl-N,N-diisopropyl-1-methylcycloprop-
2-enecarboxamide (4bb)
The reaction was performed according to a typical procedure,
employing cyclopropene 1b (296 mg, 1.64 mmol) and benzyl
bromide (206 mL, 295 mg, 1.72 mmol) as an electrophile to afford
3.2. 2-Benzyl-N,N-diethyl-1-methylcycloprop-
2-enecarboxamide (4ab)
the title compound as yellow viscous oil, Rf 0.25 (hexanes/EtOAc,
2:1). Yield 376 mg (1.39 mmol, 85%); 1H NMR (400.13 MHz, CDCl3)
d
7.54 (d, J¼7.1 Hz, 2H), 7.35 (app. t, J¼7.3 Hz, 2H), 7.25 (app. t,
Typical procedure: An oven dried 25 mL round-bottomed flask
was charged with lithium hexamethyldisilazide (400 mg,
2.39 mmol, 1.50 equiv) and anhydrous THF (5 mL). The mixture was
stirred at ꢀ30 ꢁC, and cold solution of cyclopropene 1a (244 mg,
1.59 mmol, 1.00 equiv) in dry THF (5 mL) was added via cannula to
obtain bright orange-red solution. The mixture was stirred for
J¼7.3 Hz, 1H), 6.77 (t, J¼2.3 Hz, 1H), 4.53 (br septet, J¼5.8 Hz, 1H),
3.35 (br septet, J¼6.3 Hz, 1H), 2.05 (dd, J¼9.9, 2.3 Hz, 1H), 1.48 (s,
3H), 1.44 (dd, J¼9.9, 2.3 Hz, 1H), 1.42 (d, J¼5.8 Hz, 3H), 1.37 (d,
J¼6.3 Hz, 3H), 1.33 (d, J¼5.8 Hz, 3H), 1.27 (d, J¼6.3 Hz, 3H); 13C NMR
(100.67 MHz, CDCl3)
d
170.0, 137.3, 129.8, 128.5 (þ, 2C), 127.2 (þ),
126.7 (þ, 2C), 117.4 (þ), 48.9 (þ), 45.8 (þ), 24.3, 21.7 (þ), 21.0 (þ),
20.7 (þ), 20.5 (þ), 20.2 (þ), 17.0 (ꢀ); IR (film, cmꢀ1): 2999, 2966,
2930, 2870, 1636, 1452, 1435, 1367, 1329, 1211, 1153, 1040, 746, 694,
509; GC: tR 12.06 min; HRMS (TOF ES): found 278.2099, calculated
for C18H25NOLi (MþLi) 278.2096 (1.1 ppm).
5 min at ꢀ30 ꢁC before benzyl bromide (200
mL, 286 mg,1.67 mmol,
1.05 equiv) was added via syringe. Then the mixture was stirred for
2 h at ꢀ30 ꢁC, when GC showed the reaction complete. Brine
(20 mL) and ethyl acetate (20 mL) were added, organic layer was
separated, and aqueous phase was extracted with ethyl acetate
(2ꢂ10 mL). Combined organic phases were dried with MgSO4,
filtered, and concentrated in vacuum. Preparative column chro-
matography on Silica gel (eluent hexanes/EtOAc, 2:1) afforded
yellow viscous oil, Rf 0.25, yield 285 mg (1.13 mmol, 71%); 1H NMR
3.6. N,N-Diethyl-2-(2-hydroxypropan-2-yl)-1-
methylcycloprop-2-enecarboxamide (4ac)
The reaction was performed according to a typical procedure,
(500.19 MHz, CDCl3)
d
7.54 (d, J¼7.9 Hz, 2H), 7.35 (app. t, J¼7.9 Hz,
employing cyclopropene 1a (274 mg, 1.64 mmol) and acetone
2H), 7.25 (t, J¼7.9 Hz, 1H), 6.82 (app. t, J¼2.2 Hz, 1H), 3.67 (br, 2H),
3.43 (br, 1H), 3.35 (br, 1H), 2.06 (dd, J¼9.5, 2.2 Hz, 1H), 1.50 (s, 3H),
1.49 (dd, J¼9.5, 2.2 Hz, 1H), 1.29 (br, 3H), 1.14 (br, 3H); 13C NMR
(126
compound as colorless viscous oil, Rf 0.24 (hexanes/EtOAc, 5:1).
Yield 376 mg (1.39 mmol, 85%); 1H NMR (500.19 MHz, CDCl3)
6.50
mL, 100 mg, 1.72 mmol) as an electrophile to afford the title
d
(125.76 MHz, CDCl3)
d
170.6, 137.3, 129.7, 128.5 (þ, 2C), 127.3 (þ),
(s, 1H), 5.74 (br s, 1H), 3.50 (q, J¼7.3 Hz, 2H), 3.36 (dq, J¼14.2, 7.3 Hz,
1H), 3.12 (dq, J¼14.2, 7.3 Hz, 1H), 1.45 (s, 3H), 1.39 (s, 3H), 1.33
(s, 3H), 1.15 (t, J¼7.3 Hz, 3H), 1.03 (s, J¼7.3 Hz, 3H); 13C NMR
126.8 (þ, 2C), 118.0 (þ), 41.5 (ꢀ), 39.1 (ꢀ), 23.2, 22.0 (þ), 17.1 (ꢀ),
14.1 (þ), 12.6 (þ); IR (film, cmꢀ1): 2972, 2934, 2873, 1780, 1720,
1634, 1454, 1427, 1381, 1221, 1157, 748, 696, 505; GC: tR 11.75 min;
HRMS (TOF ES): found 244.1700, calculated for C16H22NO (MþH)
244.1701 (0.4 ppm).
(125.67 MHz, CDCl3)
d
176.2, 133.0, 101.8 (þ), 66.9, 42.1 (ꢀ), 38.8
(ꢀ), 29.1 (þ), 28.8 (þ), 27.9, 22.5 (þ), 14.2 (þ), 12.5 (þ); IR (film,
cmꢀ1): 3329 (br), 3105, 2974, 2934, 2876, 1765, 1703, 1599, 1462,

R. Kim et al. / Tetrahedron 66 (2010) 4947e4953
4951
1429, 1377, 1362, 1315, 1285, 1219, 1169, 1105, 945, 683, 608, 538;
GC: tR 8.70 min; HRMS (TOF ES): found 212.1650, calculated for
C12H22NO (MþH) 212.1651 (0.4 ppm).
benzophenone the reaction mixture was heated to 65 ꢁC overnight
to force the complete conversion) to afford the title compound as
colorless solid, mp 140e142 ꢁC, Rf 0.17 (hexanes/EtOAc, 5:1). Yield
465 mg (1.28 mmol, 79%); 1H NMR (400.13 MHz, CDCl3)
d 7.64e7.58
3.7. 2-(2-Hydroxypropan-2-yl)-N,N-diisopropyl-
1-methylcycloprop-2-enecarboxamide (4bc)
(m, 2H), 7.36e7.21 (m, 8H), 6.91 (s, 1H), 4.47 (septet, J¼6.6 Hz, 1H),
3.31 (septet, J¼6.6 Hz, 1H), 1.60 (br s, 1H), 1.41 (d, J¼6.6 Hz, 3H), 1.35
(d, J¼6.6 Hz, 3H), 1.27 (d, J¼6.6 Hz, 3H),1.19 (d, J¼6.6 Hz, 3H),1.13 (s,
The reaction was performed according to a typical procedure,
3H); 13C NMR (100.67 MHz, CDCl3)
d 175.8, 146.3, 144.7, 132.9, 128.0
employing cyclopropene 1b (296 mg, 1.64 mmol) and acetone
(þ, 2C), 127.9 (þ), 127.1 (þ), 126.9 (þ, 2C), 126.5 (þ, 2C), 126.2
(þ, 2C), 104.9 (þ), 74.7, 50.0 (þ), 45.6 (þ), 30.2, 21.2 (þ), 21.0 (þ),
20.6 (þ), 20.3 (þ), 20.2 (þ); IR (film, cmꢀ1): 3339 (br), 3032, 3001,
2966, 2932, 2872, 1759, 1591, 1447, 1369, 1340, 1207, 1151, 1036,
1018, 750, 698, 638, 615, 577, 554, 505; GC: tR 14.50 min; HRMS
(TOF ES): found 363.2205, calculated for C24H29NO2 (Mþ) 363.2198
(1.9 ppm).
(126 mL, 100 mg, 1.72 mmol) as an electrophile to afford the title
compound as colorless solid, mp 78e79 ꢁC, Rf 0.17 (hexanes/EtOAc,
5:1). Yield 278 mg (1.16 mmol, 71%); 1H NMR (400.13 MHz, CDCl3)
d
6.55 (s,1H), 6.01 (br s,1H), 4.48 (septet, J¼6.8 Hz,1H), 3.30 (septet,
J¼6.8 Hz, 1H), 1.54 (s, 3H), 1.48 (s, 3H), 1.40 (d, J¼6.8 Hz, 3H), 1.39
(s, 3H), 1.35 (d, J¼6.8 Hz, 3H), 1.28 (d, J¼6.8 Hz, 3H), 1.19 (d,
J¼6.8 Hz, 3H); 13C NMR (100.67 MHz, CDCl3)
176.1,134.1,101.6 (þ),
d
66.8, 49.9 (þ), 45.4 (þ), 29.4, 29.2 (þ), 28.8 (þ), 22.4 (þ), 21.0 (þ),
20.6 (þ), 20.4 (þ), 20.2 (þ); IR (film, cmꢀ1): 3250 (br), 3119, 2966,
2923, 1763, 1589, 1537, 1473, 1458, 1429, 1373, 1340, 1209, 1153,
1040, 970, 951, 895, 735, 671, 608; GC: tR 9.10 min; HRMS (TOF ES):
found 239.1876, calculated for C14H25NO2 (Mþ) 239.1885 (3.8 ppm).
3.11. 2-[3-Methyl-3-(piperidin-1-ylcarbonyl)cycloprop-
1-en-1-yl]propan-2-ol (4cc)
The reaction was performed according to a typical procedure,
employing cyclopropene 1c (249 mg, 1.51 mmol) and acetone
(117
compound as colorless viscous oil, Rf 0.16 (hexanes/EtOAc, 3:1).
Yield 259 mg (1.16 mmol, 77%); 1H NMR (500.19 MHz, CDCl3)
6.58
(s, 1H), 5.79 (br s, 1H), 3.71e3.42 (m, 4H), 1.70e1.53 (m, 6H), 1.54 (s,
3H), 1.47 (s, 3H), 1.41 (s, 3H); 13C NMR (125.67 MHz, CDCl3)
175.3,
mL, 92 mg, 1.59 mmol) as an electrophile to afford the title
3.8. 2-(3-Hydroxypentan-3-yl)-N,N-diisopropyl-
1-methylcycloprop-2-enecarboxamide (4bd)
d
The reaction was performed according to a typical procedure,
d
employing cyclopropene 1b (303 mg, 1.68 mmol) and diethyl
ketone (186 mL, 152 mg, 1.76 mmol) as an electrophile to afford the
132.9, 101.9 (þ), 67.0, 47.3 (ꢀ), 42.8 (ꢀ), 29.1 (þ), 28.9 (þ), 27.6, 26.6
(ꢀ), 25.4 (ꢀ), 24.4 (ꢀ), 22.5 (þ); IR (film, cmꢀ1): 3317 (br), 3101;
2974, 2935, 2856, 1765, 1601, 1531, 1443, 1373, 1358, 1271, 1259,
1240, 1224, 1165, 1115, 1011, 972, 953, 854, 727, 688, 608, 528, 416;
GC: tR 10.26 min; HRMS (TOF ES): found 206.1540, calculated for
C13H20NO (MꢀOH) 206.1545 (2.4 ppm).
title compound as yellowish viscous oil, Rf 0.35 (hexanes/EtOAc,
4:1). Yield 349 mg (1.31 mmol, 78%); 1H NMR (500.19 MHz, CDCl3)
d
6.60 (s,1H), 5.98 (br s,1H), 4.47 (septet, J¼6.6 Hz,1H), 3.27 (septet,
J¼6.6 Hz, 1H), 1.79e1.64 (m, 4H), 1.38 (d, J¼6.6 Hz, 3H), 1.35 (s, 3H),
1.32 (d, J¼6.6 Hz, 1H), 1.26 (d, J¼6.9 Hz, 1H), 1.16 (d, J¼6.9 Hz, 1H),
0.92e0.88 (m, 6H); 13C NMR (100.67 MHz, CDCl3)
d
175.9, 133.1,
3.12. 3-[3-Methyl-3-(piperidin-1-ylcarbonyl)cycloprop-
1-en-1-yl]pentan-3-ol (4cd)
103.7 (þ), 73.2, 49.7 (þ), 45.2 (þ), 32.1 (ꢀ), 32.0 (ꢀ), 28.2, 22.4 (þ),
20.9 (þ), 20.5 (þ), 20.1 (þ), 20.0 (þ), 8.5 (þ), 7.9 (þ); IR (film, cmꢀ1):
3269 (br), 3103, 3001, 2966, 2935, 2878, 1759, 1597, 1537, 1443,
1370, 1339, 1213, 1153, 1138, 1105, 1038, 968, 943, 901, 833, 769, 721,
658, 604, 555, 530, 511, 492; GC: tR 10.35 min; HRMS (TOF ES):
found 267.2200, calculated for C16H29NO2 (Mþ) 267.2198 (0.7 ppm).
The reaction was performed according to a typical procedure,
employing cyclopropene 1c (249 mg, 1.51 mmol) and diethyl
ketone (168 mL, 137 mg, 1.59 mmol) as an electrophile to afford
a title compound as yellowish viscous oil, Rf 0.28 (hexanes/EtOAc,
2:1). Yield 262 mg (1.12 mmol, 74%); 1H NMR (500.19 MHz, CDCl3)
3.9. 2-(1-Hydroxycyclohexyl)-N,N-diisopropyl-
d 6.64 (s, 1H), 5.76 (br s, 1H), 3.70e3.40 (m, 4H), 1.81e1.68 (m, 4H),
1-methylcycloprop-2-enecarboxamide (4be)
1.68e1.50 (m, 6H), 1.38 (s, 3H), 0.94 (t, J¼7.6 Hz, 3H), 0.92 (t,
J¼7.6 Hz, 3H); 13C NMR (125.67 MHz, CDCl3)
d 175.3, 131.8, 103.8
The reaction was performed according to a typical procedure,
employing cyclopropene 1b (286 mg, 1.59 mmol) and cyclohexa-
(þ), 73.3, 47.3 (ꢀ), 42.8 (ꢀ), 31.99 (ꢀ), 31.96 (ꢀ), 26.58, 26.54 (ꢀ),
25.4 (ꢀ), 24.4 (ꢀ), 22.7 (þ), 8.6 (þ), 8.1 (þ); IR (film, cmꢀ1): 3308
(br), 3097, 2966, 2937, 2858, 1715, 1601, 1529, 1443, 1373, 1271,
1259, 1240, 1155, 1115, 1011, 968, 874, 852, 723, 687, 602, 530; GC: tR
11.45 min; HRMS (TOF ES): found 252.1967, calculated for
C15H26NO2 (MþH) 252.1963 (1.6 ppm).
none (173 mL, 164 mg, 1.67 mmol) as an electrophile to afford a title
compound as yellowish solid, mp 52e53 ꢁC, Rf 0.32 (hexanes/
EtOAc, 5:1). Yield 368 mg (1.32 mmol, 83%); 1H NMR (400.13 MHz,
CDCl3)
d
6.65 (s, 1H), 6.21 (br s, 1H), 4.48 (septet, J¼6.6 Hz, 1H), 3.29
(septet, J¼6.8 Hz, 1H), 1.97e1.88 (m, 2H), 1.82e1.64 (m, 5H),
1.54e1.44 (m, 3H), 1.39 (d, J¼6.8 Hz, 3H), 1.37 (s, 3H), 1.34 (d,
J¼6.8 Hz, 3H), 1.27 (d, J¼6.6 Hz, 3H), 1.17 (d, J¼6.6 Hz, 3H); 13C NMR
3.13. 1-[3-Methyl-3-(piperidin-1-ylcarbonyl)cycloprop-
1-en-1-yl]cyclohexanol (4ce)
(100.67 MHz, CDCl3)
d
176.1, 132.8, 103.6 (þ), 69.4, 49.8 (þ), 45.4
(þ), 38.5 (ꢀ), 37.8 (ꢀ), 28.1, 25.5 (ꢀ), 23.30 (ꢀ), 23.27 (ꢀ), 22.4 (þ),
21.0 (þ), 20.6 (þ), 20.4 (þ), 20.2 (þ); IR (film, cmꢀ1): 3285 (br),
3001, 2964, 2932, 2856, 1599, 1443, 1369, 1337, 1211, 1155, 1038,
968, 600, 507; GC: tR 11.50 min; HRMS (TOF ES): found 279.2193,
calculated for C17H29NO2 (Mþ) 279.2198 (1.8 ppm).
The reaction was performed according to a typical procedure,
employing cyclopropene 1c (249 mg, 1.51 mmol) and cyclohexa-
none (164 mL, 156 mg, 1.59 mmol) as an electrophile to afford the
title compound as colorless viscous oil, Rf 0.27 (hexanes/EtOAc,
3:1). Yield 330 mg (1.25 mmol, 83%); 1H NMR (500.19 MHz, CDCl3)
d
6.68 (s, 1H), 5.96 (br s, 1H), 3.72e3.41 (m, 4H), 1.98e1.92 (m, 1H),
1.82e1.62 (m, 8H), 1.60e1.45 (m, 5H), 1.40 (s, 3H), 1.35e1.26 (m,
3H); 13C NMR (125.67 MHz, CDCl3)
47.3 (ꢀ), 42.8 (ꢀ), 38.6 (ꢀ), 37.8 (ꢀ), 26.6 (ꢀ), 26.3, 25.43 (ꢀ), 25.36
(ꢀ), 24.4 (ꢀ), 23.30 (ꢀ), 23.27 (ꢀ), 22.5 (þ); IR (film, cmꢀ1): 3300
(br), 3097, 2932, 2854, 1763, 1601, 1528, 1445, 1371, 1348, 1273, 1157,
1115, 1078, 1030, 1011, 968, 905, 852, 725, 685, 598, 529; GC: tR
3.10. 2-(Hydroxydiphenylmethyl)-N,N-diisopropyl-
1-methylcycloprop-2-enecarboxamide (4bf)
d
175.4, 131.7, 103.9 (þ), 69.7,
The reaction was performed according to a typical procedure,
employing cyclopropene 1b (292 mg, 1.62 mmol) and benzophe-
none (310 mg, 1.70 mmol) as an electrophile (after addition of

4952
R. Kim et al. / Tetrahedron 66 (2010) 4947e4953
11.75 min; HRMS (TOF ES): found 264.1963, calculated for
C16H26NO2 (MþH) 264.1963 (0.0 ppm).
J¼16.9, 10.2, 6.5 Hz, 1H), 5.78 (s, 1H), 5.14 (ddt, J¼16.9, 1.9, 1.6 Hz,
1H), 5.11 (ddt, J¼10.2, 1.6, 1.3 Hz, 1H), 3.82e3.77 (m, 4H), 3.29 (dq,
J¼6.6, 1.3 Hz, 2H), 3.07e3.01 (m, 4H), 1.93 (s, 3H); 13C NMR
3.14. 2-[3-Methyl-3-(morpholin-4-ylcarbonyl)cycloprop-
1-en-1-yl]propan-2-ol (4dc)
(125.76 MHz, CDCl3)
d
ppm 176.3, 147.3, 134.1 (þ), 116.5 (ꢀ), 108.9
(þ), 67.2 (ꢀ, 2C), 51.1 (ꢀ, 2C), 32.7 (ꢀ), 29.9, 9.5 (þ); IR (film, cmꢀ1):
3080, 2959, 2918, 2893, 2853, 1772, 1649, 1576, 1450, 1371, 1296,
1261, 1223, 1117, 1070, 920, 847, 804, 569; HRMS (TOF ES): found
206.1185, calculated for C12H16NO2 (MꢀH) 206.1181 (1.9 ppm).
The reaction was performed according to a typical procedure,
employing cyclopropene 1d (167 mg, 1.00 mmol) and acetone
(77
compound as colorless viscous oil, Rf 0.34 (hexanes/EtOAc 1:5).
Yield 179 mg (0.79 mmol, 79%); 1H NMR (500.19 MHz, CDCl3)
6.59
(s, 1H), 5.39 (s, 1H), 3.77e3.45 (br m, 8H), 1.54 (s, 3H), 1.47 (s, 3H),
1.41 (s, 3H); 13C NMR (125.67 MHz, CDCl3)
mL, 61 mg, 1.05 mmol) as an electrophile to afford the title
3.18. 2-Allyl-2-methyl-1-(piperidin-1-yl)hept-6-en-3-yn-
1-one (7c)
d
d
175.7, 132.6, 101.8 (þ),
The reaction was performed according to a typical procedure,
employing cyclopropene 1c (249 mg, 1.51 mmol), lithium hexam-
ethyldisilazide (633 mg, 3.78 mmol, 2.50 equiv), and allyl iodide
67.2, 66.79 (br s., ꢀ, 2C), 46.8 (br s., ꢀ), 42.2 (br s., ꢀ), 29.1 (þ), 28.9
(þ), 27.2, 22.3 (þ); IR (film, cmꢀ1): 3024 (br), 2974, 2926, 2860,
1601, 1462, 1434, 1213, 1153, 1113, 1030, 839; GC: tR 10.47 min;
HRMS (TOF ES): found 225.1368, calculated for C12H19NO3 (Mþ)
225.1365 (1.3 ppm).
(291 mL, 533 mg, 3.17 mmol, 2.10 equiv) as an electrophile the af-
ford a title compound as yellowish viscous oil, Rf 0.33 (hexanes/
EtOAc, 3:1). Yield 245 mg (1.00 mmol, 66%); 1H NMR (500.19 MHz,
CDCl3)
d
5.89 (dddd, J¼17.7, 9.5, 8.2, 6.3 Hz, 1H), 5.79 (ddt, J¼17.0,
3.15. [3-Methyl-3-(morpholin-4-ylcarbonyl)cycloprop-
1-en-1-yl](phenyl)methanol (4dg)
10.2, 5.2 Hz,1H), 5.27 (ddt, J¼17.0,1.9,1.6 Hz,1H), 5.12e5.11 (m,1H),
5.10 5.06 (m, 2H), 3.86 (br s., 2H), 3.56 (br s., 2H), 2.98 (dt, J¼5.4,
1.7 Hz, 2H), 2.61 (ddt, J¼13.6, 6.5, 1.6 Hz, 1H), 2.39 (dd, J¼13.7,
8.0 Hz, 1H), 1.61e1.67 (m, 2H), 1.60e1.52 (m, 4H), 1.40 (s, 3H); 13C
The reaction was performed according to a typical procedure,
employing cyclopropene 1d (150 mg, 0.90 mmol) and freshly
distilled benzaldehyde (203 mL, 212 mg, 2 mmol) as an electrophile
NMR (125.67 MHz, CDCl3)
d
170.1, 134.3 (þ), 132.7 (þ), 118.0 (ꢀ),
115.9 (ꢀ), 84.3, 81.4, 47.9 (br s, ꢀ), 44.4 (br s., ꢀ), 44.4 (ꢀ), 40.4, 25.9
(br s., ꢀ), 25.7 (þ), 24.6 (ꢀ), 23.1 (ꢀ, 2C); GC: tR 10.97 min; IR (film,
cmꢀ1): 3060, 2972, 2934, 2874, 1634, 1454, 1427, 1381, 1221, 1157,
748, 696, 638, 627, 505; HRMS (TOF ES): found 246.1855, calculated
for C16H24NO (MþH) 246.1858 (1.2 ppm).
to afford the title compound as light-yellow viscous oil, Rf 0.42
(CH2Cl2/EtOAc, 3:2). Yield 184 mg (0.67 mmol, 75%), dr 2:1; 1H
NMR (500.19 MHz, CDCl3)
d 7.57e7.74 (m, 2H), 7.39e7.74 (m, 2H),
7.32e7.27 (m, 1H), [6.75 (s) and 6.68 (s), S1H], 6.07 (br s, 1H), [5.88
(s) and 5.68 (s), S1H], 3.75e3.50 (m, 8H), [1.39 (s) and 1.13 (s), S3H];
13C NMR (125.67 MHz, CDCl3)
d 175.6, 175.5, 142.0, 140.9, 129.7,
3.19. 2-Allyl-2-methyl-1-morpholinohept-6-en-3-yn-1-one (7d)
129.5, 128.4 (þ), 127.7 (þ), 127.6 (þ), 126.14 (þ), 126.09 (þ), 105.1
(þ), 103.4 (þ), 67.5 (þ), 67.3 (þ), 66.8 (ꢀ, br), 46.8 (ꢀ), 46.5 (ꢀ), 42.6
(ꢀ), 42.3 (ꢀ), 27.6, 27.1, 21.6 (þ), 21.5 (þ); IR (film, cmꢀ1): 3303 (br),
3061, 2964, 2922, 2856, 1632, 1493, 1275, 1256, 1213, 1153, 1115,
1030, 700; HRMS (TOF ES): found 274.1441, calculated for
C16H20NO3 (MþH) 274.1443 (0.7 ppm).
The reaction was performed according to a typical procedure,
employing cyclopropene 1d (179 mg, 1.07 mmol), lithium hexame-
thyldisilazide (449 mg, 2.68 mmol, 2.50 equiv), and allyl iodide
(206
the title compound as yellow viscous oil, Rf 0.34 (hexanes/EtOAc, 3:1).
Yield 148 mg (0.60 mmol, 56%); 1H NMR (500.13 MHz, CDCl3)
5.88
mL, 377 mg, 2.25 mmol, 2.10 equiv) as an electrophile to afford
d
3.16. [2-(1-Hydroxy-1-phenylethyl)-1-methylcycloprop-
2-en-1-yl](morpholin-4-yl)methanone (4dh)
(dddd, J¼17.3, 9.6, 8.2, 6.3 Hz, 1H), 5.79 (ddt, J¼17.0, 10.1, 5.4 Hz, 1H),
5.27 (dq, J¼17.0, 1.6 Hz, 1H), 5.14 (br m, 1H), 5.12e5.09 (m, 2H),
3.70e3.66 (m, 8H), 3.98(dt, J¼5.3,1.6 Hz, 2H), 2.62(dd, J¼13.9, 6.3 Hz,
1H), 2.40 (dd, J¼13.9, 8.2 Hz, 1H), 1.43 (s, 3H); 13C NMR (125.76 MHz,
The reaction was performed according to a typical procedure,
employing cyclopropene 1d (150 mg, 0.90 mmol) and acetophe-
none (233 mL, 240 mg, 2 mmol) as an electrophile to afford a title
CDCl3)
d
170.6,133.9 (þ),132.4 (þ),118.4 (ꢀ),116.2 (ꢀ), 83.9, 82.3, 66.8
(ꢀ), 66.7 (ꢀ), 48.2 (ꢀ), 48.1 (ꢀ), 44.3 (ꢀ), 40.4, 25.7 (ꢀ), 23.1 (þ); IR
(film, cmꢀ1): 3076, 2976, 2920, 2854, 1643, 1420, 1209, 1153, 1117,
1030, 916, 505; GC: tR 10.99 min; HRMS (TOF ES): found 248.1644,
calculated for C15H22NO2 (MþH) 248.1650 (2.4 ppm).
compounds as light-yellow viscous oil, Rf 0.29 (hexanes/EtOAc,1:2).
Yield 161 mg (0.56 mmol, 62%), dr 1:1; 1H NMR (500.19 MHz,
CDCl3)
d 7.63e7.58 (m, 2H), 7.39e7.33 (m, 2H), 7.29e7.25 (m, 1H),
[6.77 (s) and 6.64 (s), S1H], [6.30 (br s) and 6.23 (br s), S1H],
3.75e3.50 (m, 8H), [1.86 (s) and 1.78 (s), S3H], [1.53 (s) and 1.00 (s),
S3H]; 13C NMR (125.67 MHz, CDCl3)
d 175.6, 175.4, 146.4, 145.1,
Acknowledgements
132.5, 132.0, 128.1 (þ, 2C), 128.0 (þ, 2C), 127.0 (þ), 126.9 (þ), 125.2
(þ, 2C), 124.8 (þ, 2C),103.3 (þ), 102.4 (þ), 71.0, 70.5, 66.7 (ꢀ, br, 4C),
46.8 (ꢀ, br, 2C), 42.2 (ꢀ, br, 2C), 30.6 (þ), 29.6 (þ), 28.1, 27.9, 22.3
(þ), 21.0 (þ); IR (film, cmꢀ1): 3279 (br), 3109, 2972, 2922, 2856,
1605, 1462, 1439, 1364, 1277, 1256, 1215, 1153, 1115, 1067, 1030, 768,
702, 623, 592; HRMS (TOF ES): found 287.1519, calculated for
C17H21NO3 (Mþ) 287.1521 (0.7 ppm).
Financial support from the University of Kansas and the National
Science Foundation (EEC-0310689) is gratefully acknowledged.
Supplementary data
Spectral charts for all new compounds. Supplementary data
associated with this article can be found in the online version, at
doi:10.1016/j.tet.2010.04.123.
3.17. [1-Methyl-2-(prop-2-en-1-yl)cycloprop-2-en-1-yl]
(morpholin-4-yl)methanone (4di)
References and notes
The reaction was performed according to a typical procedure,
1. (a) Lavecchia, A.; Greco, G.; Novellino, E.; Vittorio, F.; Ronsisvalle, G. J. Med.
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employing cyclopropene 4d (100 mg, 0.60 mmol) and allyl bromide
(53
pound as yellow oil, Rf 0.36 (hexanes/EtOAc 6:1). Yield 117 mg
(0.56 mmol, 90%); 1H NMR (500.13 MHz, CDCl3)
ppm 5.93 (ddt,
mL, 76 mg, 0.63 mmol) as an electrophile to afford a title com-
d

R. Kim et al. / Tetrahedron 66 (2010) 4947e4953
4953
Al-Azawi, F. N. J. Heterocycl. Chem. 1977, 14, 1347; (c) Breslow, R.; Douek, M. J.
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Castellucci, N. C.; Kato, M.; Zenda, H.; Masamune, S. J. Chem. Soc., Chem. Com-
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and measure it into the reaction vessels by mass. This allowed for accurate
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lective mono-deprotonation.
21. For iodide-assisted ring-opening of cyclopropene-3-carboxylates, see for
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