Cyclopropyl building blocks for organic synthesis, 139.[1] ethyl cyclopropylidenepyruvate as a novel multifunctional cyclopropyl building block: Facile preparation and basic reaction patterns

Article abstract of DOI:10.1002/adsc.200600617

Tin(II) chloride-mediated Barbier-type coupling of ethyl glyoxylate with 2,3-dibromopropene followed by Simmons-Smith cyclopropanation and subsequent Dess-Martin oxidation, afforded ethyl 3-(1-bromocycloprop-1-yl)-2-oxopropionate (5), a stable precursor o

Full text of DOI:10.1002/adsc.200600617

FULL PAPERS
DOI: 10.1002/adsc.200600617
Cyclopropyl Building Blocks for Organic Synthesis, 139.[1] Ethyl
Cyclopropylidenepyruvate as a Novel Multifunctional Cyclopropyl
Building Block: Facile Preparation and Basic Reaction Patterns
Viktor Bagutskia and Armin de Meijerea,*
a
Institut für Organische und Biomolekulare Chemie der Georg-August-Universität Gçttingen, Tammannstrasse 2, 37077
Gçttingen, Germany
Fax : +49-551-399-475; e-mail: Armin.deMeijere@chemie.uni-gçttingen.de
Received: December 1, 2006
Supporting information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: Tin(II) chloride-mediated Barbier-type yields), Diels–Alder reactions with cyclopentadiene
coupling of ethyl glyoxylate with 2,3-dibromopro- (65%) and 2,3-dimethylbuta-1,3-diene (66%) as well
pene followed by Simmons–Smith cyclopropanation as [4+2] cycloadditions across the enone moiety of
and subsequent Dess–Martin oxidation, afforded 1j (hetero-Diels–Alder reactions) with furan and
ethyl
3-(1-bromocycloprop-1-yl)-2-oxopropionate enol ethers (65–79%), thus opening up a ready
(5), a stable precursor of ethyl cyclopropylidenepyru- access to a wide range of new variously functional-
vate (1j), in good overall yield (65%), even on a ized cyclopropane derivatives.
multi-gram scale. The potentially rich chemistry of
this novel cyclopropyl building block was illustrated Keywords: bicyclic compounds; cycloadditions;
by some basic transformations such as Michael addi- Diels–Alder reactions; methylenecyclopropanes; Mi-
tions of N-, S-, O- and C-nucleophiles (10–91% chael addition; spiro compounds
Introduction
methyl 2-halo-2-cyclopropylideneacetates 1g, h have
been used to prepare a large variety of spirocyclopro-
In view of the wide variety of biologically active com- panated carbo- and heterocyclic compounds[3,9] includ-
pounds containing a cyclopropane moiety, not only ing a penicillin analogue[10] as well as cyclopropyl-
have cyclopropanations of alkenes gained increasing group containing amino acids.[11]
importance, but also the applications of highly func-
tionalized molecular building blocks already contain-
ing a cyclopropane ring, which will be retained in the
target structures. A series of 1’-substituted methylene-
cyclopropane derivatives 1 (Scheme 1) has demon-
strated a range of reactivity patterns potentially
useful for the synthesis of certain natural products
and spirocyclopropanated analogues of biologically
active compounds.[2,3] For example, bicyclopropylidene
(1a) has been employed in various palladium-cata-
lyzed cascade reactions,[2] and (benzyloxymethylene)-
cyclopropane (1b) was used in the synthesis of a spi-
rocyclopropane-annelated sugar[4] as well as interest-
ing azetidine derivatives.[5] Several previously pre-
pared acceptor-substituted methylenecyclopropanes
1c–h come along with a particularly broad spectrum
of applications.[3] Ethyl cyclopropylideneacetate (1c,
R=Et) has recently been employed in new assem-
Scheme 1. Previously known methylenecyclopropanes 1a–i
with functionalities on the methylene group and retrosyn-
thetic considerations concerning the newly conceived cyclo-
blies of the skeletons of the highly cytotoxic illu-
dines[6] as well as other natural products,[7,8] and propylidenepyruvate 1j.
Adv. Synth. Catal. 2007, 349, 1247 – 1255
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Viktor Bagutski and Armin de Meijere
FULL PAPERS
In line with our long-standing interest in the design raphy (silica gel, Florisilꢂ and alumina were tested) or
and development of new cyclopropyl building blocks by distillation. However, Dess–Martin[23] oxidation of
for organic synthesis, we envisaged an enhanced reac- 5 followed by “dry-column” flash chromatography[24]
tivity of an alkyl cyclopropylidenepyruvate like 1j in furnished sufficiently pure ethyl 3-(1-bromocyclopro-
which the methylenecyclopropane double bond would pyl)pyruvate (6). The final dehydrobromination of 6
be activated by the a-oxo ester moiety, and we here was accomplished by stirring an ethereal solution of 6
report the first synthesis of ethyl cyclopropylidenepyr- with anhydrous sodium carbonate overnight. The ob-
1
uvate (1j) as well as some of its potentially useful tained product showed no impurities in its H NMR
transformations.
spectrum (purity>95% according to GC) and was
fully characterized by spectroscopic methods. Ethyl
cyclopropylidenepyruvate (1j) is stable at room tem-
perature in dilute solution, but as a neat compound ir-
reversibly forms oligomeric products upon storage at
Results and Discussion
In anticipation of the extreme reactivity of 1j, it ap- ambient temperature even for short times. Even so,
peared to be most reasonable to first assemble its an attempted “Kugelrohr” distillation of crude 1j af-
carbon framework and eventually elaborate the re- forded a pure sample albeit in poor yield (about
quired functionalities by mild and highly efficient 30%). This indicates that 1j is thermally stable at
functional group transformations (Scheme 2). The temperatures not higher than 1008C towards possible
thus conceived four-step synthesis started with an unimolecular processes such as rearrangements or ex-
iodide-accelerated Barbier-type reductive allylation of trusions.
[19]
ethyl glyoxylate (3) in the presence of SnCl2 to give
The new cyclopropylidenepyruvate (1j) was first
4-bromo-2-hydroxypent-4-enoate (4) in good yield tested in reactions with a set of carbo- and heteronu-
(72%). After some optimization, this procedure cleophiles. Because of its tendency to undergo oligo-
turned out to be easily scalable to produce 4 on a merization, 1j is best generated in situ from its stable
molar scale. The bromovinyl group in 4 was smoothly precursor, ethyl 3-(1-bromocyclopropyl)-2-oxopropio-
cyclopropanated[20] with
a
3.3-fold excess of nate (6) in the presence of the respective reaction
CF3COOZnCH2I (so-called Shiꢁs carbenoid)[21] to partner. In order to achieve reasonable yields of the
afford the key intermediate 5 in excellent yield desired Michael adducts of 1j, three different proto-
(92%). Remarkably, the vinyl bromide 4 could be cy- cols were developed (Table 1) depending on the re-
clopropanated with a significantly smaller excess of quired base strength and on the nucleophilicity of the
the reagent mixture than a vinyl chloride as reported applied nucleophile. Thus, one additional equivalent
by Evans et al.[22]
of the nucleophile, when it is a sufficiently strong
An initially attempted Swern oxidation of the 3-(1- non-ionic base itself, such as a secondary aliphatic
bromocyclopropyl)-2-hydroxypropionate (5) failed, as amine (Table 1, entry 1), or added triethylamine, in
it gave a complex mixture containing, along with vari- the case of weak bases such as phenols or mercaptans
ous by-products, the target ethyl cyclopropylidenepyr- (Table 1, entry 2), were used to accomplish sequential
1
uvate 1j (about 50%, according to an H NMR spec- elimination and Michael addition. With sodium azide
trum of the reaction mixture), but the latter could not and sodium nitrite (Table 1, entries 4 and 5), no addi-
be isolated in pure form either by column chromatog- tional base was required to eliminate hydrogen bro-
mide from 6 thus liberating the respective conjugate
acid, which in turn trapped the simultaneously formed
1j. Whereas diethylamine, thiophenol, sodium azide
and sodium nitrite gave the corresponding adducts 7,
8, 10, 11 in good yields, p-methoxyphenol in the pres-
ence of triethylamine gave an inseparable mixture in
which the respective Michael adduct was present to
1
an extent of 10% (according to H NMR), and Mi-
chael additions of aliphatic alcohols onto 1j could not
be achieved at all, since 1j apparently does not toler-
ate hard bases such as hydroxide or alkoxide anions.
Acid catalysis turned out to be ineffective, too. Treat-
ment of 1j or its precursor 6 with slightly basic water
even for a short time caused complete loss of them.
Therefore, the standard work-up procedure after the
Dess–Martin oxidation, i.e., removal of the acidic by-
products by washing with aqueous NaOH, had to be
replaced by flash chromatography (see above).
Scheme 2. Synthesis of ethyl cyclopropylidenepyruvate (1j).
Reagents and conditions: (a) 2,3-dibromopropene (2) (1.1
equivs.), SnCl2·2H2O (1.2 equivs.), NaI, THF, 258C, 24 h
(1.2 equivs.); (b) Et2Zn (3.3 equivs.), CF3CO2H (3.3 equivs.),
CH2I2 (3.3 equivs.), CH2Cl2, À5 to 08C, 1.5 h, then 258C,
60 h; (c) Dess–Martin periodinane (1.1 equivs.), CH2Cl2,
258C, 1 h; (d) Na2CO3 (5 equivs.), Et2O, 25 8C, 24 h.
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Cyclopropylidenepyruvate as a Multifunctional Cyclopropyl Building Block
FULL PAPERS
Table1. Michael additions of various nucleophiles to ethyl cyclopropylidenepyruvate (1j) in situ generated from ethyl 3-(1-
bromocyclopropyl)-2-oxopropionate (6).
Entry
Nucleophile
Base (equivs.)
Conditions
Product
Nu
Yield [%]
1
2
3
4
5
HNEt2
PhSH
HNEt2 (1.1)
NEt3 (1.1)
DBU (1.5)
–
–
CH2Cl2, 08C, 1 h
CH2Cl2, 08C, 1 h
THF, LiI (60 mol%), 258C, 2 h
Et2O, 18-crown-6 (5 mol%), 258C, 3 h
Et2O, 18-crown-6 (5 mol%), 258C, 3 h
7
8
9
10
11
Et2N
PhS
90
91
43
92
96
CH2
A
A
NaN3
NaNO2
N3
O2N
As Michael additions of carbon nucleophiles to 1’- an inverse electron-demand cycloaddition of 1j acting
acceptor-substituted methylenecyclopropanes do as a heterodiene. Indeed, ethyl vinyl ether and 4,5-di-
occur readily,[25] they were also tested for 1j. An ini- hydrofuran also smoothly reacted with 1j at ambient
tially attempted reaction with sodium cyanide in temperature to give the corresponding hetero-Diels–
DMF, EtOH or Et2O with 6 led to a complex mixture Alder (HDA) adducts 15 and 16 in 79 and 37% yield,
of products, which must be due to the presence of the respectively. Furan furnished the spirocyclopropanat-
electrophilic carbonyl group in 6, its dehydrobromina- ed bicyclic HDA adduct 17 in good yield (65%) as
tion product 1j, as well as the initial Michael adduct well. Being unstable towards either aqueous work-up
of type 7.[26] However, the enolate of dimethyl malo- or column chromatography, 17 underwent further
nate, generated with 1,8-diazabicyclo[5.3.0]undecene transformations, affording the ring-opening product
A
(DBU) in the presence of lithium iodide,[27] did pro- 18, which may also be referred to as a formal Michael
vide the adduct 9, but in moderate yield (43%). Most adduct of furan to 1j, along with a small amount of 19
probably, though, this yield may be significantly im- by addition of water to the dihydrofuran moiety in 17
proved by appropriate modification of the reaction (Scheme 4)
conditions.
The lower yield of the cycloadduct 16 may be
The reactivity of 1j in Diels–Alder reactions was in- caused by a steric effect; thus, the slightly more steri-
itially tested with cyclopentadiene and 2,3-dimethyl- cally demanding 3,4-dihydropyran did not react with
buta-1,3-diene by dissolving 1j in an excess of the 1j at all under the same reaction conditions. Simple
diene and leaving the mixture at ambient temperature cycloalkenes also did not undergo this cycloaddition.
for 1 day (Scheme 3). The cyclopentadiene adduct 12
The unexpectedly high reactivity of 1j in inverse
was obtained in 65% yield as a 3:1 mixture of endo- electron-demand HDA (no heating, no high pressure,
and exo-diastereomers. Surprisingly, the reaction of 1j no Lewis acid catalyst required) may originate from
with 2,3-dimethylbutadiene afforded in 82% yield a the preferred s-cis conformation of the enone moiety
4:1 mixture of the expected [4+2] cycloadduct 13 and in 1j.
the 6-oxaspiro
A
The HDA adducts of 1j can also be obtained by
treating the stable precursor 6 of 1j in an excess of
the corresponding enol ether with triethylamine. In
fact, under these conditions, the reactions were com-
plete in significantly shorter time (1–2 h) and some-
times provided better yields of the respective adducts,
(e.g., under these conditions 16 was obtained in 65%
yield), which may be due to a catalytic acceleration of
the reaction by the formed triethylamine hydrobro-
mide.
Conclusions
In conclusion, a short and highly efficient synthesis of
the new multifunctional cyclopropyl building block,
ethyl cyclopropylidenepyruvate (1j), has been devel-
oped, and the efficiency of the latter in a number of
Scheme 3. Diels–Alder reactions of ethyl cyclopropylidene-
pyruvate (1j). Reagents and conditions: diene (2 mL per
mmol of 1j) neat, 258C, 24 h.
Adv. Synth. Catal. 2007, 349, 1247 – 1255
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Viktor Bagutski and Armin de Meijere
FULL PAPERS
Scheme 4. Inverse electron-demand hetero-Diels–Alder reactions of ethyl cyclopropylidenepyruvate (1j), and further trans-
formations of the furan adduct of 1j. Reagents and conditions: alkene (2 mL per mmol of 1j), neat, 258C, 24 h.
synthetically useful transformations such as Michael Ethyl 4-Bromo-2-hydroxypent-4-enoate (4)
additions, Diels–Alder and inverse-electron demand
To a stirred solution of SnCl2·2H2O (86.9 g, 385 mmol) and
hetero-Diels–Alder reactions has been demonstrated.
NaI (57.7 g, 385 mmol) in THF (600 mL) were added ethyl
The new building block displayed a reactivity pattern,
glyoxylate (3) (64 mL of a ~50% solution in toluene,
which is complementary in several aspects to those
which the previously known acceptor-substituted
methylenecyclopropanes feature.[28]
~320 mmol)
and
2,3-dibromopropene
(2)
(70.4 g,
352 mmol), with occasional cooling of the reaction mixture
with ice/water. After the slightly exothermic reaction had
ceased, the cooling bath was removed, and the mixture was
stirred at ambient temperature for 24 h, then poured into a
half-saturated aqueous solution of NH4Cl (600 mL). The or-
ganic layer was separated and the aqueous phase was re-ex-
tracted with diethyl ether (3”200 mL). The combined or-
ganic phases were washed with half-diluted brine (2”
400 mL; iodine was removed by addition of a minimal
amount of crystalline Na2S2O3 during the first washing),
brine (500 mL), and dried with MgSO4. Removal of the sol-
vent left 66.4 g of a pale-yellow crude product, which was
rectified under reduced pressure through a 20 cm Vigreux
column, affording pure 3 as a colorless oil; yield: 51.6 g
Experimental Section
General Remarks
1H NMR and 13C NMR spectra were recorded on Bruker
1
AM 250 (250 for H, 62.9 MHz for 13C) and Varian Unity
1
300 (300 for H and 75.6 MHz for 13C) instruments. Multi-
˜
(72%); bp 62–638C (0.02 mbar). IR (film): n=3466, 2982,
plicities were determined by DEPT (distortionless enhance-
ment by polarization transfer; Bruker), or by APT (attached
proton test; Varian) measurements. The residual signal of
CHCl3 served as an internal standard. IR: Bruker IFS 66
(FT-IR) spectrometer, samples were measured as KBr pel-
lets or oils between KBr plates. MS (EI, 70 eV) or MS
(70 eV, DCI, NH3): Finnigan MAT 95 spectrometer. TLC:
2938, 2907, 1739, 1735, 1633, 1473, 1445, 1419, 1369, 1274,
1
1217, 1131, 1099, 1033, 1017, 952, 894, 863 cmÀ1; H NMR
(300 MHz, CDCl3): d=1.32 (t, J=7.2 Hz, 3H), 2.73 (ddd,
J=14.7, J=8.3, J=0.8 Hz, 1H), 2.88 (bs, 1H), 2.92 (dddd,
J=14.7, J=4.0, J=1.2, 0.5 Hz, 1H), 4.27 (q, J=7.2 Hz, 2H),
4.45 (dd, J=8.3, 4.0 Hz, 1H), 5.57 (dd, J=1.8, J=0.8 Hz,
1H), 5.74 (ddd, J=1.8, J=1.2, 0.5 Hz, 1H); 13C NMR
(75.5 MHz, CDCl3, APT): d=14.2 (CH3), 46.0 (CH2), 62.1
(CH2), 68.4 (CH), 120.4 (CH2), 128.1 (C), 173.8 (C); MS
(70 eV, DCI, NH3): m/z (%)=257/259 (4/5) [M+NH3 +
NH4]+, 242/240 (92/100) [M+NH4]+, 162 (2) [M+
NH4ÀBr]+, 143 (4) [MÀBr]+; anal. calcd. for C7H11BrO3
(223.06): C 37.69, H 4.97; found: C 37.68, H 5.00.
Macherey–Nagel precoated sheets, 0.25 mm Sil G/UV254
.
Column chromatography: Merck silica gel 60 (70–230
mesh). Analytical gas chromatography: Varian CP-3800.
Flash chromatography: Merck silica gel 60 230–400 mesh;
the “dry column technique”[24] was applied. Elemental anal-
yses were performed by Mikroanalytisches Laboratorium
des Instituts für Organische und Biomolekulare Chemie der
Universität Gçttingen, with an elemental analyzer CHN-
2000 (Leco). Starting materials and solvents: tetrahydrofur-
an (THF) was distilled from sodium/benzophenone. Anhy-
drous dichloromethane was distilled from phosphorus pent-
oxide under nitrogen and stored over molecular sieves 3 Š.
Triethylamine was distilled from calcium hydride under ni-
trogen. 2,3-Dibromopropene (3) was prepared according to
a published procedure.[29] All other chemicals were used as
commercially available without further purification.
Ethyl 3-(1-Bromocycloprop-1-yl)-2-hydroxypro-
pionate(5)
To a mechanically stirred solution of ZnEt2 (50 mL, 0.488
mol) in anhydrous CH2Cl2 (450 mL) chilled at À258C under
nitrogen, was added trifluoroacetic acid (36 mL, 0.486 mol)
within 1 h at such a rate that the temperature did not
exceed 08C (Caution! Gas evolution! Full size adapters, gas
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Cyclopropylidenepyruvate as a Multifunctional Cyclopropyl Building Block
FULL PAPERS
inlets and bubblers charged with paraffin oil must be used
to avoid clogging of holes with solid particles from the reac-
tion mixture). After additional stirring at 08C for 15 min,
CH2I2 (40 mL, 0.496 mol) was added all at once, keeping the
temperature around 08C with occasional cooling (ice/salt
bath), and the reaction mixture was vigorously stirred at this
temperature until it had become completely homogeneous
(25–30 min). To this carbenoid solution was added 4 (33 g,
0.148 mol) dropwise at 08C within 15 min. After stirring at
this temperature for an additional 30 min, the cooling bath
was removed, and the mixture was stirred at ambient tem-
perature for 60 h (at that point, a gas chromatogram of the
reaction mixture showed only about 1% of the starting ma-
terial to be left). The vigorously stirred reaction mixture was
then cooled to 08C (ice/salt bath), and 2M aqueous H2SO4
(250 mL) was gradually added (the first 50 mL was added
slowly and carefully). The phases were separated and the
aqueous layer was extracted with diethyl ether (3”200 mL).
The combined organic phases were subsequently washed
with 2N NaOH (250 mL), brine (2”150 mL) and dried over
MgSO4. The residue obtained after evaporation of the sol-
vents was distilled under reduced pressure to give pure 5 as
Ethyl Cyclopropylidenepyruvate (1j)
Compound 6 (1.18 g, 5.02 mmol) was added to a suspension
of oven-dried finely powdered Na2CO3 (2.65 g, 25.0 mmol)
in anhydrous diethyl ether (25 mL), and the mixture was
stirred at ambient temperature for 24 h. Filtration and sol-
vent evaporation at 08C afforded sufficiently pure 1j as a
˜
colorless or pale-yellow liquid. IR (film): n=3055, 2986,
2940, 2908, 2876, 2855, 1745, 1733, 1677, 1476, 1466, 1448,
1401, 1394, 1371, 1315, 1268, 1250, 1175, 1143, 1102, 1037,
1
1016, 970, 925, 874, 814, 770, 732 cmÀ1; H NMR (250 MHz,
CDCl3): d=1.32–1.52 (m, 4H), 1.37 (t, J=7.1 Hz, 3H), 4.34
(q, J=7.1 Hz, 2H), 6.78 (tt, J=1.9, 1.7 Hz, 1H); 13C NMR
(62.5 MHz, CDCl3, DEPT): d=2.8 (CH2), 5.0 (CH2), 14.0
(CH3), 62.4 (CH2), 116.1 (CH), 152.9 (C), 164.3 (C), 185.6
(C); MS (70 eV, EI): m/z (%)=154 (7) [M+], 126 (14)
[M+ÀCO], 109 (2) [M+ÀC2H5O], 98 (10) [M+À2 CO], 81
+
+
(100) [M+ÀC2H5OÀCO], 53 (54) [C4H5 ], 51 (6) [C4H3 ], 42
(2). The neat compound thus obtained has to be used imme-
diately, since it is extremely susceptible to undergo oligome-
rization.
General Procedure for Reaction of 6 with Neutral
Nucleophiles (GP 1)
a
pale-yellow oil; yield: 32.3 g (92%); bp 75–768C
˜
(0.1 mbar). IR (film): n=3485, 2983, 2939, 2908, 2874, 1735,
1473, 1465, 1458, 1448, 1419, 1370, 1272, 1224, 1149, 1108,
1
To an ice-cold solution of 6 (470 mg, 2.0 mmol) in anhydrous
CH2Cl2 (4 mL) the respective nucleophile (2 mmol) was
added all at once, and triethylamine (2.1 mmol, 212 mg) was
gradually added within 5 min. After additional stirring at
28C for 1 h, the reaction mixture was diluted with anhy-
drous ether (20 mL), and filtered. Evaporation of the sol-
vents left a crude product, which was purified by chromatog-
raphy on silica gel.
1045, 1023, 941, 860, 819, 772, 684 cmÀ1; H NMR (300 MHz,
CDCl3): d=0.78–0.90 (m, 1H), 1.00–1.08 (m, 1H), 1.12–1.26
(m, 2H), 1.32 (t, J=7.2 Hz, 3H), 1.67 (dd, J=14.8, J=
8.8 Hz, 1H), 2.46 (ddd, J=14.8, J=3.5, J=1.2 Hz, 1H), 2.82
(bs, 1H), 4.18–4.33 (m, 2H), 4.54 (dd, J=8.8, 3.5 Hz, 1H);
13C NMR (75.5 MHz, CDCl3, APT): d=14.1 (CH3), 15.5
(CH2), 16.4 (CH2), 30.9 (C), 46.2 (CH2), 61.9 (CH2), 69.9
(CH), 174.7 (C) ppm; MS (70 eV, EI): m/z (%)=238/236
(0.5) [M+], 165/163 (3/3) [M+ÀC2H5OÀCO], 157 (18)
[M+ÀBr], 139 (2) [M+ÀBrÀH2O], 129 (8) [M+ÀBrÀC2H5],
Ethyl 3-[1-(N,N-Diethylamino)cycloprop-1-yl]-2-oxo-
propionate(7)
111
(13)
[M+ÀBrÀH2O],
104
(27)
83
(31)
[M+ÀBrÀC2H5OHÀCO], 76 (17), 75 (10), 67 (6), 55 (100),
53 (20), 45 (3); anal. calcd. for C8H13BrO3 (237.09): C 40.53,
H 5.53; found: C 40.50, H 5.50.
According to GP 1, 6 reacted with diethylamine (146 mg,
2 mmol) to afford after flash chromatography on silica gel
(10 g), eluting with hexane/ethyl acetate/ethanol, 40/10/1 to
20/10/1, 409 mg of pure 7 (90%), as a 2:1 mixture of tauto-
mers.
Ethyl 3-(1-Bromocycloprop-1-yl)-2-oxopropionate(6)
Major tautomer: 1H NMR (250 MHz, CDCl3): d=0.55–
0.61 (m, 2H), 0.65–0.71 (m, 2H), 0.88 (t, J=7.1 Hz, 3H),
0.95 (t, J=7.2 Hz, 6H), 2.48 (q, J=7.2 Hz, 4H), 2.74 (s,
2H), 3.88 (q, J=7.1 Hz, 2H); 13C NMR (62.5 MHz, C6D6):
d=13.5 (CH3), 14.3 (2 CH2), 15.0 (2 CH3), 39.7 (CH2), 41.5
(C), 46.9 (2 CH2), 61.9 (CH2), 162.5 (C), 193.9 (C).
Compound 5 (4.74 g, 20 mmol) was added in one portion to
a
stirred solution of Dess–Martin periodinane (9.33 g,
22 mmol) in anhydrous CH2Cl2 (20 mL), and the mixture
was stirred at ambient temperature until the starting materi-
al had completely disappeared (60–80 min, TLC control).
The mixture was then diluted with pentane (100 mL), and
the obtained suspension was passed through a short plug of
flash silica gel (80 mL, Ø65 mm) eluting with hexane/
EtOAc, 5:1 (5”100 mL), to afford sufficiently pure 5; yield
4.61 g (98%). The thus obtained product is sufficiently
stable at ambient temperature in solution; the neat com-
pound could be stored infinitely at temperatures below
Minor tautomer: 1H NMR (250 MHz, CDCl3): d=0.49–
0.54 (m, 2H), 0.70–0.75 (m, 2H), 0.93 (t, J=7.2 Hz, 6H),
0.98 (t, J=7.1 Hz, 3H), 2.01 (q, J=7.2 Hz, 4H), 4.06 (q, J=
7.1 Hz, 2H), 5.41 (s, 1H); 13C NMR (62.5 MHz, C6D6): d=
13.8 (2 CH3), 14.0 (CH3), 14.3 (2CH2), 42.4 (C), 46.4 (CH2),
60.8 (CH2), 115.2 (CH), 145.1 (C), 164.4 (C); MS (70 eV,
DCI, NH3): m/z (%)=455 (2) [2M+H]+, 228 (100) [M+H],
154 (5) [M+ÀEt2NH]; anal. calcd. for C12H21NO3 (227.30): C
63.41, H 9.31, N 6.16; found: C 63.15, H 9.08, N 5.99.
˜
À208C. IR (film): n=3088, 3005, 2985, 2940, 2907, 2875,
1748, 1731, 1474, 1446, 1391, 1371, 1306, 1266, 1230 1143,
1097, 1068, 1028, 1015, 975, 936, 912, 860, 848, 819, 787, 763,
744, 689 cmÀ1 1H NMR (250 MHz, CDCl3): d=0.94–1.00
;
Ethyl 3-(1-Phenylsulfonylcycloprop-1-yl)-2-oxopro-
pionate(8)
(m, 2H), 1.24–1.30 (m, 2H), 1.38 (t, J=7.2 Hz, 3H), 3.29 (s,
2H), 4.33 (q, J=7.2 Hz, 2H); 13C NMR (62.5 MHz, CDCl3,
DEPT): d=13.9 (CH3), 16.3 (2 CH2), 25.2 (C), 50.3 (CH2),
62.7 (CH2), 160.9 (C), 190.8 (C).
According to GP 1, 6 reacted with thiophenol (220 mg,
2 mmol) to afford after column chromatography on silica
Adv. Synth. Catal. 2007, 349, 1247 – 1255
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asc.wiley-vch.de
1251

Viktor Bagutski and Armin de Meijere
FULL PAPERS
gel (30 g), eluting with hexane/ethyl acetate, 8:1 to 6:1, pure
ganic layers were washed with brine (4 mL) and dried with
MgSO4. Chromatographic purification of the residue ob-
tained after solvent removal, afforded the pure product.
˜
8; yield: 480 mg (91%). IR (film): n=3077, 3060, 3003,
2985, 2965, 2939, 2903, 1750, 1728, 1584, 1479, 1440, 1392,
1370, 1294, 1261, 1241, 1172, 1158, 1092, 1069, 1058, 1025,
1015, 980, 858, 849, 828, 741, 692 cmÀ1; H NMR (250 MHz,
1
Ethyl 3-(1-Azidocycloprop-1-yl)-2-oxopropionate(10)
CDCl3): d=1.01–1.09 (m, 2H), 1.12–1.20 (m, 2H), 1.34 (t,
J=7.2 Hz, 3H, CH3), 3.09 (s, 2H, CH2), 4.29 (q, J=7.2 Hz,
2H, CH2), 7.18–7.42 (m, 5H); 13C NMR (62.5 MHz, CDCl3,
DEPT): d=13.9 (CH3), 15.7 (2 CH2), 21.3 (C), 46.3 (CH2),
62.5 (CH2), 126.4 (CH), 129.0 (2 CH), 129.3 (2 CH), 135.5
(C), 161.3 (C), 192.2 (C); MS (70 eV, EI): m/z (%)=264
(16) [M+], 246 (18) [M+ ÀH2O], 235 (9), 217 (2), 200 (8),
191 (41), 173 (16), 163 (62), 148 (28), 135 (100), 129 (58),
123 (26), 115 (23), 109 (57), 91 (94), 85 (8), 81 (37), 77 (28),
71 (8), 69 (13), 65 (34), 55 (13), 53 (45), 51 (24), 45 (29), 41
(5); anal. calcd. for C14H16O3S (264.34): C 63.61, H 6.10;
found: C 63.46, H 5.93.
According to GP 3, 6 reacted with sodium azide (158 mg,
2.4 mmol) to afford, after column chromatography on silica
gel (40 g), eluting with hexane/ethyl acetate, 8:1, pure 10 as
˜
a pale-yellow oil; yield: 363 mg (92%). IR (film): n=3005,
2986, 2941, 2907, 2117, 2101, 1750, 1733, 1363, 1309, 1284,
1
1262, 1172, 1160, 1069, 1027, 1015 cmÀ1; H NMR (250 MHz,
CDCl3): d=0.75–0.80 (m, 2H), 1.03–1.08 (m, 2H), 1.37 (t,
J=7.1 Hz, 3H), 3.11 (s, 2H), 4.33 (q, J=7.1 Hz, 2H);
13C NMR (62.5 MHz, CDCl3, DEPT): d=12.3 (2 CH2), 13.9
(CH3), 39.0 (C), 45.9 (CH2), 62.7 (CH2), 160.7 (C), 191.7
(C); MS (70 eV, DCI, NH3): m/z (%)=412 (10) [2M+
NH4]+, 232 (32) [M+NH3 +NH4]+, 215 (100) [M+NH4]+,
187 (8), 170 (12)143 (5); anal. calcd. for C8H11N3O3 (197.19):
C 48.73, H 5.62, N 21.31; found: C 48.68, H 5.52, N 21.10.
General Procedure for Michael Additions of b-Dicar-
bonyl Compounds to in situ Generated 1j (GP 2)
To a stirred solution of 6 (470 mg, 2 mmol), LiI (161 mg
1.2 mmol) in anhydrous THF (4 mL) and DBU (457 mg,
3 mmol) were added within 10 min keeping the mixture
around 208C with occasional cooling (cold water). After stir-
ring at ambient temperature for 2 h, the reaction was
quenched by addition of 5% aqueous H2SO4 (2 mL), the or-
ganic layer was separated, and the aqueous phase was re-ex-
tracted with diethyl ether (3”2 mL). The combined organic
phases were washed with brine (2”5 mL) and dried with
MgSO4. Solvent removal left a crude product, which was pu-
rified by chromatography on silica gel.
Ethyl 3-(1-Nitrocycloprop-1-yl)-2-oxopropionate(11)
According to GP 3, 6 (2.95 g, 12.5 mmol) reacted with
sodium nitrite (1.04 g, 15 mmol) to afford, after flash chro-
matography on silica gel (50 mL), eluting with hexane/ethyl
acetate, 8:1 to 3:1, pure 11 as a viscous colorless oil which
crystallized in the refrigerator; yield: 2.43 g (96%); mp 55–
˜
568C. IR (film): n=3115, 2987, 2942, 2910, 2880, 1751, 1733,
1538, 1474, 1468, 1461, 1446, 1396, 1375, 1354, 1315, 1273,
1256, 1159, 1080, 1064, 1013, 991, 969, 938, 920, 878, 849,
815, 743, 729, 691, 584 cmÀ1 1H NMR (300 MHz, CDCl3):
;
d=1.15–1.30 (m, 2H), 1.39 (t, J=7.1 Hz, 3H), 1.95–2.10 (m,
2H), 3.53 (s, 2H), 4.36 (q, J=7.1 Hz, 2H); 13C NMR
(50.3 MHz, CDCl3, APT): d=13.9 (CH3), 17.9 (2 CH2), 41.9
(CH2), 60.1 (C), 62.9 (CH2), 160.2 (C), 189.1 (C); MS
(70 eV, DCI, NH3): m/z (%)=236 (34) [M+NH3 +NH4]+,
219 (100) [M+NH4]+, 205 (67), 189 (24), 174 (65), 172 (81),
156 (2), 135 (9), 103 (4); anal. calcd. for C8H11NO5 (201.18):
C 47.76, H 5.51; found: C 47.80, H 5.47.
Dimethyl 2-[1-(3-Ethoxy-2,3-dioxopropyl)cyclopropyl]-
malonate(9)
According to GP 2, 6 reacted with dimethyl malonate
(264 mg, 2 mmol) to afford, after column chromatography
on silica gel (50 g), eluting with hexane/ethyl acetate, 4:1,
pure 9 as a viscous colorless oil; yield: 246 mg (43%). IR
˜
(film): n=3085, 3003, 2988, 2957, 2907, 2847, 1750, 1734,
1437, 1395, 1369, 1321, 1301, 1267, 1195, 1157, 1095, 1071,
1
1057, 1034, 949, 746 cmÀ1; H NMR (250 MHz, CDCl3): d=
0.69–0.73 (m, 4H), 1.36 (t, J=7.1 Hz, 3H), 3.00 (s, 1H), 3.13
(s, 2H), 3.72 (s, 6H), 4.30 (q, J=7.1 Hz, 2H). 13C NMR
(62.5 MHz, CDCl3, DEPT): d=12.1 (2CH2), 14.0 (CH3),
15.6 (C), 43.8 (CH2), 52.5 (2 CH3), 57.1 (CH), 62.4 (CH2),
160.9 (C), 168.7 (2 C), 192.7 (C); MS (70 eV, EI): m/z (%)=
286 (0.2) [M+], 255 (12), 227 (10), 223 (8), 213 (100), 199
(8), 195 (4), 185 (16), 181 (72), 167 (4), 153 (42), 139 (5), 125
(46), 121 (17), 111 (5), 95 (7), 85 (15), 81 (5), 67 (6), 59 (13),
53 (6), 41 (4); ESI-HR-MS: m/z=325.06841, calcd. for
C13H18O7 [M+K]+: 286.10525.
General Procedure for Diels–Alder Reactions of 1j
or its Precursor 6 (GP 4)
Method A: Freshly prepared 1j (154 mg, 1 mmol) was dis-
solved in the respective diene or enol ether (2 mL) and the
solution was left at ambient temperature for 24 h. After the
excess of the diene or enol ether had been removed under
reduced pressure, the residue was purified by chromatogra-
phy to give a sufficiently pure adduct.
Method B: To a stirred solution of 6 (235 mg, 1 mmol) in
excess of the respective alkene (2 mL) anhydrous triethyl-
amine (101 mg, 1 mmol) was added all at once, and the mix-
ture was stirred at ambient temperature for 2 h. Then the re-
action mixture was poured into the water (2 mL) and ex-
tracted with diethyl ether (3”2 mL). The combined extracts
were washed with half-saturated brine (3 mL), brine (5 mL)
and dried over MgSO4. The residue, obtained after removal
of the volatile materials under reduced pressure, was sub-
jected to column chromatography to afford an appropriately
pure adduct.
General Procedure for Reactions of 6 with
Nucleophilic Salts (GP 3)
To a stirred suspension of the respective salt (2.4 mmol) and
18-crown-6 (26.4 mg, 0.1 mmol) in anhydrous diethyl ether
(4 mL), 6 (573 mg, 2 mmol) was added all at once and the
reaction mixture was stirred at ambient temperature for 3 h.
Then water (2 mL) was added, and the aqueous phase was
extracted with diethyl ether (2”2 mL). The combined or-
1252
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ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2007, 349, 1247 – 1255

Cyclopropylidenepyruvate as a Multifunctional Cyclopropyl Building Block
FULL PAPERS
˜
Compound 14: Colorless oil. IR (film): n=3079, 2982,
2952, 2935, 2872, 1728, 1638, 1456, 1446, 1395, 1371, 1341,
1321, 1305, 1275, 1236, 1213, 1172, 1140, 1105, 1087, 1027,
Ethyl endo-/exo-Spiro[cyclopropane-1,2’-norborn-5’-
en-3’-yl]oxoacetate (12)
981, 954, 902, 866, 854, 765 cmÀ1
;
1H NMR (300 MHz,
According to GP 4A, 1j (154 mg, 1 mmol) reacted with cy-
clopentadiene (2 mL) to afford, after column chromatogra-
phy on silica gel (50 mL), eluting with hexane/t-BuOMe,
20:1, an inseparable mixture of endo- and exo-diastereomers
CDCl3): d=0.72–0.80 (m, 4H), 1.30 (t, J=7.1 Hz, 3H), 1.43
(s, 3H), 1.71 (d, J=13.8 Hz, 1H), 1.78 (dd, J=1.3, 0.6 Hz,
3H), 1.85 (d, J=13.8 Hz, 1H), 4.14–4.34 (m, 2H), 4.86 (dq,
J=1.5, 1.3 Hz), 4.98 (dq, J=1.5, 0.6 Hz), 5.61 (s, 1H);
13C NMR (125.7 MHz, CDCl3, APT): d=14.2 (CH3), 14.6
(CH2), 15.0 (C), 15.2 (CH2), 19.0 (CH3), 25.1 (CH3), 40.1
(CH2), 60.8 (CH2), 80.5 (C), 110.8 (CH2), 119.4 (CH), 142.4
(C), 146.6 (C), 162.9 (C); MS (70 eV, EI): m/z (%)=236
(39) [M+], 221 (3), 207 (8), 191 (8), 175 (9), 162 (62), 147
(55), 135 (86), 119 (73), 107 (100), 105 (40), 93 (47), 91 (53),
82 (16), 79 (25), 69 (5), 67 (21), 65 (12), 55 (13), 53 (25), 51
(7), 43 (7), 41 (27); HR-MS (ESI, MeOH/H2O+FA): m/z=
237.14852, calcd. for [M+H]+: 237.14907.
1
(endo/exo ratio according to H NMR 3:1) of pure 12 as a
˜
colorless oil; yield: 143 mg (65%). IR (film): n=3065, 2978,
2940, 2908, 2871, 1747, 1726, 1653, 1558, 1457, 1331, 1270,
1255, 1215, 1159, 1117, 1075, 1017, 947, 904, 861, 716 cmÀ1.
endo-12: 1H NMR (250 MHz, CDCl3): d=0.45–0.64 (m,
4H), 1.35 (t, J=7.1 Hz, 3H), 1.58–1.63 (m, 1H), 1.85–1.90
(m, 1H), 2.08–2.12 (m, 1H), 3.27–3.31 (m, 1H), 3.72 (d, J=
3.2 Hz, 1H), 4.27 (q, J=7.1 Hz, 2H), 6.10 (dd, J=5.7,
2.8 Hz, 1H), 6.31 (dd, J=5.7, 3.2 Hz, 1H); 13C NMR
(125.7 MHz, CDCl3, APT): d=7.8 (CH2), 11.1 (CH2), 13.9
(CH3), 28.2 (C), 47.8 (CH), 49.2 (CH2), 52.5 (CH), 54.4
(CH), 62.1 (CH2), 133.6 (CH), 137.4 (CH), 162.0 (C), 194.9
(C).
Ethyl 7-Ethoxy-6-oxaspiro[2.5]oct-4-ene-5-carboxy-
A
exo-12: 1H NMR (250 MHz, CDCl3): d=0.65–0.74 (m,
4H), 1.35 (t, J=7.1 Hz, 3H), 1.47–1.53 (m, 1H), 1.99–2.04
(m, 1H), 2.05–2.07 (m, 1H), 2.99 (d, J=1.6 Hz, 1H), 3.05–
3.09 (m, 1H), 4.28 (q, J=7.1 Hz, 2H), 6.27 (dd, J=5.7,
3.0 Hz, 1H), 6.34 (dd, J=5.7, 2.9 Hz, 1H); 13C NMR
(125.7 MHz, CDCl3, APT): d=8.9 (CH2), 9.0 (CH2), 13.9
(CH3), 28.6 (C), 47.0 (CH2), 47.4 (CH), 51.6 (CH), 51.9
(CH), 62.3 (CH2), 136.1 (CH), 138.3 (CH), 161.6 (C), 196.8
(C); MS (70 eV, EI): m/z (%)=220 (2) [M+], 192 (7), 174
(2), 163 (3), 147 (65), 119 (53), 117 (39), 104 (7), 91 (100), 81
(30), 79 (17), 77 (18), 66 (44), 53 (20), 51 (7), 41 (39); anal.
calcd. for C13H16O3 (220.26): C 70.89, H 7.32; found: C
70.85, H 7.07.
late(15)
According to GP 4A, 1j (154 mg, 1 mmol) reacted with
ethyl vinyl ether (2 mL) to afford, after column chromatog-
raphy on silica gel (50 mL), eluting with hexane/t-BuOMe,
8:1, pure 15 as a colorless oil; yield: 179 mg (79%). IR
˜
(film): n=3080, 2979, 2929, 2873, 1729, 1640, 1480, 1468,
1461, 1445, 1390, 1371, 1332, 1310, 1260, 1232, 1201, 1171,
1160, 1125, 1090, 1050, 1037, 1004, 964, 934, 870, 860, 846,
765 cmÀ1 1H NMR (300 MHz, CDCl3): d=0.63–0.88 (m,
;
4H), 1.21 (t, J=7.1 Hz, 3H), 1.30 (t, J=7.1 Hz, 3H), 1.64
(ddd, J=13.6, 4.4, 0.8 Hz, 1H), 1.95 (dd, J=13.6, 2.6 Hz,
1H), 3.64 (dq, J=9.8, 7.1 Hz, 1H), 3.92 (dq, J=9.8, 7.1 Hz,
1H), 4.21 (q, J=7.1 Hz, 2H), 5.22 (dd, J=4.4, 2.6 Hz, 1H),
5.69 (d, J=0.8 Hz, 1H); 13C NMR (75.5 MHz, CDCl3, APT):
d=13.9 (C), 14.0 (CH2), 14.2 (CH3), 15.1 (CH3), 16.1 (CH2),
36.4 (CH2), 60.9 (CH2), 64.3 (CH2), 98.2 (CH), 121.4 (CH),
140.6 (C), 162.7 (C); MS (70 eV, EI): m/z (%)=226 (8)
[M+], 197 (17), 181 (5), 153 (30), 151 (20), 135 (3), 125 (38),
123 (36), 107 (59), 97 (32), 95 (17), 81 (41), 79 (56), 77 (19),
69 (19), 67 (54), 55 (13), 53 (47), 43 (39), 41 (100); anal.
calcd. for C12H18O4 (226.27): C 63.70, H 8.02; found: C
63.85, H 7.84.
Reaction of 1j with 2,3-Dimethylbutadiene
According to GP 4A, 1j (154 mg, 1 mmol) reacted with 2,3-
dimethylbutadiene (2 mL) to afford, after column chroma-
tography on silica gel (100 mL), eluting with hexane/t-
BuOMe, 20:1, pure ethyl (6,7-dimethylspiro
yl)-2-oxoacetate (13; yield: 156 mg, 66%) and sufficiently
pure ethyl 7-methyl-7-(1-isopropenyl)-6-oxaspiro[2.5]oct-4-
A
AHCTREUNG
ene-5-carboxylate (14; yield: 38 mg, 16%). Alternatively,
after 1j (940 mg, 4 mmol) had been subjected to the GP 4B,
13 (yield: 605 mg, 64%) and 14 (yield: 39 mg, 4%) were iso-
lated.
Ethyl cis-4,4-Ethano-2H-dihydrofuro[2,3-b]pyran-6-yl-
carboxylate(16)
G
˜
Compound 13: Colorless oil. IR (film): n=3075, 2989,
2911, 2883, 2862, 2827, 1746, 1725, 1464, 1445, 1427, 1384,
1369, 1298, 1268, 1230, 1121, 1074, 1040, 1022, 979, 948, 932,
According to GP 4B, 6 (235 mg, 1 mmol) reacted with 2,3-
dihydrofuran (2 mL) to afford, after column chromatogra-
phy on silica gel (50 mL), eluting with hexane/ethyl acetate,
5:1, pure 16 as a colorless oil; yield: 146 mg (65%). IR
905, 858, 832, 787, 766, 733 cmÀ1
;
1H NMR (300 MHz,
CDCl3): d=0.34–0.41 (m, 2H), 0.43–0.50 (m, 1H), 0.63–0.70
(m, 1H), 1.22–1.30 (m, 1H, 8-H), 1.36 (t, J=7.1 Hz, 3H),
1.54–1.56 (m, 3H), 1.65–1.67 (m, 3H), 2.25–2.35 (m, 3H),
2.62 (ddd, J=5.0, 3.7, 0.9 Hz, 1H), 4.23–4.39 (m, 2H, CH2);
13C NMR (75.5 MHz, CDCl3, APT): d=10.6 (CH2), 13.3
(CH2), 14.0 (CH3), 16.9 (C), 18.8 (CH3), 18.9 (CH3), 30.9
(CH2), 39.3, (CH2), 49.0 (CH), 62.1 (CH2), 123.4 (C), 125.2
(C), 164.1 (C), 196.9 (C); MS (70 eV, EI): m/z (%)=236 (3)
[M+], 208 (2), 189 (2), 163 (17), 147 (6), 145 (24), 135 (66),
133 (13), 120 (27), 117 (7), 107 (100), 105 (28), 93 (39), 91
(40), 89 (6), 79 (19), 77 (15), 69 (4), 67 (5), 65 (7), 55 (13),
53 (8), 43 (8), 41 (20); anal. calcd. for C14H20O3 (236.31): C
71.16, H 8.53; found: C 70.89, H 8.33.
˜
(film): n=3080, 2980, 2955, 2939, 2901, 1726, 1642, 1456,
1429, 1395, 1373, 1340, 1303, 1255, 1217, 1173, 1128, 1084,
1052, 1028, 1012, 970, 929, 908, 886, 864, 842, 763, 731 cmÀ1
;
1H NMR (300 MHz, CDCl3): d=0.72–1.00 (m, 4H, 2 CH2),
1.31 (t, J=7.1 Hz, 3H), 1.79–2.04 (m, 3H), 3.83–3.99 (m,
1H), 4.17–4.33 (m, 3H), 5.44 (d, J=3.2 Hz, 1H), 5.54 (d, J=
1.0 Hz, 1H); 13C NMR (75.5 MHz, CDCl3, APT): d=13.1
(CH2), 14.4 (CH3), 17.0 (C), 18.4 (CH2), 27.4 (CH2), 47.0
(CH), 61.3 (CH2), 68.6 (CH2), 100.2 (CH), 117.4 (CH), 141.0
(C), 162.6 (C); MS (70 eV, EI): m/z (%)=224 (10) [M+],
195 (18), 151 (72), 122 (9), 107 (6), 105 (27), 95 (10), 93 (8),
81 (10), 79 (13), 77 (9), 71 (100), 67 (9), 55 (8), 53 (16), 43
Adv. Synth. Catal. 2007, 349, 1247 – 1255
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1253

Viktor Bagutski and Armin de Meijere
FULL PAPERS
(22), 41 (27); anal. calcd. for C12H16O4 (224.25): C 64.27, H
7.19; found: C 64.93, H 6.96.
Acknowledgements
This work was supported by the State of Niedersachsen and
KAdemCustomChem GmbH, Gçttingen. The authors are
grateful to R. Machinek, G. Udvarnoki and Dr. H. Frauen-
dorf for analytical support.
Ethyl cis-7,7-Ethano-7,7a-dihydro-3aH-furo[3,2-b]-
pyran-5-carboxylate(17)
A
Thus, according to GP 4A, 1j (154 mg, 1 mmol) reacted with
furan (2 mL) to afford after flash chromatography on silica
gel (50 mL), eluting with hexane/ethyl acetate, 5:1 to 3:1,
sufficiently pure 17 as a colorless oil; yield: 146 mg (65%).
Compound 17 turned out to be sensitive to silica gel and
thus could not be purified completely by column chromatog-
References
[1] Part 139 in the series “Cyclopropyl Building Block for
Organic Synthesis”, for Part 138, see: L. Zhao, B.
Yücel, R. P. Scheurich, A. de Meijere, Chem. Asian J.
2007, 273; Part 137: M. Ahmar, M. Knoke, A. de Mei-
jere, B. Cazes, Synthesis 2007, 442.
[2] For reviews see: a) A. de Meijere, S. I. Kozhushkov,
A. F. Khlebnikov, in: Topics in Current Chemistry, Vol.
207, (Ed.: A. de Meijere), Springer, Berlin, 2000, p 89;
b) A. de Meijere, S. I. Kozhushkov, T. Späth, M. von
Seebach, S. Lçhr, H. Nüske, T. Pohlmann, M. Es-
Sayed, S. Bräse, Pure Appl. Chem. 2000, 72, 1745; c) A.
de Meijere, S. I. Kozhushkov, Eur. J. Org. Chem. 2000,
3809.
[3] For reviews, see: a) A. Brandi, S. Cicchi, F. M. Cordero,
A. Goti, Chem. Rev. 2003, 103, 1213; b) A. de Meijere,
S. I. Kozhushkov, L. P. Hadjiarapoglou, in: Topics in
Current Chemistry, Vol. 207, (Ed.: A. de Meijere),
Springer, Berlin, 2000, p 149; c) A. de Meijere, L. Wess-
johann, Synlett 1990, 20.
1
raphy, it was characterized by NMR spectra only. H NMR
(250 MHz, CDCl3): d=0.91–1.07 (m, 4H), 1.28 (t, J=
7.1 Hz, 3H), 3.89 (ddd, J=6.1, 1.5, 0.6, Hz, 1H), 4.22 (dq,
J=9.8, 7.1 Hz, 1H), 4.23 (dq, J=9.8, 7.1 Hz, 1H), 5.13 (ddd,
J=6.1, 2.7, 0.5 Hz, 1H), 5.41 (dd, J=2.7, 2.7 Hz, 1H), 5.64
(d, J=1.5 Hz, 1H), 6.62 (ddd, J=2.7, 0.6, 0.5 Hz, 1H);
13C NMR (62.5 MHz, CDCl3, DEPT): d=12.9 (CH2), 14.2
(CH3), 16.6 (C), 17.6 (CH2), 61.1 (CH2), 78.5 (CH), 85.8
(CH), 103.4 (CH), 116.2 (CH), 144.0 (C), 151.4 (CH), 162.3
(C).
Ethyl 3-(1-Furylcycloprop-1-yl)-2-oxopropionate(18)
and Ethyl (exo, cis)-7,7-Ethano-2-hydroxy-2,3,3a,7a-
tetrahydrofuro[3,2-b]pyran-5-carboxylate(19)
G
According to GP 4A, 1j (154 mg, 1 mmol) and furan (2 mL)
gave after work-up with 5% aqueous Na2CO3 and subse-
quent column chromatography of the crude residue on silica
gel (20 mL), eluting with hexane/ethyl acetate, 6:1 (Rf =0.3)
to 4:1, the furan derivative 18 as a colorless oil; yield:
107 mg (48%). Further elution with hexane/ethyl acetate/
MeOH, 20:5:1, afforded the pure heterocyclic hemiacetal 19
as exo-isomer (dr>90%, according to its 1H NMR spec-
trum); yield: 30 mg (12%).
[4] A. de Meijere, A. Leonov, T. Heiner, M. Noltemeyer,
M. T. Bes, Eur. J. Org. Chem. 2003, 472.
[5] I. Nakamura, T. Nemoto, Y. Yamamoto, A. de Meijere,
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Compound 18: IR (film): n=3119, 3090, 3004, 2986, 2939,
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1069, 1057, 1014, 932, 913, 857, 796, 734 cmÀ1 1H NMR
;
(250 MHz, CDCl3): d=0.85–0.90 (m, 2H), 1.09–1.14 (m,
2H), 1.34 (t, J=7.1 Hz, 3H), 3.13 (s, 2H), 4.28 (q, J=
7.1 Hz, 2H), 5.94 (dd, J=3.2, 0.8 Hz, 1H), 6.23 (dd, J=3.2,
1.8 Hz, 1H), 7.21 (dd, J=1.8, 0.8 Hz, 1H); 13C NMR
(62.5 MHz, CDCl3, DEPT): d=13.7 (2 CH2), 13.9 (CH3),
15.2 (C), 45.6 (CH2), 62.4 (CH2), 104.2 (CH), 110.3 (CH),
140.7 (CH), 156.9 (C), 161.4 (C), 192.8 (C); MS (70 eV, EI):
m/z (%)=222 (25) [M+], 204 (20), 193 (5), 149 (70), 131
(22), 121 (82), 107 (30), 93 (21), 91 (23), 81 (100), 77 (31), 65
(23), 53 (10), 51 (7).
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1
Compound 19: H NMR (300 MHz, CDCl3): d=0.82–0.99
(m, 3H), 1.26–1.32 (m, 1H), 1.28 (t, J=7.1 Hz, 3H), 2.10
(ddd, J=14.6, 4.3, 4.3 Hz, 1H), 2.73 (dd, J=14.6, 5.8 Hz,
1H), 3.39 (d, J=3.2 Hz, 1H), 3.70 (dd, J=1.8, 1.5 Hz, 1H),
4.17–4.27 (m, 2H, CH2), 4.49 (dd, J=4.3, 1.8 Hz, 1H), 5.59
(d, J=1.5 Hz, 1H), 5.73 (ddd, J=5.8, 4.3, 3.2 Hz, 1H);
13C NMR (75.5 MHz, CDCl3, APT): d=12.7 (CH2), 14.2
(CH3), 17.0 (C), 17.2 (CH2), 42.3 (CH2), 61.0 (CH2), 76.9
(CH), 80.8 (CH), 97.8 (CH), 116.9 (CH), 142.5 (C), 162.3
(C); MS (70 eV, EI): m/z (%)=240 (46) [M+], 211 (8), 193
(30), 179 (96), 165 (19), 149 (26), 137 (33), 121 (100), 109
(40), 95 (32), 93 (60), 81 (96), 77 (42), 65 (24), 57 (64), 53
(62), 41 (26).
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2004, 346, 760.
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ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2007, 349, 1247 – 1255

Cyclopropylidenepyruvate as a Multifunctional Cyclopropyl Building Block
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asc.wiley-vch.de
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