A general stereoselective method for the synthesis of cyclopropanecarboxylates. A new version of the homologous Horner-Wadsworth- Emmons reaction

Article abstract of DOI:10.1039/b712145h

The synthesis of α-, β- and γ-substituted α-phosphono-γ-lactones was accomplished using different ring closure and ring homologation strategies. It was found that the lactones could be selectively transformed into the corresponding ethyl cyclopropanecarboxylates by treatment with sodium ethoxide in boiling THF. The reported reaction provides an attractive alternative to the classical homologous Horner-Wadsworth-Emmons approach to the construction of cyclopropanes with electron-withdrawing functionalities. This journal is The Royal Society of Chemistry.

Full text of DOI:10.1039/b712145h

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A general stereoselective method for the synthesis of
cyclopropanecarboxylates. A new version of the homologous
Horner–Wadsworth–Emmons reaction†
Henryk Krawczyk,*a Katarzyna Wasek,a Jacek Kedzia,a Jakub Wojciechowskib and Wojciech M. Wolfb
ꢀ
ꢀ
Received 8th August 2007, Accepted 25th October 2007
First published as an Advance Article on the web 28th November 2007
DOI: 10.1039/b712145h
The synthesis of a-, b- and c-substituted a-phosphono-c-lactones was accomplished using different ring
closure and ring homologation strategies. It was found that the lactones could be selectively
transformed into the corresponding ethyl cyclopropanecarboxylates by treatment with sodium ethoxide
in boiling THF. The reported reaction provides an attractive alternative to the classical homologous
Horner–Wadsworth–Emmons approach to the construction of cyclopropanes with
electron-withdrawing functionalities.
evident synthetic advantage, this cyclopropanation reaction has
not found wider application.3
Introduction
The stereocontrolled synthesis of cyclopropanecarboxylates re-
mains an important and active subject in organic chemistry due
to the wide occurrence of these structural motifs in a number
of biologically active natural products and several unnatural
analogues.1
The homologous Horner–Wadsworth–Emmons (HWE)-type
reaction of a-phosphonoalkanoate anions with epoxides provides
an attractive route to differently substituted cyclopropanecarboxy-
lates 4.2 The commonly accepted mechanism of this reaction,
in particular that involving phosphonoacetate anion 1, has been
described as follows (Scheme 1).2d,e
The crucial role of c-oxyalkylphosphonates in the formation of
cyclopropanecarboxylates and their potentially easy accessibility
by independent preparative methods prompted us to attempt
modification of the standard homologous Horner–Wadsworth–
Emmons reaction procedure. We believed that we would be able
to generate c-oxyalkylphosphonate anions 6 with different sub-
stitution patterns and to transform them into the corresponding
cyclopropanecarboxylates 7 using a novel, simple and effective
reaction sequence. We showed that an alternative and convenient
source of the anions 6 could be the base-catalyzed ethanolysis
of the appropriate a-phosphono-c-butyrolactones 5.4 Futher con-
version of these anions into the target cyclopropanecarboxylates
7 was realized using consecutive reaction steps and preparative
procedures similar to those involved in the classical cyclopropa-
nation. Additionally, we observed that this modified version
of cyclopropanation was highly stereoselective. The substituted
a-phosphono-c-lactones of various regio- and stereochemistry
were cleanly transformed into individual diastereoisomeric cyclo-
propanes (Scheme 2).
Scheme 1
The cyclopropanation is initiated by epoxide ring opening
(promoted by the anion 1), leading to the c-oxyalkylphosphonates
2, which are then converted into the phosphates 3 by 1,4-migration
of a phosphoryl functionality from carbon to oxygen. Subsequent
c-elimination of the elements of phosphoric acid from the latter
results in a cyclopropane ring closure. Surprisingly, despite the
aInstitute of Organic Chemistry, Technical University (Politechnika),
˙
Zeromskiego 116, Ło´dz´, Poland. E-mail: henkrawc@p.lodz.pl; Fax: +48
Scheme 2
42 636 55 30; Tel: +48 42 631 31 04
bInstitute of General and Ecological Chemistry, Technical University
In our previous work on a novel approach to cyclopropanecar-
boxylates, we generally used readily obtainable and simple a-
phosphono-c-lactones 5 as model substrates. We hoped that broad
˙
(Politechnika), Zeromskiego 116, Ło´dz´, Poland
† Electronic supplementary information (ESI) available: Additional exper-
imental information; crystal structure data. See DOI: 10.1039/b712145h
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Table 1 Preparation of b-substituted-a-phosphono-c-lactones 10a–c
access to more functionalized starting materials would allow us to
recognize better the scope of the synthesis.
This paper reports on effective, stereoselective, and in a
large part original preparation of a series of mono-, di- and
trisubstituted a-phosphono-c-lactones bearing alkyl, alkenyl and
aryl substituents. We present the most favorable conditions
and stereochemistry of the homologous Horner–Wadsworth–
Emmons-like cyclopropanation reaction performed with all these
lactones. An important correction concerning the relative con-
figuration assigned to the previously reported a,b-disubstituted
cyclopropanecarboxylates 7g and 7h is also included. Finally,
we describe here successful attempts for the preparation of a-
phosphono-c-oxyalkanoate anions containing selected c-electron-
withdrawing groups and their employment as excellent substrates
for the synthesis of cyclopropanecarboxylates functionalized with
these groups on the b-carbon atom.
Entry
R
Rꢀ
Product
Yield (%)
1
2
3
H (8a)
H (8a)
Me (8b)
n-Bu (9a)
Ph (9b)
Ph (9b)
10a
10b
10c
64
58
82
Reagents and conditions: a) RꢀMgBr (3 equiv.), CuI (cat.), THF, −78 ◦C,
2.5 h; b) RꢀMgBr (3 equiv.), CuI (cat.), Et2O, 0 ◦C, 2.5 h.
not be interpreted unequivocally. Therefore, taking into account
the method of preparation and the structural similarity of the
lactones of 10c and 10a,b, we by analogy also assigned trans-
stereochemistry to the lactones 10a and 10b.
Results and discussion
Conjugate addition of organometallic reagents to various a,b-
unsaturated-a-phosphono-c-lactones represents a mild, effective
and fully trans-diastereoselective approach to the corresponding
b-substituted-a-phosphono-c-lactones.5 We have already used the
conjugate addition method to obtain the lactones 5e and 5f with
b-located alkyl and alkenyl groups, respectively.4 Now we want to
extend this list by adding the lactones 10a–c.
A separate strategy has been employed to carry out the synthesis
of model a-alkyl, a-aryl-monosubstituted and a,c-disubstituted-c-
lactones. We expected that particularly attractive precursors of
these lactones would have the same carbon framework as a-
phosphono-c-hydroxyalkanoates, which could be obtained by a
few consecutive, commonly known transformations of the appro-
priate c-oxoalkylphosphonates or a-phosphono-c-alkenoates.
Thus, the usual protection of carbonyl functionality in the
selected c-oxoalkylphosphonates 116 and 157 with triethyl or-
thoformate or ethylene glycol gave the ketals 12 and 16. The
ketals 12 and 16 as well as 198 were then ethoxycarbonylated
using Savigniac’s well-known procedure.9 Their metallation with
LDA followed by ethoxycarbonylation of the resultant lithium
derivatives with diethyl carbonate provided the appropriate a-
phosphono-c,c-diethoxyalkanoates 13 and 20 and a-phosphono-
c-dioxolanylalkanoate 17. Acid-catalyzed hydrolytic deprotection
of the ethoxycarbonylated ketals 13, 17 and 20 afforded a-
phosphono-c-oxoalkanoates 14,10 1811 and 21,12 crucial interme-
diates in further projected transformations (Scheme 3).
While the lactone 10c was smoothly prepared by standard
reaction of a simple a,b-unsatured lactone 8b5c,d with phenylmag-
nesium bromide in the presence of CuI in diethyl ether at 0 ◦C,
the preparation of the lactones 10a and 10b required a different
protocol. Synthesis of the lactones 10a and 10b could be achieved
in a satisfactory manner when the starting a,b-unsatured lactone
8a5a was subjected to the reaction with a large excess (3 equiv.) of
the corresponding Grignard reagents 9a and 9b, respectively, in
the presence of CuI in THF at −78 ◦C (Table 1).
The trans stereochemistry of the lactone 10c was assigned on
1
the basis of H and 13C NMR data. The observed values of the
coupling constants 3JH3,H4 12.2 Hz, 3JP,H4 15.7 Hz and 3JP,C5 13.6 Hz
clearly proved the trans arrangement of the phosphoryl and phenyl
groups.5d Unfortunately, the spectra of lactones 10a and 10b could
Similarly, functionalized intermediates 24a and 24b with a-
alkyl and a-aryl groups were synthesized in a two-step sequence
Scheme 3 Reagents and conditions: a) (EtO)3CH, Amberlyst 15, 0 ◦C, 10 h; b) HOCH2CH2OH, p-TSA (cat.), toluene, reflux, 24 h; c) LDA, THF, −78 ◦C,
=
d) (EtO)2C O, r.t., 20 h; e) 3 N HCl/THF, r.t., 24 h.
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◦
Scheme 4 Reagents and conditions: a) NaH, THF, 0 C, 0,5 h; b) CH2 CHCH2Br, r.t., 20 h; c) EtOH, O3, −78 ◦C; d) Me2S, r.t., 20 h.
=
involving alkylation of generally accessible a-phosphonoal-
kanoates 22a and 22b with allyl bromide, and consecutive standard
ozonolysis of the resulting allylation products 23a and 23b
(Scheme 4).
proven useful as a concise entry to new a-alkyl-c-aryl and a,c-
dialkyl-a-phosphono-c-lactones 26i, 26j, 26k and 26l, respectively.
All alkylation reactions proceeded with quite high stereoselectivity.
Unfortunately, attempts to separate particular stereoisomers were
unsuccessful (Table 3).
All the lactones prepared were subjected to the modified homol-
ogous HWE reaction under the previously optimized conditions.
Treating these compounds with sodium ethoxide in THF–ethanol
solution (100 : 2) at reflux for a few hours led to the expected
cyclopropanecarboxylates in high or satisfactory yield (Tables 4
and 5).
1H and 13C NMR analysis revealed that the 2-substituted
cyclopropanation products 27a,13 27b,13 and 27c14 obtained from
a-phosphono-c-lactones 10a, 10b as well as 26b, and 27c, respec-
tively, had the trans-configuration, while the products 27a13 and
27d15 derived from the lactones 26c and 26d, respectively, consisted
of trans and cis stereoisomers, each in a ratio 93 : 7. Using
NMR spectroscopy, we established also that 1,2-disubstituted
cyclopropanecarboxylates 27e–l were single diastereoisomers.
However, the assignment of their configuration required a different
approach. X-Ray crystallographic analysis carried out on 1-
benzyl-2-phenylcyclopropanecarboxylic acid (which was prepared
With the a-phosphono-c-oxoalkanoates 14, 18, 21 and 24a,b in
hand, we turned our attention to their effective conversion into
various a-phosphono-c-hydroxyalkanoates as well as a cyclization
reaction of the latter producing designed, specific a-phosphono-
c-lactones. Thus, reduction of c-oxoalkanoates 14 and 18
with KBH4 smoothly afforded a-phosphono-c-hydroxyalkanoates
25a,b, while addition of n-BuMgBr and BnMgBr to the c-
oxoalkanoates 21, 24a and 24b gave the c-hydroxyalkanoates
27. In both cases, the c-hydroxyalkanoates formed underwent
spontaneous cyclization under the reaction conditions, producing
the target c-alkyl- (26a, 26c, 26d), c-aryl- (26b), a,c-dialkyl- (26e,
26f) and a-aryl-c-alkyl- (26g, 26h) substituted lactones as mixtures
of inseparable diastereoisomers (Scheme 5 and Table 2).
Moreover, we developed a convenient homologation of some
previously obtained a-unsubstituted a-phosphono-c-lactones
based on their alkylation reaction. Sequential treatment of a-
phosphono-c-lactones 26b, 26c and 26d with LDA, and then with
3-methyl-2-butenyl bromide, allyl bromide or benzyl bromide, has
Scheme 5 Reagents and conditions: a) KBH4, MeOH, 0 ◦C, 1 h; b) 3 N HCl (aq.), r.t.
Table 2 Preparation of a,c-disubstituted-a-phosphono-c-lactones 26c–h
Entry
R
Rꢀ
Yield (%)
Diastereoisomer ratio
Product
1
2
3
4
5
6
H (21)
n-Bu
Bn
n-Bu
Bn
n-Bu
Bn
70
75
68
71
79
75
56 : 44
67 : 33
80 : 20
80 : 20
90 : 10
92 : 8
26c
26d
26e
26f
26g
26h
H (21)
Me (24a)
Me (24a)
Ph (24b)
Ph (24b)
Reagents and conditions: a) RꢀMgBr, THF, 0 ◦C, 24 h; b) 1 N HCl (aq.).
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Table 3 Preparation of a,c-disubstituted-a-phosphono-c-lactones 26i–l
Entry
R
Rꢀ
Yield (%)
Diastereoisomer ratio
Product
1
2
3
4
Ph (26b)
Ph (26b)
n-Bu (26c)
Bn (26d)
Bn
75
89
78
79
93 : 7
26i
26j
26k
26l
=
(CH3)2C CHCH2
Bn
CH2 CHCH2
70 : 30
84 : 16
84 : 16
=
Reagents and conditions: a) LDA, THF, −78 ◦C; b) RꢀMgBr, THF, −78 ◦C then r.t.
Table 4 Preparation of 2-substituted cyclopropanecarboxylates 27a–d
Entry
1
Lactone
Reaction time/h
8
Product
Yield (%)
82
70
74
65
86
65
2
3
4
5
6
7
8
8
8
8
by base-catalyzed hydrolysis of the cyclopropanecarboxylate 27i)16
showed that the ring substituents of this compound remain in a cis
relationship (Fig. 1). Details of the structure determination were
published elsewhere.17 Such a geometry unequivocally proves the
trans-configuration of the parent cyclopropanecarboxylate 27i.
This unexpected position of the “largest” groups in the rep-
resentative 1,2-disubstituted cyclopropanation product disposed
us to examine once again the structure of the previously de-
scribed 1-benzyl-2-methylcyclopropanecarboxylate 7h. The car-
boxylate 7h was converted in a standard manner into the
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Table 5 Preparation of 1,2-disubstituted cyclopropanecarboxylates 27e–l
Entry
1
Lactone
Reaction time/h
8
Product
Yield (%)
55
2
3
4
5
6
7
8
8
8
8
8
6
8
8
53
58
62
80
74
62
61
dicyclohexylammonium salt of the parent acid,18 which was
analyzed by X-ray diffraction. Results of this analysis allowed
us to assign trans-stereochemistry to the salt, and indirectly to the
carboxylate 7h (Fig. 2). The cyclopropane ring shows high level of
the endocyclic C–C bond length asymmetry. The shortest bond is
located opposite to the axial carboxylate group. This shortening
The crystal is constituted from centrosymmetric dimers in which
all carboxylate groups are involved in the hydrogen bonding with
the neighbouring dicyclohexylammonium cations.
The observed trans selectivity of the representative homo-
logous HWE-type reactions providing 1,2-disubstituted cyclo-
propanecarboxylates entitles us to correct the previously reported
cis-configuration of the carboxylates 7g and 7h.4 On the other
hand, it speaks simultaneously for trans-configuration for the
of the distal bond presumably results from interactions of the
19
=
endocyclic r(C–C) and exocyclic antibonding p*(C O) orbitals.
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Fig. 1 The molecular structure of the cyclopropanecarboxylic acid
derived from ester 27i as published in ref. 17. Displacement ellipsoids are
drawn at the 50% probability level. H atoms are represented by circles of
an arbitrary radius. The endocyclic cyclopropane bond lengths are: C1–C2
˚
1.480(2), C2–C3 1.540(2), C1–C3 1.510(2) A.
Scheme 6
particularly important objective of these attempts was the devel-
opment of a simple approach to appropriately c-functionalized-a-
phosphono-c-hydroxyalkanoate intermediates for the cyclopropa-
nation reaction. We reasoned that such a type of compound
should be accessible by nucleophilic addition of selected ambident
anions or enolates to the already mentioned a-phosphono-c-
oxoalkanoates. We decided to use cyanide, diethyl phosphite and
triethyl phosphonoacetate anions as model nucleophiles.
Surprisingly, the reaction of a-phosphono-c-oxobutanoate
21 with acetone cyanohydrin serving as a cyanide anion
equivalent20 was found to proceed in a rather unexpected way
(Scheme 7). The only isolated product of this reaction was
neither a-phosphono-c-cyano-c-hydroxybutanoate 29 nor the
corresponding a-phosphono-c-cyanolactone but the c-cyano-c-
phosphoryloxybutanoate 30 resulting from the previously men-
tioned 1,4-transfer of phosphoryl group from the a-carbon to
the c-oxygen atom within the first of these compounds. Similarly,
hydrophosphonylation of the same c-oxobutanoate 21 with diethyl
phosphite in the presence of catalytic sodium ethoxide21 afforded c-
phosphono-c-phosphoryloxybutanoate 32 exclusively (Scheme 8).
The butanoates 30 and 32, when subjected to reaction with NaH
in THF solution, readily underwent completely regioselective
cyclization, providing trans-cyclopropanecarboxylates 3122 and
33,23 respectively.
Fig.
2
The molecular structure of 1-benzyl-2-methylcyclopropane-
carboxylate anion derived from the ester 7h.† In the crystal the anion
is hydrogen-bonded to the dicyclohexylammonium cation. The latter has
been removed from the plot for clarity. Displacement ellipsoids are drawn
at the 50% probability level. H atoms are represented by circles of an
arbitrary radius. The endocyclic cyclopropane bond lengths are: C1–C2
˚
1.475(2), C2–C3 1.523(2), C1–C3 1.514(2) A.
remaining newly obtained cyclopropanecarboxylates 27e–h and
27j–l.
Such a stereochemical course of the cyclopropanation reaction
can be rationalized by assuming that metal ion of the enolate
intermediate involved in a ring closure is chelated by the oxygen
=
atom of the P O group. The resulting nine-membered complex
28 with an E- (rather than Z-) configured enolate functionality
should be the predominant structure. The phosphate group in the
chelate 28 undergoes intramolecular substitution by its enolate
carbon atom according to steric requirements of a classical SN2
mechanism. Of the two competitive pathways which are possible
for this reaction, that with the transition state A minimizing the
transannular steric interaction of the enolate substituent R2 should
be kinetically favored. Therefore, the chelates with R1 = H and
R2 = alkyl and/or aryl would be preferentially converted into trans
2-substituted cyclopropanecarboxylates. When both R1 and R2
were alkyl and/or aryl, the corresponding trans-1,2-disubstituted
cyclopropanecarboxylates with syn-oriented substituents would
be the dominant cyclization products (Scheme 6).
Intending to demonstrate the generality of our methodology,
we attempted to employ it also for the preparation of cyclo-
propanecarboxylates with various functional groups on C-2. A
Scheme 7 Reagents and conditions: a) (CH3)2C(OH)CN, Ti(OiPr)4, r.t.,
20 h; b) NaH, THF, reflux, 5 h.
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boxylates are formed as trans isomers exclusively. This method
also allowed the synthesis of cyclopropanecarboxylates bearing
C-2 electron-withdrawing substituents. The described approach to
cyclopropanecarboxylates is equivalent to that of a conventional
Horner–Wadsworth–Emmons-type cyclopropanation.
Experimental
General
NMR spectra were recorded on a Bruker DPX 250 instrument
Scheme 8 Reagents and conditions: a) (EtO)2P(O)H, EtOH, EtONa (cat.),
rt, 0.5 h; b) NaH, THF, reflux, 5 h.
1
at 250.13 MHz for H and 62.9 MHz for 13C and 101.3 MHz
for 31P NMR, respectively, using tetramethylsilane as internal
standard and 85% H3PO4 as external standard. The multiplicities
of carbons were determined by DEPT experiments. IR spectra
were measured on a Specord M80 (Zeiss) instrument. Elemental
analyses were performed on a Perkin-Elmer PE 2400 analyzer.
Melting points were determined in open capillaries and are
uncorrected. Flash chromatography was carried out using Fluka
silica gel 60 (230–400 mesh). Thin layer chromatography was
carried out on commercially available pre-coated plates (Fluka
Silica gel on TLC plates).
Considering the well-known chemical behavior of b-
and c-hydroxyalkylphosphonates bearing a-electron-withdrawing
groups, one could have expected that the adduct 34 of triethyl
phosphonoacetate anion and a-phosphono-c-oxobutanoate 21
would be able to split off the elements of phosphoric acid by
means of both the HWE reaction and its homologous version
to give olefin 35 and cyclopropanecarboxylate 36, respectively.
To the best of our knowledge no reports have addressed direct
competition between those two transformations. We established
that the olefination and cyclopropanation reactions occurring with
the adduct 34 were kinetically parallel and that they provided the
expected products 35 and 36 in a 4 : 1 ratio. Both 35 and 36 were
separated and their trans-stereochemistry was corroborated using
NMR spectroscopy (Scheme 9).
General procedure for the preparation of cyclopropanecarboxy-
lates 27a–l. To a suspension of sodium hydride (0.14 g, 6.0 mmol)
and a-diethoxyphosphoryl-c-lactone 10a–c or 26b–l (6.0 mmol)
in tetrahydrofuran (15 ml) was added dropwise under argon
atmosphere at room temperature a solution of ethanol (0.40 ml,
6.6 mmol) in tetrahydrofuran (5 ml). The reaction mixture was
stirred for 0.5 h and then was heated at reflux for the time
given in Table 4 and Table 5. After cooling to room temperature,
saturated NaCl solution (5 ml) was added and tetrahydrofuran
was evaporated under reduced pressure. The residue was extracted
with methylene chloride (3 × 15 ml) and dried (Na2SO4). After
evaporation of the solvent under reduced pressure, the crude
products were purified by column chromatography.
2-Butylcyclopropanecarboxylic acid ethyl ester (27a)13. Purifi-
cation (CHCl3, Rf = 0.63) gave the cyclopropanecarboxylate 27a
3
as a colourless oil (0.84 g, 82%); dH (CDCl3) 0.68 (ddd, JHH
9.7 Hz, 3JHH = 5.7 Hz, 2JHH = 4.0 Hz, 1H, CHH); 0.89 (t, 3JHH
=
=
6.7 Hz, 3H, CH3); 1.11–1.17 (m, 1H, CHH); 1.26 (t, 3JHH = 7.2 Hz,
3H, CH3CH2O); 1.30–1.38 (m, 8H, CH, CH, 3 × CH2); 4.11 (q,
3JHH = 7.2 Hz, 2H, CH2O).
2-Phenylcyclopropanecarboxylic acid ethyl ester (27b)13. Pu-
rification (CHCl3–hexane 80 : 20, Rf = 0.50) gave the cyclo-
propanecarboxylate 27b as a colourless oil (0.80 g, 70%); dH
3
(CDCl3) 1.26 (t, JHH = 7.0 Hz, 3H, CH3CH2O); 1.28–1.32 (m,
1H, CH); 1.58 (ddd, 3JHH = 8.5 Hz, 3JHH = 6.5 Hz, 2JHH = 4.2 Hz,
Scheme 9 Reagents and conditions: a) NaH, THF, reflux, 5 h.
3
3
2
1H, CHH); 1.88 (ddd, JHH = 8.5 Hz, JHH = 5.2 Hz, JHH
=
3
3
4.2 Hz, 1H, CHH); 2.52 (ddd, JHH = 9.0 Hz, JHH = 6.5 Hz,
3JHH = 5.2 Hz, 1H, CH); 4.17 (q, JHH = 7.0 Hz, 2H, CH2O);
3
Conclusions
7.08–7.28 (m, 5H, CHAr).
In summary, we have developed a concise and efficient synthesis
of a variety of a-phosphono-c-lactones. We have shown that
such a-phosphono-c-lactones can be efficiently transformed into
the corresponding ethyl cyclopropanecarboxylates. It has been
proven that 2-substituted and 1,2-disubstituted cyclopropanecar-
2,2-Dimethyl-3-phenylcyclopropanecarboxylic acid ethyl ester
(27c)14. Purification (CHCl3–hexane 50 : 50, Rf = 0.36) gave the
cyclopropanecarboxylate 27c as a colourless oil (1.00 g, 85%); dH
(CDCl3) 1.05 (s, 3H, CH3); 1.23 (t, 3JHH = 7.0 Hz, 3H, CH3CH2O);
314 | Org. Biomol. Chem., 2008, 6, 308–318
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3
1.56 (s, 3H, CH3); 1.85 (d, JHH = 6.5 Hz, 1H, CH); 2.47 (d,
(dd, 3JHH = 7.0 Hz, 2JHH = 3.7 Hz, 1H, CHH); 1.79 (dd, 3JHH
=
=
3JHH = 6.5 Hz, 1H, CH); 4.00 (q, JHH = 7.0 Hz, 2H, CH2O);
9.0 Hz, 2JHH = 3.7 Hz, 1H, CHH); 2.05 (dd, 2JHH = 8.5 Hz, 3JHH
3
3
3
7.20–7.39 (m, 5H, CHAr).
5.0 Hz, 1H, CHH); 2.18 (dddd, JHH = 9.0 Hz, JHH = 8.5 Hz,
3
3JHH = 7.0 Hz, 3JHH = 5.0 Hz, 1H, CH); 3.12 (dd, 2JHH = JHH
=
2-Benzylcyclopropanecarboxylic acid ethyl ester (27d)15. Pu-
rification (CHCl3–hexane 50 : 50, Rf = 0.45) gave the cyclo-
propanecarboxylate 27d as a colourless oil (0.53 g, 65%); dH
(CDCl3) 0.86 (ddd, 3JHH = 9.0 Hz, 3JHH = 6.0 Hz, 2JHH = 4.0 Hz,
3
8.5 Hz, 1H, CHH); 4.14 (q, JHH = 7.0 Hz, 2H, CH2O); 6.94–
7.33 (m, 10H, CHAr); dC (CDCl3) 13.06 (CH3CH2O); 18.88 (CH2);
29.11 (CH); 31.04 (CH2); 33.40 (CH); 59.19 (CH2O); 125.25 (2 ×
CHAr); 125.96 (2 × CHAr); 126.00 (CHAr); 126.78 (CHAr); 129.64
(2 × CHAr); 132.60 (2 × CHAr); 138.05 (CAr); 141.04 (CAr); 171.20
3
1H, CHH); 1.24 (t, JHH = 7.0 Hz, 3H, CH3CH2O); 1.32 (ddd,
3JHH = 9.5 Hz, JHH = 6.2 Hz, 1H, JHH = 4.0 Hz, CHH); 1.50
3
2
=
(C O). C19H20O2: requires C 81.40, H 7.19; found C 81.34, H 7.16.
3
3
3
(ddd, JHH = 9.0 Hz, JHH = 6.5 Hz, JHH = 6.2 Hz, 1H, CH);
1.67–1.78 (m, 1H, CH); 2.54 (dd, 2JHH = 14.0 Hz, 3JHH = 7.0 Hz,
1H, CHH); 2.76 (dd, 2JHH = 14.0 Hz, 3JHH = 6.5 Hz, 1H, CHH);
4.13 (q, 3JHH = 7.0 Hz, 2H, CH2O); 7.20–7.31 (m, 5H, CHAr).
1-Benzyl-2-phenylcyclopropanecarboxylic acid ethyl ester (27i).
Purification (CHCl3–hexane 50 : 50, Rf = 0.26) gave the cyclo-
propanecarboxylate 27i as a colourless oil (1.22 g, 74%); mmax 1764;
3
dH (CDCl3) 1.18 (t, JHH = 7.0 Hz, 3H, CH3CH2O); 1.41 (dd,
2-Butyl-1-methylcyclopropanecarboxylic acid ethyl ester (27e).
Purification (CHCl3–hexane 50 : 50, Rf = 0.27) gave the cyclo-
propanecarboxylate 27e as a colourless oil (0.40 g, 55%); mmax
1764; dH (CDCl3) 0.59–0.70 (m, 1H, CHH); 0.82 (t, 3JHH = 6.7 Hz,
2
3
3JHH = 7.0 Hz, JHH = 5.0 Hz, 1H, CHH); 1.88 (dd, JHH
=
9.2 Hz, 2JHH = 5.0 Hz, 1H, CHHꢀ); 2.00 (d, 2JHH = 15.5 Hz, 1H,
CHH); 2.84 (dd, 3JHH = 9.2 Hz, 3JHH = 7.0 Hz, 1H, CH); 3.20 (d,
2JHH = 15.5 Hz, 1H, CHH); 4.12 (q, 3JHH = 7.0 Hz, 1H, CHHO);
4.13 (q, 3JHH = 7.0 Hz, 1H, CHHO); 7.12–7.30 (m, 10H, CHAr);
dC (CDCl3) 14.01 (CH3CH2O); 17.78 (CH2); 30.77 (CH2); 31.00
(C); 32.52 (CH); 60.72 (CH2O); 125.74 (2 × CHAr); 126.86 (2 ×
CHAr); 127.93 (CHAr); 128.24 (CHAr); 128.55 (2 × CHAr); 129.20
3
2
3H, CH3); 1.07 (dd, JHH = 6.2 Hz, JHH = 3.7 Hz, 1H, CHH);
3
1.18 (t, JHH = 7.0 Hz, 3H, CH3CH2O); 1.20–1.37 (m, 6H, 3 ×
CH2); 1.45 (s, 3H, CH3); 1.78 (ddt, 3JHH = 9.2 Hz, 3JHH = 6.7 Hz,
3JHH = 6.2 Hz, 1H, CH); 4.08 (q, JHH = 7.0 Hz, 2H, CH2O);
3
dC (CDCl3) 13.77 (CH3); 14.18 (CH3CH2O); 18.68 (CH3); 21.27
(CH2); 23.13 (CH2); 24.12 (CH2); 29.27 (CH); 31.18 (CH2); 33.74
=
(2 × CHAr); 136.58 (CAr); 140.26 (CAr); 174.40 (C O). C19H20O2:
requires C 81.40, H 7.19; found C 81.57, H 7.17.
=
(CH); 60.63 (CH2O); 174.66 (C O). C11H20O2: requires C 71.70,
H 10.94; found C 71.56, H 10.99.
1-(3-Methylbut-2-enyl)-2-phenylcyclopropanecarboxylic
acid
ethyl ester (27j). Purification (CHCl3–hexane 80:20, Rf = 0.66)
2-Benzyl-1-methylcyclopropanecarboxylic acid ethyl ester (27f).
Purification (CHCl3–hexane 50 : 50, Rf = 0.41) gave the cyclo-
propanecarboxylate 27f as a colourless oil (0.39 g, 53%); mmax
gave the cyclopropanecarboxylate 27j as a colourless oil (0.96 g,
62%); mmax 1764, 1664; dH (CDCl3) 1.22 (dd, 3JHH = 7.2 Hz, 2JHH
=
3
5.0 Hz, 1H, CHH); 1.27 (t, JHH = 7.0 Hz, 3H, CH3CH2O);
1.39 (s, 3H, CH3); 1.57 (dd, 2JHH = 15.2 Hz, 3JHH = 6.7 Hz, 1H,
CHH); 1.61 (s, 3H, CH3); 1.66 (dd, 3JHH = 9.0 Hz, 2JHH = 5.0 Hz,
1H, CHH); 2.26 (dd, 2JHH = 15.2 Hz, 3JHH = 6.7 Hz, 1H, CHH);
3
1748; dH (CDCl3) 1.18 (t, JHH = 7.0 Hz, 3H, CH3CH2O); 1.27
(dd, 3JHH = 6.5 Hz, 2JHH = 3.7 Hz, 1H, CHH); 1.46 (s, 3H, CH3);
1.69 (dd, 3JHH = 9.0 Hz, 2JHH = 3.7 Hz, CHH); 2.00 (dd, 2JHH
=
8.7 Hz, 3JHH = 5.0 Hz, 1H, CHH); 2.18–2.31 (m, 1H, CH); 3.12
2.81 (dd, 3JHH = 9.0 Hz, 3JHH = 7.2 Hz, 1H, CH); 4.17 (q, 3JHH
=
(dd, 2JHH = JHH = 8.7 Hz, 1H, CHH); 4.18 (q, 3JHH = 7.0 Hz, 2H,
3
3
7.0 Hz, 1H, CHHO); 4.18 (q, JHH = 7.0 Hz, 1H, CHHO); 5.59
(t, 3JHH = 6.7 Hz, 1H, CH); 7.19–7.32 (m, 5H, CHAr); dC (CDCl3)
13.22 (CH3CH2O); 16.64 (CH3); 24.72 (CH2); 26.04 (CH3); 29.45
(CH); 31.01 (C); 35,41 (CH2), 59.65 (CH2O); 120.90 (CH); 125.66
(2 × CHAr); 127.11 (CHAr); 128.29 (2 × CHAr); 131.15 (C); 135.90
CH2O); 7.10–7.24 (m, 5H, CHAr); dC (CDCl3) 13.06 (CH3CH2O);
17.73 (CH3); 18.88 (CH2); 29.11 (CH); 31.42 (CH2); 33.40 (CH);
60.33 (CH2O); 126.00 (2 × CHAr); 127.88 (CHAr); 127.65 (2 ×
=
CHAr); 138.48 (CAr); 171.47 (C O). C14H18O2: requires C 77.03,
H 8.31; found C 77.27, H 8.27.
=
(CAr); 173.88 (C O). C17H22O2: requires C 79.03, H 8.58; found
C 78.87, H 8.54.
2-Butyl-1-phenylcyclopropanecarboxylic acid ethyl ester (27g).
Purification (CHCl3–hexane 50 : 50, Rf = 0.32) gave the cyclo-
propanecarboxylate 27g as a colourless oil (0.53 g, 58%); mmax 1768;
dH (CDCl3) 0.48–0.55 (m, 1H, CHH); 0.81 (t, 3JHH = 7.0 Hz, 3H,
1-Benzyl-2-butylcyclopropanecarboxylic acid ethyl ester (27k).
Purification (CHCl3–hexane 50 : 50, Rf = 0.33) gave the cyclo-
propanecarboxylate 27k as a colourless oil (1.25 g, 80%); mmax
3
2
3
2
CH3); 1.08 (dd, JHH = 6.5 Hz, JHH = 4.0 Hz, 1H, CHH); 1.15
(t, 3JHH = 7.2 Hz, 3H, CH3CH2O); 1.18–1.25 (m, 2H, CH2); 1.27–
1.38 (m, 4H, 2 × CH2); 1.80 (ddt, 3JHH = 9.0 Hz, 3JHH = 6.5 Hz,
1740; dH (CDCl3) 0.58 (dd, JHH = 6.0 Hz, JHH = 3.7 Hz, 1H,
CHH); 0.91 (t, 3JHH = 6.7 Hz, 3H, CH3); 1.12 (t, 3JHH = 7.0 Hz,
3H, CH3CH2O); 1.22–1.59 (m, 8H, 3 × CH2, CHH, CH); 2.66 (d,
2JHH = 15.5 Hz, 1H, CHH); 3.23 (d, 2JHH = 15.5 Hz, 1H, CHH);
4.03 (q, 3JHH = 7.0 Hz, 1H, CHHO); 4.04 (q, 3JHH = 7.0 Hz, 1H,
CHHO); 7.15–7.23 (m, 5H, CHAr); dC (CDCl3) 13.87 (CH3), 14.01
(CH3CH2O); 21.08 (CH2); 22.45 (CH2); 27.93 (CH2); 28.03 (CH2);
29.04 (C); 31.68 (CH); 33.46 (CH2); 60.40 (CH2O); 124.52 (CHAr);
3JHH = 6.2 Hz, 1H, CH); 4.05 (q, JHH = 7.2 Hz, 1H, CHHO);
3
3
4.12 (q, JHH = 7.2 Hz, 1H, CHHO); 7.22–7.31 (m, 5H, CHAr);
dC (CDCl3) 13.99 (CH3); 14.15 (CH3CH2O); 21.27 (CH2); 22.39
(CH2); 28.49 (CH2); 29.96 (CH); 31.32 (CH2); 33.74 (CH); 60.83
(CH2O); 126.84 (CHAr); 127.79 (2 × CHAr); 131.32 (2 × CHAr);
=
136.52 (CAr); 174.66 (C O). C16H22O2: requires C 78.01, H 9.00;
=
128.02 (2 × CHAr); 128.53 (2 × CHAr); 140.72 (CAr); 175.31 (C O).
found C 78.12, H 8.97.
C17H24O2: requires C 78.42, H 9.29; found C 78.67, H 9.27.
2-Benzyl-1-phenylcyclopropanecarboxylic acid ethyl ester (27h).
Purification (CHCl3–hexane 50 : 50, Rf = 0.41) gave the cyclo-
propanecarboxylate 27h as a colourless oil (0.50 g, 62%); mmax
1740; dH (CDCl3) 1.20 (t, JHH = 7.0 Hz, 3H, CH3CH2O); 1.31
1-Allyl-2-benzylcyclopropanecarboxylic acid ethyl ester (27l).
Purification (CHCl3–hexane 50 : 50, Rf = 0.50) gave the cyclo-
propanecarboxylate 27l as a colourless oil (0.24 g, 61%); mmax
1720, 1640; dH (CDCl3) 0.84 (dd, JHH = 6.5 Hz, JHH = 4.0 Hz,
3
3
2
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3
3
3
1H, CHH); 1.20 (t, JHH = 7.0 Hz, 3H, CH3CH2O); 1.30 (dd,
16.08 (d, JPC = 5.6 Hz, CH3CH2OP); 25.95 (dd, JPC = 7.2 Hz,
3JHH = 9.0 Hz, 2JHH = 4.0 Hz, 1H, CHH); 1.52–1.60 (m, 1H, CH);
4JPC = 4.3 Hz, CH2); 29.38 (d, JPC = 41.7 Hz, CH2); 60.12 (s,
2
2
3
2.00 (dd, JHH = 15.7 Hz, JHH = 7.0 Hz, 1H, CHH); 2.12 (dd,
CH2O); 62.58 (s, 2 × CH2OP); 62.97 (s, 2 × CH2OP); 71.65
2JHH = 15.7 Hz, JHH = 6.0 Hz, 1H, CHH); 2.51 (dd, JHH
=
(dd, JPC = 171.2 Hz, JPC = 7.2 Hz, CHO); 172.05 (s, C O).
3
2
1
2
=
3
2
12.0 Hz, JHH = 7.0 Hz, 1H, CHH); 2.74 (dd, JHH = 12.0 Hz,
C14H30O9P2: requires C 41.59, H 7.48; found C 41.68, H 7.44.
3JHH = 6.0 Hz, 1H, CHH); 4.11 (q, JHH = 7.0 Hz, 2H, CH2O);
3
5.07 (d, 3JHH = 9.7 Hz, 1H, CHH); 5.08 (d, 3JHH = 17.7 Hz, 1H,
CHH); 5.90 (dddd, 3JHH = 17.7 Hz, 3JHH = 9.5 Hz, 3JHH = 7.0 Hz,
3JHH = 6.0 Hz, 1H, CH); dC (CDCl3) 13.73 (CH3CH2O); 21.81
(CH2); 22.12 (CH); 30.24 (CH2); 32.11 (C); 61.11 (CH2O); 114.75
(CH2); 125.13 (2 × CHAr); 127.06 (CHAr); 128.69 (2 × CHAr);
General procedure for the preparation of cyclopropanecarboxy-
lates 31 and 33. To a suspension of sodium hydride (0.048 g,
2.0 mmol) in tetrahydrofuran (10 ml), phosphate 30 or 32
(2.0 mmol) was added and the resulting mixture was stirred for
0.5 h at room temperature and then heated at reflux for 5 h.
Saturated NaCl solution (5 ml) was added and tetrahydrofuran
was evaporated under reduced pressure. The residue was extracted
with methylene chloride (3 × 15 ml). The combined organic layers
were dried (MgSO4) and then evaporated under pressure to give a
crude product, which was purified by column chromatography.
=
135.21 (CH); 135.94 (CAr); 175.30 (C O). C16H20O2: requires C
78.65, H 8.25; found C 78.89, H 8.28.
4-Cyano-4-(diethoxyphosphoryloxy)butyric acid ethyl ester (30).
To a solution of phosphonate 21 (0.80 g, 3.0 mmol) and acetone
cyanohydrin (1.10 ml, 1.2 mmol) in methylene chloride (10 ml)
titanium(IV) isopropoxide (0.89 g, 3.0 mmol) was added. The
resulting solution was stirred at room temperature for 20 h.
Water (10 ml) was added, the organic layer was separated and the
aqueous layer was extracted with methylene chloride (2 × 15 ml).
The combined organic layers were washed with 1 N HCl (5 ml)
then dried (MgSO4) and evaporated under reduced pressure. The
residue was chromatographed (CHCl3–acetone 90 : 10, Rf = 0.26)
Trans-2-Cyanocyclopropanecarboxylic acid ethyl ester (31)22.
Purification (CHCl3, Rf = 0.46) gave the ester 31 as a colourless oil
(0.20 g, 68%); dH (CDCl3) 1.26 (t, 3JHH = 7.0 Hz, 3H, CH3CH2O);
3
3
2
1.42 (ddd, JHH = 9.0 Hz, JHH = 6.0 Hz, JHH = 4.5 Hz, 1H,
CHH); 1.50 (ddd, 3JHH = 8.7 Hz, 3JHH = 6.2 Hz, 2JHH = 4.5 Hz,
3
3
3
1H, CHH); 1.94 (ddd, JHH = 9.0 Hz, JHH = 6.2 Hz, JHH
4.7 Hz, 1H, CH); 2.25 (ddd, 3JHH = 8.7 Hz, 3JHH = 6.0 Hz, 3JHH
4.7 Hz, 1H, CH); 4.18 (q, 3JHH = 7.0 Hz, 2H, CH2O).
=
=
to give the ester 30 as a colourless oil (0.84 g, 95%); mmax 2200,
3
1748, 1260, 1042; dP (CDCl3) −2.14; dH (CDCl3) 1.26 (t, JHH
=
Trans-2-(Diethoxyphosphoryl)cyclopropanecarboxylic acid ethyl
ester (33)23. Purification (CHCl3–acetone 90 : 10, Rf = 0.24) gave
the ester 33 as a colourless oil (0.35 g, 70%); dP (CDCl3) 22.64; dH
(CDCl3) 1.00–1.11 (m, 2H, CH2-C3); 1.12 (t, 3JHH = 7.0 Hz, 3H,
7.0 Hz, 3H, CH3CH2O); 1.35 (td, 3JHH = 7.0 Hz, 4JPH = 0.5 Hz,
3
4
3H, CH3CH2OP); 1.37 (td, JHH = 7.0 Hz, JPH = 0.5 Hz, 3H,
CH3CH2OP); 2.30 (t, 3JHH = 6.5 Hz, 2H, CH2); 2.52–2.63 (m, 2H,
3
3
3
CH2); 4.18 (q, JHH = 7.0 Hz, CH2O); 4.20 (dq, JPH = JHH
=
3
4
CH3CH2O); 1.37 (td, JHH = 7.0 Hz, JPH = 0.5 Hz, 6H, 2 ×
7.0 Hz, 4H, 2 × CH2OP); 5.15 (dt, 3JPH = 8.5 Hz, 3JHH = 6.50 Hz,
3
3
3
CH2OP); 1.54 (dddd, JPH = 15.2 Hz, JHH = 10.0 Hz, JHH
=
1H, CH); dC (CDCl3) 13C NMR dC (CDCl3) 13.24 (s, CH3CH2O);
3
2
6.2 Hz, JHH = 6.0 Hz, 1H, CH); 2.10 (dddd, JPH = 20.0 Hz,
3JHH = 9.5 Hz, 3JHH = 6.5 Hz, 3JHH = 6.0 Hz, 1H, CH); 4.09 (q,
3
3
15.74 (d, JPC = 5.8 Hz, CH3CH2OP); 15.80 (d, JPC = 5.6 Hz,
CH3CH2OP); 25.04 (d, 4JPC = 3.7 Hz, CH2); 28.87 (s, CH2); 60.04
(s, CH2O); 60.29 (s, 2 × CH2OP); 69.11 (d, 2JPC = 6.7 Hz, CHO);
3JHH = 7.0 Hz, 2H, CH2O); 4.12 (dq, 3JPH = JHH = 7.00 Hz, 2H,
3
CH2OP); 4.13 (dq, 3JPH = JHH = 7.0 Hz, 2H, CH2OP).
3
=
117.28 (s, CN); 170.14 (s, C O). C11H20NO6P: requires C 45.05,
H 6.87, N 4.78; found C 45.27, H 6.82, N 4.81.
(E)-5-(Diethoxyphosphoryl)hex-2-enedioic acid diethyl ester
(35) and 2-[(diethoxyphosphoryl)ethoxycarbonylmethyl]cyclopro-
panecarboxylic acid ethyl ester (36). To a suspension of sodium
hydride (0.072 g, 3.0 mmol) in tetrahydrofuran (10 ml), triethyl
phosphonoacetate (0.6 ml, 3.0 mmol) was added at room temper-
ature and the mixture was stirred for 0.5 h. Then phosphate 21
(0.8 g, 3.0 mmol) was added and the resulting mixture was heated
at reflux for 5 h. Water (10 ml) was added and tetrahydrofuran was
evaporated under reduced pressure. The residue was extracted with
methylene chloride (4 × 15 ml) and dried (MgSO4). Evaporation
of the solvent afforded crude products 35 and 36, which were
separated by column chromatography using ethyl acetate as eluent.
4-(Diethoxyphosphoryl)-4-(diethoxyphosphoryloxy)butyric acid
ethyl ester (32). To a solution of phosphonate 21 (0.80 g,
3.0 mmol) and diethyl phosphite (0.52 ml, 3.0 mmol) in ethanol
(10 ml), a catalytic amount of sodium ethoxide (15 mg) was added
and the mixture was stirred for 0.5 h at room temperature. Water
(5 ml) was added and ethanol was evaporated under reduced
pressure. The residue was extracted with methylene chloride (3 ×
15 ml). The combined organic layers were washed with saturated
NaCl solution (5 ml) then dried (MgSO4) and evaporated under
reduced pressure. The residue was chromatographed (CHCl3–
acetone 90 : 10, Rf = 0.20) to give the ester 32 as a colourless
oil (0.97 g, 80%); mmax 1748, 1226, 1024; dP (CDCl3) −0.67 (d,
Compound 35. Yield (0.1 g, 13%); colourless oil; (Rf = 0.49);
mmax 1748, 1720, 1648, 1226, 1032; dP (CDCl3) 21.51; dH (CDCl3)
1.27 (td, 3JHH = 7.0 Hz, 4JPH = 1.0 Hz, 3H, CH3CH2OP); 1.31 (td,
3JPP = 22.2 Hz); 19.51 (d, JPP = 22.2 Hz); dH (CDCl3) 1.26 (t,
3
3JHH = 7.0 Hz, 3H, CH3CH2O); 1.35 (t, JHH = 7.0 Hz, 6H, 2 ×
3
CH3CH2OP); 1.36 (t, 3JHH = 7.0 Hz, 6H, 2 × CH3CH2OP); 2.07–
2.19 (m, 1H, CHH); 2.23–2.36 (m, 1H, CHH); 2.56–2.64 (m, 2H,
3JHH = 7.0 Hz, JPH = 1.0 Hz, 3H, CH3CH2OP); 1.34 (t, JHH
=
4
3
7.0 Hz, 3H, CH3CH2O); 1.35 (t, 3JHH = 7.0 Hz, 3H, CH3CH2O);
CH2); 4.15 (dq, 3JPH = JHH = 7.0 Hz, 8H, 4 × CH2OP); 4.20 (q,
2.76 (dddd, 3JPH = 11.5 Hz, 3JHH = 7.0 Hz, 3JHH = 4.0 Hz, 4JHH
=
3
3
2
3
3
3
2H, JHH = 7.0 Hz, CH2O), 4.69 (dddd, JPH = 15.2 Hz, JPH
=
1.5 Hz, 1H, CHH); 2.82 (dddd, JHH = 10.5 Hz, JPH = 8.5 Hz,
4 2
10.5 Hz, 3JHH = 8.0 Hz 3JHH = 4.7 Hz, 1H, CHO); dC (CDCl3) 13.81
3JHH = 7.0 Hz, JHH = 1.50 Hz, 1H, CHH); 3.09 (ddd, JPH
=
3
3
3
(s, CH3CH2O); 15.66 (d, JPC = 7.0 Hz, CH3CH2OP); 15.68 (d,
22.7 Hz, JHH = 10.5 Hz, JHH = 4.0 Hz, 1H, CH); 4.10–4.26
3JPC = 6.9 Hz, CH3CH2OP); 16.05 (d, 3JPC = 5.6 Hz, CH3CH2OP);
316 | Org. Biomol. Chem., 2008, 6, 308–318
(m, 8H, 2 × CH2O, 2 × CH2OP); 5.89 (dt, JHH = 15.5 Hz,
3
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4JHH = 1.5 Hz, 1H, CH); 6.86 (dt, 3JHH = 15.5 Hz, 3JHH = 7.0 Hz,
1H, CH); dC (CDCl3) 14.03 (s, CH3CH2O); 14.15 (s, CH3CH2O);
16.28 (d, 3JPC = 5.7 Hz, 2 × CH3CH2OP); 29.34 (d, 2JPC = 3.8 Hz,
CH2); 44.38 (d, 1JPC = 131.3 Hz, CHP); 60.31 (s, CH2O); 61.65 (s,
CH2O); 62.84 (d, 2JPC = 7.15 Hz, CH2OP); 62.97 (d, 2JPC = 7.2 Hz,
2 (a) D. B. Denney and M. J. Boskin, J. Am. Chem. Soc., 1959, 81, 6330;
(b) W. S. Wadsworth and W. D. Emmons, J. Am. Chem. Soc., 1961, 83,
1733; (c) D. B. Denney, J. J. Vill and M. J. Boskin, J. Am. Chem. Soc.,
1962, 84, 3944; (d) I. To¨mo¨sko¨zi, Tetrahedron, 1963, 19, 1969; (e) R. A.
Izydore and R. G. J. Ghirardelli, J. Org. Chem., 1973, 38, 1790.
3 (a) B. J. Fitzsimmons and B. Fraser-Reid, Tetrahedron, 1984, 40, 1279;
(b) R. C. Petter, Tetrahedron Lett., 1989, 30, 399; (c) R. C. Petter,
S. Banerjee and S. Englard, J. Org. Chem., 1990, 55, 3088; (d) J. A.
Robl, E. Sieber-McMaster and R. Sulsky, Tetrahedron Lett., 1996, 37,
8985; (e) V. Padmavathi, K. Sharmila, A. S. Reddy and D. B. Reddy,
Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem., 2001, 40, 11;
(f) A. K. Singh, M. N. Rao, J. H. Simpson, W. S. Li, J. E. Thornton,
D E. Kuehner and D. J. Kacsur, Org. Process Res. Dev., 2002, 6, 618;
(g) A. K. Singh, J. S. Prasad and E. J. Delaney, Asymmetric Catalysis
on Industrial Scale: Challenges, Approaches and Solutions, Wiley-VCH,
Weinheim, 2004, p. 335; (h) A. Armstrong and J. N. Scutt, Org. Lett.,
2003, 5, 2331; (i) A. Armstrong and J. N. Scutt, Chem. Commun., 2004,
510; (j) G. Sturtz, Bull. Soc. Chim. Fr., 1964, 2349; (k) M. Baboulene
and G. Sturtz, Phosphorus Relat. Group V Elem., 1973, 2, 195; (l) T. E.
Jacks, H. Nibbe and D. F. Wiemer, J. Org. Chem., 1993, 58, 4584.
CH2OP); 123.45 (s, CH); 144.21 (d, 3JPC = 15.7 Hz, CH); 165.96
2
=
=
(s, C O); 167.99 (d, JPC = 4.7 Hz, C O). C14H25O7P: requires C
50.00, H 7.49; found C 49.77, H 7.44.
Compound 36. Yield (0.13 g, 13%); colourless oil; (Rf = 0.63);
mmax 1764, 1724, 1220, 1024; dP (CDCl3) 23.16; dH (CDCl3) 1.18 (td,
4
3JHH = 7.0 Hz, JPH = 1.2 Hz, 3H, CH3CH2OP); 1.20–1.38 (m,
12H, 2 × CH3CH2O, CH3CH2OP, CH2, CH); 2.24 (ddddd, 3JHH
=
=
3
3
3
3
11.0 Hz, JHH = 10.5 Hz, JPH = 7.0 Hz, JHH = 6.0 Hz, JHH
5.0 Hz, 1H, CH); 3.12 (dd, 2JPH = 23.2 Hz, 3JHH = 10.5 Hz, 1H,
CH); 4.11–4.24 (m, 8H, 2 × CH2O, 2 × CH2OP); dC (CDCl3) 14.03
(s, CH3CH2O); 15.13 (s, CH3CH2O); 16.28 (d, 3JPC = 5.7 Hz, 2 ×
CH3CH2OP); 21.10 (d, 3JPC = 2.6 Hz, CH2); 28.95 (s, CH); 30.88
(d, 2JPC = 3.0 Hz, PCH); 41.41 (d, 1JPC = 131.3 Hz, CHP); 61.28
4 H. Krawczyk, K. Wasek and J. Kędzia, Synlett, 2005, 2648.
ꢀ
5 (a) T. Minami, Y. Kitajima and T. Chikugo, Chem. Lett., 1986, 1229;
(b) T. Minami, K. Watanabe, T. Chikugo and Y. Kitajima, Chem. Lett.,
1987, 2369; (c) T. Janecki, A. Kus´, H. Krawczyk and E. Błaszczyk,
Synlett, 2000, 611; (d) T. Janecki and E. Błaszczyk, Synthesis, 2001,
403.
2
(s, CH2O); 62.14 (s, CH2O); 62.63 (d, JPC = 6.2 Hz, CH2OP);
62.95 (d, 2JPC = 6.1 Hz, CH2OP); 168.92 (d, 2JPC = 3.1 Hz, C O);
=
6 C. K. McClure and K.-Y. Jung, J. Org. Chem., 1991, 56, 867.
7 T. C. Myers, R. G. Harvey and E. V. Jensen, J. Am. Chem. Soc., 1955,
77, 3101.
=
175.14 (s, C O). C14H25O7P: requires C 50.00, H 7.49; found C
50.19, H 7.45.
8 J. M. Varlet, G. Fabre, F. Sauveur, N. Collignon and P. Savignac,
Tetrahedron, 1981, 37, 1377.
9 M. K. Tay, E. About-Jandet, N. Collignon, M. P. Teulade and P.
Savignac, Synth. Commun., 1988, 18, 1349.
10 I. Truel, A. Mohamed-Hachi, E. About-Jaudet and N. Collignon,
Synth. Commun., 1997, 27, 1165.
11 S. Touil and H. Zantour, Phosphorus, Sulfur Silicon Relat. Elem., 1997,
131, 183.
12 G. A. Kraus and P. K. Choudhury, Eur. J. Org. Chem., 2004, 2193.
13 D.-J. Cho, S.-J. Jean, H.-S. Kim, C.-S. Cho, S.-C. Shim and T.-J. Kim,
Tetrahedron: Asymmetry, 1999, 10, 3833.
14 S. Ahmad, L. M. Doweyko, S. Dugar, N. Grazier, K. Ngu, S. C. Wu,
K. J. Yost, B.-C. Chen, J. Z. Gougoutas, J. D. DiMarco, S.-J. Lan, B. J.
Gavin, A. Y. Chen, C. R. Dorso, R. Serafino, M. Kirby and K. S. Atwal,
J. Med. Chem., 2001, 44, 3302.
Crystal structure determination of 1-benzyl-2-methylcyclopro-
panecarboxylate anion derived from the ester 7h. C12H13NO2·
C12H24N, Mw = 371.55, colourless crystal 0.40 × 0.20 × 0.10 mm,
˚
triclinic, a = 10.2817(1), b = 10.6027(1), c = 11.7395(2) A, a =
◦
3
˚
64.164(1), b = 86.195(1), c = 73.578(1) , V = 1102.46(2) A ,
space group P1, Z = 2, qcalc = 1.20 g cm−3, l = 0.537 mm−1,
¯
F(000) = 408, semi-empirical absorption correction based on
multiple scanned equivalent reflections (0.827 < T < 0.943), k(Cu-
˚
Ka) = 1.54178 A, T = 293 K, x scans, 12 592 reflections collected
( h, k, l), 2hmax = 142◦, 4052 unique reflections (Rint = 0.014),
392 refined parameters, refinement on F2, final R = 0.048 for
3765 observed reflections [Fo > 4r(Fo)], Rall = 0.050, wRall(F2) =
15 A. G. M. Barret, D. C. Braddock, I. Lenoir and H. Tone, J. Org. Chem.,
2001, 66, 8260.
−3
˚
0.140, residual electron density Dqmax = 0.19 Dqmin = −0.22 e A ,
16 Spectral data of trans-1-benzyl-2-phenylcyclopropanecarboxylic acid.
all hydrogen atoms refined with individual isotropic temperature
factors. X-Ray data were collected with a Bruker SMART APEX
CCD area detector diffractometer. Computer programs used:
data collection: SMART APEX,24 data reduction: SAINT-Plus,25
absorption correction: SADABS,26 structure solution, refinement
and molecular graphics: SHELXTL.27 CCDC reference number
653900. For crystallographic data in CIF or other electronic
format see DOI: 10.1039/b712145h
White crystals (m.p. 90–92 ◦C); mmax 1744; dH (CDCl3) = 1.40 (dd,
2
3
3JHH = 7.0 Hz, JHH = 5.0 Hz, 1H, CHH); 1.86 (dd, JHH = 9.2 Hz,
2JHH = 5.0 Hz, 1H, CHH); 2.01 (d, 2JHH = 15.0 Hz, 1H, CHH); 2.80
(dd, 3JHH = 9.2 Hz, 3JHH = 7.0 Hz, 1H, CH); 3.22 (d, 2JHH = 15.0 Hz,
1H, CHH); 7.23–7.30 (m, 5H, CHAr); dC (CDCl3): 17.80 (CH2); 30.95
(CH2); 31.14 (C); 32.27 (CH); 125.64 (2 × CHAr); 128.01 (2 × CHAr);
=
128.42 (CHAr); 140.60 (CAr); 179.98 (C O). C19H20O2: requires C 81.40,
H 7.19; found C 81.64, H 7.15.
17 H. Krawczyk, K. Wasek, J. Kędzia, J. Wojciechowski and W. M. Wolf,
ꢀ
Acta Crystallogr., Sect. C: Cryst. Struct. Commun., 2007, in press.
18 Spectral data of the dicyclohexylammonium salt of trans-1-benzyl-2-
methylcyclopropanecarboxylic acid. Light yellow crystals (m.p. 91–
94 ◦C); mmax 1760, 1150; dH (CDCl3) = 0.62 (dd, 3JHH = 6.7 Hz, 2JHH
=
Acknowledgements
4.0 Hz, 1H, CHH); 1.11–1.36 (m, 9H, 3 × CH2, CH3), 1.42–1.68 (m,
7H, 3 × CH2, CHH); 1.60 (dd, 3JHH = 9.2 Hz, 3JHH = 6.7 Hz, 3JHH
=
The authors thank Professor Ryszard Bodalski (Technical Uni-
versity of Lodz) for stimulating discussions.
6.2 Hz, 1H, CH); 1.69 1.80 (m, 4H, 2 × CH2); 1.98–2.06 (m, 4H, 2 ×
2
CH2); 2.76 (d, JHH = 16.0 Hz, 1H, CHH); 2.80–3.05 (m, 2H, 2 ×
CHN); 3.22 (d, 2JHH = 16.0 Hz, 1H, CHH); 7.23–7.30 (m, 5H, CHAr);
dC (CDCl3): 14.00 (CH3); 21.75 (CH2); 22.27 (CH); 24.32 (2 × CH2);
24.75 (4 × CH2); 27.69 (C); 33.04 (4 × CH2); 33.26 (CH2); 24.32 (2 ×
CH); 125.64 (2 × CHAr); 128.01 (2 × CHAr); 128.37 (CHAr); 140.60
References and notes
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