Asymmetric cyclopropanation of optically active (1-diethoxyphosphoryl)vinyl p-tolyl sulfoxide with sulfur ylides: A rationale for diastereoselectivity

Article abstract of DOI:10.1002/ejoc.200400587

The title sulfoxide (S)-(+)-1a was found to react with sulfur ylides affording the corresponding cyclopropanes in high yields. With fully deuterated dimethyl(oxo)sulfonium methylide, (CD₃)₂S(O)CD ₂, the cyclopropanation re

Full text of DOI:10.1002/ejoc.200400587

FULL PAPER
Asymmetric Cyclopropanation of Optically Active (1-Diethoxyphosphoryl)vinyl
p-Tolyl Sulfoxide with Sulfur Ylides: A Rationale for Diastereoselectivity
Wanda H. Midura,[a] Jerzy A. Krysiak,[a] Marek Cypryk,[a] Marian Mikołajczyk,*[a]
Michał W. Wieczorek,[b] and Agnieszka D. Filipczak[c]
Dedicated to Professor Mieczysław Makosza on the occasion of his 70th birthday
Keywords: Asymmetric synthesis / Cyclopropanes / Density functional calculations / Diastereoselectivity / Vinyl sulfoxides
The title sulfoxide (S)-(+)-1a was found to react with sulfur
ylides affording the corresponding cyclopropanes in high
yields. With fully deuterated dimethyl(oxo)sulfonium methyl-
ide, (CD3)2S(O)CD2, the cyclopropanation reaction occurred
in a highly diastereoselective manner producing the cyclo-
propane 4a-d2 as a major diastereomer in which the newly
formed quaternary α-carbon atom is chiral due to isotopic
stereomeric ratio in both reactions was found to be ca. 10:1.
The reaction of (S)-(+)-1a with diphenylsulfonium isopropyl-
ide yielded the cyclopropane (+)-7 as a single diastereomer.
X-ray structural studies of the crystalline 1-phosphorylvinyl
sulfoxide 9 as well as density functional calculations (B3LYP/
6-31G*) on (1-phosphoryl)vinyl sulfoxides revealed the ori-
gin of the experimentally observed diastereoselectivities and
substitution (CH2 vs. CD2). The diastereomer 4b-d2, having allowed us to propose a transition state model for the cyclo-
the opposite configuration at the α-carbon atom, was ob-
propanation reaction of chiral 1-phosphorylvinyl sulfoxides.
tained starting form the 2,2-dideuterio substituted vinyl sul-
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
foxide, (S)-(+)-1a-d2, and the nondeuterated ylide. The dia- Germany, 2005)
Introduction
such vinyl sulfoxides have been described and have been
found to occur efficiently and with high stereoselectivity.[5]
Recently, chiral alkylidene bis(sulfoxides) have been demon-
strated as excellent acceptors in totally diastereoselective
Michael additions.[6]
The sulfinyl group has proved to be one of the most ef-
ficient chiral auxiliaries because of its extraordinary ability
to control the stereoselectivity of asymmetric processes.[1Ϫ3]
Among a great number of optically active sulfinyl com-
pounds, chiral enantiomerically pure vinyl sulfoxides, which
have recently found a wide application in numerous asym-
metric reactions, are especially important. However, the use
of simple, unsubstituted enantiopure vinyl sulfoxides in
asymmetric synthesis is restricted due to their low reactivity
and moderate stereoselectivity. The reactivity of a sulfinyle-
thylene can be increased by introduction of electron-with-
drawing group(s) at the α- and/or β-positions of the
carbonϪcarbon double bond, the carbonyl and alkoxycar-
bonyl groups having been most frequently used for this pur-
pose.[4] In fact, many asymmetric DielsϪAlder reactions of
In the course of our studies on the applications of chiral
vinyl sulfoxides in asymmetric synthesis, we designed a new
group of activated enantiomerically pure vinyl sulfoxides,
namely (1-diethoxyphosphoryl)vinyl p-tolyl sulfoxide 1a
and its β-substituted analogues.[7,8] The presence of the elec-
tron-withdrawing phosphoryl group increases not only the
reactivity of the carbon-carbon double bond in 1 but also
the degree of stereocontrol because of the bulky, tetrahedral
structure of the diethoxyphosphoryl group. The optically
pure sulfoxide 1a and its analogues were found to be good
Michael acceptors and reactive DielsϪAlder dienophiles.
Moreover, they could also be used as key reagents for the
[a]
Centre of Molecular and Macromolecular Studies, Polish
Academy of Sciences,
´
90-363 Lodz, Sienkiewicza 112, Poland
Fax: (internat.) ϩ 48-42-6847126
E-mail: marmikol@bilbo.cbmm.lodz.pl
[b]
[c]
Institute of Chemistry and Environmental Protection,
Pedagogical University of Czestochowa,
42-200 Czestochowa, Al. Armii Krajowej 13/15, Poland
Institute of General Food Chemistry, Technical University of
´
Lodz,
´
90-924 Lodz, Stefanowskiego 4/10, Poland
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M. Mikołajczyk et al.
FULL PAPER
construction of monocyclic compounds and condensed Results and Discussion
carbo- and heterocycles via tandem Michael addition/intra-
molecular HornerϪWittig reactions. Scheme 1 shows selec- Reaction of (S)-(؉)-(1-Diethoxyphosphoryl)vinyl p-Tolyl
ted reactions of 1a illustrating its typical reactivity.
Sulfoxide 1a with Sulfur Ylides
Initially, the reactivity of our sulfoxide towards a sulfur
ylide was examined. Thus, (S)-(ϩ)-1a was treated with an
excess of dimethyl(oxo)sulfonium methylide in DMSO at
room temperature. After ca. 3 hours this reaction afforded
the expected cyclopropane (S)-(ϩ)-4 as the only product
which was isolated by flash chromatography on silica gel in
90% yield [Equation (1)].
(1)
Since the above reaction does not generate a new stereog-
enic carbon centre, the optical activity of the cyclopropane
4 is due to the chiral sulfoxide moiety. However, by using
the fully deuterated dimethyl(oxo)sulfonium methylide as
the CD2 transfer reagent it should be possible to carry out
the asymmetric version of this reaction. In such a case the
newly formed quaternary α-carbon atom is stereogenic due
to isotopic substitution (CH2 vs. CD2). As expected, under
comparable reaction conditions, (S)-(ϩ)-1a gave the corre-
sponding cyclopropane in 92% isolated yield upon treat-
ment with the deuterated sulfur ylide [Equation (2)].
Scheme 1. Examples of typical reactions of (S)-(ϩ)-(1-diethoxy-
phosphoryl)vinyl p-tolyl sulfoxides 1
In this paper we wish to disclose the results of the reac-
tions of (S)-(ϩ)-1a with sulfur ylides which afford the corre-
sponding cyclopropanes in a highly or fully diastereoselec-
tive way.[9] Herein we also report the results of X-ray struc-
tural studies and theoretical calculations of α-phosphorylvi-
nyl sulfoxides which corroborate the transition state model
proposed by us in our preliminary communication for the
asymmetric cyclopropanation reaction of (S)-(ϩ)-1a with
diphenyldiazomethane.[9,10]
Our interest in this new asymmetric cyclopropanation re-
action was stimulated by two facts. The first was that a wide
variety of natural products and currently used insecticides
contain the chiral cyclopropane unit.[11] Secondly, at the be-
ginning of this study, there were only two reports describing
asymmetric cyclopropanation using the enantiopure vinyl
sulfoxides 2 and 3 as chiral reagents.[12,13]
(2)
The 31P NMR spectrum of the crude product revealed
only one sharp signal at δP ϭ 22.3 ppm. The 1H NMR spec-
trum (500 MHz, C6D6) of the isolated product showed high
intensity signals for the methylene protons which appeared
in the spectrum as doublets of doublets at δ ϭ 1.18 ppm
3
(2JH,H ϭ 4.9 and JH,P ϭ 14.0 Hz) and 1.30 ppm (2JH,H
ϭ
3
4.9 and JH,P ϭ 9.9 Hz) (Figure 1, a). These signals have
In the meantime, we reported the highly diastereoselec- been ascribed to the methylene protons of the expected
tive cyclopropanation reactions of (S)-(ϩ)-1a and (S)-(ϩ)- cyclopropane 4a-d2. However, at lower field at ca. 1.4 and
(1-dimethoxyphosphoryl-2-phenyl)vinyl p-tolyl sulfoxide 1.6 ppm, some signals of low intensity (ca. 10%) were ob-
with ethyl (dimethylsulfuranylidene)acetate (EDSA) which served which could indicate the presence of the second,
paved the way to enantiopure cyclopropylphosphonate ana- minor diastereomer, 4b-d2, having the opposite configura-
logues of nucleotides and 2-amino-3-phenylcyclopropyl- tion at the α-carbon atom. To identify these signals and to
phosphonic acid (a constrained analogue of phaclofen), solve the problem of the diastereoselectivity of this reaction,
respectively.[14,15]
we decided to synthesise 4b-d2 from the cyclopropanation
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Asymmetric Cyclopropanation of an Optically Active Sulfoxide with Sulfur Ylides
FULL PAPER
reaction between dimethyl(oxo)sulfonium methylide and vinyl sulfoxide (S)-(ϩ)-1a-d2 was produced. After purifi-
the 2,2-dideuterio-substituted vinyl sulfoxide, (S)-(ϩ)-1a-d2. cation by column chromatography it was isolated in 87%
In accord with the established approach of E. Fischer for yield.
inversion of configuration at the tetrahedral asymmetric
The reaction of (S)-(ϩ)-1a-d2, obtained as above, with
carbon atom,[16] the use of the latter reagent should lead to dimethyl(oxo)sulfonium methylide in [D6]DMSO gave the
the cyclopropane 4b-d2 with reversed positions of the CH2 corresponding cyclopropane in 90% yield [Equation (3)].
and CD2 groups compared with 4a-d2. The required vinyl
sulfoxide 1a-d2 was obtained by the sequence of reactions
outlined in Scheme 2.
(3)
1
An analysis of its H NMR spectrum (500 MHz, C6D6)
revealed the presence of high intensity signals for the meth-
ylene protons of 4b-d2 at δ ϭ 1.43 ppm (2JH,H ϭ 4.3 and
3
3JH,P ϭ 15.1 Hz) and 1.65 ppm (2JH,H ϭ 4.3 and JH,P
ϭ
8.8 Hz). Moreover, the low intensity doublets of doublets
appearing in the spectrum at δ ϭ 1.18 and 1.30 ppm were
found to be identical to those of 4a-d2 (Figure 1, b). Hence,
in this cyclopropanation reaction, two diastereomeric cyclo-
propanes 4b-d2 and 4a-d2 were produced in a 91:9 ratio as
determined by integration of the above discussed CH2 sig-
nals.
Figure 1. Cyclopropyl methylene proton signals in the 1H NMR
spectrum of (a) the cyclopropanation product of reaction 2 (4a-d2-
major) and (b) the cyclopropanation product of reaction 3 (4b-
d2-major
Most probably, the major diastereomer 4a-d2 formed in
the reaction between (S)-(ϩ)-1a and deuterated sulfonium
ylide [Equation (2)] also contains 4b-d2 as a minor isomer.
However, the exact determination of the diastereomeric ra-
tio in this case is difficult because the methylene protons of
the latter are obscured by other signals most likely due to
the mono- and nondeuterated cyclopropane 4 which was
also present in the reaction product in small amounts. In
fact, the mass spectrum of the reaction product showed, in
addition to the molecular peak ([M ϩ H]ϩ, m/z: 319) for
4a-d2, two other [M ϩ H]ϩ peaks for the monodeuterated
cyclopropane 4-d1 (m/z: 318) and nondeuterated cyclopro-
pane 4 (m/z: 317).
Encouraged by the high diastereoselectivity observed in
the cyclopropanation reaction discussed above, we carried
out the reaction of (S)-(ϩ)-1 with diphenylsulfonium iso-
propylide[17] under the standard reaction conditions (THF,
Ϫ70 °C, 3 h) (Scheme 3). It was gratifying to find that the
cyclopropane (ϩ)-7 formed in this reaction and isolated in
65% yield was a single diastereomer as indicated by its 31P
and 1H NMR spectra. Thus, the 1H NMR spectrum of (ϩ)-
7 displayed two sharp singlets for the cyclopropyl methyl
Scheme 2. Synthesis of (S)-(ϩ)-(1-diethoxyphosphoryl-2,2-dideu-
terio)vinyl p-tolyl sulfoxide 1a-d2
In the first step, (S)-(ϩ)-diethoxyphosphorylmethyl p-to- protons at δ ϭ 1.48 and 1.63 ppm, and two doublets of
lyl sulfoxide (5) was subjected to alkylation with trideuteri- doublets at δ ϭ 1.77 ppm (2JH,H ϭ 5.6, 3JH,P ϭ 8.9 Hz) and
3
omethyl iodide to give the corresponding monoalkylation 1.99 ppm (2JH,H ϭ 5.6 and JH,P ϭ 16.3 Hz) characteristic
product 6 in 74% yield as a mixture of two diastereomers. of the cyclopropyl methylene protons. In order to addition-
Then, in a one-pot reaction involving selenenylation of 6 ally confirm the full diastereomeric purity of (ϩ)-7, it was
with phenylselenenyl bromide and subsequent oxidative oxidised to the optically active sulfone (ϩ)-8 in which the
benzeneselenenic acid elimination, the desired deuterated only stereogenic atom was the newly formed quaternary α-
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M. Mikołajczyk et al.
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1
carbon atom. The H NMR spectrum of the sulfone (ϩ)-9 reactive fragment of 1-phosphorylvinyl sulfoxide 9 is stabil-
recorded in the presence of (R)-(ϩ)-tert-butylphenylphos- ised by an intramolecular hydrogen bond formed by the sul-
phinothioic acid as a chiral solvating agent[18] did not show finyl oxygen atom O1 and the vinylic proton at C2
˚
a typical doubling of the cyclopropyl methyl and methylene [d(H···O1) ϭ 2.305 A]. It is interesting to point out that a
˚
protons thereby providing unequivocal evidence of the full similar intramolecular hydrogen contact of 2.257 A has also
enantiomeric purity of (ϩ)-8 and, consequently, of the full been found in the solid-state conformation of (E)-(1-meth-
diastereomeric purity of its precursor i.e. the cyclopropane ylsulfenyl-2-phenyl)vinyl p-tolyl sulfoxide.[20] A recent X-ray
(ϩ)-7.
analysis of (S,S)-1,1-bis(p-tolylsulfinyl)-2-phenylethylene
˚
also revealed a short contact of 2.28 A between the vinylic
hydrogen and the sulfinyl oxygen.[6]
Scheme 3. Synthesis of cyclopropane (ϩ)-7 and sulfone (ϩ)-8
Synthesis, Crystal and Molecular Structures of Racemic
(1-Diphenylphosphinoyl)vinyl p-Tolyl Sulfoxide 9
To understand the origin of the observed diastereoselec-
tivities in the cyclopropanation reaction of (S)-(ϩ)-1a, we
decided firstly to determine the structures and confor-
mations of (1-phosphoryl)vinyl sulfoxides. Since our re-
agent (S)-(ϩ)-1a is a liquid, our study started with the syn-
thesis of the closely structurally related crystalline sulfoxide
(1-diphenylphosphinoyl)vinyl p-tolyl sulfoxide 9. It was eas-
ily obtained from racemic (diphenylphosphinoyl)methyl p-
tolyl sulfoxide 10[19] and formaldehyde in the presence of
piperidine and acetic acid [Equation (4)]. The crude product
was purified by column chromatography and suitable crys-
tals for X-ray analysis were obtained by slow crystallisation
from benzene.
Figure 2. Solid state structure of (Ϯ)-9 with selected bond lengths
(thermal ellipsoids drawn at 50% probability for non-hydrogen
atoms; hydrogen atoms are shown as spheres with arbitrary radii)
The crystal packing of the molecules of 9 in the unit cell
is presented in Figure 3 in which intermolecular short con-
tacts are depicted. In the crystalline state, the molecules of
9 are held together by two intermolecular hydrogen bonds
(4)
˚
(2.460 A) between the sulfinyl oxygen atom O1 and the p-
tolyl methyl hydrogen atom at C17 forming a linear struc-
ture. Such arrays of 9 then form a pleasingly ordered supra-
molecular structure via two intermolecular hydrogen bonds
of 2.420 A in length between the phosphoryl oxygen atom
O11 and the aromatic ring hydrogen atom at C34.
A three-dimensional view of the molecule of 9 and the
atom numberings are shown in Figure 2. Selected bond
lengths are also shown. An analysis of the structural param-
eters obtained for 9 indicates that the sulfinyl oxygen atom
O1 is located almost in the plane formed by the ethylenic
carbon atoms and both heteroatoms, i.e. phosphorus and
˚
Theoretical Calculations
˚
sulfur. Its distance from this plane is 0.128 A and the tor-
To gain a deeper understanding of the factors controlling
sional angle C2ϪC1ϪS1ϪO1 is equal to Ϫ3.2°. The phos- the stereoselectivity of the cyclopropanation reactions of 1-
phoryl oxygen atom was found to be deflected from this phosphorylvinyl sulfoxides 1 and especially to determine
˚
plane by 0.658 A. The torsional angle C2ϪC1ϪP1ϪO11 is the gas phase conformation of 1, calculations using density
equal to 150.2°. Moreover, both polar sulfinyl and phos- functional theory (DFT) at the B3LYP/6-31G* level were
phoryl groups adopt an anti orientation in the crystalline carried out. In this context, it is interesting to note that
state (the torsional angle P1ϪO11···S1ϪO1 is equal to Tietze and co-workers[21] have recently described the results
153.4°), the former being syn-coplanar with the of DFT calculations on 1-carbonyl-substituted vinyl sulfox-
carbonϪcarbon double bond. Such a conformation of the ides. However, since there is a distinct difference between
656
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Asymmetric Cyclopropanation of an Optically Active Sulfoxide with Sulfur Ylides
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Figure 3. Crystal packing diagram for 9
the phosphoryl and carbonyl groups with regards to steric Table 1. The most stable conformations are, in both cases,
and electronic effects, our computational studies on 1-phos- very similar and closely analogous to the X-ray structure of
phoryl-substituted vinyl sulfoxides were additionally justi- the 1-phosphorylvinyl sulfoxide 9 (see Figure 4). The SϭO
fied.
bond is almost syncoplanar with the vinyl group (the tor-
The model compounds (dimethoxyphosphoryl)vinyl sional angle CϪCϪSϪO ϭ 1° and 5.7° for 11 and 12,
methyl sulfoxide 11 and (dimethoxyphosphoryl)vinyl phe- respectively) resulting in a high anisotropy of the steric hin-
nyl sulfoxide 12 were chosen, both having the (S) configura- drance around the vinyl group. The next stable confor-
tion at the sulfur atom. These vinyl sulfoxides closely re- mations for both models are higher in energy by ca. 2 kcal/
semble the sulfoxide (S)-(ϩ)-1a used in our experimental mol (Scheme 4, Table 1). The concentrations of the most
studies but due to smaller sizes of the models, the cost of stable conformation A in equilibrium with B were estimated
the calculations was more reasonable.
from the equation K ϭ eϪ∆G/RT and were found to be
98Ϫ99% and 96Ϫ97% for the sulfoxides 11 and 12, respec-
tively.
For both model sulfoxides, the conformational search
was performed at the AM1 semiempirical level. The four
most stable conformations were further optimised at the
B3LYP/6-31G* level. For the two most stable confor-
mations of 11, the intermediate products of addition of the
isopropylide anion and the final products of cyclopropan-
ation were also constructed and optimised. Depending on
the direction of a nucleophilic attack of the carbanion, two
diastereomeric products were generated. The calculations
were performed to compare the energetics of the reactions
involving various conformations of the starting reagent and
different directions of the approach of a nucleophile.
The two most stable conformations of 11 and 12 are pre-
sented in Scheme 4. The calculated energies (in Hartrees)
and relative enthalpies at 298 K (in kcal/mol) are given in ides 11 and 12
Scheme 4. Calculated most stable conformations for vinyl sulfox-
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M. Mikołajczyk et al.
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It should be pointed out that the role of the phosphoryl
group in preferential stabilisation of any conformation is
insignificant. Total energies of electronic interactions of the
phosphoryl group with the CϭC bond estimated by the
NBO deletion procedure are very similar, i.e. 23.0 and 24.2
kcal/mol for the conformers 11A and 11B, respectively.
Thus, the phosphoryl group shows mainly the steric effect
directing the nucleophilic attack on the β-carbon atom. It
also shows the inductive effect which causes diversification
of atomic charges on both vinyl carbon atoms. Thus, the
charges are Ϫ0.72 e and Ϫ0.35 e on the α- and β-carbon
atoms, respectively, in 11 (the differences between confor-
mations A and B being insignificant), while they are Ϫ0.49
e (α-carbon atom) and Ϫ0.41 e (β-carbon atom) in methyl
vinyl sulfoxide where the phosphoryl group has been re-
placed by hydrogen. Hence, the phosphoryl group reduces
the negative NBO charge on the β-carbon atom making it
more electron-deficient and more susceptible towards nucle-
ophilic attack.
Table 1. Total electronic energies, corrections for enthalpy and
Gibbs free energy at 298 K and relative enthalpies for model species
obtained from the DFT calculations
-E (a.u.)
∆H298 (a.u.) ∆G298 (a.u.) ∆Hrel (kcal/mol)
11A 1237.82311 0.18022
11B 1237.81977 0.18041
12A 1429.60589 0.23538
12B 1429.60269 0.23549
13A 1355.78359 0.26801
13B 1355.78275 0.26800
0.12138
0.12283
0.16868
0.16879
0.20253
0.20255
0.20278
0.20349
0
2.2
0
2.1
2.1
2.6
2.2
0
13C 1355.78339 0.26798
13D 1355.78693 0.26804
All isomers of the intermediate product generated by ad-
dition of the isopropylide anion to the sulfoxide 11 mol-
ecule are very close in energy. Their enthalpies at 298 K
differ by less than 0.8 kcal/mol. This result suggests that the
thermodynamics of the intermediate product formation are
probably not the factor determining the steric course of
the reaction.
A comparison of the energies of the diastereomers 13
formed by cyclopropane ring closure shows that the most
stable is the isomer 13D obtained by the attack of a nucle-
ophile on the less hindered side occupied by the electron
lone pair at sulfur (Scheme 5, the most stable isomer is
shown in a frame; Table 1). The geometry of the most stable
cyclopropane isomer 13D is in qualitative agreement with
the X-ray structure reported for 1-diethoxyphosphoryl-2,2-
diphenyl-1-(p-tolylsulfinyl)cyclopropane.[10]
Figure 4. Calculated structure of 12 with the selected bond lengths
Stabilisation of the conformations 11A and 12A arises,
at least in part, from electronic effects. The NBO analysis
indicates that the ‘‘planar’’ CCSO arrangement is stabilised
by the nSǞσ*CϭC
,
nSǞπ*CϭC
,
σSϪCǞπ*CϭC and
πCϭCǞσ*SϪC delocalisation interactions. The overall
energy of these interactions estimated by the NBO
deletion procedure is 10.9 kcal/mol. The energy of the
interactions stabilising the conformations 11B and 12B,
i.e., πCϭCǞσ*SϪO, πCϭCǞσ*SϪC and σSϪCǞσ*CϭC, is
6.8 kcal/mol. Additional stabilisation of the conformations
11A and 12A may be due to the intramolecular hydrogen
bonding between the sulfinyl oxygen atom and the vinyl
hydrogen atom. The distances between interacting atoms
˚
are 2.342 and 2.315 A in 11A and 12A, respectively, and the
Wiberg bond order is 0.015 for both species. According to
NBO deletion analysis, stabilisation resulting from this
interaction ranges from 1.1 kcal/mol for the sulfoxide 11 to
2.0 kcal/mol for the sulfoxide 12. Based on NBO analysis,
a similar stabilisation mechanism was postulated by Tietze
to explain the stability of the ‘‘coplanar’’ conformation of
methyl vinyl sulfoxide.[21]
Scheme 5. Calculated most stable conformations of diastereomeric
cyclopropanes 13
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Asymmetric Cyclopropanation of an Optically Active Sulfoxide with Sulfur Ylides
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chemical shifts are expressed with a positive sign, in ppm, relative
to an external standard of 85% H3PO4. High resolution mass spec-
tra were recorded on a Finnigan MAT 95 apparatus. IR spectra
were measured on an ATI Mattson spectrometer. Optical rotations
were measured on a PerkinϪElmer 241 MC photopolarimeter at
20 °C. Reactions were monitored by TLC chromatography (Merck
Transition State Model for Cyclopropanation of
1-Phosphorylvinyl Sulfoxides
Although some simplifications were assumed in our cal-
culations (simple, less hindered structures of vinyl sulfox-
ides, the use of the isopropylide anion as a model for the
sulfur ylide, neglecting the solvent effect), the results ob- Kieselgel 60254). Column chromatography was performed using
Merck silica gel (70Ϫ230 mesh).
tained are in very good agreement with the experimental
observations. First of all, the crystalline state and gas phase
conformations of 1-phosphorylvinyl sulfoxides were found
to be almost identical. In both conformations there are two
sterically different diastereotopic faces, the less hindered be-
(S)-(؉)-1-Diethoxyphosphoryl-1-(p-tolylsulfinyl)cyclopropane (4):
To a solution of DMSO (2 mL) and THF (5 mL) was added NaH
(48 mg, 2 mmol) and the mixture was heated for 30 min at 70 °C.
After this time, it was cooled to 0 °C and trimethyl(oxo)sulfonium
ing occupied by the lone pairs of electrons on the sulfur iodide (240 mg, 1.2 mmol) was added. The reaction mixture was
stirred for 10 min at 0 °C and sulfoxide (S)-(ϩ)-1a (300 mg,1 mmol)
dissolved in THF (5 mL) was then added. After stirring at room
temperature for 3 h, the reaction mixture was quenched with an
aqueous solution of ammonium chloride (10 mL), extracted with
CHCl3 (2 ϫ 20 mL) and the CHCl3 solution was dried with anhy-
drous MgSO4. The solvents were removed under vacuum (30 °C/
0.05 Torr). The crude product was purified by column chromatog-
raphy (petroleum ether/acetone, 10:1, Rf ϭ 0.37) and isolated as a
colourless oil (285 mg) in 90% yield. [α]2D0 ϭ ϩ51 (c ϭ 0.22 in ace-
atom and the phosphoryl oxygen atom. Then, the role of
hydrogen bonding in stabilising the syncoplanar arrange-
ment of the carbonϪcarbon double bond and sulfinyl
group was confirmed. Moreover, the calculations revealed
that steric and not thermodynamic factors are responsible
for the observed stereoselectivity of the cyclopropanation
reaction. If we make the very reasonable assumption that
the conformation of 1-phosphorylvinyl sulfoxide in solution
is the same as that in the solid-state and in the gas phase,
tone). 31P NMR (81 MHz, CDCl3): δ ϭ 22.3 ppm. 1H NMR
3
all these observations may then be explained in terms of (500 MHz, C6D6): δ ϭ 0.86 (t, JH,H ϭ 7.1 Hz, 3 H, CH3CH2O),
0.95 (t, 3JH,H ϭ 7.1 Hz, 3 H, CH3CH2O), 1.17Ϫ1.35 (m, 2 H, CH2),
the transition state model of the cyclopropanation reaction
shown below (Scheme 6) where steric approach control is a
decisive factor. Hence, the approach of a sulfur ylide to the
carbonϪcarbon double bond in (S)-(ϩ)-1a takes place pref-
erentially or exclusively from the less hindered dia-
stereotopic face occupied by the lone pairs of electrons on
1.40Ϫ1.69 (m, 2 H, CH2), 1.98 (s, 3 H, CH3Ph), 3.61-3.74 (m, 1 H,
CH2O), 3.75Ϫ3.83 (m, 3 H, CH2O), 6.89 and 7.65 ppm (A2B2, 4
H, aromatic). IR (film): ν˜ ϭ 2982, 2960, 1260, 1230, 1042, 1023
cmϪ1. C14H21O4PS (316.3): calcd. C 53.11, H 6.63, P 9.80, S 10.12;
found C 53.24, H 6.72, P 9.68, S 9.98.
(S)-(؉)-2,2,2-Trideuterio-1-(diethoxyphosphoryl)ethyl p-Tolyl Sul-
foxide (6): To a solution of sulfoxide (S)-(ϩ)-5 (1.06 g, 4 mmol)
in THF (20 mL) was added a solution of n-butyllithium (1.8 mL,
4.2 mmol) in hexane at Ϫ78 °C. The reaction mixture was stirred
at this temperature for 10 min and a solution of trideuteriomethyl
iodide (0.86 g, 6 mmol) in THF (5 mL) was then added. The mix-
ture was warmed slowly to room temperature and quenched with
aqueous ammonium chloride. The aqueous layer was extracted
with CHCl3 (3 ϫ 10 mL). The chloroform solution was dried with
anhydrous MgSO4 and the solvents were evaporated to give the
crude product which was purified by chromatography (hexane/ace-
tone, 2:1) and isolated as a pale yellow oil (0.91 g) in 74% yield.
[α]2D0 ϭ ϩ49 (c ϭ 0.21 in acetone). 31P NMR (81 MHz, CDCl3):
the sulfur atom and the phosphoryl oxygen atom (top-face
attack). The bottom-face attack of a sulfur ylide is much
less probable due to steric hindrance exerted by the p-tolyl
function and the two alkoxy groups.
1
δ ϭ 21.9 and 23.5 ppm (1:3 ratio). H NMR (200 MHz, CDCl3):
3
3
δ ϭ 1.28 (t, JH,H ϭ 7.1 Hz, 3 H, CH3CH2O), 1.31 (t, JH,H
ϭ
2
7.1 Hz, 3 H, CH3CH2O), 2.39 (s, 3 H, CH3Ph), 2.86 (d, JH,P
ϭ
17.7 Hz, 1 H, CH), 4.00Ϫ4.25 (m, 4 H, CH2O), 7.29Ϫ7.55 ppm
(m, 4 H, aromatic) ppm. 13C NMR (50 MHz, CDCl3): δ ϭ 15.7 (d,
1JC,P ϭ 5.7 Hz), 22.3, 56.7, 59.6, 63.6, 125.2, 129.9, 130.9,
142.5 ppm. HRMS (EI): calcd. for C13H18D3O4PS: 307.10929;
found 307.10865.
Scheme 6. The preferred steric course of the reaction of (S)-(ϩ)-1a
with sulfur ylides
Based on this model it is possible to assign the absolute
configuration to the cyclopropanes 4a-d2, 4b-d2 and 7 ob-
tained in the context of this work as (1S,SS), (1R,SS) and
(1S,SS), respectively.
(S)-(؉)-2,2-Dideuterio-1-(diethoxyphosphoryl)vinyl p-Tolyl Sulfox-
ide (1a-d2): To a stirred THF solution (15 mL) of sulfoxide (ϩ)-6
(0.91 g, 3 mmol) was added
a solution of nBuLi (1.45 mL,
3.3 mmol) at Ϫ78 °C. After 5 min, a solution of phenylselenenyl
bromide (3 mmol), prepared by addition of an equimolar amount
of bromine to a solution of diphenyl diselenide in THF (5 mL),
was added at once. The reaction mixture was stirred for 2Ϫ3 min
and then poured into a 1:1 mixture (15 mL) of diethyl ether and
Experimental Section
General Remarks: NMR spectra were recorded with Bruker instru-
ments at 200 MHz and 500 MHz for 1H, 81 MHz for 31P and aqueous solution of sodium carbonate at 0 °C. The organic layer
1
50.3 MHz for 13C. H and 13C chemical shifts are reported in ppm
was separated, dried with anhydrous MgSO4 and the solvent evapo-
rated. The residue was dissolved in CH2Cl2 (5 mL) and treated with
relative to Me4Si as an external standard. 31P NMR downfield
Eur. J. Org. Chem. 2005, 653Ϫ662
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© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
659

M. Mikołajczyk et al.
FULL PAPER
a solution of H2O2 and water (1:1 mixture, 3 mL). The reaction
mixture was stirred for 30 min and the solvents were evaporated.
The crude sulfoxide 1a-d2 was then purified by column chromatog-
C14H19D2O4PS: 319.1102; found 319.1103. 4b-d2: 1H NMR
(500 MHz, C6D6): δ 0.86 (t, 3JH,H ϭ 7.1 Hz, 3 H, CH3CH2O), 0.95
(t, 3JH,H ϭ 7.1 Hz, 3 H, CH3CH2O), 1.43 (dd, 2JH,H ϭ 4.3, 3JH,P ϭ
2
3
raphy and isolated as a pale yellow oil (0.79 g) in 87% yield. [α]2D0
ϭ
15.1 Hz, 1 H, CH2), 1.65 (dd, JH,H ϭ 4.3, JH,P ϭ 8.8 Hz, 1 H,
ϩ148 (c ϭ 2.0 in acetone). 31P NMR (81 MHz, CDCl3): δ ϭ CH2), 1.96 (s, 3 H, CH3Ph), 3.61-3.68 (m, 1 H, CH2O), 3.77Ϫ3.85
9.9 ppm. 1H NMR (200 MHz, CDCl3): δ ϭ 1.21 (t, 3JH,H ϭ 7.1 Hz, (m, 3 H, CH2O), 6.88 and 7.69 ppm (A2B2, 4 H, aromatic).
6 H, CH3CH2O), 2.40 (s, 3 H, CH3Ph), 3.81Ϫ4.11 (m, 4 H, CH2O),
(؉)-1-Diethoxyphosphoryl-2,2-dimethyl-1-(p-tolylsulfinyl)cyclo-
7.32Ϫ7.59 (m, 4 H, aromatic) ppm. 13C NMR (50 MHz, CDCl3):
propane (7): To a stirred solution of ethyldiphenylsulfonium tetra-
1
2
δ ϭ 15.7 (d, JC,P ϭ 7.9 Hz), 21.2, 63.1 (d, JC,P ϭ 5.1 Hz), 126.2,
129.3, 132.1, 138.64, 142.2 ppm. C13H17D2O4PS (304.3): calcd. C
51.31, H 6.95; found C 51.36, H 6.73.
fluoroborate (484 mg 1.7 mmol) [prepared by addition of diphenyl
sulfide to an equimolar amount of triethyloxonium tetrafluorobo-
rate in dichloromethane, room temp., 24 h] in dry dichloromethane
(0.165 mL, 1.7 mmol) and freshly distilled DME (15 mL) was ad-
Cyclopropanation Reaction of (S)-(؉)-1a with (CD3)2S(O)CD2: So-
dium hydride (16 mg) was added to a solution of [D6]DMSO ded LDA (1.8 mmol) under argon at Ϫ78 °C. The mixture was
(1 mL) and THF (2 mL). The mixture was heated at 70 °C for stirred at Ϫ78 °C for 30 min and methyl iodide (passed through
30 min, then cooled to 0 °C and deuterated trimethylsulfoxonium
iodide (80 mg, 4 mmol) [prepared by addition of CD3I to
(CD3)2SO] was added. After stirring at 0 °C for 10 min, sulfoxide
basic alumina immediately prior to use) (0.115 mL, 1.7 mmol) was
added. This caused the yellow-green colour to fade and formation
of a colourless precipitate after 5 min. After stirring between Ϫ70
(S)-(ϩ)-1a (0.1 g 0.33 mmol) dissolved in THF (2 mL) was added. and Ϫ50 °C for 2 h, an additional amount of LDA (1.8 mmol) was
The reaction mixture was stirred at room temperature for 3 h and
then quenched with aqueous ammonium chloride solution (3 mL).
The organic layer was extracted with CHCl3 (3 ϫ 5 mL) and dried
added. The bright orange-coloured solution was stirred at Ϫ70 °C
for 1.5 h and sulfoxide (S)-(ϩ)-1a (270 mg 0.9 mmol) was added in
DME (2 mL). The solution was stirred between Ϫ70 and Ϫ20 °C
with MgSO4. The solvent was removed under vacuum and the for 3 h. The colourless mixture was quenched with aqueous
crude product purified by column chromatography (hexane/acetone
saturated ammonium chloride (10 mL), allowed to warm to ambi-
10:1) to give the cyclopropane 4a-d2 (90%) contaminated with 4b-
ent temperature and extracted with diethyl ether (3 ϫ 15 mL). The
d2, 4-d1 and 4 (ca. 10%) (96 mg) in 92% yield. [α]2D0 ϭ ϩ49 (c ϭ organic layer was dried with anhydrous MgSO4 and the solvent
0.21 in acetone). 31P NMR (81 MHz, CDCl3): δ ϭ 22.3 ppm; 4a-
evaporated. Purification by column chromatography (hexane/ace-
1
3
d2: H NMR (500 MHz, C6D6): δ ϭ 0.86 (t, JH,H ϭ 7.1 Hz, 3 H, tone, 12:1; Rf ϭ 0.34) gave the cyclopropane 7 (200 mg) as a colour-
CH3CH2O), 0.95 (t, JH,H ϭ 7.1 Hz, 3 H, CH3CH2O), 1.18 (dd, less oil in 65% yield; [α]2D0 ϭ ϩ22.0 (c ϭ 0.19 in acetone). 31P NMR
3
2JH,H ϭ 4.9, JH,P ϭ 14.0 Hz, 1 H, CH2), 1.30 (dd, JH,H ϭ 4.9, (81 MHz, CDCl3): δ ϭ 21.6 ppm. 1H NMR (200 MHz, CDCl3):
3
2
3JH,P ϭ 9.9 Hz, 1 H, CH2), 1.98 (s, 3 H, CH3Ph), 3.61Ϫ3.74 (m, 1 δ ϭ 0.84 and 1.34 (2 ϫ t, JH,H ϭ 7.0 Hz, 6 H, CH3CH2O), 1.48
3
2
3
H, CH2O), 3.75-3.83 (m, 3 H, CH2O), 6.89 and 7.65 ppm (A2B2, 4
H, aromatic) ppm. HRMS (CI) [M ϩ H]ϩ: calcd. for C14H19
D2O4PS: 319.1102; found 319.1106.
(s, 3 H, CH3), 1.63 (s, 3 H, CH3), 1.77 (dd, JH,H ϭ 5.6, JH,P ϭ
2
3
8.9 Hz, 1 H, CH2), 1.99 (dd, JH,H ϭ 5.6, JH,P ϭ 16.3 Hz, 1 H,
CH2), 2.42 (s, 3 H, CH3Ph), 3.40Ϫ3.68 (m, 2 H, CH2O), 4.15 (m,
2 H, CH2O), 7.28 and 7.47 ppm (A2B2, JH,H ϭ 8.0 Hz, 4 H, aro-
3
Oxidation to the Sulfone: The cyclopropane prepared as above
(100 mg, 0.33 mmol) was dissolved in CH2Cl2 (10 mL) and m-chlo-
roperbenzoic acid (156 mg, 1 mmol) was added. The mixture was
stirred vigorously for 6 h. It was then washed with a saturated
aqueous solution of sodium carbonate (2 ϫ 10 mL), the solvent
evaporated and the crude product purified by column chromatog-
raphy (hexane/acetone, 10:1, Rf ϭ 0.42) giving the sulfone (100 mg)
matic). 13C NMR (50 MHz, CDCl3): δ ϭ 15.5, 16.1, 21.3, 22.6,
24.4, 27.2, 28.6, 61.1, 63.6, 125.2, 128.9, 138.9, 140.4 ppm. IR
(neat): ν˜ ϭ 2980, 2926 (CH3), 1260 (OCH3), 1160 (PϭO), 1026
cmϪ1 (SϭO). HRMS(CI) [M ϩ H]ϩ: calcd. for C16H26O4PS:
345.12869; found 345.1276.
(؉)-1-Diethoxyphosphoryl-2,2-dimethyl-1-(p-tolylsulfonyl)cyclo-
propane (8): Cyclopropane 7 (150 mg, 0.4 mmol) was oxidised with
m-chloroperbenzoic acid (180 mg, 1 mmol) in CH2Cl2 solution
as a colourless oil in 97% yield. 31P NMR (81 MHz, CDCl3): δ ϭ
3
18.5 ppm. 1H NMR (500 MHz, CDCl3): δ ϭ 1.18 (t, JH,H
ϭ
7.1 Hz, 6 H, CH3CH2O), 1.51Ϫ1.64 (m, 2 H, CH2), 1.75Ϫ1.85 (m, (5 mL) in the same way as described above. Purification by column
2 H, CH2), 2.44 (s, 3 H, CH3Ph), 3.96Ϫ4.08 (q, 4 H, CH2O), 7.26, chromatography (hexane/acetone, 12:1; Rf ϭ 0.38) gave the sulfone
7.75 ppm (A2B2, 4 H, aromatic). C14H19D2O5PS (334.36): calcd. C 8 (150 mg) as a colourless oil in 96% yield. [α]2D0 ϭ ϩ8.5 (c ϭ 0.19
50.24, H 6.88, P 9.27, S 9.57; found C 50.21, H 7.08, P 9.39, S 9.37.
in acetone). 31P NMR (81 MHz, CDCl3): δ ϭ 18.9 ppm. 1H NMR
(200 MHz, CDCl3): δ ϭ 1.53 (s, 3 H, CH3), 1.68 (s, 3 H, CH3), 1.98
(dd, 2JH,H ϭ 5.3, 3JH,P ϭ 16.3 Hz, 1 H, CH2), 2.08 (dd, 2JH,H ϭ 5.3,
3JH,P ϭ 9.5 Hz, 1 H, CH2), 2.43 (s, 3 H, CH3Ph), 3.40Ϫ3.68 (m, 2
H, CH2O), 4.15 (m, 2 H, CH2O), 7.30 and 7.52 ppm (A2B2,
3JH,H ϭ 8.2 Hz, 4 H, aromatic). 13C NMR (50 MHz, CDCl3): δ ϭ
Cyclopropanation Reaction of (S)-(؉)-1a-d2 with (CH3)2S(O)CH2:
To a solution of [D6]DMSO (2 mL) and THF (5 mL) was added
NaH (48 mg, 2 mmol) and the mixture was heated at 70 °C for
30 min. After this time, the mixture was cooled to 0 °C and trimeth-
ylsulfoxonium iodide (240 mg 12 mmol) was added. After stirring
at 0 °C for 10 min, sulfoxide (S)-(ϩ)-1a-d2 (300 mg, 1 mmol) dis-
solved in THF (5 mL) was added. The reaction mixture was kept
at room temperature for 3 h and was then quenched with aqueous
ammonium chloride solution (10 mL). The water layer was ex-
1
14.1, 16.3 (d, JC,P ϭ 5.2 Hz), 21.6, 22.6, 24.4, 29.6, 30.9, 63.39 (d,
2JC,P ϭ 7.8 Hz), 128.9, 131.0, 136.7, 140.4 ppm. C16H25O5PS
(360.4): calcd. C 53.32, H 6.94, P 8.60, S 8.79; found C 53.28, H
6.69, P 8.61, S 9.18.
tracted with CHCl3 (3 ϫ 10 mL). The chloroform extract was dried (؎)-1-(Diphenylphosphinoyl)vinyl p-Tolyl Sulfoxide (9): To a solu-
with anhydrous MgSO4 and the solvents were evaporated under
vacuum (30 °C/0.05 Torr) The crude product was purified by col-
umn chromatography (petroleum ether/acetone, 10:1; Rf ϭ 0.37)
affording a mixture of 4b-d2 and 4a-d2 (91:9) as a colourless oil
(286 mg) in 90% yield. [α]2D0 ϭ ϩ52 (c ϭ 0.19 in acetone). 31P NMR
tion of paraformaldehyde (0.9 g, 15 mmol) in benzene (20 mL) was
added piperidine (0.42 g, 5 mmol). The reaction mixture was heated
to reflux for 3 h. Sulfoxide 10 (0.36 g, 6 mmol) and acetic acid were
then added. The reaction mixture was kept at 30Ϫ40 °C for 48 h.
After evaporation of the solvents, the residue was washed with di-
(81 MHz, CDCl3): δ 22.3 ppm. HRMS (CI) [M ϩ H]ϩ: calcd. for ethyl ether (3 ϫ 20 mL). The crude sulfoxide 9, in the form of a
660 © 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim www.eurjoc.org
Eur. J. Org. Chem. 2005, 653Ϫ662

Asymmetric Cyclopropanation of an Optically Active Sulfoxide with Sulfur Ylides
FULL PAPER
yellow oil, was purified by column chromatography (hexane/ace-
tone, 1:3) and crystallised from diethyl ether to give white crystals
of 9 (1.09 g) in 60% yield. For X-ray analysis 9 was recrystallised
The structure solution was carried out with SHELXS[23] and the
structure refinement with SHELXL.[24] CCDC-229638 contains the
supplementary crystallographic data for this paper. These data can
from benzene, m.p. 156Ϫ158 °C. 31P NMR (81 MHz, CDCl3): δ ϭ be obtained free of charge from The Cambridge Crystallographic
24.7 ppm. 1H NMR (200 MHz, CDCl3): δ ϭ 2.23 (s, 3 H, CH3Ph),
Data Centre via www.ccdc.cam.ac.uk/data request/cif.
2
3
6.16 (dd, 1 H, JH,H ϭ 0.6, JH,P ϭ 16.1 Hz; CH2), 7.03 (dd, 1 H,
Computational Method: For the DFT calculations, Becke’s three
parameter hybrid functional (B3)[25] together with the correlation
functional of Lee, Yang and Parr (LYP)[26] with the 6-31G* basis
set were employed. All calculations were performed for the gas
phase conditions using the Gaussian 98 package.[27] Equilibrium
geometries of model compounds were found at the B3LYP/6-31G*
level. Stationary points were confirmed by frequency calculations.
Vibrational components of the thermal energy were scaled by 0.98.
All enthalpy and Gibbs free energy values were corrected to 298 K.
Final single-point energies were calculated at the B3LYP/6-
311ϩG(2d,p) level for the B3LYP/6-31G* geometries. Orbital
populations, atomic charges and Wiberg bond indices were calcu-
lated with the NBO 3.0 program included in the Gaussian package
using the HF/6-31G* method.[28] The energies of orbital interac-
tions were calculated as the difference between the electronic en-
ergy, regarding a full orbital interaction pattern, and the energy for
the molecular system with deletion of the Fock matrix elements
corresponding to the particular interaction.[28]
2JH,H ϭ 0.6, JH,P ϭ 35.1 Hz; CH2), 6.96 and 7.42 (A2B2, JH,H
ϭ
3
3
12.4 Hz, 4 H, Tol), 7.20Ϫ7.53 (m, 10 H, Ph) ppm. 13C NMR
(50 MHz, CDCl3): δ ϭ 21.3, 126.0, 128, 128.2, 128.5, 128.7, 129.4,
1
131.0, 131.3, 131.4, 132.5, 138.3, 152.1 (d, JC,P ϭ 86.4 Hz) ppm.
C21H19O2PS (366.4): calcd. C 68.78, H 5.19, P 8.46, S 8.73; found
C 68.99, H 5.14, P 8.38, S 8.90.
Crystal Structure Determination: The crystal and molecular struc-
tures of the sulfoxide 9 were determined using data collected at low
temperature on
a KUMA (Oxford Instruments KM4) dif-
fractometer[22] with graphite-monochromated Mo-Kα radiation.
Compound 9 crystallises in the monoclinic system, space group
P21/c, with the unit cell consisting of 4 molecules. Crystal data and
experimental details are shown in Table 2. The lattice constants
were refined by a least-squares fit of 5841 reflections in the θ range
3.68Ϫ35.60°. A total of 5809 independent reflections with I Ͼ 0
were used to solve the structure by direct methods and to refine it
by full-matrix least-squares using F2.[23,24] Hydrogen atoms were
found from a difference Fourier map and refined isotropically. An-
isotropic thermal parameters were refined for all nonhydrogen
atoms. The final refinement converged to R ϭ 0.0541 for 302 re-
fined parameters and 5032 observed reflections with I Ն 2σ(I).
Data processing was carried out with the KM4CCD software.[22]
Acknowledgments
Thanks are due to the State Committee for Scientific Research
(KBN) for financial support of this work.
Table 2. Crystal data for 9 and experimental details
[1]
Empirical formula
Formula mass
Crystal stem
C21H19O2PS
366.39
monoclinic
M. C. Carren˜o, Chem. Rev. 1995, 95, 1717Ϫ1760.
[2]
M. Mikołajczyk, J. Drabowicz, P. Kielbasinski, Chiral Sulfur
Reagents: Applications in Asymmetric and Stereoselective Syn-
Space group
P21/c
19.348(4)
8.839(3)
11.080(3)
103.18(3)
1845.0(9)
4
1.319
0.273
0.60 ϫ 0.60 ϫ 0.15
71.20
Mo-Kα, 0.71073
ω
Ϫ25 to 24, Ϫ14to 11, Ϫ17 to 14
5841
5809
5032
302
0.584
Ϫ0.648
0.001
0.0541
0.1261
1.082
thesis, CRC Press, Boca Raton, New York, 1997.
[3]
˚
´
a (A)
I. Fernandez, N. Khiar, Chem. Rev. 2003, 103, 3651Ϫ3705.
[4]
˚
´
b (A)
For a recent paper dealing with this problem see: M. Ordon˜ez,
˚
c (A)
V. Guerrero de la Rosa, F. Alcudia, J. M. Llera, Tetrahedron
2004, 60, 871Ϫ875 and references cited therein.
β (°)
3
[5]
[6]
˚
´
V (A )
Z
J. L. Garcıa Ruano, B. Cid, Topics in Current Chemistry (Ed.:
P. C. B. Page), Springer, Berlin, 1999, vol. 204, pp. 1Ϫ126.
Dc (g/cm3)
F. Brebion, B. Delouvrie, F. Najera, L. Fensterbank, M. Mal-
´
µ (mmϪ1
)
acria, J. Vaissermann, Angew. Chem. 2003, 115, 5500Ϫ5503;
Angew. Chem. Int. Ed. 2003, 42, 5342Ϫ5345.
W. H. Midura, M. Mikołajczyk, Tetrahedron: Asymmetry 1992,
3, 1515Ϫ1518.
W. H. Midura, J. A. Krysiak, Tetrahedron, 2004, 60,
12217Ϫ12229.
For a preliminary communication of this work see: W. H. Mid-
ura, J. A. Krysiak, M. W. Wieczorek, W. R. Majzner, M. Mi-
kołajczyk, Chem. Commun. 1998, 1109Ϫ1110.
See also: W. H. Midura, J. A. Krysiak, M. Mikołajczyk, Tetra-
hedron 1999, 55, 14791Ϫ14802.
H.-U. Reissig in Organic Synthesis Highlights III (Eds.: J.
Mulzer, H. Waldmann), Wiley-VCH, Weinheim 1998, pp.
35Ϫ39; W. A. Donaldson, Tetrahedron 2001, 57, 8589Ϫ8627;
H. Lebel, J.-F. Marcoux, C. Molinaro, A. B. Charette, Chem.
Rev. 2003, 103, 977Ϫ1050.
C. Hamdouchi, Tetrahedron Lett. 1992, 33, 1701Ϫ1704.
T. Imanishi, T. Ohara, K. Sugiyama, Y. Ueda, Y. Takemoto, C.
Iwata, J. Chem. Soc. Chem. Commun. 1992, 296Ϫ297.
W. H. Midura, J. A. Krysiak, M. Mikołajczyk, Tetrahedron:
Asymmetry 2003, 14, 1245Ϫ1249.
Crystal dimensions (mm)
Maximum 2θ (°)
Radiation, λ (A)
Scan mode
hkl ranges
No. of runique eflections
With I Ͼ 0σ(I)
Obsd. with I Ͼ 2σ(I)
No. of parameters refined
Largest diff. peak (e·A
Largest diff. hole (e·A
Shift/esd. max.
Robsd.
wRobsd.
[7]
[8]
[9]
˚
[10]
[11]
Ϫ3
˚
˚
)
Ϫ3
)
Sobsd.
Weighting coeff.[a]
m, n
0.0513, 1.9768
[12]
[13]
Rint
Tmeasd.
F(000)
0.0553
100(2)
768
[14]
[15]
[16]
W. H. Midura, M. Mikołajczyk, Tetrahedron Lett. 2002, 43,
3061Ϫ3065.
E. Fischer, F. Brauns, Ber. Dtsch. Chem. Ges. 1914, 47, 3181.
[a]
2
Weighting scheme w ϭ [σ2(Fo ) ϩ (mP)2 ϩ nP]Ϫ1 where P ϭ
2
2
(Fo ϩ 2Fc )/3.
Eur. J. Org. Chem. 2005, 653Ϫ662
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
661

M. Mikołajczyk et al.
FULL PAPER
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[26]
[27]
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lam, A. D. Daniels, K. N. Kudin, M. C. Strain, O. Farkas, J.
Tomasi, V. Barone, M. Cossi, R. Cammi, B. Mennucci, C. Po-
melli, C. Adamo, S. Clifford, J. Ochterski, G. A. Petersson, P.
Y. Ayala, Q. Cui, K. Morokuma, N. Rega, P. Salvador, J. J.
Dannenberg, D. K. Malick, A. D. Rabuck, K. Raghavachari,
J. B. Foresman, J. Cioslowski, J. V. Ortiz, A. G. Baboul, B. B.
Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R.
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Early View Article
Published Online December 14, 2004
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662
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