C2-symmetric fluorous diamines and diimines as ligands for metal-catalysed asymmetric cyclopropanation of styrene

Article abstract of DOI:10.1002/ejoc.200400436

Perfluoroalkyl-substituted, enantiopure C₂-symmetric N and N,O ligands showing affinity either for standard organic solvents or perfluorocarbons have been conveniently prepared from readily available precursors. Preformed cobalt(II) and in-situ-generated copper(I) complexes of these ligands were tested as catalysts in the metal-catalysed cyclopropanation of styrene with diazoacetates. Under optimised reaction conditions, which include the use of a fluorous biphasic system and short reaction times, the copper complex of a C₂-symmetric diamine afforded promising results (yield = 77%, trans/cis = 67:33, ee of the trans isomer = 62%) and could be easily separated from the products by simply decanting the fluorous phase. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.

Full text of DOI:10.1002/ejoc.200400436

FULL PAPER
C -Symmetric Fluorous Diamines and Diimines as Ligands for Metal-
2
Catalysed Asymmetric Cyclopropanation of Styrene
[a]
[a]
[a]
[b]
Ian Shepperson, Silvio Quici, Gianluca Pozzi,* Marcello Nicoletti, and
David O’Hagan*[
b]
Keywords: Asymmetric catalysis / Biphasic catalysis / Cobalt / Copper / N ligands
Perfluoroalkyl-substituted, enantiopure C
2
-symmetric N and
2
and short reaction times, the copper complex of a C -sym-
N,O ligands showing affinity either for standard organic solv-
ents or perfluorocarbons have been conveniently prepared
from readily available precursors. Preformed cobalt(II) and
metric diamine afforded promising results (yield = 77%,
trans/cis = 67:33, ee of the trans isomer = 62%) and could be
easily separated from the products by simply decanting the
fluorous phase.
in-situ-generated copper(I) complexes of these ligands were
tested as catalysts in the metal-catalysed cyclopropanation of
styrene with diazoacetates. Under optimised reaction condi-
tions, which include the use of a fluorous biphasic system
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2004)
Introduction
the catalyst after the cyclopropanation reaction and to re-
use it. To this end bis(oxazolines) (and other ligands) have
been attached to heterogeneous inorganic and organic sup-
ports to allow filtration and the facile recovery of the cata-
Asymmetric cyclopropanation was the first example of
the use of a chiral metal complex to catalyse the conversion
of a prochiral substrate into a chiral product with an excess
of one enantiomer.[1] Since then much research has been
carried out in order to gain a better understanding of the
mechanism of cyclopropanation in which a diazoacetate de-
composes to generate a metal carbenoid, which in turn is
inserted into the double bond of an olefin.[ At the same
time various metals and ligands have been tested in an ef-
fort to improve the trans/cis selectivity and the enantioselec-
tivity of the reaction.[ At present, some of the best systems
for asymmetric cyclopropanation use C -symmetric bis(ox-
azoline) ligands with Cu metal complexes.
gands give high enantioselectivities, up to 99% ee for the
trans isomer and 97% ee for the cis isomer using ethyl di-
azoacetate. The trans/cis selectivity depends heavily on the
diazoacetate used but varies between 66:34 and 94:6. How-
[9]
lyst after the reaction. However, while the selectivities of
such supported catalysts are equal to those of their homo-
geneous equivalents, their activities are generally lower.
Moreover, although this approach ensures the successful
separation of the catalyst from reaction products, recycling
2]
[10]
of the recovered catalysts is much less effective. A soluble
support such as PEG can be used so that the reaction can
be run under homogeneous conditions and therefore give
similar activities to those of unsupported catalysts. Once
the reaction is complete the PEG-supported catalyst can be
precipitated out, filtered and reused. Depending on the
3]
2
I
[4Ϫ6]
These li-
linker between the bis((oxazoline) and the PEG the catalyst
[11]
can be recycled up to 13 times.
Compared with these
now well-established methods, the application of fluorous
[12Ϫ14]
immobilisation and separation techniques
to metal-
ever bis(oxazolines) are not the only C -symmetric chiral
ligand that can be used for cyclopropanation: other ligands
2
catalysed asymmetric cyclopropanation is much less devel-
I
oped. The only reported example concerns the Cu -pro-
[7]
such as chiral binaphthyldiimines and bis(ferrocenyl)di-
moted cyclopropanation of styrene in the presence of chiral
[
8]
amines have been tested. Both the diimines and especially
the diamines give good enantioselectivities (up to 96% ee) and
trans/cis selectivities (up to 90:10) using ethyl diazoacetate.
Whichever chiral complex is used, they are difficult and
expensive to make, so it is desirable to be able to separate
[15]
fluorous bis(oxazoline) (F-box) ligands.
Good selectivit-
ies and activities were observed, but attempts to recycle the
active metal complex were foiled by decomposition prod-
ucts of the diazoacetates inhibiting the catalyst. Therefore,
our interest moved towards the use of alternative C -sym-
2
[
a]
metric fluorous N and N,O ligands.
CNR-Istituto di Scienze e Tecnologie Molecolari,
Via Golgi 19, 20133 Milano, Italy
Fax: (internat.) ϩ 39-02-503-14159
E-mail: gianluca.pozzi@istm.cnr.it
[
b]
Results and Discussion
School of Chemistry and Centre for Biomolecular Sciences,
University of St Andrews,
North Haugh, St Andrews, Fife, KY16 9ST, UK
Fax: (internat.) ϩ 44-1334-463808
Synthesis of Fluorous Chiral Nitrogen Ligands: In the last
few years, we have developed several heavy-fluorous (F con-
E-mail: do1@st-andrews.ac.uk
Eur. J. Org. Chem. 2004, 4545Ϫ4551
DOI: 10.1002/ejoc.200400436
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4545

I. Shepperson, S. Quici, G. Pozzi, M. Nicoletti, D. O’Hagan
FULL PAPER
Figure 1. Ligands tested in the asymmetric cyclopropanation of styrene
tent Ͼ 60%) C -symmetric bi- and tetradentate N and N,O
2
ligands which have been successfully used in catalytic asym-
metric reactions such as the epoxidation of alkenes and the
[
16]
enantioselective hydrogen transfer reduction of ketones.
Most of these ligands are derivatives of commercially avail-
able, enantiomerically pure trans-1,2-diaminocyclohexane
and can be prepared on a multigram scale by straightfor-
ward condensation of the chiral diamine with fluorous benz-
aldehydes, followed by reduction of the imino functionali-
[17]
ties when required. Salen ligand 1, diimine 6 and diamine
[
18]
8
(Figure 1) were selected from this set of compounds for
this study. Two new light-fluorous (F content Ͻ 60%) C2-
symmetric diamines, (S,S)-10 and (R,R)-11 (Figure 1), were
also studied as they can be readily prepared from the en-
antiomers of the inexpensive chiral building block 1-pheny-
lethylamine 12 (Scheme 1).
Perfluoroalkyl iodides 13 and 14 were reacted with (S)-
1
2 and (R)-12, respectively, in the presence of K CO as
2 3
a base. Under these conditions, the enantiomerically pure
primary amine was selectively N-alkylated to afford the chi-
ral secondary amines (S)-15 (yield ϭ 55%) and (R)-16
(yield ϭ 70%), respectively, as the only products. A partial
loss of the perfluoroalkyl iodide 13 occurred due to HI
elimination, which accounts for the lower yield of (S)-15.
This side reaction did not occur with iodide 14, which has
an extra methylene spacer inserted between the perfluoro-
alkyl chain and the iodine atom. Indeed, unchanged 14
Scheme 1. Synthesis of diamines (S,S)-10 and (R,R)-11
could be recovered from the product mixture at the end of LAH in THF at 0 °C. In the event (S,S)-10 was recovered
the reaction. Ethanediamides (S,S)-17 (yield ϭ 53%) and in a moderate yield (56%), however the reduction of (R,R)-
(R,R)-18 (yield ϭ 67%) were obtained by the reaction of 18 was accompanied by product degradation and diamine
two molar equivalents of (S)-15 and (R)-16, respectively, (R,R)-11 was obtained in only 15% yield. Attempts at using
with oxalyl chloride. These intermediates were reduced to milder reducing agents such as NaBH and BH ·THF failed
4
3
the corresponding diamines (S,S)-10 and (R,R)-11 using to improve this.
4546
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 4545Ϫ4551

Metal-Catalysed Asymmetric Cyclopropanation of Styrene
As expected on the basis of the relatively low fluorine
FULL PAPER
The CoII complexes of ligands 2Ϫ5, which bear either
content, both (S,S)-10 and (R,R)-11 are readily soluble in electron-withdrawing or -donating substituents at the C5
non-fluorinated solvents and show similarly low partition and C5Ј positions, were also examined to better assess the
coefficients P between perfluorocarbons and organic sol- role of the perfluoroalkyl substituents. As shown in Table 1,
vents [e.g. P ϭ 1 in C F /dichloromethane (50:50, v/v)].
these catalysts exhibited only minor variations relative to
8
18
II
Catalytic Activity of Co Complexes: Enantiomerically CoϪ1. Complex CoϪ2 (Entry 2) with strong electron-with-
pure metallosalen complexes are among the most widely drawing nitro groups behaved like CoϪ1 with no trans/cis
investigated chiral catalysts in asymmetric synthesis. Kat- selectivity. Enhancing the electron-donor character of the
suki and co-workers have recently demonstrated that cyclo- substituents at C5 and C5Ј slightly increased both reaction
propanation of styrene with α-diazoacetates (Scheme 2) yields and transϪcis selectivities (Entries 3Ϫ5), which, how-
proceeds with moderate-to-high diastereo- and enantiose- ever, remained low. The stereoelectronic characteristics of
II
[19]
lectivity in the presence of Co Ϫsalen complexes.
Such the C5 and C5Ј substituents have little influence on the en-
II
a reaction was attempted using the Co complex of salen 1 antioselectivity of the reaction: with all the catalysts tested,
(CoϪ1), an effective fluorous catalyst for the asymmetric (1R,2R)-21a was obtained as the major trans-enantiomer
hydrolytic kinetic resolution (HKR) of terminal epox- with ee’s in the range of 60Ϫ67%.
[
20]
ides.
The reaction of styrene with ethyl α-diazoacetate
It was concluded that the low diastereoselectivity and re-
19a proceeded slowly in the presence of CoϪ1 and N-meth- action yield observed with CoϪ1 cannot be ascribed to the
ylimidazole in THF, affording a 1:1 mixture of cis- and presence of perfluoroalkyl substituents at the C5 and C5Ј
trans-cyclopropanes 20a/21a with moderate enantioselectiv- positions of the ligand. These preliminary experiments con-
II
ity (Table 1, Entry 1). These results are comparable to those vinced us that fluorous Co Ϫsalen complexes are poten-
II
obtained with most Co Ϫsalen complexes tested in the lit- tially useful catalysts for cyclopropanation reactions, but
erature under the same conditions.[
19]
critical modifications to the ligand design are required to
obtain catalytic activities comparable to those of Cu com-
I
plexes of chiral fluorous bis(oxazoline) ligands.
I
Catalytic Activity of Cu Complexes: Catalytic systems
based on combinations of bidentate chiral nitrogen ligands
I
and Cu salts operate efficiently in the asymmetric cyclopro-
panation of styrene derivatives. Besides binaphthyldiimines
[
7,8]
and bis(ferrocenyl)diamine-based systems,
positive re-
sults have been obtained using enantiopure C -symmetric
2
diimines and diamines derived from trans-1,2-diphenyl-1,2-
ethanediamine and related compounds featuring a 1,2-
cyclohexanediamine-like skeleton derived from sugars.[
The cyclopropanation of styrene (5 mol equiv.) with ethyl
α-diazoacetate 19a (1 mol equiv.) was first attempted under
fluorous biphasic (FB) conditions identical to those pre-
viously reported in the case of F-box-catalysed reactions.[
Ligand 8 (20 mol %) and Cu(OTf) (10 mol %) were stirred
together in degassed perfluorooctane at 50 °C. After 30 mi-
nutes the solids had dissolved and the resulting solution was
cooled to room temperature. After the addition of styrene,
21,22]
15]
Scheme 2. Cyclopropanation of styrene with α-diazoacetates
19a dissolved in dichloromethane was added dropwise over
1
0 h using a syringe pump. The biphasic mixture was stirred
II
Table 1. Asymmetric cyclopropanation of styrene using Co Ϫsalen
complexes as catalysts
for a further 14 h. The upper organic layer containing the
products and unchanged styrene was separated and the cis-
and trans-cyclopropanes 20a/21a were isolated by flash col-
umn chromatography (overall yield based on 19a ϭ 53%).
As shown in Table 2 (Entry 1), the ee of the major trans-
(1R,2R)-21a isomer was only 11% and the trans/cis ratio
close to 1:1. Such results are in agreement with those ob-
tained in the FB cyclopropanation of styrene catalysed by
Entry
Catalyst[a]
Yield (%)[b]
21a/20a[c]
ee 21a (%)[d][e]
1
2
3
4
5
CoϪ1
CoϪ2
CoϪ3
CoϪ4
CoϪ5
12
10
6
24
15
50:50
50:50
52:48
54:46
57:43
65
60
67
59
66
F-box.
[
a]
Further experiments showed that the nature of the CuI
Catalyst: 5 mol%; T ϭ 20 °C; t ϭ 24 h; solvent ϭ THF; addi-
[19]
tive ϭ N-methylimidazole (10 mol%). See ref. for experimental precursor strongly affects the outcome of the FB reaction.
[
b]
[c]
1
details. Overall isolated yield (20a ϩ 21a). Determined by H
NMR analysis of the crude reaction products. [ Determined by
HPLC analysis of isolated 21a (Daicel Chiralcel OD chiral col-
The use of Cu(CH CN) BF (Entry 2) and Cu(CH CN) -
PF (Entry 3) instead of Cu(OTf) led to increases in the
reaction yields, the trans/cis ratios and significantly higher
ee’s for the major isomer (1R,2R)-21a (approx. 60%).
3
4
4
3
4
d]
6
[
e]
umn). Configuration (1R,2R) as determined by comparison with
an authentic sample.
Eur. J. Org. Chem. 2004, 4545Ϫ4551
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4547

I. Shepperson, S. Quici, G. Pozzi, M. Nicoletti, D. O’Hagan
Table 2. Asymmetric cyclopropanation of styrene: optimisation of reaction conditions
FULL PAPER
I
[a]
Yield (%)[b]
21a/20a[c]
ee 21a (%)[d][e]
Entry
Cu X
Solvent
Time (h)
1
2
3
Cu(OTf)
C
C
C
C
8
8
8
8
F
F
F
F
18/CH
18/CH
18/CH
18/CH
2
2
2
2
Cl
Cl
Cl
Cl
2
2
2
2
53
72
78
64
30
13
77
5
24
24
24
24
24
24
1.5
1.5
1.5
1.5
53:47
67:33
66:34
66:34
64:36
63:37
67:33
67:33
11
61
59
40
45
7
62
43
29
Cu(CH
Cu(CH
Cu(CH
Cu(CH
Cu(CH
Cu(CH
Cu(CH
Cu(CH
Cu(CH
3
3
3
3
3
3
3
3
3
CN)
CN)
CN)
CN)
CN)
CN)
CN)
CN)
CN)
4
4
4
4
4
4
4
4
4
BF
4
PF
PF
PF
PF
PF
PF
PF
PF
6
6
6
6
6
6
6
6
[
f]
4
5
6
7
8
9
1
CH
2
Cl
2
C
8
C
8
C
8
C
8
C
8
F18/CH
F18/CH
F18/CH
F18/CH
F18/CH
3
2
2
2
2
CN
Cl
Cl
Cl
Cl
2
2
2
2
[
[
g]
h]
[i]
[j]
97
53
82:18
64:36
0[k]
13
[
a]
I
[b]
Ligand 8: 20 mol %; Cu X: 10 mol %; T ϭ 20 °C. See Expt. Sect. and text for experimental details. Overall isolated yield for (20a
[
c]
1
[d]
ϩ 21a). Determined by H NMR analysis of the crude reaction products.
Determined by HPLC analysis of isolated 21a (Daicel
[e]
[f]
Chiralcel OD chiral column). Configuration (1R,2R) as determined by comparison with an authentic sample. Ligand 8: 10 mol %;
I
[g]
[h]
[i]
[j]
[k]
I
Cu X: 10 mol %. T ϭ 0 °C. tert-Butyl α-diazoacetate (19b) was used. 21b/20b. ee 21b. Ligand 8: 1 mol %; Cu X: 0.5 mol %.
The ratio of the diamine to the copper is crucial, with a observed in FB asymmetric catalysis, lowering the tempera-
2
(
:1 ratio giving higher enantioselectivities than a 1:1 ratio ture had negative effects on the activity of the system (Entry
Entry 4). Kanemasa et al. observed the same behaviour in 8). The complex prepared in situ at 50 °C partly precipi-
cyclopropanation reactions catalysed by non-fluorous di- tated as a waxy solid when the FB mixture was cooled to 0
[
21]
amines.
This was explained by a change in the pre-cata- °C and, as found in pure organic solvents (Entry 5), the
lyst structure leading to a change in selectivity, however the catalytic activity dropped. Attempts to improve the enanti-
change in structure when more diamine is used cannot be oselectivity of the reaction by using more bulky diazoacet-
explained easily as these complexes are difficult to charac- ates, for example, tert-butyl α-diazoacetate 19b did not
terize. Our attempts to isolate and characterize the different work (Entry 9). The presence of the tert-butyl group signifi-
I
fluorous copper species depending on the 8/Cu ratio also cantly increases the trans/cis ratio as it makes the cis tran-
failed.
sition state sterically less favourable. However, the major
The fluorous-tagged diamine 8 is better suited to a FB trans-cyclopropane isomer (1R,2R)-21b was obtained with
system as under homogeneous conditions (Entry 5) the cop- an ee of only 29%. Finally, lower catalyst to substrate load-
per complex is poorly soluble and therefore is less active. ings (Entry 10) led to lower enantioselectivities and yields,
Solvents other than dichloromethane were also tested as the consistent with those previously observed using F-box cata-
organic phase of the FB mixture, but disappointing results lysts.
were obtained, as exemplified by the reaction in C F /
Having optimised the catalytic system, the recycling
ability of the catalyst under FB conditions was next exam-
8
18
CH CN (Entry 6).
3
Interestingly, there was no effect on the yield of the FB ined (Table 3, Entries 1Ϫ3). The catalyst derived from li-
reaction when addition time was reduced to 60 min and the gand 8 was easily removed from the reaction mixture by
overall reaction time to 90 min, respectively (Entry 7 vs. En- simple phase-separation of the two immiscible organic and
try 3). Usually in homogeneous catalytic systems faster ad- fluorous layers. The C F layer was washed twice with
8
18
dition leads to increased diazoacetate self-coupling and a CH Cl and used as such in a subsequent run. A drop in
2
2
drop in the recovered yield of the cyclopropane.[23] As often the enantioselectivity was observed in the second and, even
2
Table 3. Asymmetric cyclopropanation of styrene using C -symmetric bidentate N ligands
Entry
1
Ligand[a]
Solvent
Yield (%)[b]
21a/20a[c]
ee 21a (%)[d]
Conf.
8
FB conditions[e]
FB conditions
FB conditions
77
78
43
67
43
65
67
57
67:33
65:35
61:39
66:34
60:40
66:43
58:42
58:42
62
46
8
52
6
19
16
11
(1R,2R)
[
[
f]
f]
2
3
4
5
6
7
8
9
CH
2
Cl
2
(1R,2R)
(1S,2S)
(1S,2S)
(1R,2R)
(1S,2S)
6
FB conditions
7
CH
CH
CH
2
2
2
Cl
Cl
Cl
2
2
2
[
g]
(S,S)-10
(R,R)-11
[
a]
[b]
3 4 6
Ligand: 20 mol %; Cu(CH CN) PF : 10 mol %; T ϭ 20 °C; t ϭ 90 min. See Expt. Sect. and text for experimental details. Overall
1 [d]
[c]
isolated yield for (20a ϩ 21a). Determined by H NMR analysis of the crude reaction products. Determined by HPLC analysis of
isolated 21a (Daicel Chiralcel OD chiral column). [ Fluorous biphasic conditions: perfluorooctane/CH
e]
[f]
2
2
Cl , 1:1 (v/v). Recycling experi-
ment: the fluorous layer recovered from the previous run was used (see Expt. Sect.). [ t ϭ 24 h.
g]
4548
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 4545Ϫ4551

Metal-Catalysed Asymmetric Cyclopropanation of Styrene
FULL PAPER
more clearly, in the third run. This was due to the partial
The application of enantiopure fluorous diamines in
1
decomposition of the chiral ligand, as evidenced by H and other catalytic reactions is currently in progress in our
1
9
F NMR analysis of the residue obtained after decom- laboratories.
plexation of the ligand with an aqueous solution containing
cyanide ions carried out on the recovered fluorous layer.
In the case of the fluorous diamines derived from trans- Experimental Section
,2-cyclohexanediamine, the presence of perfluoroalkyl
1
General Remarks: Solvents were purified by standard methods and
dried if necessary, except for perfluorocarbons that were used as
received. All commercially available reagents were used as received.
chains does not interfere to any significant extent with the
formation of the chiral catalytic species. Indeed, homo-
geneous reactions run in the presence of diamine 9, which
features bromine atoms at the C3, C3Ј, C5 and C5Ј posi-
tions, gave slightly lower activity and selectivity than those
obtained using the fluorous diamine 8 in a FB system (En-
try 4). There was a major difference between the fluorous
II
[19,20,25,26]
[18]
[27]
Co Ϫsalen complexes 1Ϫ5,
diimines 6
and 7,
and
diamine 8[ were prepared as described in the literature. Melting
points (uncorrected) were determined using a capillary melting
point apparatus Büchi SMP-20. Optical rotations were measured
18]
1
with a PerkinϪElmer 241 polarimeter in a 1-dm cell at 20 °C. H
1
3
19
diamine 8 and the corresponding diimine ligand 6, the latter (300 MHz), C (75.4 MHz) and F NMR (282 MHz) spectra were
showing lower enantioselectivity and the opposite enanti- recorded in CDCl with a Bruker AC 300 spectrometer with tetra-
omer was favoured (Entry 5). The same behaviour was ob- methylsilane (δ ϭ 0 ppm), CDCl (δ ϭ 77 ppm) and CFCl (δ ϭ
ppm) as internal standards, respectively. Mass spectrometry was
performed with the following instruments: Electrospray ionization
ESI) mass spectrometry: Bruker APEX II ICR-FTMS mass spec-
3
3
3
0
served when the reaction was run in the presence of the
non-fluorous diimine 7 (Entry 6). This is due to the di-
amines and diamines having different modes of coordi-
(
trometer (source: nano ESI at 45°); matrix-assisted laser desorption
ionisation-time of flight (MALDI-TOF) mass spectrometry: TOF-
Spec-2E high performance mass spectrometer. Cyclopropanation
nation. Indeed, some C -symmetric diamines are able to
2
create a narrow five-membered transoid chiral pocket
around the copper, enabling efficient enantioface discrimi-
nation by the approaching olefin.[ As experimentally con-
II
reactions catalysed by Co Ϫsalen complexes were carried out as
24]
[19]
described in ref. . The ee of compound 21a was determined by
firmed in the case of diamino ligands derived from α-- HPLC on a chiral stationary phase (column: Chiracel OD; eluent:
Ϫ1
glucose, enantiomerically pure trans-cyclohexanediamine- hexane/iPrOH, 99:1; flow rate: 1 mL·min ; λ ϭ 210 nm; t
R
of
like structures are able to retain their C -symmetry upon (1R,2R)-21a ϭ 6.65 min; t
R
of (1S,2S)-21a ϭ 10.31 min). The abso-
lute configurations of the enantiomers were determined by com-
parison of the retention times with those of authentic samples. Ab-
2
coordination to the copper ion, giving rise to such a chiral
[
22]
pocket.
Diamine 8 seems to work similarly, whereas the
f
breviations used in this article: R for perfluoroalkyl.
light-fluorous diamines (S,S)-10 (Entry 7) and (R,R)-11
(Entry 8) are possibly too flexible to generate a stereodiffer- (1R,2R)-N,NЈ-Bis(3,5-dibromobenzyl)cyclohexane-1,2-diamine (9):
entiating environment around the reactive metal center.
In a flame-dried Schlenk tube the diimine 7 (1.50 g, 2.46 mmol)
was dissolved in dry CH Cl (25 mL). NaBH(OAc) (1.56 g,
.38 mmol) was added followed by CH COOH (0.5 mL). The mix-
ture was stirred at room temp. for 24 h. Aqueous 10% NaOH
5 mL) was added and the reaction stirred for a further 30 min. The
reaction was extracted three times with CH Cl and the combined
organic layers were washed with H O, brine and dried with
Na SO . The solvent was evaporated to leave a brown sticky resi-
due, which was purified by column chromatography (silica gel, hex-
2
2
3
7
3
Conclusions
(
Enantiopure α-diamines and diimines possessing C sym-
2
2
2
metry are particularly attractive in asymmetric synthesis
and organometallic asymmetric catalysis. In this work, en-
antiopure fluorous derivatives of trans-1,2-diaminocy-
2
2
4
clohexane and two new light-fluorous C -symmetric di-
20
2
ane/EtOAc, 1:1) to yield 9 (1.37 g, 91%) as a white solid. [α]
D
ϭ
1
amines derived from 1-phenylethylamine 12 have been used ϩ52 (c ϭ 0.1, CH Cl ). H NMR (300 MHz, CDCl ): δ ϭ
2
2
3
as ligands in the asymmetric cyclopropanation of styrene 0.90Ϫ1.40 (m, 4 H), 1.60Ϫ1.80 (m, 2 H), 2.00Ϫ2.30 (m, 4 H), 3.63
II
I
promoted by Co or Cu . We have shown that neither the (d, J ϭ 21 Hz, 2 H), 3.87 (d, J ϭ 21 Hz, 2 H), 7.42 (d, J ϭ 2.6 Hz,
1
3
2
δ
H), 7.54 (t, J ϭ 2.6 Hz, 4 H) ppm. C NMR (75.4 MHz, CDCl
24.9 (CH CH CHN), 31.5 (CH CH CHN), 49.9
CHN), 70.0 (ArCH N), 122.9 (arom. quat. C), 129.8
arom.), 132.5 (arom. C), 145.1 (arom. quat. C) ppm. HRMS (ESI):
3
):
introduction of perfluoroalkyl substituents in the ligand
structure nor the use of FB conditions has a detrimental
effect on the chemical yields and selectivities. This is in con-
ϭ
2
2
2
2
(CH
2
CH
2
2
(
trast with that observed for cyclopropanations carried out
ϩ
ϩ
4 2
m/z ϭ 610.8503 [M ϩ H] ; calcd. for [C20H23Br N ] 610.8554.
in the presence of fluorous bis(oxazolines).[
15]
FB con-
ditions proved to be superior to homogeneous conditions 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-Heptadecafluoro-N-[(1S)-1-
phenylethyl]-1-decanamine [(S)-15]: A mixture of (1S)-1-phenyl-
ethylamine (S)-12 (1.69 g, 13.9 mmol), K CO (2.07 g, 15 mmol)
2 3
when relatively rigid diamines derived from trans-1,2-di-
aminocyclohexane were tested in Cu -catalysed reactions.
I
and 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluorodecyl iod-
ide (13, 4.01 g, 7.0 mmol) in dry CH CN (30 mL) was refluxed with
Under optimised FB reaction conditions the copper com-
plex of diamine 8 afforded promising results (yield ϭ 77%,
trans/cis ϭ 67:33, ee trans isomer ϭ 62%) and could be
quickly separated from the products by simply decanting
the fluorous phase. However, the issue of catalyst recycling
3
stirring under nitrogen for 24 h. After filtration of the solid the
solvent was evaporated, and the product was purified by column
chromatography (silica gel, hexane/EtOAc, 7:3) to yield the title
20
compound (2.1 g, 54%) as a yellow oil. [α]
D
ϭ Ϫ16.2 (c ϭ 0.5,
1
remains open, since partial decomposition of the ligand CH Cl ). H NMR (300 MHz, CDCl ): δ ϭ 1.32 (d, J ϭ 6.6 Hz, 3
2
2
3
f
occurs.
H, CH
3
), 1.40 (br. s, 1 H, NH), 2.11Ϫ2.41 (m, 2 H, CH
2
R ),
Eur. J. Org. Chem. 2004, 4545Ϫ4551
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4549

I. Shepperson, S. Quici, G. Pozzi, M. Nicoletti, D. O’Hagan
FULL PAPER
2
.69Ϫ2.90 (m, 2 H, CH
2
NH), 3.78 (q, J ϭ 6.6 Hz, 1 H, CH),
inorganic salts, the liquid layer was washed with H
2
O (2 ϫ 15 mL),
. The sol-
13
7.21Ϫ7.38 (m, 5 H, arom. C) ppm. C NMR (75.4 MHz, CDCl
3
): saturated aqueous NH Cl (15 mL) and dried with MgSO
ϭ
4
4
2
f
3
δ ϭ 24.3 (CH
3
), 31.6 (t, JC,F ϭ 21.5 Hz, R CH
), 58.3 (CH), 107.5Ϫ122.3 (m, C
28.6, 145.0 (arom. C) ppm. 19F NMR (282 MHz, CDCl
2
), 39.2 (t, JC,F
vent was evaporated under vacuum and the residue was purified by
3
1
.8 Hz, NHCH
2
8
F17), 126.4, 127.1,
flash column chromatography (silica gel, hexane/EtOAc, 4:1) to
20
3
D
): δ ϭ yield (R)-16 (1.22 g, 70%) as a pale yellow oil. [α] ϭ ϩ13.2 (c ϭ
1
Ϫ126.7 (br. s, 2 F), Ϫ124.2 (br. s, 2 F), Ϫ123.7 (br. s, 2 F), Ϫ122.8 0.2, Et
to Ϫ121.7 (m, 6 F), Ϫ114.2 (br. s, 2 F), Ϫ81.6 to Ϫ81.2 (m, 3 F, 3 H, CH
CF
2
O). H NMR (300 MHz, CDCl
3
): δ ϭ 1.45 (d, J ϭ 6.6 Hz,
), 1.65Ϫ1.76 (m, 2 H, R ϪCH ϪCH ), 1.98Ϫ2.20 (m, 2
H, R ϪCH ϪCH ), 2.43Ϫ2.63 (m, 2 H, CH ϪNH), 3.73 (q, J ϭ
6.6 Hz, 1 H, CH), 7.23Ϫ7.35 (m, 5 H, arom. C) ppm. C NMR
75.4, CDCl ): δ ϭ 21.1 (CH ), 24.4 (CH ϪCH ϪCH ), 28.8 (t,
), 46.4 (NHϪCH ), 58.4 (CH),
17), 126.1, 127.9, 128.6 (arom. C), 145.5
f
3
2
2
ϩ
f
3
) ppm. HRMS (CI): m/z ϭ 568.0914 [M ϩ H] ; calcd. for
2
2
2
ϩ
13
18 15
[C H F17N] 568.0933.
(
3
3
2
2
2
1
2
N ,N -Bis(3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoro-
decyl)-N ,N -bis[(1S)-1-phenylethyl]ethanediamide [(S,S)-17]: Oxal-
yl chloride (0.12 mL, 1.3 mmol) was added dropwise to a solution
2
f
J
C,F
ϭ
21.9 Hz, R ϪCH
07.5Ϫ122.3 (m, C
arom. quat. C) ppm. F NMR (282 MHz, CDCl
br. s, 2 F), Ϫ123.9 to Ϫ123.1 (m, 4 F), Ϫ123.3 (br. s, 6 F), Ϫ114.7
br. s, 2 F), Ϫ81.2 (br. s, 3 F, CF ) . HRMS (ESI): m/z ϭ 582.1129
2
2
1
2
1
8
F
19
(
(
(
3
): δ ϭ Ϫ126.5
of the amine (S)-15 (1.36 g, 2.4 mmol) and Et
.6 mmol) in dry CH Cl (20 mL) at 0 °C. The mixture was stirred
under nitrogen for 6 h. The organic layer was washed with water
20 mL), a saturated CuSO solution (20 mL) and then dried with
MgSO . The solvents were evaporated to give the title compound
as a mixture of four rotamers in a ratio of 2:2:1:0.5 (white solid,
3
N (0.5 mL,
3
2
2
3
ϩ
ϩ
[
M ϩ H] ; calcd. for [C19
H
17
F
17N] 582.1089.
(
4
4
1
2
N ,N -Bis(4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,11-heptadecafluoro-
1
2
undecyl)-N ,N -bis[(1R)-1-phenylethyl]ethanediamide
Amine (R)-16 (1.15 g, 1.97 mmol) and Et N (0.39 mL, 2.81 mmol)
were dissolved in dry Et O (20 mL) and the solution was cooled to
°C. Oxalyl chloride (0.08 mL, 0.94 mmol) dissolved in dry Et
was added dropwise to the solution. The solution was stirred at 0
C for one hour then warmed to room temperature and left stirring
overnight. The reaction was filtered and the filtrate washed with
water and brine and dried with Na SO . The diethyl ether was re-
[(R,R)-18]:
0
.74 g, 53%), which was used in the next step without further puri-
3
[
28] 1
fication.
6
CH
H NMR (300 MHz, CDCl
), 2.35Ϫ2.60 (m, 4 H, CH
2
NH), 5.49 (q, J ϭ 6.6 Hz, 2 H, CH), 7.30Ϫ7.47 (m, 10 H,
3
): δ ϭ 1.74 (d, J ϭ 7.1 Hz,
2
f
H, CH
3
2
R ), 3.27Ϫ3.56 (m, 4 H,
0
2
O
1
3
arom. C) ppm. C NMR (75.4 MHz, CDCl
3
): δ ϭ 17.5 (CH
), 36.7 (NCH ), 51.9 (CH),
F17), 127.2, 128.5, 128.7, 128.9, 129.0, 129.1
3
),
°
4.4, (t, 2
08.0Ϫ120.3 (m, C
J
C,F ϭ 24.9 Hz, R CH
f
3
1
2
2
8
2
4
19
(
(
arom. C), 138.2 (arom. quat. C), 164.9 (CϭO) ppm. F NMR
282 MHz, CDCl ): δ ϭ Ϫ127.5 to Ϫ126.1 (m, 4 F), Ϫ124.9 to
moved under vacuum and the crude product purified by column
chromatography (silica gel, hexane/EtOAc, 4:1) to afford the title
compound as a mixture of four rotamers in a ratio of 2:1:1:0.2
3
Ϫ123.1 (m, 4 F), Ϫ123.5 to Ϫ120.9 (m, 16 F), Ϫ115.9 to Ϫ114.9
m, 4 F), Ϫ81.8 to Ϫ81.1 (m, 6 F, CF ) ppm. HRMS (MALDI-
TOF): m/z 1211.1008 [M
(
3
1
(
1
colourless oil, 0.76 g, 67%). H NMR (300 MHz, CDCl
.56Ϫ2.03 (m, 14 H, CH
3
): δ ϭ
), 3.07Ϫ3.31 (m, 4
), [5.04 (q, J ϭ 7.2 Hz), 5.15 (q, J ϭ 7.2 Hz), 5.79 (q,
J ϭ 7.2 Hz), 5.92, (q, J ϭ 7.2 Hz)] (ratio ϭ 1:2:0.2:1, 2 H, PhCH),
ϩ
ϭ
ϩ
Na] ; calcd. for
f
3 2 2
and R ϪCH ϪCH
ϩ
[C
38
H
26
F
34
N
2
O
2
Na] 1211.1004.
H, NCH
2
1
2
N ,N -Bis(3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoro-
1
3
1
2
7.27Ϫ7.42 (m, 10 H, arom. C) ppm. C NMR (75.4, CDCl
3
): δ ϭ
), 28.8,
), 41.3, 41.6, 44.4, 44.8 (NCH ),
2.0, 52.2, 56.4, 56.6 (CH), 108.0Ϫ120.3 (m, C 17), 127.7, 127.8,
27.9, 128.5, 128.7, 128.8, 129.2 (arom. C), 139.0, 139.3, 139.9
decyl)-N ,N -bis[(1S)-1-phenylethyl]-1,2-ethanediamine [(S,S)-10]: A
solution of (S,S)-17 (0.74 g, 0.63 mmol) in dry THF (5 mL) was
added by syringe to a suspension of LAH (0.12 g, 3.1 mmol) in
THF (5 mL) at 0 °C. The reaction mixture was stirred under nitro-
gen for 12 h at room temp. The excess of hydride was then de-
stroyed by adding water dropwise until white crystals were formed.
The suspension was then filtered and the solid washed with diethyl
ether. The combined organic layers were collected and dried with
f
1
2
5
1
3 2 2
6.9, 17.1, 18.2, 18.7 (CH ), 19.9, 21.9, 22.2 (R CH CH
2
f
9.1 (t,
J
C,F ϭ 22.9 Hz, R CH
2
2
8
F
1
9
(
arom. quat. C), 165.4, 165.6 (CϭO) ppm. F NMR (282 MHz,
CDCl ): δ ϭ Ϫ126.6 (br. s, 4 F), Ϫ124.0 (br. s, 4 F), Ϫ123.2 (br. s,
F), Ϫ122.4 (br. s, 12 F), Ϫ114.8 to Ϫ114.3 (m, 4 F), Ϫ81.3 to
Ϫ81.1 (m, 6 F, CF ) ppm. HRMS (ESI): m/z ϭ 1239.1742 [M ϩ
3
4
3
MgSO
4
. The solvents were evaporated to afford compound (S,S)-
O/MeOH
ϩ
ϩ
Na] ; calcd. for [C40
H
30
F
34
N
2
O
2
Na] 1239.1661.
1
0 as a white solid that was recrystallised from Et
2
1
0.41 g, 56%). [α]2
0
). H NMR
), 1.92Ϫ2.13
), 2.55Ϫ2.83 (m,
2
NH), 3.64 (q, J ϭ 6.7 Hz, 1 H, CH),
(
(
(
D 2 2
ϭ ϩ6.47 (c ϭ 0.14, CH Cl
1
2
N ,N -Bis(4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,11-heptadecafluoro-
300 MHz, CDCl ): δ ϭ 1.22 (d, J ϭ 6.7 Hz, 6 H, CH
m, 4 H, CH R ), 2.26Ϫ2.45 (m, 4 H, CH CH
2 2 2
3
3
1
2
f
undecyl)-N ,N -bis[(1R)-1-phenylethyl]ethanediamine
[(R,R)-11]:
f
LAH (35 mg, 0.91 mmol) was suspended in dry THF (10 mL) and
cooled to 0 °C. Ethanediamide (R,R)-18 (0.55 g, 0.45 mmol) was
dissolved in dry THF (10 mL) and added dropwise to the suspen-
sion. The reaction was stirred for 30 minutes at 0 °C and then
hydrolysed by the dropwise addition of water until a white precipi-
tate formed. The reaction was filtered and the filtrate dried with
J ϭ 7.8 Hz, 4 H, R CH
13
7.11Ϫ7.26 (m, 10 H, arom. C) ppm. C NMR (75.4, CDCl
3
): δ ϭ
), 49.6
8
F17), 127.05,
2
f
1
6.9 (CH
CH
27.5, 128.2 (arom. C), 143.5 (arom. quat. C) ppm. F NMR
): δ ϭ Ϫ126.8 to Ϫ126.5 (m, 4 F), Ϫ124.2 to
Ϫ123.8 (m, 4 F), Ϫ123.3 (br. s, 2 F), Ϫ122.7 to Ϫ122.1 (m, 12 F),
3
), 29.5 (t, JC,F ϭ 20.4 Hz, R CH
2 2
), 42.4 (NHCH
(NHCH
2
2
NH), 60.1 (CH), 105.0Ϫ122.3 (m, C
19
1
(282 MHz, CDCl
3
Na
purified by column chromatography (silica gel, hexane/EtOAc, 4:1).
Finally the crude product was recrystallised from Et O/MeOH to
give pure (R,R)-11 as a white solid (80 mg, 15%). M.p. 64Ϫ66 °C.
2 4
SO . The solvent was evaporated to leave a residue which was
3
3
Ϫ114.8 to Ϫ114.4 (m, 4 F), Ϫ81.3 (t, JF,F ϭ 10.3 Hz, 6 F, CF )
ppm. HRMS (MALDI TOF): m/z ϭ 1161.1932 [M ϩ H] ; calcd.
for [C38
ϩ
2
ϩ
31 34 2
H F N ] 1161.1943.
2
0
1
[
α]
(d, J ϭ 6.7 Hz, 6 H, CH
H), 2.27Ϫ2.51 (m, 8 H), 3.74 (q, J ϭ 6.7 Hz, 2 H, CH), 7.18Ϫ7.30
D
ϭ Ϫ1 (c ϭ 0.2, Et
2
O). H NMR (300 MHz, CDCl
3
): δ ϭ 1.27
4
,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,11-Heptadecafluoro-N-[(1R)-1-
3
), 1.51Ϫ1.63 (m, 4 H), 1.83Ϫ2.08 (m, 4
phenylethyl]-1-undecanamine [(R)-16]: A mixture of (1R)-1-phenyl-
ethylamine (R)-12 (0.37 g, 3.0 mmol), K CO
,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,11-heptadecafluoroundecyl iod-
1
3
2
3
(1.38 g, 10 mmol) and (m, 10 H, arom. C) ppm. C NMR (75.4, CDCl
3
): δ ϭ 16.3 (CH
C,F ϭ 21.5 Hz, R ϪCH
3
),
), 49.9
N), 60.0 [PhCH(CH )N],
f
2
f
4
19.2 (R CH
2
CH
2
), 29.0 (t,
CH N), 50.2 (NCH
J
2
f
ide 14 (1.82 g, 3.1 mmol) in dry CH
stirring under nitrogen for 8 h. The suspension was cooled to room
temperature and diluted with Et O (40 mL). After filtration of the quat. C) ppm. F NMR (282 MHz, CDCl ): δ ϭ Ϫ126.6 (br. s, 4
3
CN (20 mL) was refluxed with
(R CH
2
CH
2
2
2
CH
2
3
f
105.0Ϫ122.3 (m, R ), 127.2, 128.0, 128.4 (arom. C), 144.3 (arom.
1
9
2
3
4550
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 4545Ϫ4551

Metal-Catalysed Asymmetric Cyclopropanation of Styrene
FULL PAPER
[
[
[
[
2]
3]
4]
5]
F), Ϫ124.0 (br. s, 4 F), Ϫ123.2 (br. s, 4 F), Ϫ122.4 (br. s, 12 F),
W. Kirmse, Angew. Chem. 2003, 115, 1120Ϫ1125; Angew.
Chem. Int. Ed. 2003, 42, 1088Ϫ1093.
M. P. Doyle, in Catalytic Asymmetric Synthesis (Ed.: I. Ojima),
2nd ed., John Wiley & Sons, New York, 2000, chapter 5.
R. E. Lowenthal, A. Abiko, S. Masamune, Tetrahedron Lett.
Ϫ114.5 (br. s, 4 F), Ϫ81.2 (t, 3
J
F,F ϭ 10.5 Hz, 6 F, CF
3
) ppm.
ϩ
HRMS (ESI): m/z
ϭ 1189.2271 [M ϩ H] ; calcd. for
ϩ
40 35 34 2
[C H F N ] 1189.2256.
1
990, 31, 6005Ϫ6008.
Cyclopropanation of Styrene: The following reactions carried out
with ligands 8 and 9 are illustrative of FB and homogeneous cyclo-
propanation, respectively.
D. A. Evans, K. A. Woerpel, M. M. Hinman, M. M. Faul, J.
Am. Chem. Soc. 1991, 113, 726Ϫ728.
[6]
For a review on bis(oxazoline) chemistry, see: A. K. Ghosh, P.
Mathivanan, J. Cappiello, Tetrahedron: Asymmetry 1998, 9,
Fluorous Biphasic Conditions: Diamine 8 (118 mg, 0.06 mmol) and
1Ϫ45.
[
7]
Cu(CH
3
CN)
4
PF
6
(11 mg, 0.03 mmol) were stirred together in de-
H. Suga, A. Kakehi, S. Ibata, T. Fudo, Y. Wanatabe, Y. Kino-
shita, Bull. Chem. Soc. Jpn. 2003, 76, 189Ϫ199 and references
cited therein.
D. Cho, S. Jeon, H. Kim, C. Cho, S. Shim, T. Kim, Tetra-
hedron: Asymmetry 1999, 10, 3833Ϫ3848.
D. Rechavi, M. Lemaire, Chem. Rev. 2002, 102, 3467Ϫ3494.
O. Reiser, Chimica Oggi 2002, 20, 73Ϫ76.
M. Glos, O. Reiser, Org. Lett. 2000, 2, 2045Ϫ2048.
I. T. Horv a´ th, J. R a´ bai, Science 1994, 266, 72Ϫ75.
J. A. Gladysz, D. P. Curran, Tetrahedron 2002, 58, Special
Issue.
gassed perfluorooctane (2 mL) at 50 °C. After 30 minutes the solid
had dissolved and the solution had become dark blue. The reaction
mixture was cooled to room temperature and styrene (0.16 mL,
[
[
8]
9]
1
.5 mmol) was added; the mixture was stirred for a further 5 mi-
nutes. Ethyl diazoacetate 19a (0.034 mL, 0.3 mmol) dissolved in de-
gassed CH Cl (2 mL) was added dropwise over one hour using a
[10]
2
2
[11]
[12]
[13]
syringe pump. After its addition the reaction mixture was stirred
for a further 30 minutes, after which stirring was stopped to allow
the two phases to separate under nitrogen. The dichloromethane
layer containing the products was removed and the fluorous phase
was stirred with dichloromethane (2 mL) for 5 minutes and then
this too was removed. More styrene was added to the fluorous
layer and the reaction repeated as before (Table 3). The combined
[14]
For an overview of fluorous technologies in high-throughput
organic synthesis, see: W. Zhang, Tetrahedron 2003, 59,
4
475Ϫ4489.
[
[
15]
16]
R. Annunziata, M. Benaglia, M. Cinquini, F. Cozzi, G. Pozzi,
Eur. J. Org. Chem. 2003, 1191Ϫ1197.
For a review, see: G. Pozzi, I. Shepperson, Coord. Chem. Rev.
2 2
CH Cl layers were evaporated to leave a residue, an aliquot of
1
which was analysed by H NMR to determine the relative amounts
of the two diastereoisomers. The residue was purified by flash col-
umn chromatography (silica gel, hexane/EtOAc, 95:5) to give a
mixture of 20a and 21a. Pure 21a for HPLC determination of the
ee was obtained by flash column chromatography of the 20a/21a
2
003, 242, 115Ϫ124.
[17]
M. Cavazzini, A. Manfredi, F. Montanari, S. Quici, G. Pozzi,
Eur. J. Org. Chem. 2001, 4639Ϫ4649.
[
[
[
[
[
18]
19]
20]
21]
22]
D. Maillard, G. Pozzi, S. Quici, D. Sinou, Tetrahedron 2002,
58, 3971Ϫ3976.
mixture (silica gel, hexane/EtOAc, 95:5). R
20a) ϭ 0.16.
f
(21a) ϭ 0.22, R
f
T. Niimi, T. Uchida, R. Irie, T. Katsuki, Adv. Synth. Catal.
2
001, 343, 79Ϫ88.
M. Cavazzini, S. Quici, G. Pozzi, Tetrahedron 2002, 58,
943Ϫ3949.
(
3
Homogeneous Conditions: Diamine 9 (37 mg, 0.06 mmol) and
Cu(CH CN) PF (11 mg, 0.03 mmol) were stirred together in de-
gassed CH Cl (2 mL) for 10 minutes at room temperature until
the reaction became a deep blue colour. Styrene (0.16 mL,
.5 mmol) was added to the reaction, which was stirred for a
further 5 minutes. Ethyl diazoacetate 19a (0.034 mL, 0.3 mmol) dis-
solved in CH Cl (2 mL) was added dropwise over one hour using
S. Kanemasa, S. Hamura, E. Harada, H. Yamamoto, Tetra-
hedron Lett. 1994, 35, 7985Ϫ7988.
3
4
6
2
2
C. Borriello, M. E. Cucciolito, A. Panunzi, F. Ruffo, Tetra-
hedron: Asymmetry 2001, 12, 2467Ϫ2471.
[23]
1
There are, however, some exceptions as seen in the case of
II
cyclopropanation catalysed by Co Ϫporphyrin complexes: L.
2
2
Huang, Y. Chen, G. Gao, X. Zhang, J. Org. Chem. 2003, 68,
8179Ϫ8184.
L. Cavallo, M. Cucciolito, A. De Martino, F. Giordano, I. Ora-
bona, A. Vitagliano, Chem. Eur. J. 2000, 6, 1127Ϫ1138.
Z. Qin, C. M. Thomas, S. Lee, G. W. Coates, Angew. Chem.
a syringe pump. After its addition the reaction was stirred for a
further 30 minutes, after which the volatiles were evaporated under
vacuum to leave the crude products, which were separated and ana-
lysed as described above.
[
[
24]
25]
2
003, 115, 5642Ϫ5645; Angew. Chem. Int. Ed. 2003, 42,
5
484Ϫ5487.
[
[
[
26]
27]
28]
W. Sun, C.-G. Xia, P.-Q. Zhao, J. Mol. Catal. A 2002, 184,
51Ϫ55.
Acknowledgments
Z. Li, R. W. Quan, E. N. Jacobsen, J. Am. Chem. Soc. 1995,
117, 5889Ϫ5890.
For an example of rotamerism in tetrasubstituted oxamides,
see: A. R. Katritzky, J. R. Levell, D. P. M. Pleynet, Synthesis
We gratefully acknowledge the European Union (Contract no.
HPRN-CT-2000-00002, Development of Fluorous Phase Technol-
ogy for Oxidation Processes) for financial support.
1998, 153Ϫ156.
Received June 22, 2004
Early View Article
Published Online October 7, 2004
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Eur. J. Org. Chem. 2004, 4545Ϫ4551
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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