Asymmetric cyclopropanation catalyzed by fluorous bis(oxazolines)-copper complexes

Article abstract of DOI:10.1016/j.tetasy.2006.05.023

Fluorous bis(oxazoline)-copper(I) complexes generated in situ were tested as catalysts in the metal-catalyzed cyclopropanation of styrene with various α-diazoacetates. Under optimized conditions in CH₂Cl₂, quite good yields were obta

Full text of DOI:10.1016/j.tetasy.2006.05.023

Tetrahedron: Asymmetry 17 (2006) 1568–1572
Asymmetric cyclopropanation catalyzed by fluorous
bis(oxazolines)–copper complexes
Jerome Bayardon,a Orsolya Holczknecht,b Gianluca Pozzib and Denis Sinoua,*
a
`
´
´
Laboratoire de Synthese Asymetrique, UMR 5181, ESCPE Lyon, Universite Claude Bernard Lyon 1, 43,
Boulevard du 11 Novembre 1918, 69622 Villeurbanne ce´dex, France
bCNR-Istituto di Scienze e Tecnologie Molecolari (ISTM), Via Golgi 19, 201 33 Milano, Italy
Received 2 May 2006; accepted 29 May 2006
Abstract—Fluorous bis(oxazoline)–copper(I) complexes generated in situ were tested as catalysts in the metal-catalyzed cyclopropana-
tion of styrene with various a-diazoacetates. Under optimized conditions in CH2Cl2, quite good yields were obtained. Diastereoselectiv-
ities were found to be substrate and, to a lesser extent, ligand dependent, with trans/cis ratios ranging from 62/38 (cyclopropanation with
a-ethyldiazoacetate 2a using ligand 1a) to 98/2 (cyclopropanation with methyl phenyldiazoacetate 2c using ligand 1b). Enantioselectiv-
ities up to 84% ee for the trans-isomer and 81% ee for the cis-isomer were observed using ligand 1b. Fluorous bis(oxazoline)–copper(I)
complexes could be very easily separated from the products by simple precipitation using hexane, and recycled without loss of stereo- as
well as enantioselectivities.
ꢀ 2006 Published by Elsevier Ltd.
1. Introduction
clay or silica) and organic (such as polystyrene) supports
using non-covalent or covalent bonds. However, the activ-
ities of these supported catalysts are generally lower than
those of the homogeneous analogues, while the observed
selectivities are the same. Heterogeneization of these
bis(oxazolines) by tethering to soluble organic polymers,
for example poly(ethyleneglycol), seems more promising,
since the cyclopropanation can be run under homogeneous
conditions, giving similar activities to those displayed by
the non-supported catalyst. At the end of the reaction,
the supported catalyst can be precipitated by the addition
of another solvent, filtered, and efficiently reused.10,11
Chiral bis(oxazolines) are one of the most important fam-
ilies of chiral ligands, and have been successfully applied
in the asymmetric catalysis of a large variety of reactions
during the last decade.1–3 For example, some of the best
systems for asymmetric cyclopropanation4 of styrene deriv-
atives use C2-symmetric bis(oxazoline) ligands associated
with Cu(I)–metal complexes.5–7 High enantioselectivities,
up to 99% ee for the trans isomer, and 97% ee for the cis
isomer, have been obtained using alkyl diazoacetates, while
the trans/cis stereoselectivity depends on the nature of the
diazoacetate used. However, one of the major drawbacks
of these catalytic systems is the high catalytic loading (1–
10%) generally required in order to obtain total conversion.
Hence the separation of the catalyst after the cyclopropa-
nation reaction and its reuse is highly desirable, if we are
expected to apply these generally costly ligands for large-
scale preparative purposes.
A relatively new approach for the immobilization of chiral
ligands is the fluorous-phase approach.12 In brief, the
introduction of a certain number of fluorinated ponytails
on a ligand allows its solubility in fluorous solvents or its
retention on a solid fluorous support, and thus its easy
recovery and eventually reuse. Despite the high potential
of bis(oxazolines) as chiral ligands in asymmetric catalysis,
there have been only a few reports of the synthesis and
applications of such fluorous ligands. Benaglia et al.13,14
prepared some chiral fluorous bis(oxazolines) that were
employed in the ene reaction, the Mukayama aldol addi-
tion, and the cyclopropanation of styrene in the presence
of CuOTf. In the latter case, enantioselectivities up to
Various types of immobilized bis(oxazolines) have been
tested for this cyclopropanation reaction.8,9 Bis(oxazolines)
have been attached to heterogeneous inorganic (such as
*
Corresponding author. Tel.: +33 4 72 44 81 83; fax: +33 4 78 89 89 14;
e-mail: sinou@univ-lyon1.fr
0957-4166/$ - see front matter ꢀ 2006 Published by Elsevier Ltd.
doi:10.1016/j.tetasy.2006.05.023

J. Bayardon et al. / Tetrahedron: Asymmetry 17 (2006) 1568–1572
1569
78% ee were obtained for the trans isomer, as well as good
selectivities and activities; however, the active metal com-
plex could not be recycled, only the fluorous bis(oxazoline)
was recovered and reused. We independently described an
easy access to various chiral fluorous bis(oxazolines), which
were used in palladium-catalyzed allylic alkylation and in
copper-catalyzed allylic oxidation.15 In the latter reaction,
recycling of the Cu(I)-catalyst was demonstrated. More re-
cently, one of us16 reported the synthesis of C2-symmetric
fluorous diamines and diimines that were used as ligands
in the cyclopropanation of styrene; if ee’s up to 62% were
obtained for the trans isomer, a drop in the enantioselectiv-
ity was unfortunately observed in the second run. Here we
report on the use of chiral fluorous bis(oxazolines) 1a–c
(Scheme 1) in the asymmetric Cu(I)-catalyzed cyclopropa-
nation reaction of styrene.
64% yield by condensation of 2,20-methylenebis[(4S)-4-
tert-butyl-2-oxazoline] with 2 equiv of 1-iodo-(1H,1H,2H,
2H,3H,3H)-perfluoroundecane in DMF in the presence of
NaH. The fluorine contents of these ligands are 55.7%,
54.4%, and 52.7%, for 1a, 1b, and 1c, respectively.
The catalytic activity of the fluorous bis(oxazoline) 1a as
the model ligand was evaluated in the cyclopropanation
of styrene with ethyl a-diazoacetate 2a under homogeneous
conditions in CH2Cl2 (Scheme 1). Ligand 1a (10 mol %)
and Cu(CH3CN)4PF6 (9 mol %) were stirred together in
degassed CH2Cl2 at 40 ꢁC. After 30 min, the homogeneous
solution was cooled to room temperature, and styrene then
added. Ethyl a-diazoacetate 2a dissolved in CH2Cl2 was
then added dropwise over a period of 4 h using a syringe
pump, and the solution stirred for a further time. The prod-
ucts and unchanged styrene were separated and the trans-
and cis-cyclopropanes 3a/4a were isolated by flash
chromatography.
CO2R2
R1
Ph
R1
CO2R2
Ph
Ph
Cu(I), 1
N2CR1CO2R2
+
+
solvent
As shown in Table 1 (entry 1), the chemical yield was 58%
(based on 2a), the trans:cis ratio being close to 6:4. The ee’s
of the trans-3a and cis-4a were 66% and 65%, respectively.
Only a slight decrease in the reaction yield was observed
when decreasing the catalyst loading to 8% and 2%, while
the selectivities remained unchanged (Table 1, entries 2
and 3). Consequently, reactions were carried out in the
presence of 2% of the ligand. A decrease in reaction yield
and in enantioselectivity was observed by substitution of
dichloromethane by dichloroethane (Table 1, entry 4),
although the diastereoselectivity obtained remained
unchanged. Slow addition of the diazo compound (Table 1,
entry 5) or shortening the addition time (Table 1, entry 6)
resulted in lower reaction yields (34% and 44%, respec-
tively), although the selectivities were not affected.
4a-c
2a-c
3a-c
a : R1 = H, R2 = Et ; b : R1 = H, R2 = t-Bu; c : R1 = Ph, R2 = Me
C8F17
C8F17
O
R
O
N
N
R
1
a : R = -CHMe2; b : R = -CMe3; c : R = -Ph
Scheme 1.
2. Results and discussion
The same selectivities were obtained when the reaction was
carried out at either 0 ꢁC or at 40 ꢁC (Table 1, entries 7 and
8). However, at 40 ꢁC, a significant increase in the isolated
The synthesis of chiral fluorous bis(oxazolines) 1a and 1c
has already been published.15 Ligand 1b was prepared in
Table 1. Asymmetric cyclopropanation of styrene with ethyl diazoacetate 2a in the presence of CuIX/1a: optimization of reaction conditionsa
Entry
CuIX
Ligand 1a (mol %)b
Solvent
T (ꢁC)
Time (h)c
Yield (%)d
3a/4ae
ee 3a (%)f,g
ee 4a (%)f,h
1
2
3
4
5
6
7
8
9
Cu(MeCN)4PF6
Cu(MeCN)4PF6
Cu(MeCN)4PF6
Cu(MeCN)4PF6
Cu(MeCN)4PF6
Cu(MeCN)4PF6
Cu(MeCN)4PF6
Cu(MeCN)4PF6
Cu(MeCN)4PF6
Cu(MeCN)4PF6
Cu(MeCN)4BF4
Cu(OTf)
10
8
2
2
2
2
2
2
2
2
2
2
CH2Cl2
CH2Cl2
CH2Cl2
ClCH2CH2Cl
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
Styrene
CH2Cl2
CH2Cl2
20
20
20
20
20
20
0
40
40
40
40
40
4 + 16
4 + 16
4 + 16
4 + 16
8 + 12
1 + 19
4 + 24
4 + 1
1 + 1
4 + 1
4 + 1
4 + 1
58
53
53
34
34
44
25
77
68
60
73
60
61:39
61:39
61:39
61:39
61:39
62:38
61:39
62:38
62:38
59:41
63:37
63:37
66
65
65
58
66
65
63
63
63
63
66
65
65
64
64
59
63
63
63
63
63
60
65
65
10
11
12
a [Styrene]/[2a] = 5:1; [CuIX]/[1a] = 0.9:1. See Section 4 for experimental details.
b With respect to 2a.
c Time of addition of the diazoacetate + time of reaction.
d Overall isolated yield for (3a + 4a).
e Determined by GC analysis of the isolated mixture (3a + 4a).
f Determined by HPLC analysis (Daicel Chiracel OJ-H chiral column).
g (1R,2R) is the major enantiomer.
h (1S,2R) is the major enantiomer.

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J. Bayardon et al. / Tetrahedron: Asymmetry 17 (2006) 1568–1572
yield (77% chemical yield) was observed with a shorter
reaction time, while a decrease (25% chemical yield) was
noticed when the reaction was performed at 0 ꢁC. Shorten-
ing the addition time at 40 ꢁC to 1 h gave again a lower
chemical yield: only 68% versus 77% (Table 1, entry 9).
When the cyclopropanation reaction was performed with-
out dichloromethane, slightly inferior results were obtained
(Table 1, entry 10).
line) ligand. For ethyl a-diazoacetate 2a (Table 2, entries
1–6), the highest ees, up to 84%, were obtained using ligand
1b bearing sterically hindered tert-butyl substituents. The
same was observed when using diazoacetate 2b bearing
the less bulky i-propyl substituents, but differences among
the various ligands were less pronounced (Table 2, entries
7–12). Although very high diastereoselectivities, up to
98% in favor of the trans isomer, were obtained using
methyl phenyldiazoacetate 2c in the cyclopropanation reac-
tion (Table 2, entries 13–18), the observed enantioselectivi-
ties were lower than those obtained with 2a and 2b; ee’s up
to 65% were obtained using ligand 1a, while enantioselectiv-
ities dropped significantly in the case of the more bulky
ligands 1b and 1c.
Finally other copper precursors such as Cu(CH3CN)4BF4
and Cu(OTf) were tested under the optimized conditions;
if the same selectivities were observed, Cu(OTf) gave a
lower chemical yield (Table 1, entries 11 and 12).
Next we evaluated the different fluorous bis(oxazolines)
1a–c in the asymmetric cyclopropanation of styrene at 20
and 40 ꢁC under the optimized conditions using different
a-diazoacetates, such as ethyl a-diazoacetate 2a, tert-butyl
a-diazoacetate 2b, and methyl phenyldiazoacetate 2c (Ta-
ble 2). As expected, higher chemical yields were obtained
when the reaction was performed at 40 ꢁC than at 20 ꢁC,
while the selectivities were almost the same. As a general
rule, the use of more bulky a-diazoacetates resulted in a
higher trans/cis ratio, whatever the ligand used. For exam-
ple, diastereoisomeric mixtures containing 98% trans- and
only 2% cis isomer were obtained using 2c in the presence
of ligands 1a and 1b (Table 2, entries 13–16). Slightly lower
de were obtained when the same reaction was carried out in
the presence of ligand 1c bearing 4,40-phenyl substituents
(Table 2, entries 17 and 18).
Finally, catalyst recycling was investigated in the case of
the cyclopropanation of styrene using a-diazoacetate 2a.
Reactions involving fluorous ligands 1a and 1b were per-
formed in dichloromethane; then, following a recovery pro-
cedure we recently reported for fluorous bis(oxazoline)–
copper complexes,15 the solvent was evaporated and the
catalyst was precipitated by addition of hexane. Decanta-
tion of the supernatant liquid containing the products
afforded the catalyst that could be reused in another cyclo-
propanation reaction without further addition of copper or
ligand. When the cyclopropanation reaction was run at
20 ꢁC in the presence of ligand 1a, the bis(oxazoline)-com-
plex could be reused three times with the same diastereo-
and enantioselectivities (Table 3, entries 1–4), although
the yield decreased drastically at the third recycling.
For a given a-diazoester, the observed enantioselectivities
were found to be strongly dependent upon the nature of
the substituents at the 4- and 40-position of the bis(oxazo-
The same trends were observed when using bis(oxazoline)
1b as the ligand (Table 3, entries 5–8). The recycling of
ligand 1b was also studied at 40 ꢁC, the catalyst loading
Table 2. Asymmetric cyclopropanation of styrene in the presence of CuIX/fluorous bis(oxazoline) 1a
Entry
Diazoacetate
Ligand
T (ꢁC)
Time (h)b
Yield (%)c
3/4d
ee 3 (%)e,f
ee 4 (%)e,g
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
2a
2a
2a
2a
2a
2a
2b
2b
2b
2b
2b
2b
2c
2c
2c
2c
2c
2c
1a
1a
1b
1b
1c
1c
1a
1a
1b
1b
1c
1c
1a
1a
1b
1b
1c
1c
20
40
20
40
20
40
20
40
20
40
20
40
20
40
20
40
20
40
16
1
16
1
16
1
16
1
16
1
16
1
48
14
14
14
14
14
58
77
22
63
63
72
55
63
24
55
58
64
74
70
36
76
44
92
61:39
62:38
62:38
64:36
68:32
69:31
73:27
74:26
75:25
76:24
82:18
82:18
98:2
66
63
84
80
65
64
66
64
74
78
74
74
63
65
10
27
23
26
65
63
81
79
57
56
nd
nd
nd
nd
nd
nd
nd
nd
nd
nd
nd
nd
98:2
98:2
98:2
97:3
96:4
a [Styrene]/[2]/[Cu(MeCN)4PF6]/[1] = 250:50:0.9:1; solvent CH2Cl2. See Section 4 for experimental details.
b Time of reaction, time of addition of the diazoacetate being 4 h in all the experiments.
c Overall isolated yield for (3 + 4).
d Determined by GC analysis of the isolated mixture (3 + 4).
e Determined by HPLC analysis (Daicel Chiracel OJ-H chiral column).
f (1R,2R) is the major enantiomer.
g (1S,2R) is the major enantiomer.

J. Bayardon et al. / Tetrahedron: Asymmetry 17 (2006) 1568–1572
1571
Table 3. Asymmetric cyclopropanation of styrene with ethyl diazoacetate 2a in the presence of CuIX/1a: recycling experimentsa
Entry
Ligand (mol %)
T (ꢁC)
Run
Time (h)b
Yield (%)c
3a/4ad
ee 3a (%)e,f
ee 4a (%)e,g
1
2
3
4
5
6
7
8
9
10
11
12
13
14
1a (10)
1a (10)
1a (10)
1a (10)
1b (10)
1b (10)
1b (10)
1b (10)
1b (2)
20
20
20
20
20
20
20
20
40
40
40
40
40
40
1
2
3
4
1
2
3
4
1
2
3
4
5
6
16
16
16
16
16
16
16
16
1
1
1
1
1
58
58
54
31
50
50
41
34
63
63
56
42
38
46
64:36
63:37
63:37
63:37
64:36
63:37
63:37
63:37
64:36
63:37
63:37
63:37
63:37
61:39
66
66
67
65
83
81
81
81
80
79
79
81
78
70
65
64
64
63
83
80
80
80
79
78
79
80
77
68
1b (2)
1b (2)
1b (2)
1b (2)h
1b (2)i
1
a [Styrene]/[2a] = 5:1; [Cu(MeCN)4PF6]/[1] = 0.9:1; solvent CH2Cl2. See Section 4 for experimental details.
b Time of reaction, time of addition of the diazoacetate being 4 h in all the experiments.
c Overall isolated yield for (3a + 4a).
d Determined by GC analysis of the isolated mixture (3a + 4a).
e Determined by HPLC analysis (Daicel Chiracel OJ-H chiral column).
f (1R,2R) is the major enantiomer.
g (1S,2R) is the major enantiomer.
h Phenylhydrazine was added to the reaction mixture.
i 1 mol % of Cu(MeCN)4PF6 was added to the reaction mixture.
being only 2%. Again we noticed that the diastereoselectiv-
ities (trans/cis 63:37) and enantioselectivities (up to 80%)
were maintained over five runs (Table 3, entries 9–13),
although a slight decrease in chemical yield was observed.
Neither the addition of phenylhydrazine (in order to reduce
Cu(II) species possibly formed during the recovery step),
nor the addition of a small amount of fresh CuX could re-
store the original activity (Table 3, entries 13 and 14). This
behavior is in line with that observed using, for instance,
soluble bis(oxazolines) immobilized in ionic liquids,17 and
can be similarly explained by the gradual extraction of
the free fluorous ligands to the hexane phase. Careful de-
sign of the chiral bis(oxazolines) with an increased affinity
for fluorous solvents or fluorous solid supports would help
solve this problem.
4. Experimental
4.1. General
Solvents were purified by standard methods and dried if
necessary. All commercially available reagents were used
as received. Methyl phenyldiazoacetate 2c was prepared
according to literature procedure.18 Fluorous bis(oxazo-
lines) 1a and 1c were prepared as already described.15
Reactions involving organometallic catalysis were carried
out in a Schlenk tube under an inert atmosphere. Optical
rotations were recorded using a Perkin–Elmer 241 polari-
meter. The NMR spectra (1H: 300 MHz, 13C: 75.4 MHz,
19F: 282 MHz) were recorded on a Bruker AC 300 instru-
ment with Me4Si, CDCl3, and CFCl3 as the internal stan-
dard, respectively. The ee of compounds 3a–c and 4a–c
was determined by HPLC on a chiral stationary phase
(column: Chiracel OJ-H; eluent, hexane/i-PrOH 99.5:0.5;
flow rate: 1 mL minꢀ1; k = 210 nm). The absolute configu-
rations of the enantiomers were determined by comparison
of the retention times with those of authentic samples.
3. Conclusion
In conclusion, under the optimized conditions, good iso-
lated yields and diastereoselectivities were obtained in the
homogeneous fluorous bis(oxazolines)–copper catalyzed
cyclopropanation of styrene. Enantioselectivities up to
84% have been obtained, although this enantioselectivity
is strongly dependent upon the structures of the diazoace-
tate and the ligand used. Recovery and reuse of these cat-
alysts was also demonstrated without any decrease in
diastereo- as well as enantioselectivities over five runs.
These results compare well with those obtained using
PEG-supported aza-bis(oxazolines)10 or bis(oxazolines),11
and are superior to those observed with heterogeneous cat-
alysts.8 Overall, the present catalytic system based on chiral
fluorous bis(oxazolines) seems to be one of the more effi-
cient recyclable system tested so far in the asymmetric
cyclopropanation, with room still for improvement.
4.2. 12,12-Bis[(4S)-4-tert-butyl-1,3-oxazolin-2-yl](9H,9H,
10H,10H,11H,11H,13H,13H,14H,14H,15H,15H)-
perfluorotricosane 1b
To a solution of 2,20-methylenebis[(4S)-4-tert-butyl-2-
oxazoline] (532 mg, 2 mmol) in anhydrous DMF (20 mL)
was added NaH (144 mg, 6 mmol). After the mixture was
stirred for 1 h at rt, a solution of C8F17(CH2)3I (2.7 g,
4.6 mmol) in anhydrous DMF (7 mL) was slowly added.
After being stirred at 80 ꢁC for 16 h, the DMF was
removed under reduced pressure. Water (20 mL) was then
added, and the resulting mixture extracted with ether
(4 · 20 mL). Concentration of the organic solution under

1572
J. Bayardon et al. / Tetrahedron: Asymmetry 17 (2006) 1568–1572
reduced pressure followed by column chromatography on
silica gel using petroleum ether/ethyl acetate (6:1) as the
eluent afforded bis(oxazoline) 1b (1.52 g, 64% yield) as a
Acknowledgements
`
The support of the Ministere de l’Education Nationale
yellow oil: Rf 0.41 (petroleum ether/ethyl acetate 6:1);
(scholarship to J.B.) and CNR-ISTM (scholarship to
O.H.) is gratefully acknowledged.
25
½aꢁD ¼ ꢀ24 ðc 1; CHCl3Þ; 1H NMR (CDCl3) d 0.88 (s,
CH3, 18H), 1.60–1.63 (m, 4H, CH2), 1.91–2.11 (m, 8H,
CH2), 3.89 (dd, J = 10.1, 7.7 Hz, 2H, CHN), 4.05 (dd,
J = 8.6, 7.7 Hz, 2H, CH2O), 4.17 (dd, J = 10.1, 8.6 Hz,
References
2H, CH2O); 13C (CDCl3)
d 15.8, 26.1, 31.6 (t,
J = 22.3 Hz), 33.3, 34.1, 46.2, 69.1, 75.9, 166.4; 19F NMR
(CDCl3) d ꢀ126.7 (m, 4F), ꢀ124.0 (m, 4F), ꢀ123.3 (m,
4F), ꢀ122.5 (m, 12F), ꢀ114.7 (m, 4F), ꢀ81.4 (t,
J = 10.3 Hz, 6F). Anal. Calcd for C37H38F34N2O2: C,
37.43; H, 3.03. Found: C, 37.31; H, 2.97.
1. Bolm, C. Angew. Chem., Int. Ed. Engl. 1991, 30, 542–543.
2. Gosh, A. K.; Mathivanan, P.; Cappiello, J. Tetrahedron:
Asymmetry 1998, 9, 1–45.
3. Johnson, J. S.; Evans, D. A. Acc. Chem. Res. 2000, 33, 325–
335.
4. Comprehensive Asymmetric Catalysis; Jacobsen, E. N., Pfaltz,
A., Yamamoto, H., Eds.; Springer: Berlin, 1999; Vol. 2, pp
513–603.
4.3. General procedure for the cyclopropanation of styrene
5. Lowenthal, R. E.; Akibo, A.; Masamune, S. Tetrahedron
Lett. 1990, 31, 6005–6008.
6. Evans, D. A.; Woerpel, K. A.; Hinnman, M. M.; Faul, M. M.
J. Am. Chem. Soc. 1991, 113, 726–728.
Fluorous bisoxazoline 1 (10 lmol) and Cu(I)-complex
(9 lmol) were stirred together in degassed CH2Cl2 (3 mL)
for 30 min at 40ꢁC under nitrogen. Styrene (260 mg,
2.5 mmol) was added to the reaction mixture, which was
allowed to stir for a further 10 min. The diazoacetate
(0.5 mmol) dissolved in CH2Cl2 (4 mL) was added drop-
wise over 4 h using a syringe pump and the mixture then
stirred for a further hour. The volatiles were then evapo-
rated under vacuum to leave a thick oil, an aliquot of
which was analyzed by GC to determine the relative
amounts of the two diastereoisomers. The residue was puri-
fied by flash chromatography (silica gel, hexane/EtOAc
95:5 for 3a/4a, hexane/EtOAc 97:3 for 3b/4b, hexane/
EtOAc 93:7 for 3c/4c). The enantiomeric excesses of the
two diastereoisomers 3 and 4 were determined by HPLC
analysis on a chiral stationary phase.
7. Muller, D.; Umbricht, G.; Weber, B.; Pfaltz, A. Helv. Chim.
¨
Acta 1991, 74, 232–240.
8. Rechavi, D.; Lemaire, M. Chem. Rev. 2002, 102, 3467–3494.
9. Burguete, M. I.; Fraile, J. M.; Garcia-Verdugo, E.; Luis, S.
V.; Matrinez-Merino, V.; Mayoral, J. A. Ind. Eng. Chem. Res.
2005, 44, 8580–8587.
10. Glos, M.; Reiser, O. Org. Lett. 2000, 2, 2045–2048.
11. Annunziata, R.; Benaglia, M.; Cinquini, M.; Cozzi, F.;
Pitillo, M. J. Org. Chem. 2001, 66, 3160–3166.
12. Handbook of Fluorous Chemistry; Gladysz, J. A., Curran, D.
´
P., Horvath, I. T., Eds.; Wiley-VCH: Weinheim, 2004.
13. Annunziata, R.; Benaglia, M.; Cinquini, M.; Cozzi, F.; Pozzi,
G. Eur. J. Org. Chem. 2003, 1191–1197.
14. Simonelli, B.; Orlandi, S.; Benaglia, M.; Pozzi, G. Eur. J. Org.
Chem. 2004, 2669–2673.
15. (a) Bayardon, J.; Sinou, D. J. Org. Chem. 2004, 69, 3121–
3128; (b) Bayardon, J.; Sinou, D. Tetrahedron:Asymmetry
2005, 16, 2965–2972.
16. Shepperson, I.; Quici, S.; Pozzi, G.; Nicoletti, M.; O’Hagan,
D. Eur. J. Org. Chem. 2004, 4545–4551.
4.4. Recycling experiment
To carry out the recycling experiments, the reaction was
performed on a threefold scale. After the reaction, the sol-
vent was evaporated. Hexane (3 · 4 mL) was added, and
the catalyst precipitated as a pale-orange solid, which was
recovered by decanting of the supernatant liquid. The cat-
alyst was reused in a subsequent run without further addi-
tion of copper or ligand. Evaporation of hexane afforded a
residue that was purified by column chromatography, and
analyzed as described above.
´
17. See for instance: (a) Fraile, J. M.; Garcia, J. I.; Herrerıas, C.
I.; Mayoral, J. A.; Reiser, O.; Vaultier, M. Tetrahedron Lett.
´
2004, 45, 6765–6768; (b) Fraile, J. M.; Garcia, J. I.; Herrerıas,
C. I.; Mayoral, J. A.; Gmough, S.; Vaultier, M. Green Chem.
2004, 6, 93–98.
18. Davies, H. M. L.; Hansen, T.; Churchill, M. R. J. Am. Chem.
Soc. 2000, 122, 3063–3070.