First example of supported microwave-assisted synthesis of new chiral bipyridines and a terpyridine - Use in asymmetric cyclopropanation

Article abstract of DOI:10.1002/1099-0682(200109)2001:10<2669::aid-ejic2669>3.0.co;2-y

We present herein the first alumina-supported synthesis of chiral bipyridines and of a chiral C2-symmetric terpyridine conducted under microwave irradiation, and our preliminary results from copper-mediated enantioselective cyclopropanation with this terpyridine. Reaction yields were excellent and enantioselectivities of up to 87percent were observed. Moreover, with trans-β-methylstyrene, a remarkable diastereoselectivity (ratio trans/cis = 7:93) was observed.

Full text of DOI:10.1002/1099-0682(200109)2001:10<2669::aid-ejic2669>3.0.co;2-y

FULL PAPER
First Example of Supported Microwave-Assisted Synthesis of New Chiral
Bipyridines and a Terpyridine ؊ Use in Asymmetric Cyclopropanation
[a]
[a]
Isabelle Sasaki,*[a] Jean-Claude Daran,[a] Jerome Hydrio,
´ ˆ
´ ´
Frederic Pezet,
[b]
[a]
¨
Hassan Aıt-Haddou,* and Gilbert Balavoine
Keywords: N ligands / Asymmetric catalysis / Cyclopropanation / Copper / Zinc
We present herein the first alumina-supported synthesis of ation with this terpyridine. Reaction yields were excellent
chiral bipyridines and of a chiral C2-symmetric terpyridine
conducted under microwave irradiation, and our preliminary
and enantioselectivities of up to 87% were observed. More-
over, with trans-β-methylstyrene, a remarkable diastereose-
results from copper-mediated enantioselective cyclopropan- lectivity (ratio trans/cis = 7:93) was observed.
Introduction
has been used for Suzuki coupling reactions of hetero-
cycles,[13] to the best of our knowledge this is the first utilis-
ation of microwave irradiation to form pyridyl rings. We
also report the preparation and the characterisation of the
corresponding CuII and ZnII complexes, and the prelimin-
ary results of the catalytic activities of the terpyridine cop-
per complex in asymmetric cyclopropanation.
Nitrogen-containing ligands for asymmetric homogen-
eous and heterogeneous catalysis have been highly de-
veloped.[1] Enantioselective reactions of olefins and diazo-
acetates catalyzed by a variety of metal complexes are also
well known.[2,3] N,N-donor ligands led to remarkable ee
values with copper complexes of bis-oxazolines[4,5] and sem-
icorrins.[6] Chiral bipyridines were used for the first time by
Katsuki[7,8] and very recently, Kwong and Lee[9] reported
good enantioselective cyclopropanation with chiral C2-sym-
metric terpyridine ligands.[10,11] Herein, we report a con-
Results and Discussion
Synthesis of polypyridine ligands usually requires a Stille
venient synthesis of new chiral bi- and terpyridine ligands coupling[14] or a Krönke reaction.[12] We used the latter, and
derived from the Kröhnke’s method,[12] by using solvent- carried out the preparation of the ligands in an expedient
free microwave irradiation. Although microwave irradiation three-step synthesis: (Ϫ)-β-Pinene [(Ϫ)-1] was ozonolized to
Scheme 1. Synthesis of the polypyridyl ligands
produce enantiomerically pure (ϩ)-nopinone [(ϩ)-2],[15,16]
[a]
Laboratoire de Chimie de Coordination, CNRS, UPR 8241,
which was converted into the corresponding Mannich base
205, route de Narbonne, 31077 Toulouse, France
3 with the ratio 92:8 (determined by 1H NMR) in favour of
Fax: (internat.) ϩ 33-5/6155-3003
E-mail: sasaki@lcc-toulouse.fr
University of Texas at Austin, Department of Chemistry and
Biochemistry,
the (1R,3R,5R) diastereoisomer (Scheme 1). Condensation
of the mixture of the two diastereoisomers of 3 with one
equivalent of 4[17] or 5, or with half an equivalent of 6 under
[b]
Austin, Texas, USA
Eur. J. Inorg. Chem. 2001, 2669Ϫ2674
WILEY-VCH Verlag GmbH, 69451 Weinheim, 2001
1434Ϫ1948/01/1010Ϫ2669 $ 17.50ϩ.50/0
2669

F. Pezet, I. Sasaki, J.-C. Daran, J. Hydrio, H. A¨ıt-Haddou, G. Balavoine
FULL PAPER
the usual conditions (AcOH or formamide, NH4OAc, 100
°C) led to 7, 8, or 9, respectively, in very low yields (traces).
The polar solvents used for this reaction absorb micro-
waves very efficiently,[18] so we decided to carry out
Kröhnke’s synthesis under microwave irradiation. The
yields increased to 10% (130 W, 5Ϫ15 min.), but the high
temperatures decomposed most of the reactants or interme-
diates. In order to decrease the temperature dramatically,
we tested solvent-free alumina-supported reaction condi-
tions under microwave irradiation.[19] The alumina was
mixed with ammonium acetate as an ammonia source. We
expected that the strong affinity between alumina and salt
reactants would provide a cleaner chemical conversion into
the intermediate 1,5-diketone. Indeed, the microwave irradi-
ation of this solvent-free mixture at 260 W for a few minutes
led to the expected ligands 7, 8,[20] and 9 with good yields
(45%, 50%, and 33%, respectively). Thus, the microwave ir-
radiation eliminated the necessity of heating the reaction
under reflux in the aggressive solvent (AcOH) that is re-
quired under the standard procedure, and the reaction time
was reduced from approximately 4 hours to only a few mi-
nutes. Ligand 7 is particularly interesting for further study
as it is a key product for the synthesis of polypyridines (by
homocoupling to C2-symmetrical chiral quaterpyridines,
or, after heterocoupling, to non-symmetrical chiral quater-
pyridines).
Scheme 2. Synthesis of the complexes
Figure 2. Molecular view of complex 10 with atom labelling
scheme; ellipsoids are drawn at 30% probability
Crystals suitable for X-ray crystallography were obtained
In order to investigate the coordination chemistry of this
by slow evaporation of a solution of 9 in chloroform. The new terpyridine 9, its copper complex was synthesised.
molecular structure of 9, as determined by X-ray analysis, Heating ligand 9 with CuCl2·H2O in EtOH for 3 hours un-
is shown with its atom labelling scheme in Figure 1. Import- der reflux resulted in the formation of 10 (Scheme 2). Crys-
ant bond lengths and bond angles are given in Table 1.
tals suitable for X-ray crystallography were obtained by
The main part of the molecule is roughly planar with recrystallization from dichloromethane/ether. The zinc
˚
the largest deviation being 0.211 A at C(25). However, the complex 11 was also synthesised by reacting ligand 9 with
external pyridine rings are slightly twisted with respect to ZnCl2 in refluxing THF for 3 hours. Crystals suitable for X-
the central one, resulting in dihedral angles of 10.95° and ray crystallography were obtained by recrystallization from
6.32° for rings 2 and 3, respectively. Consequently, the C dichloromethane/ether. As the two complexes 10 and 11 are
atoms of the pinene fragment are not symmetrically distrib- isostructural, only the copper one is shown, along with its
uted with respect to the main plane of the terpyridine frag- atom labelling scheme, in Figure 2. Selected bond lengths
ment, C(243) and C(343) being twisted away from it by and bond angles are given in Table 2.
˚
˚
1.622 A and Ϫ0.712 A, whereas C(245) and C(345) are loc-
In both complexes, the metal atom is surrounded by the
˚
˚
ated Ϫ0.468 A and 1.428 A on each side of this plane. As three nitrogens of the terpyridine ligand and the two chlor-
observed in the related dipineno-[4,5:4ЈЈ,5ЈЈ]-fused ine atoms in a distorted trigonal bipyramidal geometry
2,2Ј:6Ј,2ЈЈ-terpyridine[11] and in other terpyridine sys- (Table 2). The axial positions are occupied by two nitrogen
tems,[21] the nitrogen atoms are in the trans position with atoms N(2) and N(3) [N(2)ϪCuϪN(3) ϭ 157.2(2)° and
respect to each other in order to minimise the interactions 150.9(1)° for the Cu and Zn complexes, respectively]. The
between the nitrogen lone pairs.
equatorial plane is made up of the two chlorine atoms and
the nitrogen N(1) of the terpyridine moiety. The two MϪCl
bonds are identical within experimental errors [MϪCl(1)ϭ
˚
˚
2.317(1), 2.250(1) A and MϪCl(2) ϭ 2.314(1), 2.258(1) A
for the Cu and Zn complexes, respectively]. Although such
a geometry has been observed for related five-coordinate
ZnCl2 species,[22] it is unusual for five-coordinate CuCl2
complexes, which normally prefer square pyramidal con-
formations.[23] However, a similar pseudo trigonal-bipyram-
idal geometry has been observed in [Cu(terpy)X2] (Xϭ Br,
I, NCS) complexes.[24] The occurrence of a trigonal bipyr-
amidal geometry might be related to the presence of the
bulky pinene substituents.
Figure 1. Molecular view of 9 with atom labelling scheme; ellips-
oids represent 30% probability
2670
Eur. J. Inorg. Chem. 2001, 2669Ϫ2674

Supported Microwave-Assisted Synthesis of New Chiral Bipyridines and a Terpyridine
FULL PAPER
˚
Table 1. Selected bond lengths [A] and angles [°] for 9, 10, and 11
9
10
11
N(1)ϪC(11)
N(1)ϪC(15)
N(2)ϪC(25)
N(2)ϪC(21)
N(3)ϪC(35)
N(3)ϪC(31)
C(11)ϪC(12)
C(11)ϪC(21)
C(12)ϪC(13)
C(13)ϪC(14)
C(14)ϪC(15)
C(15)ϪC(31)
C(21)ϪC(22)
C(22)ϪC(23)
C(23)ϪC(24)
C(24)ϪC(25)
C(31)ϪC(32)
C(32)ϪC(33)
C(33)ϪC(34)
C(34)ϪC(35)
C(11)ϪN(1)ϪC(15)
C(25)ϪN(2)ϪC(21)
C(35)ϪN(3)ϪC(31)
N(1)ϪC(11)ϪC(12)
N(1)ϪC(11)ϪC(21)
C(12)ϪC(11)ϪC(21)
C(13)ϪC(12)ϪC(11)
C(14)ϪC(13)ϪC(12)
C(13)ϪC(14)ϪC(15)
N(1)ϪC(15)ϪC(14)
N(1)ϪC(15)ϪC(31)
C(14)ϪC(15)ϪC(31)
N(2)ϪC(21)ϪC(22)
N(2)ϪC(21)ϪC(11)
C(22)ϪC(21)ϪC(11)
C(23)ϪC(22)ϪC(21)
C(22)ϪC(23)ϪC(24)
1.340(3)
1.344(2)
1.336(2)
1.353(3)
1.341(3)
1.346(3)
1.379(3)
1.482(3)
1.374(3)
1.371(3)
1.382(3)
1.480(3)
1.378(3)
1.376(3)
1.381(3)
1.392(3)
1.378(3)
1.386(3)
1.370(3)
1.390(3)
118.6(2)
117.8(2)
117.3(2)
122.4(2)
116.0(2)
121.6(2)
118.6(2)
119.7(3)
119.1(2)
121.7(2)
116.1(2)
122.17(19)
122.0(2)
115.9(2)
122.11(19)
119.4(2)
119.6(2)
Cu(1)ϪN(1)
Cu(1)ϪN(2)
Cu(1)ϪN(3)
Cu(1)ϪCl(1)
Cu(1)ϪCl(2)
N(1)ϪC(11)
N(1)ϪC(15)
N(2)ϪC(25)
N(2)ϪC(21)
N(3)ϪC(35)
N(3)ϪC(31)
N(1)ϪCu(1)ϪN(2)
N(1)ϪCu(1)ϪN(3)
N(2)ϪCu(1)ϪN(3)
N(1)ϪCu(1)ϪCl(1)
N(2)ϪCu(1)ϪCl(1)
N(3)ϪCu(1)ϪCl(1)
N(1)ϪCu(1)ϪCl(2)
N(2)ϪCu(1)ϪCl(2)
N(3)ϪCu(1)ϪCl(2)
Cl(1)ϪCu(1)ϪCl(2)
C(11)ϪN(1)ϪC(15)
C(11)ϪN(1)ϪCu(1)
C(15)ϪN(1)ϪCu(1)
C(25)ϪN(2)ϪC(21)
C(25)ϪN(2)ϪCu(1)
C(21)ϪN(2)ϪCu(1)
C(35)ϪN(3)ϪC(31)
C(35)ϪN(3)ϪCu(1)
C(31)ϪN(3)ϪCu(1)
1.974(4)
2.074(4)
2.081(4)
2.3169(12)
2.3136(13)
1.333(5)
1.334(6)
1.340(6)
1.367(6)
1.348(6)
1.364(5)
78.50(16)
78.80(16)
157.24(15)
118.63(11)
97.57(11)
94.68(9)
122.68(11)
93.72(11)
97.11(10)
118.68(5)
121.1(4)
119.5(3)
119.1(3)
118.1(4)
127.4(3)
113.7(3)
118.0(4)
128.0(3)
113.9(3)
Zn(1)ϪN(1)
Zn(1)ϪN(2)
Zn(1)ϪN(3)
Zn(1)ϪCl(1)
Zn(1)ϪCl(2)
N(1)ϪC(11)
N(1)ϪC(15)
N(2)ϪC(25)
N(2)ϪC(21)
N(3)ϪC(35)
N(3)ϪC(31)
N(1)ϪZn(1)ϪN(2)
N(1)ϪZn(1)ϪN(3)
N(2)ϪZn(1)ϪN(3)
N(1)ϪZn(1)ϪCl(1)
N(2)ϪZn(1)ϪCl(1)
N(3)ϪZn(1)ϪCl(1)
N(1)ϪZn(1)ϪCl(2)
N(2)ϪZn(1)ϪCl(2)
N(3)ϪZn(1)ϪCl(2)
Cl(1)ϪZn(1)ϪCl(2)
C(11)ϪN(1)ϪC(15)
C(11)ϪN(1)ϪZn(1)
C(15)ϪN(1)ϪZn(1)
C(25)ϪN(2)ϪC(21)
C(25)ϪN(2)ϪZn(1)
C(21)ϪN(2)ϪZn(1)
C(35)ϪN(3)ϪC(31)
C(35)ϪN(3)ϪZn(1)
C(31)ϪN(3)ϪZn(1)
2.074(3)
2.217(3)
2.218(3)
2.2505(9)
2.2580(9)
1.337(4)
1.341(5)
1.337(4)
1.357(4)
1.327(5)
1.356(5)
75.25(10)
75.62(11)
150.86(11)
118.78(8)
98.19(8)
95.35(7)
117.41(8)
95.61(8)
98.06(7)
123.81(4)
120.8(3)
119.3(2)
119.5(2)
118.5(3)
126.8(2)
114.5(2)
119.2(3)
125.7(2)
113.6(2)
Table 2. Crystallographic data
9
10
11
Formula
C29H31N3
421.6
C29H31Cl2N3Cu
C29H31Cl2N3Zn
557.84
Fw (g)
556.01
180 (2)
Trigonal
P61
Temperature, K
Crystal system
Space group
293 (2)
180 (2)
Monoclinic
P21
Trigonal
P61
˚
a, A
13.0610 (11)
6.3367 (8)
15.5512 (14)
90.0
10.3549 (8)
10.3549 (8)
42.080 (4)
90.0
10.4288 (4)
10.4288 (4)
42.213 (2)
90.0
˚
b, A
˚
c, A
α, °
β, °
γ, °
113.64 (9)
90.0
90.0
120.0
90.0
120.0
3
˚
U/A
1179.1 (2)
2
3907.5 (6)
6
3976.0 (3)
6
Z
ρ (calcd.), g,cmϪ3
µ (Mo-Kα), cmϪ1
θ range, °
1.187
0.698
1.418
10.67
1.398
11.51
2.68 Ͻ θ Ͻ 26.13
11778
2.27 Ͻ θ Ͻ 20.95
11611
2.25 Ͻ 2θ Ͻ 20.96
14569
Reflections measured
Independent reflections (Rint
Data/restraints/parameters
R1, wR2 [I Ͼ 2σ(I)]
R1, wR2 (all data)
(∆/σ)max
)
4509 (0.0586)
4509/1/293
0.0372, 0.0693
0.0921, 0.0848
0.001
2680 (0.0565)
2680/1/320
0.0274, 0.0405
0.0398, 0.0429
0.001
2805 (0.0468)
2805/1/320
0.0256, 0.0536
0.0293, 0.0552
0.001
∆ρmin/∆ρmax
GOF
Ϫ0.13/0.11
0.881
Ϫ0.21/0.22
0.922
Ϫ0.16/0.16
1.023
Eur. J. Inorg. Chem. 2001, 2669Ϫ2674
2671

F. Pezet, I. Sasaki, J.-C. Daran, J. Hydrio, H. A¨ıt-Haddou, G. Balavoine
FULL PAPER
Owing to some hydrogen interactions occurring between
the H attached to carbon C(12) and Cl(1)[20] [CϪH···Cl:
˚
˚
˚
CϪH ϭ 0.95 A, C···Cl ϭ 3.501(5) A, H···Cl ϭ 2.568(1) A,
CϪH···Clϭ 167.6(1)°] the packing in the cell displays a
right-handed helix arrangement of the complexes around
the 61 axes (Figure 3). Such an arrangement explains the
long c axes relative to a and b. The crystallisation in this
space group is certainly induced by the shape and the (R,R)
configuration of the terpyridine ligand.
Scheme 3. Cyclopropanation of olefins
Table 3. Catalytic asymmetric cyclopropanation with ethyl diazo-
acetate and chiral copper (II)terpyridine complex
Figure 3. View along the 0 0 1 axis showing the right handed helix
packing of the complexes around the 61 axes
To explore the catalytic potential of the copper terpyrid-
ine we examined the well-investigated cyclopropanation of
various olefins with ethyl diazoacetate (Scheme 3). This
commercially available diazoester, which is neither chiral
nor a bulky reactant, has a very poor effect on the asym-
metric induction, and allows one to evaluate the inherent
capacity of the terpyridine to be a chiral controller. The
reactions were carried out in the presence of 2mol % cop-
per(II)triflate (2 mol % chiral ligand) in dichloromethane at
ambient temperature. The use of other solvents such as
[a]
[b]
GC. Ϫ
HPLC chiral column Pharmachir 7C (hexane/2-pro-
[c]
1
panol 99:1 flow: 0.7 mL/min). Ϫ Determined by H NMR spec-
troscopy with Eu (hfc)3. Ϫ
3-methyl-cis-2-phenyl cyclopropanecarboxylate; minor diastereo-
[d]
Major diastereoisomer: ethyl trans-
toluene or THF led to much lower catalytic efficiency. The isomer: ethyl trans-3-methyl-trans-2-phenylcyclopropanecarb-
[e]
oxylate. Ϫ
Determined by 1H NMR integration of methylene
complex was found to be an efficient catalyst, converting
alkenes and ethyldiazoacetate to optically active cyclopro-
panes (Table 3). Reaction of the mono-substituted olefins
showed excellent yields of chiral cyclopropanes with good
trans-selectivity, but moderate levels of enantioselectivity
(6Ϫ66% ee) were observed. When ethyl diazoacetate was
changed for the bulkier commercially available trimethylsi-
lyldiazomethane, the diastereoselectivity increased slightly
(COOCH2CH3). Ϫ [f] GC analytic chiral column Supelco-120 (oven
temperature 120 °C to 200 °C 0.5 °C/min). Ϫ [g] Determined by 1H
[h]
NMR integration of the cyclopropyl protons. Ϫ Determined by
chiral GC after transesterification with (Ϫ)-menthol (99% ee).
N.D.: absolute configuration not determined
Based on the results and the sense of asymmetric induc-
to a trans/cis ratio of 90:10, which has been observed with tion, the metal carbenoid attack could be compared to the
other copper catalysts.[7,8,25] Styrene derivatives bearing model previously reported by Pfaltz for N,N-bidentate li-
electron-donating groups showed lower enantioselectivity gands,[6] and by Kwong for N,N,N-tridentate ligands.[9] Us-
than those with electron-withdrawing groups, but higher re- ing 1,1Ј- or 1,2-disubstituted olefins led to better results,
activity (shorter reaction time). This result indicates that showing that the steric interaction between the ligand and
the active catalyst species is a strong electrophilic carbene these olefins increased with respect to monosubstituted
copper complex.
ones. For instance, a good ee of up to 87% was observed
2672
Eur. J. Inorg. Chem. 2001, 2669Ϫ2674

Supported Microwave-Assisted Synthesis of New Chiral Bipyridines and a Terpyridine
FULL PAPER
the ligand was extracted with CH2Cl2 and purified by column chro-
matography on aluminium oxide (eluent: 3% AcOEt in pentane)
with trans-stilbene. In contrast to the other substrates,
trans-β-methylstyrene showed a remarkable reversed cis-se-
lectivity, as already observed by Katsuki[8] with chiral bipyr-
idine. The ratio cis/trans ϭ 93:7 is of the same order as
the results described by Nishiyama[26] with hydroxymethyl
derivative of pybox and (ϩ)-menthyl diazoacetate.
Ligand 7: Following the above procedure with 4, and the usual
workup, gave 7 (0.142 g, 43%). Ϫ [α]2D0 ϭ ϩ 23.0 (c ϭ 1, CH2Cl2).
Ϫ M.p. 122 °C. Ϫ 1H NMR (CDCl3): δ ϭ 8.33 (dd, 3J ϭ 7.5, 4J ϭ
3
1.0 Hz, 1 H), 8.15 (d, J ϭ 7.5 Hz, 1 H), 7. 60 (t, 3J ϭ 7.5 Hz, 1
3
3
4
H), 7.51 (d, J ϭ 7.5 Hz, 1 H), 7.41 (dd, J ϭ 7.5, J ϭ 1.0 Hz, 1
H), 3.04 (t, 3J ϭ 5.5 Hz, 1 H), 2.97 (d, 3J ϭ 2.5 Hz, 2 H,), 2.73 (td,
2J ϭ 9.5, J ϭ 5.5 Hz, 1 H), 2.33 (m sept, J ϭ 2.8 Hz, 1 H), 1.43
(s, 3 H), 1.32 (d, 2J ϭ 9.5 Hz, 1 H), 0.67 (s, 3 H). Ϫ 13C NMR
(CDCl3): δ ϭ 165.9, 158.0, 150.3, 141.3, 139.0, 135.9, 131.4, 127.2,
119.5, 119.2, 50.5, 40.0, 39.2, 31.3, 30.8, 26.0, 21.2. Ϫ MS (DCI,
NH3): m/z (%) ϭ 317 (98), 319 (100) [MHϩ]. Ϫ C17H17BrN2
(329.24): calcd. C 62.02, H 5.20, N 8.51; found C 62.12, H 4.99,
N 8.34.
3
3
Conclusion
We have successfully synthesised new chiral ligands by
microwave irradiation. The copper complex of the terpyrid-
ine derivative is an active catalyst for cyclopropanation and
ees up to 87% were observed. Cyclopropanation of trans-β-
methylstyrene showed a very high cis-selectivity with ethyl
diazoacetate. Further studies on other disubstituted olefins
are under investigation.
Ligand 8: Following the above procedure with 5, and the usual
workup, gave 8 (0.125 g, 50%). Ϫ [α]2D0 ϭ ϩ 17.6 (c ϭ 1, CH2Cl2).
Ϫ M.p. 84 °C. Ϫ 1H NMR (CDCl3): δ ϭ 8.61 (ddd, 3J ϭ 4.8, 4J ϭ
1.4 Hz, 5J ϭ 0.7 Hz, 1 H), 8.34 (d, 3J ϭ 8.0 Hz, 1 H), 8.12 (d, 3J ϭ
3
4
3
7.8 Hz, 1 H), 7.76 (dt, J ϭ 7.8, J ϭ 1.8 Hz, 1 H), 7.53 (d, J ϭ
3
3
4
Experimental Section
7.8 Hz, 1 H), 7.19 (ddd, J ϭ 8.5, J ϭ 4.8 Hz, J ϭ 1.1 Hz, 1 H),
3.08 (dd, J ϭ 5.6, J ϭ 5.6 Hz, 1 H), 2.98 (d, J ϭ 2.5 Hz, 2 H),
3
3
3
2
3
3
2.74 (td, J ϭ 9.7, J ϭ 5.9 Hz, 1 H), 2.34 (m sept, J ϭ 2.8 Hz, 1
General: All reactions were carried out under an inert argon atmo-
sphere. Chemicals were of reagent-grade quality and were obtained
commercially. NMR spectra were recorded with a Bruker AM-250
H), 1.43 (s, 3 H), 1.34 (d, J ϭ 9.7 Hz, 1 H), 0.69 (s, 3 H). Ϫ 13C
2
NMR (CDCl3): δ ϭ 165.9, 156.7,152.0, 149.1, 136.7, 135.9, 130.6,
123.0, 120.9, 118.7, 50.5, 40.0, 39.2, 31.3, 30.8, 26.0, 21.2. Ϫ MS
(DCI, NH3): m/z (%) ϭ 251 [MH]ϩ. Ϫ C17H18N2 (250.34): calcd.
C 81.56, H 7.15, N 11.19; found C 81.59, H 7.13, N 11.15.
1
(250 MHz) or AMX-400 (400 MHz) spectrometer for H and 13C
and chemical shifts are reported in ppm downfield from Me4Si in
CDCl3 or in CD2Cl2. All melting points are uncorrected and were
measured on a SMP1 Stuart Scientific melting point apparatus. CI
mass spectra and FAB mass spectra (m-nitrobenzyl alcohol matrix)
were recorded with a quadrupolar Nermag R10Ϫ10H instrument.
Optical rotations were measured on a PerkinϪElmer 241 polari-
meter. Elemental analyses were performed by LCC (Laboratoire de
Chimie de Coordination) Microanalytical Service. Column chro-
matography purifications were performed with Merck aluminum
oxide (70Ϫ230 mesh ASTM), deactivated with 8% water. (ϩ)-Nop-
inone was obtained from ozonolysis of (Ϫ)-β-pinene.[15]
Ligand 9: Following the above procedure with half an equivalent
of 6, and the usual workup, gave 9 (0.080 g, 38%) Ϫ [α]2D0 ϭ Ϫ 8.4
1
(c ϭ 1, CH2Cl2). Ϫ M.p. 255 °C. Ϫ H NMR (CDCl3): δ ϭ 8.38
(d, 3J ϭ 3.8 Hz, 2 H), 8.35 (d, 3J ϭ 3.8 Hz, 2 H), 7.86 (t, 3J ϭ
3
3
3
7.8 Hz, 1 H), 7.56 (d, J ϭ 7.8 Hz, 2 H), 3.09 (dd, J ϭ 5.6, J ϭ
3
2
3
5.6 Hz, 2 H), 2.99 (d, J ϭ 2.5 Hz, 4 H), 2.74 (td, J ϭ 9.7, J ϭ
3
5.9 Hz, 2 H), 2.35 (m sept, J ϭ 2.8 Hz, 2 H), 1.44 (s, 6 H), 1.35
(d, 2J ϭ 9.7 Hz, 2 H), 0.70 (s, 6 H). Ϫ 13C NMR (CDCl3): δ ϭ
165.7, 155.7, 152.3, 137.6, 135.9, 130.5, 120.2, 118.8, 50.5, 40.1,
39.2, 31.3, 30.9, 26.0, 21.3. Ϫ MS (DCI, NH3): m/z (%) ϭ 422
[MH]ϩ. Ϫ C29H31N3 (421.58): calcd. C 82.11, H 7.63, N 10.26;
found C 82.51, H 7.28, N 9.55.
Mannich Base of the Nopinone 3: N,N-dimethylmethyleneiminium
chloride (6.8 g) was added to nopinone (2; 9 g) in 135 mL of dry
acetonitrile. After stirring at room temperature for four days the
white precipitate was filtered off and rinsed with acetonitrile. The
filtrate was concentrated and more of the product was recovered
Synthesis of Copper Complex 10: Complex 10 was synthesized by
mixing ligand 9 (0.1 mmol) and copper(II) chloride dihydrate
(0.05 mmol) in absolute EtOH (6 mL). The mixture was heated un-
der reflux for 3 hours and the precipitate then collected. The green-
yellow complex crystallised by slow diffusion of ether into a solu-
tion of 10 in dichloromethane (16 mg, 58% yield). Ϫ Positive ion
FAB-MS: m/z ϭ 519 [M Ϫ Cl]ϩ, 484 [M Ϫ 2Cl]ϩ.
1
(9.1 g, 60% yield). Ϫ M.p. 188 °C Ϫ H NMR (CDCl3): δ ϭ 12.12
(m, 1 H), 3.5 (dd, 2J ϭ 12.8, 3J ϭ 3.6 Hz, 1 H), 3.23 (dd, 2J ϭ
3
12.8, J ϭ 10.0 Hz, 1 H), 2.92 (s, 6 H), 2.87 (m, 1 H), 2.66 (m, 2
H), 2.54 (m, 2J ϭ 14.0, 3J ϭ 2.4 Hz, 1 H), 2.34 (m sept, 3J ϭ
2.8 Hz, 1 H), 2.23 (ddd, 2J ϭ 14.0, 3J ϭ 3.6, 3J ϭ 3.6 Hz, 1 H),
1.34 (s, 3 H), 1.29 (d, 2J ϭ 10.8 Hz, 1 H), 0.94 (s, 3 H). Ϫ 13CNMR
(CDCl3): δ ϭ 211.9, 64.0, 58.4, 41.0, 40.7, 40.4, 29.7, 27.1, 26.2,
22.9. Ϫ MS (DCI, NH3): m/z (%) ϭ 196 (100), 197 (15). Ϫ
C12H24ClNO2·0.25H2O: calcd. C 61.01, H 10.16, N 5.93; found C
60.92, H 9.23, N 6.01.
Synthesis of Zinc Complex 11: Complex 11 was synthesised by add-
ing ligand 9 (0.1 mmol) in THF (20 mL) to a stirred solution of
zinc(II) chloride (0.1 mmol) in THF (10 mL). The mixture was then
heated under reflux for 3 hours. After cooling, the solvent was
evaporated and the white solid was recrystallized from a mixture
of dichloromethane and ether (38 mg, 70% yield). Ϫ 1H NMR
General Procedure for the Synthesis of Ligands 7 to 9 Under Micro-
wave Irradiation: The aluminium oxide was prepared by mixing 10 g
of aluminium oxide 90, 5 g of ammonium acetate, and 1 mL of
AcOH in a mortar.
3
(CD2Cl2): δ ϭ 8.16 (m, 3 H), 7.98 (d, J ϭ 7.9 Hz, 2 H), 7.73 (d,
3
3
3J ϭ 7.9 Hz, 2 H), 4.25 (dd, J ϭ 5.5, J ϭ 5.5 Hz, 2 H), 3.10 (d,
3J ϭ 2.5 Hz, 4 H), 2.89 (m, 2 H), 2.39 (m sept, J ϭ 2.8 Hz, 2 H),
3
Freshly prepared aluminium oxide (3 g) was then added to a solu-
1.55 (s, 6 H), 1.41 (d, 2J ϭ 10.1 Hz, 2 H), 0.76 (s, 6 H). Ϫ 13C
tion of 3 (1 mmol) and the pyridinium salt (1 mmol) in MeOH (30 NMR (CD2Cl2): δ ϭ 169.1, 151.5, 144.1, 142.4, 138.4, 136.6, 121.4,
mL). The solvent was evaporated and the resulting mixture was
119.5, 49.6, 40.2, 39.9, 32.5, 30.8, 26.3, 21.8. Ϫ Positive ion FAB-
irradiated in the microwave oven for 4 min. at 260 W. After cooling, MS: m/z ϭ 520 [M Ϫ Cl]ϩ, 484 [M Ϫ 2Cl]ϩ.
Eur. J. Inorg. Chem. 2001, 2669Ϫ2674
2673

F. Pezet, I. Sasaki, J.-C. Daran, J. Hydrio, H. A¨ıt-Haddou, G. Balavoine
FULL PAPER
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M. P. Doyle, M. N. Protopopova, Tetrahedron 1998, 54,
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in dichloromethane and allowing diethyl ether to diffuse into the
solution. Data for 9, 10, and 11 were collected on a Stoe IPDS
diffractometer. The final unit cell parameters were obtained by the
least-squares refinement of 8000 reflections. Only statistical fluctu-
ations were observed in the intensity monitors over the course of
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2299Ϫ2308.
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D. Lötscher, S. Rupprecht, H. Stoeckli-Evans, A. Von Zelew-
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[11]
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The absolute structure for 10 and absolute configuration for 11
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The weighting scheme used in the last refinement cycles was w ϭ
1/[σ2(F2o) ϩ (aP)2 ϩ bP], where P ϭ (F2o ϩ 2F2c)/3 Models reached
convergence with R ϭ Σ (||Fo| Ϫ |Fc||)/Σ(|Fo|) and wR2ϭ {Σw(F2o Ϫ
F2c)2/Σw (F2o)2}1/2 with the values listed in Table 2. The calculations
were carried out using the SHELXL-97 program[29] running on a
PC. Molecular views were realised with the help of ORTEP32.[30]
Crystallographic data (excluding structure factors) for the struc-
ture(s) included in this paper have been deposited with the Cam-
bridge Crystallographic Data Centre as supplementary publication
no. CCDC-158858 (9), -158859 (10) and -158860 (11). Copies of
the data can be obtained free of charge on application to CCDC,
12 Union Road, Cambridge CB2 1EZ, UK [Fax: (internat.) ϩ 44-
1223/336-033; E-mail: deposit@ccdc.cam.ac.uk].
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The ee of the isolated nopinone is superior to 98% {optical
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4.0, MeOH)}
[17]
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Procedure for Copper-Catalysed Cyclopropanation: A solution of
0.2 mmol of ligand and 0.2 mmol of Cu(OTf)2 in dichloromethane
(2 mL) under argon was stirred for 2 hours at room temperature.
The alkene (4 mmol) and the ethyl diazoacetate (0.2 mmol) were
then added and the mixture was stirred for 30 min. The reduction
of CuII to CuI could also be activated by gentle heating of the
solution (the colour of the solution changing from green to red-
dish). Slow addition of 2 mL of a 0.5 m solution of the diazo
compound in CH2Cl2 was carried out over a period of 3 hours,
using a syringe pump. The mixture was allowed to stir overnight
at room temperature then worked up by removing the solvent and
purifying the crude product by column chromatography (pentane/
ethyl acetate). All isolated cyclopropanes were known compounds
and were characterised by 1H and 13C NMR spectroscopy, and
mass spectrometry.
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Acknowledgments
We are grateful for financial support by the Centre National de la
Recherche Scientifique (CNRS) and for a doctoral fellowship for
A. Altomare, M. C. Burla, M. Camalli, G. L. Cascarano, C.
Giacovazzo, A. Guagliardi, A. G. G. Moliterni, G. Polidori,
R. Spagn, SIR97 a program for automatic solution of crystal
structures by direct methods, J. Appl. Cryst. 1999, 32, 115Ϫ119.
`
F.P. by the Ministere de l’Education Nationale, de la Recherche et
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de la Technologie. We also wish to thank Y. Coppel for recording
NMR spectra of compound 3 on the 400 MHz spectrometer.
[28b]
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Received March 7, 2001
[I01091]
2674
Eur. J. Inorg. Chem. 2001, 2669Ϫ2674