Palladium-catalyzed asymmetric hydrogenation of N-hydroxya-imino phosphonates using bronsted acid as activator: The first catalytic enantioselective approach to chiral N-hydroxy-aamino phosphonates

Article abstract of DOI:10.1002/adsc.201200170

The enantioselective synthesis of ring-substituted [N-(hydroxy)amino] ACHTUNGTRENUNG(phenyl)methylphos- ACHTUNGTRENUNGphonic esters via asymmetric hydrogenation of the corresponding N-hydroxy-a-imino phosphonates with up to 90% ee was developed using cata

Full text of DOI:10.1002/adsc.201200170

FULL PAPERS
DOI: 10.1002/adsc.201200170
Palladium-Catalyzed Asymmetric Hydrogenation of N-Hydroxy-
a-imino Phosphonates Using Brønsted Acid as Activator: The
First Catalytic Enantioselective Approach to Chiral N-Hydroxy-a-
amino Phosphonates
Nataliya S. Goulioukina,a,* Ilya A. Shergold,a Grigorii N. Bondarenko,a
Mikhail M. Ilyin,b Vadim A. Davankov,b and Irina P. Beletskayaa,*
a
Department of Chemistry, Moscow State University, Leninskie Gory, GSP-1, Moscow 119991, Russia
Fax : (+7)-495-939-1854; e-mail: goulioukina@org.chem.msu.ru or beletska@org.chem.msu.ru
Institute of Organoelement Compounds, Russian Academy of Sciences, 28 Vavilov str., Moscow 119991, Russia
b
Received: February 29, 2012; Revised: July 25, 2012; Published online: October 5, 2012
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201200170.
Abstract: The enantioselective synthesis of ring-sub- 2,2,2-trifluoroethanol with a Brønsted acid as an acti-
stituted
[N-(hydroxy)amino]ACTHNGUTERN(UNG phenyl)methylphos- vator.
ACHTUNGTRENNUNGphonic esters via asymmetric hydrogenation of the
corresponding N-hydroxy-a-imino phosphonates Keywords: asymmetric catalysis; Brønsted acids; hy-
with up to 90% ee was developed using catalytic drogenation; N-hydroxy-a-amino phosphonates; N-
amounts of palladium(II) acetate and (R)-BINAP in hydroxy-a-imino phosphonates; palladium
Introduction
ising antimalarial drug candidate that has been suc-
cessfully used in clinical trials.[6] N-Hydroxy-a-amino
The interest towards the application of homogeneous phosphonic acids are phosphorus isosters of N-hy-
palladium catalysis for asymmetric hydrogenation was droxy-a-amino acids, which are important in many
generated in 2001, when Amii et al. first reported metabolic and biological processes.[7] N-Hydroxy-a-
enantioselective reduction of imino esters with a amino phosphonates exert herbicidal and growth-reg-
PdACHTUNGTRENNUNG
(OCOCF3)2/(R)-BINAP complex.[1] In the past ulating activity[8] and were announced as suitable syn-
decade, the method was successfully applied to a wide thons for pseudopeptides, prospective, in part, as
scope of prochiral substrates containing C=N,[2] C=C
haptens for reactive immunization.[9] They also find
À
N,[3] or C=O[4] double bonds, thus promising to synthetic applications for the preparation of a-amino
become an effective tool for both routine and ad- phosphonates[10] and phosphonylated nitrones. The
vanced organic synthesis. In our ongoing efforts to- latter are of interest as spin-trapping agents[11] and
wards the development of a general synthetic ap- convenient precursors for ring-substituted 2-phos-
proach to chiral a-functionalized phosphonates based
ACHTUNGTRENNUNG
on the enantioselective hydrogenation of carbon-
carbon and especially carbon-heteroatom unsaturated sis of racemic N-hydroxy-a-amino phosphonic acids
precursors,[4b,5] we became interested in exploring ho- and esters, including phosphonylation of oximes[14] or
mogeneous Pd catalysis for a practical synthesis of op- nitrones,[15] borane reduction of N-hydroxy- or N-ben-
tically active N-hydroxy-a-amino phosphonates. This zyloxy-a-imino phosphonates,[16–18] controlled reduc-
task seemed particularly intriguing since successful tion of a-nitro or a-nitrozo phosphonates,[19] a Mitsu-
examples of asymmetric hydrogenation of oximes are nobu reaction of a-hydroxy phosphonates with phenyl
sparse.
[(tert-butoxycarbonyl)oxy]carbamate,[9] SN2 reaction
N-Hydroxyamino phosphonic acids and their deriv- of phosphonomethyl triflates with tert-butyldimethyl-
atives are known as biologically active organic com- silyloxyamine,[13] and others.[8] To the best of our
pounds of practical significance. One bright example knowledge, the sole reported approach to optically
is the antibiotic fosmidomycin, 3-[N-formyl-N-(hy- active N-hydroxy-a-amino phosphonates relies on the
droxy)amino]propylphosphonic acid, which is a prom- addition of phosphites to chiral nitrones,[10,20] and thus
Adv. Synth. Catal. 2012, 354, 2727 – 2733
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Nataliya S. Goulioukina et al.
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requires the application of a stoichiometric amount of completely over 1 h and the signal from diethyl [N-
chiral auxiliary. (hydroxy)amino](phenyl)methylphosphonate (2a)
AHCTUNGTRENNUNG
Herein we wish to report the first example of the arising at dP =21.1 ppm. At the same time, the more
catalytic synthesis of optically active N-hydroxy-a- thermodynamically stable isomer (E)-1a remained un-
amino phosphonates by homogeneous Pd-catalyzed reactive (Table 1, entry 1).
asymmetric hydrogenation of N-hydroxy-a-imino
phosphonates.
Variation of the ligand [(R)-BINAP, (R)-TolBINAP,
(R)-MeO-BIPHEP, (S,S)-CHIRAPHOS, (S,S)-MeDu-
PHOS], precatalyst [Pd
ACHTUTGNRNENUG(OAc)2, PdACHTUNTGRNE(NUGN OCOCF3)2,
Pd2A(dba)3·CHCl3], solvent (TFE, MeOH, toluene,
CTHUNGTRENNUNG
Results and Discussion
EtOAc, CH2Cl2), hydrogen pressure (1–100 atm),
temperature (20–808C), addition of 4ꢂ molecular sie-
A model substrate – diethyl [N-(hydroxy)imino]- ves,[2b] or prolongation of the reaction time were to no
ACHTUNGTRENNUNG(phenyl)methylphosphonate (1a) – was prepared ac- avail. Under drastic conditions, slow degradation of
cording to Berlinꢁs method[16,21] by condensation of di- (E)-1a was observed without increasing the yield of
ethyl benzoylphosphonate with hydroxylamine. The the target product 2a. The situation changed dramati-
product was obtained as a 66:34 mixture of E- and Z- cally after a catalytic amount of (1S)-(+)-10-camphor-
isomers which are easily distinguishable by 31P NMR sulfonic acid (CSA) was added as an activator. In the
spectroscopy. The major thermodynamically more presence of CSA (10 mol%) the yield of 2a rose up to
stable E-isomer resonates at dP =9.7 ppm whereas the 91% at 92% conversion of 1a, albeit, the optical yield
signal from the minor thermodynamically less stable was only 33% ee (Table 1, entry 2).
Z-isomer undergoes an upfield shift due to a shielding
effect from the lone pairs of the oxime oxygen and isomers of prochiral oximes is known to proceed with
appears at dP =5.7 ppm.[21b] different enantioselectivity,[22] the examination was
Since the asymmetric hydrogenation of E- and Z-
In the initial experiments, the above mixture of iso- made as to how the E/Z composition of the initial
mers 1a was subjected to the reduction under 50 atm substrate 1a affects the optical purity of the product
of hydrogen pressure at 608C in 2,2,2-trifluoroethanol 2a. It was found that the ee increases up to 69% in
(TFE) with the Pd
(Scheme 1). The course of the reaction was monitored achieves 85% for the individual (E)-1a (entry 4).
by 31P NMR. Only (Z)-1a appeared to undergo the
The observed relationship between the enantiomer-
ACHTUNGRTEN(NUNG OAc)2/(R)-BINAP system the case of an 86:14 E/Z-isomer ratio (entry 3) and
hydrogenation, the signal at dP =5.7 ppm disappearing ic excess of the product 2a and the E/Z ratio of the
Scheme 1. Comparative abilities of Z- and E-isomers of oxime 1a for hydrogenation.
Table 1. The effect of E/Z ratio on the reactivity of 1a and the enantioselectivity of the formation of 2a.[a]
Entry
E/Z ratio
Conversion of 1a [%][b]
Yield of 2a [%][b]
ee [%][c]
1[d]
2
3
66:34
66:34
86:14
100:0
35
92
92
93
34
91
91
91
n.a.
33
69
4
85
[a]
Unless otherwise stated, reactions were performed in TFE (4 mL) on a 0.144-mmol scale: Pd
(R)-BINAP (7 mmol, 5 mol%), CSA (14 mmol, 10 mol%), H2 (50 atm), 608C, 1 h.
Determined by 31P NMR analysis of the crude reaction mixture.
Determined by chiral HPLC analysis; n.a.=not analyzed.
Without CSA.
ACHTUNGRTEN(NUGN OAc)2 (7 mmol, 5 mol%),
[b]
[c]
[d]
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Palladium-Catalyzed Asymmetric Hydrogenation of N-Hydroxy-a-imino Phosphonates
starting oxime 1a clearly indicates that the crucial factory conversion of (E)-1a. In comparison with
role of the Brønsted acid activator cannot be ex- CSA, the use of achiral TsOH (entry 13) or racemic
plained in terms of the lowering of the energy barrier 1,1’-binaphthyl-2,2’-diyl hydrogen phosphate (BNPA)
of Z/E isomerization via protonation and the estab- (entry 14) gave the expected product 2a with similar
lishment of rapid equilibrium between the two forms ee values but in decreased yields. Lower enantioselec-
under acidic conditions. In several recent publica- tivity, yield, and conversion were observed when the
tions[3b–e] on Pd-catalyzed hydrogenation of C=N CSA loading was increased to 20 mol% (entry 15). In
bonds, isotopic labeling experiments were described the presence of 5 mol% CSA the conversion de-
that agree with the reaction mechanism in which a se- creased substantially (entry 16), so a 10 mol% amount
quential H+/HÀ transfer takes place. If so, the role of of CSA was found to be optimal. The possible asym-
the Brønsted acid can be explained in terms of forma- metric induction from optically active CSA was also
tion of the iminium intermediate that should exhibit checked. When (S)-BINAP was used instead of (R)-
enhanced reactivity towards nucleophilic attack, and BINAP, the optical yield stayed roughly constant
the Z/E isomerization process is slower than hydroge- within the measurement error (entry 17). Accordingly,
nation. The similar strategy of C=N double bond acti- application of (Æ)-BINAP furnished the racemic
vation has been previously applied in Ir-, Ru-, and product 2a (entry 18). Consequently, the stereoinduc-
Rh-catalyzed hydrogenation processes[23] and became tion is controlled by the chiral ligand only.
a hot point in the Pd-catalyzed homogeneous hydro-
genation of prochiral imines and heteroaromatic com- tion temperature on the enantioselectivity and reac-
pounds while the present work was in progress.[2d,3]
tivity of the hydrogenation was examined. The hydro-
Finally, the effect of hydrogen pressure and reac-
In a control experiment, the chemical and configu- gen pressure had only a weak effect on the conversion
rational stability of the product 2a under the reaction of (E)-1a and the yield of 2a (entries 19–21). The op-
conditions was tested and proved. We further per- tical yield slightly decreased with a pressure increase
formed a systematic screening of the reaction condi- to 70–90 atm (entries 20 and 21) and significantly
tions of the asymmetric hydrogenation of the individ- dropped at 30 atm (entry 19). The lowering of the
ual (E)-1a, which is easily available on treating the temperature resulted in the enhancement of enantio-
mixture of isomers with hydrogen chloride in etha- selectivity (entries 25, 1, 23). The best ee value (90%)
nol.[21b] The results are summarized in Table 2. Solvent was obtained at 408C, however, the reaction almost
experiments revealed that no hydrogenation reaction stopped at 68% conversion (entry 23). Prolongation
was observed in toluene, MeOH, and CH2Cl2 (en- of the reaction time up to 6 h resulted in just an insig-
tries 2–4), and TFE was the only effective one. This nificant increase in yield (entry 24).
particular solvent behaviour of TFE is widespread in
The product 2a was isolated by column chromatog-
1
homogeneous catalysis[1,2a–d,3,4,24] and has been ration- raphy and characterized by IR, 31P, H, and 13C NMR
alized in some cases.[1,24]
spectroscopy, which were in agreement with the liter-
Other palladium precursors were also tested in the ature data.[16] The IR spectrum along with the charac-
reaction. In comparison with palladium(II) acetate, teristic pattern of the diethoxyphosphoryl moiety re-
[25]
À
Pd
G
at
1
similar ee values (entry 5). PdCl2 and Pd
(dba)3·CHCl3 3240 cmÀ1. The H and 13C NMR spectra show two
were totally ineffective (entries 6 and 7). Next, several sets of signals for the diastereotopic ethoxy groups.
commercially available axial chiral bidentate bisphos- The doublets of the methyne proton at dH =4.50 ppm
phine ligands were examined. Electron-rich (S,S)-Me- (2JH,P =18.4 Hz) and a-C-atom at dC =65.5 ppm
DuPhos and (S,S)-CHIRAPHOS forming a quite (1JC,P =146.5 Hz) are the main characteristic features.
rigid five-membered chelate ring[2f] had almost no cat- It is noteworthy that the spectral data unambiguously
alytic activity (entries 8 and 9). Atropoisomeric li- indicate the product 2a to be N-hydroxy-a-amino
gands bearing a binaphthyl motif providing a larger phosphonate rather than the a-amino phosphonate.[26]
bite angle and chelate ring flexibility, gave reasonable
To assign the absolute configuration at the new ste-
results (entries 1 and 10), and (R)-BINAP was found reogenic center, a sample of 2a was transformed with
to be superior to the other ligands in both reactivity some racemization to diethyl a-aminobenzylphospho-
and enantioselectivity. The effect of the catalyst nate (3) by hydrogenation in the presence of Pearl-
amount was also tested. Reducing the catalyst loading manꢁs catalyst[10b] (Scheme 2). The (S) configuration
to 3–4 mol% led to a noticeable formation of by-
products (entries 11 and 12).
Thereafter, a number of Brønsted acids were
screened. When a catalytic amount of trifluoroacetic
acid was used, the conversion of (E)-1a was full but
the desired product 2a was not obtained. Benzoic or
5-sulfosalicylic acids (10 mol%) did not afford satis- Scheme 2. Assignment of the absolute configuration.
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Nataliya S. Goulioukina et al.
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Table 2. Screening of reaction conditions for the asymmetric hydrogenation of oxime 1a.[a]
Entry Pd-precursor
Ligand
Brønsted
acid
Solvent Pressure
[atm]
T
Conversion Yield ee
G
[8C] of 1a [%][b]
of 2a
[%][c]
[%][b]
1
2
3
4
5
6
7
8
9
Pd
Pd
Pd
Pd
Pd
N
(R)-BINAP
(R)-BINAP
(R)-BINAP
(R)-BINAP
(R)-BINAP
(R)-BINAP
CSA
CSA
CSA
CSA
CSA
CSA
CSA
CSA
CSA
TFE
50
60
60
60
60
60
60
60
60
60
93
20
3
8
78
5
3
32
10
91
0
0
0
67
0
0
24
0
85
toluene 50
MeOH 50
CH2Cl2 50
TFE
TFE
TFE
TFE
TFE
n.a.
n.a.
n.a.
84
n.a.
n.a.
n.a.
n.a.
50
50
50
50
50
PdCl2
Pd
Pd
Pd
N
A
ACHTUNGTRENNUNG
PHOS
10
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
N
(R)-TolBINAP
(R)-BINAP
(R)-BINAP
(R)-BINAP
(R)-BINAP
(R)-BINAP
(R)-BINAP
(S)-BINAP
(Æ)-BINAP
(R)-BINAP
(R)-BINAP
(R)-BINAP
(R)-BINAP
(R)-BINAP
(R)-BINAP
(R)-BINAP
CSA
CSA
CSA
TsOH
BNPA
CSA[f]
CSA[g]
CSA
CSA
CSA
CSA
CSA
CSA
CSA
CSA
CSA
TFE
TFE
TFE
TFE
TFE
TFE
TFE
TFE
TFE
TFE
TFE
TFE
TFE
TFE
TFE
TFE
50
50
50
50
50
50
50
50
50
30
70
90
50
50
50
50
60
60
60
60
60
60
60
60
60
60
60
60
20
40
40
80
91
90
88
83
88
88
58
93
84
90
88
87
43
68
74
88
84
76
69
78
77
79
49
91
83
88
86
85
43
68
72
84
74
11[d]
12[e]
13
n.a.
n.a.
86
83
72
n.a.
83
0
74
82
82
n.a.
90
86
80
14
15
16
17
18
19
20
21
22
23
24[h]
25
[a]
Unless otherwise stated, reactions were carried out with (E)-1a (0.144 mmol), Pd precursor (7 mmol, 5 mol%), ligand
(7 mmol, 5 mol%), Brønsted acid (14 mmol, 10 mol%), and 4 mL of solvent under directed conditions for 1 h.
Determined by 31P NMR analysis of the crude reaction mixture.
Determined by chiral HPLC analysis; n.a.=not analyzed.
(E)-1a (0.155 mmol), PdACHTUGNTRENNNUG
[b]
[c]
[d]
[e]
(E)-1a (0.221 mmol), PdACHTUGNTRENNNUG
TFE were used.
[f]
20 mol% CSA was used.
5 mol% CSA was used.
Reaction time was 6 h.
[g]
[h]
of a-amino phosphonate 3 was proven by comparison were obtained. Substitution at the para-position has
of the sign of the optical rotation with published a detrimental effect on the enantioselectivity. The
data,[27] confirming that the major enantiomer of 2a reason is not clear. We can only cite similar observa-
has the (S)-N-hydroxy-a-amino phosphonate struc- tions in Pd-catalyzed hydrogenations of prochiral ke-
ture.
tones[4c] and 2,5-disubstituted pyrroles.[3a] It is note-
Next, to explore the scope of the reaction, a series worthy that oxime (E)-1e reveals very low reactivity
of para-substituted diethyl [N-(hydroxy)imino]- which may be ascribed to significant stabilization of
ACHTUNGTRENNUNG(phenyl)methylphosphonates (E)-1b–f was subjected the iminium intermediate by a mesomeric effect of
to hydrogenation under the optimal conditions, found the MeO group. In the case of the bromo-substituted
above, and the results are summarized in Table 3. In substrate (E)-1f no desirable product was obtained.
general, high yields and good enantioselectivities The competitive oxidative addition of the aryl bro-
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Palladium-Catalyzed Asymmetric Hydrogenation of N-Hydroxy-a-imino Phosphonates
Table 3. Pd-catalyzed asymmetric hydrogenation of oximes (E)-1a–g.[a]
Substrate
Ar
R
Conversion [%][b]
Yield of 2 [%][b]
ee [%][c]
(E)-1a
(E)-1b
(E)-1c
(E)-1d
(E)-1e
(E)-1f
(E)-1g
Ph
Et
Et
Et
Et
Et
Et
iPr
94
90
87
85
61
20
91
92
89
87
85
61
<10
91
85
81
75
72
78
-
p-FC6H4
p-ClC6H4
p-MeC6H4
p-MeOC6H4
p-BrC6H4
p-FC6H4
90
[a]
Reactions were carried out with (E)-1a–g (0.144 mmol), PdACHTNUTRGNEUNG(OAc)2 (7 mmol, 5 mol%), (R)-BINAP (7 mmol, 5 mol%),
CSA (14 mmol, 10 mol%), and 4 mL of solvent under directed conditions for 1 h.
Determined by 31P NMR analysis of the crude reaction mixture.
Determined by chiral HPLC analysis.
[b]
[c]
mide onto the palladium(0) species is probably re- anhydrous TFE under an argon atmosphere. The mixture
sponsible for this failure.[4a]
was gently heated to 708C with stirring until (R)-BINAP
was completely dissolved and the solution became brown-
ish-red. After cooling, (E)-1a (37.0 mg, 0.144 mmol) and
CSA (3.2 mg, 14 mmol) were added under Ar. The mixture
was stirred until total homogenization and transferred with
a syringe into a steel autoclave with a glass inlet, equipped
with a stirring bar and filled with dry argon. The autoclave
was sealed, pressurized with H2 to 50 atm, the temperature
was increased to 608C, and the reaction mixture was stirred
for 1 h. After the end of the experiment, TFE was removed
under reduced pressure and the residue was dissolved in
CDCl3 to be analyzed by 31P NMR. The product 2a was iso-
lated by column chromatography on silica gel (CH2Cl2/
MeOH 40:1). The enantiomeric excess was determined by
HPLC analysis in comparison with authentic racemic mate-
rial.
Stereoselectivity of the process essentially depends
on the steric demands from the dialkoxyphosphoryl
group, and diisopropyl ester substitution gave a sub-
stantial improvement in enantiomeric excess of up to
90% ee [cf. results for (E)-1b and (E)-1g]. The only
inconvenience is the lability of the diisopropyl phos-
phonates in the presence of strong acids, such as HCl,
hence column chromatography has to be used for iso-
lating the individual (E)-1g isomer.
Conclusions
In summary, ring-substituted [N-(hydroxy)imino]-
(phenyl)methylphosphonic esters, which are stable
and easily available in the E-configuration, can be hy-
Diethyl [N-(hydroxy)amino]ACHTUNGRTEN(NUNG phenyl)methylphosphonate
(2a): White solid; 85% ee; Rf =0.3 (CH2Cl2/MeOH 40:1),
drogenated in TFE medium using Pd
(OAc)2/(R)- mp 117.6–119.08C (benzene); 31P NMR (162 MHz, CDCl3):
1
d=21.1; H NMR (400 MHz, CDCl3): d=1.17 (t, J=7.0 Hz,
BINAP as a catalyst and a Brønsted acid as an activa-
tor with enantioselectivities of up to 90% ee. The pro-
posed method provides the first catalytic, most
straightforward, and atom-economical approach to
enantioenriched N-hydroxy-a-amino phosphonates, as
well as demonstrating the possibility to expand homo-
geneous asymmetric palladium catalysis to oximes hy-
drogenation.
3H, CH3), 1.27 (t, J=7.0 Hz, 3H, CH3), 3.85–4.07 (m, 4H,
CH2), 4.50 (d, J=18.4 Hz, PCH), 5.10 and 5.79 (two br. s,
each 1H, NH and OH), 7.32 (m, 1H, aryl), 7.37 (m, 2H,
aryl), 7.46 (m, 2H, aryl); 1H NMR (400 MHz, DMSO-d6):
d=1.04 (t, J=7.1 Hz, 3H, CH3), 1.18 (t, J=7.1 Hz, 3H,
CH3), 3.69–3.89 (m, 2H, CH2), 3.97 (m, 2H, CH2), 4.33 (d,
J=20.4 Hz, PCH), 6.08 and 7.63 (two s, each 1H, NH and
OH), 7.26 (m, 1H, aryl), 7.32 (m, 2H, aryl), 7.43 (m, 2H,
aryl); 13C NMR (101 MHz, CDCl3): d=16.2 (d, J=5.7 Hz),
16.3 (d, J=5.9 Hz), 62.9 (d, J=6.8 Hz), 63.1 (d, J=6.7 Hz),
65.5 (d, J=146.5 Hz, CP), 128.3, 128.5, 128.6, 134.2 (d, J=
Experimental Section
À
5.9 Hz); IR (Nujol): n=3240 (OH), 1250 (P=O), 1060 (O
C), 1040 (O C), 980 (POC C) cmÀ1
;
HR-MS: m/z=
À
À
Typical Experimental Procedure for the Asymmetric
Hydrogenation of Oxime (E)-1a
541.1839, calcd. for [2M+Na]+ (C22H36N2O8P2Na):
541.1844; [a]D: À33.58 (c 1.91, MeOH) for an enantiomeri-
cally enriched sample of 85% ee; HPLC (Kromasil Amy-
Coat column, hexane/i-PrOH 9:1, 220 nm): tr (minor enan-
tiomer)=9.6 min, tr (major enantiomer)=13.6 min.
A Schlenk tube dried at 1208C for 1 h, equipped with stir-
ring bar and septum cap, was charged with Pd
ACHTUNGERTN(NUNG OAc)2
(1.6 mg, 7 mmol), (R)-BINAP (4.5 mg, 7 mmol), and 4 mL of
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Acknowledgements
This work was carried out in the framework of the French-
Russian International Associated Laboratory “LAMREM”.
We are grateful for financial support from Russian Founda-
tion for Basic Researches (grant N 09-03-01128-a). We are in-
debted to the Department of Structural Studies of Zelinsky
Institute of Organic Chemistry, Moscow and Professor V. P.
Ananikov for recording the high resolution mass spectra.
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