Novel type of trifunctional chiral N-heterocyclic carbene (NHC) precursors

Article abstract of DOI:10.1016/j.tetasy.2008.03.002

The synthesis of (S)-2-amino-3-(3-methyl-1H-imidazol-3-ium-1-yl)propanoate as the parent homologue of a novel generation of chiral NHC precursors is described. Crystallographic data for the novel chiral Ni^II complex, and Boc-protected amino acid containing imidazolium moiety are also given. The silver(I) carbene complex of the Boc-protected amino acid has been obtained.

Full text of DOI:10.1016/j.tetasy.2008.03.002

Available online at www.sciencedirect.com
Tetrahedron: Asymmetry 19 (2008) 756–760
Novel type of trifunctional chiral N-heterocyclic
carbene (NHC) precursors
Yuri N. Belokon,a,* Andrey V. Grachev,a Victor I. Maleev,a Victor N. Khrustalev,a
Alexander S. Peregudova and Michael Northb
aA.N. Nesmeyanov Institute of Organo-Element Compounds, Russian Academy of Sciences, 119991 Vavilov 28, Moscow, Russia
bSchool of Natural Sciences and URC in Catalysis and Intensified Processing, Bedson Building,
University of Newcastle, Newcastle upon Tyne NE1 RU7, UK
Received 6 February 2008; accepted 3 March 2008
Abstract—The synthesis of (S)-2-amino-3-(3-methyl-1H-imidazol-3-ium-1-yl)propanoate as the parent homologue of a novel generation
of chiral NHC precursors is described. Crystallographic data for the novel chiral NiII complex, and Boc-protected amino acid containing
imidazolium moiety are also given. The silver(I) carbene complex of the Boc-protected amino acid has been obtained.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
N Me
N
For a long time, carbenes were assumed to be an extremely
reactive species and could not be isolated in a free form.
H
COO
H2N
Interest in this class of substances dramatically increased
after the work of Arduengo et al.,1 where the authors
reported the isolation of an N-heterocyclic carbene
(NHC) in a pure form. The similarity of this type of
carbene to phosphine ligands,2 which are widely used in
modern metallocomplex catalysis, their lower toxicity,
greater air and moisture stability, and the synthetic
availability of a broad range of such compounds resulted
in their high popularity in catalysis. In the last ten years,
a lot of work devoted to the application of this type of car-
bene both as ligands in metallocomplex catalysis2b,3 and as
organocatalysts4 in different reactions has been reported.
1
Figure 1. Chiral zwitterionic carbene precursor.
Herein, we report the asymmetric synthesis of compound
1: a precursor of the new class of N-heterocyclic carb-
enes, containing an amino acid moiety as a substituent at
the nitrogen atom of the imidazolium ring (Fig. 1). This
amino acid or its analogues may in future be used as a
tridentate CNO ligand in asymmetric metallocomplex
catalysis or may be applied as an organocatalyst in different
reactions.
Some examples of chiral NHC derivatives and their appli-
cations in asymmetric catalysis have recently appeared in
the literature.3b,f,g,4a However, among the studies devoted
to the synthesis and application of chiral NHC’s in asym-
metric catalysis,3a,b,g,4a there is no mention of NHC’s con-
taining amino acid moieties, attached to the nitrogen atom
of the imidazolium ring.
2. Results and discussion
To obtain (S)-2-amino-3-(3-methyl-1H-imidazol-3-ium-1-
yl)propanoate 1, we applied a well-known approach via
the use of chiral Ni(II) complexes previously reported by
some of us,5,6 as outlined in Scheme 1.
*
Dehydroalanine complex 3 was synthesized from glycine
complex 2 in a two-step procedure (Scheme 1), as described
Corresponding author. Tel./fax: +7 499 135 63 56; e-mail: yubel@
ineos.ac.ru
0957-4166/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2008.03.002

Y. N. Belokon et al. / Tetrahedron: Asymmetry 19 (2008) 756–760
757
Me
X
N
N
O
N
O
N
O
N
O
N
N
N
Ph
H
Ph
H
Ph
H
Ph
H
O
Ni
N
O
Ni
N
O
Ni
N
O
Ni
N
i
ii
iii
X = I
5
H
H
N
N
N
N
Ph
Ph
Ph
Ph
iv
6
O
X = BF4
O
O
O
2
3
4
Scheme 1. Reagents and conditions: (i) (1) CH2O (5 equiv), KOH (1.25 equiv), MeOH, rt, 2 h then AcOH (1.1 equiv), 84.5%; (2) Ac2O (3 equiv), Na2CO3
(2 equiv), CH3CN, reflux, 2 h, 93%; (ii) imidazole (1.5 equiv), CH3CN, 50 °C, 6 h, 71%; (iii) MeI (10 equiv), CH2Cl2, rt, 24 h; (iv) ion exchange
chromatography (Dowex 1 ꢀ 8, MeOH/H2O (2:1)), 69%.
earlier.7 The addition of imidazole to the carbon–carbon
double bond of 3 led to 4. The earlier suggested procedure7
N Me
1) MeOH, HCl, reflux, 10 min
2) DOWEX H+
N
5 or 6
was modified by the additional washing of the chloroform
solution of the reaction mixture with 10% aqueous acetic
acid solution to remove residual imidazole. Treatment of
complex 4 with iodomethane gave the methylated ionic
complex 5 with an iodide ion as a counteranion. To char-
acterize the cationic complex, it was converted into a more
stable complex 6 with a tetrafluoroborate counteranion via
ion exchange on an anion exchange resin. X-ray quality red
colored single crystals of 6 were obtained from a CHCl3/
MeOH (1:1) solution (Fig. 2).
H
COO
H2N
1
Scheme 2.
To isolate target amino acid 1, cationic complex 5 or 6 was
decomposed with 6 M hydrochloric acid via a standard
procedure (Scheme 2).8 The nature of the complex counter-
anion did not influence the course of this reaction. Even the
less stable iodide complex could be hydrolyzed to the free
amino acid without any significant amount of by-product
formation. Even unpurified complex 5 (obtained simply
by evaporating the reaction mixture without any ion
exchange or other purification) could be used to provide
amino acid 1.
Amino acid 1 obtained according to the standard tech-
nique8 was additionally purified on silica. The pure isolated
amino acid is an extremely hygroscopic yellowish oil, which
Figure 3. X-ray structure of 7.
becomes glassy during prolonged drying in vacuo over par-
affin and P2O5 at 64 °C and slowly decomposes at room
temperature in air. The 2-H proton of the imidazolium
moiety undergoes H–D exchange in a D2O solution, which
can be monitored by 13C NMR spectroscopy following the
1
appearance of a triplet at 136.28 ppm with JDC = 25 Hz.
The N-Boc derivative of compound 1was obtained by reac-
tion with Boc2O in THF. Compound 7 is more stable than
1
the free amino acid 1. The H NMR spectrum (CDCl3) of
compound 7 exhibited a strong downfield resonance
(d = 9.93 ppm) for 2-H of the imidazolium ring and an
NH signal at d = 6.01 ppm.
X-ray quality white single crystals of 7 were grown from a
CH2Cl2/MeOH (1:1) solution (Fig. 3). As can be seen from
The decomposition can be detected by the appearance of a sharp smell
and a bright yellow coloring.
Figure 2. X-ray structure of 6.

758
Y. N. Belokon et al. / Tetrahedron: Asymmetry 19 (2008) 756–760
600 spectrometers at ambient temperature. Chemical shifts
N Me
Ag
N Me
Ag2O, CH2Cl2
RT, 24 h
are given in ppm relative to tetramethylsilane (d 0) and
were referenced to the indicated residual protons in the sol-
vent, and J values are quoted in Hertz. The resonances of
compounds 1, 6, 7 were assigned by Hetcor and NOESY
experiments. The 2D heteronuclear one-bond proton–car-
N
N
O
O
H
COO
H
COO
O
N
O
N
H
H
t-Bu
t-Bu
1
7
8
bon correlation experiment was performed in H-detection
mode via single-quantum coherence (HSQC). Microanaly-
ses were carried out by the staff of the Nesmeyanov’s Insti-
tute of Organoelement Compounds, Russian Academy of
Sciences Microanalytical department. Optical rotations
were measured with a Perkin–Elmer 241 polarimeter, using
a cell of 0.5 dm path length at 25 °C. The concentration c is
expressed in g/100 ml.
Scheme 3.
All reagents and starting materials were purchased from
Aldrich or Acros, and used without purification unless
otherwise stated. Silica Gel 60 (0.040–0.063 mm) (Merck)
was used for column chromatography. Dowex 50W ꢀ 8
and Dowex 1 ꢀ 8 from Aldrich were used for ion exchange
chromatography. All solvents were purified in the usual
way.12
Figure 4. Fragments of 13C NMR spectra of 7 (a) and 8 (b).
4.1. X-ray structure determination
Fig. 3, the zwitterionic structure of 7 is clearly established.
The charge on the carboxyl group is stabilized by the water
molecule of solvation.
Data were collected on Bruker SMART APEX II CCD
(for 6) and Bruker SMART 1000 CCD (for 7) diffractom-
eters (k(MoKa)-radiation, graphite monochromator, x and
u scan mode) and corrected for absorption using the SAD-
ABS program (versions 2.0313 for 6 and 2.0114 for 7). For
The usual precursors of NHC-metal complexes are the cor-
responding silver complexes, which are routinely applied as
ligand transfer reagents.9,3g To synthesize the silver-NHC
complex 8 from 7, a very simple procedure (Scheme 3),
as suggested by Lin et al., was used.10
Table 1. Crystallographic data for 6 and 7
Compound
6ꢁCH3OH
7ꢁ1/2CH2Cl2ꢁ
1/2H2O
The elemental analysis of complex 8 proved that it did
contain the Ag derivative of 7. The evidence in favor of
the formation of the desired NHC–Ag complex 8 was the
Empirical formula
Fw
T (K)
Crystal size (mm)
Crystal system
Space group
C
712.19
100(2)
33H36N5O4NiBF4 C12.5H21N3O4.5Cl
320.77
120(2)
1
disappearance of the NCHN resonance in the H NMR
0.20 ꢀ 0.20 ꢀ 0.15 0.30 ꢀ 0.08 ꢀ 0.06
at 9.93 ppm and a strong downfield shift of the signal
attributed to the NCN fragment in the 13C NMR spectrum
of 8. The latter signal changes from a sharp singlet at
Orthorhombic
P212121
Orthorhombic
P212121
8.8820(19)
14.613(3)
24.314(5)
3155.7(12)
8
1.350
1360
0.264
52
˚
a (A)
11.1950(3)
12.1158(3)
23.0563(6)
3127.27(14)
4
1.513
1480
0.692
61
˚
b (A)
139.04 ppm to
a broad doublet at 179 ppm with
1JAgC = 270 Hz (Fig. 4), which is in agreement with the
˚
c (A)
3
˚
reported silver(I)-imidazole-2-ylidenes.11
V (A )
Z
dc (g cmꢂ3
F(000)
)
l (mmꢂ1
2hmax (°)
)
3. Conclusion
Index range
ꢂ15 6 h 6 15,
ꢂ17 6 k 6 17,
ꢂ32 6 l 6 32
ꢂ10 6 h 6 10,
ꢂ17 6 k 6 17,
ꢂ29 6 l 6 30
21,489
6087
2864
In conclusion, we have reported the synthesis of a new type
of enantiomerically pure amino acid, bearing an imidazoli-
um moiety. The N-Boc derivative of the amino acid can be
easily transformed into a chiral silver carbene complex,
which potentially can be used in the future as a ligand
transfer reagent in reactions involving asymmetric metallo-
complex catalysis.
No. of reflections collected 42,470
No. of unique reflections
No. of reflections with
I > 2r(I)
9449
8386
Data/restraints/parameters 9449/1/429
6087/0/369
0.0742; 0.1717
0.2023; 0.2137
1.030
R1; wR2 (I > 2r(I))
R1; wR2 (all data)
GOF on F2
Absolute structure
parameter
0.0340; 0.0793
0.0413; 0.0825
1.024
4. Experimental
0.010(7)
0.02(16)
1H and proton decoupled 13C NMR spectra were recorded
with Bruker AVANCE 300, AVANCE 400, or AVANCE
Tmin; Tmax
0.874; 0.903
0.926; 0.986

Y. N. Belokon et al. / Tetrahedron: Asymmetry 19 (2008) 756–760
759
details see Table 1. The structures were solved by direct
methods and refined by a full-matrix least squares tech-
nique on F2 with anisotropic thermal parameters for non-
hydrogen atoms. The independent part of the unit cell of
6 contains one methanol solvate molecule, and the inde-
pendent part of the unit cell of 7 contains one methylene
chloride and one water solvate molecule. The absolute
structures of 6 and 7 were objectively determined by the
refinement of Flack parameters to 0.010(7) and 0.02(16),
respectively. The hydrogen atoms of the NH-groups in 7
as well as the solvate methanol molecule in 6 and the sol-
vate water molecule in 7 were localized in the difference-
Fourier map and included in the refinement with fixed posi-
tional and thermal parameters. The other hydrogen atoms
in both compounds were placed in calculated positions and
refined within the riding model with fixed thermal
parameters (Uiso(H) = 1.5Ueq(C) for the CH3-groups and
Uiso(H) = 1.2Ueq(C) for the other groups). All calculations
were carried out using the SHELXTL PLUS program (versions
6.1215 for 6 and 5.1016 for 7). Crystallographic data for 6
and 7 have been deposited with the Cambridge Crystallo-
graphic Data Center. CCDC 674217 and 674218 contain
the supplementary crystallographic data for this paper.
These data can be obtained free of charge from the Direc-
tor, CCDC, 12 Union Road, Cambridge CB2 1EZ, UK
(Fax: +44 1223 336033; e-mail: deposit@ccdc.cam.ac.uk
or www.ccdc.cam.ac.uk).
(C-27), 133.67 (C-21 or C-25), 134.07 (C-20), 138.39 (C-
16), 143.50 (C-5), 172.73 (C-10), 176.86 (C-3), 180.61 (C-1).
4.3. ({1-[(S)-2-({2-[(2S,1RN)-1-Benzylpyrrolidine-2-carbox-
amido]phenyl}(phenyl)methyleneamino)-2-carboxylato-
N,N0,N00,O]-nickel(II)}ethyl)-3-methyl-1H-imidazol-3-ium
tetrafluoroborate 6
To a solution of complex 4 (8 g, 0.0138 mol) in CH2Cl2
(50 ml), iodomethane (19.7 g, 8.65 ml, 0.138 mol) was
added. The reaction mixture was stirred at room tempera-
ture for 24 h, the reaction being monitored by TLC (Silica-
gel, MeOH/CH2Cl2 (1:1)). Then, the reaction mixture was
evaporated on a rotary evaporator, the residue was dis-
solved in MeOH/H2O (2:1) (20 ml), and passed through a
column containing ion exchange resin Dowex 1 ꢀ 8 in
ꢂ
BF4 form (100 g). The resulting solution was evaporated.
The residue was recrystallized from MeOH to give complex
5 in a pure form. Yield 6.5 g (69%). De >99% according to
25
1H NMR data. Mp 203–204 °C, ½aꢃD ¼ þ2386 (c 0.056,
MeOH). Anal. Calcd for C32H22BF4N5NiO3ꢁH2O: C,
55.05; H, 4.91; N, 10.03. Found: C, 54.91; H, 4.60; N,
9.95. 1H NMR (600 MHz, CDCl3/CD3OD (1:1)): 2.16
(m, 1H, d-Pro), 2.21 (m, 1H, c-Pro), 2.57 (m, 2H, b-Pro),
3.21 (m, 1H, c-Pro), 3.35 (dd, 1H, d-Pro, 3J1 7.0, 3J2
10.0), 3.48 (d, 1H, CH2(Bn), 3J 12.0), 3.54 (dd, 1H, a-
3
3
Pro, J1 8.0, J2 10.0), 3.91 (s, 3H, CH3NImid), 4.15 (dd,
3
3
3
1H, NCHCO2, J1 4.0, J2 8.0), 4.18 (d, 1H, CH2(Bn), J
2
3
4.2. [(S)-2-({2-[(2S,1RN)-1-Benzylpyrrolidine-2- carbox-
amido]phenyl}(phenyl)methyleneamino)-3-(1H-imidazol-1-
yl)propanoato-N, N0,N00,O] nickel(II) 4
12.0), 4.27 (dd, 1H, CH2–NImid, J 15.0, J 4.0), 4.68 (dd,
2
3
1H, CH2NImid, J 15.0, J 4.0), 6.68 (s. 1H, Imid), 6.69
3
3
(d, 1H, Ar, J 5.0), 6.72 (dd, 1H, Ar, J1 8.0, J2 15.0),
7.16 (m, 2H, Ar), 7.20 (m, 1H, Ar, J 5.0 cannot have m
and J), 7.35 (t, 2H, Ar, J 8.0), 7.40 (m, 1H, Ar), 7.52 (d,
1H, Imid, J 2.0), 7.61–7.70 (m, 3H, Ar), 7.99 (d, 1H, Ar,
J 9.0), 8.21 (d, 2H, Ar, J 8.0), 8.73 (s, 1H, Imid). 13C
NMR (150MHz, CDCl3/CD3OD (1:1)): 24.32 (C-13),
31.21 (C-12), 36.54 (C-19), 51.97 (C-15), 58.65 (C-14),
64.65 (C-26), 68.94 (C-2), 71.55 (C-11), 121.38 (C-8),
122.44 (C-17), 123.75 (C-9), 124.14 (C-18), 125.80 (C-4),
126.90 (C-30), 127.58 (C-21 or C-25), 128.96 (C-29,
C-31), 128.98 (C-22, C-24), 129.81 (C-23, C-7), 130.67
(C-6), 131.25 (C-28, C-32), 133.21 (C-22, C-24), 133.25
(C-27), 133.79 (C-21 or C-25), 134.11 (C-20), 138.31
(C-16),143.15 (C-5), 174.97 (C-10), 177.49 (C-3), 181.90 (C-1).
To a solution of nickel complex 3 (10 g, 0.0196 mol) in
CH3CN (100 ml), imidazole (2.1 g, 0.0309 mol) was added.
The reaction mixture was stirred at 50 °C for 6 h, the reac-
tion being monitored by TLC (Silicagel, CHCl3/acetone
5:1). Then, the reaction mixture was cooled to room tem-
perature and filtered through a glass pored filter. The solu-
tion was evaporated on a rotary evaporator and the residue
dissolved in CHCl3 (100 ml) and washed with aqueous ace-
tic acid (30 ml 10% solution). The organic layer was iso-
lated, washed with water (3 ꢀ 30 ml), and evaporated.
The residue was recrystallized from benzene/acetone (6:1)
to give complex 4 in a pure form. Yield 8 g (71%).
De >99% according to 1H NMR data. Mp 204–207 °C,
25
½aꢃD ¼ þ2356 (c 0.05, MeOH). Anal. Calcd for
4.4. (S)-2-Amino-3-(3-methyl-1H-imidazol-3-ium-1-yl)pro-
panoate 1
C31H29N5NiO3ꢁC6H6: C, 67.70; H, 5.37; N, 10.67. Found:
1
C, 67.91; H, 5.68; N, 10.81. H NMR (400 MHz, CDCl3):
1.83 (m, 1H, d-Pro), 2.03 (m, 1H, c-Pro), 2.39 (m, 1H, c-
To a solution of complex 4 (8 g, 0.0138 mol) in CH2Cl2
(50 ml), iodomethane (19.7 g, 8.65 ml, 0.138 mol) was
added. The reaction mixture was stirred at room tempera-
ture for 24 h, the reaction being monitored by TLC [Silica-
gel, MeOH/CH2Cl2 (1:1)]. Then, the reaction mixture was
evaporated on a rotary evaporator and the residue was dis-
solved in MeOH (30 ml). Next 6 M HCl (30 ml) was added
to the methanol solution and the reaction mixture was
refluxed for 10 min and then cooled to room temperature.
The solvent was evaporated and a small volume of water
was added to the residue. The resultant precipitate of (S)-
BBP hydrochloride was filtered and washed with water.
The filtrate was neutralized by aqueous ammonia to
pH ꢄ 6–7 and the remaining (S)-BBP was extracted with
3
Pro), 2.57 (m, 2H, b-Pro), 3.18 (dd, 1H, d-Pro, J1 7.3,
3J2 9.4), 3.48 (d, 1H, CH2(Bn), 3J 12.8), 3.81 (dd, 1H,
2
3
CH2–NImid, J 16.3, J 4.6), 4.26 (m, 3H, CH2(Bn), CH2–
NImid, NCHCO2), 6.67 (d, 2H, Ar, J 4.1), 6.95 (d, 1H,
Ar, J 7.1), 6.67 (s, 1H, Imid), 7.18 (m, 2H, Ar), 7.20–7.35
(m, 5H, Ar), 7.50–7.60 (m, 4H, Ar), 8.01 (d, 2H, Ar, J
7.3), 8.28 (d, 1H, Ar, J 8.7); 13C NMR (75 MHz, CDCl3):
23.24 (C-13), 30.80 (C-12), 49.03 (C-15), 57.55 (C-14),
63.68 (C-26), 70.36 (C-2), 70.63 (C-11), 120.75 (C-8, C-17
or C18), 123.63 (C-9), 125.55 (C-4), 126.87 (C-30), 127.40
(C-21 or C-25), 128.86 (C-29, C-31), 128.93 (C-22, C-24),
129.45 (C-23), 129.66 (C-7), 130.08 (C-17 or C18), 130.34
(C-6), 131.52 (C-28, C-32), 133.14 (C-22, C-24), 133.29

760
Y. N. Belokon et al. / Tetrahedron: Asymmetry 19 (2008) 756–760
1
t
CHCl3 (3 ꢀ 30 ml). The aqueous layer was filtered through
a paper filter and absorbed onto strongly acidic ion
exchange resin Dowex 50W ꢀ 8 (100 g) and carefully
washed with water, until the washings became neutral.
The desired amino acid (as was shown before5,8 no
racemization of the amino acid moiety takes place under
the reaction conditions, thus the ee of the isolated amino
acid 1 can be assumed to be equal to de of the initial
complex 4 or 6) was washed off with 5% aqueous ammonia.
The obtained solution was evaporated to give 2.3 g of
amino acid containing some impurities as a yellow oil.
(S)-(1-Methyl)-imidazol-3-ylidene-alaninate was purified
using column chromatography (Silicagel, MeOH). Con-
taminants were washed off with MeOH and the desired
28.6. H NMR (300 MHz, CDCl3): 1.42 (s, 9H, Bu), 3.76
(s, 3H, CH3), 4.33 (m, 1H, CHCO2), 4.52 (dd, 1H, CH2NI-
mid, 2J 13.8, 3J 4.2), 4.79 (d, 1H, CH2NImid, 2J 13.8), 5.55 (d,
1H, NH, J 3.3), 6.84 (s, 1H, @CHNImidCH3), 6.85 (s, 1H,
@CHNImidCH2). 13C NMR (150 MHz, CDCl3): 28.44
(C(CH3)3), 38.97 (NCH3), 52.16 (CH2), 56.30 (CHCO2),
79.37 (C(CH3)3), 120.97 (@CHNImidCH2), 123.43
(@CHNImidCH3), 155.37 (OC(O)NH), 173.19 (COOꢂ),
1
179.6 (d, NCAgN, JAgC 270).
Acknowledgments
The authors thank INTAS (05-1000008-7822), ISTC (G-
1361), and RFBR (08-03-00466) for financial support.
amino acid was washed off with MeOH/H2O (1:1). Yellow-
25
ish oil. Yield 1.7 g (73%). ½aꢃD ¼ ꢂ18:4 (c 1.4, H2O)
(ee >99% according to de >99% of the initial complex 6).
Anal. Calcd for C7H11N3O2ꢁ1/4 H2CO3: C, 47.15; H,
References
1
6.28; N, 22.75. Found: C, 47.15; H, 6.32; N, 22.12. H
NMR (400 MHz, D2O): 3.57 (t, 1H, CHCO2, J 5.8), 3.74
(s, 3H, CH3), 4.24 (d, 2H, CH2NImid, J 5.8), 7.28 (d, 1H,
@CHNImidCH3, J 2.0), 7.29 (d, 1H, @CHNImidCH2, J
2.0). 13C NMR (150 MHz, D2O): 35.7 (CH3), 53.04
(CH2), 55.88 (CHCO2), 122.63 (@CHNImidCH2), 123.62
(@CHNImidCH3), 136.28 (t, NCDN, 1J 25.0), 177.69
(COOꢂ).
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4.5. (S)-2-(tert-Butoxycarbonylamino)-3-(3-methyl-1H-
imidazol-3-ium-1-yl)propanoate 7
To an emulsion of amino acid 1 (250 mg, 1.48 mmol) in
THF (1 ml), Boc2O (438 mg, 0.46 ml, 2 mmol) was added.
The reaction mixture was stirred at room temperature for
48 h. Solvent was evaporated on a rotary evaporator and
the residue was purified using column chromatography
(Silicagel, MeOH). The desired product was obtained as
´
´
4. (a) Marion, N.; Dıez-Gonzalez, S.; Nolan, S. P. Angew.
Chem., Int. Ed. 2007, 46, 2988; (b) Enders, D.; Balensiefer, T.
Acc. Chem. Res. 2004, 37, 534; (c) Enders, D.; Niemeier, O.;
Henseler, A. Chem. Rev. 2007, 107, 5606.
white crystals. Yield 180 mg (57%). Mp 91–95 °C.
25
½aꢃD ¼ þ118 (c 1.02, CHCl3) (ee >99% according to
5. Belokon, Y. N.; Bulychev, A. G.; Vitt, S. V.; Struchkov, Y.
T.; Batsanov, A. S.; Timofeeva, T. V.; Tsyryapkin, V. A.;
Ryzhov, M. C.; Lysova, L. A.; Bakhmutov, V. I.; Belikov, V.
M. J. Am. Chem. Soc. 1985, 107, 4252.
ee >99% of the initial amino acid 1). Anal. Calcd for
C12H19N3O4ꢁH2O: C, 50.16; H, 7.37; N, 14.63. Found: C,
49.87; H, 6.81; N, 14.54. 1H NMR (300 MHz, CDCl3):
1.41 (s, 9H, tBu), 4.01 (s, 3H, CH3), 4.17 (m, 1H, CHCO2),
4.63–4.85 (m, 2H, CH2NImid), 6.01 (d, 1H, NH, J 1.2), 7.08
(s, 1H, @CHNImidCH3), 7.18 (s, 1H, @CHNImidCH2), 9.93
(s, 1H, NCHN). 13C NMR (75 MHz, CDCl3): 28.41
(C(CH3)3), 36.29 (NCH3), 51.61 (CH2), 56.15 (CHCO2),
79.39 (C(CH3)3), 121.74 (@CHNImidCH2), 123.37
(@CHNImidCH3), 139.04 (NCHN), 156.00 (OC(O)NH),
170.62 (COOꢂ).
6. Belokon’, Y. N. Janssen Chim. Acta 1992, 2, 4.
7. Belokon’, Y. N.; Sagyan, A. S.; Djamgaryan, S. M.;
Bakhmutov, V. I.; Belikov, V. M. Tetrahedron 1988, 44, 5507.
8. Belokon, Y. N.; Sagyan, A. S.; Djamgaryan, S. A.; Bakhmu-
tov, V. I.; Vitt, S. I.; Batsanov, A. S.; Struchkov, Y. T.;
Belikov, V. M. J. Chem. Soc., Perkin Trans. 1 1990, 2301.
9. (a) Lin, I. J. B.; Vasam, C. S. Coord. Chem. Rev. 2007, 251,
642; (b) Peris, E. Top. Organomet. Chem. 2007, 21, 83.
10. Wang, H. M. J.; Lin, I. J. B. Organometallics 1998, 17, 972.
´
´
11. Caballero, A.; Dıez-Barra, E.; Jalon, A. F.; Merino, S.;
Tejeda, J. J. Organomet. Chem. 2001, 617–618, 395.
12. Gordon, A. J.; Ford, R. A. The Chemist’s Companion; John
Wiley & Sons: New York, 1972.
4.6. (S)-(1-(2-(tert-Butoxycarbonylamino)-2-carboxylato-
ethyl)-3-methyl-1H-imidazol-2-ylidene)silver(I) 8
13. Sheldrick, G. M. SADABS, v. 2.03, Bruker/Siemens Area
Detector Absorption Correction Program, Bruker AXS,
Madison, Wisconsin, 2003.
14. Sheldrick, G. M. SADABS, v. 2.01, Bruker/Siemens Area
Detector Absorption Correction Program, Bruker AXS,
Madison, Wisconsin, 1998.
15. Sheldrick, G. M. SHELXTL, v. 6.12, Structure Determination
Software Suite, Bruker AXS, Madison, Wisconsin, 2001.
16. Sheldrick, G. M. SHELXTL, v. 5.10, Bruker AXS, Madison,
Wisconsin, 1998.
To a solution of Boc-protected amino acid 7 (50 mg,
0.186 mmol) in CH2Cl2 (3 ml), Ag2O (21.6 mg,
0.093 mmol) was added. The resulting suspension was stir-
red for 24 h in the dark and then filtered. Solvent was
removed on a rotary evaporator. The desired product
was obtained as a white solid. Yield 55 mg (80%). Mp
25
195 °C (decomposition). ½aꢃD ¼ þ60:0 (c 1.02, CHCl3).
Anal. Calcd for C12H18AgN3O4: C, 38.27; H, 4.82; N,
11.17; Ag, 28.68. Found: C, 38.32; H, 4.82; N, 11.17; Ag,