Synthesis of amidoalkyl imidazol-2-ylidene ligands and their application to enantioselective copper-catalysed conjugate addition

Article abstract of DOI:10.1055/s-2007-1000832

A small library of precursors to chiral amidoalkyl imidazol-2-ylidene ligand was synthesised via a two-step procedure starting from commercially available amino alcohols. Preliminary screening of these bidentate ligands for the enantioselective copper-catalysed conjugate addition of diethyl zinc to cyclohexenone revealed some moderate ee values. Related chiral iminoalkyl imidazole-2-ylidene ligands demonstrated much poorer enantioselectivity. The results indicate that chelation involving a covalent copper-nitrogen bond gives better selectivity than that arising from a dative copper-nitrogen co-ordination. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-1000832

LETTER
21
Synthesis of Amidoalkyl Imidazol-2-ylidene Ligands and Their Application to
Enantioselective Copper-Catalysed Conjugate Addition
A
midoalkyl Imi
h
dazol-2-ylid
e
ene
L
igand
o
s
Moore, Mahboub Merzouk, Neil Williams*
School of Pharmacy and Chemistry, Kingston University, Penrhyn Road, Kingston upon Thames, Surrey, KT1 2EE, UK
Fax +44(208)5477497; E-mail: N.A.Williams@kingston.ac.uk
Received 13 March 2007
have been successfully applied to the catalysis of other or-
Abstract: A small library of precursors to chiral amidoalkyl imida-
zol-2-ylidene ligand was synthesised via a two-step procedure start-
ing from commercially available amino alcohols. Preliminary
screening of these bidentate ligands for the enantioselective copper-
catalysed conjugate addition of diethyl zinc to cyclohexenone re-
vealed some moderate ee values. Related chiral iminoalkyl imida-
ganic reactions.12
In light of these results, we report the synthesis of ami-
doalkyl imidazol-2-ylidene ligand precursors in two steps
from commercially available b-amino alcohols and a pre-
liminary evaluation of their performance in copper-catal-
ysed conjugate addition of diethylzinc to cyclohexenone.
A comparison with related iminoalkyl imidazol-2-
ylidenes is also presented.
zole-2-ylidene
ligands
demonstrated
much
poorer
enantioselectivity. The results indicate that chelation involving a
covalent copper–nitrogen bond gives better selectivity than that
arising from a dative copper–nitrogen co-ordination.
Key words: asymmetric catalysis, carbenes, copper, Michael addi-
tions
The aim was to develop a short route for the synthesis of
a small library of chiral ammoniumalkyl imidazolium
salts that would serve as precursors to bidentate ami-
doalkyl imidazol-2-ylidenes.
Despite the great interest in the use of N-heterocyclic car-
benes (NHCs) as ligands in homogeneous catalysis,1 their
use in asymmetric catalysis, and more specifically conju-
gate addition, is limited compared to that of nitrogen- and
phosphorus-based ligands.2 Excellent enantioselectivities
have been reported for a number of reactions using NHCs
as ligands, such as hydrogenation3, olefin metathesis,4 and
allylic alkylation.5 Woodward et al. first showed that
NHCs accelerated the rate of copper-catalysed conjugate
addition.6 This was soon followed by the first reports of
the use of monodentate chiral NHCs in asymmetric cop-
per-catalysed conjugate addition to cyclohexenone by
Alexakis7 and Roland.8 The best results (54% ee) were ob-
tained with a matched pair imidazolidin-2-ylidene con-
taining exocyclic and endocyclic stereogenic centres.
Improved results were obtained by using silver–carbene
complexes as ligand-transfer reagents; ee as high as 93%
were obtained for the addition of diethylzinc to cyclohep-
tenone.9 Further developments involved the synthesis of
chiral, chelating hydroxyalkyl imidazolidin-2-ylidenes
via a five-step procedure from commercially available b-
amino alcohols.10 These chelating ligands, containing a
single exocyclic stereogenic centre, gave the best results
yet seen for conjugate addition to cyclohexenone using
NHCs (89% ee). Screening of the alkoxide ligands, which
contain a stereogenic centre on the NHC ring backbone,
produced modest levels of enantioselectivity.11 Silver(I)
complexes of heterobidentate ligands, containing an NHC
group coupled and an alcohol or amine moiety have been
structurally characterised.11 Copper–NHC complexes
b-Amino alcohols 1 were converted into the aminoalkyl
bromide hydrobromide salts 2 in high yields by stirring
with thionyl bromide and DMF in cyclohexane for 16
hours, according to the method of Jung (Equation 1).13
The amino group enhances the rate of bromination and the
reaction proceeds with retention of configuration. The
salts are conveniently isolated from the reaction by filtra-
tion. Aminoalkyl bromide hydrobromides were coupled
to N-substituted imidazoles 3 to give ammoniumalkyl im-
idazolium salt derivatives 4 (Equation 2). The salts were
most conveniently obtained by heating the reactants in ac-
etonitrile under reflux for 16 hours. After the volatiles
R1
R1
SO2Br, DMF
H2N
OH
BrH3N
Br
1a R = i-Bu
1b R = Bn
2a 85%
2b 55%
Equation 1 Synthesis of chiral aminoalkyl bromide hydrobromide
R1
Br
80 °C, MeCN
N
+
N
R2
N
N
R2
BrH3N
Br
R1
NH3Br
2a,b
3
4a R1 = i-Bu, R2 = Me 40%
4b R1 = i-Bu, R2 = Bn 37%
4c R1 = i-Bu, R2 = Ph 21%
4d R1 = i-Bu, R2 = Mes 20%
4e R1 = Bn, R2 = Bn 32%
SYNLETT 2008, No. 1, pp 0021–0024
x
x.
x
x.
2
0
0
7
Advanced online publication: 11.12.2007
DOI: 10.1055/s-2007-1000832; Art ID: D07507ST
Equation 2 Synthesis of chiral aminoalkyl imidazolium salts
© Georg Thieme Verlag Stuttgart · New York

22
T. Moore et al.
LETTER
were removed under vacuum, the residues were recrystal- dentate NHC ligands. One of the attractive design features
lised from acetonitrile and diethyl ether.
of our ligands is that the stereogenic centre is b to the
NHC nitrogen and fairly close to the metal centre. The
amidoalkyl imidazol-2-ylidene 4b with the stereogenic
centre b to the NHC nitrogen gave better results than the
analogous alkoxy NHC, 61% compared with 53% and
17%.11 However, Mauduit et al. obtained superior results
with ligands containing the stereogenic centre a to the
NHC nitrogen and hence further away from the metal cen-
tre, suggesting that a substituent next to the chelating
group induces a sizeable steric hindrance to enantiocon-
trol of the addition. Changing the alkyl group at the ste-
reogenic centre of the amino side chain of the ligand
precursors 417 has a substantial influence on enantioselec-
tivity. Replacing the isobutyl group with a benzyl group
results in the ee being reduced from 61% to 28%. This is
consistent with a substituent next to the chelating amido
group having an influence on the enantiocontrol of the re-
action. In comparison, Mauduit noted that varying the
alkyl substituent for ligands in which the stereogenic cen-
tre is further removed from the chelating group had only a
minor effect on enantioselectivity.
The potential of amidoalkyl imidazol-2-ylidenes, derived
from ammoniumalkyl imidazolium salt precursors, as
ligands for enantioselective copper-catalysed conjugate
addition was investigated. The addition of diethylzinc to
cyclohexenone was chosen as the test reaction. The cop-
per(II) amidoalkyl imidazol-2-ylidene catalyst was gener-
ated by adding more than three equivalents of n-
butyllithium in hexanes to a toluene solution of ammoni-
umalkyl imidazolium salt 4 and Cu(OTf)2 at –78 °C. Two
equivalents of base are required to deprotonate the ammo-
nium group to give an amido group and a further equiva-
lent is required to generate the carbene from the
imidazolium salt. A 2:3 copper-to-ligand ratio was em-
ployed, as used by Mauduit et al.10 for alkoxy imidazoli-
din-2-ylidenes. After stirring at –78 °C for 30 minutes, an
internal standard (dodecane), diethylzinc, and then cyclo-
hexenone were added. Under these conditions the reaction
is complete after three hours. Results of some initial
ligand screening are presented in Table 1. Reactions were
carried out in duplicate. Enantioselectivities were deter-
mined by chiral GC using a Supelco Alpha-dex 220 col-
umn.
Table 2 Evaluation of Ligands 4b for Enantioselective Copper-Ca-
talysed Addition of Diethyl Zinc to Cyclohexenone
Br
Table 1 Evaluation of Ligands 4a–e for Enantioselective Copper-
Catalysed Addition of Diethyl Zinc to Cyclohexenone
Ph
N
N
(3 mol%)
O
O
Br
i-Bu
NH3Br
N
N
R2
4b
+
(3 mol%)
Et2Zn
O
O
*
R1
base (12 mol%)
copper source (2 mol%)
toluene, 3 h
NH3Br
4
+
Et2Zn
*
BuLi (12 mol%),
Copper source Base
Temp (°C) Conv. (%) ee (%)
Cu(OTf)2 (2 mol%)
toluene, –78 °C, 3 h
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OAc)2
BuLi
BuLi
DBU
BuLi
–78
20
98
94
93
88
61 (S)
48 (S)
31 (S)
38 (S)
Ligand
4a
R1
R2
Conv. (%)
ee (%)
12 (S)
61(S)
9 (S)
i-Bu
i-Bu
i-Bu
i-Bu
Bn
Me
Bn
Ph
48
98
72
77
87
–78
–78
4b
4c
Results of some attempts to optimise enantioselectivity
using 4b are presented in Table 2. A lower enantioselec-
tivity is observed at higher temperature (20 °C). This is
different to the behaviour observed for alkoxy NHC,10
where higher ee were obtained at 20 °C, but similar to that
reported for other NHC systems.7 Studies on copper-catal-
ysed conjugate addition using NHC-based ligands have
shown that enantioselectivity is very sensitive to temper-
ature, solvent, substrate structure, copper source, and
base. This is attributed to the formation of different types
of copper and metal alkyl aggregates, leading to the pos-
sibility of a number of different mechanisms operating.
An organic base, DBU, was tested as an alternative base
to BuLi with ligand 4b; it gave 93% conversion but a re-
duced ee of 31%. Use of copper acetate as an alternative
copper source with 4b also resulted in a lower ee (38%).
4d
Mes
Bn
7 (S)
4e
28 (S)
The nature of the N-substituent (R2) has a profound effect
on the enantioselectivity of the reaction. The N-benzyl de-
rivative gave a significantly higher ee than the smaller
methyl derivative and the N-aryl derivatives. This differs
from the results observed for alkoxy imidazolidin-2-
ylidenes, where mesityl derivatives generally gave the
highest ee. However, N-benzyl derivatives did give higher
enantioselectivities than ligands bearing an N-phenyl sub-
stituent.10b Hoveyda14 and Gade15 have also observed dra-
matic effects on ee for copper-catalysed enantioselective
allylic substitution and rhodium-catalysed asymmetric
hydrosilylation by varying the N-substituents on heterobi-
Synlett 2008, No. 1, 21–24 © Thieme Stuttgart · New York

LETTER
Amidoalkyl Imidazol-2-ylidene Ligands
23
Chiral iminoalkyl imidazolium salts 5 have been previ- In conclusion, the synthesis of new class of chiral ami-
ously synthesised and evaluated as ligand precursors for doalkyl imidazol-2-ylidenes, via a simple two-step proce-
palladium-catalysed allylic substitution.16 A number of dure from commercially available amino alcohols, has
these ligands were screened for copper-catalysed conju- been achieved. Preliminary results indicate that the alkyl
gate addition of diethylzinc to cyclohexenone, the results group at the stereogenic centre and the N-alkyl/aryl sub-
are presented in Table 3. For these ligands 4 mol% of cat- stituent have an effect on enantioselectivity. Comparisons
alyst with 4 mol% of sodium methoxide as a base and a re- between imino- and amino-based ligands suggest that co-
action temperature of 20 °C were the most efficacious valent bonding of the nitrogen group is critical for signif-
conditions. The ligands were shown to be active towards icant enantioselectivity. Further optimisation of the
conjugate addition but only 5d gave a significant ee. An reaction conditions should realise an improvement on the
ee of only 8% was obtained when BuLi was used as a base enantioselectivities reported so far. Testing on additional
with 5d. Again the difference in performance could be due organic substrates is also planned. The synthesis of addi-
to the formation of different types of copper and metal– tional ligands, informed by the results obtained and facil-
alkyl aggregates.
itated by our conveniently simple route is ongoing.
Further variation of R2 and the use of chiral dihydroimida-
zoles to introduce additional stereogenic centres are ex-
pected to generate more selective ligands.
Table 3 Evaluation of Ligands 5a–f for Enantioselective Copper-
Catalysed Addition of Diethylzinc to Cyclohexenone
Br
N
N
R2
Acknowledgment
(4 mol%)
R1
Ph
N
O
Financial support from EPSRC is gratefully acknowledged (M.M.).
The service provided by the EPRSC mass spectrometry service cen-
tre (Swansea) is also gratefully acknowledged.
5
O
Ph
+
Et2Zn
*
Cu(OTf)2 (4 mol%)
NaOMe (4 mol%)
CH2Cl2, r.t., 3 h
References and Notes
(1) Herrmanm, W. A. Angew. Chem. Int. Ed. 2002, 41, 1291.
(2) Alexakis, A.; Benhaim, C. Eur. J. Org. Chem. 2002, 3221.
(3) Perry, M. C.; Cui, X.; Powell, M. T.; Hou, D.-R.;
Reibenspies, J. H.; Burgess, K. J. Am. Chem. Soc. 2003, 125,
114.
(4) Van Veldhuizen, J. J.; Garber, S. B.; Kingsbury, J. S.;
Hoveyda, A. H. J. Am. Chem. Soc. 2002, 124, 4954.
(5) Douthwaite, R. E. Coord. Chem. Rev. 2007, 251, 702.
(6) Fraser, P. K.; Woodward, S. Tetrahedron Lett. 2001, 42,
2747.
(7) Guillen, F.; Winn, C. L.; Alexakis, A. Tetrahedron:
Asymmetry 2001, 12, 2083.
(8) Pytkowics, J.; Roland, S.; Mangeney, P. Tetrahedron:
Asymmetry 2001, 12, 2087.
Ligand
5a
R1
R2
Conv. (%)
ee (%)
i-Bu
i-Bu
Me
Me
Me
Bn
Bn
Ph
88
97
78
85
98
92
3
2
5b
5c
Bn
Ph
7
5d
18
3
5e
Mes
Ph
5f
2
(9) Winn, C. L.; Guillen, F.; Pytkowicz, J.; Roland, S.;
Mangeney, P.; Alexakis, A. J. Organomet. Chem. 2005, 690,
5672.
(10) (a) Clavier, H.; Coutable, L.; Guillemin, J.-C.; Mauduit, M.
Tetrahedron: Asymmetry 2005, 16, 921. (b) Clavier, H.;
Toupet, L.; Coutable, L.; Guillemin, J.-C.; Mauduit, M. J.
Organomet. Chem. 2005, 690, 5237. (c) Martin, D.; Kehrli,
S.; d’Augustin, M.; Clavier, H.; Mauduit, M.; Alexakis, A.
J. Am. Chem. Soc. 2006, 128, 8416.
(11) (a) Edworthy, I. S.; Rodden, M.; Mungaur, S. A.; Davis, K.
M.; Blake, A. J.; Wilson, C.; Schroder, M.; Arnold, P. L.
J. Organomet. Chem. 2005, 690, 5710. (b) Arnold, P. L.;
Rodden, M.; Davis, K. M.; Scarisbrick, A. C.; Blake, A. J.;
Wilson, C. Chem. Commun. 2004, 1612.
The superior results observed for 4 suggest that the forma-
tion of a covalent metal–nitrogen bond, which is envis-
aged for 4, is more conducive to stereoinduction than a
dative metal–nitrogen bond that is expected for 5. Similar
observations have been made for alkoxy NHC, where pro-
tecting the hydroxyl group with a tert-butyldimethylsilyl
group to prevent covalent bonding, resulted in reduced
enantioselectivity.10 Therefore, we speculate that a copper
species with a chelating ligand (Figure 1), is a key inter-
mediate in obtaining enantiocontrol.
R1
(12) (a) Jurkauskas, V.; Sadighi, J. P.; Buchwald, S. L. Org. Lett.
2003, 5, 1157. (b) Kaur, H.; Zinn, F. K.; Stevens, E. D.;
Nolan, S. P. Organometallics 2004, 23, 1157. (c) Fructos,
M. R.; Belderrain, T. R.; Nicasio, M. C.; Nolan, S. P.; Kaur,
H.; Díaz-Requejo, M. M.; Perez, P. J. J. Am. Chem. Soc.
2004, 126, 10846. (d) Díez-González, S.; Kaur, H.;
Kauer Zinn, F.; Stevens, E. D.; Nolan, S. P. J. Org. Chem.
2005, 70, 4784.
NH
Et
N
Cu Et Zn
N
O
R2
Figure 1 Possible copper intermediate with chelating ligand
(13) Nagle, A. S.; Salvatore, R. N.; Chong, B.-D.; Woon Jung, K.
Tetrahedron Lett. 2000, 41, 3011.
Synlett 2008, No. 1, 21–24 © Thieme Stuttgart · New York

24
T. Moore et al.
LETTER
(14) Larsen, A. O.; Leu, W.; Oberhuber, C. N.; Campbell, J. E.;
Hoveyda, A. H. J. Am. Chem. Soc. 2004, 126, 11130.
(15) Gade, L. H.; Cesar, V.; Bellemin-Laponnaz, S. Angew.
Chem. Int. Ed. 2004, 43, 1014.
(16) Merzouk, M.; Williams, N. A. Tetrahedron Lett. submitted
for publication.
recrystallised from hot EtOH; yield 21% (0.42 g). 1H NMR
(400 MHz, D2O): d = 0.94 (3 H, d, 3J = 6.4 Hz), 0.97 [3 H,
d, CH(CH3)2, 3J = 6.4 Hz], 1.57–1.70 (2 H, m), 1.72–1.82 (1
H, m), 3.93–3.99 (1 H, m), 4.59 (1 H, dd, 2J = 15.0 Hz,
3J = 7.9 Hz), 4.71 (1 H, dd, 2J = 15.0 Hz, 3J = 4.8 Hz), 7.63
(5 H, m), 7.79 (1 H, s), 7.99 (1 H, s), 9.45 (1 H, s). 13C NMR
(100 MHz, D2O): d = 21.1, 21.8, 23.8, 38.9, 49.5, 51.2,
122.5 (2 C), 123, 123.5, 130.5 (2 C), 130.6, 137.2. Mp 260–
264 °C. HRMS: m/z calcd for [M – 2 Br – H]+ (C15H22N3):
244.1808; found: 244.1808. Anal. Calcd (%): C, 44.47; H,
5.72; N, 10.37. Found: C, 44.25; H, 5.70; N, 10.22.
Compound 4d: 1-mesitylimidazole (5 mmol, 0.93 g) and (S)-
1-bromo-2-amino-4-methylpentane hydrobromide (5 mmol,
1.3 g) were dissolved in anhyd MeCN (50 mL) and heated to
reflux for 20 h under a nitrogen atmosphere. The solvent was
removed under vacuum and the residue dissolved in MeCN
(3 mL), which was layered with Et2O to precipitate a white
solid. The solid was recrystallised from hot EtOH, yield 20%
(0.36 g). 1H NMR (400 MHz, D2O): d = 0.88 (3 H, d,
3J = 6.6 Hz), 0.93 (3 H, d, 3J = 6.4 Hz), 1.47 (1 H, m), 1.61–
1.73 (2 H, m), 2.02 (3 H, s), 2.03 (3 H, s), 2.31 (3 H, s), 3.92–
3.97 (1 H, m), 4.62 (1 H, dd, 2J = 14.7 Hz, 3J = 6.4 Hz), 4.70
(1 H, dd, 2J = 14.7 Hz, 3J = 6.0 Hz), 7.13 (2 H, s), 7.68 (1 H,
m) 7.87 (1 H, m), 9.18 (1 H, s). 13C NMR (100 MHz, D2O):
d = 16.6 (2 C), 20.3, 21.0, 21.9, 23.8, 39.1, 48.9, 51.5, 123.7,
125.3, 129.5 (2 C), 130.7, 134.8 (2 C), 137.7, 141.8. Mp
264–264.5 °C. HRMS: m/z calcd for [M – 2 Br – H]+:
286.2283; found: 286.2277. Anal. Calcd (%): C, 48.34; H,
6.54; N, 9.39. Found: C, 47.70; H, 6.51; N, 9.15.
Compound 4e: 1-benzylimidazole (8 mmol, 1.26 g) and (S)-
1-bromo-2-amino-3-phenylpropane hydrobromide (5 mmol,
1.48 g) were dissolved in MeCN (30 mL) and heated to
reflux for 20 h. The mixture was then allowed to cool to r.t.
and the product precipitated as a white solid. This was
isolated by filtration and dried under vacuum; yield 32%
(0.74 g). 1H NMR (400 MHz, D2O): d = 3.03 (1 H, dd,
2J = 14.2 Hz, 3J = 8 Hz), 3.12 (1 H, dd, 2J = 14.2 Hz, 3J = 6.6
Hz), 4.10–4.40 (1 H, m), 4.40–4.55 (2 H, m), 5.26 (2 H, s),
7.20–7.50 (12 H, m), 8.72 (1 H, s). 13C NMR (100 MHz,
D2O): d = 36.9, 50.7, 51.7, 53.4, 123.0, 123.3, 128.0, 129.2
(2 C), 129.3 (2 C), 129.4 (2 C), 129.6 (2 C), 129.7, 132.9,
134.1, 136.4. Mp 246–248 °C. HRMS: m/z calcd for [M – 2
Br – H]+ 292.1808; found: 292.1808.
(17) Experimental and Spectroscopic Data for Ligand
Precursors 4a–e
Compound 4a: 1-methylimidazole (5 mmol, 0.4 g) and (S)-
1-bromo-2-amino-4-methylpentane hydrobromide (5 mmol,
1.3 g) were dissolved in anhyd MeCN (50 mL) and heated to
reflux for 20 h under a nitrogen atmosphere. On cooling, a
white solid precipitated and was filtered and dried under
vacuum; yield 40% (0.68 g). 1H NMR (400 MHz, D2O):
d = 0.91 (3 H, d, 3J = 6.6 Hz), 0.95 (3 H, d, 3J = 6.6 Hz),
1.50–1.64 (2 H, m), 1.70–1.80 (1 H, m), 3.85 (1 H, m), 3.91
(3 H, s), 4.48 (1 H, dd, 2J = 15 Hz, 3J = 7.6 Hz), 4.57 (1 H,
dd, 2J = 15 Hz, 3J = 5 Hz), 7.56 (2 H, m), 8.90 (1 H, s). 13
C
NMR (100 MHz, D2O): d = 21.2, 21.9, 23.6, 36.3, 38.8, 49.5,
50.8, 122.9, 124.8, 137.2. Mp 242–244 °C. HRMS: m/z
calcd for [M – 2 Br – H]+ 182.1652; found: 182.1651. Anal.
Calcd (%): C, 35.01; H, 6.17; N, 12.25. Found: C, 34.68; H,
6.13; N, 12.13.
Compound 4b: 1-benzylimidazole (8 mmol, 1.26 g) and (S)-
1-bromo-2-amino-4-methylpentane hydrobromide (5 mmol,
1.3 g) were dissolved in anhyd MeCN (50 mL) and heated to
reflux for 20 h under a nitrogen atmosphere. On cooling, a
white solid precipitated and was filtered and dried under
vacuum; yield 37% (0.79 g). 1H NMR (400 MHz, D2O):
d = 0.86 (3 H, d, 3J = 6.5 Hz), 0.90 (3 H, d, 3J = 6.5 Hz),
1.40–1.69 (3 H, m), 3.79–3.88 (1 H, m), 4.45 (1 H, dd,
2J = 15 Hz, 3J = 7.2 Hz), 4.52 (1 H, dd, 2J = 15 Hz, 3J = 5.5
Hz), 5.41 (2 H, s), 7.45 (5 H, m), 7.59 (2 H, m), 8.97 (1 H,
s). 13C NMR (100 MHz, D2O): d = 21.1, 21.8, 23.8, 38.9,
49.2, 50.9, 53.5, 123.3, 123.6, 129 (2 C), 129.6 (2 C), 129.7,
133.2, 136.7; mp 238.5–240 °C. HRMS: m/z calcd for [M –
2 Br – H]+: 258.1968; found: 258.1965.
Compound 4c: 1-phenylimidazole (5 mmol, 0.72 g, 0.63
mL) and (S)-1-bromo-2-amino-4-methylpentane
hydrobromide (5 mmol, 1.3 g) were dissolved in anhyd
MeCN (50 mL) and heated to reflux for 20 h under a nitrogen
atmosphere. The solvent was removed under vacuum and the
residue dissolved in MeCN (3 mL), and then layered with
Et2O to precipitate a white solid. The solid was
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