Chiral bifunctional n-heterocyclic carbenes: Synthesis and application in the aza-Morita-Baylis-Hillman reaction

Article abstract of DOI:10.1055/s-2008-1067216

A series of chiral bifunctional N-heterocyclic carbene (NHC) precursors with a proximal hydroxy group were smoothly prepared from L-pyroglutamic acid. Promising enantiomeric excesses (up to 44% ee) were achieved for the bifunctional NHC-catalyzed enantioselective aza-Morita-Baylis-Hillman reaction of cyclopent-2-enone with N-tosylphenylmethanimine. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1067216

SPECIAL TOPIC
2825
Chiral Bifunctional N-Heterocyclic Carbenes: Synthesis and Application in
the Aza-Morita–Baylis–Hillman Reaction
C
hira
l
Bifunctio
i
nal N-
n
Heterocyclic Carbe
H
nes e, Yan-Rong Zhang, Xue-Liang Huang, Song Ye*
Beijing National Laboratory for Molecular Sciences, Laboratory of Chemical Biology, Institute of Chemistry,
Chinese Academy of Sciences, Beijing 100080, P. R. of China
Fax +86(10)62654449; E-mail: songye@iccas.ac.cn
Received 21 April 2008
Recently, we documented that chiral NHC precursor 8
Abstract: A series of chiral bifunctional N-heterocyclic carbene
(NHC) precursors with a proximal hydroxy group were smoothly
prepared from L-pyroglutamic acid. Promising enantiomeric ex-
cesses (up to 44% ee) were achieved for the bifunctional NHC-
could be easily prepared from inexpensive L-pyroglutam-
ic acid and it was shown to give products with very good
enantioselectivities in the catalytic Staudinger reaction of
catalyzed enantioselective aza-Morita–Baylis–Hillman reaction of ketenes with imines.16 One possible feature of NHC pre-
cyclopent-2-enone with N-tosylphenylmethanimine.
cursor 8 is that its electronic and steric properties can be
easily adjusted by variation of the substitution in the aryl
groups. Furthermore, the silyl group in NHC precursor 8
may be removed to give a free hydroxy group that can
function as hydrogen bond donor and thus resulting in bi-
functional NHCs.
Key words: N-heterocyclic carbenes, bifunctional catalysts, enan-
tioselective synthesis, aza-Morita–Baylis–Hillman reaction
N-Heterocyclic carbenes (NHCs), as Lewis basic organo-
catalysts, have been demonstrated to be very successful in
recent years.1 They have been found to be efficient cata-
lysts for the umpolung reaction of aldehydes,2 a3 to d3 um-
polung reaction of enals,3 transesterification,4 acylation,5
ring-opening polymerization,6 activation of silylated nu-
cleophiles,7 and other reactions.8 In the meantime, a num-
ber of chiral NHCs have been synthesized and applied for
enantioselective organocatalytic reactions. After Sheehan
and Hunneman’s first report of chiral thiazolium salts as
NHC precursors for organocatalytic reactions,9 Leeper,10
Enders,11 Rovis,12 Glorius,13 Herrmann,14 and others have
synthesized series of novel chiral NHCs with monocyclic,
bicyclic, or tricyclic backbones.15 Representative exam-
ples are shown in Figure 1.
In our previous publication, we found an NHC-catalyzed
aza-Morita–Baylis–Hillman (aza-MBH) reaction of cy-
clic enones with imines (Equation 1).17 It was reported
that bifunctional chiral phosphines or amines could cata-
lyze aza-MBH reactions of linear enones to give the cor-
responding adducts with high enantioselectivities.18
However, when cyclic enones were employed instead of
linear enones, low enantiomeric excesses were obtained.19
Thus, it became interesting for us to synthesize bifunc-
tional NHCs and investigate chiral NHC-catalyzed aza-
MBH reactions.
N
N
Ar2
Ar2
O
O
NHTs
NTs
NHC (10 mol%)
toluene
Ar1
Ph
Ph
Ph
Ph
Me
Ar1
N
N
N
n
N
N
n
n = 1, 2
N
N
yield: 72–99%
N
N
N
BF4
t-Bu
O
BF4
Bn
BF4
Bn
N
Cl
Equation 1 Aza-MBH reactions catalyzed by achiral NHCs
O
Me
Ph
2
3
1
4
The addition of Grignard reagents to the methyl ester of L-
pyroglutamic acid gave the diarylmethyl alcohols 9a–c
and subsequent protection of the hydroxy group with tri-
methylsilyl triflate gave the corresponding ethers 10a–c
(Scheme 1). Leeper’s and Rovis’s three-step synthesis of
triazolium salts was then applied;10,12 methylation with
Meerwein’s reagent, reaction with arylhydrazine, and cy-
clization with trimethyl orthoformate gave the NHC pre-
cursors 11a,b. Desilylation of 11a,b under acidic
conditions gave the final NHC precursors 12a,b with a
free hydroxy group. It is important to note that the tri-
methylsilyl ether was deprotected in situ under the condi-
tions of cyclization for triazolium salts 12c and 12d. As
for the cyclization of the compound prepared from 2,4,6-
trimethylphenylhydrazine, the reaction had to be carried
Ph
Ph
Ph
Ph
N
N
N
N
N
N
N
N
BF4
N
N
N
BF4
BF4
O
Br
OTBS
Ph
Ph
Ph
8
6
5
7
Figure 1 Selected chiral NHCs reported
SYNTHESIS 2008, No. 17, pp 2825–2829
Advanced online publication: 06.08.2008
DOI: 10.1055/s-2008-1067216; Art ID: C03108SS
x
x.
x
x
.
2
0
0
8
© Georg Thieme Verlag Stuttgart · New York

2826
L. He et al.
SPECIAL TOPIC
Table 1 Chiral NHC-Catalyzed Aza-MBH Reaction
a)
O
Ar1
Ar1
b)
O
O
NHTs
Ph
O
N
MeO2C
N
NHC precuror (20 mol%)
Cs2CO3 (20 mol%)
H
NTs
H
OH
9a Ar1 = Ph
9b Ar1 = 3,5-Me2C6H3
Ph
14
(0.45 mmol)
toluene, r.t.
9c Ar1 = 3,5-(CF3)2C6H3
13
15
(0.3 mmol)
N
Ar1
Ar1
c)
N
N
O
Ar2
N
Ar1
Entry
NHC precursor Yielda (%)
eeb (%)
H
OTMS
Ar1
BF4
10a Ar1 = Ph
10b Ar1 = 3,5-Me2C6H3
10c Ar1 = 3,5-(CF3)2C6H3
OTMS
1
1c
3
75
76
40
74
82
75
63
56
65
54
30
30
0
0
11a Ar1 = Ar2 = Ph
11b Ar1 = 3,5-Me2C6H3, Ar2 = Ph
2
N
d)
3
4
0
c)
N
N
Ar2
Ar1
4
5c
9
Ar1
BF4
OH
5
7
0
12a Ar1 = Ar2 = Ph
12b Ar1 = 3,5-Me2C6H3, Ar2 = Ph
6
8c
10
2
12c Ar1 = 3,5-(CF3)2C6H3, Ar2 = Ph
12d Ar1 = 3,5-(CF3)2C6H3, Ar2 = 4-MeOC6H4
12e Ar1 = Ph, Ar2 = 2,4,6-Me3C6H2
7
11ac
12a
12b
12c
12d
12e
8
8
Scheme 1 Synthesis of bifunctional NHC precursors. Reagents and
+
–
conditions: (a) RMgBr, THF; (b) TMSOTf, Et3N; (c) (i) MeO3 BF4 ;
(ii) Ar2NHNH2; (iii) HC(OEt)3, MeOH, (90 °C, 4 h for 11a, 11b, 12c,
12d; 120 °C, sealed tube, 4 d for 12e); (d) HBF4, THF, 60 °C.
9
26
44
34
–2
10
11
out in a sealed tube at 120 °C for four days and the in situ
desilylation was also observed, giving the desired com-
pound 12e.
12
a Isolated yields.
b Determined by chiral HPLC.
The bifunctional NHCs and several other NHCs reported
were then tested in the aza-MBH reaction of cyclopent-2-
enone (13) with N-tosylphenylmethanimine (14). The re-
sults are summarized in Table 1.
c 10 mol% NHC precursor and Cs2CO3 were employed.
12d (Ar2 = 4-MeOC6H4) gave products with a little worse
enantioselectivity (entry 11 vs 10). The NHC 12e
(Ar1 = Ph, Ar2 = 2,4,6-Me3C6H2) showed reversed enan-
tioselectivity, but only with –2% ee.
Although good yields were obtained, no enantioselectivi-
ties were observed for the reactions catalyzed by chiral
NHCs generated in situ from mono- or bicyclic NHC pre-
cursors 1, 3, or 4 (entries 1–3). The reaction catalyzed by
benzotricyclic NHC 5 gave the aza-MBH adduct 15 in
74% yield with 9% ee (entry 4). The C2-symmetric imida-
zolylidene NHC 7, prepared from (S)-3-phenyl-3,4-dihy-
droisoquinoline, works well but with no enantioselectivity
was observed (entry 5). The tert-butyldimethylsilyl- or tri-
methylsilyl-protected NHC precursors 8 and 11a, pre-
pared from L-pyroglutamic acid, lead to reactions in good
yields with 10% ee and 2% ee, respectively (entries 6 and
7). Removal the trimethylsilyl group gives the NHC 12a
with a free hydroxy group, which improves the enantiose-
In conclusion, a series of bifunctional NHC precursors
with a proximal hydroxy group were smoothly prepared
from L-pyroglutamic acid. The free hydroxy group in
these NHCs showed some positive impact on the catalytic
aza-MBH reaction of cyclopent-2-enone with an imine
and afforded the product with promising enantioselectivi-
ties (up to 44% ee). Further investigation of the synthesis
of bifunctional NHCs and their potential applications in
organocatalysis are underway in our laboratory.
Unless otherwise indicated, all starting materials were obtained
lectivity from 2% ee to 8% ee (entries 7 and 8). Bulkier from commercial supplies and used as received. Anhyd toluene,
THF, and Et2O were distilled from Na/benzophenone. CH2Cl2 was
substituents in NHCs 12b and 12c benefits the enantiose-
distilled from CaH2. N-Tosylphenylmethanimine,20 imidazolium
lectivities of the catalytic reactions, and 12c with electron-
1,14a 7,14b and triazolium salts 3,12c 4,10b 5,11b 8,16 11a,16 and 11b16
withdrawing group (CF3) is better than 12b, which con-
were prepared according to the literature. All reactions were carried
tains an electron-donating group (CH3) (44% ee vs 34%
out in an oven-dried flask under N2. Column chromatograph was
performed with silica gel 200–300 mesh. All 1H NMR (300 MHz)
and 13C NMR (75 MHz) spectra were recorded on a Bruker DMX
300 spectrometer in CDCl3 with TMS as internal standard. IR spec-
tra were recorded on a Jasco FT/IR-480 spectrophotometer.
ee, entries 9 and 10). The strongly electron-withdrawing
group are thought to increase the acidity of the free hy-
droxy group in NHC 12c and makes it a better hydrogen
bond donor. Thus the stronger hydrogen bond between
NHC 12c and imine 14 may result in improved enantiose-
lectivity for the reaction. The reaction catalyzed by NHC
5-[Diaryl(hydroxy)methyl]pyrrolidin-2-ones 9a–c
These were synthesized according to the literature procedure.16
Synthesis 2008, No. 17, 2825–2829 © Thieme Stuttgart · New York

SPECIAL TOPIC
Chiral Bifunctional N-Heterocyclic Carbenes
2827
(S)-5-[Bis(3,5-dimethylphenyl)(hydroxy)methyl]pyrrolidin-2-
one (9b)
White solid; yield: 40%; mp 79–80 °C.
2-Aryl-5-[diaryl(trimethylsiloxy)methyl]-6,7-dihydro-5H-pyr-
rolo[2,1-c]-1,2,4-triazol-2-ium Tetrafluoroborates 11a,b
These were synthesized according to the literature procedure.16
[a]D25 –82.3 (c 1, CHCl3).
(S)-5-[Bis(3,5-dimethylphenyl)(trimethylsiloxy)methyl]-2-phe-
nyl-6,7-dihydro-5H-pyrrolo[2,1-c]-1,2,4-triazol-2-ium Tetra-
fluoroborate (11b)
IR (KBr): 3414, 2916, 1684, 1602, 1453, 1278, 1172, 848, 747
cm–1.
1H NMR (300 MHz, CDCl3): d = 7.07 (s, 2 H), 7.04 (s, 2 H), 6.81
(s, 2 H), 5.78 (s, 1 H), 4.67 (dd, J = 5.1, 8.4 Hz, 1 H), 3.74 (s, 1 H),
2.26 (s, 6 H), 2.25 (s, 6 H), 2.36–2.19 (m, 2 H), 2.04 (m, 1 H), 1.89
(m, 1 H).
13C NMR (75 MHz, CDCl3): d = 179.4, 145.5, 143.5, 138.1, 137.6,
128.9, 128.6, 123.5, 123.4, 78.5, 60.8, 30.3, 21.6, 21.5.
Yellow solid; yield: 82%; mp 98–99 °C.
[a]D25 –96.5 (c 1, CHCl3).
IR (KBr): 3424, 2949, 1680, 1595, 1249, 1080, 845, 764 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.66 (s, 1 H), 7.66 (m, 2 H), 7.56
(m, 3 H), 7.06 (s, 1 H), 6.99 (s, 1 H), 6.88 (s, 2 H), 6.81 (s, 2 H), 5.94
(d, J = 9.0 Hz, 1 H), 3.25 (m, 1 H), 2.82 (m, 2 H), 2.30 (s, 6 H), 2.24
(s, 6 H), 2.06 (m, 1 H), –0.11 (s, 9 H).
13C NMR (75 MHz, CDCl3): d = 161.5, 138.9, 138.3, 136.8, 136.5,
133.9, 129.3, 128.9, 128.8, 128.7, 124.6, 124.4, 119.5, 81.0, 66.7,
28.4, 19.8, 19.7, 19.6, –0.01.
HRMS (P-SIMS): m/z [M + H]+ calcd for C21H26NO2: 324.1957;
found: 324.1963.
(S)-5-{Bis[3,5-bis(trifluoromethyl)phenyl](hydroxy)meth-
yl}pyrrolidin-2-one (9c)
White solid; yield: 59%; mp 157–158 °C.
MS (ESI): m/z (%) = 496.4 (100).
[a]D25 –57.2 (c 0.5, CH2Cl2).
IR (KBr): 3450, 1684, 1374, 1279, 1171, 1135, 682 cm–1.
HRMS (P-SIMS): m/z [M]+ calcd for C31H38N3OSi: 496.2778;
found: 496.2785.
1H NMR (300 MHz, CDCl3): d = 8.01 (s, 2 H), 7.88 (s, 2 H), 7.84
(s, 1 H), 7.76 (s, 1 H), 7.10 (s, 1 H), 5.37 (s, 1 H), 4.80 (m, 1 H), 2.2–
2.1 (m, 1 H), 1.80–1.70 (m, 3 H).
2-Aryl-5-[diaryl(hydroxy)methyl]-6,7-dihydro-5H-pyrrolo[2,1-
c]-1,2,4-triazol-2-ium Tetrafluoroborates 12a,b
To the soln of 11a,b (0.2 mmol) in THF (1 mL), 48% (w/w) HBF4
(0.132 mL, 1.0 mmol) was added and the mixture was stirred at
60 °C for 6 h. The mixture was extracted with EtOAc. The collected
organic soln was concentrated and the residue was purified by col-
umn chromatography to afford 12a,b.
13C NMR (75 MHz, CDCl3): d = 160.98, 147.10, 144.95, 132.70 (q,
2
3
2JC,F = 33.2 Hz), 132.30 (q, JC,F = 33.2 Hz), 125.99 (m, JC,F),
3
1
3
125.36 (m, JC,F), 130.10 (q, JC,F = 271.1 Hz), 122.29 (m, JC,F),
121.82 (m, 3JC,F), 77.77, 60.15, 29.90, 21.29.
HRMS (P-SIMS): m/z [M + H]+ calcd for C21H14F12NO2: 540.0827;
found: 540.0805.
(S)-5-[Hydroxy(diphenyl)methyl]-2-phenyl-6,7-dihydro-5H-
pyrrolo[2,1-c]-1,2,4-triazol-2-ium Tetrafluoroborates (12a)
White solid; yield: 74%; Rf = 0.21 (CH2Cl2–acetone, 4:1).
[a]D25 –58.6 (c 0.5, MeCN).
5-[Diaryl(trimethylsiloxy)methyl]pyrrolidin-2-ones 10a–c
These were synthesized according to the literature procedure.16
IR (KBr film): 3485, 3218, 1590, 1449, 1198, 1063, 763, 701 cm–1.
(S)-5-[Bis(3,5-dimethylphenyl)(trimethylsiloxy)methyl]pyrroli-
din-2-one (10b)
Yellow solid; yield: 77%; mp 82–83 °C.
[a]D25 –78.0 (c 1, CHCl3).
1H NMR (300 MHz, CDCl3): d = 8.76 (s, 1 H), 7.65–7.55 (m, 2 H),
7.55–7.40 (m, 5 H), 7.40–7.20 (m, 8 H), 5.99 (dd, J = 8.6, 2.4 Hz,
1 H), 4.32 (s, 1 H), 3.10–2.95 (m, 1 H), 2.95–2.80 (m, 1 H), 2.80–
2.60 (m, 1 H), 2.60–2.40 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 163.44, 142.65, 141.39, 136.72,
135.43, 130.70, 129.97, 129.00, 128.55, 128.41, 128.03, 126.48,
126.06, 121.36, 78.83, 67.69, 29.79, 21.39.
HRMS (P-SIMS): m/z [M]+ calcd for C24H22N3O: 368.1757; found:
368.1760.
IR (KBr): 3437, 2953, 2919, 1699, 1604, 1456, 1253, 1095, 840
cm–1.
1H NMR (300 MHz, CDCl3): d = 7.00 (m, 6 H), 6.05 (s, 1 H), 4.67
(m, 1 H), 2.37 (s, 6 H), 2.36 (s, 6 H), 2.11 (m, 3 H), 1.63 (m, 1 H),
0.00 (s, 9 H).
13C NMR (75 MHz, CDCl3): d = 176.8, 141.6, 141.4, 135.4, 135.2,
127.1, 127.0, 123.8, 123.6, 80.6, 58.4, 27.5, 20.3, 19.5, 17.2, –0.01.
Anal. Calcd for C24H22BF4N3O: C, 63.32; H, 4.87; N, 9.23. Found:
C, 63.14; H, 4.88; N, 9.21.
HRMS (P-SIMS): m/z [M + H]+ calcd for C24H34NO2Si: 396.2353;
(S)-5-[Bis(3,5-dimethylphenyl)(hydroxy)methyl]-2-phenyl-6,7-
dihydro-5H-pyrrolo[2,1-c]-1,2,4-triazol-2-ium Tetrafluorobo-
rate (12b)
Yellow solid; yield: 70%; mp 82–83 °C.
[a]D25 –110.4 (c 1, CHCl3).
found: 396.2352.
(S)-5-{Bis[3,5-bis(trifluoromethyl)phenyl](trimethyl-
siloxy)methyl}pyrrolidin-2-one (10c)
Yellow solid; yield: 94%; mp 129–130 °C.
IR (KBr): 3438, 1706, 1370, 1282, 1175, 1140, 906, 838, 678 cm–1.
IR (KBr): 3471, 2919, 1594, 1469, 1080, 850, 760, 751 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.98 (s, 1 H), 7.95 (s, 1 H), 7.84
(s, 2 H), 7.75 (s, 2 H), 6.38 (br s, 1 H), 4.79 (m, 1 H), 2.07–2.27 (m,
2 H), 1.89–2.07 (m, 1 H), 1.47–1.58 (m, 1 H), –0.05 (s, 9 H).
13C NMR (75 MHz, CDCl3): d = 179.8, 145.6, 144.6, 132.0 (q,
2JC,F = 34.0 Hz), 131.68 (q, 2JC,F = 34.0 Hz), 128.1 (m, 3JC,F), 123.1
(q, 1JC,F = 273.9 Hz), 122.4 (m, 3JC,F), 82.0, 59.8, 29.90, 29.2, 1.4.
1H NMR (300 MHz, CDCl3): d = 9.07 (s, 1 H), 7.69 (m, 2 H), 7.56
(m, 3 H), 7.03 (s, 2 H), 7.01 (s, 1 H), 6.59 (s, 1 H), 6.76 (s, 2 H), 5.98
(d, J = 6.9 Hz, 1 H), 3.45 (s, 1 H), 3.20 (m, 1 H), 2.93 (m, 1 H), 2.77
(m, 1 H), 2.35 (m, 1 H), 2.32 (s, 6 H), 2.24 (s, 6 H).
13C NMR (75 MHz, CDCl3): d = 162.1, 141.2, 140.2, 137.2, 136.6,
135.0, 133.9, 129.1, 128.3, 127.9, 122.3, 122.0, 119.9, 77.4, 66.5,
28.1, 19.9, 19.7, 19.6.
HRMS (P-SIMS): m/z [M + H]+ calcd for C24H22NF12O2Si:
612.1222; found: 612.1210.
MS (ESI): m/z (%) = 424.4 (100).
Synthesis 2008, No. 17, 2825–2829 © Thieme Stuttgart · New York

2828
L. He et al.
SPECIAL TOPIC
HRMS (P-SIMS): m/z [M]+ calcd for C28H30N3O: 424.2383; found:
HRMS (P-SIMS): m/z [M]+ calcd for C27H28N3O: 410.2226; found:
424.2397.
410.2217.
2-Aryl-5-[diaryl(hydroxy)methyl]-6,7-dihydro-5H-pyrrolo[2,1-
c]-1,2,4-triazol-2-ium Tetrafluoroborates 12c–e
2-[Phenyl(tosylamino)methyl]cyclopent-2-enone (15) by NHC-
Catalyzed Reaction of Cyclopent-2-enone (13) with N-Tosyl-
phenylmethanimine (14)
These were synthesized according to the literature procedure.16
To a soln of N-tosylphenylmethanimine (14, 116.6 mg, 0.45 mmol)
in toluene (2.0 mL) was added cyclopent-2-enone (25 mL, 0.30
mmol) via a syringe, followed by addition of triazolium salt 12c (44
mg, 0.06 mmol) and Cs2CO3 (20 mg, 0.06 mmol). The resulting
mixture was stirred at r.t. for 36 h and TLC indicated complete con-
sumption of cyclopent-2-enone. The solvent was removed under re-
duced pressure and the residue was purified by flash
chromatography (silica gel, EtOAc–petroleum ether, 1:2) to give
the desired product 1517,21 (55 mg, 54%) as a white solid.
(S)-5-{Bis[3,5-bis(trifluoromethyl)phenyl](hydroxy)methyl]-2-
phenyl-6,7-dihydro-5H-pyrrolo[2,1-c]-1,2,4-triazol-2-ium Tet-
rafluoroborates (12c)
Synthesized according to the literature procedure,16 except that the
ring closure was carried out in a flask under 90 °C for 15 h; white
solid; yield: 65%; mp 166–167 °C.
[a]D25 –24.5 (c 1, acetone).
IR (KBr): 3437, 1590, 1374, 1282, 1182, 1133, 1085, 908, 845, 764,
712, 682 cm–1.
1H NMR (300 MHz, DMSO-d6): d = 9.92 (s, 1 H), 8.51 (s, 2 H), 8.41
(s, 2 H), 8.12 (s, 1 H), 8.07 (s, 1 H), 7.65–7.87 (m, 5 H), 7.55 (s, 1
H), 6.76 (d, J = 6.3 Hz, 1 H), 3.28 (m, 2 H), 3.06 (m, 1 H), 2.63 (m,
1 H).
HPLC analysis: 44.8% ee [Daicel CHIRALPAK OJ-H column; 20
°C; 0.8 mL/min; solvent system: i-PrOH–hexanes, 20:80; tR = 31.7
min (minor), 41.6 min (major)].
[a]D25 +3.9 (c 1, CHCl3).
1H NMR (300 MHz, CDCl3): d = 7.60 (d, J = 8.3 Hz, 2 H), 7.34 (t,
J = 2.7 Hz, 1 H), 7.21–7.15 (m, 7 H), 6.17 (d, J = 8.4 Hz, 1 H), 5.28
(d, J = 8.4 Hz, 1 H), 2.52–2.05 (m, 4 H), 2.37 (s, 3 H).
13C NMR (75 MHz, DMSO-d6): d = 163.7, 145.9, 144.9, 137.8,
2
2
135.4, 131.33 (q, JC,F = 33.0 Hz), 130.87 (q, JC,F = 33.0 Hz),
129.8, 126.8, 123.08 (q, 1JC,F = 272.8 Hz), 122.5 (br s, 3JC,F), 121.9,
121.6 (br s, 3JC,F), 78.8, 66.2, 29.8, 21.1.
13C NMR (75 MHz, CDCl3): d = 208.3, 160.5, 143.5, 143.2, 138.6,
137.4, 129.3, 128.6, 127.8, 127.3, 126.7, 55.2, 34.9, 26.7, 21.4.
HRMS (P-SIMS): m/z [M]+ calcd for C28H18F12N3O: 640.1252;
found: 640.1239.
Acknowledgment
(S)-5-{Bis[3,5-bis(trifluoromethyl)phenyl](hydroxy)methyl]-2-
(4-methoxyphenyl)-6,7-dihydro-5H-pyrrolo[2,1-c]-1,2,4-triaz-
ol-2-ium Tetrafluoroborates (12d)
We are grateful for the financial support from Chinese Academy of
Sciences and Natural Sciences Foundation of China (No.
20602036).
Synthesized according to the literature procedure,16 except that the
ring closure was carried out in a flask under 110 °C for 15 h; yellow
solid; yield: 82%; mp 130–131 °C.
References
[a]D25 –23.9 (c 1, MeCN).
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IR (KBr): 3437, 1590, 1527, 1378, 1280, 1182, 1138, 1080, 900,
840, 710, 678 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.34 (s, 1 H), 8.19 (s, 2 H), 7.99
(s, 2 H), 7.88 (s, 1 H), 7.85 (s, 1 H), 7.46 (d, J = 9.3 Hz, 2 H), 6.89
(d, J = 9.3 Hz, 2 H), 6.25 (m, 1 H), 5.34 (br s, 1 H), 3.80 (s, 3 H),
3.08 (m, 2 H), 2.93 (m, 1 H), 2.70 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 163.5, 161.5, 144.2, 143.9, 135.9,
2
2
132.8 (q, JC,F = 34.0 Hz), 132.5 (q, JC,F = 34.0 Hz), 128.4, 122.8
1
3
(q, JC,F = 274.4 Hz), 126.6, 125.9, 123.6, 123.2 (br, JC,F), 122.6
(br, 3JC,F), 114.8, 78.0, 66.6, 55.5, 29.6, 21.4.
HRMS (P-SIMS): m/z [M]+ calcd for C29H20F12N3O2: 670.1358;
found: 670.1347.
(S)-5-[Hydroxy(diphenyl)methyl]-2-mesityl-6,7-dihydro-5H-
pyrrolo[2,1-c]-1,2,4-triazol-2-ium Tetrafluoroborates (12e)
Synthesized according to the literature procedure,16 except that the
ring closure was carried out in a sealed tube under 120 °C for 4 d;
white solid; yield: 59%; Rf = 0.25 (CH2Cl2–acetone, 4:1); mp 201–
202 °C.
[a]D25 –26.3 (c 0.9, MeCN).
IR (KBr film): 3486, 3143, 3062, 1587, 1450, 1191, 1056, 702 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.07 (s, 1 H), 7.51 (d, J = 7.3 Hz,
2 H), 7.33–7.20 (m, 8 H), 6.94 (s, 2 H), 6.13 (d, J = 8.3 Hz, 1 H),
4.39 (s, 1 H), 3.17–3.10 (m, 1 H), 2.97–2.85 (m, 1 H), 2.85–2.75 (m,
2 H), 2.30 (s, 3 H), 1.99 (s, 6 H).
13C NMR (75 MHz, CDCl3): d = 163.63, 142.61, 141.88, 141.35,
140.06, 134.99, 131.46, 129.44, 128.83, 128.56, 128.31, 128.10,
126.38, 126.11, 79.02, 77.20, 67.75, 29.82, 21.61, 20.98, 17.00.
Synthesis 2008, No. 17, 2825–2829 © Thieme Stuttgart · New York

SPECIAL TOPIC
Chiral Bifunctional N-Heterocyclic Carbenes
2829
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Synthesis 2008, No. 17, 2825–2829 © Thieme Stuttgart · New York