Synthesis of chiral C2-symmetric methylene- and boron-bridged bis(imidazolines)

Article abstract of DOI:10.1055/s-2007-965897

A series of C₂-symmetric boron-bridged bis(imidazolines) was obtained by lithiation of 2-imidazolines and subsequent reaction with dialkyl- or diarylhaloboranes. The corresponding 2-imidazolines were prepared by an efficient four-step sequence starting from N-tert-butoxycarbonyl-protected α-amino acids. C₂-Symmetric methylenebis(imidazolines) were readily synthesized from chiral diamines by condensation with diethyl malonimidate. The bis(imidazolines) were used as ligands in the enantioselective cyclopropanation of styrene and allylic oxidation of cyclic alkenes. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-965897

572
PAPER
Synthesis of Chiral C2-Symmetric Methylene- and Boron-Bridged
Bis(imidazolines)
S
a
al
C
-Symm
l
e
tric
M
a
ethylene-
mand Boron-Bridged
u
Bis(imidazo
rlines) ugan Ramalingam, Markus Neuburger, Andreas Pfaltz*
Department of Chemistry, University of Basel, St. Johanns-Ring 19, 4056 Basel, Switzerland
Fax +41(61)2671103; E-mail: andreas.pfaltz@unibas.ch
Received 25 July 2006; revised 3 November 2006
CN
R2
N
R2
N
Abstract: A series of C2-symmetric boron-bridged bis(imidazo-
lines) was obtained by lithiation of 2-imidazolines and subsequent
reaction with dialkyl- or diarylhaloboranes. The corresponding 2-
imidazolines were prepared by an efficient four-step sequence start-
ing from N-tert-butoxycarbonyl-protected a-amino acids. C2-Sym-
metric methylenebis(imidazolines) were readily synthesized from
chiral diamines by condensation with diethyl malonimidate. The
bis(imidazolines) were used as ligands in the enantioselective cy-
clopropanation of styrene and allylic oxidation of cyclic alkenes.
R2
N
R2
B
O
O
O
O
N
HN
N
H
R1
R1
R1
R1
R1
R1
1
2
3
R2
R2
R2
R2
R3
R3
B
N
N
N
N
Key words: chiral imidazolines, bis(imidazolines), asymmetric
catalysis, chiral ligands, copper complexes
N
N
N
HN
H
R1
R1
R1
R1
4
5
Since the introduction of C2-symmetric semicorrins 1,1 a
diverse range of structurally related bis(oxazoline)
ligands such as 2 (box) have been synthesized and used
with great success in homogeneous metal-catalyzed
asymmetric reactions (Figure 1).2,3 As a further variation
of this structural motif, anionic bis(oxazoline) ligands of
type 3 (borabox) that contain a tetrasubstituted bridging
boron atom were recently reported.4 These ligands gave
promising results in various copper-catalyzed asymmetric
reactions,4–6 especially in the enantioselective benzoyla-
tion of diols and pyridyl alcohols, where they outper-
formed box ligands. In connection with this work, we
became interested in studying analogous bis(imidazo-
lines) 4, which have a closely related structure, but offer
the possibility to tune the ligand properties by variation of
the N-substituents. In addition, we decided to synthesize
methylene-bridged bis(imidazolines) of type 5, in order to
compare these ligands with their structural counterparts
2–4. Surprisingly, bis(imidazolines) of this type have not
been previously reported.7 Herein we report efficient syn-
thetic routes to enantiopure bis(imidazolines) 4 and 5.
Figure 1
reaction were low to moderate. With aromatic amines
bearing electron-donating para-substituents, the reaction
did not proceed.
In view of these problems, we developed an alternative
route, starting from commercially available tert-butoxy-
carbonyl-protected a-amino acids (Scheme 2). Using O-
(benzotriazol-1-yl)-N,N,N¢,N¢-tetramethyluronium tetra-
fluoroborate (TBTU)9 as the coupling reagent, the corre-
sponding amides were obtained in high yield.
After removal of the tert-butoxycarbonyl group, the ami-
no acid amides were reduced with borane in tetrahydrofu-
ran to give the desired diamines in 65–85% yield.
Reduction with lithium aluminum hydride proceeded in
much lower yields. Diamines bearing isopropyl (9d,g,i) or
benzyl (9f,k) substituents were purified by Kugelrohr dis-
tillation, whereas other diamines (9e,h,j,l) were suffi-
ciently pure after workup to be used in the next step
without purification. Condensation with ethyl formimi-
An obvious possible route to boron-bridged bis(imidazo-
lines) 4 involves metalation of 2-imidazolines and subse-
quent trapping with dialkyl- or diarylhaloboranes, in
analogy to the synthesis of borabox 3.4 The corresponding
2-imidazolines can be prepared using a synthetic se-
quence recently developed by Casey et al. (Scheme 1).8
This method is attractive because the substituted nitrogen
atom is introduced in the last step, allowing easy variation
of the R2 substituents. We synthesized various 2-imidazo-
lines by this route. However, the yields in the cyclization
R1
O
OH
O
R1
H2N
SOCl2
OH
H
O
H
N
reflux, 4 h
85–90%
CHCl3
55 °C, 3 h
90–95%
H
R2
PCl5, R2NH2
Et3N
6a R1 = i-Pr
6b R1 = t-Bu
6c R1 = Bn
O
R1
N
Cl
H
N
H
CHCl3, reflux
16–44%
N
R2 = 4-CF3C6H4
R1
SYNTHESIS 2007, No. 4, pp 0572–0582
x
x
.
x
x
.2
0
0
7
Advanced online publication: 18.01.2007
DOI: 10.1055/s-2007-965897; Art ID: T11506SS
Scheme 1 Synthesis of chiral 2-imidazolines
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of Chiral C2-Symmetric Methylene- and Boron-Bridged Bis(imidazolines)
573
R2
R2
the data collection see Table 2) are very similar, showing
a (time-averaged) C2-symmetric structure with the NH
proton found on two positions and occupancy of 0.5 near
the two nitrogen atoms.
R2NH2, TBTU
DIPEA
O
OH
NH
O
O
NH
TFA
MeCN, 12 h
80–96%
CH2Cl2, r.t., 2 h
93–99%
R1
NH
R1
NH2
R1
NH
Boc
Boc
8d–l
7d–l
R2
NH⋅HCl
R2
H
NH
N
BH3⋅THF
OEt
THF, reflux
20 h
CH2Cl2, reflux
12 h, Et3N
N
R1
NH2
R1
6d–k
65–85%
85–98%
9d–l
d
e
f
g
h
R
1 = i-Pr; R2 = 4-MeC6H4
i
j
k
l
R
R
R
R
1 = i-Pr; R2 = Bn
R1 = t-Bu; R2 = 4-MeC6H4
R1 = Bn; R2 = 4-MeC6H4
R1 = i-Pr; R2 = 4-MeOC6H4
R1 = t-Bu; R2 = 4-MeOC6H4
1 = t-Bu; R2 = Bn
1 = Bn; R2 = Bn
1 = Ph; R2 = Bn
Figure 2 Crystal structure of (S,S)-4c and (S,S)-4e; hydrogen atoms
(except NH) are omitted for clarity
The bis(imidazolines) 5a–g were synthesized (Scheme 4)
in one step from the corresponding chiral diamines by the
condensation with diethyl malonimidate dihydrochloride
in moderate to good yield. The reaction was carried out in
refluxing anhydrous dichloromethane for 48 hours. In-
creasing the reaction time or refluxing in 1,2-dichloroeth-
ane did not increase the yields. The bis(imidazolines)
were purified by recrystallization from anhydrous aceto-
nitrile. As crystalline solids the protonated ligands 5a–g
were stable to air and moisture.
Scheme 2 Synthesis of chiral 2-imidazolines
date hydrochloride led to the corresponding 2-imidazo-
lines 6d–k, which were isolated in high yield after
workup.
2-Imidazolines 6 were metalated with n-butyllithium in
tetrahydrofuran10 and the resulting 2-lithioimidazolines
treated with 0.5 equivalents of dialkyl- or diarylhalobo-
rane, as described for the synthesis of borabox 3
(Scheme 3). Metalation of imidazoline 6 with n-butyllith-
ium was found to be more efficient than with tert-butyl-
lithium, in contrast to the metalation of oxazolines. In the
synthesis of 4a and 4b, a biimidazoline was observed as a
side product. In the reaction with n-butyllithium smaller
amounts of side product were formed than with tert-butyl-
lithium, resulting in higher yields of 4a and 4b. The pro-
tonated ligands 4a–f were isolated by passing the crude
product through a short silica gel column, using a mixture
of hexanes–ethyl acetate–triethylamine as eluent, and pu-
rified by flash chromatography.
R2
R2
R2
EtO
OEt
⋅2HCl
NH
N
N
NH NH
N
HN
1. CH2Cl2, reflux, 48 h
2. Et3N
R1
NH2
R1
R1
52–75%
R
1 = i-Pr; R2 = 4-MeC6H4
5a
5b
5c
5d
5e
5f
R1 = i-Pr; R2 = 4-MeOC6H4
R1 = i-Pr; R2 = Bn
R
1 = t-Bu; R2 = 4-MeC6H4
R1 = t-Bu; R2 = 4-MeOC6H4
R1 = t-Bu; R2 = Bn
R
1 = Ph; R2 = Bn
5g
R2
R2
R2
R3
N
R3
N
B
H
Scheme 4 Synthesis of bis(imidazolines)
N
N
N
1. n-BuLi, –78 °C, THF
2. R32BX (X = Cl, Br), pentane,
–78 °C, then –78 °C to 23 °C
N
To gain information about the coordination geometry of
metal complexes derived from these bis(imidazolines), a
copper(II) complex was synthesized with one of the
ligands and crystallized. Bis(imidazoline) 4a readily re-
acted with sodium tert-butoxide and copper(II) chloride to
give a homoleptic copper(II) complex in 85% yield. The
coordination geometry of this complex is best described
as distorted tetrahedral (Figure 3). The Cu–N bond dis-
R1
R1
R1
40–65%
R1 = i-Pr; R2 = 4-CF3C6H4; R3 = Et
R1 = i-Pr; R2 = 4-CF3C6H4; R3 = Ph
4a
4b
4c
4d
4e
4f
R
1 = t-Bu; R2 = 4-CF3C6H4; R3 = Et
1 = t-Bu; R2 = 4-CF3C6H4; R3 = Ph
R
R1 = t-Bu; R2 = 4-MeC6H4; R3 = Ph
1 = t-Bu; R2 = 4-MeOC6H4; R3 = Ph
R
tances [Cu–Nim = 1.964(5), 1.968(5) Å; Cu–N¢im
=
=
=
1.958(5), 1.966(6) Å] and bond angles [Nim–Cu–Nim
Scheme 3 Synthesis of boron-bridged bis(imidazolines)
94.8(2)°;
Nim–Cu–N¢im = 103.2(3)°;
Cim–B–Cim
111.8(5)°] fall within the ranges observed for copper(II)
complexes of similar bidentate ligands (3, R1 = i-Pr;
R2 = Ph: Cu–Nox = 1.956, 1.936 Å; Nox–C–Nox = 94.5°;
Crystals of 4c and 4e suitable for X-ray analysis were ob-
tained upon a cooling the solution in pentane to +4 °C.
The crystal structures of 4c and 4e (Figure 2; for details of
Synthesis 2007, No. 4, 572–582 © Thieme Stuttgart · New York

574
B. Ramalingam et al.
PAPER
Cox–B–Cox = 110.0°). Bis(imidazoline) 5b also formed an
analogous homoleptic complex [Cu(5b)2] with copper(II)
chloride in the presence of potassium carbonate as evi-
denced by mass spectrometry and elemental analysis.
Bis(imidazolines) 4a–f and 5a–f were tested in the cop-
per-catalyzed enantioselective cyclopropanation of sty-
rene with diazoacetic acid esters. The copper(I) catalysts
were generated in situ by mixing the pre-ligands with cop-
per(I) trifluoromethanesulfonate and the reaction was car-
ried out under standard conditions.4 Overall, the boron-
bridged bis(imidazolines) 4a–f gave relatively low enan-
tioselectivities compared to analogous bis(oxazolines) 2
and 3, which is surprising in view of the very similar
geometry of bis(imidazolines) and bis(oxazolines)
(Table 1). Interestingly, higher enantiomeric excess was
observed in acetonitrile than in dichloromethane or 1,2-
dichloroethane, whereas for box- or borabox-derived cat-
alysts dichloromethane is usually the best solvent. No im-
provement of enantioselectivity was observed when the
catalyst was generated from the lithium salt of 4d. Meth-
Figure 3 Crystal structure of [CuL2] (L = (R,R)-4a); hydrogen
atoms are omitted for clarity
ylene-bridged bis(imidazolines) 5a–g performed better,
but the enantiomeric excess values were still lower than
those reported for the most efficient bis(oxazolines). As
Table 1 Cyclopropanation of Stryene
O
N2
OR
Ph
Ph
+
Ph
L, 0.5 [Cu(OTf)]2⋅C6H6
CO2R
CO2R
trans
(1 mol%)
cis
12–14 h, r.t.
Entry
L
R
Solvent
Yieldb (%)
Ratioc
ee (%)d
trans/cis
trans
cis
29
50
55
11
12
42
46
48
58
56
50
46
–
1
2
4d
4d
4d
4e
4f
Et
DCEa
76
65
54
40
48
83
90
75
90
88
80
72
86
88
58:42
56:44
83:17
67:33
74:26
69:31
70:30
72:28
67:33
68:32
69:31
83:17
98:2
19
36
51
7
Et
MeCN
MeCN
MeCN
MeCN
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
3
t-Bu
Et
4
5
Et
8
6
5a
5b
5c
5d
5e
5f
Et
51
58
61
70
69
70
56
85
84
7
Et
8
Et
9
Et
10
11
12
13
14
Et
Et
5d
5d
5e
t-Bu
BHTe
BHTe
99:1
–
a 1,2-Dichloroethane.
b After column chromatography.
c Determined by 1H NMR.
d Determined by GC and HPLC analysis.
e 2,6-Di-tert-butyl-4-methylphenyl.
Synthesis 2007, No. 4, 572–582 © Thieme Stuttgart · New York

PAPER
Synthesis of Chiral C2-Symmetric Methylene- and Boron-Bridged Bis(imidazolines)
575
a-tert-Butoxycarbonylamino Acid Amides 7d–l; General Proce-
dure
with copper–bis(oxazoline) catalysts, the best enantio-
and diastereoselectivities were observed with the bulky
2,6-di-tert-butyl-4-methylphenyl diazoacetate.
TBTU (6.78 g, 21.1 mmol) was added to a soln of Boc-protected
amino acid (21.1 mmol) in CH2Cl2 (100 mL). After 5 min, DIPEA
(22.0 mL, 128 mmol) and amine (21.1 mmol) were added sequen-
tially and stirred overnight. The mixture was diluted with CH2Cl2
(200 mL), washed with H2O (250 mL) and the organic layer was
separated. The organic layer was washed with 1 M HCl (3 × 200
mL), separated and dried (Na2SO4). The crude product was purified
by flash chromatography (silica gel, h = 15 cm, ∆ = 7 cm) to give
a white solid.
Bis(imidazolines) 5a–g were also tested as ligands in the
copper-catalyzed enantioselective allylic oxidation of cy-
clopentene and cyclohexene (Scheme 5).11–13 The copper(I)
complexes prepared in situ from tetrakis(acetonitrile)cop-
per(I) hexafluorophosphate proved to be more reactive,
but somewhat less enantioselective than the analogous
bis(oxazoline) complexes and yielded the oxidation prod-
ucts in high yield (2, R1 = i-Pr, R2 = Me; n = 1; r.t., 4 d;
57% conversion; 74% ee).12a
a-Amino Amides 8d–l; General Procedure
The Boc-protected amide 7 (14.3 mmol) was dissolved in CH2Cl2
(50 mL) and stirred for 2 h after the addition of TFA (16.5 mL, 215
mmol). The excess reagent and the solvent were removed under
vacuum, redissolved in CH2Cl2 (100 mL) and cooled to 0 °C. Sat.
Na2CO3 soln was added slowly and the resulting organic layer was
washed with aq NaHCO3 (3 × 100 mL). The separated organic
phase was dried (Na2SO4) and concentrated to afford a white solid.
O
O
O
Ph
Ph
O2t-Bu
[Cu(MeCN)4]PF6 (5 mol%)
L (7.5 mol%)
( )n
Time Yield
( )n
1,2-Diamines 9d–l; General Procedure
MeCN, r.t.
A soln of amide 8 (15.2 mmol) in anhyd THF (50 mL) was cooled
to 0 °C in a flame-dried, 2-necked, round-bottom flask. 1 M
BH3·THF soln (45.6 mL, 3 equiv) was added through a syringe un-
der a flow of argon and the mixture was heated to reflux for 22 h.
After cooling the mixture to 0 °C, 6 M HCl (30 mL) was added
slowly and the THF evaporated. The acidic aqueous layer was
washed with Et2O (1 × 30 mL). The aqueous layer was brought to
pH 10 with NaOH pellets with cooling in an ice bath. After extrac-
tion with Et2O (3 × 50 mL), the organic phase was dried (Na2SO4).
The diamine 9 obtained after evaporation of the solvent was suffi-
ciently pure for the next step. Analytically pure diamine was ob-
tained by Kugelrohr distillation as a colorless viscous oil.
L
n
ee
(h)
(%)
(%)
5a
5a
5g
5g
1
2
1
1
18
48
28
36
80
91
74
54
49
44
59
65a
a At 10 °C.
Scheme 5 Allylic oxidation of cyclic alkenes
In summary, we have developed a short, practical synthe-
sis of anionic boron-bridged C2-symmetric bis(imidazo-
lines) 4 via the corresponding 2-imidazolines. In addition,
analogous methylene-bridged bis(imidazolines) 5 were
readily prepared in one step from chiral diamines. In com-
parison with their bis(oxazoline) counterparts, bis(imida-
zolines) possess an attractive additional feature, as the two
N-substituents may serve as handles to tune the electronic
and conformational properties of the ligand. Moreover,
these substituents could also serve as linkers for attaching
the ligand to a solid support. Although in the reactions
studied so far, the enantioselectivities induced by bis(im-
idazolines) were not as high as those reported for the best
bis(oxazolines), further studies of these easily accessible
modular ligands seem worthwhile.
2-Imidazolines 6d–k; General Procedure
The diamine 9 (12.1 mmol) and ethyl formimidate hydrochloride
(1.33 g, 12.1 mmol) were taken up in anhyd CH2Cl2 (50 mL) and
refluxed for 18 h under argon. At the end of the reaction, the mixture
was cooled to 0 °C and anhyd Et3N (5 mL) was added. The mixture
was washed with sat. NaHCO3 (2 × 100 mL). The organic layer was
separated and the product was purified by flash chromatography
(silica gel, h = 15 cm, ∆ = 5 cm).
Synthesis of 4a–f; General Procedure
A 1.6 M n-BuLi in hexanes soln (1.72 mL, 2.76 mmol) was added
dropwise to a soln of 2-imidazoline (2.51 mmol) in THF (40 mL) at
–78 °C. The mixture was stirred for 30 min and a soln of Et2BBr or
Ph2BCl (1.26 mmol) in pentane (5 mL) was added through a cannu-
la at –78 °C. The cooling bath was removed and mixture was stirred
at r.t. overnight. The volatile compounds were removed under vac-
uum, the foamy residue was directly transferred to a short column
(silica gel, h = 10 cm, ∆ = 2 cm, hexanes–EtOAc–Et3N, 20:2:1).
Purification by flash chromatography (h = 20 cm, ∆ = 3 cm) afford-
ed a foamy solid.
Reactions were conducted under an inert atmosphere using standard
Schlenk techniques. The solvents and reagents were dried following
standard procedures and stored under argon prior to use. 1H, 13C and
11B NMR spectra were measured on Bruker Avance 500 and 400
NMR spectrometers operating at 500.13 and 400.13 MHz, respec-
tively, for 1H NMR and at 125.8 MHz and 100.6 MHz, respectively,
for 13C NMR (internal standard set to d = 5.32 (CD2Cl2) and d = 7.26
(CDCl3). MS spectra were measured on a Finnigan MAT 312 spec-
trometer. Elemental analyses were performed by the Micro Analy-
sis Laboratory of University of Basel. Optical rotation values were
obtained in a 1 cm3 cell with a pathlength of 10 cm at r.t. Imidazo-
lines 6a–c were synthesized according to literature procedures;8
cyclopropanation4 and allylic oxidation12 reactions were performed
under standard conditions described in the literature. Ph2BCl14 and
Et2BBr15 were synthesized following literature methods.
Synthesis of 5a–g; General Procedure
To a suspension of diethyl malonimidate dihydrochloride (460 mg,
2.00 mmol) in anhyd CH2Cl2 (20 mL), diamine (4.20 mmol, 1.05
equiv) was added. After stirring for 48 h under argon at reflux, the
mixture was cooled to 0 °C and anhyd Et3N (2 mL) was added. The
mixture was diluted with CH2Cl2 (20 mL) and washed with sat.
NaHCO3 (3 × 20 mL). The organic phase was dried (Na2SO4) and
filtered. The filtrate was concentrated and the residue was recrystal-
lized (MeCN).
Synthesis 2007, No. 4, 572–582 © Thieme Stuttgart · New York

576
B. Ramalingam et al.
PAPER
Synthesis of [Cu(4a)2]
1H NMR (400 MHz, CDCl3): d = 7.50 (d, J = 8.1 Hz, 4 H, HCAr),
7.27 (d, J = 8.1 Hz, 4 H, HCAr), 3.86–3.80 (m, 2 H, HCim), 3.76–
3.71 (m, 2 H, H2Cim), 3.42–3.37 (m, 2 H, H2Cim), 1.79–1.71 [m, 2
H, HC(CH3)2], 1.07 (d, J = 6.6 Hz, 6 H, H3C), 0.97 (d, J = 6.6 Hz,
6 H, H3C), 0.66–0.63 (t, J = 7.6 Hz, 6 H, H3CCH2B), –0.19 to –0.35
(m, 4 H, H2CB).
13C NMR (100 MHz, CDCl3): d = 146.6, 144.9, 128.0, 128.8, 128.4,
126.0, 66.5, 58.8, 33.5, 19.1, 19.0, 12.0.
19F NMR (400 MHz, CDCl3): d = –63.4.
11B NMR (500 MHz, CDCl3): d = –13.3.
To a soln of 4a (151 mg, 0.26 mmol) and t-BuONa (25.0 mg, 0.26
mmol) in anhyd THF (5 mL), CuCl2 (17.5 mg, 0.13 mmol) was add-
ed under a flow of argon. The resulting soln was stirred for 4 h and
the solvent evaporated. The residue was dissolved in CH2Cl2 (20
mL) and washed with 1 M K2CO3 (2 × 10 mL). The organic layer
was dried (Na2SO4) and the solvent evaporated, yielding a pink mi-
crocrystalline solid (130 mg, 82%). Crystals suitable for X-ray anal-
ysis were obtained by dissolving the complex in CH2Cl2 and
layering the soln with Et2O; [a]D20 –518 (c 0.10, CH2Cl2).
Crystal Structure Determination
X-ray data of the crystals of compounds 4c, 4e, and [Cu(4a)2] were
collected in a four-circle Enraf-Nonius Kappa CCD X-ray diffrac-
tometer and graphite monochromatized Mo-Ka radiation was used.
The data collection was done using COLLECT software. The data
reduction was performed using the DENZO/SCALEPACK pro-
gram.16 The structure were solved by direct methods using SIR-9217
program and then refined using CRYSTALS.18 The non-hydrogens
were refined anisotropically. Crystal data and additional details of
the data collection and refinement of the structure are presented in
Table 2.
4b
White solid; yield: 30%; flash chromatography: hexanes–EtOAc–
Et3N, 28:2:1; Rf = 0.10 (hexanes–EtOAc–Et3N, 28:2:1).
1H NMR (400 MHz, CDCl3): d = 15.54 (br s, 1 H, HN), 7.00 (d,
J = 8.2 Hz, 4 H, HCAr), 6.96–6.88 (m, 10 H, HCAr), 6.23 (d, J = 8.2
Hz, 4 H, HCAr), 3.94–3.89 (ddd, J = 15.3, 10.1, 6.8 Hz, 2 H, HCim),
3.66–3.61 (m, 2 H, H2Cim), 3.36–3.31 (m, 2 H, H2Cim), 1.87–1.76
[m, 2 H, HC(CH3)2], 1.14 (d, J = 6.6 Hz, 6 H, H3C), 1.00 (d, J = 6.6
Hz, 6 H, H3C).
13C NMR (100 MHz, CDCl3): d = 186.7, 173.8, 144.5, 144.0, 134.0,
127.3, 126.7, 125.0, 124.6, 66.4, 57.5, 33.6, 19.2, 19.0.
4a
Foamy white solid; yield: 30%; flash chromatography: pentane–
CH2Cl2–Et3N, 6:4:1; Rf = 0.16 (pentane–CH2Cl2–Et3N).
19F NMR (400 MHz, CDCl3): d = –63.4.
11B NMR (500 MHz, CDCl3): d = –13.4.
Table 2 Crystal Structure Data and Refinement Details for Compounds 4c, 4e, and [Cu(4a)2]
4c
4e
[Cu(4a)2]
C60H76B2CuF12N8
1222.5
Empirical formula
C32H43BF6N4
608.5
C40H49BN4
596.7
Formula weight
Crystal system
orthorhombic
P212121
9.5011(1)
13.2942(2)
26.0217(3)
90
orthorhombic
P212121
10.5276(1)
15.2285(2)
21.9608(3)
90
orthorhombic
P212121
11.0044(5)
22.6579(12)
25.9569(13)
90
Space group
a (Å)
b (Å)
c (Å)
a, b, g (°)
V (Å3)
3286.79(7)
4
3520.75(7)
4
6472.0(6)
4
Z
Dcalc (g cm–3)
1.226
1.126
1.255
Absorption coefficient (mm-1)
F(000)
0.095
0.065
0.414
1285
1288
2556
No. of data/parameters
Goodness-of-fit on F2
Ra
4173 /444
0.842
4437/406
0.858
11914/776
0.920
0.0338
0.899
0.0361
0.1041
614436
0.0861
wRb
0.1899
CCDC deposition number
a R1 = SΩΩFoΩ–ΩFcΩΩ/ SΩFoΩ.
614435
614434
b wR2 = {Sw[(Fo2 – Fc2)2/Sw [(Fo ) ]}1/2
2 2
Synthesis 2007, No. 4, 572–582 © Thieme Stuttgart · New York

PAPER
Synthesis of Chiral C2-Symmetric Methylene- and Boron-Bridged Bis(imidazolines)
577
4c
13C NMR (100 MHz, CD2Cl2): d = 157.9, 134.8, 134.7, 129.7,
Foamy white solid; yield: 65%; flash chromatography: hexanes–
pentane–CH2Cl2–Et3N, 8:8:2:1; Rf = 0.53 (hexanes–pentane–
CH2Cl2–Et3N, 8:8:2:1).
[a]D20 –35.5 (c 0.55, CH2Cl2).
1H NMR (400 MHz, CDCl3): d = 9.13 (br s, 1 H, HN), 7.51 (d,
J = 8.3 Hz, 4 H, HCAr), 7.27 (d, J = 8.3 Hz, 4 H, HCAr), 3.88–3.83
(dd, J = 11.1, 8.1 Hz, 2 H, HCim), 3.74–3.69 (m, 2 H, H2Cim), 3.46–
3.41 (m, 2 H, H2Cim), 0.97 [s, 18 H, (H3C)3C], 0.67–0.65 (t, J = 7.6
Hz, 6 H, H3CCH2B), –0.26 to –0.33 (q, J = 7.6 Hz, 4 H, H2CB).
13C NMR (100 MHz, CDCl3): d = 146.6, 144.9, 128.1, 127.7, 126.6,
126.0, 67.0, 56.8, 33.8, 26.0, 12.2.
19F NMR (400 MHz, CDCl3): d = –63.5.
11B NMR (500 MHz, CDCl3): d = –15.1.
MS (FAB, NBA): m/z (%) = 609 (72) [M + H]+.
126.4, 124.2, 113.1, 69.9, 56.7, 55.6, 34.4, 26.0.
11B NMR (500 MHz, CD2Cl2): d = –13.2.
MS (FAB, NBA): m/z (%) = 629 (62) [M + H]+.
Anal. Calcd for C40H49BN4O2: C, 76.42; H, 7.86; N, 8.91. Found: C,
75.93; H, 7.74; N, 8.47.
5a
20
White solid; yield: 52%; [a]D –85.4 (c 0.58, CH2Cl2); Rf = 0.41
(hexanes–EtOAc–Et3N, 6:3:1).
1H NMR (400 MHz, CD2Cl2): d = 9.12 (br s, 1 H, HN), 7.08–7.02
(m, 8 H, HCAr), 4.18 [s, 1 H, HC(1)], 3.78–3.74 [t, J = 8.6 Hz, 2 H,
HAHBC(5,5¢)], 3.65–3.59 [m, 2 H, HC(4,4¢)], 3.42–3.37 [t, J = 8.6
Hz, 2 H, HBHAC(5,5¢)], 2.28 (s, 6 H, H3CPh), 1.72–1.63 [m, 2 H,
HC(CH3)2], 1.06 [d, J = 6.6 Hz, 6 H, (H3CA)2CH], 0.93 [d, J = 6.6
Hz, 6 H, (H3CB)2CH].
13C NMR (100 MHz, CD2Cl2): d = 160.5, 140.6, 133.3, 129.8,
122.7, 65.5, 59.6, 55.8, 34.4, 21.0, 19.8, 19.2.
Anal. Calcd for C32H43BF6N4: C, 63.16; H, 7.12; N, 9.21. Found: C,
63.23; H, 7.24; N, 9.27.
MS (FAB, NBA): m/z (%) = 417 (100) [M + H]+.
4d
20
Foamy white solid; yield: 58%; [a]D –101.7 (c 0.41, CH2Cl2);
flash chromatography: hexanes–pentane–Et3N, 5:5:1; Rf = 0.34
Anal. Calcd for C27H36N4: C, 77.84; H, 8.71; N, 13.45. Found: C,
77.88; H, 8.72; N, 13.47.
(hexanes–pentane–Et3N, 5:5:1).
5b
1H NMR (400 MHz, CDCl3): d = 15.68 (br s, 1 H, HN), 6.99 (d,
J = 8.1 Hz, 4 H, HCAr), 6.96–6.88 (m, 10 H, HCAr), 6.21 (d, J = 8.1
Hz, 4 H, HCAr), 3.96–3.91 (dd, J = 11.1, 8.6 Hz, 2 H, HCim), 3.60–
3.55 (t, J = 10.4 Hz, 2 H, HAHBCim), 3.42–3.37 (t, J = 8.8 Hz, 2 H,
HBHACim), 1.01 [s, 18 H, (H3C)3C].
13C NMR (100 MHz, CDCl3): d = 144.5, 134.1, 127.6, 127.5, 127.3,
127.3, 126.7, 125.5, 125.0, 124.6, 69.8, 55.4, 34.2, 26.0.
19F NMR (400 MHz, CDCl3): d = –63.4.
11B NMR (500 MHz, CDCl3): d = –13.4.
MS (FAB, NBA): m/z (%) = 705 (68) [M + H]+.
20
White solid; yield: 55%; [a]D –66.8 (c 0.53, CH2Cl2); Rf = 0.20
(hexanes–EtOAc–Et3N, 5:4:1).
1H NMR (400 MHz, CD2Cl2): d = 7.91 (br s, 1 H, HN), 7.08–7.04
(m, 4 H, HCAr), 6.82–6.77 (m, 4 H, HCAr), 3.89 [s, 1 H, HC(1)],
3.77–3.70 [m, 8 H, HAHBC(5,5¢)/H3CO], 3.64–3.58 [m, 2 H,
HC(4,4¢)], 3.36–3.32 [t, J = 8.6 Hz, 2 H, HBHAC(5,5¢)], 1.72–1.61
[m, 2 H, HC(CH3)2], 1.06 [d, J = 6.6 Hz, 6 H, (H3CA)2CH], 0.92 [d,
J = 6.6 Hz, 6 H, (H3CB)2CH].
13C NMR (100 MHz, CD2Cl2): d = 161.2, 156.7, 136.3, 125.1,
114.6, 65.7, 58.9, 56.4, 55.9, 34.3, 19.8, 19.3.
MS (FAB, NBA): m/z (%) = 449 (100) [M + H]+.
Anal. Calcd for C40H43BF6N4: C, 68.18; H, 6.15; N, 7.95. Found: C,
68.24; H, 6.21; N, 7.97.
Anal. Calcd for C27H36N4O2: C, 72.29; H, 8.09; N, 12.49. Found: C,
72.32; H, 8.10; N, 12.45.
4e
Foamy white solid; yield: 48%; [a]D20 –72.7 (c 1.04, CH2Cl2); flash
chromatography: hexanes–Et3N, 10:1; Rf = 0.43 (hexanes–Et3N,
10:1).
5c
20
White solid; yield: 61%; [a]D –35.1 (c 0.60, CH2Cl2); Rf = 0.13
(hexanes–EtOAc–Et3N, 6:3:1).
1H NMR (400 MHz, CD2Cl2): d = 15.64 (br s, 1 H, HN), 6.95–6.85
(m, 10 H, HCAr), 6.54 (d, J = 8.1 Hz, 4 H, HCAr), 5.96 (d, J = 8.1 Hz,
4 H, HCAr), 3.91–3.86 (dd, J = 11.1, 8.3 Hz, 2 H, HCim), 3.56–3.51
(dd, J = 11.1, 10.1 Hz, 2 H, HAHBCim), 3.36–3.32 (dd, J = 10.1, 8.3
Hz, 2 H, HBHACim), 2.12 (s, 6 H, H3C), 0.99 [s, 18 H, (H3C)3C].
13C NMR (100 MHz, CD2Cl2): d = 134.3, 128.1, 127.8, 127.6,
125.9, 123.6, 123.3, 69.7, 56.0, 33.9, 25.5, 20.5.
1H NMR (400 MHz, CD2Cl2): d = 9.40 (br s, 1 H, HN), 7.35–7.21
(m, 10 H, HCAr), 4.27 (d, J = 15.4 Hz, 2 H, HAHBCPh), 4.12 (d,
J = 15.4 Hz, 2 H, HBHACPh), 3.91 [s, 1 H, HC(1)], 3.52–3.43 [m, 2
H, HC(4,4¢)], 3.31–3.27 [t, J = 8.6 Hz, 2 H, HAHBC(5,5¢)], 2.83–
2.78 [t, J = 8.6 Hz, 2 H, HBHAC(5,5¢)], 1.63–1.52 [m, 2 H,
HC(CH3)2], 1.00 [d, J = 6.6 Hz, 6 H, (H3CA)2CH], 0.84 [d, J = 6.6
Hz, 6 H, (H3CB)2CH].
13C NMR (100 MHz, CD2Cl2): d = 161.2, 139.1, 128.9, 128.1,
11B NMR (500 MHz, CD2Cl2): d = –14.2.
MS (FAB, NBA): m/z (%) = 597 (66) [M + H]+.
127.5, 70.8, 55.8, 51.7, 51.1, 34.5, 33.9, 19.9, 19.6, 18.8, 18.7.
MS (FAB, NBA): m/z (%) = 417 (100) [M + H]+.
Anal. Calcd for C40H49BN4: C, 80.52; H, 8.28; N, 9.39. Found: C,
80.59; H, 8.31; N, 9.29.
Anal. Calcd for C27H36N4: C, 77.84; H, 8.71; N, 13.45. Found: C,
77.92; H, 8.74; N, 13.57.
4f
Foamy white solid; yield: 56%; [a]D20 –54.1 (c 1.07, CH2Cl2); flash
chromatography: hexanes–Et3N, 10:1; Rf = 0.25 (hexanes–Et3N,
10:1).
5d
20
White crystalline solid; yield: 42%; [a]D –42.1 (c 0.65, CH2Cl2);
Rf = 0.58 (hexanes–EtOAc–Et3N, 7:2:1).
1H NMR (400 MHz, CD2Cl2): d = 9.88 (br s, 1 H, HN), 7.08–7.02
(m, 8 H, HCAr), 4.17 [s, 1 H, HC(1)], 3.74–3.68 [m, 4 H,
HAHBC(5,5¢)/HC(4,4¢)], 3.51–3.47 [m, 2 H, HBHAC(5,5¢)], 2.27 (s,
6 H, H3CPh), 0.94 [s, 18 H, (H3C)3C].
1H NMR (400 MHz, CD2Cl2): d = 15.48 (br s, 1 H, HN), 6.94–6.87
(m, 10 H, HCAr), 6.27–6.23 (m, 4 H, HCAr), 5.99–5.96 (m, 4 H,
HCAr), 3.90–3.85 (dd, J = 11.4, 8.3 Hz, 2 H, HCim), 3.63 (s, 6 H,
H3CO), 3.55–3.52 (dd, J = 11.4, 10.1 Hz, 2 H, HAHBCim), 3.34–3.29
(dd, J = 10.1, 8.3 Hz, 2 H, HBHACim), 1.00 [s, 18 H, (H3C)3C].
Synthesis 2007, No. 4, 572–582 © Thieme Stuttgart · New York

578
B. Ramalingam et al.
PAPER
13C NMR (100 MHz, CD2Cl2): d = 160.5, 140.7, 133.2, 129.9,
122.7, 68.4, 59.3, 53.0, 34.2, 26.1, 21.0.
Anal. Calcd for C17H26N2O3: C, 66.64; H, 8.55; N, 9.14. Found: C,
66.72; H, 8.63; N, 9.17.
MS (FAB, NBA): m/z (%) = 445 (100) [M + H]+.
7e
White solid; yield: 82%; [a]D20 –15.2 (c 0.54, CH2Cl2); flash chro-
matography: hexanes–EtOAc, 8:2; Rf = 0.44 (hexanes– EtOAc,
8:2).
1H NMR (400 MHz, CDCl3): d = 8.06 (br s, 1 H, HNCO), 7.33 (d,
J = 8.1 Hz, 2 H, HCAr), 7.03 (d, J = 8.1 Hz, 2 H, HCAr), 5.49 (br d,
J = 9.4 Hz, 1 H, HNBoc), 4.08 (d, J = 9.4 Hz, 1 H, HCNH), 2.27 (s,
3 H, H3CPh), 1.41 [s, 9 H, (H3C)3Boc], 1.07 [s, 9 H, (H3C)3C].
13C NMR (100 MHz, CDCl3): d = 170.0, 156.7, 135.3, 134.4, 129.8,
120.7, 80.4, 63.4, 35.2, 28.8, 27.1, 21.3.
MS (FAB, NBA): m/z (%) = 321 (45) [M + 1]+.
Anal. Calcd for C29H40N4: C, 78.33; H, 9.07; N, 12.60. Found: C,
78.44; H, 9.06; N, 12.55.
5e
20
White solid; yield: 48%; [a]D –25.2 (c 0.59, CH2Cl2); Rf = 0.29
(hexanes–EtOAc–Et3N, 7:2:1).
1H NMR (400 MHz, CD2Cl2): d = 8.38 (br s, 1 H, HN), 7.09–7.04
(m, 4 H, HCAr), 6.81–6.77 (m, 4 H, HCAr), 3.88 [s, 1 H, HC(1)], 3.74
(s, 6 H, H3CO), 3.70–3.67 [m, 4 H, HAHBC(5,5¢)/HC(4,4¢)], 3.43–
3.40 [t, J = 6.6 Hz, 2 H, HBHAC(5,5¢)], 0.94 [s, 18 H, (H3C)3C].
13C NMR (100 MHz, CD2Cl2): d = 161.2, 156.6, 136.4, 125.0,
114.6, 68.6, 58.6, 55.9, 53.6, 34.1, 26.1.
MS (FAB, NBA): m/z (%) = 477 (100) [M + H]+.
Anal. Calcd for C18H28N2O3: C, 67.47; H, 8.81; N, 8.74. Found: C,
67.65; H, 8.87; N, 8.78.
Anal. Calcd for C29H40N4O2: C, 73.07; H, 8.46; N, 11.75. Found: C,
73.08; H, 8.48; N, 11.78.
7f
White solid; yield: 91%; [a]D20 –21.5 (c 0.61, CH2Cl2); flash chro-
matography: hexanes–EtOAc, 7:1; Rf = 0.25 (hexanes– EtOAc,
7:1).
5f
20
White solid; yield: 51%; [a]D –18.9 (c 0.57, CH2Cl2); Rf = 0.32
(hexanes–EtOAc–Et3N, 6:3:1).
1H NMR (400 MHz, CDCl3): d = 7.88 (br s, 1 H, HNCO), 7.29–7.22
(m, 7 H, HCAr), 7.05 (d, J = 8.1 Hz, 2 H, HCAr), 5.30, 4.51 (br s, 2
H, HNBoc/HCCO), 3.13 (d, J = 6.3 Hz, 2 H, H2CPh), 2.29 (s, 3 H,
H3CPh), 1.41 [s, 9 H, (H3C)3Boc].
13C NMR (100 MHz, CDCl3): d = 169.6, 136.9, 134.8, 134.2, 129.5,
129.4, 128.9, 127.1, 120.3, 80.6, 56.8, 38.7, 28.4, 21.0.
1H NMR (400 MHz, CD2Cl2): d = 9.07 (br s, 1 H, HN), 7.33–7.21
(m, 10 H, HCAr), 4.25 (d, J = 15.4 Hz, 2 H, HAHBCPh), 4.15 (d,
J = 15.4 Hz, 2 H, HBHACPh), 3.89 [s, 1 H, HC(1)], 3.62–3.58 [t,
J = 8.8 Hz, 2 H, HAHBC(5,5¢)], 3.20–3.16 [t, J = 8.8 Hz, 2 H,
HC(4,4¢)], 2.93–2.89 [t, J = 8.8 Hz, 2 H, HBHAC(5,5¢)], 0.86 [s, 18
H, (H3C)3C].
MS (FAB, NBA): m/z (%) = 355 (31) [M + H]+.
13C NMR (100 MHz, CD2Cl2): d = 164.0, 139.2, 128.9, 128.1,
127.5, 68.7, 55.2, 51.3, 51.2, 34.0, 26.1.
Anal. Calcd for C21H26N2O3: C, 71.16; H, 7.39; N, 7.90. Found: C,
71.08; H, 7.38; N, 7.92.
MS (FAB, NBA): m/z (%) = 445 (100) [M + H]+.
7g
White solid; yield: 90%; [a]D20 –36.2 (c 0.55, CH2Cl2); flash chro-
matography: hexanes–EtOAc, 6:4; Rf = 0.49 (hexanes– EtOAc,
6:4).
1H NMR (400 MHz, CDCl3): d = 8.28 (br s, 1 H, HNCO), 7.37 (d,
J = 8.6 Hz, 2 H, HCAr), 6.78 (d, J = 8.6 Hz, 2 H, HCAr), 5.34 (br s,
1 H, HNBoc), 4.08–4.04 (dd, J = 7.6, 7.3 Hz, 1 H, HCNH), 3.76 (s,
3 H, H3CO), 2.20–2.17 [br d, J = 6.8 Hz, 1 H, HC(CH3)2], 1.43 [s,
9 H, (H3C)3Boc], 1.02 (d, J = 6.8 Hz, 3 H, H3C), 0.99 (d, J = 6.8 Hz,
3 H, H3C).
Anal. Calcd for C29H40N4: C, 78.33; H, 9.07; N, 12.60. Found: C,
78.34; H, 9.12; N, 12.66.
5g
White crystalline solid; yield: 48%; [a]D20 –193.8 (c 0.52, CH2Cl2).
1H NMR (400 MHz, CD2Cl2): d = 9.16 (br s, 1 H, HN), 7.35–7.20
(m, 20 H, HCAr), 4.92 [dd, J = 8.8, 7.6 Hz, 2 H, HC(4,4¢)], 4.34 (d,
J = 15.5 Hz, 2 H, H2CPh), 4.26 (d, J = 15.5 Hz, 2 H, H2CPh), 4.16
[s, 1 H, HC(1)], 3.65 [dd, J = 8.8, 8.6 Hz, 2 H, HAHBC(5,5¢)], 3.05
[dd, J = 8.6, 7.6 Hz, 2 H, HBHAC(5,5¢)].
13C NMR (100 MHz, CD2Cl2): d = 164.3, 145.2, 145.1, 138.7,
138.6, 129.0, 128.9, 128.2, 127.7, 127.6, 127.0, 62.6, 58.3, 56.8,
51.1.
13C NMR (100 MHz, CDCl3): d = 170.3, 156.5, 156.4, 130.9, 121.9,
114.2, 80.3, 60.9, 55.6, 30.9, 28.5, 19.5, 18.3.
MS (EI): m/z (%) = 322 (17) [M]+.
Anal. Calcd for C17H26N2O4: C, 63.33; H, 8.13; N, 8.69. Found: C,
63.18; H, 8.15; N, 8.73.
MS (EI): m/z (%) = 484 (100) [M]+.
Anal. Calcd for C33H32N4: C, 81.78, H, 6.66; N, 11.56. Found: C,
81.72; H, 6.69; N, 11.58.
7h
White solid; yield: 80%; [a]D20 –16.6 (c 0.52, CH2Cl2); flash chro-
matography: hexanes–EtOAc, 8:2; Rf = 0.31 (hexanes–EtOAc,
8:2).
7d
White solid; yield: 95%; [a]D20 –37.3 (c 0.58, CH2Cl2); flash chro-
matography: hexanes–EtOAc, 7:3; Rf = 0.55 (hexanes– EtOAc,
7:3).
1H NMR (400 MHz, CDCl3): d = 8.49 (br s, 1 H, HNCO), 7.31 (d,
J = 8.6 Hz, 2 H, HCAr), 6.70 (d, J = 8.6 Hz, 2 H, HCAr), 5.64 (br d,
J = 9.4 Hz, 1 H, HNBoc), 4.15 (d, J = 9.4 Hz, 1 H, HCNH), 3.73 (s,
3 H, H3CO), 1.38 [s, 9 H, (H3C)3O], 1.08 [s, 9 H, (H3C)3C].
13C{1H} NMR (100 MHz, CDCl3): d = 169.8, 156.5, 156.4, 130.8,
122.1, 114.0, 80.0, 63.0, 55.5, 34.8, 28.5, 26.8.
1H NMR (400 MHz, CDCl3): d = 8.70 (br s, 1 H, HNCO), 7.34 (d,
J = 8.1 Hz, 2 H, HCAr), 6.99 (d, J = 8.1 Hz, 2 H, HCAr), 5.58 (d,
J = 8.6 Hz, 1 H, HNBoc), 4.17–4.14 (m, 1 H, HCNH), 2.26 (s, 3 H,
H3CPh), 2.19–2.03 [br m, 1 H, HC(CH3)2], 1.42 [s, 9 H,
(H3C)3Boc], 1.02 (d, J = 6.8 Hz, 3 H, H3C), 0.99 (d, J = 6.8 Hz, 3 H,
H3C).
MS (FAB, NBA): m/z (%) = 337 (48) [M + H]+.
13C NMR (100 MHz, CDCl3): d = 170.5, 156.7, 135.4, 134.4, 129.8,
120.5, 80.6, 61.2, 39.1, 31.2, 28.7, 21.3, 19.8.
Anal. Calcd for C18H28N2O4: C, 64.26; H, 8.39; N, 8.33. Found: C,
64.20; H, 8.48; N, 8.34.
MS (EI): m/z (%) = 306 (15) [M]+.
Synthesis 2007, No. 4, 572–582 © Thieme Stuttgart · New York

PAPER
Synthesis of Chiral C2-Symmetric Methylene- and Boron-Bridged Bis(imidazolines)
579
7i
1.70 (s, 2 H, H2N), 1.03 (d, J = 7.1 Hz, 3 H, H3C), 0.87 (d, J = 7.1
Hz, 3 H, H3C).
13C NMR (100 MHz, CDCl3): d = 172.4, 135.3, 133.7, 129.5, 119.6,
60.5, 30.9, 21.0, 19.9, 16.1.
White solid; yield: 80%; [a]D20 –9.2 (c 0.55, CH2Cl2); flash chroma-
tography: hexanes–EtOAc, 7:3; Rf = 0.43 (hexanes–EtOAc, 7:3).
1H NMR (400 MHz, CDCl3): d = 7.32–7.23 (m, 5 H, HCAr), 6.55 (br
s, 1 H, HNCO), 5.15 (br d, J = 7.8 Hz, 1 H, HNBoc), 4.48–4.43 (dd,
J = 14.9, 5.8 Hz, 1 H, H2CPh), 4.41–4.36 (dd, J = 14.9, 5.8 Hz, 1 H,
H2CPh), 3.96–3.92 (dd, J = 8.6, 6.6 Hz, 1 H, HCNH), 2.16–2.12 [br
d, J = 6.6 Hz, 1 H, HC(CH3)2], 1.40 [s, 9 H, (H3C)3Boc], 0.95 (d,
J = 6.8 Hz, 3 H, H3C), 0.92 (d, J = 6.8 Hz, 3 H, H3C).
13C NMR (100 MHz, CDCl3): d = 171.8, 156.1, 138.2, 128.8, 127.8,
127.6, 80.0, 60.3, 43.5, 30.7, 28.3, 19.5, 18.0.
MS (FAB, NBA): m/z (%) = 307 (22) [M + 1]+.
MS (EI): m/z (%) = 206 (7) [M]+.
Anal. Calcd for C12H18N2O: C, 69.87; H, 8.80; N, 13.58. Found: C,
69.40; H, 8.63; N, 13.47.
8e
White solid; yield: 99%; [a]D20 –69.5 (c 0.50, CH2Cl2).
1H NMR (400 MHz, CDCl3): d = 8.94 (br s, 1 H, HNCO), 7.46–7.44
(m, 2 H, HCAr), 7.12 (d, J = 8.3 Hz, 2 H, HCAr), 3.28 (s, 1 H, HC-
NH), 2.31 (s, 3 H, H3C), 1.84 (br s, 2 H, H2N), 1.05 [s, 9 H,
(H3C)3C].
Anal. Calcd for C17H26N2O3: C, 66.64; H, 8.55; N, 9.14. Found: C,
66.56; H, 8.57; N, 9.24.
13C NMR (100 MHz, CDCl3): d = 171.6, 135.3, 133.7, 129.6, 119.8,
7j
64.8, 34.6, 26.9, 21.0.
White solid; yield: 80%; flash chromatography: hexanes–EtOAc,
7:3; Rf = 0.51 (hexanes–EtOAc, 7:3).
MS (EI): m/z (%) = 220 (5) [M]+.
1H NMR (400 MHz, CDCl3): d = 7.33–7.24 (m, 5 H, HCAr), 6.19 (br
s, 1 H, HNCO), 5.30 (br d, J = 8.8 Hz, 1 H, HNBoc), 4.50–4.45 (dd,
J = 14.7, 5.8 Hz, 1 H, H2CPh), 4.40–4.35 (dd, J = 14.7, 5.7 Hz, 1 H,
H2CPh), 3.85 (d, J = 9.4 Hz, 1 H, HCNH), 1.41 [s, 9 H, (H3C)3Boc],
0.99 [s, 9 H, (H3C)3C].
Anal. Calcd for C13H20N2O: C, 70.87, H, 9.15; N, 12.72. Found: C,
70.69; H, 9.07; N, 12.70.
8f
White solid; yield: 99%; [a]D20 –135.4 (c 0.57, CH2Cl2).
1H NMR (400 MHz, CDCl3): d = 9.34 (br s, 1 H, HNCO), 7.48 (d,
J = 8.1 Hz, 2 H, HCAr), 7.33–7.24 (m, 5 H, HCAr), 7.14 (d, J = 8.1
Hz, 2 H, HCAr), 3.73–3.70 (dd, J = 9.5, 4.0 Hz, 1 H, HCCO), 3.39–
3.35 (dd, J = 13.8, 4.0 Hz, 1 H, H2CPh), 2.81–2.75 (dd, J = 13.8, 9.5
Hz, 1 H, H2CPh), 2.32 (s, 3 H, H3C), 1.46 (s, 2 H, H2N).
13C NMR (100 MHz, CDCl3): d = 172.3, 137.9, 135.3, 133.8, 129.6,
129.4, 128.9, 127.0, 119.6, 56.9, 40.8, 21.0.
13C NMR (100 MHz, CDCl3): d = 171.1, 156.0, 138.0, 128.8, 128.0,
127.7, 79.9, 62.6, 60.5, 34.6, 28.5, 26.8.
MS (FAB, NBA): m/z (%) = 321 (21) [M + 1]+.
Anal. Calcd for C18H28N2O3: C, 67.47; H, 8.81; N, 8.74. Found: C,
67.52; H, 8.87; N, 8.78.
7k
MS (EI): m/z (%) = 254 (5) [M]+.
White solid; yield: 94%; [a]D20 –0.9 (c 0.52, CH2Cl2); flash chroma-
tography: hexanes–EtOAc, 6:4; Rf = 0.55 (hexanes–EtOAc, 6:4).
Anal. Calcd for C16H18N2O: C, 75.56; H, 7.13; N, 11.01. Found: C,
75.30; H, 7.14; N, 11.02.
1H NMR (400 MHz, CDCl3): d = 7.30–7.08 (m, 10 H, HCAr), 6.15
(br s, 1 H, HNCO), 5.09 (br s, 1 H, HNBoc), 4.35, 4.34 (2 s, 3 H,
H2CNH/HCNH), 3.13–3.03 (m, 2 H, H2CCH), 1.39 [s, 9 H,
(H3C)3Boc].
8g
White solid; yield: 95%; [a]D20 –73.6 (c 0.54, CH2Cl2).
1H NMR (400 MHz, CDCl3): d = 9.37 (s, 1 H, HNCO), 7.52–7.48
(m, 2 H, HCAr), 6.87–6.83 (m, 2 H, HCAr), 3.78 (s, 3 H, H3CO), 3.37
(d, J = 3.5 Hz, 1 H, HCNH2), 2.48–2.37 [m, 1 H, HC(CH3)2], 1.66
(s, 2 H, H2N), 1.03 (d, J = 7.1 Hz, 3 H, H3C), 0.87 (d, J = 7.1 Hz, 3
H, H3C).
13C NMR (100 MHz, CDCl3): d = 172.3, 156.3, 131.2, 121.2, 114.2,
60.4, 55.6, 30.8, 19.9, 16.1.
13C NMR (100 MHz, CDCl3): d = 171.2, 155.5, 137.8, 129.8, 129.5,
128.8, 128.7, 127.8, 127.6, 127.1, 80.1, 56.2, 43.6, 38.7, 28.4.
MS (FAB, NBA): m/z (%) = 355 (46) [M + 1]+.
Anal. Calcd for C21H26N2O3: C, 71.16; H, 7.39; N, 7.90. Found: C,
71.26; H, 7.41; N, 7.90.
7l
MS (EI): m/z (%) = 222 (15) [M]+.
20
White solid; yield: 88%; [a]D –83.8 (c 1.01, CHCl3); flash chro-
matography: hexanes–EtOAc, 7:3; Rf = 0.52 (hexanes–EtOAc,
Anal. Calcd for C12H18N2O2: C, 64.84; H, 8.16; N, 12.60. Found:
C, 64.90; H, 8.21; N, 12.62.
7:3).
1H NMR (400 MHz, CDCl3): d = 7.37–7.09 (m, 10 H, HCAr), 6.41
(br s, 1 H, HNCO), 5.89 (br s, 1 H, HNBoc), 5.24 (br s, 1 H, HCCO),
4.39 (d, J = 5.7, 2 H, H2CPh), 1.38 [s, 9 H, (H3C)3Boc].
13C NMR (100 MHz, CDCl3): d = 170.3, 155.3, 138.5, 137.7, 129.1,
128.7, 128.4, 127.6, 127.5, 127.3, 80.2, 58.7, 43.7, 28.4.
8h
White solid; yield: 99%; [a]D20 –47.2 (c 0.47, CH2Cl2).
1H NMR (400 MHz, CDCl3): d = 8.90 (br s, 1 H, HNCO), 7.48 (d,
J = 9.1 Hz, 2 H, HCAr), 6.85 (d, J = 9.1 Hz, 2 H, HCAr), 3.78 (s, 3 H,
H3CO), 3.29 (s, 1 H, HCNH), 1.95 (br s, 2 H, H2N), 1.06 [s, 9 H,
(H3C)3C].
MS (FAB, NBA): m/z (%) = 341 (84) [M + 1]+.
Anal. Calcd for C20H24N2O3: C, 70.56; H, 7.11; N, 8.23. Found: C,
70.51; H, 6.93; N, 8.32.
13C {1H} NMR (100 MHz, CDCl3): d = 171.7, 156.6, 131.4, 121.8,
114.6, 65.1, 55.9, 34.9, 27.3.
MS (EI): m/z (%) = 236 (12) [M]+.
8d
White solid; yield: 97%; [a]D20 –72.6 (c 0.51, CH2Cl2).
Anal. Calcd for C13H20N2O2: C, 66.07; H, 8.53; N, 11.85. Found: C,
66.13; H, 8.49; N, 11.82.
1H NMR (400 MHz, CDCl3): d = 9.43 (s, 1 H, HNCO), 7.50–7.47
(m, 2 H, HCAr), 7.12 (d, J = 8.3 Hz, 2 H, HCAr), 3.38 (d, J = 3.5 Hz,
1 H, HCNH2), 2.45–2.41 [m, 1 H, HC(CH3)2], 2.31 (s, 3 H, H3C),
8i
White solid; yield: 98%; [a]D20 –27.2 (c 0.54, CH2Cl2).
Synthesis 2007, No. 4, 572–582 © Thieme Stuttgart · New York

580
B. Ramalingam et al.
PAPER
1H NMR (400 MHz, CDCl3): d = 7.66 (br s, 1 H, HNCO), 7.34–7.27
(m, 5 H, HCAr), 4.51–4.46 (dd, J = 14.9, 5.8 Hz, 1 H, H2CPh), 4.45–
4.40 (dd, J = 14.9, 5.8 Hz, 1 H, H2CPh), 3.29 (d, J = 3.8 Hz, 1 H,
HCNH2), 2.40–2.32 [m, 1 H, HC(CH3)2], 1.47 (s, 2 H, H2N), 1.00
(d, J = 6.8 Hz, 3 H, H3C), 0.84 (d, J = 6.8 Hz, 3 H, H3C).
13C NMR (100 MHz, CDCl3): d = 174.3, 138.7, 128.7, 127.9, 127.4,
60.3, 43.2, 30.9, 19.9, 16.1.
Anal. Calcd for C12H20N2: C, 74.95; H, 10.48; N, 14.57. Found: C,
75.38; H, 10.53; N, 14.65.
9e
Colorless oil; yield: 80%; [a]D20 +46.5 (c 0.50, CH2Cl2); Kugelrohr
distillation: 145 °C/0.06 mbar.
1H NMR (400 MHz, CDCl3): d = 7.00–6.97 (m, 2 H, HCAr), 6.59–
6.56 (m, 2 H, HCAr), 3.37–3.34 (dd, J = 11.4, 2.0 Hz, 1 H, HHC-
NH), 2.71–2.61 (m, 2 H, HHCNH/HCNH2), 2.24 (s, 3 H,
H3CC6H4), 0.96 [s, 9 H, (H3C)3C].
Anal. Calcd for C12H18N2O: C, 69.87; H, 8.80; N, 13.58. Found: C,
69.93; H, 8.96; N, 13.64.
8j
13C NMR (100 MHz, CDCl3): d = 146.7, 129.8, 126.6, 113.4, 59.7,
46.2, 33.9, 26.3, 20.5.
White solid; yield: 89%; [a]D20 –17.5 (c 0.56, CH2Cl2).
1H NMR (400 MHz, CDCl3): d = 7.33–7.26 (m, 5 H, HCAr), 7.14 (br
s, 1 H, HNCO), 4.42 (d, J = 6.1 Hz, 2 H, H2CPh), 3.14 (s, 1 H, HC-
NH), 1.72 (s, 2 H, H2N), 0.99 [s, 9 H, (H3C)3C].
13C NMR (100 MHz, CDCl3): d = 173.7, 138.9, 129.1, 128.3, 127.8,
64.8, 43.6, 34.6, 27.2.
MS (EI): m/z (%) = 206 (17) [M]+.
Anal. Calcd for C13H22N2: C, 75.68; H, 10.75; N, 13.58. Found: C,
75.69; H, 10.82; N, 13.64.
9f
Colorless oil; yield: 80%; [a]D20 +26.7 (c 0.51, CH2Cl2); Kugelrohr
MS (FAB, NBA): m/z (%) = 221 (100) [M + 1]+.
distillation: 225 °C/0.02 mbar.
Anal. Calcd for C13H20N2O: C, 70.87; H, 9.15; N, 12.72. Found: C,
70.70; H, 9.02; N, 12.82.
1H NMR (400 MHz, CDCl3): d = 7.35–7.22 (m, 5 H, HCAr), 7.01 (d,
J = 8.3 Hz, 2 H, HCAr), 6.57 (d, J = 8.3 Hz, 2 H, HCAr), 4.02 (br s,
1 H, HN), 3.29–3.22 (m, 2 H, HCNH2/HHCPh), 2.98–2.93 (dd,
J = 12.0, 8.1 Hz, 1 H, HHCPh), 2.91–2.86 (dd, J = 13.4, 5.1 Hz, 1
H, H2CNH), 2.63–2.58 (dd, J = 13.4, 8.4 Hz, 1 H, H2CNH), 2.26 (s,
3 H, H3CPh), 1.35 (br s, 2 H, H2N).
13C NMR (100 MHz, CDCl3): d = 146.6, 139.2, 130.1, 129.7, 129.0,
127.0, 126.8, 113.6, 52.6, 50.8, 43.2, 20.8.
MS (EI): m/z (%) = 240 (11) [M]+.
8k
White solid; yield: 99%; [a]D20 –65.3 (c 0.58, CH2Cl2).
1H NMR (400 MHz, CDCl3): d = 7.60 (br s, 1 H, HNCO), 7.33–7.21
(m, 10 H, HCAr), 4.50–4.45 (dd, J = 14.9, 6.1 Hz, 1 H, H2CNH),
4.43–4.40 (dd, J = 14.9, 6.1 Hz, 1 H, H2CNH), 3.70–3.67 (dd,
J = 9.1, 4.0 Hz, 1 H, HCNH2), 3.33–3.28 (dd, J = 13.6, 4.0 Hz, 1 H,
H2CCH), 2.80–2.74 (dd, J = 13.6, 9.1 Hz, 1 H, H2CCH), 1.53 (s, 2
H, H2N).
Anal. Calcd for C16H20N2: C, 79.96; H, 8.39; N, 11.66. Found: C,
79.20; H, 8.33; N, 11.13.
13C NMR (100 MHz, CDCl3): d = 174.1, 138.5, 137.9, 129.5, 128.8,
128.7, 127.9, 127.5, 126.9, 56.6, 43.2, 41.1.
9g
MS (FAB, NBA): m/z (%) = 255 (100) [M + 1]+.
Colorless oil; yield: 76%; [a]D20 +27.1 (c 0.74, CH2Cl2); Kugelrohr
Anal. Calcd for C16H18N2O: C, 75.56; H, 7.13; N, 11.01. Found: C,
75.33; H, 7.18; N, 11.06.
distillation: 175 °C/0.06 mbar.
1H NMR (400 MHz, CDCl3): d = 6.79–6.77 (m, 2 H, HCAr), 6.62–
6.60 (m, 2 H, HCAr), 3.74 (s, 3 H, H3CO), 3.21–3.17 (dd, J = 11.4,
3.0 Hz, 1 H, H2CNH), 2.81–2.76 (dd, J = 11.4, 9.4 Hz, 1 H,
H2CNH), 2.76–2.70 (m, 1 H, HCNH2), 1.70–1.62 [m, 2 H,
HC(CH3)2/HN], 1.30 (br s, 2 H, H2N), 0.97 (d, J = 7.1 Hz, 3 H,
H3C), 0.95 (d, J = 7.1 Hz, 3 H, H3C).
13C NMR (100 MHz, CDCl3): d = 152.2, 143.1, 115.0, 114.4, 56.3,
56.0, 49.3, 32.7, 19.5, 18.0.
MS (EI): m/z (%) = 208 (24) [M]+.
8l
White solid; yield: 93%; [a]D20 –75.5 (c 1.09, CH2Cl2).
1H NMR (400 MHz, CDCl3): d = 7.49 (s, 1 H, HNCO), 7.41–7.21
(m, 10 H, HCAr), 4.55 (s, 1 H, HCCO), 4.45 (dd, J = 15.2, 6.1 Hz, 1
H, H2CPh), 4.41 (dd, J = 15.2, 5.8 Hz, 1 H, H2CPh), 1.81 (s, 2 H,
H2N).
13C NMR (100 MHz, CDCl3): d = 173.0, 141.1, 138.4, 128.9, 128.7,
128.1, 127.7, 127.5, 127.0, 60.0, 43.3.
Anal. Calcd for C12H20N2O: C, 69.19; H, 9.68; N, 13.45. Found: C,
69.34; H, 9.63; N, 13.65.
MS (FAB, NBA): m/z (%) = 241 (100) [M + 1]+.
Anal. Calcd for C15H16N2O: C, 74.97; H, 6.71; N, 11.66. Found: C,
74.78; H, 6.73; N, 11.51.
9h
Colorless oil; yield: 85%; [a]D20 +44.4 (c 0.58, CH2Cl2); Kugelrohr
9d
distillation: 205 °C/0.07 mbar.
Colorless oil; yield: 68%; [a]D20 +30.4 (c 0.49, CH2Cl2); Kugelrohr
1H NMR (400 MHz, CDCl3): d = 6.80–6.76 (m, 2 H, HCAr), 6.63–
6.59 (m, 2 H, HCAr), 3.73 (s, 3 H, H3CO), 3.35–3.26 (dd, J = 12.6,
11.9 Hz, 1 H, HHCNH), 2.66–2.57 (m, 2 H, HHCNH/HCNH2), 0.94
[s, 9 H, (H3C)3C].
13C NMR (100 MHz, CDCl3): d = 151.8, 142.9, 114.6, 114.1, 59.4,
55.5, 46.4, 33.4, 26.0.
distillation: 165 °C/0.05 mbar.
1H NMR (400 MHz, CDCl3): d = 7.00–6.98 (m, 2 H, HCAr), 6.57 (d,
J = 8.3, 2 H, HCAr), 4.03 (br s, 1 H, HN), 3.24–3.21 (dd, J = 11.6,
3.3 Hz, 1 H, H2CNH), 2.85–2.79 (dd, J = 11.6, 9.1 Hz, 1 H,
H2CNH), 2.76–2.72 (m, 1 H, HCNH2), 2.24 (s, 3 H, H3CC6H4),
1.72–1.44 [m, 1 H, HC(CH3)2], 0.96 (br s, 2 H, H2N), 0.96 (d,
J = 7.1 Hz, 3 H, H3C), 0.94 (d, J = 7.1 Hz, 3 H, H3C).
MS (EI): m/z (%) = 222 (18) [M]+.
13C NMR (100 MHz, CDCl3): d = 146.6, 129.8, 126.6, 113.3, 56.2,
48.6, 32.6, 20.5, 19.5, 18.0.
Anal. Calcd for C13H22N2O: C, 70.23; H, 9.97; N, 12.60. Found: C,
70.30; H, 10.04; N, 12.62.
MS (EI): m/z (%) = 192 (15) [M]+.
Synthesis 2007, No. 4, 572–582 © Thieme Stuttgart · New York

PAPER
Synthesis of Chiral C2-Symmetric Methylene- and Boron-Bridged Bis(imidazolines)
581
9i
H3CPh), 1.87–1.79 [m, 1 H, HC(CH3)2], 1.02 (d, J = 6.8 Hz, 3 H,
H3C), 0.94 (d, J = 6.8 Hz, 3 H, H3C).
13C NMR (100 MHz, CDCl3): d = 148.5, 137.7, 130.4, 129.8, 113.8,
72.1, 48.7, 32.9, 20.3, 18.6, 18.0.
Colorless oil; yield: 65%; [a]D20 +30.4 (c 0.55, CH2Cl2); Kugelrohr
distillation: 145 °C/0.06 mbar.
1H NMR (400 MHz, CDCl3): d = 7.33–7.23 (m, 5 H, HCAr), 3.84 (d,
J = 13.1 Hz, 1 H, H2CPh), 3.77 (d, J = 13.1 Hz, 1 H, H2CPh), 2.75–
2.71 (dd, J = 11.6, 3.5 Hz, 1 H, H2CNH), 2.64–2.60 (m, 1 H,
HCNH2), 2.43–2.37 (dd, J = 11.6, 9.4 Hz, 1 H, H2CNH), 1.61–1.55
[m, br s, 4 H, HC(CH3)2/HN/H2N], 0.91 (d, J = 6.8 Hz, 3 H, H3C),
0.89 (d, J = 6.8 Hz, 3 H, H3C).
13C NMR (100 MHz, CDCl3): d = 140.9, 128.8, 128.5, 127.3, 56.9,
54.5, 53.9, 32.8, 19.8, 18.3.
MS (FAB, NBA): m/z (%) = 193 (100) [M + 1]+.
MS (EI): m/z (%) = 202 (10) [M]+.
Anal. Calcd for C13H18N2: C, 77.18; H, 8.97; N, 13.85. Found: C,
77.24; H, 9.04; N, 13.88.
6e
White solid; yield: 87%; flash chromatography: hexanes–EtOAc–
Et3N, 6:3:1; Rf = 0.47 (hexanes–EtOAc–Et3N, 6:3:1).
1H NMR (400 MHz, CDCl3): d = 7.54 [d, J = 2.0 Hz, 1 H, HC(2)],
7.12–7.10 (m, 2 H, HCAr), 6.83 (d, J = 8.6 Hz, 2 H, HCAr), 4.01–
3.95 [m, 1 H, HC(4)], 3.65–3.60 [dd, J = 10.9, 9.4 Hz, 1 H, H2C(5)],
3.46–3.41 [dd, J = 9.4, 9.1 Hz, 1 H, H2C(5)], 2.29 (s, 3 H, H3CPh),
0.95 [s, 9 H, (H3C)3C].
Anal. Calcd for C12H20N2: C, 74.95; H, 10.48; N, 14.57. Found: C,
75.10; H, 10.54; N, 14.63.
9j
Colorless oil; yield: 65%; Kugelrohr distillation: 135 °C, 0.08 mbar.
13C NMR (100 MHz, CDCl3): d = 148.8, 138.0, 130.7, 130.2, 114.1,
1H NMR (400 MHz, CDCl3): d = 7.34–7.21 (m, 5 H, HCAr), 3.84 (d,
J = 13.1 Hz, 1 H, H2CPh), 3.75 (d, J = 13.1 Hz, 1 H, H2CPh), 2.84–
2.81 (dd, J = 11.4, 2.5 Hz, 1 H, H2CNH), 2.54–2.50 (dd, J = 10.6,
2.5 Hz, 1 H, H2CNH), 2.30–2.25 (dd, J = 11.4, 10.6 Hz, 1 H,
HCNH2), 1.48 (br s, 3 H, HN/H2N), 0.88 [s, 9 H, (H3C)3C].
76.0, 47.5, 34.0, 26.0, 20.7.
MS (EI): m/z (%) = 216 (8) [M]+.
Anal. Calcd for C14H20N2: C, 77.73; H, 9.32; N, 12.95. Found: C,
77.82; H, 9.38; N, 13.02.
13C NMR (100 MHz, CDCl3): d = 141.0, 128.8, 128.5, 127.3, 60.5,
6g
54.5, 51.7, 34.0, 26.7.
White solid; yield: 76%; [a]D20 –36.2 (c 0.55, CH2Cl2); flash chro-
matography: hexanes–EtOAc–Et3N, 5:4:1; Rf = 0.36 (hexanes–
EtOAc–Et3N, 5:4:1).
MS (FAB, NBA): m/z (%) = 207 (100) [M + 1]+.
Anal. Calcd for C13H22N2: C, 75.68; H, 10.75; N, 13.58. Found: C,
75.73; H, 10.82; N, 13.69.
1H NMR (400 MHz, CDCl3): d = 7.45 [d, J = 1.8 Hz, 1 H, HC(2)],
6.86 (s, 4 H, HCAr), 4.04–3.98 [m, 1 H, HC(4)], 3.77 (s, 3 H, H3CO),
3.70–3.65 [dd, J = 10.6, 9.1 Hz, 1 H, H2C(5)], 3.37–3.32 [dd,
J = 9.1, 8.8 Hz, 1 H, H2C(5)], 1.86–1.78 [m, 1 H, HC(CH3)2], 1.02
(d, J = 6.8 Hz, 3 H, H3C), 0.93 (d, J = 6.8 Hz, 3 H, H3C).
13C NMR (100 MHz, CDCl3): d = 154.3, 149.0, 134.0, 115.3, 114.7,
72.2, 55.4, 49.2, 32.9, 18.6, 18.1.
9k
Colorless oil; yield: 68%; Kugelrohr distillation: 155 °C/0.04 mbar.
1H NMR (400 MHz, CDCl3): d = 7.33–7.18 (m, 10 H, HCAr), 3.83
(d, J = 13.1 Hz, 1 H, H2CNH), 3.76 (d, J = 13.1 Hz, 1 H, H2CNH),
3.15–3.09 (m, 1 H, HCNH2), 2.81–2.73 (m, 2 H, H2CCHNH2),
2.54–2.48 (m, 2 H, H2CCH), 1.56 (s, 3 H, H2N/HN).
13C NMR (100 MHz, CDCl3): d = 140.5, 139.3, 129.4, 128.6, 128.5,
128.3, 127.1, 126.4, 55.6, 54.2, 52.7, 42.9.
MS (FAB, NBA): m/z (%) = 219 (100) [M + 1]+.
Anal. Calcd for C13H18N2O: C, 71.53; H, 8.31; N, 12.83. Found: C,
71.61; H, 8.38; N, 12.91.
MS (FAB, NBA): m/z (%) = 241 (93) [M + 1]+.
6h
Anal. Calcd for C16H20N2: C, 79.96; H, 8.39; N, 11.66. Found: C,
80.04; H, 8.47; N, 11.69.
White solid; yield: 97%; [a]D20 –122.6 (c 0.68, CH2Cl2); flash chro-
matography: hexanes–EtOAc–Et3N, 7:2:1; Rf = 0.23 (hexanes–
EtOAc–Et3N, 7:2:1).
1H NMR (400 MHz, CDCl3): d = 7.45 [d, J = 1.8 Hz, 1 H, HC(2)],
6.87 (s, 4 H, HCAr), 4.00–3.94 [m, 1 H, HC(4)], 3.78 (s, 3 H, H3CO),
3.64–3.59 [dd, J = 10.9, 9.3 Hz, 1 H, H2C(5)], 3.44–3.40 [dd,
J = 9.3, 9.1 Hz, 1 H, H2C(5)], 0.94 [s, 9 H, (H3C)3C].
9l
Colorless oil; yield: 62%; [a]D20 –6.7 (c 1.28, CHCl3).
1H NMR (400 MHz, CDCl3): d = 7.34–7.22 (m, 10 H, HCAr), 4.06
(dd, J = 8.3, 4.8 Hz, 1 H, HCNH2), 3.83 (d, J = 13.4 Hz, 1 H,
H2CPh), 3.80 (d, J = 13.4 Hz, 1 H, H2CPh), 2.86 (dd, J = 11.6, 4.8
Hz, 1 H, H2CNH), 2.76 (dd, J = 11.6, 8.3 Hz, 1 H, H2CNH), 1.78 (s,
3 H, H2N/HN).
13C{1H} NMR (100 MHz, CDCl3): d = 154.6, 149.2, 134.3, 115.6,
115.1, 76.1, 55.8, 47.9, 33.9, 26.0.
13C NMR (100 MHz, CDCl3): d = 144.7, 140.4, 128.7, 128.5, 128.2,
MS (EI): m/z (%) = 232 (11) [M]+.
127.3, 127.1, 126.6, 57.2, 55.7, 54.0.
Anal. Calcd for C14H20N2O: C, 72.38, H, 8.68; N, 12.06. Found: C,
72.14; H, 8.52; N, 12.03.
MS (FAB, NBA): m/z (%) = 227 (100) [M + 1]+.
Anal. Calcd for C15H18N2: C, 79.61; H, 8.02; N, 12.38. Found: C,
79.58; H, 8.42; N, 12.52.
6i
White solid; yield: 96%.
6d
1H NMR (400 MHz, CDCl3): d = 7.36–7.22 (m, 5 H, HCAr), 6.99 [d,
J = 1.8 Hz, 1 H, HC(2)], 4.32 (d, J = 14.9 Hz, 1 H, H2CPh), 4.21 (d,
J = 14.9 Hz, 1 H, H2CPh), 3.88–3.81 [m, 1 H, HC(4)], 3.21–3.16
[dd, J = 10.4, 9.1 Hz, 1 H, H2C(5)], 2.78–2.73 [dd, J = 9.6, 9.1 Hz,
1 H, H2C(5)], 1.75–1.67 [m, 1 H, HC(CH3)2], 0.96 (d, J = 6.8 Hz, 3
H, H3C), 0.84 (d, J = 6.8 Hz, 3 H, H3C).
White solid; yield: 89%; flash chromatography: hexanes–EtOAc–
Et3N, 5:4:1; Rf = 0.48 (hexanes–EtOAc–Et3N, 5:4:1).
1H NMR (400 MHz, CDCl3): d = 7.53 [d, J = 2.0 Hz, 1 H, HC(2)],
7.10 (d, J = 8.6 Hz, 2 H, HCAr), 6.82 (d, J = 8.6 Hz, 2 H, HCAr),
4.05–3.99 [m, 1 H, HC(4)], 3.71–3.66 [dd, J = 10.6, 9.1 Hz, 1 H,
H2C(5)], 3.38–3.33 [dd, J = 9.1, 8.8 Hz, 1 H, H2C(5)], 2.29 (s, 3 H,
13C NMR (100 MHz, CDCl3): d = 156.2, 137.1, 128.8, 127.8, 127.7,
73.1, 51.8, 50.8, 33.3, 19.2, 18.5.
Synthesis 2007, No. 4, 572–582 © Thieme Stuttgart · New York

582
B. Ramalingam et al.
PAPER
(3) Reviews: (a) Ghosh, A. K.; Mathivanan, P.; Cappiello, J.
MS (EI): m/z (%) = 202 (4) [M]+.
Tetrahedron: Asymmetry 1998, 9, 1. (b) McManus, H. A.;
Guiry, P. J. Chem. Rev. 2004, 104, 4151. (c) Desimoni, G.;
Faita, G.; Jørgensen, K. A. Chem. Rev. 2006, 106, 3561.
(4) Mazet, C.; Köhler, V.; Pfaltz, A. Angew. Chem. Int. Ed.
2005, 44, 4888.
(5) Mazet, C.; Roseblade, S.; Köhler, V.; Pfaltz, A. Org. Lett.
2006, 8, 1879.
(6) (a) Köhler, V. Dissertation; University of Basel:
Switzerland, 2005. (b) Mazet, C.; Roseblade, S.; Köhler, V.;
Toussaint, A.; Pfaltz, A. Chimia 2006, 60, 195.
(7) For analogous biimidazolines, see: (a) Müller, D. W.
Dissertation; University of Basel: Switzerland, 1993.
(b) Boland, N. A.; Casey, M.; Hynes, S. J.; Matthews, J. W.;
Müller-Bunz, H.; Wilkes, P. Org. Biomol. Chem. 2004, 2,
1995. (c) Dupont, J.; Ebeling, G.; Delgado, M. R.; Consorti,
C. S.; Burrow, R.; Farrar, D. H.; Lough, A. J. Inorg. Chem.
Commun. 2001, 4, 471. (d) Ryan, R.; Casey, M.; Wilkes, P.
Abstracts of the 13th IUPAC International Symposium on
Organometallic Chemistry Directed Towards Organic
Synthesis; Geneva: Switzerland, 2005, P-507.
Anal. Calcd for C13H18N2: C, 77.18; H, 8.97; N, 13.85. Found: C,
77.26; H, 9.08; N, 13.85.
6j
White solid; yield: 98%.
1H NMR (400 MHz, CDCl3): d = 7.37–7.23 (m, 5 H, HCAr), 7.03 [d,
J = 1.5 Hz, 1 H, HC(2)], 4.33 (d, J = 13.2 Hz, 1 H, H2CPh), 4.24 (d,
J = 13.1 Hz, 1 H, H2CPh), 3.86–3.81 [m, 1 H, HC(4)], 3.16–3.11
[dd, J = 10.9, 9.6 Hz, 1 H, H2C(5)], 2.87–2.80 [dd, J = 10.9, 8.3 Hz,
1 H, H2C(5)], 0.86 [s, 9 H, (H3C)3C].
13C NMR (100 MHz, CDCl3): d = 156.2, 137.0, 128.8, 127.8, 127.7,
76.5, 51.8, 49.1, 33.7, 26.1.
MS (FAB, NBA): m/z (%) = 217 (100) [M + 1]+.
Anal. Calcd for C14H20N2: C, 77.73; H, 9.32; N, 12.95. Found: C,
77.86; H, 9.47; N, 12.92.
6k
White solid; yield: 98%; [a]D20 –61.7 (c 0.65, CH2Cl2); flash chro-
matography: EtOAc–MeOH–Et3N, 8:1:1; Rf = 0.55 (EtOAc–
MeOH–Et3N, 8:1:1).
(8) (a) Boland, N. A.; Casey, M.; Hynes, S. J.; Matthews, J. W.;
Smyth, M. P. J. Org. Chem. 2002, 67, 3919. (b) Casey, M.;
Smyth, M. P. Synlett 2003, 102.
1H NMR (400 MHz, CDCl3): d = 7.33–7.13 (m, 10 H, HCAr), 7.06
[d, J = 1.5 Hz, 1 H, HC(2)], 4.42–4.33 [m, 1 H, HC(4)], 4.32 (d,
J = 14.9 Hz, 1 H, H2CN), 4.23 (d, J = 14.9 Hz, 1 H, H2CN), 3.18–
3.13 [dd, J = 9.9, 9.1 Hz, 1 H, H2C(5)], 3.12–3.07 [dd, J = 13.6, 5.3
Hz, 1 H, H2CC(4)], 2.89–2.84 [dd, J = 9.1, 8.1 Hz, 1 H, H2C(5)],
2.71–2.65 [dd, J = 13.6, 8.3 Hz, 1 H, H2CC(4)].
(9) Su, J. T.; Vachal, P.; Jacobsen, E. N. Adv. Synth. Catal.
2001, 343, 197.
(10) Jones, R. C. F.; Nichols, J. R. Tetrahedron Lett. 1990, 31,
1771.
(11) Kharasch, M. S.; Sosnovsky, G. J. Am. Chem. Soc. 1958, 80,
756.
(12) (a) Gokhale, A. S.; Minidis, A. B. E.; Pfaltz, A. Tetrahedron
Lett. 1995, 36, 1831. (b) Sekar, G.; DattaGupta, A.; Singh,
V. K. J. Org. Chem. 1998, 63, 2961. (c) Ginotra, S. K.;
Singh, V. K. Tetrahedron 2006, 62, 3573.
13C NMR (100 MHz, CDCl3): d = 156.6, 138.6, 136.7, 129.4, 128.9,
128.5, 127.8, 127.7, 126.4, 67.6, 52.5, 51.7, 42.3.
Anal. Calcd for C17H18N2: C, 81.56; H, 7.25; N, 11.19. Found: C,
81.63; H, 7.28; N, 11.24.
(13) (a) Andrus, M. B.; Argade, A. B.; Chen, C.; Pamment, M. G.
Tetrahedron Lett. 1995, 36, 2945. (b) Andrus, M. B.; Zhou,
Z. J. Am. Chem. Soc. 2002, 124, 8806.
(14) Abel, E. W.; Dandegaonker, S. H.; Gerrard, W.; Lappert, M.
F. J. Chem. Soc. 1956, 4697.
Acknowledgement
Financial support from the Swiss National Science Foundation is
gratefully acknowledged.
(15) Koester, R.; Grassberger, M. A. Justus Liebigs Ann. Chem.
1969, 719, 169.
(16) COLLECT Software, Nonius BV, 1997–2001
(17) SIR-92: A program for automatic solution of crystal
structures by direct methods: Altomare, A.; Cascarano, G.;
Giacovazzo, G.; Guagliardi, A.; Burla, M. C.; Polidori, G.;
Camalli, M. J. Appl. Crystallogr. 1994, 27, 435.
(18) Betteridge, P. W.; Carruthers, J. R.; Cooper, R. I.; Prout, K.;
Watkin, D. J. J. Appl. Crystallogr. 2003, 36, 1487.
References
(1) (a) Fritschi, H.; Leutenegger, U.; Pfaltz, A. Helv. Chim. Acta
1988, 71, 1553. (b) Pfaltz, A. Acc. Chem. Res. 1993, 26,
339.
(2) (a) Lowenthal, R. E.; Abiko, A.; Masamune, S. Tetrahedron
Lett. 1990, 31, 6005. (b) Evans, D. A.; Woerpel, K. A.;
Hinman, M. M.; Faul, M. M. J. Am. Chem. Soc. 1991, 113,
726. (c) Corey, E. J.; Imai, N.; Zhang, H.-Y. J. Am. Chem.
Soc. 1991, 113, 728. (d) Hall, J.; Lehn, J.-M.; DeCian, A.;
Fischer, J. Helv. Chim. Acta 1991, 74, 1. (e) Helmchen, G.;
Krotz, A.; Ganz, K. T.; Hansen, D. Synlett 1991, 257.
(f) Onishi, M.; Isagawa, K. Inorg. Chim. Acta 1991, 179,
155. (g) Yang, R.-Y.; Chen, Y.-H.; Dai, L.-X. Acta Chim.
Sin. 1991, 49, 1038; Chem. Abstr., 1992, 116, 41342v.
(h) Müller, D.; Umbricht, G.; Weber, B.; Pfaltz, A. Helv.
Chim. Acta 1991, 74, 232.
Synthesis 2007, No. 4, 572–582 © Thieme Stuttgart · New York