Synthesis of new derivatives from a Troeger base via exchange of the methano bridge with carbonyl compounds

Article abstract of DOI:10.1016/j.tetasy.2012.01.009

A simple one-pot method has been developed for the preparation of new Troeger base derivatives by an exchange reaction with the methano bridge of rac-Troeger base derivatives with carbonyl compounds in the presence of TiCl₄ or POCl₃.

Full text of DOI:10.1016/j.tetasy.2012.01.009

Tetrahedron: Asymmetry 23 (2012) 108–116
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Synthesis of new derivatives from a Tröger base via exchange
of the methano bridge with carbonyl compounds
⇑
Mariappan Periasamy , Sundaram Suresh, Sakilam Satishkumar
School of Chemistry, University of Hyderabad, Central University P.O., Hyderabad 500 046, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A simple one-pot method has been developed for the preparation of new Tröger base derivatives by an
exchange reaction with the methano bridge of rac-Tröger base derivatives with carbonyl compounds
in the presence of TiCl4 or POCl3. The use of chiral (S,S)-N,N-bis(a-methylbenzyl)formamide as a carbonyl
compound gave the corresponding methano Tröger base derivatives with the diastereomeric ratios of up
Received 21 November 2011
Accepted 17 January 2012
Available online 18 February 2012
to 77:23.
Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction
We have observed that the reaction of Tröger base with benzal-
dehyde in the presence of TiCl4 under refluxing 1,2-dichloroethane
Tröger base 1a, a molecule with two bridgehead stereogenic
nitrogen atoms is generally prepared by the condensation reaction
of p-toludine and formaldehyde promoted by acids. Many structur-
ally diverse Tröger base derivatives have been made with synthetic
alterations on the aromatic core1 as well as the saturated aliphatic
core.2 Tröger base derivatives are useful as ligand in asymmetric
catalysis,3 as a chiral solvating agent,4 in molecular replication
studies,5 in biomimitic systems6 and as DNA-interacting probes.7
Recently, we have reported methods for the Lewis acid promoted
synthesis, resolution, and applications of Tröger base and its deriv-
atives.8 Herein we report a Lewis acid promoted synthesis of new
Tröger base derivatives by substitution of the methylene bridge
with carbonyl compounds in a single pot operation.
(DCE) affords the 5,11-substituted derivative 2a in a 59% yield
(Schemes 2 and 3).
N
N
PhCHO/TiCl4
1,2-dichloroethane
reflux, 14 h
N
N
Ph
2a
1a
Scheme 2.
Several other aldehydes and ketones can be exchanged with the
methano group in the Tröger base in this manner to obtain the
products in moderate to good yields. The results are summarized
in Table 1. The spiro compound 2i was obtained from the reaction
with cyclopentanone. The structure of this compound was further
confirmed by X-ray crystal structure analysis. The crystal structure
of the compound 2i is shown in Figure 1.10
We have also examined the reaction of the Tröger base with
benzaldehyde in the presence of several Lewis acids. Whereas
BF3ꢀOEt2 and ZnBr2 were not effective in the reaction with
benzaldehyde in the presence of POCl3 in toluene at 80 °C, the
5,11-substituted Tröger base 2a was obtained in moderate yields
(Scheme 4). We observed that the reaction using 1,2-dichloroeth-
ane under refluxing conditions (i.e., 83 °C) for 3 h instead of using
toluene solvent at 80 °C gave relatively lower yields (42%) in a run
using benzaldehyde. The reaction also takes place with other
aldehydes; the results are summarized in Table 2.
2. Result and discussion
Tröger base derivatives with substitution at the 5,11-methano
position are generally synthesized by the reaction of cyclic second-
ary amines with carbonyl compounds, which in turn needs to be
obtained from the corresponding Tröger base (Scheme 1).9
H
N
N
RCHO
benzene or toluene
reflux
NH
N
R
Scheme 1.
We have observed that the DMF can be used as a carbonyl
partner in the reaction with POCl3 to obtain the corresponding
5,11-substituted product 3a in a 63% yield (Table 3, entry 1). The
optimum results were obtained using CH2Cl2 as the solvent
⇑
Corresponding author. Tel.: +91 40 23134814; fax: +91 40 23012460.
E-mail address: mpsc@uohyd.ernet.in (M. Periasamy).
0957-4166/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2012.01.009

M. Periasamy et al. / Tetrahedron: Asymmetry 23 (2012) 108–116
109
Cl
Ti
Cl
Cl
Cl
TiCl4
Cl
O
N
N
N
O
H
Ph
N
N
N
Ph
OTiCl3
1a
Ph
TiCl4
+
HCHO
N
N
2a
Ph
Scheme 3. Tentative mechanism for the formation of 5,11-substituted derivatives.
Table 1
Reaction of Tröger base 1a with aldehydes and ketones in the presence of TiCl4
a
Entry
Aldehyde/ketone
Product
Yieldb,c (%)
O
1
2a
59
H
O
H
H3C
2
3
4
5
6
7
2b
2c
2d
2e
2f
61
62
53
35
52
61
O
H3CO
Cl
H
O
H
O
O2N
O
H
O
Figure 1. ORTEP representation of the crystal structure of compound 2i. Thermal
ellipsoids are drawn at 20% probability and all the hydrogen atoms are removed for
clarity.
H
H
O
O
2g
H
O
N
N
ArCHO
8
9
2h
2i
50
41
POCl3, toluene
O
N
N
º
Ar
80 C, 3 h
a
1a
Ar = Ph
2a
All reactions were carried out by using racemic Tröger base 1a (5 mmol), car-
bonyl compounds (5.1 mmol) and TiCl4 (10 mmol) in 1,2-dichloroethane (15 mL) at
25 °C and refluxed for 14 h.
b
The yields are of isolated products.
Scheme 4.
c
The products were characterized by spectroscopic data (IR, 1H NMR, 13C NMR).
(Table 3). In addition to the 5,11-substituted derivative 3a, the ring
opened product 4 was also obtained in small amounts (Table 3, en-
tries 2–9 and Scheme 5).
tentative mechanism was considered for this transformation
involving Vilsmeier type iminium ion intermediates (Scheme 6).
We envisaged the possibility of the asymmetric synthesis of
Tröger base derivatives using a chiral formamide instead of di-
methyl formamide. Thus, we examined the reaction of rac-1a and
We have also examined the POCl3 promoted reaction of other
Tröger base derivatives with DMF. The results are summarized in
Table 4. The reaction of methoxy Tröger base 1b and DMF with
POCl3 gave the corresponding 5,11-substituted derivative 3b in a
84% yield. In order to further examine the scope of this reaction,
we prepared other Tröger base derivatives without any substitu-
tion at the ortho or para positions with respect to the nitrogens.
The steric effect of the ortho substitution by a methyl group de-
creases the yield of the reaction significantly (Table 4, entry 5). A
(S,S)-N,N-bis(a-methylbenzyl)formamide as formyl partner in the
presence of POCl3 at 25 °C. In this reaction, the corresponding
5,11-substituted Tröger base derivative was obtained in a 75% yield
(Scheme 7). The 1H NMR spectrum of the product showed that the
product was a diastereomeric mixture with a 75:25 ratio. The reac-
tion was carried out using various solvents. Optimum results were
obtained in dichloromethane solvent (Table 5, entry 1). Lowering

110
M. Periasamy et al. / Tetrahedron: Asymmetry 23 (2012) 108–116
Table 2
diastereomeric ratio of 75:25 (Table 6, entry 3). In this case, the
a
Reaction of Tröger base 1a with various aldehydes in the presence of POCl3
diastereomeric mixture could not be isolated in pure form by col-
umn chromatography. However, crystallization of the product
mixture 8 from acetone solvent gave the major diastereomer 8a
in pure form with a 51% chemical yield. The Tröger base derivative
1d gave the corresponding 5,11-substituted product 9 in a 52%
yield with a diastereomeric ratio of 58:42 (Table 6, entry 4). In this
case, the major diastereomer 9a was also isolated in pure form
with a 50% chemical yield by crystallization of product mixture 9
from acetone solvent. The X-ray structural analysis of a single crys-
tal of 9a revealed that the product was a 5,11-substituted deriva-
tive with an (R,R)-configuration at the newly formed stereogenic
nitrogen centers. The ORTEP diagram for the major product is
shown in Figure 2.11 The reaction of Tröger base derivative 1e with
Entry
1
Aromatic aldehyde Ar-CHO
Product
Yieldb,c (%)
60
2a
Ar =
CH3
Ar =
2
3
4
2b
2c
2d
65
68
55
OCH3
Ar =
Cl
Ar =
Ar =
O
5
2g
60
(S,S)-N,N-bis(a-methylbenzyl)formamide did not give the desired
a
All reactions were carried out by using racemic Tröger base 1a (5 mmol), then
adding the aromatic aldehyde (5.1 mmol) and POCl3 (8.75 mmol) in toluene (15 mL)
at 0 °C, bringing the mixtures to 25 °C and then heating at 80 °C for 3 h.
5,11-substituted product (Table 6, entry 5); the starting materials
were recovered under the reaction conditions. This is presumably
because the ortho and meta methyl substituents greatly hinder this
reaction.
b
The yields are of isolated products.
The products were characterized by spectroscopic data (IR, 1H NMR, 13C NMR).
c
The asymmetric induction in the formation of the major prod-
uct in the diastereoselective synthesis of the Tröger base deriva-
tives can be rationalized as outlined in Scheme 8. The reaction of
Table 3
racemic Tröger base 1a with (S,S)-N,N-bis(a-methylbenzyl)form-
a
Reaction of Tröger base 1a with DMF in the presence of POCl3
amide in the presence of POCl3 leads to iminium ion intermediates,
which should be in equilibrium (Scheme 8). Invariance of the dia-
stereomeric ratio (75:25) for the products (Table 6) obtained from
the unhindered substrates 1a, 1b, and 1c indicates the thermody-
namic control of the reaction.15
Entry
POCl3 (equiv)
Solvent
Yieldb,c (%) 3a
Yieldb,c (%) 4
1
2
3
3
4
5
6
7
8
9
10
1.75
1.75
2.0
1.5
1.25
1.0
1.75
1.75
1.75
1.75
1.75
DMFd
DCM
DCM
DCM
DCM
DCM
CHCl3
DCE
Toluene
Acetonitrile
MeOH
63
93
89
91
74
70
56
42
52
35
0f
0
Tracee
Tracee
5
12
19
7
9
9
3. Conclusion
In conclusion, we have developed TiCl4 or POCl3 promoted
one-pot methods to readily access 5,11-substituted Tröger base
derivatives. During the preparation of this manuscript, reports have
appeared describing the POCl3 promoted exchange reaction of the
methano bridge reported using achiral amides.12 However, the
methods described here are generally applicable for aldehydes,
ketones, and amides. In addition, we have also devised a method
for the diastereoselective synthesis of Tröger base derivatives using
11
0f
a
Unless otherwise mentioned, all reactions were carried out using racemic
Tröger base 1a (2 mmol), DMF (2.1 mmol), solvent (15 mL) at 25 °C for 1 h.
b
The yields are of isolated products.
The products were characterized by spectroscopic data (IR, 1H NMR, 13C NMR).
c
d
Reaction was carried out by using racemic Tröger base 1a (5 mmol) and POCl3
(8.75 mmol) in DMF (5 mL) at 0 °C and then heated at 80 °C for 3 h.
Identified by 1H NMR.
e
(S,S)-N,N-bis(a-methylbenzyl)formamide as a carbonyl group part-
f
ner. Furthermore, asymmetric induction in the synthesis of chiral
Tröger base derivatives using a chiral reagent to exchange the
5,11 methano bridge has been reported for the first time. Since
the chiral Tröger base derivatives 6–9 containing a reduced chiral
guanidine moiety are readily accessible, the method described
herein has considerable potential for further synthetic applications.
No reaction.
the temperature to 0 °C did not improve the selectivity of the Trö-
ger base formed (Table 5, entry 6). Further lowering of the temper-
ature to ꢁ10 °C gave only a trace amount of the desired product
(Table 5, entry 7). However, the diastereomers obtained could
not be separated by chromatography or crystallization.
4. Experimental
We also examined the POCl3 promoted reaction of other Tröger
base derivatives with (S,S)-N,N-bis(a-methylbenzyl)formamide
under the experimental conditions. The results are summarized
4.1. Materials and methods
in Table 6. The reaction of Tröger base derivative 1c and (S,S)-
Tröger base derivatives 1a, 1b, 1d, 1e were prepared by follow-
ing the method reported from this laboratory. Tröger base 1c13 and
N,N-bis(a-methylbenzyl)formamide 5 with POCl3 gave the corre-
sponding 5,11-substituted derivative 8 in a 68% yield with a
H
O
N
N
N
R
R
R
DMF/POCl3
DCM
R
R
R
N
N
NH
º
25 C, 1 h
N
1a
4
3a
R = CH3
Scheme 5.

M. Periasamy et al. / Tetrahedron: Asymmetry 23 (2012) 108–116
111
Table 4
Vilsmeier–Haack type reaction of Tröger base derivatives with DMFa
Entry
Substrate
Product
Yieldb,c (%)
N
N
N
N
1
93
84
88
1a
N
3a
N
N
O
O
O
O
N
N
2
3
1b
N
3b
N
N
N
N
N
N
3c
1c
N
4
86
N
N
N
1d
3d
N
N
5
65
N
N
1e
N
3e
a
b
c
All reactions were carried out using racemic Tröger base derivatives (2 mmol), DMF (2.1 mmol) and POCl3 (3.5 mmol) in dry CH2Cl2 (15 mL) at 25 °C for 1 h.
The yields are of isolated products.
The products were characterized by spectroscopic data (IR, 1H NMR, 13C NMR).
PO2Cl2
N
N
POCl3
H
Cl
H
Cl
P
O
Cl
O
O
Cl
Cl
N
O
N
N
N
H
N
N
N
N
N
N
3a
Cl
Cl
O
O
Ring inversion
P
P
O
Cl
Cl
Cl
N
Cl
N
( )-1a
N
N
N
N
N
N
N
N
H
Cl
Cl
3a
P
O
O
Scheme 6. Tentative mechanism for the POCl3 promoted reaction.

112
M. Periasamy et al. / Tetrahedron: Asymmetry 23 (2012) 108–116
Ph
Ph
N
N
N
POCl3
N
+
+
DCM, 12 h
N
N
N
H
O
N
N
Ph
Ph
Ph
Ph
6b
6a
1a
5
major
minor
Scheme 7.
4.1.1.1. 2,8-Dimethyl-13-phenyl-6H,12H-5,11-methanodibenzo
[b,f][1,5]diazocine 2a. Yield: 0.96 g (59%); mp 180–182 °C
(lit.9a mp 182–183 °C); IR (KBr) 3012, 2908, 1493 cmꢁ1 1H NMR
Table 5
Reaction of Tröger base with (S,S)-N,N-bis(
presence of POCl3
a
-methylbenzyl)formamide
5
in the
a
;
(400 MHz, CDCl3): d 7.61–7.59 (m, 2H), 7.32–7.22 (m, 3H), 7.19
(d, J = 8.0 Hz, 1H), 7.13 (d, J = 8.0 Hz, 1H), 7.0–6.97 (m, 2H), 6.80
(s, 1H), 6.48 (s, 1H), 5.34 (s, 1H), 4.83 (d, J = 16.4 Hz, 1H), 4.35 (d,
J = 16.4 Hz, 1H), 4.13 (d, J = 16.8 Hz, 1H), 3.91 (d, J = 16.8 Hz, 1H),
2.26 (s, 3H), 2.15 (s, 3H); 13C NMR (100 MHz, CDCl3): d 147.6,
143.7, 138.5, 133.3, 132.9, 128.3, 128.2, 128.0, 127.7, 127.5,
127.3, 127.2, 126.9, 125.4, 125.0, 74.6, 60.8, 52.6, 20.9, 20.8; MS
(EI): m/z 327.0 (M+1); Anal. Calcd for C23H22N2: C, 84.63; H, 6.79;
N, 8.58. Found: C, 84.75; H, 6.72; N, 8.51.
Entry
Solvent
Temperature (°C)
Yieldb,c (%)
drd (%)
1
2
3
4
5
6
7
DCM
25
25
25
25
25
0
75
40
38
47
23
32
75:25
75:25
75:25
75:25
75:25
75:25
—
CHCl3
Toluene
DCE
CH3CN
DCM
DCM
ꢁ10
Trace (<5%)e
a
All reactions were carried out using racemic Tröger base 1a (2 mmol), (S,S)-N,N-
a-methylbenzyl)formamide 5 (2.1 mmol) and POCl3 (3.5 mmol) in 15 mL DCM
bis(
for 12 h.
b
4.1.1.2. 2,8-Dimethyl-13-(4-methylphenyl)-6H,12H-5,11-metha-
The yields are of isolated products.
c
The products were characterized by spectroscopic data (IR, 1H NMR, 13C NMR).
The diastereomeric ratios were estimated from 1H NMR (400 MHz) data. The
nodibenzo[b,f][1,5]diazocine 2b.
Yield: 1.03 g (61%); mp
d
168–170 °C; IR (KBr) 3011, 2993, 1491 cmꢁ1
;
1H NMR (400 MHz,
diastereomeric ratios 77:23 were also estimated by HPLC using chiral cell phe-
nomenex cellulose-1 column.
CDCl3): d 7.47 (d, J = 8.0 Hz, 2H), 7.18 (d, J = 8.0 Hz, 1H), 7.13–
7.09 (m, 3H), 7.0–6.97 (m, 2H), 6.79 (s, 1H), 6.47 (s, 1H), 5.31 (s,
1H), 4.80 (d, J = 16.4 Hz, 1H), 4.32 (d, J = 16.4 Hz, 1H), 4.14 (d,
J = 16.8 Hz, 1H), 3.90 (d, J = 16.8 Hz, 1H), 2.31 (s, 3H), 2.25 (s, 3H),
2.15 (s, 3H); 13C NMR (100 MHz, CDCl3): d 147.7, 143.8, 136.9,
135.5, 133.3, 132.9, 128.9, 128.3, 128.0, 127.8, 127.5, 127.3,
127.0, 125.4, 125.1, 74.5, 60.8, 52.6, 21.2, 21.0, 20.9; MS (EI): m/z
341.1 (M+1); Anal. Calcd for C24H24N2: C, 84.67; H, 7.11; N, 8.23.
Found: C, 84.51; H, 7.16; N, 8.12.
e
dr not estimated.
(S,S)-N,N-bis(a
-methylbenzyl)foramide14 were prepared following
a reported procedure. POCl3 and DMF were purchased from
commercial sources and used as received. Dichloromethane was
distilled from calcium hydride under nitrogen. The melting points
reported herein are uncorrected and were determined using a
superfit capillary point apparatus. IR spectra were recorded on a
JASCO FT-IR spectrophotometer Model 5300. 1H NMR and 13C
NMR spectra were recorded on a Bruker Advance-400 MHz Spec-
trometer with chloroform-d as a solvent and TMS as reference.
Optical rotations were measured in an AUTOPOL-IV digital polar-
imeter (readability 0.001°). Liquid chromatography (LC) and mass
analysis (LC–MS) were performed on SHIMADZU-LCMS-2010A.
Elemental analyses were carried out using a Perkin-Elmer elemen-
tal analyzer model-240C and a Thermo Finnigan analyzer series
Flash EA1112. HPLC analyses were performed on an SCL-10ATVP
SHIMADZU instrument. The dr values were determined from 1H
NMR signals and chiral cell phenomenex cellulose-1 column with
eluents:hexane/2-propanol.
4.1.1.3. 2,8-Dimethyl-13-(4-methoxyphenyl)-6H,12H-5,11-meth
anodibenzo[b,f][1,5]diazocine 2c.
152–154 °C (lit.9a mp 155–156 °C); IR (KBr) 3015, 2908,
1491 cmꢁ1 1H NMR (400 MHz, CDCl3): d 7.51 (d, J = 8.4 Hz, 2H),
Yield: 1.1 g (62%); mp
;
7.19 (d, J = 8.0 Hz, 1H), 7.13 (d, J = 8.0 Hz, 1H), 7.0–6.98 (m, 2H),
6.83 (d, J = 8.0 Hz, 2H), 6.79 (s, 1H), 6.49 (s, 1H), 5.29 (s, 1H), 4.82
(d, J = 16.4 Hz, 1H), 4.32 (d, J = 16.4 Hz, 1H), 4.15 (d, J = 16.8 Hz,
1H), 3.90 (d, J = 16.8 Hz, 1H), 3.77 (s, 3H), 2.26 (s, 3H), 2.16 (s,
3H); 13C NMR (100 MHz, CDCl3): d 158.7, 147.6, 143.7, 133.3,
132.9, 130.6, 128.7, 128.2, 128.0, 127.8, 127.3, 126.9, 125.4,
125.1, 113.6, 74.3, 60.8, 55.1, 52.4, 20.9, 20.8; MS (EI): m/z
357.35 (M+1); Anal. Calcd for C24H24N2O: C, 80.87; H, 6.79; N,
7.86; O, 4.49. Found: C, 80.68; H, 6.72; N, 7.95.
4.1.1. General procedure for the preparation of the 5,11-
substituted derivatives 2a–2i of Tröger base using TiCl4
To a reaction flask cooled under N2, was added Tröger base
(1.25 g, 5 mmol) in 1,2-dichloroethane (15 mL) and TiCl4 (1.9 g,
1.1 mL, 10 mmol). Next, the carbonyl compound (5.1 mmol) was
added at 25 °C and the reaction mixture was refluxed for 14 h. It
was then cooled to 0 °C and quenched with saturated K2CO3 solu-
tion. The aqueous layer was extracted with CH2Cl2 (2 ꢂ 15 mL) and
the combined organic extracts were washed successively with
water, brine and dried over anhydrous Na2SO4. After removal of
the solvent, the residue was subjected to chromatography on silica
gel using 2–5% ethyl acetate in hexane to give the desired 5,11-
substituted derivative.
4.1.1.4. 2,8-Dimethyl-13-(4-chlorophenyl)-6H,12H-5,11-metha-
nodibenzo[b,f][1,5]diazocine 2d.
Yield: 0.954 g (53%); mp
156–158 °C; IR (KBr) 3015, 2995, 1491 cmꢁ1
;
1H NMR (400 MHz,
CDCl3): d 7.55 (d, J = 8.8 Hz, 2H), 7.26 (d, J = 8.0 Hz, 2H), 7.18 (d,
J = 8.0 Hz, 1H), 7.12 (d, J = 8.0 Hz, 1H), 7.0–6.98 (m, 2H), 6.79 (s,
1H), 6.48 (s, 1H), 5.28 (s, 1H), 4.80 (d, J = 16.4 Hz, 1H), 4.33 (d,
J = 16.4 Hz, 1H), 4.10 (d, J = 16.8 Hz, 1H), 3.90 (d, J = 16.8 Hz, 1H),
2.26 (s, 3H), 2.16 (s, 3H); l3C NMR (l00 MHz, CDCl3): d 147.4,
143.4, 137.0, 133.5, 133.2, 130.0, 129.1, 128.4, 128.1, 127.5,
127.2, 126.9, 125.4, 125.1, 74.1, 60.6, 52.5, 20.9, 20.8; MS (EI): m/
z 361 (M+1); Anal. Calcd for C23H21ClN2: C, 76.55; H, 5.87; N,
7.76; Cl, 9.82. Found: C, 76.45; H, 5.81; N, 7.68.

M. Periasamy et al. / Tetrahedron: Asymmetry 23 (2012) 108–116
113
Table 6
Diastereoselective synthesis of various 5,11-substituted methano bridged Tröger base derivativesa
Entry
Substrate
Products
Yieldb,c (%)
drd (%)
N
N
N
N
N
N
N
1
75
75:25
75:25
75:25
N
1a
Ph
Ph
Ph
Ph
6b
6a
N
N
N
O
O
O
O
O
O
N
N
N
N
2
66
N
1b
Ph
Ph
Ph
Ph
7a
7b
N
N
N
N
N
N
3
N
68
N
1c
Ph
Ph
Ph
Ph
8a
8b
N
N
N
N
N
N
4
52
58:42
N
N
1d
Ph
Ph
Ph
Ph
9a
9b
N
5
No reaction
—
—
—
N
1e
a
All reactions were carried out using racemic Tröger base derivatives (2 mmol), (S,S)-N,N-bis(
a-methylbenzyl)foramide 5 (2.1 mmol) and POCl3 (3.5 mmol) in 15 mL DCM
at 25 °C for 12 h.
b
The yields are of isolated products.
c
The products were characterized by spectroscopic data (IR, 1H NMR, 13C NMR).
d
The diastereomeric ratios were estimated from the 1H NMR (400 MHz) data. The diastereomeric ratios were also estimated for 6 (77:23), 7 (77:23), and 9 (60:40) by HPLC
using a chiral cell phenomenex cellulose-1 column.
4.1.1.5. 2,8-Dimethyl-13-(4-nitrophenyl)-6H,12H-5,11-methano
dibenzo[b,f][1,5]diazocine 2e. Yield: 0.65 g (35%); mp 159–
161 °C (lit.9a mp 160.5–161 °C); lR (KBr) 2920, 2852, 1493 cmꢁ1
(d, J = 8.0 Hz, 1H), 7.05–7.0 (m, 2H), 6.81 (s, 1H), 6.48 (s, 1H),
5.35 (s, 1H), 4.83 (d, J = 16.4 Hz, 1H), 4.36 (d, J = 16.4 Hz, 1H),
4.12 (d, J = 17.2 Hz, 1H), 3.94 (d, J = 17.2 Hz, 1H), 2.27 (s, 3H),
2.16 (s, 3H); 13C NMR (l00 MHz, CDCl3): d 192.1, 147.4, 145.4,
143.3, 135.5, 133.7, 133.4, 129.7, 128.5, 128.3, 128.2, 128.0,
127.4, 127.3, 126.9, 125.4, 125.0, 74.5, 60.6, 52.7, 20.9, 20.8; MS
(EI): m/z 355.2 (M+1); Anal. Calcd for C24H22N2O: C, 81.33; H,
6.26; N, 7.90; O, 4.51. Found: C, 81.23; H, 6.32; N, 7.83.
;
1H NMR (400 MHz, CDCl3): d 8.14 (d, J = 8.0 Hz, 2H), 7.81 (d,
J = 8.0 Hz, 2H), 7.19 (d, J = 8.0 Hz, 1H), 7.12 (d, J = 8.0 Hz, 1H),
7.0–6.99 (m, 2H), 6.80 (s, 1H), 6.48 (s, 1H), 5.34 (s, 1H), 4.82 (d,
J = 16.4 Hz, 1H), 4.35 (d, J = 16.4 Hz, 1H), 4.06 (d, J = 17.2 Hz, 1H),
3.94 (d, J = 17.2 Hz, 1H), 2.26 (s, 3H), 2.15 (s, 3H); 13C NMR
(100 MHz, CDCl3): d 147.2, 147.1, 145.8, 143.0, 133.8, 133.6,
128.7, 128.6, 128.2, 127.9, 127.2, 127.0, 126.9, 125.5, 125.1,
123.5, 74.2, 60.5, 52.6, 20.9, 20.8; MS (EI): m/z 372.2 (M+1); Anal.
Calcd for C23H21N3O2: C, 74.37; H, 5.70; N, 11.31; O, 8.61. Found:
C, 74.48; H, 5.63; N, 11.25.
4.1.1.7. 2,8-Dimethyl-13-(2-furyl)-6H,12H-5,11-methanodibenzo
[b,f][1,5]diazocine 2g.
Yield: 0.96 g (61%); mp 133–135 °C
(lit.9a mp 135–135.5 °C); IR (KBr) 3014, 2916, 1493 cmꢁ1
;
1H NMR
(400 MHz, CDCl3): d 7.42 (s, 1H), 7.18 (d, J = 8.4 Hz, 1H), 7.13 (d,
J = 8.0 Hz, 1H), 7.0–6.98 (m, 2H), 6.76 (s, 1H), 6.57 (s, 1H), 6.27–6.26
(m, 1H), 6.11–6.10 (m, 1H), 5.38 (s, 1H), 4.80 (d, J = 16.8 Hz, 1H),
4.25 (d, J = 16.4 Hz, 1H), 4.17 (d, J = 16.8 Hz, 1H), 3.99 (d, J = 16.8 Hz,
1H), 2.25 (s, 3H), 2.19 (s, 3H); 13C NMR (l00 MHz, CDCl3): d 151.6,
146.2, 143.5, 142.3, 133.8, 133.4, 128.3, 128.2, 127.5, 127.4, 127.2,
4.1.1.6. 2,8-Dimethyl-13-(4-formylphenyl)-6H,12H-5,11-metha-
nodibenzo[b,f][1,5]diazocine 2f.
82 °C; IR (KBr) 3012, 2918, 2727, 1493 cmꢁ1
CDCl3): d 9.96 (s, 1H), 7.82 (s, 4H), 7.22 (d, J = 8.2 Hz, 1H), 7.14
Yield: 0.92 g (52%); mp 80–
;
1H NMR (400 MHz,

114
M. Periasamy et al. / Tetrahedron: Asymmetry 23 (2012) 108–116
133.0, 128.4, 128.1, 126.6, 126.1, 70.2, 54.6, 33.3, 26.0, 22.1, 20.9;
MS (EI): m/z 319.2 (M+1); Anal. Calcd for C22H26N2: C, 82.97; H,
8.23; N, 8.80. Found: C, 82.79; H, 8.28; N, 8.72.
4.1.1.9. 2,8-Dimethyl-13-spiro[cyclopentane-6H,12H-5,11-meth
anodibenzo[b,f][l,5]diazocine] 2i.
Yield: 0.62 g (41%); mp
182–184 °C; IR (KBr) 2922, 2854, 1493 cmꢁ1
;
1H NMR (400 MHz,
CDCl3): d 7.04–6.95 (m, 4H), 6.69 (s, 2H), 4.70 (d, J = 17.2 Hz, 2H),
4.10 (d, J = 17.2 Hz, 2H), 2.22 (s, 6H), 2.04–1.99 (m, 2H), 1.83–
1.70 (m, 6H); 13C NMR (100 MHz, CDCl3): d 146.7, 133.1, 127.9,
127.8, 126.8, 125.8, 80.7, 55.6, 35.9, 23.9, 20.9; MS (EI): m/z
305.2 (M+1); Anal. Calcd for C21H24N2: C, 82.85; H, 7.95; N, 9.20.
Found: C, 82.68; H, 7.89; N, 9.26.
4.1.2. General procedure for the preparation of 5,11-substituted
derivatives of Tröger base using POCl3
To a reaction flask cooled under N2, was added Tröger base
(1.25 g, 5 mmol) in toluene (15 mL) and POCl3 (0.8 mL, 8.75 mmol)
slowly at 0 °C under N2. Next, the carbonyl compound (5.1 mmol)
was added at 0 °C. The reaction mixture was brought to 25 °C and
allowed to stir for 3 h at 80 °C. Then it was diluted with ethyl ace-
tate and neutralized with a 10% aq NaOH solution. The aqueous
layer was extracted with ethyl acetate and the combined organic
extracts were successively washed with water, brine and dried
over anhydrous Na2SO4. After removal of the solvent, the residue
was subjected to chromatography on silica gel using 2–5% ethyl
acetate in hexane to elute the desired 5,11-substituted derivatives
of Tröger base. Following, this procedure Tröger base derivatives
2a, 2b, 2c, 2d, and 2g were prepared (Table 2).
Figure 2. ORTEP representation of the crystal structure of compound 9a. Thermal
ellipsoids are drawn at 35% probability and all hydrogen atoms are removed for
clarity.
126.9, 125.4, 125.1, 110.3, 109.1, 71.3, 60.6, 53.5, 20.9; MS (EI): m/z
317.2 (M+1); Calcd for C21H20N2O: C 79.72, H 6.37, N 8.85, O 5.06.
Found: C 79.62, H 6.41, N 8.76.
4.1.3. General procedure for the preparation of Tröger base
derivatives 1d and 1e
4.1.1.8. 2,8-Dimethyl-13-spiro[cyclohexane-6H,12H-5,11-meth-
anodibenzo[b,f][1,5]diazocine] 2h.
192–194 °C (lit.9a mp 195–196 °C); IR (KBr) 2920, 2854,
1493 cmꢁ1 1H NMR (400 MHz, CDCl3): d 7.04–6.98 (m, 4H), 6.66
Yield: 0.79 g (50%); mp
To a solution of substituted anilines (10 mmol) and paraformal-
dehyde (0.60 g, 20 mmol) in CH2Cl2 (40 mL) was added AlCl3
(1.33 g, 10 mmol) under an N2 atmosphere. The reaction mixture
was allowed to stir for 12 h at 25 °C and the reaction was quenched
with cold water. The reaction mixture was extracted using CH2Cl2
;
(s, 2H), 4.57 (d, J = 16.8 Hz, 2H), 4.03 (d, J = 17.2 Hz, 2H), 2.21 (s,
6H), 1.82–1.47 (m, 10H); 13C NMR (l00 MHz, CDCl3): d 146.0,
Cl
Cl
O
P
Cl
O
Cl
N
N
N
N
Ph
H
Ph
O
N
N
N
Ph
O
N
N
N
O
P
Cl
Ph
Cl
Ph
Ph
Ph
Ph
N
5
6a
major product
POCl3
CH2Cl2
N
Ring inversion
Cl
Cl
P
Cl
O
O
( )-1a
Cl
N
N
N
N
N
N
N
N
Ph
Ph
N
Ph
O
P
Ph
Ph
Cl
Ph
6b
Cl
O
minor product
Scheme 8.

M. Periasamy et al. / Tetrahedron: Asymmetry 23 (2012) 108–116
115
and the combined organic extracts were successively washed with
water, brine solution and dried over anhydrous Na2SO4. After re-
moval of the solvent, the residue was subjected to chromatography
on silica gel using 2–5% ethyl acetate in hexane to give the desired
Tröger base derivatives. For Tröger base derivatives 1d and 1e, the
spectroscopic data were identical to the previously reported
values.13
134.4, 126.4, 126.3, 124.0, 123.9, 123.8, 123.7, 89.8, 58.3, 50.3,
41.7, 21.1, 21.0, 18.1, 17.9; MS (EI): m/z 322.35 (M+1); Anal. Calcd
for C21H27N3: C, 78.46; H, 8.47; N, 13.07. Found: C, 78.51; H, 8.52;
N, 12.95.
4.1.4.5. 2,4,8,10-Tetramethyl-13-(N,N-dimethylamino)-6H,12H-
5,11-methanodibenzo[b,f][1,5] diazocine 3e.
(65%); white solid, mp 100–102 °C; IR (KBr) 2943, 1475, 1271,
815 cmꢁ1 1H NMR (400 MHz, CDCl3): d 6.88 (s, 1H), 6.84 (s, 1H),
Yield: 0.418 g
4.1.4. General procedure for the preparation of 5,11-substituted
derivatives 3a–3e using POCl3
;
6.60 (s, 1H), 6.55 (s, 1H), 4.49 (d, J = 16.8 Hz, 1H), 4.43 (d,
J = 16.8 Hz, 1H), 3.97 (d, J = 16.8 Hz, 1H), 3.84 (s, 1H), 3.63 (d,
J = 16.8 Hz, 1H), 2.40 (s, 6H), 2.36 (s, 6H), 2.20 (s, 3H), 2.18 (s,
3H); 13C NMR (100 MHz, CDCl3): d 144.3, 139.8, 133.2, 132.9,
132.7, 129.6, 129.5, 128.3, 124.5, 124.4, 91.0, 56.0, 48.4, 41.6,
21.0, 20.9, 17.0, 16.9; MS (EI): m/z 322.35 (M+1); Anal. Calcd for
To a solution of Tröger base derivatives 1a–1e (2 mmol) and
DMF (0.153 g, 0.16 mL, 2.1 mmol) in CH2Cl2 (15 mL) was added
POCl3 (0.535 g, 0.32 mL, 3.5 mmol) at 25 °C under an N2 atmo-
sphere and stirred for 1 h. It was then cooled to 0 °C and quenched
with a 10% aq NaOH solution. The aqueous layer was extracted
with CH2Cl2 (2 ꢂ 15 mL) and the combined organic extracts were
washed successively with water, brine and dried over anhydrous
Na2SO4. After removal of the solvent, the residue was subjected
to chromatography on silica gel using 5–10% ethyl acetate in hex-
ane to elute the desired Tröger base derivatives (Table 4).
C21H27N3: C, 78.46; H, 8.47; N, 13.07. Found: C, 78.31; H, 8.41; N,
13.16.
4.1.4.6. 2,8-Dimethyl-11,12-dihydro-6H-dibenzo[b,f] [1,5] dia-
zocine-5-carbaldehyde 4.
mp 159–162 °C; IR (KBr) 3346, 2966, 2932, 2887, 1655,
1502 cmꢁ1 1H NMR (400 MHz, CDCl3): d 8.42 (s, 1H), 7.07–7.02
Yield: 0.102 g (19%); white solid,
4.1.4.1.
methano-dibenzo[b,f][1,5]diazocine
(93%); White solid, mp 102–104 °C; IR (KBr) 2991, 1494, 1421,
1205, 835 cmꢁ1 1H NMR (400 MHz, CDCl3): d 7.04–6.92 (m, 4H),
2,8-Dimethyl-13-(N,N-dimethylamino)-6H,12H-5,11-
;
3a. Yield: 0.546 g
(m, 3H), 6.94 (d, J = 7.6 Hz, 1H), 6.86 (d, J = 7.6 Hz, 1H), 6.52 (d,
J = 8.0 Hz, 1H), 4.83 (s, 2H), 4.28 (s, 2H), 3.96 (br s, 1H), 2.32 (s,
3H), 2.22 (s, 3H); 13C NMR (100 MHz, CDCl3): d 162.7, 146.2,
138.5, 137.5, 134.7, 133.3, 130.9, 129.8, 129.5, 129.1, 125.4,
123.3, 119.3, 50.9, 50.2, 20.9, 20.4; MS (EI): m/z 267.20 (M+1);
Anal. Calcd for C17H18N2O: C, 76.66; H, 6.81; N, 10.52; O, 6.01.
Found: C, 76.51; H, 6.75; N, 10.45.
;
6.73 (s, 1H), 6.69 (s, 1H), 4.62 (d, J = 8.8 Hz, 1H), 4.58 (d,
J = 8.8 Hz, 1H), 4.18 (d, J = 16.4 Hz, 1H), 3.85 (m, 2H), 2.42 (s, 6H),
2.23 (s, 3H), 2.20 (s, 3H); 13C NMR (100 MHz, CDCl3): d 146.4,
142.1, 133.2, 133.0, 128.2, 128.0, 127.8, 127.0, 126.9, 125.4,
125.2, 90.4, 59.5, 51.6, 41.6, 21.0, 20.9; MS (EI): m/z 294.25
(M+1); Anal. Calcd for C19H23N3: C, 77.78; H, 7.90; N, 14.32. Found:
C, 77.65; H, 7.93; N, 14.21.
4.1.5. General procedure for the diastereoselective synthesis of
Tröger base derivatives 6–9
To a solution of Tröger base derivatives 1a–1e (2 mmol) and
4.1.4.2. 2,8-Dimethoxy-13-(N,N-dimethylamino)-6H,12H-5,11-
(S,S)-N,N-bis(a-methylbenzyl)foramide (0.531 g, 2.1 mmol) in
methanodibenzo[b,f][1,5]diazocine
(84%); White solid, mp 111–113 °C; IR (KBr) 2999, 1494, 1458,
1240, 835 cmꢁ1 1H NMR (400 MHz, CDCl3): d 7.05 (d, J = 8.8 Hz,
3b.
Yield:
0.545 g
CH2Cl2 (15 mL) was added POCl3 (0.535 g, 0.32 mL, 3.5 mmol) at
25 °C under an N2 atmosphere and stirred for 12 h. It was then
cooled to 0 °C and quenched with 10% aq NaOH solution. The aque-
ous layer was extracted with CH2Cl2 (2 ꢂ 15 mL) and the combined
organic extracts were successively washed with water, brine, and
dried over anhydrous Na2SO4. After removal of the solvent, the res-
idue was subjected to chromatography on silica gel using 3–10%
ethyl acetate in hexane to give the desired Tröger base derivatives
(Table 6).
;
1H), 6.99 (d, J = 8.8 Hz, 1H), 6.76–6.69 (m, 2H), 6.42 (d,
J = 10.4 Hz, 2H), 4.61 (d, J = 9.6 Hz, 1H), 4.56 (d, J = 9.2 Hz, 1H),
4.14 (d, J = 16.8 Hz, 1H), 3.84–3.80 (m, 2H), 3.71 (s, 3H), 3.69 (s,
3H), 2.41 (s, 6H); 13C NMR (100 MHz, CDCl3): d 156.0, 155.8,
141.9, 137.7, 129.3, 129.1, 126.5, 126.3, 113.9, 113.7, 110.7,
110.4, 90.5, 59.6, 55.4, 55.3, 51.9, 41.5; MS (EI): m/z 326 (M+1);
Anal. Calcd for C19H23N3O2: C, 70.13; H, 7.12; N, 12.91. Found: C,
70.35; H, 7.16; N, 12.81.
4.1.5.1. 2,8-Dimethyl-13-bis(1-phenylethylamino)-6H,12H-5,11-
methanodibenzo[b,f][1,5]diazocine.
Data for a product mix-
4.1.4.3. 13-(N,N-Dimethylamino)-6H,12H-5,11-methanodibenzo
ture of 6: yield: 0.712 g (75%); dr = 75:25; White solid, mp 81–
[b,f][1,5]diazocine 3c.
Yield: 0.464 g (88%); White solid, mp
83 °C. ½a 2D5
¼ ꢁ97:6 (c 0.38, CHCl3). The diastereomeric ratio was
ꢃ
141–143 °C; IR (KBr) 3063, 2945, 1481, 1448, 1275, 833 cmꢁ1
;
1H
calculated on the basis of 1H NMR analysis of the –CH3 protons
NMR (400 MHz, CDCl3): d 7.17–7.07 (m, 4H), 6.97–6.86 (m, 4H),
4.68 (d, J = 9.2 Hz, 1H), 4.64 (d, J = 9.2 Hz, 1H), 4.25 (d, J = 16.4 Hz,
1H), 3.93 (d, J = 16.4 Hz, 1H), 3.88 (s, 1H), 2.43 (s, 6H); 13C NMR
(100 MHz, CDCl3): d 149.0, 144.8, 128.7, 128.4, 127.2, 127.0,
126.6, 126.5, 125.7, 125.4, 123.8, 123.7, 90.1, 59.5, 51.6, 41.6; MS
(EI): m/z 266.2 (M+1); Anal.Calcd for C17H19N3: C 76.95, H 7.22,
N 15.84. Found: C 77.23, H 6.48, N 15.76.
of the (S,S)-N,N-bis(a-methylbenzyl) moiety [for the major 1.51
(d, J = 8.0 Hz, 6H), and for the minor 1.63 (d, J = 8.0 Hz, 2H)].
Furthermore, dr = 77:23 was estimated by chiral HPLC analysis
on Chiral cell phenomenex cellulose-1 column, hexane/2-propa-
nol = 99.5:0.5, flow rate 1 mL/min; IR (KBr) 2924, 1493, 1450,
;
1209, 833 cmꢁ1 1H NMR (400 MHz, CDCl3): d 7.16–6.93 (m,
14H), 6.78–6.51 (m, 7H), 6.12 (d, J = 8.0 Hz, 0.3H), 5.05 (d,
J = 16.0 Hz, 0.3H), 4.76 (m, 1H), 4.60 (m, 2.5H), 4.35 (d,
J = 16.0 Hz, 1H), 4.10–3.94 (m, 1.7H), 3.73 (d, J = 16.0 Hz, 1H),
3.39 (d, J = 16.0 Hz, 1H), 2.24–218 (m, 8H), 1.63 (d, J = 8.0 Hz,
2H), 1.51 (d, J = 8.0 Hz, 6H); 13C NMR (100 MHz, CDCl3): d 146.9,
146.7, 144.3, 142.7, 142.2, 133.1, 132.7, 129.2, 128.9, 128.0,
127.7, 127.6, 127.4, 127.2, 126.9, 126.5, 126.2, 125.8, 125.6,
125.4, 125.0, 83.5, 82.8, 59.9, 59.8, 52.5, 51.1, 51.0, 21.0, 20.9,
16.1; MS (EI): m/z 474.35 (M+1); Anal. Calcd for C33H35N3: C,
83.68; H, 7.45; N, 8.87. Found: C, 83.49; H, 7.51; N, 8.95.
4.1.4.4. 1,3,7,9-Tetramethyl-13-(N,N-dimethylamino)-6H,12H-
5,11-methanodibenzo[b,f][1,5] diazocine 3d.
(86%); White solid, mp 227–229 °C; IR (KBr) 2995, 2914, 1435,
1280, 852 cmꢁ1 1H NMR (400 MHz, CDCl3): d 6.83 (s, 1H), 6.77
Yield: 0.551 g
;
(s, 1H), 6.64 (s, 1H), 6.62 (s, 1H), 4.46 (d, J = 16.4 Hz, 1H), 4.39 (d,
J = 16.4 Hz, 1H), 4.15 (d, J = 16.4 Hz, 1H), 3.87 (d, J = 16.4 Hz, 1H),
3.79 (s, 1H), 2.41 (s, 6H), 2.26 (s, 3H), 2.24 (s, 3H), 2.07 (s, 6H);
13C NMR (100 MHz, CDCl3): d 149.3, 144.8, 136.5, 136.0, 135.0,

116
M. Periasamy et al. / Tetrahedron: Asymmetry 23 (2012) 108–116
4.1.5.2. (2,8-Dimethyoxy-13-bis(1-phenylethylamino)-6H,12H-
5,11-methanodibenzo[b,f][1,5] diazocine. Data for a prod-
7.17–7.16 (m, 6H), 6.82–6.65 (m, 8H), 4.80 (s, 1H), 4.58 (d,
J = 8.0 Hz, 2H), 4.32 (d, J = 16.0 Hz, 1H), 4.13 (d, J = 16.0 Hz,
1H), 3.29 (q, J = 16.0 Hz, 2H), 2.29 (s, 3H), 2.26 (s, 3H), 2.07
(s, 3H), 1.85 (s, 3H), 1.52 (d, J = 8.0 Hz, 6H); 13C NMR
(100 MHz, CDCl3): d 149.8, 144.6, 144.5, 136.2, 135.6, 134.9,
134.0, 128.8, 127.2, 126.0, 125.8, 125.1, 124.5, 123.8, 123.7,
81.8, 58.3, 52.3, 49.9, 21.0, 20.9, 17.9, 17.5, 15.4; MS (EI): m/
z 502.45 (M+1). Anal. Calcd for C35H39N3: C, 83.79; H, 7.84;
N, 8.38. Found: C, 83.65; H, 7.78; N, 8.26.
uct mixture of 7: yield: 0.665 g (66%); dr = 75:25; White solid,
mp 90–92 °C; ½a 2D5
¼ ꢁ92 (c 0.88, CHCl3). The diastereomeric ratio
ꢃ
was calculated on the basis of 1H NMR analysis of the –CH3 protons
of the (S,S)-N,N-bis(a- methylbenzyl) moiety [For major 1.56 (d,
J = 8.0 Hz, 6H), and for minor 1.67 (d, J = 8.0 Hz, 2H)]. Furthermore,
dr = 77:23 was estimated by chiral HPLC analysis on Chiral cell
phenomenex cellulose-1 column, hexane/2-propanol = 99.5:0.5,
flow rate 1 mL/min; IR (KBr) 2932, 1493, 1450, 1209, 835 cmꢁ1
;
1H NMR (400 MHz, CDCl3): d 7.21–7.06 (m, 11.5H), 6.82–6.75 (m,
6H), 6.48–6.44 (m, 1.6H), 6.35–6.34 (m, 1.3H), 6.18 (d, J = 8.0 Hz,
0.4H), 5.30 (s, 1H), 5.09 (d, J =16.0 Hz, 0.4H), 4.83–4.78 (m, 1.3H),
4.66–4.62 (m, 2.8H), 4.46 (d, J = 16.0 Hz, 1H), 4.14–3.96 (m,
1.7H), 3.75–3.73 (m, 8.5H), 3.38 (d, J = 16.0 Hz, 1H), 1.67 (d,
J = 8.0 Hz, 2H), 1.56 (d, J = 8.0 Hz, 6H); 13C NMR (100 MHz, CDCl3):
d 155.9, 155.7, 155.1, 144.4, 142.4, 142.2, 138.3, 137.7, 130.5,
129.8, 129.7, 128.8, 128.4, 128.2, 127.9, 127.4, 126.7, 126.6,
126.5, 126.1, 125.8, 113.7, 113.3, 110.5, 110.4, 109.6, 83.7, 83.0,
60.0, 55.4, 52.5, 51.3, 16.0, 15.8; MS (EI): m/z 506.45 (M+1); Anal.
Calcd for C33H35N3O2: C, 78.38; H, 6.98; N, 8.31; O, 6.33. Found:
C, 78.51; H, 6.91; N, 8.25.
Acknowledgements
SS thanks the CSIR (New Delhi) for a research fellowship. DST
support through a J. C. Bose Fellowship grant to MP is gratefully
acknowledged. The authors also thank the DST for the 400 MHz
NMR facility under FIST program and for the National single crystal
X-ray diffractometer facility. Support of the UGC under the
‘‘University of Potential for Excellence’’ and the Center for Ad-
vanced Study and UGC-MHRD Chemistry Resources Centre
Programmes.
References
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2. Harmata, M.; Rayanil, K.-O.; Barnes, C. L. Supramol. Chem. 2006, 18, 581–586;
(b) Lenev, D. A.; Chervin, I. I.; Lyssenko, K. A.; Kostyanovsky, R. G. Tetrahedron
Lett. 2007, 48, 3363–3366; (c) Mahon, A. B.; Craig, D. C.; Try, A. C. Synthesis
2009, 5, 636–642; (d) Hamada, Y.; Mukai, S. Tetrahedron: Asymmetry 1996, 7,
2671–2674.
3. (a) Harmata, M.; Kahraman, M. Tetrahedron: Asymmetry 2000, 11, 2875–2879;
(b) Shen, Y.-M.; Zhao, M.-X.; Xu, J.; Shi, Y. Angew. Chem. Int. Ed. 2006, 45, 8005–
8008.
4.1.5.3. Product mixture 8.
Yield: 0.605 g (68%); dr = 75:25;
White solid, mp 169–161 °C; the diastereomeric ratio was calculated
on the basis of 1H NMR analysis of the –CH3 protons of the (S,S)-N,N-
bis(a-methylbenzyl) moiety [Formajor 1.57 (d, J = 7.2 Hz, 6H), andfor
minor 1.69 (d, J = 7.2 Hz, 2H)]. The diastereomeric mixture was crys-
tallized from acetone to obtain compound 8a in pure form.
13-Bis(1-phenylethylamino)-6H,12H-5,11-methanodibenzo[b,f]
[1,5]diazocine 8a white solid, mp 161–163 °C; ½a D25
¼ ꢁ189:4 (c
ꢃ
4. Wilen, S. H.; Qi, J. Z. J. Org. Chem. 1991, 56, 485–487.
0.32, CHCl3); IR (KBr) 3024, 2928, 1496, 1449, 1212, 852 cmꢁ1
;
5. Bag, B. G.; Kiedrowski, G. Angew. Chem. Int. Ed. 1999, 38, 3713–3714.
6. Wilcox, C. S.; Geer, L. M.; Lynch, V. J. J. Am. Chem. Soc. 1987, 109, 1865–1867.
7. Tatibouët, A.; Demeunynck, M.; Andraud, C.; Collet, A.; Lhomme, J. . Chem.
Commun. 1999, 161–162.
8. (a) Satishkumar, S.; Periasamy, M. Tetrahedron: Asymmetry 2006, 17, 1116–
1119; (b) Satishkumar, S.; Periasamy, M. Tetrahedron: Asymmetry 2009, 20,
2257–2262; (c) Satishkumar, S.; Periasamy, M. Indian J. Chem. 2008, 47B, 1080–
1083.
9. (a) Copper, F. C.; Partridge, M. W. J. Chem. Soc. 1957, 2888–2893; (b) Mahon, A.
B.; Craig, D. C.; Try, A. C. ARKIVOC 2008, xii, 148–163.
10. Compound 2i was characterized by X-ray crystallography. Crystal data for the
compound 2i Molecular formula: C21H24N2, MW = 304.42, monoclinic, space
1H NMR (400 MHz, CDCl3): d 7.22–7.15 (m, 10H), 7.05–7.01 (m,
2H), 6.96–6.94 (m, 1H), 6.82–6.79 (m, 5H), 4.88 (s, 1H), 4.64 (d,
J = 8.0 Hz, 2H), 4.50 (d, J = 16.8 Hz, 1H), 4.22 (d, J = 16.4 Hz, 1H),
3.79 (d, J = 16.4 Hz, 1H), 3.49 (d, J = 16.8 Hz, 1H), 1.57 (d,
J = 7.2 Hz, 6H); 13C NMR (100 MHz, CDCl3): d 149.6, 144.9, 144.3,
129.8, 129.2, 128.8, 127.5, 126.9, 126.8, 126.6, 126.3, 126.1,
125.8, 125.7, 123.7, 123.6, 82.6, 59.8, 52.6, 51.2, 15.9; MS (EI): m/
z 446.35 (M+1); Anal. Calcd for C31H31N3: C, 83.56; H, 7.01; N,
9.43. Found: C, 83.65; H, 7.12; N, 9.36.
group: C2/c, a = 14.7341(11) Å, b = 8.3650(6) Å, c = 13.5544(10) Å,
b = 91.7610(10), = 90°,
= 1669.8(2) Å3, Z = 4, c = 1.211 mg mꢁ3
= 0.071 mmꢁ1
T = 298(2) K. Of the 8679 reflections collected, 1639
a = 90°,
c
v
q
l
,
4.1.5.4. Product mixture 9
reflections were unique (Rint = 0.0238). Refinement on all data converged at
R1 = 0.0607, wR2 = 0.1399 (CCDC deposition number: 853836).
Yield: 0.525 g (52%); dr = 58:42; White solid, mp 220–221 °C;
The diastereomeric ratio was calculated on the basis of 1H NMR
11. Compound 9a was characterized by X-ray crystallography. Crystal data for the
compound 9a Molecular formula:
C
35H39N3, MW = 501.69, orthorhombic,
analysis of the –CH3 protons of the (S,S)-N,N-bis(a-methylbenzyl)
space group: P2(1)2(1)2(1), a = 9.3077(10) Å, b = 14.8229(16) Å, c = 20.866(2)
moiety [For major 1.57 (d, J = 7.2 Hz, 6H), and for minor 1.69 (d,
J = 7.2 Hz, 4.4H)]. Further, dr = 60:40 was estimated by chiral HPLC
analysis on Chiral cell phenomenex cellulose-1 column, hexane/2-
propanol = 99.5:0.5, flow rate 0.6 mL/min; The diastereomeric
mixture was crystallized from acetone to obtain compound 9a in
pure form.
Å,
l
a
= 90°, b = 90°,
c
= 90°,
v
= 2878.9(5) Å3, Z = 4, c = 1.158 mg mꢁ3
q
= 0.067 mmꢁ1
,
T = 298(2) K. Of the 30439 reflections collected, 5069
reflections were unique (Rint = 0.0700). Refinement on all data converged at
R1 = 0.1172, wR2 = 0.2165 (CCDC deposition number: 853835).
12. (a) Malik, Q. M.; Mahon, A. B.; Craig, D. C.; Try, A. C. Tetrahedron 2011, 67,
8509–8514; (b) Reddy, M. B.; Manjula, A.; Rao, B. V.; Sridhar, B. Eur. J. Org.
Chem. 2011, 312–319.
13. Didier, D.; Tylleman, B.; Lambert, N.; Velde, C. M. L. V.; Blockhuys, F.; Collas, A.;
Sergeyev, S. Tetraheron 2008, 64, 6252–6262.
14. Iseki, K.; Kuroki, Y.; Kobayashi, Y. Tetraheron: Asymmetry 1998, 9, 2889–2894.
(1,3,7,9-Tetramethyl-13-bis(1-phenylethylamino)-6H,12H-
5,11-methanodibenzo[b,f][1,5]diazocine 9a: White solid, mp
221–223 °C; ½a 2D5
ꢃ
¼ ꢁ264 (c 0.10, CHCl3). IR (KBr) 3026, 2926,
15. The authors are thankful to
mechanism to our attention.
a reviewer for bringing this aspect of the
1494, 1448, 1211, 850 cmꢁ1
;
1H NMR (400 MHz, CDCl3): d