N,N'-bisacylimidazolidines from 1,2-diamines

Article abstract of DOI:10.1055/s-1998-2176

A variety of novel 1,3-bisacylimidazolidines were prepared in a one-pot procedure from 1,2-diamines. Condensation of 1,2-diaminoethane or a selection of chiral 1,2-diamines with a variety of aldehydes under dehydrating conditions gives rise to 1,3-bisunsubstituted imidazolidines. These imidazolidines were not isolated, but were treated with acid chlorides or anhydrides to give the novel 1,3-bisacylimidazolidines.

Full text of DOI:10.1055/s-1998-2176

October 1998
SYNTHESIS
1463
N,N'-Bisacylimidazolidines from 1,2-Diamines
a
a
a
b
Iain Coldham,* Philippe M. A. Houdayer, Robert A. Judkins and David R. Witty
a
Department of Chemistry, University of Exeter, Stocker Road, Exeter EX4 4QD, UK
Fax +44(1392)263434; E-mail: I.Coldham@exeter.ac.uk
b
SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK
Received 12 March 1998
Abstract: A variety of novel 1,3-bisacylimidazolidines were pre-
pared in a one-pot procedure from 1,2-diamines. Condensation of
PhCOCl. The product 1,3-dibenzoylimidazolidine (4a), R
H, R' = Ph (73%) was isolated by column chromatogra-
=
1
,2-diaminoethane or a selection of chiral 1,2-diamines with a
variety of aldehydes under dehydrating conditions gives rise to
,3-bisunsubstituted imidazolidines. These imidazolidines were
phy and recrystallised to give material of microanalytical
purity. This approach was successful for the synthesis of
a range of 1,3-bisacylimidazolidines 4a–g, using the 1,2-
diamine 2 and condensation with a variety of aldehydes
(1.2 equiv) and acid chlorides (Table 1).
1
not isolated, but were treated with acid chlorides or anhydrides to
give the novel 1,3-bisacylimidazolidines.
Key words: diamines, imidazolidines, heterocycles, C -symmetry
2
Imidazolidines 1 are the fully saturated form of the hetero-
cycle imidazole. Methods for the preparation of 1,3-di-
alkylimidazolidines 1, R = alkyl, commonly require the
synthesis of dialkylated 1,2-diamines and their condensa-
1, 2
tion with aldehydes or ketones. In comparison, the for-
mation and use of 1,3-bisacylimidazolidines 1, R = COR',
is rare. Scattered reports of their synthesis include the 1,3- Table 1. Synthesis of 1,3-Bisacylimidazolidines 4
bisacylation of imidazole (or dihydroimidazole) with in
Entry
R
Equiv
RCHO
R'COX
R'
Product Yield
(%)
situ reduction (or reaction) of the unsaturated ring sys-
3
tem, the condensation of a mono- or bisacylated diamine
4, 5
with a carbonyl compound, the cycloaddition of a dihy-
1
2
3
4
5
6
7
8
9
H
Me
Et
H
Me
Et
2.6
1.2
1.2
2.6
1.2
1.2
2.6
2.6
1.2
1.0
PhCOCl
PhCOCl
PhCOCl
EtCOCl
EtCOCl
EtCOCl
Ph
Ph
Ph
Et
Et
Et
4a
4b
4c
4d
4e
4f
73
50
56
73
64
53
66
65
72
68
36
6
droimidazole with a chromium carbene, or the cycliza-
7
tion of an aminal onto an alkene. These approaches re-
quire the prior synthesis of a novel functionalised diamine
or an intact five-membered ring before the desired novel
1,3-bisacylimidazolidine can be prepared. To our knowl-
H
H
MeOCOCl OMet
4g
4h
4i
edge, there are only a few reports of the formation in mod-
Boc O
OBu
OBut
OBut
OBut
2
erate yield of 1,3-bisacylimidazolidines from N,N'-bisun-
Me
Bu
CH Ph 1.0
Boc2O
8
, 9
10
Boc O
4j
4k
substituted 1,2-diamines.
2
11
Boc O
2
2
As an alternative to quenching with an acid chloride, we
found that the intermediate 1,3-bisunsubstituted imidazol-
idine 3 could be trapped with the acid anhydride Boc O in
2
the absence of the base pyridine, to give other novel 1,3-
bisacylimidazolidines 4h–k (Table 1).
As part of a project involved with the formation of α-ami-
no-organolithium species, we wanted access to chiral 1,3-
bisacylimidazolidines as potential chiral acyl anion equiv-
1
,2-Diamines 5, other than 1,2-diaminocyclohexane 2,
can be used as substrates for imidazolidine formation.
Commercially available ethylenediamine 5, R = H and
1
0
alents. We decided to investigate in a more systematic
and thorough way, the preparation of this heterocycle by
cyclization of simple 1,2-diamines with aldehydes and in
situ acylation of the derived 1,3-bisunsubstituted imidazo-
lidines. After some experimentation, we used the condi-
(+)-1,2-diphenylethylenediamine 5, R = Ph allowed effi-
12
cient formation of the imidazolidines 6a–f (Table 2).
The range of examples was broadened further, by prepar-
ing the diamine (+)-7, by a modification of the reported
procedure and the diamines (+)-8 and (–)-9; these
were converted to the bisacylated imidazolidines 10–12
13
14
15
16
1
1
tions employed by Gao for selective monoacylation of
diamines via imidazolidines. The racemic 1,2-diamine 2
was treated with paraformaldehyde (2.6 equiv) in chloro-
form, in the presence of the dehydrating agents MgSO4
and K CO . After stirring for 17 hours, the mixture con-
using paraformaldehyde with trapping by Boc O.
2
2
3
taining the 1,3-bisunsubstituted imidazolidine 3, R = H
was cooled to –20°C and two equivalents of pyridine were
added, followed by 2.2 equivalents of the acid chloride

SYNTHESIS
1
464
Papers
Table 2. Synthesis of 1,3-Bisacylimidazolidines 6
were stirred for 24 h. Di-tert-butyl dicarbonate (0.271 g, 1.24 mmol)
was added and the mixture was stirred for a further 17 h. The mixture
was filtered, evaporated, added to sat. brine (10 mL) and washed with
Entry
R
Equiv
CH O)
R'COX
R'
Product Yield
(%)
(
CH Cl2 (3 × 5 mL). The combined organic extracts were dried
2
n
2
(
Na SO ), filtered, evaporated and purified by chromatography [silica
2 4
1
2
3
4
5
6
H
H
H
H
Ph
Ph
2.6
2.6
2.6
2.6
1.0
1.0
PhCOCl
EtCOCl
MeOCOCl OMe
Ph
Et
6a
6b
6c
6d
6e
6f
88
68
70
64
54
57
gel, petroleum ether (bp 40–60°C)/EtOAc 5:1] to give the imidazoli-
dine 10 (0.140 g, 75%) as needles; mp 80–82°C; R 0.38 [petroleum
ether (bp 40–60°C)/EtOAc 5:1]; [α] +3.7 (c = 1.0, CHCl ).
f
Boc O
OBut
–1
D
3
2
IR (KBr): ν = 1705 cm (C=O).
Boc O
OBut
1
2
H NMR (CDCl ): δ = 4.68 (2H, s, NCH N), 3.77 (2H, bs,
3
2
MeOCOCl OMe
NCHCHN), 1.46 [18H, s, 2 × C(CH ) ], 1.19 (6H, d, J = 6.5 Hz, CH ).
3
3
3
1
3
C NMR (CDCl ): δ = 152.9, 80.1, 58.8, 58.2, 28.4, 18.8.
3
+
HRMS: Found M , 300.2054. C H N O requires M, 300.2049.
MS: m/z (%) = 300 (0.1, M ), 243 [66, M – C(CH ) ], 187 [100, M –
15
28
2
4
+
3
3
2
× C(CH ) ], 143 [81, M – CO C(CH ) – C(CH ) )].
3 3 2 3 3 3 3
Anal.: Found C, 59.92; H, 9.63; N, 9.31. C H N O requires C,
15
28
2
4
59.97; H, 9.41; N, 9.33.
(
(
(
4R,5R)-1,3-Bis(tert-butoxycarbonyl)-4,5-dipropylimidazolidine
11):
4R,5R)-4,5-Diaminooctane dihydrochloride15 (0.2 g, 0.92 mmol),
paraformaldehyde (28 mg, 0.92 mmol), K CO (0.4 g) and MgSO
2
3
4
(
0.4 g) in CHCl (15 mL) were stirred for 66 h. Di-tert-butyl dicarbon-
3
ate (0.402 g, 1.84 mmol) was added and the mixture was stirred for a
further 17 h. The mixture was filtered, evaporated, added to sat. brine
(
10 mL) and washed with CH Cl (3 × 5 mL). The combined organic
2 2
extracts were dried (Na SO ), filtered, evaporated and purified by
2
4
chromatography [silica gel, petroleum ether (bp 40–60°C)/EtOAc
0:1] to give the imidazolidine 11 (192 mg, 58%) as an oil; R 0.30
1
f
[petroleum ether (bp 40–60°C)/EtOAc 10:1)]; [α]D +12.7 (c = 1.0,
CHCl3).
–1
IR (film): ν = 1710 cm (C=O).
1
H NMR (CDCl ): δ = 4.75–4.54 (2H, m, NCH N), 3.83–3.62 (2H,
3
2
m, NCHCHN), 1.45 [18H, s, 2 × C(CH ) ], 1.41–1.21 (8H, m, 2 ×
3
3
CH CH ), 0.92 (6H, t, J = 7 Hz, 2 × CH ).
2
2
3
13
C NMR (CDCl ): δ = 153.3, 153.1, 80.1, 60.6, 60.1, 59.3, 35.7,
3
3
5.3, 28.4, 19.1, 18.9, 13.9.
+
HRMS: Found M , 356.2675. C H N O requires M, 356.2675.
MS: m/z (%) = 356 (0.2, M ), 299 [7, M – C(CH ) ], 255 [8, M –
The convenient one pot preparation described herein rep-
resents an efficient and rapid access to 1,3-bisacylimid-
azolidines. The imidazolidines are prepared from N,N'-
bisunsubstituted diamines with a choice of aldehyde to al-
low formation of the five-membered ring and a choice of
electrophile for N-acylation.
19 36
2
4
+
3
3
CO C(CH ) ], 57 [100, C(CH ) ].
2
3 3
3 3
(4S,5S)-1,3-Bis(tert-Butoxycarbonyl)-4,5-bis(methoxymethyl)im-
idazolidine (12):
(2S,3S)-2,3-Diamino-1,4-dimethoxybutane16 (50 mg, 0.338 mmol)
was added to paraformaldehyde (10 mg, 0.338 mmol), K CO (0.2 g)
2
3
and MgSO (0.2 g) in CHCl (5 mL). After 24 h, di-tert-butyl dicar-
4
3
Experimental information concerning solvents, spectroscopic equip-
ment, etc. has been reported previously.
1
7
bonate (147 mg, 0.676 mmol) was added and the mixture was stirred
for a further 24 h. The mixture was filtered, evaporated, added to sat.
brine (10 mL) and washed with CH Cl (3 × 3 mL). The combined
2
2
Imidazolidines; General Procedure:
organic extracts were dried (Na SO ), filtered, evaporated and puri-
2
4
The diamine (4.4 mmol) was added to the aldehyde (5.2 mmol),
K CO (2.0 g) and MgSO (2.0 g) in CHCl (25 mL) under N at r.t.
fied by chromatography [silica gel, petroleum ether (bp 40–60°C)/
EtOAc 7:1] to give the imidazolidine 12 (88 mg, 72%) as an oil; Rf
2
3
4
3
2
After 17 h, either di-tert-butyl dicarbonate (1.91 g, 8.77 mmol), or
pyridine (0.8 mL, 9.65 mmol) and the acid chloride (9.65 mmol) were
added and the resulting solution stirred for a further 1–20 h. The mix-
ture was filtered, evaporated and purified by column chromatography
0
1
.21 [petroleum ether (bp 40–60°C)/EtOAc 17:1]; [α]D –36.8 (c =
.07, CHCl3).
–1
IR (film): ν = 1700 cm (C=O).
1
H NMR (CDCl ): δ = 4.65 (2H, bs, NCH N), 4.23–4.02 (2H, m,
3
2
[silica gel, petroleum ether (bp 40–60°C)/EtOAc 10:1] to give the
NCHCHN), 3.51–3.42 (4H, m, 2 × OCH ), 3.45 (6H, s, 2 × OCH ),
2
3
required imidazolidine, which could normally be recrystallized from
1
.47 [18H, s, 2 × C(CH ) ].
3 3
EtOH/H O.
13
2
C NMR (CDCl ): δ = 153.0, 80.4, 72.6, 60.9, 59.1, 57.5, 28.4.
3
Spectroscopic data for imidazolidines 4a–k can be found in Table 3.
Spectroscopic data for imidazolidines 6a–f can be found in Table 4.
+
HRMS: Found M , 360.2264. C H N O requires M, 360.2260.
MS: m/z (%) = 360 (2, M ), 315 (28, M – CH OCH ), 303 [26, M –
17
32
2
6
+
2
3
C(CH ) ], 259 [34, M – CO C(CH ) ], 57 [100, C(CH ) ].
3
3
2
3 3
3 3
(
(
(
4S,5S)-1,3-Bis(tert-butoxycarbonyl)-4,5-dimethylimidazolidine
10):
2S,3S)-2,3-Diaminobutane dihydrochloride1 (0.1 g, 0.62 mmol),
3
We thank the E.P.S.R.C. for a studentship (to RAJ), the ERASMUS
Programme for partial support (to PMAH) and SmithKline Beecham
Pharmaceuticals for a CASE award (to RAJ).
paraformaldehyde (18.6 mg, 0.62 mmol), Et N (0.173 mL,
1
3
.24 mmol), K CO (0.3 g) and MgSO (0.3 g) in CHCl (10 mL)
2 3 4 3

October 1998
SYNTHESIS
HRMSa
1465
Table 3. Data for Products 4a–k
Prod-
uct
MP
(°C)
1H NMR (CDCl3)
δ, J (Hz)
13C NMR (CDCl3)
δ
4
a
118–120
7.52–7.33 (10 H, m, 2 × Ph), 4.99 (2 H, s, NCH N), 3.44– 170.9, 136.2, 130.7, 128.5,
2
3
.34 (2 H, m, NCHCHN), 2.29–2.16 (2 H, m, CH ), 1.78– 127.2, 65.5, 64.7, 29.9,
2
1
.66 (2 H, m, CH ), 1.42–1.18 (4 H, m, CH CH )
24.4
2
2
2
+
4
b
oil
7.66–7.31 (10 H, m, 2 × Ph), 5.83 (1 H, q, J = 5.5, NCHN), 170.5, 137.2, 136.6, 133.3, Found: M , 348.1826.
3
1
1
.50–3.39 (2 H, m, NCHCHN), 2.63–2.31 (2 H, m, CH2), 130.6, 129.8, 128.6, 127.3, C H N O requires
22 24 2 2
.78–1.52 (2 H, m, CH ), 1.41 (3 H, d, J = 5.5, CH ), 1.37– 126.1, 72.2, 65.2, 62.3, M, 348.1838
2
3
.07 (4 H, m, CH CH )
31.0, 29.5, 24.6, 24.2, 20.5
2
2
+
4
c
140–142
7.53–7.32 (10 H, m, 2 × Ph), 6.04–5.95 (1 H, m, NCHN), 171.2, 169.9, 137.4, 136.9, Found: M , 362.1999.
3
3
.44 (1 H, td, J = 10 and 3, NCH), 3.34 (1 H, td, J = 10 and 130.5, 129.7, 128.5, 128.4, C H N O requires
23 26 2 2
, NCH), 2.40–2.20 (2 H, m, CH ), 1.94–1.77 (2 H, m, 127.5, 126.1, 75.3, 65.6, M, 362.1994
2
CH CH ), 1.75–1.55 (2 H, m, CH ), 1.29–1.06 (4 H, m, 63.4, 30.9, 29.8, 27.8, 24.7,
2
3
2
CH CH ), 0.86 (3 H, t, J = 7.5, CH CH )
24.2, 9.1
2
2
2
3
4d
4e
4f
78–80
92–93
oil
4.87 (2 H, 5, NCH N), 3.22–3.12 (2 H, m, NCHCHN), 2.88 173.3, 64.2, 62.8, 30.3,
2
(
2 H, bs, CH ), 2.37–2.20 (4 H, m, 2 × CH CH ), 1.90–1.79 28.6, 24.4, 8.7
2
2
3
(
2 H, m, CH ), 1.58–1.42 (2 H, m, CH ), 1.42–1.29 (2 H, m,
2
2
CH ), 1.13 (6 H, t, J = 7.5, 2 × CH CH )
2
2
3
5.68 (1 H, bs, NCHN), 3.40–3.26 (1 H, m, NCH), 3.24–3.10 174.2, 171.2, 69.8, 64.2,
(
1 H, m, NCH), 2.40–2.20 (4 H, m, 2 × CH CH ), 2.00–1.63 31.9, 30.3, 28.3, 28.1, 24.9,
2 3
(
4 H, m, 2 × CH ), 1.58–1.22 (7 H, m, CH CH and CHCH ), 24.2, 20.6, 9.0, 8.9
2
2
2
3
1
.20–1.05 (6 H, m, 2 × CH CH )
2
3
+
5.70 (1 H, bs, NCHN), 3.32 (1 H, td, J = 13 and 3, NCH), 174.8, 171.9, 73.5, 64.3,
Found: M , 266.1994.
3
.12 (1 H, td, J = 13 and 3, NCH), 2.94 (1 H, bs, CH), 2.52 62.9, 31.8, 30.2, 28.4, 28.2, C H N O requires
15
26
2
2
(
1 H, bs, CH), 2.38–2.19 (4 H, m, 2 × COCH CH ), 1.94– 27.9, 25.2, 24.2, 9.3, 9.0, M, 266.1994
2 3
1
.72 (4 H, m, 2 × CH ), 1.44–1.23 (4 H, m, CH CH ), 1.18– 8.9
2
2
2
1
.04 (6 H, m, 2 × COCH CH ), 0.93 (3 H, t, J = 7.5,
2 3
CHCH CH )
2
3
4g
4h
4i
79–82
4.70 (2 H, s, NCH N), 3.67 (6 H, s, 2 × OMe), 3.07–2.98 (2 155.2, 63.8, 62.6, 52.3,
2
H, m, NCHCHN), 2.74 (2 H, bd, J = 11, CH ), 1.83–1.76 (2 29.5, 24.1
2
H, m, CH ), 1.46–1.27 (4 H, CH CH )
2
2
2
118–120
101–104
4.63 (2 H, s, NCH N), 3.05–2.92 (2 H, m, NCHCHN), 2.75– 154.3, 80.3, 63.8, 62.8,
2
2
2
.63 (2 H, m, CH ), 1.82–1.71 (2 H, m, CH ), 1.45 [18 H, s, 29.8, 28.4, 24.2
2
2
× C(CH ) ], 1.42–1.24 (4 H, m, CH CH )
3
3
2
2
5.27 (1 H, q, J = 5.5, NCHN), 3.09 (1 H, td, J = 10.5 and 3, 155.2, 152.6, 80.1, 80.0,
NCH), 2.99 (1 H, td, J = 10.5 and 3, NCH), 2.78 (2 H, bd, J 70.3, 64.5, 60.7, 30.9, 29.5,
=
10.5, CH), 2.62 (1 H, bd, J = 10.5, CH), 1.84–1.76 (2 H, 28.5, 28.3, 24.7, 24.1, 19.9
m, CH ), 1.47 [18 H, s, 2 × C(CH ) ], 1.38 (3 H, d, J = 5.5,
2
3 3
CH ) and 1.33–1.18 (4 H, m, CH CH )
3
2
2
4
j
87–90
87–90
5.31 (1 H, t, J = 5, NCHN), 3.08 (1 H, td, J = 11 and 3, NCH), 155.7, 152.8, 80.1, 79.9,
2.96 (1 H, td, J = 11 and 3, NCH), 2.72 (1 H, bd, J = 12, CH), 73.4, 64.8, 61.8, 34.7, 31.2,
2
.58 (1 H, bd, J = 12, CH), 1.87–1.61 (4 H, m, 2 × CH ), 1.46 29.8, 28.5, 28.4, 26.9, 25.0,
2
[
18 H, s, 2 × C(CH ) ], 1.39–1.13 (8H, m, 4 × CH ), 0.90 (3 24.2, 22.8, 14.1
3
3
2
H, t, J = 7.5, CH3)
+
4
k
7.29–7.18 (3 H, m, Ph), 7.14–7.09 (2 H, m, Ph), 5.46 (1 H, t, 155.4, 152.5, 136.8, 130.7, Found: MH , 417.2759.
J = 3.5, NCHN), 3.19 (1 H, td, J = 10.5 and 2.5, NCH), 3.14 128.0, 126.5, 80.4, 80.0, C H N O requires
2
4
38
2
4
A
B
(
1 H, dd, J = 14 and 3.5, CH H Ph), 2.86 (1 H, td, J = 2.5 73.9, 64.3, 61.7, 38.4, 30.4, MH, 417.2753
A
B
and 10.5, NCH), 2.49 (2 H, m, CH H Ph and CH), 1.96 (1 29.6, 28.5, 24.7, 23.9
H, m, CH), 1.66–1.53 (2 H, m, 2 × CH), 1.49 [9H, s,
C(CH ) ], 1.46 [9H, s, C(CH ) ], 1.39–1.26 (1 H, m, CH),
3
3
3 3
1.24–1.11 (1 H, m, CH), 0.95–0.87 (2 H, m, CH2)
a
Satisfactory microanalyses obtained 4a, d, e, g–j: C ± 0.15, H ± 0.28, N ± 0.23.

SYNTHESIS
1
466
Papers
Table 4. Data for Products 6c–fa
Lambert, J. B.; Huseland, D. E.; Want, G. Synthesis 1986, 657.
Eynde, J. J. V.; Delfosse, F.; Lor, P.; Van Haverbeke, Y. Tetra-
hedron 1995, 51, 5813.
Periasamy, M.; Reddy, M. R.; Kanth, J. V. B. Tetrahedron Lett.
1996, 37, 4767.
Prod-
uct
mp
(˚C)
1H NMR (CDCl3)
δ, J
13C NMR
(CDCl3)
δ
(
3) Bauer, L. J. Org. Chem. 1961, 26, 1649.
Butula, I. Liebigs Ann. Chem. 1968, 718, 260.
Smith, F. T.; Atigadda, R. V. J. Heterocycl. Chem. 1991, 28,
6
6
6
ab
bb
c
1813.
(4) Huffman, W. F.; Holden, K. G.; Buckley, T. F.; Gleason, J. G.;
Wu, L. J. Am. Chem. Soc. 1977, 99, 2352.
90–92
4.72 (2 H, s, NCH N), 3.73 154.1, 60.1,
2
(
6 H, s, 2 × OCH ), 3.61 52.7, 43.8
3
(5) Luk'Yanov, O. A.; Pokhvisneva, G. V.; Ternikova, T. V. Bull.
Acad. Sci. USSR Div. Chem. Sci. (Engl. Transl.) 1994, 1452.
(
4 H, s, NCH CH N)
2
2
6
d
e
100–104
124–127
4.62 (2 H, s, NCH N), 3.54 153.1, 80.4,
(6) Ronan, B.; Hegedus, L. S. Tetrahedron 1993, 49, 5549.
(7) van Benthem, R. A. T. M.; Hiemstra, H.; Longarela, G. R.;
Speckamp, W. N. Tetrahedron Lett. 1994, 35, 9281.
2
(
4 H, s, NCH CH N), 1.46 59.9, 43.8,
2 2
[
18 H, s, 2 × C(CH ) ]
28.4
3
3
(
(
8) Kanemasa, S.; Onimura, K. Tetrahedron 1992, 48, 8631.
9) Katritzky, A. R.; Murugan, R.; Luce, H.; Zerner, M. C. J. Chem.
Soc., Perkin Trans. 2 1987, 1695.
6
7.42–7.24 (10 H, m, 2 × Ph), 152.8, 141.8,
5
4
1
.18 (2 H, s, NCHCHN), 128.8, 127.7,
.98 (2 H, bs, NCH N), 125.7, 80.8,
2
Katritzky, A. R.; Murugan, R.; Luce, H.; Chen, B. C.; Brey, W.
S.; Zerner, M. C. J. Chem. Soc., Perkin Trans. 2 1987, 1701.
Kang, J. B.; Sen, G.; Thyagarajan, B. S. J. Heterocycl. Chem.
.31 [18 H, s, 2 × C(CH ) ] 67.4, 61.9,
3
3
28.2
1
973, 10, 439.
6
f
oil
7.48–7.31 (10 H, m, 2 × Ph), 153.9, 140.9,
(
10) Coldham, I.; Houdayer, P. M. A.; Judkins, R. A.; Witty, D. R.
Synlett 1996, 1109.
11) Wang, W.; Liang, T. C.; Zheng, M.; Gao, X. Tetrahedron Lett.
5.29 (2 H, s, NCHCHN), 129.1, 128.1,
4
.99 (2 H, s, NCH N), 3.63 125.6, 67.3,
2
(
(6 H, s, 2 × OMe)
61.8, 52.9
1
995, 36, 1181.
a
(12) The formation of imidazolidine 6e was accomplished using mo-
nomeric formaldehyde: Schlosser, M.; Jenny, T.; Guggisberg,
Y. Synlett 1990, 704.
Satisfactory microanalyses obtained 6c–e: C ± 0.04, H ± 0.03, N ±
+
0
3
.18. 6f HRMS Found M 340.1422. C H N O requires M
19 20 2 4
40.1423.
b
Data consistent with that in ref 9.
(13) Chooi, S. Y. M.; Leung, P.; Ng, S.; Quek, G. H.; Sim, K. Y.
Tetrahedron: Asymmetry 1991, 2, 981.
(
14) Reduction of the diazide to the diamine 713 was achieved using
hydrogenation over 10% Pd/C in MeOH, rather than using
LiAlH4.
(
1) Buckle, D. R.; Pinto, I. L In Comprehensive Organic Functional
Group Transformations, Vol. 4; Katritzky, A. R.; Meth-Cohn,
O.; Rees, C. W., Eds.; Pergamon: Oxford, 1995; Chapter 4.09;
p 403.
(15) Neumann, W. L.; Rogic, M. M.; Dunn, T. J. Tetrahedron Lett.
1991, 32, 5865.
(16) Haines, A. H.; Morley, C.; Murrer, B. J. Med. Chem. 1989, 32,
742.
(
2) Cuvinot, D.; Mangeney, P.; Alexakis, A.; Normant, J.-F.; Lel-
(17) Coldham, I.; Collis, A. J.; Mould, R. J.; Robinson, D. E. Synthe-
sis 1995, 1147.
louche, J.-P. J. Org. Chem. 1989, 54, 2420.