A new protocol for the synthesis of N(1)-unsubstituted 2-substituted 2 imidazolines

Article abstract of DOI:10.1016/S0040-4020(00)00108-3

Lateral metallation at C-2(α) of 1-tert-butoxycarbonyl-2-methyl-2- imidazoline followed by reaction with a range of C-electrophiles and deprotection with TFA reliably affords N(1)-unsubstituted 2-substituted 2- imidazolines; P- or Se-electrophiles lead to 2-alkenyl-2-imidazolines via Wadsworth-Emmons or selenoxide elimination protocols. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(00)00108-3

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 2061±2074
A New Protocol for the Synthesis of N(1)-Unsubstituted
2-Substituted 2-Imidazolines
*
Raymond C. F. Jones and Paschalis Dimopoulos
Chemistry Department, The Open University, Walton Hall, Milton Keynes MK7 6AA, UK
Received 10 November 1999; revised 12 January 2000; accepted 3 February 2000
AbstractÐLateral metallation at C-2(a) of 1-tert-butoxycarbonyl-2-methyl-2-imidazoline followed by reaction with a range of C-electro-
philes and deprotection with TFA reliably affords N(1)-unsubstituted 2-substituted 2-imidazolines; P- or Se-electrophiles lead to 2-alkenyl-2-
imidazolines via Wadsworth±Emmons or selenoxide elimination protocols. q 2000 Elsevier Science Ltd. All rights reserved.
Introduction
simultaneous double metallation at N-1 and C-2(a) is
limited to 2-arylmethyl-2-imidazolines such as
(Scheme 1).
5
We have for a number of years been engaged in a
programme to utilise the heterocycle 2-imidazoline (4,5-
dihydroimidazole; 1) as a vehicle for carbon atom-transfer,1
and have reported protocols for transfer of C1,2 C2,3 CCN4
and CNC5 fragments. In addition, these methodologies
provide access to new derivatives of the imidazoline
pharmacophore observed in many bioactive molecules, for
example in the cardiovascular arena.6 A key component in
this work has been elaboration at C-2 via lateral metallation
of a C-2 substituent, and our early reports utilised lithiation
at C-2(a) of 1-benzyl-2-methyl-2-imidazoline 2 to achieve
this.3 In combination with a dissolving metal N-debenzyl-
ation, this provided a route to N(1)-unsubstituted imidazo-
lines,3a and for successive functionalisations at C-2(a) and
N-1 of imidazolines.7
Results and Discussion
Limitations to our earlier sequence of C-2(a) elaboration
and N-debenzylation were highlighted by attempts to
prepare 2-(3-butenyl)-2-imidazoline 7 by treatment of the
1-benzyl derivative 6 with Na±NH3(l.). This led to low
recoveries of 7 along with 2-butyl-2-imidazoline 8 (e.g.
with 2.5 equiv. Na, a 2:1 mixture of 7 and 8 in 31%
yield). Imidazoline 8 is possibly derived by an intra-
molecular electron-transfer reduction from the benzyl
substituent before debenzylation.9 In line with our previous
report,7 attempts to avoid N-protection by double deproto-
nation of commercial 2-methyl-2-imidazoline 9 (2 equiv.
n-BuLi, THF, 208C) met with mixed success. For example,
quenching with 3-bromobut-1-ene (1 equiv.) did give
C-alkylation product 7 but only in low yield (10%), and
2 equiv. of the bromide afforded N,C-dialkylation product
11 in only a moderate 45% yield (1 equiv. each of base and
halide leads exclusively to the N-alkylation product 10). In
contrast, similar treatment of 2-benzyl-2-imidazoline 12
Recently we have uncovered limitations to this debenzyl-
ation and we now report a much more widely applicable
protocol using tert-butoxycarbonyl (Boc) as the N-1 protect-
ing group in 3 for elaboration of an imidazoline C-2(a)
nucleophile 4 with a range of electrophiles to generate
ultimately N(1)-unsubstituted imidazolines. Protection at
N-1 is necessary, as we7 and others8 have found that ef®cient
Scheme 1.
Keywords: N(1)-unsubstituted imidazolines; 2-alkenyl imidazolines; Wadsworth±Emmons protocols; selenoxide elimination protocols.
* Corresponding author. Tel.: 144-1509-222557; fax: 144-1509-223926; e-mail: r.c.f.jones@lboro.ac.uk
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00108-3

2062
R. C. F. Jones, P. Dimopoulos / Tetrahedron 56 (2000) 2061±2074
Scheme 2.
resulted in ef®cient N,C-dialkylation to afford imidazoline
13 (91%), con®rming that the extra stabilisation afforded by
a 2-arylmethyl group is needed to effectively support a
dimetallated species (Scheme 2).8
imidazolines 15a±c (Scheme 3), Table 1 entries 9±11.
Treatment of the N-Boc-2-methylimidazoline 3 with
2.2 equiv. each of sec-BuLi and 3-bromopropene (THF,
TMEDA, 2788C) afforded a mixture of monoalkylated
material 14b (56%) and dialkylated imidazoline 15a
(22%), Table 1 entry 12. Attempts at a third alkylation by
deprotonation of 15 were not successful.11 Deprotection of
the C-alkylated imidazolines 14 and 15 was achieved using
acidic conditions (TFA, 208C) to afford NH-heterocycles
16a±k in good yields (65±87%), Table 1. This completes
a simple and robust sequence for elaboration of 2-methyl-2-
imidazoline 9.
A suitable alternative N-protecting group was found to
be tert-butoxycarbonyl (Boc).10 1-tert-Butoxycarbonyl-2-
methyl-2-imidazoline 3 was easily prepared from 2-methyl-
2-imidazoline 9 (Boc2O, Et3N, CH2Cl2, 0!208C; 77%) and
metallated using sec-BuLi (THF, TMEDA, -788C) to afford
a bright yellow solution of lithio-derivative 4. Use of n-BuLi
or LDA, or the absence of TMEDA, produced much less
satisfactory results. The lithiomethyl derivative 4 may be
stabilised by interaction with the carbamate carbonyl
group (Fig. 1). Alkylation was readily accomplished by
reaction with a range of haloalkanes (Scheme 3), to afford
the imidazolines 14a±h in good yields (64±92%), Table 1
entries 1±8. It was possible to complete a second alkylation
under the same conditions to give C-2(a)-branched
The lithio derivative 4 could be quenched with a range of
other electrophiles. Acylation with the esters ethyl acetate,
methyl propenoate and methyl benzoate afforded the
enaminoketones 17a±c (72, 42 and 64%, respectively)
(Scheme 3). Formulation as the enaminoketone tautomers
is supported by spectroscopic data, e.g. dC(CO) 185±195,
and by an X-ray crystal structure determination for 17c
(Fig. 2).12,13 Enediamines 17a and 17c were ef®ciently
deprotected, again using TFA at 208C, to afford 18a and
18c as crystalline solids (81 and 90%).
A major target for our C-2 elaboration is to generate
N-unsubstituted 2-(1-alkenyl)-2-imidazolines, to be accessed
via C-2(a)-heteroatom-substituted derivatives. We have
earlier reported synthesis of the N-benzyl analogues, from
Figure 1.
Scheme 3. Reagents: (i) Boc2O, Et3N, CH2Cl2, 0!208C; (ii) sec-BuLi, THF, TMEDA, 2788C; (iii) R1Hal, 278!208C; (iv) TFA, 208C; (v) R2Hal,
278!208C; (vi) MeCOOEt (for 17a), CH2vCHCOOMe (for 17b) or PhCO2Me (for 17c), 278!208C.

R. C. F. Jones, P. Dimopoulos / Tetrahedron 56 (2000) 2061±2074
Table 1. Alkylation of N-Boc-2-imidazoline 3 and deprotection of imidazolines 14 and 15
2063
Entry
R1Hal
Imidazoline 14
(yield %)
R2Hal
Imidazoline 15
(yield %)
Imidazoline 16
(yield %)
1
2
3
4
5
6
7
8
MeCH2CH2I
CH2vCHCH2Br
CH2vCHCH2CH2Br
CH2vCHCHvCHCH2Br
MeCHvCHCHvCHCH2Br
PhCH2Br
2±PhC6H4CH2Br
2±FurylCH2Cl
14a (86)
14b (82)
14c (64)
14d (67)
14e (81)
14f (92)
14g (81)
14h (71)
14b
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
16a (87)
16b (82)
±
±
16e (67)
16f (73)
16g (80)
16h (65)
16i (67)
16j (67)
16k (81)
9
±
±
CH2vCHCH2Br
PhCH2Br
CH2vCHCH2Br
15a (84)
15b (76)
15c (87)
15a (22)
10
11
12
14b
14c
14b (56)
±
CH2vCHCH2Br (2.2 equiv.)
isolation of the phosphonomethylimidazoline 19, but in
slightly lower overall yield. Again, deprotection with TFA
cleanly afforded the NH compounds 21a±c in good yields
(82, 64 and 91%, respectively), providing chromatography
was performed on alumina rather than silica.14
Using other heteroatom electrophiles, the lithiomethyl
imidazoline 4 was quenched with diphenyl disulphide
to afford the mono-sulphenylated product 24 (42%)
(Scheme 5), along with the disubstituted derivative 22
(28%). Deprotection of the imidazoline 24 (TFA, 208C)
afforded 2-phenylthiomethyl-2-imidazoline 25 (81%). Use
of diphenyl diselenide as electrophile led to 2-phenyl-
selenomethyl-2-imidazoline 26 (52%), again accompanied
by a low yield (8%) of the disubstituted product 23.
Figure 2. X-Ray crystal structure of acylation product 17c.
reaction of 1-benzyl-2-diethylphosphonomethyl-2-imidazo-
line,14 but removal of the N-benzyl group proved impos-
sible. These targets could be prepared from lithiomethyl
intermediate 4 through reaction with heteroatom electro-
philes. Treatment with diethyl chlorophosphate afforded
the phosphonomethyl imidazoline 19 (51%) (Scheme 4).
Deprotonation of phosphonate 19 under the same conditions
(sec-BuLi, THF, TMEDA, 2788C), followed by addition of
an aldehyde gave the 2-(1-alkenyl)imidazolines 20a±c as
products of Wadsworth±Emmons condensation (67, 65
and 66%, using butanal, 2-butenal or benzaldehyde, respec-
tively). The products 20b,c were isolated as E-isomers of
the new double bond, whereas 20a was initially isolated as a
2:1 mixture E:Z which slowly (several days) converted to
E-isomer on standing at 208C. The phosphonylation-
condensation could also be performed in one-pot without
In an alternative approach to 2-(1-alkenyl)-2-imidazolines,
when the phenylselenomethyl derivative 26 was deproto-
nated (sec-BuLi, THF, TMEDA, 2788C) and treated
with a haloalkane (1-iodopropane, 3-bromopropene or benzyl
bromide) the C-2(a) alkylated products 27a±c were formed
(79, 80 and 90%, respectively) (Scheme 5). Attempts to
Scheme 4. Reagents: (i) sec-BuLi, THF, TMEDA, 2788C; (ii) (EtO)2P(O)Cl, 278!208C; (iii) RCHO, 278!208C; (iv) TFA, 208C.

2064
R. C. F. Jones, P. Dimopoulos / Tetrahedron 56 (2000) 2061±2074
Scheme 5. Reagents: (i) sec-BuLi, THF, TMEDA, 2788C; (ii) PhSSPh, 2788C!208C; (iii) TFA, 208C; (iv) PhSeSePh, 2788C!208C; (v)sec-BuLi, THF,
TMEDA, 2788C, RCH2Hal; (vi) mCPBA, CH2Cl2, 08C!208C.
form the selenoxides from imidazolines 27 were unsuccess-
ful. On the other hand, when the N-tert-butoxycarbonyl
group was removed (TFA, 208C), the imidazolines 28a±c
were isolated in good yields (71, 91 and 80%, respectively).
Selenium oxidation (mCPBA, CH2Cl2, 08!208C) followed
by spontaneous elimination15 now proceeded smoothly to
afford in high yield the 2-(1-alkenyl)imidazolines 21c±e
(90, 92 and 92%, respectively), that again had to be puri®ed
over alumina.
methane (120 cm3) at 08C. Di-tert-butyl dicarbonate
(31.11 g, 0.14 mol) was added in small portions and the
reaction mixture stirred at 08C for 10 min. The ice-bath
was removed and the reaction stirred at 208C overnight.
Water was added and the organic layer extracted with
dichloromethane (3£100 cm3). The combined organic
extracts were washed with saturated aq. NaHCO3
(100 cm3), dried and concentrated. The crude product was
distilled under reduced pressure and the title compound
obtained as a white solid (16.75 g, 77%), bp 82±868C at
0.15 mmHg, mp 44±468C (Found: M1 184.1212:
C9H16N2O2 requires: M 184.1212); nmax(®lm)/cm21 2995,
1714; dH (400 MHz) 1.45 [9H, s, C(CH3)3], 2.28 (3H, s,
CH3), 3.68 (4H, s, NCH2CH2N); dC (100 MHz), 17.9
(2-CH3), 28.1 [C(CH3)3], 46.4 and 51.7 (NCH2), 81.4
[C(CH3)3], 150.9 (CO), 158.1 (NCN); m/z 184 (M1, 7%),
128 (7), 84 (20), 70 (24), 57 (100).
We have thus demonstrated the use of 1-tert-butyloxy-
carbonyl-2-(lithiomethyl)-2-imidazoline 4 (prepared by
metallation of 1-tert-butyloxycarbonyl-2-methyl-2-imidazo-
line 3) in a simple and reliable protocol for the elaboration
at C-2(a) of 2-methyl-2-imidazoline.
Experimental
1-Benzyl-2-(but-3-enyl)-2-imidazoline 6. n-Butyllithium
(14 cm3 of a 1.8 M solution in hexanes, 25.28 mmol) was
injected into 1-benzyl-2-methyl-2-imidazoline 2 (4.00 g,
23.00 mmol) in dry THF (80 cm3) stirred at 2788C under
nitrogen. The solution was stirred at 2788C for 30 min and
3-bromobut-1-ene (2.18 cm3, 25.28 mmol) was injected.
The reaction mixture was stirred at 2788C for 4 h and at
208C for 1.5 h, before wet diethyl ether (50 cm3) was added
followed by water (100 cm3). The layers were separated and
the aqueous phase was extracted with diethyl ether
(3£100 cm3). The combined organic extracts were washed
with brine (100 cm3), dried and concentrated. The crude
product was puri®ed by column chromatography on silica
gel eluting with isopropylamine:chloroform (1:99 v/v) to
give the title compound as a yellow oil (3.85 g, 78%)
(Found: MH1 213.1392. C14H13N2 requires: MH
213.1392); nmax(®lm)/cm21 3065, 2934, 2863, 1612, 1496,
1453, 1274, 737; dH (300 MHz) 2.39±2.49 (4H, br m,
CH2CH2CHvCH2), 3.20 and 3.69 (each 2H, t, Jˆ9.7 Hz,
NCH2CH2N), 4.28 (2H, s, CH2Ph), 4.98±5.10 (2H, m,
CHvCH2), 5.82±5.93 (1H, m, CHvCH2), 7.22±7.37
(5H, m, Ar-H); dC (75 MHz) 27.3 and 30.5 (CH2), 50.3
(NCH2) 50.7 (CH2Ph), 53.5 (NCH2), 115.4 (CHvCH2),
General
Melting points were measured on a Ko¯er hot-stage and are
uncorrected. IR spectra were recorded on a Perkin±Elmer
1710 FTIR spectrometer in chloroform unless otherwise
stated. NMR spectra were recorded in deuteriochloroform
unless otherwise stated (internal standard TMS) on JEOL
LAMBDA300 or JEOL EX400 spectrometers; 1H spectra at
300 or 400 MHz and 13C spectra at 75 MHz or 100 MHz,
respectively. Low resolution mass spectra were obtained
using an AEI MS902 spectrometer in EI-positive mode.
Solvents were dried and distilled before use: chloroform
and dichloromethane from CaH2; tetrahydrofuran (THF)
from K immediately before use. Column chromatography
was performed under medium pressure using silica gel
(Kieselgel 60; 220±440 mesh) or neutral alumina
(150 mesh) as indicated. Organic extracts were dried over
anhydrous MgSO4 for 20 min.
1-tert-Butyloxycarbonyl-2-methyl-2-imidazoline 3. Tri-
ethylamine (19.78 cm3, 0.14 mol) was added dropwise to
2-methyl-2-imidazoline (10.00 g, 0.12 mol) in dichloro-

R. C. F. Jones, P. Dimopoulos / Tetrahedron 56 (2000) 2061±2074
2065
127.2, 127.4 and 128.8 (ArCH), 137.4 (CHvCH2), 137.8
(ArC), 166.4 (NCN); m/z 214 (M1, 1%) 213 (2), 203 (1),
190 (1), 174 (3), 160 (1), 149 (2), 133 (41), 120 (59), 106
(21), 91 (100), 77 (3), 65 (15).
(M2H)1 239.1545. C16H20N2´0.2H20 requires: C, 78.81;
H, 8.37; N, 11.49%; M2H 239.1548); nmax(®lm)/cm21
2932, 2862, 1641, 1611, 1416, 1210, 1074, 917, 702; dH
(400 MHz) 2.49±2.56 and 2.84±2.91 (each 1H, m,
CHCH2), 3.13±3.21 and 3.26±3.33 (each 1H, dd, Jˆ8.8
and 17.1 Hz, NCH2CHvCH2), 3.43±3.49 (2H, m,
NCH2CH2N), 3.60±3.65 (1H, dd, Jˆ5.9 and 15.2 Hz,
CHCH2), 3.69±3.84 (2H, m, NCH2CH2N), 4.92±4.97 (2H,
m, CHCH2CHvCH2), 5.01±5.07 (2H, m, NCH2CHvCH2),
5.40±5.50 (1H, m, CHCH2CHvCH2), 5.69±5.75 (1H, m,
NCH2CHvCH2), 7.20±7.32 (5H, m, Ar-H); dC (100 MHz)
39.8 (CH2), 44.5 (CH), 49.1, 50.2 and 52.6 (NCH2), 116.5
and 117.1 (CHvCH2), 127.1, 128.2 and 128.8 (Ar-C),
134.0 and 136.7 (CHvCH2), 140.6 (Ar-C), 167.3 (NCN);
m/z 240 (M1, 51%), 226 (5), 211 (11), 199 (43), 184 (5), 170
(8), 156 (17), 149 (31), 135 (9), 129 (13), 121 (14), 103 (13),
91 (24), 82 (15), 77 (23).
1-(Prop-2-enyl)-2-methyl-2-imidazoline 10. n-Butyl-
lithium (14.28 cm3 of a 2.0 M solution in hexanes,
28.57 mmol) was injected into 2-methyl-2-imidazoline
(2.00 g, 23.80 mmol) in dry THF (150 cm3) stirred at 208C
under nitrogen. The yellow suspension was stirred at 208C
for 50 min. The reaction mixture was cooled to 08C and
3-bromopropene (2.47 cm3, 28.57 mmol) was injected.
The reaction mixture was stirred at 08C for 15 min. and at
208C overnight before the reaction was quenched with water
(100 cm3). The organic layer was extracted with diethyl
ether (3£100 cm3), the combined organic extracts were
washed successively with brine (100 cm3) and water
(100 cm3), dried and concentrated. The crude product was
puri®ed by column chromatography on silica gel
(0:100!3:97 v/v isopropylamine:ethyl acetate) to give the
title compound as a yellow oil (1.30 g, 44%) (Found: M1
124.0999. C7H12N2 requires: M 124.1000); nmax(®lm)/cm21
2934, 2866, 1616, 1490, 1420, 1258, 934; dH (400 MHz)
1.93 (3H, s, CH3), 3.26±3.31 and 3.63±3.68 (each 2H, t,
Jˆ9.8 Hz, NCH2CH2N), 3.72 (2H, d, Jˆ 5.8 Hz,
NCH2CHvCH2), 5.17±5.22 (2H, m, CHvCH2), 5.72±
5.82 (1H, m, CHvCH2); dC (100 MHz), 13.9 (CH3), 49.4,
49.9 and 51.9 (NCH2), 117.1 (CHvCH2), 133.1
(CHvCH2), 164.3 (NCN); m/z 124 (M1, 27%), 110 (1),
97 (5), 83 (24), 67 (19), 54 (100), 42 (30), 28 (17).
General method for synthesis of 2-substituted 1-tert-
butyloxycarbonyl-2-imidazolines 14 and 15
sec-Butyllithium (solution in hexanes) was injected
into 1-tert-butyloxycarbonyl-2-methyl-2-imidazoline 3 or
1-tert-butyloxycarbonyl-2-substituted-2-imidazoline 14 in
dry THF/TMEDA (25±30:1 v/v; 0.1 M in imidazoline) stir-
red at 2788C under nitrogen. The bright yellow solution
produced was stirred for 20 min at 2788C. The organo-
halide electrophile was injected (when liquid) or added by
cannula as a solution in THF (when solid) to the reaction
mixture at 2788C under nitrogen. The reaction was allowed
to warm to 208C overnight. The reaction was quenched with
water (100 cm3), the organic layer was extracted with
diethyl ether (3£100 cm3) and the combined extracts were
washed successively with saturated aq. NaHCO3 (100 cm3),
water (100 cm3) and brine (100 cm3), dried and concen-
trated. The crude product was puri®ed by column chromato-
graphy on silica (1:9!2:3 v/v ethyl acetate:hexane) to give
the compound 14 or 15, respectively.
2-(But-3-enyl)-1-(prop-2-enyl)-2-imidazoline 11. Prepared
by the method described above for 10, but using n-butyl-
lithium (25.88 cm3 of a 1.8 M solution in pentanes,
46.62 mmol), 2-methyl-2-imidazoline
3 (1.78 g, 21.19
mmol) and 3-bromopropene (4.00 cm3, 46.62 mmol). A
milky suspension was observed before addition of the
bromide, when a clear solution was formed. Column
chromatography on silica gel (0:100!4:96 v/v isopropyl-
amine:ethyl acetate) gave the title compound as a yellow
oil (1.56 g, 45%) (Found: M1 165.1391. C10H16N2 requires:
M 165.1391); nmax(®lm)/cm21 2977, 2932, 2862, 1642,
1615, 1486, 1418, 1258, 1213, 995, 915; dH (300 MHz)
2.24±2.29 (2H, m, CH2CH2CHvCH2), 2.37±2.44 (2H, m,
CH2CH2CHvCH2), 3.27 and 3.69 (each 2H, t, Jˆ9.7 Hz,
NCH2CH2N), 3.71 (2H, d, Jˆ4.0 Hz, NCH2CHvCH2),
4.97±5.10 (2H, m, CH2CH2CHvCH2), 5.15±5.22 (2H, m,
NCH2CHvCH2), 5.71±5.92 (2H, m, 2£CHvCH2); dC
(75 MHz), 27.1 and 30.4 (CH2), 49.2, 50.1 and 52.2
(NCH2), 115.1 and 117.0 (CHvCH2), 133.8 and 137.5
(CHvCH2), 166.5 (NCN); m/z 164 (M1, 1%), 163 (4),
149 (4), 135 (2), 123 (10), 109 (3), 98 (2), 83 (32), 70
(100), 55 (29), 41 (65).
2-Butyl-1-tert-butyloxycarbonyl-2-imidazoline 14a. Pre-
pared by the general method, using 1-tert-butyloxycarbonyl-
2-methyl-2-imidazoline 3 (2.00 g, 10.86 mmol), sec-butyl-
lithium (9.19 cm3 of
a 1.3 M solution in hexanes,
11.95 mmol) and 1-iodopropane (1.16 cm3, 11.95 mmol).
The title compound was obtained as a colourless oil (2.10 g,
86%) (Found: C, 63.29; H, 9.42; N, 12.29%; M1 226.1681.
C12H22N2O2 requires: C, 63.69; H, 9.80; N, 12.38%; M
226.1681); nmax(®lm)/cm21 2960, 2875, 1722, 1642, 1369,
1322, 1151, 1004; dH (400 MHz) 0.92 (3H, t, Jˆ7.3 Hz,
CH2CH3), 1.40 (2H, m, CH2CH3), 1.50 [9H, s, C(CH3)3]
1.63 (2H, m, CH2CH2CH3), 2.72 (2H, t, Jˆ8.0 Hz,
CH2CH2CH2CH3), 3.75 (4H, s, NCH2CH2N); dC (75 MHz),
13.9 (CH2CH3), 22.5 (CH2), 28.2 [C(CH3)3], 28.7 and 30.6
(CH2), 46.7 and 51.80 (NCH2), 81.5 [C(CH3)3], 150.8 (CO),
161.6 (NCN); m/z 226 (M1, 0.8%), 184 (1), 171 (2), 128 (2),
85 (3), 58 (8).
2-(1-Phenylbut-3-enyl)-1-(prop-2-enyl)-2-imidazoline 13.
Prepared by the method described above for 10, but using
n-butyllithium (15.70 cm3 of a 2.5 M solution in hexanes,
39.37 mmol), 2-benzyl-2-imidazoline 12 (3.00 g, 18.75
mmol) and 3-bromopropene (3.40 cm3, 39.37 mmol). A
yellow suspension was observed before addition of the
bromide, when a clear yellow solution was formed. Column
chromatography gave the title compound as a yellow oil
(4.10 g, 91%) (Found: C, 78.72; H, 8.36; N, 11.41%;
2-(But-3-enyl)-1-tert-butyloxycarbonyl-2-imidazoline 14b.
Prepared by the general method, using 1-tert-butyloxy-
carbonyl-2-methyl-2-imidazoline 3 (4.00 g, 21.74 mmol),
sec-butyllithium (26.08 cm3 of a 1 M solution in hexanes,
26.08 mmol) and 3-bromo-1-propene (2.25 cm3, 26.08
mmol). The title compound was obtained as a colourless

2066
R. C. F. Jones, P. Dimopoulos / Tetrahedron 56 (2000) 2061±2074
oil (4.00 g, 82%) (Found: C, 63.20; H, 8.78; N, 12.72%;
MH1 225.1603. C12H20N2O2´0.2H2O requires: C, 63.24;
H, 9.02; N, 12.29%; MH 225.1603); nmax(®lm)/cm21
2960, 2934, 1720, 1640, 1369, 1150; dH (400 MHz) 1.50
[9H, s, C(CH3)3], 2.40 (2H, q, Jˆ8.0 Hz, CH2CHvCH2),
2.78 (2H, t, Jˆ8.0 Hz, CH2CH2CHvCH2), 3.77 (4H, s,
NCH2CH2N), 5.00±5.10 (2H, m, CHvCH2), 5.84 (1H, m,
CHvCH2); dC (100 MHz) 27.9 [C(CH3)3], 30.0 and 30.4
(CH2), 46.6 and 51.8 (NCH2), 81.4 [C(CH3)3], 114.8
(CHvCH2), 137.3 (CHvCH2), 150.7 (CO), 160.57
(NCN); m/z 225 (MH1, 0.9%), 208 (1), 169 (17), 124
(12), 97 (4), 84 (5), 58 (16).
Jˆ7.2 Hz, CHvCHCH2CH2), 2.76 (2H, t, Jˆ8.0 Hz,
CHvCHCH2CH2), 3.72 (4H, s, NCH2CH2N), 5.58±5.63
and 5.98±6.10 (each 2H, m, CHvCHCHvCH); dC
(100 MHz) 17.9 (CH3CHvCH), 28.2 [C(CH3)3], 29.3 and
30.6 (CH2), 46.7 and 51.9 (NCH2), 81.5 [C(CH3)3], 127.2,
130.2, 130.8 and 131.4 (CH), 150.8 (CO), 160.7 (NvC±N);
for E,Z-isomer dH (400 MHz) 1.11 (3H, d, Jˆ6.8 Hz,
CH3CHvCH), 1.50 [9H, s, C(CH3)3], 2.42 (2H, q,
Jˆ7.2 Hz, CHvCHCH2CH2), 2.76 (2H, t, Jˆ8.0 Hz,
CHvCHCH2CH2), 3.72 (4H, s, NCH2CH2N), 4.97 (1H, d,
Jˆ10.2 Hz, CHvCHCHvCH), 5.12 (1H, d, Jˆ17.1 Hz,
CHvCHCHvCH), 5.98±6.10 and 6.28±6.35 (each 1H, m,
CHvCHCHvCH); dC (100 MHz) 17.9 (CH3CHvCH),
28.2 [C(CH3)3], 34.3 and 37.5 (CH2), 46.7 and 51.9
(NCH2), 81.5 [C(CH3)3], 127.1, 128.5, 137.6 and 139.1
(CH), 150.8 (CO), 160.7 (NCN); m/z 264 (M1, 0.7%), 208
(65), 193 (35), 179 (23), 149 (33), 135 (19), 123 (20), 109
(48), 83 (39), 57 (100).
1-tert-Butyloxycarbonyl-2-(pent-4-enyl)-2-imidazoline
14c. Prepared by the general method, using 1-tert-butyloxy-
carbonyl-2-methyl-2-imidazoline 3 (1.50 g, 8.15 mmol),
sec-butyllithium (6.89 cm3 of a 1.3 M solution in hexanes,
8.96 mmol) and 4-bromobut-1-ene (0.91 cm3, 8.96 mmol).
The title compound was obtained as a colourless oil (1.25 g,
64%) (Found: MH1 239.1759. C13H22N2O2 requires: MH
239.1759); nmax(®lm)/cm21 2977, 2934, 1719, 1641, 1369,
1148; dH (400 MHz) 1.50 [9H, s, C(CH3)3], 1.73±1.80 (2H,
m, CH2CH2CHvCH2), 2.13±2.18 (2H, m, CH2CHvCH2),
2.71 (2H, t, J 7.5, CH2CH2CH2CHvCH2), 3.73 (4H, s,
NCH2CH2N), 4.97±5.07 (2H, m, CHvCH2), 5.78±5.88
(1H, m, CHvCH2); dC (100 MHz), 25.7 (CH2), 28.0
[C(CH3)3], 30.3 and 33.4 (CH2), 46.6 and 51.8 (NCH2),
81.6 [C(CH3)3], 114.9 (CHvCH2), 138.3 (CHvCH2),
150.9 (CO), 161.5 (NCN); m/z 239 (MH1, 3%), 201 (9),
183 (26), 157 (16), 140 (26), 129 (10), 88 (18), 57 (100).
1-tert-Butyloxycarbonyl-2-(2-phenylethyl)-2-imidazoline
14f. Prepared by the general method, using 1-tert-butyloxy-
carbonyl-2-methyl-2-imidazoline 3 (1.00 g, 5.43 mmol),
sec-butyllithium (0.71 cm3 of a 1.3 M solution in hexanes,
5.97 mmol) and benzyl bromide (0.71 cm3, 5.97 mmol).
The title compound was obtained as a colourless oil
(1.36 g, 92%) (Found: C, 70.04; H, 8.07; N, 10.16%; M1
274.1681. C16H22N2O2 requires: C, 70.04; H, 8.08; N, 10.21;
M 274.1681); nmax(®lm)/cm21 2977, 2934, 1718, 1644,
1370, 1143; dH (400 MHz) 1.50 [9H, s, C(CH3)3], 3.00
(4H, br s, CH2CH2Ph), 3.75 (4H, s, NCH2CH2N), 7.20±
7.50 (5H, m, Ar-H); dC (100 MHz) 28.2 [C(CH3)3], 32.5
and 32.6 (CH2), 46.8 and 52.0 (NCH2), 81.5 [C(CH3)3],
125.9, 128.3, 128.4 and 141.3 (Ar-C), 151.0 (CO), 160.90
(NCN); m/z 274 (M1, 0.6%), 218 (49), 174 (8), 145 (6), 97
(11).
1-tert-Butyloxycarbonyl-2-(hexa-3,5-dienyl)-2-imidazo-
line 14d. Prepared by the general method, using 1-tert-butyl-
oxycarbonyl-2-methyl-2-imidazoline 3 (1.20 g, 6.52 mmol),
sec-butyllithium (6.01 cm3 of a 1.3 M solution in hexanes,
7.82 mmol) and 1-bromopenta-2,4-diene (1.l5 g, 7.82
mmol). The title compound was obtained as a colourless
oil (1.09 g, 67%) (Found: C, 65.70; H, 8.84; N, 10.94%;
MH1 251.1755. C14H22N2O2´0.4H2O requires: C, 65.42;
H, 8.86; N, 10.88%; MH 251.1759); nmax(®lm)/cm21
2977, 1718, 1643, 1369, 1317, 1256, 1143, 1005, 768; dH
(300 MHz) 1.50 [9H, s, C(CH3)3], 2.48 (2H, q, Jˆ7.1 Hz,
CHvCHCH2CH2), 2.79 (2H, t, Jˆ7.8 Hz, CHvCHCH2CH2),
3.74 (4H, s, NCH2CH2N), 4.97 (1H, dd, Jˆ1.2 and 11.6 Hz,
CHvCHH), 5.10 (1H, dd, Jˆ1.2 and 16.8 Hz, CHvCHH),
5.72±5.81, 6.05±6.14 and 6.10±6.34 (each 1H, m,
CHvCHCHvCH2); dC (75 MHz) 28.2 [C(CH3)3], 29.4 and
30.5 (CH2), 46.8 and 52.0 (NCH2), 81.6 [C(CH3)3], 115.2
(CH2vCH), 130.9, 133.7 and 137.1 (CHvCHCHvCH2),
150.9 (CO), 160.7 (NCN); m/z 251 (MH1, 100%), 195
(21), 185 (10), 151 (11), 135 (2), 129 (4), 99 (2), 85 (9).
1-tert-Butyloxycarbonyl-2-[2-(2-phenyl)phenylethyl]-2-
imidazoline 14g. Prepared by the general method, using
1-tert-butyloxycarbonyl-2-methyl-2-imidazoline 3 (1.00 g,
5.43 mmol), sec-butyllithium (5.43 cm3 of a 1.1 M solution
in hexanes, 5.97 mmol) and 2-phenylbenzyl bromide
(1.09 cm3, 5.97 mmol). The title compound was obtained
as a colourless oil (1.55 g, 81%) (Found: C, 74.79; H,
7.52; N, 7.53%; M1 350.1995. C22H26N2O2´0.1H2O
requires: C, 75.00; H, 7.44; N, 7.95%; M 350.1994);
n
max(®lm)/cm21 2977, 2934, 1718, 1642 1480, 1370,
1145; dH (400 MHz) 1.47 [9H, s, C(CH3)3], 2.85 (2H, t,
Jˆ8.0 Hz, CH2Ar), 2.98 (2H, t, Jˆ8.0 Hz, CH2CH2Ar),
3.65 (4H, s, NCH2CH2N), 7.15±7.40 (9H, m, Ar-H); dC
(100 MHz) 28.0 [C(CH3)3], 29.5 and 32.3 (CH2), 46.6 and
51.9 (NCH2), 81.4 [C(CH3)3], 125.9, 126.7, 127.5, 128.1,
129.2, 130.1, 138.7, 141.7 and 141.9 (Ar-C), 150.8 (CO),
160.7 (NCN); m/z 350 (M1, 9%), 294 (48), 249 (60), 217
(12), 165 (39), 115 (97), 97 (11), 71 (14), 57 (100).
1-tert-Butyloxycarbonyl-2-(hepta-3,5-dienyl)-2-imidazo-
line 14e. Prepared by the general method, using 1-tert-butyl-
oxycarbonyl-2-methyl-2-imidazoline 3 (1.50 g, 8.15 mmol),
sec-butyllithium (6.89 cm3 of a 1.3 M solution in hexanes,
8.96 mmol) and 1-bromohexa-2,4-diene (1.44 g, 8.96 mmol).
The title compound was obtained as a mixture of geometric
isomers (4:1 E,E:E,Z) as a colourless oil (1.55 g, 81%)
(Found: M1 264.1474. C15H24N2O2 requires: M 264.1473);
1-tert-Butyloxycarbonyl-2-[2-(2-furyl)ethyl]-2-imidazo-
line 14h. Prepared by the general method, using 1-tert-
butyloxycarbonyl-2-methyl-2-imidazoline 3 (2.00 g, 10.86
mmol), sec-butyllithium (14.94 cm3 of a 0.8 M solution in
hexanes, 11.95 mmol) and furfuryl chloride (1.20 g,
11.97 mmol). The title compound was obtained as a colour-
less oil (2.03 g, 71%) (Found: C, 60.88; H, 7.48; N, 10.08%;
M1 264.1474. C14H20N2O2´0.8H2O requires: C, 60.34; H,
n
max(®lm)/cm21 2977, 2934, 1718, 1644, 1479, 1369, 1331,
1222, 1147, 1000; for E,E-isomer dH (400 MHz) 1.50 [9H, s,
C(CH3)3], 1.71 (3H, d, Jˆ6.8 Hz, CH3CHvCH), 2.42 (2H, q,

R. C. F. Jones, P. Dimopoulos / Tetrahedron 56 (2000) 2061±2074
2067
7.18, N, 10.05%; M 264.1473); nmax(®lm)/cm21 2977, 2934,
1718, 1644, 1479, 1369, 1331, 1222, 1147, 1000; dH
(400 MHz) 1.45 [9H, s, C(CH3)3], 2.92±3.02 (4H, br m,
CH2CH2Furyl), 3.68 (4H, s, NCH2CH2N), 5.95 (1H, d,
Jˆ2.9 Hz, Furyl H-3), 6.18 (1H, dd, Jˆ1.5 and 2.9 Hz,
Furyl H-4), 7.28 (1H, d, Jˆ1.5 Hz, Furyl H-5); dC
(100 MHz) 25.0 (CH2), 28.2 [C(CH3)3], 29.5 (CH2), 46.8
and 51.9 (NCH2), 81.8 [C(CH3)3], 105.0, 110.1 and 140.9
(Furyl-C), 150.8 (CO), 154.9 (Furyl-C), 160.4 (NCN); m/z
264 (M1, 2%), 208 (68), 191 (16), 163 (41), 135 (55), 121
(24), 94 (17), 84 (15), 81 (33), 70 (14), 58 (100).
cm21 3076, 2977, 2933, 2878, 1718, 1640, 1479, 1455,
1363, 1321, 1215, 1175, 1157, 1005; dH (400 MHz) 1.50
[9H, s, C(CH3)3], 1.60±1.70 and 1.77±1.84 (each 1H, m,
CH2CH2CHvCH2), 2.03±2.15 (2H, m, CH2CH2CHvCH2),
2.26±2.34 and 2.39±2.49 (each 1H, m, CHCH2CHvCH2),
3.50±3.58 (1H, m, CHCH2CHvCH2), 3.77 (4H, s,
NCH2CH2N), 4.90±5.07 (4H, m, 2£CHvCH2), 5.75±5.86
(2H, m, 2£CHvCH2); dC (100 MHz), 28.5 [C(CH3)3], 31.4,
31.5 and 37.4 (CH2), 37.7 (CH), 47.2 and 51.9 (NCH2),
114.7 and 116.7 (CHvCH2), 136.1 and 138.9 (CHvCH2),
151.0 (CO), 164.1 (NCN); m/z 279 (MH1, 12%), 223 (82),
179 (14), 168 (12), 137 (8), 123 (9), 97 (13), 67 (11), 57
(100).
1-tert-Butyloxycarbonyl-2-[1-(prop-2-enyl)but-3-enyl]-
2-imidazoline 15a. Prepared by the general method, using
2-(but-3-enyl)-1-tert-butyloxycarbonyl-2-imidazoline 14b
(0.60 g, 2.67 mmol), sec-butyllithium (2.67 cm3 of a
1.1 M solution in hexanes, 2.94 mmol) and 3-bromopropene
(0.25 cm3, 2.94 mmol). The title compound was obtained as
a colourless oil (0.59 g, 84%) (Found: MH1 265.1916.
C15H24N2O2 requires: M 265.1916); nmax(®lm)/cm21 2996,
2972, 1720, 1644, 1483, 1369, 1329, 1149, 1010, 915; dH
(400 MHz) 1.52 [9H, s, C(CH3)3], 2.29±2.35 and 2.40±2.50
(4H, 2£m, 2£CH2CHvCH2), 3.58 (1H, apparent t,
Jˆ6.6 Hz, CHCH2CHvCH2), 3.77 (4H, s, NCH2CH2N),
4.98±5.08 (4H, m, 2£CHvCH2), 5.75±5.86 (2H, m,
2£CHvCH2); dC (75 MHz), 28.3 [C(CH3)3], 36.6 and
37.8 (CH2), 47.1 and 51.9 (NCH2), 81.7 [C(CH3)3], 116.6
(CHvCH2), 136.1 (CHvCH2), 150.8 (CO), 163.6 (NCN);
m/z 265 (MH1, 2%), 209 (19), 191 (5), 165 (27), 154 (14),
149 (14), 123 (25), 108 (8), 83 (3), 57 (100).
General method for synthesis of 2-alkyl-substituted
2-imidazolines 16
TFA was added to the 2-substituted 1-tert-butyloxycarbonyl-
2-imidazoline 14 or 15 and the resulting solution was stirred
at 208C for 20±60 min. The TFA was removed under
reduced pressure and the imidazoline tri¯uoroacetate salt
was dissolved in dichloromethane (100 cm3). The solution
was then washed with aq. NaOH (10% w/v; 100 cm3) and
the organic layer was dried and concentrated. The crude
product was puri®ed by column chromatography on silica
(0:100!2:98 v/v isopropylamine:ethyl acetate) to give the
imidazoline 16.
2-Butyl-2-imidazoline 16a. Prepared by the general
method, using 2-butyl-1-tert-butyloxycarbonyl-2-imidazo-
line 14a (1.25 g, 5.53 mmol) and TFA (3 cm3). The title
compound was obtained as white crystals (0.61 g, 87%),
mp 39±418C (Found: C, 66.32; H, 10.94; N, 21.96%;
MH1 127.1235. C7H14N2 requires C, 66.62; H, 11.18; N,
22.20%; M 127.1235); nmax(KBr)/cm21 3230, 2958, 2871,
1615, 1495, 1467, 1289, 1268; dH (400 MHz) 0.92 (3H, t,
Jˆ7.2 Hz, CH3), 1.31±1.41 (2H, m, CH2CH3), 1.57±1.64
(2H, m, CH2CH2CH3), 2.32 (2H, t, Jˆ7.8 Hz,
CH2CH2CH2CH3), 3.70 (4H, s, NCH2CH2N); dC
(75 MHz) 13.8 (CH3), 22.5, 28.8 and 29.2 (CH2), 49.9
(NCH2), 168.1 (NCN); m/z 127 (M1, 80%), 115 (5), 98
(8), 84 (100), 73 (15), 69 (11), 57 (15), 44 (23).
1-tert-Butyloxycarbonyl-2-(1-phenylmethylbut-3-enyl)-
2-imidazoline 15b. Prepared by the general method, using
2-(but-3-enyl)-1-tert-butyloxycarbonyl-2-imidazoline 14b
(0.30 g, 1.34 mmol), sec-butyllithium (1.47 cm3 of a
1.0 M solution in hexanes, 1.47 mmol) and benzyl bromide
(0.18 cm3, 1.47 mmol). The title compound was obtained as
a yellow oil (0.32 g, 76%) (Found: C, 71.82; H, 8.38; N,
9.45%; M1 314.1995. C14H18N2 requires: C, 71.49; H, 8.67;
N, 9.26%; M 314.1994); nmax(®lm)/cm21 2976, 1669, 1610,
1296, 1200, 1178, 1130; dH (400 MHz) 1.50 [9H, s,
C(CH3)3], 2.27±2.34 and 2.40±2.47 (each 1H, m,
CH2CHvCH2), 2.78±2.84 (1H, dd, Jˆ7.8 and 13.6 Hz,
CHHPh), 3.02±3.07 (1H, dd, Jˆ7.6 and 13.6 Hz,
CHHPh), 3.60±3.77 (4H, m, NCH2CH2N), 3.87±3.92 (1H,
m, CHCH2Ph), 5.00±5.05 (2H, m, CHvCH2), 5.65±5.75
(1H, m, CHvCH2), 7.15±7.28 (5H, m, Ar-H); dC
(100 MHz), 28.2 [C(CH3)3], 36.6 and 38.8 (CH2), 39.6
(CH), 46.9 and 51.8 (NCH2), 81.5 [C(CH3)3], 116.6
(CHvCH2), 126.0, 128.1 and 129.3 (Ar-C), 135.9
(CHvCH2), 139.9 (Ar-C), 150.6 (CO), 163.5 (NCN); m/z
315 (MH1, 2%), 259 (24), 217 (26), 213 (15), 173 (24), 167
(28), 123 (26), 91 (21), 57 (100).
2-(But-3-enyl)-2-imidazoline 16b. Prepared by the general
method, using 2-(but-3-enyl)-1-tert-butyloxycarbonyl-2-
imidazoline 14b (1.45 g, 6.47 mmol) and TFA (3 cm3).
The title compound was obtained as a white solid (0.66 g,
82%), mp 29±318C (Found: MH1 124.1000. C7H12N2
requires: M 124.1000); nmax(®lm)/cm21 3200, 2934, 1610,
1540, 1369, 1150; dH (400 MHz) 2.37±2.45 (4H, br m,
CH2CH2), 3.72 (4H, s, NCH2CH2N), 4.89 (1H, br s, NH),
5.00±5.11 (2H, m, CHvCH2), 5.78±5.87 (1H, m,
CHvCH2); dC (75 MHz) 28.6 and 30.5 (CH2), 49.7
(NCH2), 115.4 (CHvCH2), 137.3 (CHvCH2), 167.2
(NCN); m/z 124 (M1, 2%) 123 (87), 113 (22), 109 (9), 84
(21), 67 (24), 55 (49), 43 (51).
1-tert-Butyloxycarbonyl-2-[1-(prop-2-enyl)pent-4-enyl]-
2-imidazoline 15c. Prepared by the general method, using
1-tert-butyloxycarbonyl-2-(pent-4-enyl)-2-imidazoline 14c
(0.77 g, 3.23 mmol), sec-butyllithium (2.73 cm3 of a
1.3 M solution in hexanes, 3.55 mmol) and 3-bromopropene
(0.31 cm3, 3.55 mmol). The title compound was obtained as
a yellow oil (0.78 g, 87%) (Found: C, 67.14; H, 9.18, N,
9.81%; MH1 279.2084. C16H26N2O2´0.5H20 requires: C,
66.89, H, 9.05, N, 9.75%; MH 279.2072); nmax (®lm)/
2-(Hepta-3,5-dienyl)-2-imidazoline 16e. Prepared by the
general method, using 1-tert-butyloxycarbonyl-2-(hepta-
3,5-dienyl)-2-imidazoline 14e (1.20 g, 4.54 mmol) and
TFA (3 cm3). The title compound was obtained as a mixture
of geometric isomers (4:1 E,E:E,Z) as a white solid (0.50 g,
67%), mp 68±708C (Found: M1 164.1317. C10H16N2

2068
R. C. F. Jones, P. Dimopoulos / Tetrahedron 56 (2000) 2061±2074
requires: M 164.1313); nmax(KBr)/cm21 3154, 3017, 2932,
2862, 1606, 1505, 1475, 1451, 1376, 1284, 1146; for E,E-
isomer dH (400 MHz) 1.73 (3H, d, Jˆ6.8 Hz,
CH3CHvCH), 2.28±2.42 (4H, m, CHvCHCH2CH2),
3.58 (4H, s, NCH2CH2N), 3.80 (1H, br s, NH), 5.52±5.68
and 5.98±6.10 (each 2H, m, CHvCHCHvCH); dC
(100 MHz), 18.0 (CH3), 29.2 and 29.4 (CH2), 49.9
(NCH2), 127.9, 130.3, 131.3 and 136.9 (CH), 167.4
(NCN); for E,Z-isomer dH (400 MHz) 1.08 (3H, d,
and 27.8 (CH2), 49.8 (NCH2), 105.3, 110.2, 141.1 and
154.6 (Furyl-C), 166.7 (NCN); m/z 164 (M1, 100%), 135
(92), 121 (40), 110 (11), 94 (17), 84 (65), 54 (37).
2-[1-(Prop-2-enyl)but-3-enyl]-2-imidazoline 16i. Prepared
by the general method, using 1-tert-butyloxycarbonyl-2-[1-
(prop-2-enyl)but-3-enyl]-2-imidazoline 15a (1.20 g, 4.54
mmol) and TFA (3 cm3). The title compound was obtained
as a yellow oil (0.50 g, 67%) (Found: MH1 165.1388.
C10H16N2 requires: MH 165.1392); nmax(®lm)/cm21 3196,
3077, 2977, 2864, 1642, 1612, 1495, 1472, 1452, 1288;
dH (400 MHz) 2.25±2.35 (4H, m, 2£CHCH2CHvCH2),
2.46 (1H, m, CHCH2CHvCH2), 3.52 (4H, s, NCH2CH2N),
3.95 (1H, br s, NH), 4.95±5.10 (4H, m, CHvCH2), 5.70±
5.86 (2H, m, CHvCH2); dC (100 MHz) 36.9 (CH2), 39.7
(CH), 49.5 (NCH2), 116.8 (CHvCH2), 135.9 (CHvCH2),
169.9 (NCN); m/z 165 (MH1, 100%), 149 (14), 135 (14),
121 (34), 110 (10), 94 (4), 82 (9), 67 (6).
Jˆ6.8 Hz,
CH3CHvCH),
2.28±2.42
(4H,
m,
CHvCHCH2CH2), 3.58 (4H, s, NCH2CH2N), 3.80 (1H, br
s, NH), 5.04 (1H, d, Jˆ10.2 Hz, CHvCHCHvCH), 5.12
(1H, d, Jˆ17.2 Hz, CHvCHCHvCH), 5.98±6.10 and
6.24±6.34 (each 1H, m, CHvCHCHvCH); dC
(100 MHz), 20.1 (CH3), 29.2 and 29.4 (CH2), 49.9
(NCH2), 115.9, 130.3, 131.3 and 139.1 (CH), 166.5
(NCN); m/z 164 (M1, 57%), 149 (93), 135 (57), 123 (25),
97 (22), 84 (100), 79 (44), 54 (35).
2-(2-Phenylethyl)-2-imidazoline 16f. Prepared by the
general method, using 1-tert-butyloxycarbonyl-2-(2-
phenylethyl)-2-imidazoline 14f (2.00 g, 7.29 mmol) and
TFA (4 cm3). The title compound was obtained as a white
solid (0.93 g, 73%), mp 102±1048C (Found: C, 75.83; H,
8.12; N, 15.86%; M1 174.1146. C11H14N2 requires: C,
75.82; H, 8.10; N, 16.07%; M 174.1157); nmax(KBr)/cm21
3158, 3059, 3001, 2926, 2859, 1606, 1498, 1286; dH
(400 MHz) 2.52±2.56 (2H, t, Jˆ7.9 Hz, CH2CH2Ph),
2.94±2.98 (2H, t, Jˆ7.9 Hz, CH2CH2Ph), 3.56 (4H, br s,
NCH2CH2N), 7.20±7.50 (5H, m, Ar-H); dC (100 MHz)
31.1 and 32.8 (CH2), 49.4 (NCH2), 126.2, 128.2, 128.4
and 141.1 (Ar-C), 167.2 (NCN); m/z 174 (M1, 33%), 173
(100), 144 (8), 117 (16), 97 (38), 91 (25), 84 (10), 65 (33).
2-(1-Phenylmethylbut-3-enyl)-2-imidazoline 16j. Prepared
by the general method, using 2-(1-phenylmethylbut-3-
enyl)-1-tert-butyloxycarbonyl-2-imidazoline 15b (0.20 g,
0.64 mmol) and TFA (1 cm3). The title compound was
obtained as a white solid (0.09 g, 67%), mp 76±788C
(Found: M1 214.1470. C14H18N2 requires: M 214.1470);
n
max(KBr)/cm21 3120, 2976, 1669, 1610, 1296, 1200,
1178, 1130; dH (400 MHz) 2.35±2.41 and 2.48±2.56
(each 1H, m, CHCH2CHvCH2), 2.91±2.98 and 3.02±3.09
(each 1H, dd, Jˆ7.6 and 13.6 Hz, CHCH2Ph), 3.20±3.30
(1H, m, CHCH2), 3.99±3.87 (4H, m, NCH2CH2N), 5.05
(1H, d, Jˆ10.2 Hz, CHvCHH), 5.15 (1H, d, Jˆ17.1 Hz,
CHvCHH), 5.65±5.75 (1H, m, CHvCH2), 7.15±7.30 (5H,
m, Ar-H); dC (100 MHz) 36.1 and 37.8 (CH2), 40.2 (CH),
44.7 (NCH2), 118.2 (CHvCH2), 126.9, 128.6, 128.9
(Ar-C), 133.81 (CHvCH2), 137.4 (Ar-C), 173.3 (NCN);
m/z 214 (M1, 18%), 213 (36), 173 (61), 171 (24), 167
(10), 137 (16) 123 (100), 108 (12), 91 (38), 77 (10), 65
(20), 57 (57).
2-[2-(2-Phenyl)phenylethyl]-2-imidazoline 16g. Prepared
by the general method, using 2-[2-(2-phenyl)phenylethyl]-
1-tert-butyloxycarbonyl-2-imidazoline 14g (1.38 g, 3.94
mmol) and TFA (3 cm3). The title compound was obtained
as a white solid (0.79 g, 80%), mp 118±1208C (Found: C,
81.68; H, 7.25; N, 11.17%; (M2H)1 249.1382. C22H26N2O2
requires: C, 81.56; H, 7.25; N, 11.18%; M2H 249.1392);
2-[1-(Prop-2-enyl)pent-4-enyl)-2-imidazoline 16k. Prepared
by the general method, using 1-tert-butyloxycarbonyl-2-[1-
(prop-2-enyl)pent-4-enyl)-2-imidazoline 15c (0.50 g, 1.80
mmol) and TFA (2 cm3). The title compound was obtained
as a pale yellow oil (0.26 g, 81%) (Found: MH1 179.1548.
C11H18N2 requires: MH 179.1548); nmax(®lm)/cm21 3176,
3077, 2976, 2933, 2863, 1641, 1611, 1495, 1472, 1455,
1289; dH (400 MHz) 1.58±176 (2H, m, CHCH2CH2),
2.05±2.15 and 2.26±2.34 (each 2H, m, CH2CHvCH2),
2.38±2.44 (1H, m, CHCH2), 3.56 (4H, s, NCH2CH2N),
4.08 (1H, br s, NH), 4.95±5.10 (4H, m, 2£CHvCH2),
5.72±5.86 (2H, m, 2£CHvCH2); dC (100 MHz), 31.3,
31.8 and 37.6 (CH2), 39.4 (CH), 49.6 (NCH2), 114.4 and
116.5 (CHvCH2), 135.9 and 138.1 (CHvCH2), 169.9
(NCN); m/z 178 (M1, 9%), 163 (18), 135 (32), 124 (86),
123 (100), 109 (28), 97 (49), 67 (21).
n
max(®lm)/cm21 3152, 3104, 2932, 1608, 1558, 1538, 1505,
1479, 1310, 1279; dH (400 MHz) 2.30±2.33 (2H, t,
Jˆ8.0 Hz, CH2CH2Ar), 2.92±2.95 (2H, t, Jˆ8.0 Hz,
CH2CH2Ar), 3.47 (4H, s, NCH2CH2N), 4.11 (1H, br s,
NH), 7.15±7.40 (9H, m, Ar-H); dC (100 MHz), 30.2 and
30.7 (CH2), 50.2 (NCH2), 126.3, 127.0, 127.6, 128.2,
129.1, 129.2, 130.2, 138.3, 141.5 and 141.8 (Ar-C), 167.1
(NCN); m/z 250 (M1, 33%), 249 (100), 173 (30), 165 (40),
152 (13), 115 (10), 97 (25), 71 (22).
2-[2-(2-Furyl)ethyl]-2-imidazoline 16h. Prepared by the
general method, using 1-tert-butyloxy-carbonyl-2-[2-(2-
furyl)ethyl]-2-imidazoline 14h (0.300 g, 1.13 mmol) and
TFA (1 cm3). The title compound was obtained as a white
solid (0.12 g, 65%), mp 98±1008C (Found: M1 164.0950.
C9H12N2 requires: M 164.0949); nmax(KBr)/cm21 3165,
3118, 2927, 2862, 1606, 1511, 1377, 1289, 1001; dH
(400 MHz) 2.48±2.52 (2H, t, Jˆ7.8 Hz, CH2CH2Furyl),
2.88±2.93 (2H, t, Jˆ7.8 Hz, CH2CH2Furyl), 3.48 (4H, s,
NCH2CH2N), 4.31 (1H, br s, NH), 5.95 (1H, d, Jˆ3.0 Hz,
Furyl H-3), 6.21 (1H, dd, Jˆ3.0 and 1.9 Hz, Furyl H-4),
7.29 (1H, d, Jˆ1.9 Hz, Furyl H-5); dC (100 MHz), 25.1
General method for synthesis of 1-tert-butyloxy-
carbonyl-2-(2-oxoalkylidene)imidazolidines 17
sec-Butyllithium (solution in hexanes) was injected into
1-tert-butyloxycarbonyl-2-methyl-2-imidazoline 3 in dry
THF/TMEDA (20:1 v/v; 0.1 M in imidazoline) stirred at
2788C under nitrogen. The bright yellow solution produced

R. C. F. Jones, P. Dimopoulos / Tetrahedron 56 (2000) 2061±2074
2069
was stirred for 20 min at 2788C. Freshly distilled ester
electrophile was injected to the reaction mixture at 2788C
under nitrogen. The mixture was allowed to warm to 208C
overnight. The reaction was quenched with water (100 cm3),
the organic layer was extracted with diethyl ether
(3£50 cm3) and the combined extracts were washed succes-
sively with saturated aq. NaHCO3 (100 cm3), water
(100 cm3) and brine (100 cm3), dried and concentrated.
The crude product was puri®ed by column chromatography
on silica gel (1:9!1:1 v/v ethyl acetate:hexane) to give the
compound 17.
and 3.88 (each 2H, t, Jˆ8.5 Hz, NCH2CH2N), 6.69 (1H, s,
CH), 7.86±7.95 (5H, m, Ar-H), 10.47 (1H, br s, NH); dC
(75 MHz) 28.1 [C(CH3)3], 41.2 and 45.1 (NCH2), 78.8
(CH), 82.9 [C(CH3)3], 126.9, 128.1, 130.4 and 140.5
(Ar-C), 150.5 (CO), 159.1 (NCN), 188.2 (CO); m/z 288
(M1, 11%), 232 (22), 215 (8), 204, (7), 187 (100), 159
(24), 146 (3), 131 (8), 111 (41), 105 (33), 77 (34).
X-Ray crystal structure data for 17c.16 C16H20N2O3,
Mˆ288.34, orthorhombic, aˆ10.6561(2), bˆ15.5737(3),
Ê
Ê 3
cˆ17.8997(3) A, Uˆ2970.54(9) A , Tˆ162(2) K, space
group Pbca, monochromated Mo-Ka radiation, lˆ
0.71073 A, Zˆ8, Dcˆ1.289 Mg m23, F(000)ˆ1232, colour-
Ê
1-tert-Butyloxy-2-(2-oxopropylidene)imidazolidine 17a.
Prepared by the general method, using 1-tert-butyloxy-
carbonyl-2-methyl-2-imidazoline 3 (0.55 g, 2.99 mmol),
sec-butyllithium (3.58 cm3 of a 1.0 M solution in hexanes,
3.58 mmol) and ethyl acetate (0.70 cm3, 6.00 mmol). The
title compound was obtained as white crystals (0.49 g,
72%), mp 125±1278C (Found: C, 58.12; H, 8.11; N,
12.11%; M1 226.1317. C11H18N2O3 requires: C, 58.39; H,
8.02; N, 12.37%; M 226.1317); nmax(KBr)/cm21 3253,
2976, 2936, 1725, 1622, 1557, 1318, 1253, 1149; dH
(400 MHz) 1.45 [9H, s, C(CH3)3], 2.03 (3H, s, CH3), 3.57
and 3.80 (each 2H, t, Jˆ9.0 Hz, NCH2CH2N), 5.92 (1H, s,
CH), 9.96 (1H, br s, NH); dC (100 MHz) 28.0 [C(CH3)3],
29.3 (CH3), 41.1 and 44.9 (NCH2), 81.6 (CH), 82.7
[C(CH3)3], 150.4 (CO), 157.6 (NCN), 195.2 (CO); m/z
226 (M1, 10%), 170 (32), 153 (10), 126 (31), 111 (68), 84
(41), 70 (12), 57 (100), 43 (29).
less bipyramid crystals, dimensions 0.20£0.20£0.20 mm,
m(Mo2Ka)ˆ0.090 mm21, 2.58,2u,26.008, 23802 re¯ec-
tions measured, 2910 unique re¯ections. The structure was
solved by direct methods and re®ned by full-matrix least-
squares on F2. The ®nal cycle (for 270 parameters)
converged with R1ˆ0.0467, wR2ˆ0.0947 (for all data)
and R1ˆ0.0356, wR2ˆ0.0893 [F2.2s(F2)].
2-(2-Oxopropylidene)imidazolidine 18a. TFA (1 cm3)
was added to 1-tert-butyloxy-2-(2-oxopropyl-idene)-2-
imidazoline 17a (0.20 g, 0.88 mmol) and the resulting solu-
tion was stirred at 208C for 60 min. The TFA was removed
under reduced pressure, the imidazolidine salt dissolved in
dichloromethane (20 cm3), and the solution then washed
with aq. NaOH (20 cm3, 10% w/v). The organic layer was
dried and concentrated, and the crude product puri®ed by
column chromatography on silica (0:100!3:97 v/v isopro-
pylamine:chloroform) to give the title compound as a yellow
solid (0.09 g, 81%), mp 157±1598C (Found: M1 126.0793.
C6H10N2O requires: M 126.0793); nmax(KBr)/cm21 3279,
3116, 1605, 1557, 1490, 1323; dH (400 MHz) 1.98 (3H, s,
CH3), 3.55 and 3.70 (each 2H, t, Jˆ7.8 Hz, NCH2CH2N),
4.77 (1H, s, CH), 5.40 and 9.20 (each 1H, br s, NH); dC
[100 MHz; (CD3)2SO] 28.5 (CH3), 41.8 and 43.5 (NCH2),
76.0 (CH), 164.4 (NCN), 188.1 (CO); m/z 126 (M1, 44%),
111 (100), 97 (12), 84 (39), 70 (23), 54 (40), 43 (73).
1-tert-Butyloxy-2-(2-oxobut-3-enylidene)imidazolidine
17b. Prepared by the general method, using 1-tert-butyloxy-
carbonyl-2-methyl-2-imidazoline 3 (2.00 g, 10.87 mmol),
sec-butyllithium (11.95 cm3 of a 1.0 M solution in hexanes,
11.95 mmol) and methyl propenoate (1.86 cm3, 11.95
mmol). The title compound was obtained as white crystals
(1.05 g, 42%), mp 145±1478C (Found: C, 60.63; H, 7.69; N,
11.77%; MH1 239.1383. C12H17N2O3 requires: C, 60.74; H,
7.22; N, 11.80%; MH 239.1396); nmax(KBr)/cm21 3245,
2971, 2930, 1732, 1601, 1541, 1514, 1476, 1313, 1250,
1151, 1040; dH (400 MHz) 1.55 [9H, s, C(CH3)3], 3.67
and 3.88 (each 2H, t, Jˆ7.8 Hz NCH2CH2N), 5.44±5.47
(1H, dd, Jˆ2.0 and 10.4 Hz, CHvCHH), 6.06 (1H, s,
CvCHCO), 6.11±6.16 (1H, dd, Jˆ2.0 and 16.2 Hz,
CHvCHH), 6.34±6.41 (1H, dd, Jˆ10.4 and 17.2 Hz,
CHvCH2), 10.48 (1H, br s, NH); dC (100 MHz) 28.0
[C(CH3)3], 41.3 and 44.0 (NCH2), 81.9 (CvCHCO), 83.0
[C(CH3)3], 122.1 (CHvCH2), 138.3 (CHvCH2), 150.4
(CO), 159.1 (NCN), 186.3 (CO); m/z 239 (M1, 5%), 183
(12), 165 (3), 149 (5), 139 (12), 123 (2), 108 (6), 87 (5), 57
(100).
2-(2-Oxo-2-phenylethylidene)imidazolidine 18c. Prepared
by the method described above for 18a, using TFA (4 cm3)
and 1-tert-butyloxy-2-(2-oxo-2-phenylethylidene)imidazoli-
dine 17c to give the title compound as white crystals
(0.70 g, 90%), mp 203±2058C (lit.17 2088C) (Found: C,
69.88; H, 6.48; N, 14.73%; (M2H)1 187.0864.
C11H12N2O requires: C, 70.19; H, 6.43; N, 14.88%; M2H
187.0871); nmax(KBr)/cm21 3310, 2987, 2860, 1603, 1582,
1554, 1503, 1477, 1451, 1332, 1290, 1213, 1054, 720; dH
[300 MHz; (CD3)2SO] 3.45 and 3.59 (each 2H, t, Jˆ8.0 Hz,
NCH2CH2N), 5.54 (1H, s, CH), 7.30±7.39 (3H, m, Ar-H),
7.69±7.75 (2H, m, Ar-H), 9.28 (1H, br s, NH); dC [75 MHz;
(CD3)2SO], 41.8 and 43.5 (NCH2), 73.1 (CH), 126.1, 127.9,
129.4 and 141.5 (Ar-C), 165.4 (NCN), 181.9 (CO); m/z 188
(M1, 67%), 159 (30), 131 (18), 111 (100), 105 (37), 81 (8),
77 (85).
1-tert-Butyloxy-2-(2-oxo-2-phenylethylidene)imidazoli-
dine 17c. Prepared by the general method, using 1-tert-
butyloxycarbonyl-2-methyl-2-imidazoline 3 (2.00 g, 10.86
mmol), sec-butyllithium (10.86 cm3 of a 1.1 M solution in
hexanes, 11.95 mmol) and methyl benzoate (1.48 cm3,
11.95 mmol). The title compound was obtained as white
crystals (2.00 g, 64%), mp 170±1728C (Found: C, 66.50;
H, 7.00; N, 9.63%; MH1 289.1545. C16H20N2O3 requires:
C, 66.65; H, 6.99; N, 9.71%; MH 289.1552); nmax(KBr)/
cm21 3253, 2979, 1733, 1608, 1557, 1581, 1532, 1358,
1317, 1146; dH (300 MHz) 1.57 [9H, s, C(CH3)3], 3.67
1-tert-Butyloxycarbonyl-2-(diethylphosphonomethyl)-2-
imidazoline 19. sec-Butyllithium (18.39 cm3 of a 1.3 M
solution in hexanes, 23.91 mmol) was injected into 1-tert-
butyloxycarbonyl-2-methyl-2-imidazoline 3 (4.00 g, 21.74
mmol) in dry THF (200 cm3) and TMEDA (5 cm3) stirred at
2788C under nitrogen. The bright yellow solution produced

2070
R. C. F. Jones, P. Dimopoulos / Tetrahedron 56 (2000) 2061±2074
was stirred for 20 min at 2788C under nitrogen before
diethyl chlorophosphate (3.45 cm3, 23.91 mmol) was
injected into the reaction mixture. The mixture was allowed
to warm to 208C overnight and the reaction was quenched
with water (100 cm3). The organic layer was extracted with
diethyl ether (3£100 cm3) and the combined organic
extracts were washed successively with saturated aq.
NaHCO3 (100 cm3), water (50 cm3) and brine (50 cm3),
dried and concentrated. The crude product was puri®ed by
column chromatography on silica gel (0:100!1:99 v/v
isopropylamine:chloroform) to give the title compound as
a yellow oil (3.56 g, 51%) (Found: C, 45.14; H, 7.86; N,
7.90%; M1 320.1501. C13H25N2O5P´1.5H2O requires: C,
44.95; H, 8.13; N, 8.06%; M 320.1501); nmax(®lm)/cm21
2981, 2935, 1713, 1639, 1371, 1254, 1165, 1028; dH
(400 MHz) 1.31±1.34 (6H, t, Jˆ7.2 Hz, 2£CH3CH2), 1.50
[9H, s, C(CH3)3], 3.56±3.62 (2H, d, Jˆ22.0 Hz, CH2P), 3.80
(4H, s, NCH2CH2N), 4.14±4.21 (4H, q, Jˆ7.6 Hz,
CH3CH2); dC (100 MHz) 16.1 (CH3CH2), 27.9 [C(CH3)3],
40.2 (CH3CH2), 46.6 and 52.2 (NCH2), 62.6 (CH2P), 82.1
[C(CH3)3], 150.8 (CO), 153.6 (NCN); m/z 321 (MH1, 2%),
220 (18), 192 (8), 179 (8), 166 (11), 138 (8), 123 (2), 110
(9), 84 (95), 57 (100).
0.92 (3H, t, Jˆ7.2 Hz, CH3CH2), 1.48±1.53 (2H, m,
CH3CH2), 1.52 [9H, s, C(CH3)3], 2.42±2.47 (2H, q,
Jˆ7.6 Hz, CH2CHvCH), 3.71±3.76 and 3.86±3.90 (each
2H, t, Jˆ9.2 Hz, NCH2CH2N), 5.92 (1H, m, CH2CHvCH),
6.42 (1H, d, Jˆ11.6 Hz, CH2CHvCH); dC (100 MHz) 13.9
(CH3), 22.5 (CH2), 28.2 [C(CH3)3], 31.4 (CH2), 45.9 and
52.8 (NCH2), 81.6 [C(CH3)3], 118.8 and 141.3 (CHvCH),
151.1 (CO), 155.8 (NCN); m/z 239 (MH1, 100%), 183 (84),
167 (16), 139 (39), 123 (14), 109 (25), 84 (5), 81 (11), 57
(99).
1-tert-Butyloxycarbonyl-2-(penta-1,3-dienyl)-2-imidazo-
line 20b. Prepared by the general method, using 1-tert-
butyloxycarbonyl-2-(diethylphosphonomethyl)-2-imidazo-
line 19 (1.42 g, 4.44 mmol), sec-butyllithium (6.10 cm3 of a
0.8 M solution in cyclohexane, 4.48 mmol) and 2-butenal
(0.40 ml, 4.48 mmol). The title compound was obtained
after chromatography on silica gel (1:9!2:8 v/v ethyl
acetate:hexane) as an orange solid (0.68 g, 65%), mp 58±
608C (Found: C, 65.82; H, 8.56; N: 11.43%; MH1 237.1603.
C13H20N2O2 requires: C, 66.07; H, 8.53; N, 11.85%; MH
237.1603); nmax(KBr)/cm21 2977, 2934, 1714, 1646,
1617, 1596, 1375, 1166, 1140, 1011; dH (400 MHz) 1.52
[9H, s, C(CH3)3], 1.83 (3H, d, Jˆ6.8 Hz, CH3CH), 3.80 (4H,
s, NCH2CH2N), 5.96±6.01 (1H, m, CH3CH), 6.20 (1H, dd,
Jˆ13.0 and 13.2 Hz, CH3CHvCH), 6.78±6.82 (1H, d,
Jˆ15.6 Hz, CH3CHvCHCHvCH), 7.15±7.21 (1H, dd,
Jˆ13.2 and 15.6 Hz, CH3CHvCHCH); dC (100 MHz)
18.5 (CH3), 28.3 [C(CH3)3], 46.9 and 52.1 (NCH2), 81.7
[C(CH3)3], 117.9, 131.1, 135.7 and 139.3 (CH), 151.2
(CO), 157.5 (NCN); m/z 237 (MH1, 18%), 221 (49), 181
(38), 165 (100), 135 (17), 121 (52), 107 (12), 83 (92), 57
(100).
General method for the synthesis of 1-tert-butyloxy-
carbonyl-2-alkenyl-2-imidazolines 20
sec-Butyllithium (solution in cyclohexane) was added
dropwise to 1-tert-butyloxycarbonyl-2-(diethylphos-phono-
methyl)-2-imidazoline 19 in dry THF/TMEDA (25:1 v/v;
0.1 M in imidazoline) stirred at 2788C under nitrogen.
The red solution produced was stirred for 20 min at
2788C. Freshly distilled aldehyde electrophile was injected
rapidly into the reaction mixture at 2788C under nitrogen.
The reaction was allowed to warm to 208C overnight. The
reaction was quenched with water (100 cm3), the organic
layer extracted with diethyl ether (3£100 cm3) and the
combined organic extracts were washed successively with
saturated aq. NaHCO3 (100 cm3) and brine (100 cm3), dried
and concentrated. The crude product was puri®ed by
column chromatography on silica gel (ethyl acetate:hexane)
to give the compound 20.
1-tert-Butyloxycarbonyl-2-(2-phenylethenyl)-2-imidazo-
line 20c. Prepared by the general method, using 1-tert-
butyloxycarbonyl-2-(diethylphosphonomethyl)-2-imidazo-
line 19 (0.50 g, 1.56 mmol), sec butyllithium (1.72 cm3 of a
1 M solution in cyclohexane, 1.72 mmol) and benzaldehyde
(0.17 cm3, 1.72 mmol). The title compound was obtained
after chromatography on silica gel (1:9!2:3 v/v ethyl
acetate:hexane) as a white solid (0.28 g, 66%), mp 63±
658C (Found: C, 69.90; H, 7.45; N, 9.89%; M1 272.1525.
C16H20N2O2´0.1H2O requires: C, 70.08; H, 7.37; N, 10.22%;
M 272.1525); nmax(KBr)/cm21 2979, 1713, 1641, 1608,
1371, 1316, 1148, 1015, 756; dH (400 MHz) 1.50 [9H, s,
C(CH3)3], 3.80 (4H, s, NCH2CH2N), 7.22±7.32 (4H, m,
PhCHvCH, and Ar-H), 7.47 (3H, m PhCHvCH and
Ar-H); dC (100 MHz), 28.2 [C(CH3)3], 46.9 and 52.1
(NCH2), 81.7 [C(CH3)3], 117.2 (PhCH), 127.5, 128.6,
128.9 and 135.9 (Ar-C), 138.2 (PhCHvCH), 151.1 (CO),
157.4 (NCN); m/z 272 (M1, 13%), 244 (13), 215 (100), 199
(25), 171 (100), 143 (29), 115 (55), 107 (62), 91 (73), 79
(71), 57 (100).
1-tert-Butyloxycarbonyl-2-(pent-1-enyl)-2-imidazoline
20a. Prepared by the general method, using 1-tert-butyloxy-
carbonyl-2-(diethylphosphonomethyl)-2-imidazoline 19 (0.50
g, 1.56 mmol), sec butyl-lithium (1.72 cm3 of a 1 M solution
in cyclohexane, 1.72 mmol) and butanal (0.15 cm3,
1.72 mmol). The title compound was obtained after chroma-
tography on silica gel (1:9!1:1 v/v ethyl acetate:hexane) as
a colourless oil (0.25 g, 67%; 0.19 g of E-isomer and 0.06 g
of Z-isomer) (Found: C, 63.51; H, 9.22; N, 11.74%; MH1
239.1760. C13H22N2O2´0.4.H2O requires: C, 63.31; H, 9.25;
N, 11.36%; MH 239.1759). The Z-isomer converts to the
E-isomer upon standing; data for E-isomer: nmax(®lm)/cm21
2961, 2932, 1718, 1654, 1614, 1370, 1149, 1014; dH
(400 MHz) 0.93 (3H, t, Jˆ7.2 Hz, CH3CH2), 1.48±1.53
(2H, m, CH3CH2), 1.52 [9H, s, C(CH3)3], 2.15±2.20 (2H,
dt, Jˆ7.2 and 7.6 Hz, CH2CHvCH), 3.78 (4H, s,
NCH2CH2N), 6.72 (2H, s, CHvCH); dC (100 MHz), 13.9
(CH3), 21.7 (CH2), 28.2 [C(CH3)3], 35.3 (CH2), 46.8 and
52.0 (NCH2), 81.6 [C(CH3)3], 119.6 and 141.8 (CHvCH),
151.1 (CO), 157.3 (NCN). Data for Z-isomer: dH (400 MHz)
General method for the one-pot synthesis of 1-tert-butyl-
oxycarbonyl-2-alkenyl-2-imidazolines 20
sec-Butyllithium (1.3 M solution in cyclohexane) was
injected into 1-tert-butyloxycarbonyl-2-methyl-2-imidazo-
line 3 in dry THF/TMEDA stirred at 2788C under nitrogen.
The bright yellow solution produced was stirred at 2788C
for 20 min, when diethyl chlorophosphate was injected and

R. C. F. Jones, P. Dimopoulos / Tetrahedron 56 (2000) 2061±2074
2071
the pale yellow solution produced was stirred at 2788C for
1 h and at 208C for 4 h under nitrogen. The reaction mixture
was cooled to 2788C and a second equiv. of sec-butyl-
lithium (1.3 M solution in cyclohexane) was added. The
bright red solution produced was stirred at 2788C for
20 min and freshly distilled aldehyde was injected into it.
The reaction mixture was stirred overnight and allowed to
warm to 208C. The reaction was quenched with water
(100 cm3), the organic layer was extracted with diethyl
ether (3£100 cm3) and the combined organic extracts were
washed successively with saturated aq. NaHCO3 (100 cm3),
water (50 cm3) and brine (50 cm3), dried and concentrated.
The crude product was puri®ed by column chromatography
on silica gel (1:4!2:3 v/v ethyl acetate:hexane) to give the
imidazoline 20.
white gum (0.095 g, 82%) (Found: M1 138.1157. C8H14N2
requires: M 138.1157); nmax(KBr)/cm21 3197, 2956, 2932,
2871, 1699, 1603, 1580, 1500, 1470, 1278, 973; dH
(400 MHz) 0.85 (3H, t, Jˆ7.2 Hz, CH3CH2), 1.37±1.43
(2H, m, CH3CH2), 2.07±2.13 (2H, dt, Jˆ7.2 and 7.6 Hz,
CH2CHvCH), 3.60 (4H, s, NCH2CH2N), 5.95±6.00 (1H,
d, Jˆ16.1 Hz, CH2CHvCH), 6.17±6.24 (1H, m,
CH2CHvCH); dC (100 MHz) 13.6 (CH3), 21.7 and 34.6
(CH2), 50.0 (NCH2), 120.9 and 139.9 (CHvCH), 164.2
(NCN); m/z 138 (M1, 61%), 123 (31), 109 (100), 94 (37),
81 (96), 67 (26), 56 (34), 41(48).
2-(Penta-1,3-dienyl)-2-imidazoline 21b. Prepared by
general method A, using 1-tert-butyloxycarbonyl-2-(penta-
1,3-dienyl)-2-imidazoline 20b (0.54 g, 2.28 mmol) and
TFA (1 cm3). The title compound was obtained after column
chromatography (0:100!2:98 v/v isopropylamine:ethyl
acetate) as a white solid (0.20 g, 64%), mp 112±1148C
(Found: M1 136.1000. C8H12N2 requires: M 136.1000);
One-pot synthesis of 1-tert-butyloxycarbonyl-2-(pent-1-
enyl)-2-imidazoline 20a. Prepared by the general method,
using 1-tert-butyloxycarbonyl-2-methyl-2-imidazoline
3
(2.00 g, 10.86 mmol), sec butyllithium (2£9.19 cm3 of a
1.3 M solution in cyclohexane, 2£11.95 mmol), diethyl
chlorophosphate (1.32 cm3, 10.86 mmol) and butanal
(1.05 cm3, 11.95 mmol) in THF (108 cm3) and TMEDA
(3 cm3). The title compound was obtained as a yellow oil
(0.85 g, 33%; 0.68 g of trans isomer and 0.17 g of cis
isomer), identical to that reported above.
n
max(KBr)/cm21 3178, 2936, 2870, 1651, 1630, 1505,
1475, 1276, 988; dH (400 MHz) 1.83 (3H, d, Jˆ6.8 Hz,
CH3CH), 3.68 (4H, s, NCH2CH2N), 4.40 (1H, br s, NH),
5.95±6.00 (1H, m, CH3CH), 6.02±6.06 (1H, d, Jˆ15.6 Hz,
CH3CHvCHCHvCH), 6.14±6.20 (1H, dd, Jˆ13.0 and
13.2 Hz, CH3CHvCHCHvCH), 6.72±6.68 (1H, dd, Jˆ
13.2 and 15.6 Hz, CH3CHvCHCHvCH); dC (100 MHz)
18.5 (CH3), 49.6 (NCH2), 118.4, 130.5, 135.8 and 138.0
(CH), 164.3 (NCN); m/z 136 (M1, 100%), 135 (64), 121
(49), 106 (66), 92 (26), 79 (38), 66 (22), 41 (18), 18 (16).
One-pot synthesis of 1-tert-butyloxycarbonyl-2-(penta-
1,3-dienyl)-2-imidazoline 20b. Prepared by the general
method, using 1-tert-butyloxycarbonyl-2-methyl-2-imida-
zoline
3
(4.00 g, 21.70 mmol), sec-butyllithium (2£
2-(2-Phenylethenyl)-2-imidazoline 21c. Prepared by
general method A, using 1-tert-butyloxycarbonyl-2-(2-
phenylethenyl)-2-imidazoline 20c (0.17 g, 0.62 mmol) and
TFA (2 cm3). The title compound was obtained after column
chromatography (0:100!2:98 v/v isopropylamine:chloro-
form) as a white solid (0.098 g, 91%), mp 154±1568C
(Found: M1 172.1000. C11H12N2 requires: M 172.1000);
18.4 cm3 of a 1.3 M in cyclohexane, 2£23.90 mmol),
diethyl chlorophosphate (3.45 cm3, 23.90 mmol) and
2-butenal (1.98 cm3, 23.90 mmol) in THF (217 cm3) and
TMEDA (3 cm3). The title compound was obtained as a
white solid (1.75 g, 33%), identical to that reported above.
One-pot synthesis of 1-tert-butyloxycarbonyl-2-phenyl-
ethenyl-2-imidazoline 20c. Prepared by the general
method, using 1-tert-butyloxycarbonyl-2-methyl-2-imida-
zoline 3 (2.00 g, 10.86 mmol), sec butyllithium (2£
n
max(KBr)/cm21 3171, 2926, 2867, 1651, 1597, 1581,
1501, 1292, 982, 760; dH (400 MHz) 3.70 (4H, s,
NCH2CH2N), 4.32 (1H, br s, NH), 6.68 and 7.05 (each 1H,
d, Jˆ16.6 Hz, CHvCH), 7.30 (3H, m, Ar-H), 7.46 (2H, m,
Ar-H); dC (100 MHz) 50.0 (NCH2), 118.3 (CH), 127.2,
128.8, 128.9 and 135.4 (Ar-C), 136.7 (CH), 164.1 (NCN);
m/z 172 (M1, 65%), 171 (79), 143 (23), 128 (13), 115 (100),
103 (8), 77 (17), 57 (36).
9.19 cm3 of
11.95 mmol),
a
1.3 M solution in cyclohexane, 2£
diethyl chlorophosphate
(1.32 cm3,
10.86 mmol) and benzaldehyde (1.21 cm3, 11.95 mmol) in
THF (108 cm3) TMEDA (3 cm3). The title compound was
obtained as a white solid (1.20 g, 40%), identical to that
reported above.
1-tert-Butyloxycarbonyl-2-phenylthiomethyl-2-imidazo-
line 24 and 1-tert-butyloxycarbonyl-2,2-bis(phenylthio)-
methyl-2-imidazoline 22. sec-Butyllithium (4.97 cm3 of a
1.2 M solution in cyclohexane, 5.97 mmol) was injected into
1-tert-butyloxycarbonyl-2-methyl-2-imidazoline 3 (1.00 g,
5.43 mmol) in dry THF (54 cm3) and TMEDA (2 cm3) stir-
red at 2788C under nitrogen. The bright yellow solution
produced was stirred at 2788C for 20 min, when diphenyl
disulphide (1.30 g, 5.97 mmol) in THF (20 cm3) was added
via cannula at 2788C under nitrogen. The reaction mixture
was allowed to warm to 208C overnight. The reaction was
quenched with water (100 cm3), the organic layer was
extracted with diethyl ether (3£100 cm3) and the combined
organic extracts were washed successively with saturated
aq. NaHCO3 (100 cm3), water (50 cm3) and brine
(50 cm3), dried and concentrated. The crude product was
puri®ed by column chromatography on silica gel
General method A for synthesis of 2-alkenyl-2-imidazo-
lines 21
TFA was added to the 2-substituted 1-tert-butyloxycar-
bonyl-2-imidazoline 20 and the resulting solution was
stirred at 208C for 20±60 min. The TFA was removed
under reduced pressure and crude product was puri®ed by
column chromatography on neutral alumina (activation
grade 3) to give the imidazoline 21.
2-(Pent-1-enyl)-2-imidazoline 21a. Prepared by general
method A, using 1-tert-butyloxycarbonyl-2-(pent-1-enyl)-
2-imidazoline 20a (0.20 g, 0.84 mmol) and TFA (1 cm3).
The title compound was obtained after column chromato-
graphy (0:100!2:98 v/v isopropylamine:chloroform) as a

2072
R. C. F. Jones, P. Dimopoulos / Tetrahedron 56 (2000) 2061±2074
(1:9!2:3 v/v ethyl acetate:hexane) to give the monosulphe-
nated 2-imidazoline 24 as a white solid (0.60 g, 38%), mp
77±798C (Found: C, 61.55; H, 6.98; N, 9.50%; M1
292.1245. C15H20N2O2S requires: C, 61.62; H, 6.89; N,
9.58%; M 292.1245); nmax(KBr)/cm21 2974, 1703, 1635,
1483, 1379, 1142, 737; dH (400 MHz) 1.46 (9H, s,
[C(CH3)3], 3.70 (4H, s, NCH2CH2N), 4.07 (2H, s,
PhSCH2), 7.22±7.35 (3H, m, Ar-H), 7.38±7.42 (2H, m,
Ar-H); dC (100 MHz) 28.1 [C(CH3)3], 34.0 (PhSCH2),
46.8 and 52.2 (NCH2), 82.2 [C(CH3)3], 126.4, 128.9,
129.8 and 136.0 (Ar-C), 150.6 (CO), 157.7 (NCN); m/z
292 (M1, 8%), 236 (41), 219 (5), 203 (14), 191 (13), 159
(22), 123 (12), 109 (10), 57 (100); and the disulphenated
2-imidazoline 22 as a white solid (0.65 g, 28%), mp 91±
938C (Found: C, 62.93; H, 6.13; N, 7.03%; M1 400.1279.
C15H20N2O2S requires: C, 62.97; H, 6.04; N, 6.99%; M
400.1279); nmax(KBr)/cm21 2977, 1698, 1634, 1482,
1364, 1133, 1006, 739; dH (400 MHz) 1.52 [9H, s,
C(CH3)3], 3.66±3.68 and 3.74±3.77 (each 2H, t,
Jˆ8.0 Hz, NCH2CH2N), 6.20 (1H, br s, CH), 7.31±7.35
(6H, m, Ar-H), 7.48±7.51 (4H, m, Ar-H); dC (100 MHz)
28.7 [C(CH3)3], 47.5 and 52.4 (NCH2), 54.5 (CH), 82.7
[C(CH3)3], 128.6, 129.2, 132.7 and 134.4 (Ar-C), 150.7
(CO), 157.8 (NCN); m/z 400 (M1, 2%), 291 (19), 235
(100), 191 (38), 139 (43), 121 (27), 110 (21), 97 (80), 77
(18), 70 (23), 57 (85).
aq. NaHCO3 (100 cm3), water (50 cm3) and brine
(50 cm3), dried and concentrated. The crude product was
puri®ed by column chromatography on silica gel
(1:9!2:3 v/v ethyl acetate:hexane) to give the monoselene-
nated 2-imidazoline 26 as a white solid (2.86 g, 52%), mp
76±788C (Found: C, 53.13; H, 6.03; N, 8.29%; M1
340.0689. C15H20N2O2Se requires: C, 53.10; H, 5.94; N,
8.26%; M 340.0689); nmax(KBr)/cm21 2974, 1702, 1636,
1480, 1380, 1141, 732; dH (400 MHz) 1.55 [9H, s,
C(CH3)3], 3.76 (4H, s, NCH2CH2N), 4.05 (2H, s, PhSeCH2),
7.25 (3H, m, Ar-H), 7.60 (2H, m, Ar-H); dC (100 MHz) 26.2
(PhSeCH2), 28.5 [C(CH3)3], 46.6 and 52.2 (NCH2), 82.2
[C(CH3)3], 127.5, 128.7, 130.6 and 133.3 (Ar-C), 150.7
(CO), 159.1 (NCN); m/z 340 (M1, 1.5%), 282 (12), 215
(17), 203 (11), 159 (45), 127 (7), 91 (8), 57 (100); and the
diselenenated 2-imidazoline 23 as a yellow oil (0.63 g, 8%)
(Found: C, 51.58; H, 4.85; N, 5.59%; M1 496.0163.
C21H24N2O2Se2 requires: C, 51.02; H, 4.89; N, 5.67%; M
496.0168); nmax(®lm)/cm21 2977, 2930, 1708, 1628, 1477,
1371, 1141, 1002; dH (300 MHz) 1.47 [9H, s, C(CH3)3],
3.63 and 3.68 (each 2H, t, Jˆ7.0 Hz, NCH2CH2N), 6.14
(1H, br s, CH), 7.25±7.29 (6H, m, Ar-H), 7.59±7.71 (4H,
m, Ar-H); dC (75 MHz) 28.2 [C(CH3)3], 37.5 (CH), 47.3 and
51.9 (NCH2), 82.1 [C(CH3)3], 128.7, 129.1, 135.1 and 131.5
(Ar-C), 150.4 (CO), 159.1 (NCN); m/z 494 (M1, 2%), 439
(1), 397 (1), 395 (1), 339 (2), 314 (12) 283 (11), 234 (7), 157
(100), 130 (8), 117 (21), 97 (18), 77 (100).
2-Phenylthiomethyl-2-imidazoline 25. TFA (2 cm3) was
added to 1-tert-butyloxycarbonyl-2-phenylthiomethyl-2-
imidazoline 24 (0.30 g, 1.02 mmol) and the solution was
stirred at 208C for 1 h. The TFA was removed under reduced
pressure and the imidazoline salt was dissolved in chloro-
form (10 cm3). The solution was then washed with aq.
NaOH (10% w/v; 10 cm3) and the organic layer was dried
and concentrated. The crude product was then puri®ed by
column chromatography on alumina (grade 3) (0:100!1:99
v/v isopropylamine:chloroform) to give the title compound
as a white solid (0.16 g, 81%), mp 83±858C (Found: C,
62.38; H, 6.37; N, 14.51%; M1 192.0721. C10H12N2S
requires: C, 62.47; H, 6.29; N, 14.56%; M 192.0721);
1-tert-Butyloxycarbonyl-2-(1-phenylseleneno-2-phenyl-
ethyl)-2-imidazoline 27a. sec-Butyllithium (0.62 cm3 of a
1.2 M solution in cyclohexane, 0.74 mmol) was injected
into 1-tert-butyloxycarbonyl-2-phenylselenenomethyl-2-
imidazoline 26 (0.21 g, 0.62 mmol) in dry THF (7 cm3)
and TMEDA (0.5 cm3) stirred at2788C under nitrogen.
The brown solution produced was stirred for 20 min at
2788C, when benzyl bromide (0.09 cm3, 0.74 mmol) was
injected to the reaction mixture. The reaction mixture
was allowed to warm to 208C overnight. The reaction was
quenched with water (100 cm3) and the organic layer was
extracted with diethyl ether (3£100 cm3) and the combined
organic extracts were washed successively with saturated
aq. NaHCO3 (100 cm3), water (100 cm3) and brine
(100 cm3), dried and concentrated. The crude product was
puri®ed by column chromatography on silica gel (1:9!2:3
v/v ethyl acetate:hexane) to give the title compound as a
yellow oil (0.21 g, 79%) (Found: C, 60.66; H, 6.27; N,
6.33%; M1 430.1159. C22H26N2O2Se´0.2H2O requires: C,
60.86; H, 6.08; N, 6.45%; M 430.1159); nmax(®lm)/cm21
2977, 1713, 1630, 1370, 1144, 999, 766, 696; dH
(400 MHz) 1.48 [9H, s, C(CH3)3], 3.10±3.18 (1H, m,
CHHPh), 3.38±3.48 (1H, dd, Jˆ6.8 and 13.8 Hz,
CHHPh), 3.60±3.77 (4H, m, NCH2CH2N), 5.15 (1H, br s,
CH), 7.15±7.40 (8H, m, Ar-H), 7.53 (2H, m, Ar-H); dC
(100 MHz) 28.2 [C(CH3)3], 39.0 (CH2Ph), 39.2 (CH), 46.8
and 51.8 (NCH2), 81.8 [C(CH3)3], 126.3, 128.1, 128.4,
128.6, 128.8, 136.5, 137.1 and 139.4 (Ar-C), 150.5 (CO),
160.8 (NCN); m/z 430 (M1, 1%), 374 (5), 324 (5), 293 (3),
217 (32), 173 (24), 141 (19), 123 (31), 77 (18), 57 (100).
n
max(KBr)/cm21 3207, 3057, 2928, 1613, 1482, 1464,
1448, 1439, 1292, 1278, 1094, 980, 734; dH (400 MHz)
3.57 (4H, s, NCH2CH2N), 3.75 (2H, s, PhSCH2), 4.58
(1H, br s, NH), 7.22±7.35 (3H, m, Ar-H), 7.42±7.45 (2H,
m, Ar-H); dC (100 MHz) 31.9 (PhSCH2), 50.2 (NCH2),
126.5, 128.8, 129.3 and 135.0 (Ar-C), 164.3 (NCN); m/z
192 (M1, 100%), 177 (5), 159 (55), 123 (9), 109 (39), 81
(50), 65 (25), 54 (74).
1-tert-Butyloxycarbonyl-2-phenylselenomethyl-2-imi-
dazoline 26 and 1-tert-butyloxycarbonyl-2,2-bis(phenyl-
seleneno)methyl-2-imidazoline 23. sec-Butyllithium (12.32
cm3 of a 1.3 M solution in cyclohexane, 16.02 mmol) was
injected into 1-tert-butyloxycarbonyl-2-methyl-2-imidazo-
line 3 (2.95 g, 16.02 mmol) in dry THF (100 cm3) and
TMEDA (0.5 cm3) stirred at 2788C under nitrogen. The
bright yellow solution produced was stirred at 2788C for
20 min, when diphenyl diselenide (5.00 g, 16.02 mmol) in
THF (60 cm3) was added via cannula. The reaction mixture
was allowed to warm to 208C overnight. The reaction was
quenched with water (100 cm3) and the organic layer was
extracted with diethyl ether (3£100 cm3) and the combined
organic extracts were washed successively with saturated
1-tert-Butyloxycarbonyl-2-(1-phenylselenenobutyl)-2-
imidazoline 27b. Prepared by the general method,
using sec-butyllithium (5.38 cm3 of a 1.3 M solution in
cyclohexane, 7.00 mmol), 1-tert-butyloxycarbonyl-2-

R. C. F. Jones, P. Dimopoulos / Tetrahedron 56 (2000) 2061±2074
2073
phenylselenenomethyl-2-imidazoline 26 (2.00 g, 5.89
mmol) and 1-iodopropane (0.70 cm3, 7.00 mmol) to give
the title compound as a yellow oil (1.80 g, 80%) (Found:
C, 56.98; H, 7.23; N, 7.48%; M1 382.1158. C18H26N2O2Se
solid (1.00 g, 91%), mp 67±698C (Found: C, 55.55; H, 6.56;
N, 9.96%; M1 282.0635. C13H18N2Se requires: C, 55.52; H,
6.45; N, 9.96%; M 282.0635); nmax(KBr)/cm21 3176, 2955,
1605, 1495, 1466, 1276, 978, 746, 694; dH (400 MHz) 0.87
(3H, t, Jˆ7.4 Hz, CH3), 1.34±1.52 (2H, m, CH3CH2), 1.70±
1.80 and 1.86±1.96 (each 1H, m, CH2CH), 3.45 (4H, s,
NCH2CH2N), 3.85 (1H, t, Jˆ8.8 Hz, CH2CH), 4.40 (1H,
br s, NH), 7.28 (3H, m, Ar-H), 7.52 (2H, m, Ar-H); dC
(100 MHz) 13.5 (CH3), 21.4 and 35.1 (CH2), 41.0 (CH),
50.1 (NCH2), 127.9, 128.5, 128.9 and 134.5 (Ar-C), 167.8
(NCN); m/z 282 (M1, 3.5%), 253 (2), 240 (2), 201 (11), 160
(7), 125 (5), 97 (7), 84 (9).
requires: C, 56.69; H, 6.87; N, 7.34; M 382.1158); nmax
-
(®lm)/cm21 2960, 1713, 1613, 1368, 1146; dH (400 MHz)
0.82 (3H, t, Jˆ7.2 Hz, CH3), 1.45 (2H, m, CH3CH2), 1.52
[9H, s, C(CH3)3], 1.68±1.75 and 1.83±1.91 (each 1H, m,
CH2CH), 3.57±3.80 (4H, m, NCH2CH2N), 4.71 (1H, br s,
CH), 7.25 (3H, m, Ar-H), 7.53 (2H, m, Ar-H); dC
(100 MHz) 13.6 (CH3), 21.0 (CH2), 28.2 [C(CH3)3], 33.6
(CH2), 38.8 (CH), 46.8 and 51.8 (NCH2), 81.8 [C(CH3)3],
128.4, 128.5, 128.8 and 136.8 (Ar-C), 150.68 (CO), 161.3
(NCN); m/z 382 (M1, 7%), 326 (33), 284 (15), 245 (32), 201
(27), 169 (30), 141 (14), 125 (58), 123 (13), 78 (9), 57 (100).
2-(1-Phenylselenenobut-3-enyl)-2-imidazoline 28c. Prepared
by the general method, using TFA (1 cm3) and 1-tert-butyl-
oxycarbonyl-2-(1-phenylselenenobut-3-enyl)-2-imidazo-
line 27c (0.29 g, 0.76 mmol). Column chromatography
on silica gel (0:100!4:96 v/v isopropylamine:ethyl acetate)
gave the title compound as a yellow oil (0.17 g, 80%) which
solidi®ed upon standing, mp 41±438C (Found: C, 55.00; H,
5.72; N, 9.40%; M1 280.0478. C13H16N2Se´0.2H2O
requires: C, 54.99; H, 5.78; N; 9.87%; M 280.0478);
1-tert-Butyloxycarbonyl-2-(1-phenylselenenobut-3-enyl)-
2-imidazoline 27c. Prepared by the general method, using
sec-butyllithium (3.09 cm3 of a 1.1 M solution in cyclo-
hexane, 3.4 mmol), 1-tert-butyloxycarbonyl-2-phenyl-
selenenomethyl-2-imidazoline 26 (1.05 g, 3.09 mmol)
and 3-bromopropene (0.29 cm3, 3.40 mmol) to give the
title compound as a yellow oil (1.06 g, 90%) (Found: M1
380.1002. C18H24N2O2Se requires: M 380.1002); nmax(®lm)/
cm21 2977, 1714, 1631, 1478, 1147; dH (400 MHz) 1.52
[9H, s, C(CH3)3], 2.45±2.52 and 2.67±2.74 (each 1H, m,
CH2CHvCH2), 3.60±3.80 (4H, m, NCH2CH2N), 4.75 (1H,
br s, PhSeCH), 5.00±5.09 (2H, m, CHvCH2), 5.80±5.90
(1H, m, CHvCH2), 7.25 (3H, m, Ar-H), 7.55 (2H, m,
Ar-H); dC (100 MHz) 28.2 [C(CH3)3], 37.7 (CH2), 38.3
(PhSeCH), 46.9 and 51.8 (NCH2), 81.8 [C(CH3)3], 116.6
(CHvCH2), 128.2, 128.4 and 128.5 (Ar-C), 135.8
(CHvCH2), 136.8 (Ar-C), 150.6 (CO), 160.6 (NCN); m/z
380 (M1, 1%), 243 (10), 224 (6), 169 (49), 141 (16), 123
(56), 78 (8), 70 (10), 57 (100).
n
max(®lm)/cm21 3175, 3073, 2932, 1607, 1477, 1438,
1286, 919, 740; dH (400 MHz) 2.55±2.60 and 2.70±2.80
(each 1H, m, CH2CHvCH2), 3.50 (4H, s, NCH2CH2N),
3.90 (1H, t, Jˆ8.8 Hz, PhSeCH), 4.75 (1H, br s, NH),
5.10±5.20 (2H, m, CHvCH2), 5.80±5.90 (1H, m,
CHvCH2), 7.26±7.32 (3H, m, Ar-H), 7.57 (2H, m,
Ar-H); dC (100 MHz), 37.2 (CH2), 40.2 (CH), 50.1
(NCH2), 117.4 (CHvCH2), 128.2, 129.1 and 134.9
(Ar-C), 135.2 (CHvCH2), 137.5 (Ar-C), 167.4 (NCN);
m/z 280 (M1, 9%), 279, (17), 239 (13), 199 (61), 157
(12), 123 (100), 97 (14), 77 (19), 67 (16).
General method B for synthesis of 2-alkenyl-2-imidazo-
lines 21
2-(1-Phenylseleneno-2-phenylethyl)-2-imidazoline 28a:
TFA (4 cm3) was added to 1-tert-butyloxycarbonyl-2-(1-
phenylseleneno-2-phenylethyl)-2-imidazoline 27a (1.25 g,
2.91 mmol) and the solution was stirred at 208C for 1 h.
The TFA was removed under reduced pressure and the
imidazoline salt was dissolved in dichloromethane
(20 cm3). The solution was then washed with aq. NaOH
(10% w/v; 30 cm3) and the organic layer was dried and
concentrated. The crude product was puri®ed by column
chromatography on silica gel (ethyl acetate) to give the
title compound as a white solid (0.68 g, 71 %), mp 103-
1058C (Found: C, 61.27; H, 5.53; N, 8.91%; M1
330.0634. C17H18N2Se´0.2H2O requires C, 61.14; H, 5.51;
N, 8.39%; M 330.0634); nmax(®lm)/cm21 3061, 2926, 1601,
1498, 1270, 740, 693; dH (400 MHz) 3.00±3.10 and 3.26±
3.35 (each 1H, dd, Jˆ6.8 and 13.7 Hz, CH2Ph), 3.42 (4H, m,
NCH2CH2N), 4.03 (1H, t, Jˆ6.8 Hz, PhSeCH), 7.10±7.28
(8H, m, Ar-H), 7.48 (2H, m, Ar-H); dC (100 MHz) 39.3
(CH2), 42.1 (CH), 50.1 (NCH2), 126.7, 128.2, 128.4,
128.9, 129.0, 134.4, 134.9 and 138.7 (Ar-C), 167.4
(NCN); m/z 330 (M1, 6%), 249 (62), 239 (26), 173 (100),
158 (12), 132 (14), 115 (15), 105 (26), 91 (22), 77 (22).
A solution of 3-chloroperbenzoic acid in dry dichloro-
methane was added via cannula to the 2-(1-seleneno)-2-
imidazoline 28 in dry dichloromethane at 08C under nitro-
gen. The resulting yellow solution was stirred at 08C for 1 h
and at room temperature for a further 2 h. The dichloro-
methane was removed under reduced pressure and the
crude product was puri®ed by column chromatography on
neutral alumina (activation grade 3) to give the 2-alkenyl-2-
imidazolines 21.
2-(2-Phenylethenyl)-2-imidazoline 21c. Prepared by
general method B, using 2-(1-phenylseleneno-2-phenyl-
ethyl)-2-imidazoline 28a (0.30 g, 0.91 mmol) and 3-chloro-
perbenzoic acid (0.17 g, 1.00 mmol). Chromatography on
alumina (0:100!3:97 v/v isopropylamine:ethyl acetate)
afforded the title compound as a white solid (0.16 g,
90%), m.p 154±1568C, identical to that reported above,
method A.
2-(But-1-enyl)-2-imidazoline 21d. Prepared by general
method B, using 2-(1-phenylselenenobutyl)-2-imidazoline
28b (0.30 g, 1.06 mmol) and 3-chloroperbenzoic acid
(0.20 g, 1.17 mmol). Chromatography on alumina
(0:100!5:95 v/v isopropylamine:ethyl acetate) gave the
title compound as a thick colourless oil (0.12 g, 92%)
(Found: M1 124.1000. C7H12N2 requires: M 124.1000);
2-(1-Phenylselenenobutyl)-2-imidazoline 28b. Prepared
by the general method, using TFA (3 cm3) and 1-tert-butyl-
oxycarbonyl-2-(1-phenylselenenobutyl)-2-imidazoline 27b
(1.50 g, 3.93 mmol) to give the title compound as a yellow

2074
R. C. F. Jones, P. Dimopoulos / Tetrahedron 56 (2000) 2061±2074
max(®lm)/cm21 3197, 2965, 2864, 2873, 1663, 1602, 1500,
R. C. F.; Saunders, J. J. Chem. Soc., Perkin Trans. 1 1986, 1995±
n
1998.
1461, 1274, 986; dH (400 MHz) 1.00 (3H, t, Jˆ 7.2 Hz,
CH3), 2.10±2.20 (2H, m, CH2), 3.60 (4H, s, NCH2CH2N),
3.95 (1H, br s, NH), 5.98 (1H, d, Jˆ 16.6 Hz,
CHvCHCH2), 6.23±6.32 (1H, m, CHvCHCH2); dC
(100 MHz) 12.6 (CH3), 25.6 (CH2), 51.6 (NCH2), 119.9
(CHvCHCH2), 141.3 (CHvCHCH2), 164.0 (NCN); m/z
124 (M1, 84%), 123 (55), 109 (56), 94 (88), 80 (29), 67
(100).
4. Jones, R. C. F.; Hirst, S. C. Tetrahedron Lett. 1989, 30, 5365±
5368; Jones, R. C. F.; Turner, I.; Howard, K. J. Tetrahedron Lett.
1993, 34, 6329±6332.
5. Jones, R. C. F.; Howard, K. J.; Snaith, J. S. Tetrahedron Lett.
1996, 37, 1707±1710; Jones, R. C. F.; Howard, K. J.; Snaith, J. S.
Tetrahedron Lett. 1996, 37, 1711±1713; Jones, R. C. F.; Howard,
K. J.; Snaith, J. S. Tetrahedron Lett. 1997, 38, 1647±1650; Jones,
R. C. F.; Howard, K. J.; Nichols, J. R.; Snaith, J. S. J. Chem. Soc.,
Perkin Trans. 1 1998, 2061±2072.
2-(Buta-1,3-dienyl)-2-imidazoline 21e. Prepared by
general method B, using 2-(1-phenylseleneno-but-3-enyl)-
2-imidazoline 28c (0.30 g, 1.07 mmol) and 3-chloro-
perbenzoic acid (0.22 g, 1.29 mmol). Chromatography on
alumina (0:100!2:98 v/v isopropylamine:ethyl acetate)
gave the title compound as a white solid (0.12 g, 92%),
mp 2208C (decomp.) (Found: M1 122.0844. C7H10N2
requires M 122.0844); nmax(KBr)/cm21 3176, 2936, 2864,
1643, 1614, 1566, 1497, 1276, 1000, 982; dH (400 MHz)
3.70 (4H, s, NCH2CH2N), 4.40 (1H, br s, NH), 5.35±
5.40 (1H, d, Jˆ10.0 Hz, CHvCHH), 5.50 (1H, d,
Jˆ16.6 Hz, CHvCHH), 6.20±6.26 (1H, d, Jˆ16.6 Hz,
CHvCHCHvCH2), 6.43±6.55 (1H, m, CHvCH2), 6.71±
6.80 (1H, dd, Jˆ10.0 and 16.2 Hz, CHvCHCHvCH2); dC
(100 MHz) 50.4 (NCH2), 121.9 (CHvCH2), 122.4, 135.7
and 137.0 (CH), 163.8 (NCN); m/z 122 (M1, 100%), 121
(52), 106 (16), 93 (75), 66 (57), 53 (23).
6. See, for example: Grout, R. J. In The Chemistry of Amidines and
Imidates; Patai, S., Ed.; Wiley: London, 1975, p 255 et seq.;
Ruffolo, R. R.; Bondinell, W. E.; Hieble, J. P.; J. Med. Chem.
1995, 38, 3681±3716.
7. Jones, R. C. F.; Scho®eld, J. J. Chem. Soc., Perkin Trans. 1
1990, 375±383.
8. Dalko, P. I.; Brun, V.; Langlois, Y. Tetrahedron Lett. 1998, 39,
8979±8982; Dalko, P. I.; Langlois, Y. J. Org. Chem. 1998, 63,
8107±8117.
9. For a reduction of N(1)-unsubstituted 2-imidazolines with
sodium-ethanol, see: Shi, G.; Gu, H.; Synth. Commun. 1997, 27,
2701±2707.
10. Cf. Gilbert, I. H.; Rees, D. C.; Crockett, A. K.; Jones, R. C. F.
Tetrahedron 1995 51, 6315±6336.
11. This limitation was also observed with 1-benzyl-2-imidazo-
lines: Anderson, M. W.; Jones, R. C. F. Unpublished results.
12. Cf. Anderson, M. W.; Begley, M. J.; Jones, R. C. F. J. Chem.
Soc., Perkin Trans. 1 1984, 2599±2602, wherein we illustrate the
1-benzyl-2-acetyl analogue of 17c as the imino-enol tautomer,
although no hydrogen atom bonded to N or O could be located
in the X-ray crystal structure. The spectral data for this compound
are very similar to those for 17c, and we suggest that the 1-benzyl
compounds may also be better represented as the enaminoketones.
13. Reaction of C-2(a)-lithiated 1-benzyl-2-alkyl-2-imidazolines
with nitriles affords the enamino-imidazoline product tautomer:
Fustero, S.; Diaz, M. D.; Asensio, A.; Navarro, A.; Kong, J. S.;
Aguilar, E. Tetrahedron 1999, 55, 2695±2712.
Acknowledgements
We thank the Open University for a studentship (P. D.), the
EPSRC National Mass Spectrometry Service Centre
(Swansea) for some MS data, and the EPSRC National
X-Ray Crystallography Service Centre (Southampton) for
the structure determination of acylation product 17c.
References
14. Jones, R. C. F.; Snaith, J. S.; Anderson, M. W.; Smallridge,
M. J. Tetrahedron 1997, 53, 1111±1122.
1. For other work in this area of tetrahydrofolate coenzyme
mimics, see: Pandit, U. K. Pure Appl. Chem. 1994, 66, 759±764
and references therein.
15. Reich, H. J.; Renga, J. M.; Reich, I. L. J. Org. Chem. 1974, 39,
2133±2135; Sharpless, K. B.; Young, M. W. J. Org. Chem. 1975,
40, 947±949 and references. therein.
2. Jones, R. C. F.; Nichols, J. R. Tetrahedron Lett. 1990, 31,
1767±1770.
16. Crystal data for compound 17c are deposited with the
Cambridge Crystallographic Database.
17. Nair, M. D.; Desai, J. A. Indian J. Chem. 1982, 21B, 4±7.
3. (a) Anderson, M. W.; Jones, R. C. F.; Saunders, J. J. Chem.
Soc., Perkin Trans. 1 1986, 205±209; (b) Anderson, M. W.; Jones,