N-Boc-N-(benzotriazol-1-ylmethyl)benzylamine as a 1,1-dipole equivalent in stereoselective synthesis of 4,5-disubstituted imidazolidin-2-ones

Full text of DOI:10.1021/jo001615h

2858
J . Org. Chem. 2001, 66, 2858-2861
Notes
Sch em e 1
N-Boc-N-(ben zotr ia zol-1-ylm eth yl)ben zyl-
a m in e a s a 1,1-Dip ole Equ iva len t in
Ster eoselective Syn th esis of
4,5-Disu bstitu ted Im id a zolid in -2-on es
Alan R. Katritzky,*,‡ Zhushou Luo,‡ Yunfeng Fang,‡ and
Peter J . Steel§
Center for Heterocyclic Compounds, Department of
Chemistry, University of Florida, Gainesville, Florida
32611-7200, and Department of Chemistry, University of
Canterbury, Christchurch, New Zealand
katritzky@chem.ufl.edu
Received November 13, 2000
In tr od u ction
The formation and reactions of dipole-stabilized car-
banions adjacent to nitrogen atoms have been well
documented.1a-g Benzyl or allyl activation can supple-
ment dipole stabilization in the formation of a carbanion
intermediate,1a but heteroaromatic ring activation suf-
ficient to generate a carbanion between two nitrogen
atoms, to the best of our knowledge, has not been well
studied. Since benzotriazole activates an R-CH toward
proton loss more than phenyl or vinyl,2 N-Boc-N-(benzo-
triazol-1-ylmethyl)benzylamine (1) should be lithiated
selectively at the carbon adjacent to the benzotriazole
residue. Benzotriazole R to a heteroatom can act as a good
leaving group to form a carbocation. We now report that
N-Boc-N-(benzotriazol-1-ylmethyl)benzylamine (1) can
behave as the 1,1-dipole equivalent 4 (cf. Scheme 1) for
the stereoselective synthesis of 4,5-disubstituted imida-
zolidin-2-ones 5a -k via benzotriazole intermediates of
type 2.
interest to explore novel synthetic routes for this type of
compounds although a number of methods have been
reported. Previous methods for the stereoselective gen-
eration of 1,2-diamines comprise the following: (i) trans-
formations of diols, diazides,4 aziridines,5a,b and R-bromo
oxime ethers;6 (ii) reduction of diimines derived from
diketones or dialdehydes;7a,b (iii) reduction of 2-amino-
nitroalkanes;8 (iv) conversion of enantiopure amino ac-
ids;9 (v) addition of Grignard reagents to R-amino ni-
trones;10 (vi) addition of R-nitrogen carbanions to imines;1d,e
(vii) aza-Michael additions to nitroalkenes;11 (viii) nitro-
Mannich reactions;12 (ix) addition of organozinc reagents
to 1,4-diazadienes.13 Although reaction of stabilized
R-nitrogen carbanions with imines affords trans-4,5-
disubstituted imidazolidin-2-ones in good yields and with
good stereoselectivities, the examples published1d,e are
limited to the preparation of 4-aryl and 4,5-diaryl deriva-
tives. The present method using N-Boc-N-(benzotriazol-
1-ylmethyl)benzylamine as a 1,1-dipole synthon enables
the efficient introduction of a variety of substituents at
the 4 position of 5-aryl- and 5-heteroaryl-4,5-imidazoli-
din-2-ones stereospecifically and in good yields.
4,5-Disubstituted imidazolidin-2-ones are protected
precursors of vicinal diamines. Vicinal diamine structural
units are very important as structural fragments of
biologically active natural products, in medicinal chem-
istry, and in the asymmetric synthesis as chiral ligands
and chiral auxiliaries.3a-c Thus, it is still of considerable
Resu lts a n d Discu ssion
‡ University of Florida.
P r ep a r a t ion of Ben zot r ia zolylim id a zolid in on e
Der iva tives 2a -e. Starting material 1 is easily synthe-
sized by a two-step procedure. Protection of benzylamine
with (Boc)2O afforded N-Boc-benzylamine,1c which re-
§ University of Canterbury.
(1) (a) Beak, P.; Zajdel, W. J .Chem. Rev. 1984, 84, 471. (b) Curtis,
M. D.; Beak, P. J . Org. Chem. 1999, 64, 2996. (c) Wu, S.; Lee, S.; Beak,
P. J . Am. Chem. Soc. 1996, 118, 715. (d) Kise, N.; Kashiwagi, K.;
Watanabe, M.; Yoshida, J .-I. J . Org. Chem. 1996, 61, 428. (e) Park, Y.
S.; Boys, M. L.; Beak, P. J . Am. Chem. Soc. 1996, 118, 3757. (f) Beak,
P.; Lee, W. K. J . Org. Chem. 1993, 58, 1109. (g) Rein, K. S.; Gawley,
R. E. J . Org. Chem. 1991, 56, 1564.
(6) Shatzmiller, S.; Bercovici, S. Liebigs Ann. Chem. 1992, 1005.
(7) (a) Nantz, M. H.; Lee, D. A.; Bender, D. M.; Roohi, A. H. J . Org.
Chem. 1992, 57, 6653. (b) Enders, D.; Meiers, M. Angew. Chem., Int.
Ed. Engl. 1996, 35, 2261.
(2) Katritzky, A. R.; Lan, X.; Yang, J . Z.; Denisko, O. V. Chem. Rev.
1998, 98, 409.
(3) (a) Lucet, D.; Gall, T. L.; Mioskowski, C. Angew. Chem., Int. Ed.
Engl. 1998, 37, 2581. (b) Kojima, H.; Nakatsubo, N.; Kikuchi, K.;
Kawahara, S.; Kirino, Y.; Nagoshi, H.; Hirata, Y.; Nagano, T. Anal.
Chem. 1998, 70, 2446. (c) Denmark, S. E.; Su, X.; Nishigaichi, Y.; Coe,
D. M.; Wong, K.-T.; Winter, S. B. D.; Choi, J . Y. J . Org. Chem. 1999,
64, 1958.
(8) Sturgess, M. A.; Yarberry, D. J . Tetrahedron Lett. 1993, 34, 4743.
(9) Reetz, M. T.; J aeger, R.; Drewlies, R.; Hu¨bel, M. Angew. Chem.,
Int. Ed. Engl. 1991, 30, 103.
(10) Merino, P.; Lanaspa, A.; Merchan, F. L.; Tejero, T. Tetrahe-
dron: Asymmetry 1997, 8, 2381.
(11) Enders, D.; Wiedemann, J . Synthesis 1996, 1443.
(12) Adams, H.; Anderson, J . C.; Peace, S.; Pennell, A. M. K. J . Org.
Chem. 1998, 63, 9932.
(4) Pini, D.; Iuliano, A.; Rosini, C.; Salvadori, P. Synthesis 1990,
1023.
(5) (a) Meguro, M.; Asao, N.; Yamamoto, Y. Tetrahedron Lett. 1994,
35, 7395. (b) Orlek, B. S.; Stemp, G. Tetrahedron Lett. 1991, 32, 4045.
(13) Alvaro, G.; Grepioni, F.; Savoia, D. J . Org. Chem. 1997, 62,
4180.
10.1021/jo001615h CCC: $20.00 © 2001 American Chemical Society
Published on Web 03/29/2001

Notes
J . Org. Chem., Vol. 66, No. 8, 2001 2859
Ta ble 1. P r ep a r a tion of Ben zotr ia zole Der iva tives 2a -e
a n d 3a -e
Ta ble 2. Su bstitu tion of th e Ben zotr ia zole Moiety in
2a -e by Ca r bon Nu cleop h iles
entry
R1
product yield (%) product yield (%)
starting
entry material
yield
(%)
R1
R2
product
1
2
3
4
5
Ph
2a
2b
2c
2d
2e
82
74
80
61
70
3a
3b
3c
3d
3e
82
76
72
70
66
4-Me-C6H4
4-MeO-C6H4
4-F-C6H4
2-furyl
1
2
3
4
5
6
7
8
9
2a
2b
2c
2d
2e
2a
2a
2a
2e
2a
2a
Ph
4-Me-C6H4
4-MeO-C6H4 Ph
4-F-C6H4
2-furyl
Ph
Ph
Ph
5a
5b
5c
5d
5e
5f
5g
5h
5i
68
50
65
60
66
74
68
67
40
64
70
Ph
Ph
Sch em e 2
Ph-CtC
CH2dCH
CH2dCH-CH2
CH2dCH-CH2
PhC(dO)CH2
c-C4H8CHCO
Ph
Ph
2-furyl
Ph
10
11
5j
5k
Ph
Rea ction s of Syn th on s 2 w ith Allyltr im eth ylsi-
la n e a n d Vin yloxysila n es. Treatment of 2a with SnCl4
at -78 °C for 30 min followed by the addition of
allyltrimethylsilane afforded trans-4,5-disubstituted imi-
dazolidinone (5h ) (20%) along with the â-H elimination
product 6 (50%) (Scheme 2). When BF3•Et2O was used,
exclusively 5h was produced in 67% yield (Table 2) and
with high trans selectivity (trans/cis >99:1 according to
NMR of the reaction mixture). Under the same reaction
conditions, 5i was prepared in 40% yield.
Reactions of trimethyl[(1-phenylvinyl)oxy]silane or (1-
cyclohexen-1-yloxy)trimethylsilane with 2a gave products
5j-k in good yields and specifically (trans/cis >99:1
according to NMR of the reaction mixtures). In the case
of 5k , no stereochemical control at the carbon R to the
carbonyl group in the cyclohexanone substituent was
observed. The H4 was shown as a doublet in 1H NMR
and the coupling constant between H4 and H5 was 4.0
Hz in 5k , indicating that H4 and H5 were in trans
configuration.
Compound 7 was easily obtained from the reduction
of 5h 14 (Scheme 2), which made it possible for the indirect
stereospecific introduction of an alkyl group in the 4
position of 4,5-disubstituted imidazolidinones.
acted further (without purification) with formaldehyde
and benzotriazole in the presence of a catalytic amount
of TsOH using a Dean-Stark apparatus to remove the
water azeotropically to give N-Boc-N-(benzotriazol-1-
ylmethyl)benzylamine (1) in 70% overall yield. Treatment
of 1 with 1 equiv of s-BuLi in THF at -78 °C for 0.5 h,
followed by the addition of imines as electrophiles,
produced the benzotriazolyl-substituted imidazolidinones
2a -e (Scheme 1). When imines derived from aromatic
aldehydes (electron-donating substituent, entry 3; electron-
withdrawing substituent, entry 4) or a heteroaromatic
aldehyde (entry 5) were used, the corresponding benzo-
triazole derivatives 2 were obtained in good yields (Table
1) and stereospecifically (trans/cis >99:1). According to
1H NMR and 13C NMR spectra, only one isomer was
observed and isolated from the reaction mixture in each
case.
Rea ction s of Syn th on s 2 w ith Diver se Zin c Re-
a gen ts. Treatment of 2a -e with organozinc reagents
gave compounds 5a -g (Scheme 2) in good yields and
stereospecifically (trans/cis >99:1 according to NMR of
the reaction mixtures) (Table 2). Arylzinc reagents
(entries 1-5), an alkynylzinc reagent (entry 6), and an
alkenylzinc reagent (entry 7) all afforded the correspond-
ing desired products. Various 5-substituted imidazolidi-
nones 2a -e can be used for these substitution reactions
(entries 1-5). However, alkylzinc reagents produced no
desired products but â-H elimination occurred to give
compounds such as 6 together with other products still
under investigation.
The trans configuration for compounds 2a -e, 5a -k ,
and 7 was assigned from the coupling constant J 4,5
between H4 and H5 in the heterocyclic five-membered
rings based on literature reports15,16 and X-ray crystal-
lography. It is generally accepted that the trans coupling
constant is smaller than that of the corresponding cis
coupling in a five-membered heterocyclic ring system.
When a vicinal coupling constant is smaller than 4.0 Hz
in a five-membered heterocyclic ring system, the geom-
etry is assigned as trans.15 The coupling constants in 4,5-
disubstituted imidazolidin-2-ones 2a -e were around 2.5
Hz, so these compounds were assigned the trans config-
uration. The full structure and stereochemistry of 2a was
further confirmed by a single-crystal X-ray structure
determination.17 The coupling constant J 4,5 (around 6.0
Hz) between H4 and H5 in 5a is more ambiguous in
terms of stereochemical assignment but is consistent with
similar compounds which have trans configurations.1d-e
The structure of 5a was unambiguously determined by
X-ray crystallography,17 which confirmed the trans ster-
(14) Hart, D. J .; Hong, W.-P.; Hsu, L.-Y. J . Org. Chem. 1987, 52,
4665.
(15) Nadir, U. K., Basu, N. Tetrahedron 1993, 49, 7787 and
references therein.
(16) Bergmeier, S. C.; Stanchina, D. M. J . Org. Chem. 1997, 62,
4449.
(17) See the Supporting Information for X-ray crystal structures and
data of 2a and 5a .

2860 J . Org. Chem., Vol. 66, No. 8, 2001
Notes
the internal reference. THF was distilled from sodium/benzophe-
none and CH2Cl2 was distilled from CaH2 under nitrogen
immediately prior to use. All reactions with air-sensitive com-
pounds were carried out under argon atmosphere.
Syn th esis of N-Boc-N-(ben zotr ia zol-1-ylm eth yl)ben zyl-
a m in e (1). Benzylamine (8.56 g, 0.08 mol) and triethylamine
(11.7 mL) were mixed in methylene chloride (300 mL) at 0 °C,
and then di-tert-butyl dicarbonate (17.44 g, 0.08 mol) in meth-
ylene chloride (100 mL) was added. The solution was stirred
overnight, and methylene chloride was removed under reduced
pressure. The crude product obtained can be used in the next
step without purification.
The crude product, prepared as shown above, benzotriazole
(9.52 g, 0.08 mol), paraformaldehyde (2.4 g, 0.08 mol) and a
catalytic amount of p-toluenesulfonic acid were mixed in toluene
(400 mL) and refluxed overnight with a Dean-Stark trap to
remove the water formed. After toluene was removed under
reduced pressure, the crude product was subjected directly to
silica gel column chromatography, and product 1 was obtained
as white prisms (from methylene chloride and hexanes): mp
126-127 °C; yield 70%; 1H NMR δ 1.50 (s, 9H), 4.43 (s, 2H),
6.10 (s, 2H), 7.26-7.41 (m, 7H), 7.51 (t, J ) 7.6 Hz, 1H), 8.05
(d, J ) 8.1 Hz, 1H); 13C NMR δ 28.2, 48.7, 57.3, 81.6, 111.0,
119.6, 124.2, 127.6, 127.8, 128.6, 132.5, 136.7, 146.2, 155.2. Anal.
Calcd for C19H22N4O2: C, 67.44; H, 6.55; N, 16.56. Found: C,
67.26; H, 6.70; N, 16.60.
eochemistry. Similarly, the other compounds were also
assigned as having trans geometry.
The high trans selectivity for 2a -e probably derives
from the formation of the products under thermodynamic
control; however, products 5a -k are all formed under
kinetic control indicating that both thermodynamic and
kinetic control highly favor trans products. In the pres-
ence of a Lewis acid (such as in situ generated MgBr2 or
BF3•Et2O), the benzotriazole moiety in 2a -e can be
removed to form acyliminium salts, which are attacked
by nucleophiles exclusively from the opposite face of the
R1 group affording trans products. With basic nucleo-
philes (such as alkyl in contrast to aryl zinc reagents) or
a strong Lewis acid (such as SnCl4 relative to BF3•Et2O18),
â-H elimination occurs to give products such as 6.
Under similar reaction conditions as for imines, alde-
hydes were used as electrophiles for lithiated 1 to give
analogous oxazolidinones 3a -e (Scheme 1). All the
reactions produced the trans isomers selectively in good
yields when arylaldehydes were used (Table 1). The trans
conformation assignment is based on the coupling con-
stant (J 4,5 ) 2.5 Hz), which is also consistent with the
literature report.16
Gen er a l P r oced u r e for th e Syn th esis of Com p ou n d s
2a -e a n d 3a -e. At -78 °C, s-BuLi (2 mmol, 1.3 M in hexane)
was added slowly to a solution of N-Boc-N-(benzotriazol-1-
ylmethyl)benzylamine (1) (2 mmol) in THF (25 mL), and the
reaction mixture was stirred for 0.5 h at this temperature. Then
an imine or an aldehyde (2 mmol) in THF (5 mL) was added
slowly, and the reaction solution was further stirred for 4 h.
Saturated NH4Cl aqueous solution (20 mL) was added to quench
the reaction. Ethyl acetate (50 mL) was added, and the organic
layer was separated. The aqueous layer was extracted with ethyl
acetate (2 × 25 mL). The combined organic layer was washed
with brine, dried over Na2SO4, and evaporated under reduced
pressure. The residue was subjected to silica gel chromatography
giving the pure products 2a -e and 3a -e, respectively.
tr a n s-4-(1H-1,2,3-Ben zotr ia zol-1-yl)-3-ben zyl-5-p h en yl-1-
(4-m et h oxyp h en yl)im id a zolid in -2-on e (2a ): white needles
(from methylene chloride and hexanes); mp 155-156 °C; yield
82%; 1H NMR δ 3.73 (s, 3H), 3.84 (d, J ) 15.1 Hz, 1H), 4.86 (d,
J ) 15.1 Hz, 1H), 5.29 (d, J ) 2.1 Hz, 1H), 6.20 (d, J ) 2.1 Hz,
1H), 6.80 (d, J ) 9.0 Hz, 2H), 7.08-7.19 (m, 7H), 7.30-7.40 (m,
3H), 7.43-7.45 (m, 5H), 8.08 (d, J ) 8.6 Hz, 1H); 13C NMR δ
45.4, 55.3, 64.5, 75.5, 109.7, 114.3, 116.3, 120.5, 122.3, 124.6,
125.9, 127.8, 128.2, 128.4, 128.5, 129.1, 129.4, 130.7, 135.1, 137.7,
146.9, 156.2, 156.4. Anal. Calcd for C29H25N5O2: C, 73.25; H,
5.30; N, 14.73. Found: C, 73.24; H, 5.46; N, 14.69.
Attempts to substitute the benzotriazole residue in
oxazolidinones 3a -e failed. When organozinc reagents,
organocerium reagents, organocopper reagents, Grignard
reagents and allyltrimethylsilanes were used as nucleo-
philes, either no reactions occurred or only elimination
products were isolated. Probably in these 4,5-disubsti-
tuted oxazolidin-2-ones 3a -e, the single nitrogen atom
cannot assist the removal of the benzotriazole moiety due
to its relatively electron deficient character compared to
that of the analogous nitrogen atom in 4,5-disubstituted
imidazolidin-2-ones 2.
Con clu sion
A general method using N-Boc-N-(benzotriazol-1-yl-
methyl)benzylamine as a 1,1-dipole equivalent to syn-
thesize various trans-4,5-disubstituted imidazolidinones
was reported. A number of trans-4,5-disubstituted imi-
dazolidinones were obtained in good yields and with
excellent stereoselectivity. Imidazolidin-2-ones can be
converted directly into the corresponding secondary di-
amines under basic conditions (NaOH) without affecting
the two N-protecting groups.19a,b Alternatively, removal
of one or both of the N-protecting groups1d,20a followed
by hydrolysis under acidic conditions (HCl or HBr) gives
the corresponding primary diamines.20b-d Although ben-
zotriazole derivatives 3a -e of 4,5-disubstituted oxazoli-
din-2-ones could be obtained, attempted displacement of
the benzotriazole moiety was not successful.
Cr ysta l d a ta for 2a : C29H25N5O2, MW 475.54, orthorhombic,
P212121, a ) 8.419(5) Å, b ) 15.655(9) Å, c ) 18.395(11) Å, V )
2420(2) Å3, Z ) 4, T ) -105 °C, F(000) ) 1000, µ (Mo KR) )
0.085 mm-1, Dcalcd ) 1.305 g‚cm-3, 2θmax 53° (CCD area detector,
99.4% completeness), wR(F2) ) 0.071 (all 4851 data), R ) 0.037
(3510 data with I > 2σI).
tr a n s-4-(1H -1,2,3-Ben zot r ia zol-1-yl)-3-b en zyl-5-p h en yl-
1,3-oxa zola n -2-on e (3a ): white prisms (from methylene chlo-
1
ride and hexanes); mp 110-112 °C; yield 82%; H NMR δ 3.86
(d, J ) 15.0 Hz, 1H), 4.70 (d, J ) 15.0 Hz, 1H), 5.71 (d, J ) 2.8
Hz, 1H), 6.37 (d, J ) 2.8 Hz, 1H), 7.03-7.06 (m, 2H), 7.11-7.15
(m, 2H), 7.24-7.27 (m, 2H), 7.35-7.53 (m, 7H), 8.07 (d, J ) 8.4
Hz, 1H); 13C NMR δ 46.1, 76.2, 78.9, 109.3, 120.5, 124.8, 125.0,
128.1, 128.3, 128.6, 128.7, 129.2, 129.5, 130.4, 133.6, 136.0, 146.8,
156.0; HRMS calcd for C22H19N4O2 371.1508 (M + 1), found
371.1514 (M + 1).
Exp er im en ta l Section
Gen er a l Com m en ts. Melting points were determined on a
hot-stage apparatus and are uncorrected. 1H (300 MHz) and 13C
(75 MHz) NMR spectra were recorded in CDCl3 with TMS as
Gen er a l P r oced u r e for th e Syn th esis of Com p ou n d s
5a -g a n d 6. Grignard reagent R2MgBr (2 mmol, 1.0 M in THF)
was added to ZnCl2 (2 mmol, 1.0 M in diethyl ether) in THF (10
mL) at 0 °C, and the resulting mixture was further stirred at
room temperature for 20 min. Then 2a -e (0.4 mmol) in THF (3
mL) was added, and the reaction solution was heated under
reflux for 12 h. After the solution cooled to room temperature,
saturated NH4Cl aqueous solution (20 mL) was added and the
resulting solution was extracted with ethyl acetate (3 × 30 mL).
The combined organic layers were washed with brine, dried over
(18) Comprehensive Organic Synthesis; Trost, B. M., Fleming, I.,
Eds.; Pergamon Press: Oxford, 1991; Vol. 1, p 295.
(19) (a) Anjaneyulu, B.; Nagarajan, K. Indian J . Chem. Sec. B 1991,
30, 399. (b) Kavrakova, I. K.; Lyapova, M. J . Org. Prep. Proced. Int.
1996, 28, 333.
(20) (a) Lee, H. L.; Baggiolini, E. G.; Uskokovic, M. R. Tetrahedron
1987, 43, 4887. (b) Cardillo, G.; Orena, M.; Penna, M.; Sandri, S.;
Tomasini, C. Tetrahedron 1991, 47, 2263. (c) Dunn, P. J .; Haener, R.;
Rapoport, H. J . Org. Chem. 1990, 55, 5017. (d) Shimizu, M.; Kamei,
M.; Fujisawa, T. Tetrahedron Lett. 1995, 36, 8607.

Notes
J . Org. Chem., Vol. 66, No. 8, 2001 2861
Na2SO4, and evaporated under reduced pressure. The residue
was then subjected to silica gel chromatography, and the pure
products 5a -g and 6 were obtained, respectively.
was added and extracted by CH2Cl2 (3 × 15 mL). Combined
organic layers were washed with brine, dried over Na2SO4, and
evaporated under reduced pressure. The residue was then
subjected to silica gel chromatography affording the pure
products 5h -k , respectively.
tr a n s-4-Allyl-3-ben zyl-1-(4-m eth oxyp h en yl)-5-p h en ylim -
id a zolid in -2-on e (5h ): white needles (from methylene chloride
and hexanes); mp 74-75 °C; yield 67%; 1H NMR δ 2.39-2.43
(m, 2H), 3.32-3.37 (m, 1H), 3.71 (s, 3H), 4.15 (d, J ) 15.3 Hz,
1H), 4.76 (d, J ) 5.1 Hz, 1H), 4.98 (d, J ) 15.3 Hz, 1H), 5.20-
5.26 (m, 2H), 5.66-5.75 (m, 1H), 6.73-6.78 (m, 2H), 7.17-7.33
(m, 12H); 13C NMR δ 35.8, 45.6, 55.4, 60.4, 62.7, 113.9, 119.6,
122.1, 126.4, 127.4, 127.9, 128.0, 128.6, 128.9, 132.3, 136.9, 140.3,
155.6, 158.0; HRMS Calcd for C26H27N2O2 399.2073 (M + 1),
found 399.2071 (M + 1).
tr a n s-1-Ben zyl-5-(2-oxo-2-ph en yleth yl)-3-(4-m eth oxyph en -
yl)-4-p h en ylim id a zolid in -2-on e (5j): white needles (from
methylene chloride and hexanes); mp 118-119 °C; yield 63%;
1H NMR δ 3.21 (dd, J ) 8.5, 17.4 Hz, 1H), 3.36 (dd, J ) 4.2,
17.4 Hz, 1H), 3.70 (s, 3H), 3.94-3.99 (m, 1H), 4.31 (d, J ) 15.4
Hz, 1H), 4.79 (d, J ) 15.4 Hz, 1H), 4.85 (d, J ) 3.1 Hz), 6.74 (d,
J ) 9.1 Hz, 2H), 7.20-7.43 (m, 14H), 7.55 (t, J ) 7.3 Hz, 1H),
7.78 (d, J ) 7.3 Hz, 2H); 13C NMR δ 40.9, 45.9, 55.3, 58.2, 64.3,
113.9, 121.2, 126.3, 127.4, 127.9, 128.0, 128.5, 128.6, 128.8, 132.5,
133.6, 136.2, 137.1, 139.7, 155.4, 157.4, 197.4. Anal. Calcd for
C31H28N2O3: C, 78.13; H, 5.92; N, 5.88. Found: C, 77.73; H, 6.04;
N, 5.81.
Syn th esis of tr a n s-1-Ben zyl-3-(4-m eth oxyph en yl)-4-ph en -
yl-5-p r op ylim id a zolid in -2-on e (7). Compound 5h (0.13 mmol)
and p-toluenesulfonohydrazide (1.3 mmol) were dissolved in
DME (5 mL) and heated until refluxed, NaOAc aqueous solution
(2.2 mmol, 5 mL) was added within 30 min, and the reaction
mixture was further heated under reflux for 1 h. The resulting
reaction mixture was cooled to room temperature, and water
(20 mL) was added. The solution was extracted with ethyl
acetate (3 × 20 mL), dried over Na2SO4, and evaporated under
reduced pressure. The residue was then subjected to silica gel
chromatography, and 7 was obtained as white prisms (from
methylene chloride and hexanes): mp 129-130 °C; yield 100%;
1H NMR δ 0.87 (t, J ) 7.3 Hz, 3H), 1.21-1.41 (m, 2H), 1.58-
1.64 (m, 2H), 3.25-3.28 (m, 1H), 3.71 (s, 3H), 4.10 (d, J ) 15.4
Hz, 1H), 4.69 (d, J ) 4.9 Hz, 1H), 4.95 (d, J ) 15.4 Hz, 1H), 6.74
(m, J ) 2.2 Hz, 2H), 7.17-7.32 (m, 12H); 13C NMR δ 14.1, 17.1,
33.7, 45.6, 55.3, 61.0, 63.7, 113.9, 122.0, 126.3, 127.4, 127.9,
128.0, 128.5, 128.9, 132.6, 137.1, 140.9, 155.6, 158.0. Anal. Calcd
for C26H28N2O2: N, 6.99. Found: N, 6.65.
tr a n s-1-Ben zyl-3-(4-m eth oxyp h en yl)-4,5-d ip h en ylim id a -
zolid in -2-on e (5a ): white prisms (from methylene chloride and
hexanes); mp 113-114 °C; yield 68%; 1H NMR δ 3.69 (s, 3H),
3.70 (d, J ) 14.9 Hz, 1H), 4.14 (d, J ) 6.6 Hz, 1H), 4.86 (d, J )
6.6 Hz, 1H), 5.07 (d, J ) 15.0 Hz, 1H), 6.75 (d, J ) 9.0 Hz, 2H),
7.06-7.38 (m, 17H); 13C NMR δ 45.6, 55.3, 65.7, 67.7, 113.8,
122.6, 126.4, 127.3, 127.4, 128.1, 128.5, 128.6, 128.8, 129.0, 132.2,
136.4, 138.3, 139.2, 155.8, 158.4. Anal. Calcd for C29H26N2O2:
C, 80.16; H, 6.03; N, 6.45. Found: C, 79.95; H, 6.18; N, 6.44.
Cr ysta l d a ta for 5a : C29H26N2O2, MW 434.52, orthorhombic,
Pbca, a ) 10.311(3) Å, b ) 10.693(3) Å, c ) 41.759(11) Å, V )
4602(2) Å3, Z ) 8, T ) -105 °C, F(000) ) 1840, µ (Mo KR) )
0.079 mm-1, Dcalcd ) 1.254 g‚cm-3, 2θmax 53° (CCD area detector,
99.2% completeness), wR(F2) ) 0.115 (all 4700 data), R ) 0.044
(3347 data with I > 2σI).
tr a n s-1-Ben zyl-3-(4-m eth oxyp h en yl)-4-p h en yl-5-(2-p h en -
1
yleth yn yl)im id a zolid in -2-on e (5f): yellow oil; yield 74%; H
NMR δ 3.71 (s, 3H), 4.14 (d, J ) 6.6 Hz, 1H), 4.30 (d, J ) 15.0
Hz, 1H), 5.04 (d, J ) 15.0 Hz, 1H), 6.77 (d, J ) 6.6 Hz, 1H),
6.76-6.79 (m, 2H), 7.41-7.45 (m, 17H); 13C NMR δ 46.2, 54.1,
55.3, 64.4, 84.3, 86.9, 113.9, 121.8, 122.9, 126.5, 127.5, 128.4,
128.5, 128.6, 128.9, 129.0, 131.8, 136.4, 138.4, 147.2, 156.1, 157.6.
Anal. Calcd for C31H26N2O2: N, 6.11. Found: N, 6.12.
tr a n s-1-Ben zyl-3-(4-m eth oxyp h en yl)-4-ph en yl-5-vin ylim -
id a zolid in -2-on e (5g): white prisms (from methylene chloride
1
and hexanes); mp 107-108 °C; yield 68%; H NMR δ 3.64 (dd,
J ) 7.0, 8.6 Hz, 1H), 3.70 (s, 3H), 4.05 (d, J ) 15.1 Hz, 1H), 4.73
(d, J ) 7.0 Hz, 1H), 4.91 (d, J ) 15.1 Hz, 1H), 5.06 (d, J ) 17.0
Hz, 1H), 5.30 (d, J ) 10.7 Hz, 1H), 5.82 (ddd, J ) 8.6, 10.7, 17.0
Hz, 1H), 6.75 (m, 2H), 7.16-7.29 (m, 12H); 13C NMR δ 45.7, 55.3,
64.9, 65.4, 113.8, 120.8, 122.6, 126.6, 127.3, 128.0, 128.4, 128.5,
128.7, 132.2, 135.1, 136.9, 138.8, 155.8, 158.2. Anal. Calcd for
C25H24N2O2: C, 78.10; H, 6.29; N, 7.29. Found: C, 77.59; H, 6.60;
N, 7.21.
1-Ben zyl-3-(4-m eth oxyp h en yl)-4-p h en yl-1,3-d ih yd r o-2H-
im id a zol-2-on e (6): white needles (from methylene chloride and
hexanes); mp 95-96 °C; yield 50%; 1H NMR δ 3.79 (s, 3H), 4.90
(s, 2H), 6.32 (s, 1H), 6.86 (d, J ) 8.9 Hz, 2H), 6.99-7.02 (m,
2H), 7.13-7.17 (m, 5H), 7.34-7.38 (m, 5H); 13C NMR δ 47.3,
55.4, 108.8, 114.2, 124.2, 126.9, 127.2, 127.9, 128.2, 128.3, 128.4,
128.8, 129.4, 136.7, 153.4, 158.4; HRMS calcd for C23H21N2O2
357.1603 (M + 1), found 357.1601 (M + 1).
Gen er a l P r oced u r e for th e Syn th esis of Com p ou n d s
5h -k . BF3•Et2O (2 mmol) in CH2Cl2 (2 mL) was added to 2a or
2e (0.4 mmol) in CH2Cl2 (10 mL) at -78 °C. After the reaction
Su p p or tin g In for m a tion Ava ila ble: Characterization
data for compounds 2b-e, 3b-e, and 5b-e,i,k and X-ray
crystal structures for 2a and 5a . This material is available
free of charge via the Internet at http://pubs.acs.org.
mixture was stirred for 30 min, allyltrimethylsilane or
a
vinyloxytrimethylsilane (2 mmol) was added, and the reaction
mixture was further stirred for 4 h at this temperature. Then
the reaction solution was warmed to room temperature and
stirred overnight. Saturated NH4Cl aqueous solution (20 mL)
J O001615H