Gold(I)-catalyzed intramolecular hydroamination of N-allylic N′-arylureas to form imidazolidin-2-ones

Article abstract of DOI:10.1002/adsc.201000844

Treatment of N-allylic N′-arylureas with a catalytic 1:1 mixture of di-tert-butyl-o-biphenylphoshphine gold(I) chloride and silver hexafluorophosphate (1 mol%) in chloroform at room temperature led to 5-exo-hydroamination to form the corresponding imidazolidin-2-ones in excellent yield. In the case of N-allylic ureas that possessed an allylic alkyl, benzyloxymethyl, or acetoxymethyl substituent, gold(I)-catalyzed 5-exo-hydroamination leads to formation of the corresponding trans-3,4-disubstituted imidazolidin-2-ones in excellent yield with ≥50:1 diastereoselectivity.

Full text of DOI:10.1002/adsc.201000844

FULL PAPERS
DOI: 10.1002/adsc.201000844
Gold(I)-Catalyzed Intramolecular Hydroamination of N-Allylic
N’-Arylureas to form Imidazolidin-2-ones
Hao Li,a Feijie Song,a and Ross A. Widenhoefera,*
a
Duke University, French Family Science Center, 124 Science Drive, Durham, North Carolina 27708, USA
Fax : (+1)-919-660-1605; phone: (+1)-919-660-1533; e-mail: rwidenho@chem.duke.edu
Received: November 10, 2010; Revised: December 12, 2010; Published online: April 13, 2011
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201000844.
Abstract: Treatment of N-allylic N’-arylureas with a ent, gold(I)-catalyzed 5-exo-hydroamination leads to
catalytic 1:1 mixture of di-tert-butyl-o-biphenyl- formation of the corresponding trans-3,4-disubstitut-
phoshphine gold(I) chloride and silver hexafluoro- ed imidazolidin-2-ones in excellent yield with ꢀ50:1
phosphate (1 mol%) in chloroform at room tempera- diastereoselectivity.
ture led to 5-exo-hydroamination to form the corre-
sponding imidazolidin-2-ones in excellent yield. In
the case of N-allylic ureas that possessed an allylic Keywords: alkenes; gold; intramolecular hydroami-
alkyl, benzyloxymethyl, or acetoxymethyl substitu- nation; nitrogen heterocycles
Introduction
lidin-2-ones in high yield and high diastereoselectivity
(Scheme 1).[22] These transformations occurred via
Substituted imidazolidin-2-ones are components of a two discrete steps; initial 6-exo-hydroamination of the
number of biologically active compounds[1] including N-d-allenylurea followed by 5-exo-hydroamination of
NK1 and muscarinic M3 antagonists,[2,3] HIV protease the resulting 1-vinylpiperidine (Scheme 1). Whereas
and human enterovirus 71 inhibitors,[4,5] and antipara- the former step is unremarkable, the latter step repre-
sitic[6] and immunosuppressive agents.[7] Furthermore, sents a rare example of imidazolidin-2-one ring for-
chiral, non-racemic imidazolidin-2-ones have been mation via intramolecular alkene hydroamination
employed as chiral auxiliaries[8,9] and as scaffolds for under remarkably mild conditions.[23–25] We therefore
bis(phosphine) ligands[10,11] for use in enantioselective considered that gold(I)-catalyzed intramolecular hy-
synthesis. A number of approaches to construction of droamination of acyclic N-allylic ureas might serve as
the imidazolidin-2-one ring have been developed[12–20] an expedient route to the synthesis of substituted,
including carbonylation of vicinal diamines,[13] oxida- monocyclic imidazolidin-2-ones. Herein we report the
tive diamination of alkenes with ureas,[14,15] and elec- results of this investigation.
trophilic cyclization[16] or transition metal-catalyzed
carboamination of N-allylic ureas.[17,18] In contrast,
transition metal-catalyzed alkene hydroamination,
which represents perhaps the most conceptually
simple and atom-economical approach to the cycliza-
tion of readily available N-allylic ureas, has gone
largely unexplored as a route to the imidazolidin-2-
one ring.
In the course of our continuing investigation of the
gold(I)-catalyzed intramolecular hydroamination of
allenes,[21] we recently found that treatment of N-d-al-
lenylureas with a catalytic 1:1 mixture of the gold(I)
N-heterocyclic carbene complex (IPr)AuCl [IPr=1,3-
bis(2,6-diisopropylphenyl)imidazol-2-ylidine]
and
Scheme 1. Gold(I)-catalyzed dihydroamination of an N-d-al-
AgPF6 (5 mol%) led to formation of bicyclic imidazo- lenylurea.
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Table 2. Substrate scope of the intramolecular hydroamina-
tion of N-allylic ureas catalyzed by a 1:1 mixture of
(P1)AuCl and AgPF6 (1 mol%) in CHCl3 at room tempera-
ture (PNP=4-NO2C6H4, PMP=4-MeOC6H4).
Results and Discussion
Optimization and Scope
Our starting point for the gold(I)-catalyzed intramo-
lecular hydroamination of acyclic N-allylic ureas em-
ployed the catalyst system used for the catalytic dihy-
droamination of N-d-allenylureas with the substitu-
tion of chloroform for CH2Cl2 owing to the greater
solubility of simple N-allylic ureas in the former sol-
vent. In an initial experiment, treatment of N-allylur-
ea 1a with a catalytic 1:1 mixture of (IPr)AuCl
(5 mol%) and AgPF6 (5 mol%) in chloroform at
room temperature for 12 h led to isolation of imidazo-
lidin-2-one 2a in 97% yield (Table 1, entry 1). The cat-
alyst loading was lowered to 1 mol% without dimin-
ished yield, but with the anticipated increase in reac-
tion time (Table 1, entries 2 and 3). Substitution of
the sterically hindered phosphine ligand o-biphenyl-
P(t-Bu)2 (P1) for IPr led to a ~two-fold increase in
G
reaction rate with no diminishment of product yield
(Table 1, entry 4). The effectiveness of ligand P1 in
the conversion of 1a to 2a is surprising, given the
marked superiority of IPr relative to P1 in the gold-
catalyzed dihydroamination of N-d-allenylureas.[22]
The possibility that intramolecular hydroamination of
N-allylic ureas is catalyzed by Ag+ or a Brønsted acid
generated under the reaction conditions was rigorous-
ly ruled out in our investigation of allene dihydroami-
nation.[22]
Acyclic N-allyl-N’-aryl ureas 1b–1f that possessed
either an electron-rich or electron-deficient N’-aryl
group in combination with an N-alkyl or N-aryl sub-
[a]
Isolated yields of >95% purity.
Determined by H NMR analysis of the crude reaction
[b]
1
mixture.
[c]
[d]
[e]
Catalyst loading=5 mol%.
Reaction temperature=608C.
Catalyst loading=10 mol%.
Table 1. Effect of ligand and catalyst loading on the gold(I)-
catalyzed conversion of 1a to 2a.
stituent underwent gold(I)-catalyzed intramolecular
hydroamination to form the corresponding imidazoli-
din-2-ones 2b–2f in excellent yield (Table 2, entries 1–
5). However, whereas the nature of the N’-aryl group
had little effect on the rate of cyclization, N-methylur-
eas 1b and 1d underwent intramolecular hydroamina-
tion at lower rates than those bearing an N-Cy (1a
and 1f) or N-Ph (1c and 1e) group (Table 2). Acyclic
N-allylic ureas that possessed an allylic methyl (3a),
isopropyl (3b), benzyloxymethyl (3c), or acetoxymeth-
yl (3d) substituent underwent gold(I)-catalyzed intra-
molecular hydroamination to form the corresponding
trans-3,4-disubstituted imidazolidin-2-ones 4a–4d in
excellent yield with ꢀ50:1 diastereoselectivity
(Table 2, entries 6–9). In comparison, gold(I)-cata-
lyzed intramolecular hydroamination of N-allylic urea
5 that possessed an allylic hydroxymethyl group led to
[a]
Isolated yields of >95% purity.
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Gold(I)-Catalyzed Intramolecular Hydroamination of N-Allylic N’-Arylureas
addition of the nucleophile on a cationic gold(I) p-
alkene complex followed by protodeauration,[23] al-
though little direct evidence supported this conten-
tion.[28] Since that time, we[29] and others[30] have syn-
thesized and characterized cationic gold(I) p-alkene
complexes and Toste has recently demonstrated the
stoichiometric intramolecular aminoauration of N-g-
alkenylureas with (PPh3)AuNTf2 in the presenece of
triethylamine.[31] Toste also demonstrated that treat-
ment of these (b-amino)alkyl gold complexes with
TsOH led to rapid reversion to regenerate the N-g-al-
kenylureas, which was followed by slow protodeaura-
tion to form the 1-methylpyrrolidine.[31] Although pro-
todeauration was slow, it appears reasonable that
more electron-rich supporting ligands such as P1
Scheme 2. Dearylation and hydrolysis of imidazolidin-2-one
2e.
predominant (dr=3.7:1) formation of the cis-imidazo- might facilitate protodemetallation.[32] In any event,
lidin-2-one 6 in 97% yield (Table 2, entry 10). these results both establish the outer-sphere aminoau-
Imidazolidin-2-ones also serve as precursors to vici- ration of alkenes with urea nucleophiles and also
À
nal diamines and utilization of the p-methoxyphenyl point to the potential reversibility of C N bond for-
(PMP) group allows for efficient dearylation to form mation.
primary amines. For example, oxidative removal of
From this discussion, it follows that the trans-con-
the PMP group of 2e with ceric ammonium nitrate figuration of 3,4-disubstituted imidazolidin-2-ones 4a–
(CAN)[26] followed by acid-catalyzed hydrolysis[20,27] of 4d may be determined either by C N bond formation
N H imidazolidine-2-one 7 led to isolation of the dif- in the case of irreversible aminoauration or by proto-
À
À
ferentially substituted vicinal diamine 8 in 63% yield deauration in the case of reversible aminoauration. In
À
over two steps (Scheme 2).
the case of irreversible C N bond formation, amino-
auration of gold (p-alkene) intermediate trans-I
should be favored relative to aminoauration of cis-I
owing to unfavorable interaction of both the alkenyl
=CH2 group (A1,3 strain) and the coordinated gold
Proposed Mechanism and Stereochemical Model
We have previously proposed a mechanism for the atom with the allylic substituent that is absent in the
gold(I)-catalyzed intramolecular hydroamination of case of trans-I (Scheme 3). In the case of reversible
À
alkenes with carbamates that involves outer-sphere C N bond formation, protodeauration from inter-
Scheme 3. Proposed mechanism and stereochemical model for the gold(I)-catalyzed cyclization of N-allylic ureas 3.
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Hao Li et al.
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were synthesized employing standard procedures (see Sup-
porting Information).
mediate trans-II should be favored relative to proto-
deauration of cis-II owing to the unfavorable steric in-
teraction between the exocyclic CH2Au(P1) group
and the vicinal R group of cis-II that should be felt in
the transition state for protodeauration from cis-II to
form cis-4 (Scheme 3).
Preferential formation of cis-6 in the gold(I)-cata-
lyzed cyclization of N-allylic urea 5 is enigmatic but
may result from stabilizing ligation of the allylic hy-
droxy group to gold in the transition states for conver-
sion of cis-I to cis-II and/or the conversion of cis-II to
cis-4 that overrides the inherent steric destabilization
of these transition states. Alternatively, recent compu-
tational analyses have pointed to the potential role of
solvent, and/or counterion in the transfer of proton
from the protonated nucleophile to the a-carbon
À
Typical Procedure for the Synthesis of 1-Cyclohexyl-
4-methyl-3-(4-nitrophenyl)imidazolidin-2-one (2a)
A suspension of 1a (30 mg, 0.10 mmol), (P1)AuCl (0.53 mg,
1.0ꢁ10À3 mmol), and AgPF6 (0.25 mg, 1.0ꢁ10À3 mmol) in
CHCl3 (0.5 mL) was stirred for 15 h at room temperature.
The crude reaction mixture was loaded directly onto a silica
gel column and chromatographed (hexanes-EtOAc=6:1) to
give 2a as a yellow solid; yield: 30 mg (100%). TLC (hex-
anes-EtOAc=2:1): Rf =0.4; 1H NMR: d=8.14 (d, J=
9.6 Hz, 2H), 7.66 (d, J=9.6 Hz, 2H), 4.36 (m, 1H), 3.79 (m,
1H), 3.63 (t, J=8.8 Hz, 1H), 3.04 (dd, J=4.0, 8.8 Hz, 1H),
1.80–1.64 (m, 5H), 1.42–1.22 (m, 4H), 1.32 (d, J=6.0 Hz,
atom of the gold s-complex generated via nucleophil- 3H), 1.08 (m, 1H); 13C{1H} NMR: d=155.5, 145.3, 141.5,
ic addition to a gold(I) p-complex.[33] As such, it also
124.8, 117.4, 51.4, 48.8, 45.1, 30.4, 29.8, 25.4, 25.3, 18.8; IR
(neat): n=2938, 1684, 1503, 1323, 1252, 1111, 851, 751,
appears feasible that the pendant hydroxy group of 5,
690 cmÀ1; anal. calcd (found) for C16H21N3O3: H 6.98 (6.83),
either in protonated form or as part of hydrogen-
C 63.35 (63.30).
bonded species, may function as an intramolecular
Imidazolidin-2-ones 2b–2f, 4a–4d, and 6 were synthesized
proton source for the protodeauration of cis-II lead-
employing procedures similar to that used to synthesize 2a.
ing to preferential formation of cis-6.[34]
1,4-Dimethyl-3-(4-nitrophenyl)imidazolidin-2-one
(2b):
Yellow solid; yield: 92%. TLC (hexanes-EtOAc=2:1): Rf =
0.2; 1H NMR: d=8.11 (d, J=9.2 Hz, 2H), 7.62 (d, J=
9.2 Hz, 2H), 4.34 (m, 1H), 3.61 (t, J=8.8 Hz, 1H), 3.06 (dd,
J=3.6, 8.8 Hz, 1H), 2.85 (s, 3H), 1.31 (d, J=6.4 Hz, 3H);
13C{1H} NMR: d=156.6, 145.1, 141.7, 124.8, 117.6, 51.5, 48.5,
30.8, 18.9; IR (neat): n=2927, 1697, 1496, 1312, 1267, 1111,
845, 749, 690 cmÀ1; anal. calcd. (found) for C11H13N3O3: H,
5.57 (5.47); C, 56.16 (56.22).
Conclusions
We have shown that a 1:1 mixture of (P1)AuCl [P1=
o-biphenylPACHTUNGTRENNUNG(t-Bu)2] and AgPF6 catalyzes the 5-exo-
hydroamination of N-allylic N’-aryl ureas to form
monocyclic imidazolidin-2-ones in excellent yield
under mild conditions and with low catalyst loading.
Furthermore, in the case of N-allylic ureas that pos-
sessed an allylic alkyl, benzyloxymethyl, or acetoxy-
methyl substituent, gold(I)-catalyzed 5-exo-hydroami-
nation leads to formation of the corresponding trans-
4-Methyl-3-(4-nitrophenyl)-1-phenylimidazolidin-2-one
(2c): Yellow solid; yield: 93%. TLC (hexanes-EtOAc=3:1):
1
Rf =0.4; H NMR: d=8.26 (d, J=9.0 Hz, 2H), 7.77 (d, J=
9.5 Hz, 2H), 7.60 (br d, J=7.5 Hz, 2H), 7.42 (br t, J=
7.5 Hz, 2H), 7.17 (br t, J=7.5 Hz, 1H), 4.59 (m, 1H), 4.21
(t, J=9.0 Hz, 1H), 3.61 (dd, J=4.5, 9.0 Hz, 1H), 1.50 (d, J=
3,4-disubstituted imidazolidin-2-ones in ꢀ93% yield 6.5 Hz, 3H). 13C{1H} NMR:=d 153.9, 144.5, 142.5, 139.2,
129.0, 124.8, 123.8, 118.8, 118.5, 49.7, 48.3, 19.2; IR (neat):
with ꢀ50:1 diastereoselectivity.
n=2924, 1701, 1505, 1405, 1282, 1108, 754, 688 cmÀ1; anal.
calcd. (found) for C16H15N3O3: H 5.09 (4.98), C 64.64
(64.57).
1,4-Dimethyl-3-phenylimidazolidin-2-one (2d): Colorless
oil; yield: 86%. TLC (hexanes-EtOAc=3:1): Rf =0.4;
Experimental Section
1H NMR: d=7.40 (m, 2H), 7.31 (br d, J=7.6 Hz, 2H), 7.04
(br t, J=7.2 Hz, 1H), 4.28 (quintet of doublets, J=6.4 m
8.2 Hz, 1H), 3.56 (t, J=8.4 Hz, 1H), 3.01 (dd, J=6.0,
General Remarks
Catalytic reactions were performed in sealed glass tubes
under an atmosphere of dry nitrogen unless noted other-
wise. NMR spectra were obtained on a Varian spectrometer
operating at 400 MHz for 1H NMR and 100 MHz for
13C NMR in CDCl3 unless noted otherwise. IR spectra were
obtained on a Bomen MB-100 FT-IR spectrometer. Gas
chromatography was performed on a Hewlett–Packard 5890
gas chromatograph equipped with a 25 m polydimethylsil-
oxane capillary column. Flash column chromatography was
performed employing 200–400 mesh silica gel (EM). Thin
layer chromatography (TLC) was performed on silica gel 60
F254. Elemental analyses were performed by Complete
Analysis Laboratories (Parsippany, NJ). N-Allylic ureas
8.4 Hz, 1H), 2.84 (s, 3H), 1.25 (d, J=6.4 Hz, 3H);
13C{1H} NMR: d=158.3, 138.8, 128.7, 123.3, 120.9, 52.2, 49.0,
31.0, 18.8; IR (neat): n=2927, 1694, 1494, 1431, 1367, 1261,
756, 694 cmÀ1; anal. calcd. (found) for C11H14N2O: H 7.42
(7.29), C 69.45 (69.28).
3-(4-Methoxyphenyl)-4-methyl-1-phenylimidazolidin-2-
one (2e): White solid; yield: 97%. TLC (hexanes-EtOAc=
1
3:1): Rf =0.4; H NMR: d=7.58 (d, J=8.0 Hz, 2H), 7.34 (d,
J=7.2 Hz, 2H), 7.30 (d, J=8.8 Hz, 2H), 7.04 (t, J=7.2 Hz,
1H), 6.91 (d, J=7.2 Hz, 2H), 4.27 (m, 1H), 4.00 (t, J=
8.8 Hz, 1H), 3.78 (s, 3H), 3.46 (t, J=7.6 Hz, 1H), 1.28 (d,
J=5.6 Hz, 3H); 13C{1H} NMR: d=156.9, 155.8, 140.3, 130.9,
128.8, 124.8, 122.5, 117.7, 114.3, 55.5, 50.0, 19.3; IR (neat):
958
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Gold(I)-Catalyzed Intramolecular Hydroamination of N-Allylic N’-Arylureas
n=2979, 1688, 1501, 1401, 1241, 754, 688 cmÀ1; anal. calcd.
(found) for C17H18N2O2: H 6.43 (6.33), C 72.32 (72.15).
trans=3.7:1).
TLC
(hexanes-EtOAc=1:1):
Rf =0.45.
1H NMR: d=[8.15 (d, J=9.2 Hz), 8.12 (d, J=9.6 Hz),
(3.7:1), 2H], [7.70 (d, J=9.2 Hz), 7.56 (d, J=9.2 Hz),
(1:3.7), 2H)], [4.45 (quintet, J=6.9), 4.31 (dq J=2.0,
6.4 Hz), (3.7:1), 1H)], [3.97 (m), 3.34 (m), (3.7:1), 1 H],
[3.90–3.80 (m), 3.73 (m), (3.7:1), 2H] 3.61 (tt, J=4.0, 12 Hz,
1H), [2.35 (t, J=4.5 Hz), 2.18 (t, J=4.8 Hz), (1:3.7), 1H],
1.87–1.46 (m, 6H), 1.41–1.20 (m, 3H), [1.33 (d, J=6.4 Hz),
1.31 (d, J=6.4 Hz), (3.7:1), 3H], 1.11 (tq, J=3.6, 12.8 Hz,
1H); 13C{1H} NMR: d=[157.1, 155.7, (3.7:1)], [145.4, 144.8,
(1:3.7)], [142.1, 141.4, (3.7:1)], [124.9, 124.6 (1:3.7)], [119.3,
117.0, (3.7:1)] [63.1, 60.3, (1:3.7)], [59.6, 56.3, (1:3.7)], [53.9,
53.3 (3.7:1)], [52.6, 52.0 (1:3.7)], [32.4, 31.6 (1:3.7)], [30.6,
29.9 (1:3.7)], [26.0, 25.3 (3.7:1)], [18.9, 12.3 (1:3.7)]; IR
(neat): n=2932, 1684, 1503, 1320, 1248, 1112, 850, 729,
694 cmÀ1; HR-MS: m/z=333.1676, calcd. for C17H23N3O4
(M+): 333.1689.
1-Cyclohexyl-4-methyl-3-phenylimidazolidin-2-one
(2f):
Colorless oil; yield: 92%. TLC (hexanes-EtOAc=2:1): Rf =
1
0.4; H NMR: d=7.42 (d, J=8.0 Hz, 2H), 7.30 (t, J=8.0 Hz,
2H), 7.02 (br t, J=7.2 Hz, 1H), 4.27 (quintet of doublets,
J=6.0, 8.8 Hz, 1H), 3.78 (m, 1H), 3.56 (t, J=8.8 Hz, 1H),
2.98 (dd, J=5.6, 8.4 Hz, 1H), 1.80–1.64 (m, 5H), 1.43–1.21
(m, 4H), 1.25 (d, J=6.0 Hz, 3H), 1.08 (m, 1H);
13C{1H} NMR: d=157.2, 139.1, 128.7, 123.0, 120.1, 51.2, 49.3,
45.5, 30.3, 30.1, 25.6, 18.9; IR (neat): n=2930, 1691, 1419,
1255, 755, 694 cmÀ1; anal. calcd. (found) for C16H22N2O: H
8.58 (8.60), C 74.38 (74.43).
trans-1-Cyclohexyl-4,5-dimethyl-3-(4-nitrophenyl)imidazo-
lidin-2-one (4a): Yellow solid; yield: 100%. TLC (hexanes-
EtOAc=3:1): Rf =0.6; 1H NMR: d=8.14 (d, J=9.6 Hz,
2H), 7.67 (d, J=9.2 Hz, 2H), 3.82 (dq, J=2.8, 6.0 Hz, 1H),
3.62 (tt, J=3.6, 12.0 Hz, 1H), 3.35 (dq, J=2.4, 6.0 Hz, 1H),
1.92–1.05 (m, 10H), 1.29 (d, J=6.0 Hz, 3H), 1.28 (d, J=
6.0 Hz, 3H); 13C{1H} NMR: d=154.9, 145.7, 141.4, 124.8,
117.0, 57.4, 54.5, 53.2, 32.2, 30.6, 25.9, 25.8, 25.4, 21.8, 18.2;
IR (neat): n=2932, 1645, 1491, 1328, 1302, 1238, 1110, 750,
702, 639 cmÀ1; anal. calcd. (found) for C17H23N3O3: H 7.30
(7.41), C 64.33 (64.32).
trans-1-Cyclohexyl-5-isopropyl-4-methyl-3-(4-nitrophen-
yl)imidazolidin-2-one (4b): Yellow solid; yield: 93%. TLC
(hexanes-EtOAc=3:1): Rf =0.6; 1H NMR: d=8.14 (d, J=
9.2 Hz, 2H), 7.72 (d, J=9.2 Hz, 2H), 3.96 (br q, J=6.0 Hz,
1H), 3.55 (m, 1H), 3.16 (m, 1H), 2.03–1.08 (m, 10H), 1.28
(d, J=6.0 Hz, 3H), 0.95 (d, J=6.8 Hz, 3H), 0.75 (d, J=
6.4 Hz, 3H); 13C{1H} NMR: d=155.2, 145.4, 141.2, 125.1,
116.2, 64.2, 54.0, 49.7, 31.9, 30.7, 30.4, 26.0, 25.4, 20.2, 17.9,
14.3; IR (neat): n=2935, 1698, 1495, 1297, 1246, 1107, 854,
754, 692 cmÀ1; anal. calcd- (found) for C19H27N3O3: H 7.88
(7.95), C 66.06 (65.98).
Relative Configurations of 4,5-Disubstituted
Imidazolidin-2-ones
The trans configuration of 4,5-disubstituted imidazolidin-2-
ones 4a–4d was assigned on the basis of the vicinal H-4/H-5
3
coupling constants, which ranged from JH,H ꢁ1 Hz for 4b
3
and 4c to JH,H =2.4 Hz for 4a. Published values for the vici-
nal H-4/H-5 coupling constant of trans-4,5-disubstituted imi-
dazolidin-2-ones range from 0–3 Hz,[9] while the the vicinal
H-4/H-5 coupling constant of cis-4,5-disubstituted imidazoli-
din-2-ones range from 7–9 Hz.[11,15,18] In the same way, the cis
and trans configurations of the major and minor diastereo-
mers of 6 were assigned on the basis of the vicinal H-4/H-5
3
3
coupling constants of JH,H ꢁ7 Hz (major) and JH,H ꢁ2 Hz
(minor).
N-(2-Aminopropyl)benzenamine (8)[34]
trans-4-(Benzyloxymethyl)-3-cyclohexyl-5-methyl-1-(4-ni-
trophenyl)imidazolidin-2-one (4c): Yellow oil; yield: 98%.
TLC (hexanes-EtOAc=3:1): Rf =0.5; H NMR: d=8.08 (d,
A solution of 2e (50 mg, 0.18 mmol) in CH3CN (2 mL) at
08C was treated with a solution of ceric ammonium nitrate
(CAN, 0.29 g, 0.53 mmol) in water (2.5 mL) over 3 min. The
solution was stirred for 25 min at 08C, diluted with water
(10 mL), and extracted with EtOAc (3ꢁ10 mL). The com-
bined organic extracts were dried (MgSO4) and concentrat-
ed under vacuum to give an oily residue that was chromato-
graphed (EtOAc-hexanes=2:1) to give 4-methyl-1-phenyl-
1
J=9.2 Hz, 2H), 7.62 (d, J=9.2 Hz, 2H), 7.28–7.19 (m, 5H),
4.45 (s, 2H), 4.13 (dq, J=0.8, 6.0 Hz, 1H), 3.58 (tt, J=3.6,
12.0 Hz, 1H), 3.50 (m, 1H), 3.33 (m, 1H), 1.82–1.47 (m,
6H), 1.35–1.18 (m, 3H), 1.23 (d, J=6.4 Hz, 3H), 1.03 (tq,
J=3.2, 12.8 Hz, 1H); 13C{1H} NMR: d=155.2, 145.5, 141.3,
137.3, 128.4, 127.9, 127.7, 124.9, 116.6, 73.4, 70.8, 57.9, 53.3,
53.2, 32.1, 30.5, 25.8, 25.7, 25.3, 18.7; IR (neat): n=2931,
1701, 1503, 1321, 1234, 849, 751, 697 cmÀ1; anal. calcd.
(found) for C24H29N3O4: H 6.90 (6.92), C 68.06 (67.95).
trans-(3-Cyclohexyl-5-methyl-1-(4-nitrophenyl)-2-oxoimi-
dazolidin-4-yl)methyl acetate (4d): Yellow solid; yield: 98%.
AHCTUNGTRENNUNG
(4 mL) was refluxed for 30 h and then extracted with
CH2Cl2 (3ꢁ10 mL). The aqueous layer was made basic
(pHꢀ12) with 15% NaOH and then extracted with CH2Cl2
(3ꢁ10 mL). The combined organic extracts were dried
(MgSO4) and concentrated under vacuum to give pure 8 as
1
TLC (hexanes-EtOAc=3:1): Rf =0.4; H NMR: d=8.14 (d,
1
a colorless oil; yield: 16 mg (77%). The H and 13C NMR
J=9.2 Hz, 2H), 7.69 (d, J=9.2 Hz, 2H), 4.26 (dd, J=3.6,
11.6 Hz, 1H), 4.16 (dq, J=1.6, 6.0 Hz, 1H), 3.91 (dd, J=7.2,
11.6 Hz, 1H), 3.67 (tt, J=3.6, 12.0 Hz, 1H), 3.45 (ddd, J=
1.6, 3.6, 7.2 Hz, 1H), 2.00 (s, 3H), 1.93–1.54 (m, 6H), 1.47–
1.26 (m, 3H), 1.31 (d, J=6.0 Hz, 3H), 1.11 (tq, J=3.6,
12.8 Hz, 1H); 13C{1H} NMR: d=170.6, 155.1, 145.2, 141.6,
125.0, 116.7, 64.4, 56.8, 53.4, 53.3, 32.2, 30.6, 25.8, 25.7, 25.3,
20.7, 18.8. IR (neat, cmÀ1): 2930, 1706, 1503, 1324, 1219,
spectra of 7 and 8 were identical with published data.[19,34]
Acknowledgements
1040, 858, 752, 693 cmÀ1
;
Anal. calcd (found) for
C19H25N3O5: H, 6.71 (6.62); C, 60.79 (60.64).
cis-1-Cyclohexyl-5-(hydroxymethyl)-4-methyl-3-(4-nitro-
phenyl)imidazolidin-2-one (6): Yellow oil; yield: 97% (cis:-
Acknowledgements is made to the NIH (GM-080422) for
support of this research and to the NCBC (2008-IDG-1010)
for support of the Duke University NMR facility.
Adv. Synth. Catal. 2011, 353, 955 – 962
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asc.wiley-vch.de
959

Hao Li et al.
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