A palladium-catalyzed multicomponent synthesis of imidazolinium salts and imidazolines from imines, acid chlorides, and carbon monoxide

Article abstract of DOI:10.1021/jo101858d

A palladium-catalyzed multicomponent synthesis of imidazolinium carboxylates and imidazolines is described. The palladium catalyst [Pd(CH(R ¹)N(R²)COR³)Cl]₂, or [Pd(allyl)Cl]₂, with P(t-Bu)₂(2-biphenyl) can mediate the simultaneous coupling of two imines, acid chloride, and carbon monoxide into substituted imidazolinium carboxylates within hours under mild conditions (45 °C, 4 atm of CO). The reaction proceeds in good yield with aryl-, heteroaryl-, and alkyl-substituted acid chlorides, as well as variously functionalized imines. Imidazolines are formed via the initial generation of Muenchnone intermediates, followed by their cycloaddition with an in situ generated protonated imine. The addition of an amine base can intercept catalysis at Muenchnone formation, which allows the subsequent cycloaddition of a second imine. The latter provides a route for the assembly of complex, polysubstituted imidazolinium carboxylates with independent control of all five substituents. The subsequent removal of the nitrogen substituent(s) provides an overall synthesis of imidazolines.

Full text of DOI:10.1021/jo101858d

pubs.acs.org/joc
A Palladium-Catalyzed Multicomponent Synthesis of Imidazolinium Salts and
Imidazolines from Imines, Acid Chlorides, and Carbon Monoxide
ꢀ
Kraig Worrall, Boran Xu, Sebastien Bontemps, and Bruce A. Arndtsen*
Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, Quebec, Canada H3A 2K6
bruce.arndtsen@mcgill.ca
Received September 20, 2010
A palladium-catalyzed multicomponent synthesis of imidazolinium carboxylates and imidazolines is
described. The palladium catalyst [Pd(CH(R1)N(R2)COR3)Cl]2, or [Pd(allyl)Cl]2, with P(t-Bu)2(2-
biphenyl) can mediate the simultaneous coupling of two imines, acid chloride, and carbon monoxide
into substituted imidazolinium carboxylates within hours under mild conditions (45 °C, 4 atm of
CO). The reaction proceeds in good yield with aryl-, heteroaryl-, and alkyl-substituted acid chlorides,
as well as variously functionalized imines. Imidazolines are formed via the initial generation of
€
Munchnone intermediates, followed by their cycloaddition with an in situ generated protonated
imine. The addition of an amine base can intercept catalysis at Munchnone formation, which allows
€
the subsequent cycloaddition of a second imine. The latter provides a route for the assembly of
complex, polysubstituted imidazolinium carboxylates with independent control of all five substitu-
ents. The subsequent removal of the nitrogen substituent(s) provides an overall synthesis of
imidazolines.
Introduction
antidepressants,3 antidiabetics,4 and a variety of natural pro-
ducts.5 In addition, imidazolines have been employed as com-
ponents in peptidomimetics6 and have found significant use as
metal coordinating ligands,7 precursors to chiral N-heterocyclic
carbenes,8 or building blocks in organic synthesis.9 This utility
has stimulated interest in the design of efficient routes to these
heterocycles. The classic synthesis of imidazolines involves the
Imidazolines are found in a diverse range of biologically rele-
vant compounds, including anticancer agents,1 vasoregulators,2
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Published on Web 12/10/2010
DOI: 10.1021/jo101858d
r
2010 American Chemical Society

Worrall et al.
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cyclization of substituted 1,2-diamines with electrophiles (e.g.,
esters,10 amides,11 imidates,12 or aldehydes in concert with oxi-
dants),13 or β-substituted amidines.14 Alternatively, a number
of cycloaddition strategies have also been developed for the
assembly of imidazolines. These include the reaction of isocya-
nides with imines,15 the ring expansion of aziridines with
nitriles,16 and the cycloaddition of imines with imidate-derived
azomethine ylides.17
SCHEME 1. Palladium-Catalyzed Imidazolinium Carboxylate
Formation
While each of these approaches can be effective, one
feature they typically share is the need to build up the
precursor(s) with the desired substituents prior to cycliza-
tion. The latter can take multiple steps for highly substituted
imidazolines, complicating not only its synthesis but also
product diversification. An alternative is to assemble poly-
substituted heterocycles such as imidazolines directly from
multiple, available building blocks. As we18 and others19
have previously described, metal catalysis can provide a
useful tool for mediating such reactions, by activating simple
substrates toward reaction. We have previously reported
that this approach can be applied to the synthesis of imida-
zolinium carboxylates, via the palladium-catalyzed coupling
of imines, acid chlorides, and CO (Scheme 1).20 Notably, this
route avoids the need to construct complex substrates for
cyclization and instead employs building blocks that are all
either available (carbon monoxide and acid chlorides) or
easily generated (imines, from aldehydes and amines).
SCHEME 2. Proposed Mechanism for Imidazoline Formation
The reaction in Scheme 1 has been postulated to proceed
through a series of palladium-mediated operations to form
€
compounds were initially reported by Huisgen in 1964
and are reactive 1,3-dipolar cycloaddition substrates.21 Un-
der the catalytic conditions shown in Scheme 1, protonated
imine undergoes rapid cycloaddition to 3 to form the imida-
zoline core. The addition of the amine can block this cyclo-
(10) (a) Neef, G.; Eder, U.; Sauer, G. J. Org. Chem. 1981, 46, 2824. (b)
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J. Org. Chem. 1948, 13, 830.
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(c) Ishihara, M.; Togo, H. Synlett 2006, 227. (d) Sayama, S. Synlett 2006, 1479.
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25, 461.
Munchnone intermediates 3 (Scheme 2).20 The latter dipolar
addition, by inhibiting the formation of protonated imine
€
22
leading to the catalytic synthesis of Munchnones. More
recently, Tepe23 reported the synthesis of imidazoline car-
boxylic acids via TMS-mediated cycloaddition of imines
(15) (a) Hayashi, T.; Kishi, E.; Soloshonok, V. A.; Uozumi, Y. Tetra-
hedron Lett. 1996, 37, 4969. (b) Lin, R.-Y.; Zhou, X.-T.; Dai, L.-X.; Sun, J. J.
€
with Munchnones.
ꢀ
Org. Chem. 1997, 62, 1799. (c) Aydin, J.; Kumar, K. S.; Eriksson, L.; Szabo,
Considering the efficiency of the palladium-catalyzed
synthesis in Scheme 1, we became interested in the potential
of using this methodology as a general approach to assemble
the imidazoline core. However, the original report showed
this reaction to be sluggish, typically requiring 4 days for
complete conversion. In addition, the reaction has limited
scope (R1 = Ph or Me; R3 = p-tolyl), requires the formation
of products containing two identical imines, and thus gen-
erates only symmetrically substituted products. We describe
herein our efforts toward addressing these issues. This
includes the development of a highly active palladium cata-
lyst for this synthesis, which can allow the coupling to
proceed in hours under mild conditions. In addition, via
modification of the reaction conditions, a diverse range of
substituted imidazolinium salts and imidazolines can be
generated, including the selective incorporation of different
imines into the heterocyclic core. Overall, this provides a
straightforward route to the formation of these products in a
single operation, and with high atom economy.
K. J. Adv. Synth. Catal. 2007, 349, 2585. (d) Elders, N.; Ruijter, E.; de Kanter,
F. J. J.; Groen, M. B.; Orru, R. V. A. Chem.;Eur. J. 2008, 14, 4961.
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Monteiro, N. In Multicomponent Reactions; Zhu, J., Bienayme, H., Eds.;
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2001, 40, 3228.
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1964, 3, 135. (b) Huisgen, R.; Gotthardt, H.; Bayer, H. O.; Schaefer, F. C.
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Oxazoles; Turchi, I. J., Ed.; Wiley: New York, 1986; Vol. 45, p 731. (d) Potts,
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TABLE 1. Influence of Ligands on Imidazolinium Carboxylate
Synthesisa
monodentate phosphine ligands.24 As shown in entries 5 and
6, the addition of smaller phosphines completely inhibits
catalysis, presumably due to their strong coordination to
palladium, which blocks carbonylation (step C). Interest-
ingly, bulkier triarylphosphines, while allowing catalysis
to proceed, had little influence on the rate of imidazoline
formation, with the conversion at short reaction times
similar to the results without ligand (entries 7-9). This
includes P(o-tolyl)3 (entry 7), which has been previously
demonstrated to accelerate catalysis in related carbonylation
reactions to form pyrroles and imidazoles.25
The lack of acceleration with the bulky triarylphosphine
ligands may result from the relatively poor coordinating ability
under the catalytic conditions, where there is both an excess of
carbon monoxide and imine present. Therefore, several more
strongly coordinating dialkyl- or trialkylphosphines were exam-
ined. As we had hoped, these ligands were found to significantly
accelerate catalysis. From a survey of different ligands, the di-
tert-butyl-2-biphenylphosphine 7 (entry 16) conveys the greatest
rate enhancement, allowing imidazolinium formation to proceed
to completion within a matter of hours at 45 °C. Notably, the
commercial Pd2(dba)3 CHCl3 can also be employed with this
3
ligand (entry 17), as can [Pd(allyl)Cl]2 (entry 18). With ligand 7,
the catalyst loadings can be decreased without a loss in yield
(0.5 mol % 6, entry 20).26
This optimized catalyst system provides an efficient
method for generating a number of imidazolinium carboxy-
lates (Table 2).27 For example, aryl, heteroaryl, and even
alkyl substituents can be incorporated into the 2-imidazo-
line position from the acid chloride (entries 3, 4, and 5,
respectively). A range of imines derived from aromatic
aldehydes are also viable substrates in the reaction. Ex-
amples include those with halo, thioether, ether, and even
furanyl substituents (entries 3-6, respectively). However,
enolizable imines (e.g., R1 = i-Pr) and those with bulky
nitrogen substituents (R2 = i-Pr) are not compatible with
the reaction, presumably because of the instability of these
iminium salts.28
Selective Synthesis of Diversely Substituted Imidazolium
Carboxylates. One limitation with this approach is the fact
that the products all result from the coupling of two identical
imines and thus generate only symmetrically substituted diaryl-
substituted compounds. In general, attempts to employ two
different imines in this reaction lead to mixtures of products. The
latter is an issue often encountered in multicomponent synthesis,
where two similar substrates can be difficult to differentiate.29
However, as one can see from the mechanism of this catalytic
coupling (Scheme 2), the imines are incorporated into the imi-
dazolinium structure via fundamentally different operations,
aGeneral: imine (52 mg, 0.25 mmol), benzoyl chloride (17 mg, 0.12 mmol),
5% catalyst, 800 μL of CD3CN, 4.0 atm of CO, in J. Young NMR tube,
45 °C. Yield based on 1H NMR comparison to internal standard. For entry
18, 25 mol % 7 was used.
Results and Discussion
Catalyst Development. Our initial studies focused on
developing a more active palladium catalyst for the imidazoli-
nium carboxylate formation shown in Scheme 1. In considering
the postulated mechanism for this reaction (Scheme 2), we noted
that the bidentate bipyridine ligand present on the catalyst must
be displaced by either iminium salt oxidative addition (step B) or
CO coordination (step C) during the catalytic cycle, implying
that the ligand may be slowing these steps. As shown in Table 1,
€
with the first undergoing carbonylation to form a Munchnone
(24) Dhawan, R.; Arndtsen, B. A. J. Am. Chem. Soc. 2004, 126, 468.
(25) Siamaki, A. R.; Arndtsen, B. A. J. Am. Chem. Soc. 2006, 128, 6050.
(26) In addition to enhancing the reaction rate, catalysis with bulky
phosphines proceeds rapidly with the 2:1 imine:acid chloride ratio, rather
than the excess acid chloride employed with bipyridine ligands. While the
reason for this effect is as yet unclear, we postulate that the second imine acts
as a base to accelerate HCl elimination.
(27) All products were formed as a single diastereomer and consistent
with the trans orientation of the aryl groups previously noted.20
(28) For example, enolizable imines rapidly generate enamides from
performing this same coupling with only 5% Pd2dba3 CHCl3
3
and no added ligand leads to the generation of 4a in 24 h
(entry 2), in contrast to the 4 days under analogous conditions
with bipyridine present. Similar results are observed using the
palladacycle intermediate 6 as a catalyst (generated by pretreat-
ing Pd2dba3 with imine and acid chloride, entry 3).
iminiium salts 1. BnNdC(H)t-Bu has been previously employed to generate
€
dipolar cycloaddition.
22
Munchnones, but they are presumably too bulky to allow subsequent
We have previously reported that the rate of iminium
salt 1 carbonylation can be accelerated by the addition of
(29) For example: (a) Yamamoto, Y.; Saito, S. Chem. Rev. 2000, 100,
2901. (b) Gandon, V.; Aubert, C.; Malacria, M. Chem. Commun. 2006, 2209.
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TABLE 2. Substrate Diversity in Imidazoline Carboxylate Synthesisa
SCHEME 3. A Palladium-Catalyzed Route to Diversely Sub-
stituted Imidazolinium Salts
€
of imines to Munchnones is known to lead to the formation
of β-lactams, via reaction with the ketene tautomer of 3, rather
€
than the Munchnones undergoing dipolar cycloaddition to form
imidazolinium carboxylates.30,31 This can be circumvented by
the addition of benzenesulfonic acid, which catalyzes the dipolar
€
cycloaddition of an N-allyl-substituted imine with Munchnone
3a and forms 8a within hours at ambient temperature
(Scheme 3). A small amount of the inseparable homocoupled
imidazoline product 4c is generated under these conditions. The
latter can be inhibited by the use of a slight excess of acid chloride
€
in the initial Munchnone synthesis and allows the clean genera-
tion of 8a in one pot and good yield (Table 3, entry 1).
The reaction in Table 3 provides what is to the best of our
knowledge a unique method for constructing a diversely sub-
stituted imidazoline core from four separate and tunable sub-
strates. The systematic variation of these building blocks can be
used to form diverse families of products. Perhaps most notable
is the diversity that can be incorporated into the second imine
cycloaddition step. This includes not only relatively stabilized
C-aryl-substituted imines but also a range of less stable imines.
For example, C-heteroaryl imines, which cannot be incorporated
into homocoupled imidazolines, can be used to form pyridinyl-
substituted (entry 11) and furanyl-substituted (entry 12) pro-
ducts. N-Aryl-substituted imines can be used in the cycloaddi-
tion step (entry 3), as can N-allyl-protected imines (entry 1).
Alternatively, polycyclic imidazolinium salts can be readily pre-
pared via the cycloaddition of cyclic imines (entries 9 and 10), as
can even less stable formaldimines (entries 13-16). The latter
products lack substitution at the 4-position of the imidazoline
ring. Overall, this provides a straightforward method for assem-
bling small libraries of imidazolium salts in one pot, where any of
the core substituents can be selectively modified from the
appropriate imine(s) or acid chloride.
aGeneral: imine (0.49 mmol), acid chloride (0.27 mmol), 5 (26 mg,
0.025 mmol), 7 (22 mg, 0.075 mmol), 15 mL of CH3CN, 4.0 atm of CO,
45 °C, 16 h.
and the second involved in dipolar cycloaddition. Thus, con-
struction of more complex imidazolines via the arrest of catalysis
€
at Munchnone formation should be possible (steps A-E of
Imidazoline Synthesis. In addition to imidazolium salts, we
have examined the application of this approach to the construc-
tion of imidazolines. A feature of the reaction in Table 3 is
the ability to selectively incorporate removable substituents at
either nitrogen of 8 from the appropriate imine(s). As shown in
Scheme 4, coupling the catalytic synthesis with deprotection can
allow the synthesis of variously substituted imidazoline esters.32
Scheme 2), which could then be followed by the cycloaddition of
a different imine in a subsequent step.
As we have previously reported, the addition of NEt(i-Pr)2
base to the palladium-catalyzed reaction mixture can block the
formation of imidazolinium carboxylates and instead allow the
in situ formation of Munchnone 3a (Scheme 3).22 The addition
€
(30) (a) Dhawan, R.; Dghaym, R. D.; St. Cyr, D. J.; Arndtsen, B. A. Org.
Lett. 2006, 8, 3927. (b) Croce, P. D.; Ferraccioli, R.; La Rosa, C. Tetrahedron
1995, 51, 9385. (c) Huisgen, R.; Funke, E.; Schaefer, F. C.; Knorr, R. Agnew.
Chem., Int. Ed. 1967, 6, 367.
(31) Dhawan, R.; Dghaym, R. D.; Arndtsen, B. A. In Catalysis of Organic
Reactions; Morrell, D., Ed.; Dekker: New York, 2003.
(32) Itis necessary to introduce a methyl ester protecting group before nitrogen
deprotection; otherwise, decarboxylation of the parent compound is observed.
J. Org. Chem. Vol. 76, No. 1, 2011 173

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TABLE 3. A Palladium-Catalyzed Route to Diversely Substituted Imidazoline Carboxylatesa
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TABLE 3. Continued
aGeneral: imine (0.22 mmol), acid chloride (0.31 mmol), 5% 6 (0.01 mmol), 15% 7 (10 mg, 0.03 mmol), 6 mL of a 1:1 THF/CH3CN mixture, NEt(i-Pr)2 (55 μL,
0.31 mmol), 4.0 atm of CO, 45 °C, 16 h, followed by addition of imine (0.44 mmol) and PhSO3H (28 mg, 0.18 mmol) in 2 mL of CH3CN at room temperature for 3 h.
For example, BBr3 treatment of the R1 = p-methoxybenzyl-
subtituted 8 allows the formation of imidazoline 9a in 48%
overall yield from imines and acid chloride. Alternatively, the use
of N-allyl imines for cycloaddition followed by palladium-
catalyzed deprotection can be used to form the 5-ester-substi-
tuted isomer 10a. By changing the position of the protecting
group, this strategy can access various isomers of imidazolines,
or even the stepwise formation of N,N0-unsubstituted products
(11). Relative to traditional approaches to polysubstituted
imidazolines, this represents an effective and modular synthesis
of these products from simple imines, acid chloride, and CO.
As an illustration of the potential utility of this reaction,
we have examined its application to the synthesis of imidazo-
line 12 (Scheme 5). The latter has been identified by Tepe and
J. Org. Chem. Vol. 76, No. 1, 2011 175

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SCHEME 4. Synthesis of Polysubstituted Imidazolines
SCHEME 5. Synthesis of Imidazoline 12 and Its 5-Carboxylic Acid Isomer
Sharma as a potent sensitizer for cancer treatment.33 As
shown, the palladium-catalyzed formation of 8q followed by
deprotection can provide an efficient overall synthesis of 12
in good yield. In addition to forming 12, a potentially useful
feature of this chemistry is its ability to access variants of
these products. For example, via variation of the position of
the protecting group on the imines employed, a new 5-car-
boxylic acid isomer of 12, 120, can be generated using the
same acid chloride, and a simple N-allyl imine for cycloaddi-
tion. In principle, this modularity can be applied to access a
range of new variants to these heterocycles.
provides one-pot access to imidazolines where each substituent
can be independently varied from the appropriate imine(s) or
acid chlorides. Considering the availability of the building
blocks, this provides an efficient and tunable alternative to
classic synthesis of these heterocycles. Experiments directed
toward the application of this method to alternative imidazoline
targets are currently underway.
Experimental Section
General Considerations. All manipulations were conducted in
a glovebox under a nitrogen atmosphere. Unless otherwise
noted, all reagents were purchased from commercial sources
and used without purification. Carbon monoxide (99.99%) was
used as received. Solvents were dried by being passed through
alumina except acetonitrile, which was distilled from CaH2 and
degassed. Once collected, solvents were stored under nitrogen
Conclusions
In conclusion, we have described a straightforward, palladium-
catalyzed approach to the assembly of substituted imidazoli-
nium carboxylates directly from acid chlorides, imines, and
carbon monoxide. When coupled with N-deprotection, this
over activated molecular sieves inside the glovebox. Pd2(dba)3
3
CHCl3 was prepared using literature techniques.34 Aldimines
were prepared from the condensation of aldehyde and amine
(33) Sharma, V.;Peddibhotla, S.;Tepe, J. J.J. Am. Chem. Soc. 2006, 128, 9137.
176 J. Org. Chem. Vol. 76, No. 1, 2011

Worrall et al.
JOCArticle
using concentrated aqueous NaCl as a drying agent and then
distilled under vacuum. Formaldimines were prepared follow-
ing literature procedures35 or purchased as the trisubstituted
triazine. Amide-chelated palladacycle catalysts 6 were prepared
(ii) 4,5-Bis(4-bromophenyl)-2-cyclohexyl-1,3-bis-furan-2-yl-
methyl-2-imidazolinium-4-carboxylate (4e). The product was
precipitated from ethyl acetate with diethyl ether at room
1
temperature. Yield of 42%. H NMR (400 MHz, CD3OD): δ
by pretreating Pd2(dba)3 CHCl3 with imine and acid chloride as
7.73 (m, 1H), 7.55 (d, J = 8.0 Hz, 2H), 7.44 (d, J = 8.5 Hz, 2H),
7.28 (s, 1H), 7.18 (t, J = 5.8 Hz, 4H), 6.50 (m, 1H), 6.37 (m, 1H),
6.19 (m, 1H), 5.63 (m, 1H), 5.38 (d, J = 16.1 Hz, 1H), 5.18 (d,
J= 16.1 Hz, 1H), 4.83 (d, J= 15.9 Hz, 1H), 4.13 (d, J = 15.9 Hz,
1H), 3.42-3.35 (m, 1H), 2.22-2.19 (m, 1H), 2.07-1.88 (m, 4H),
1.80-1.75 (m, 2H), 1.55-1.34 (m, 3H). 13C NMR (125.71 MHz,
CD3OD): δ 169.7, 167.9, 148.5, 145.6, 144.2, 142.2, 139.2, 133.6,
131.6, 131.55, 129.7, 123.4, 123.0, 112.0, 111.0, 110.8, 110.5,
109.0, 81.3, 72.8, 42.6, 42.4, 37.4, 27.3, 27.0, 25.5 (two carbons),
24.6. HRMS (C32H30Br2N2O4): calcd (M þ 1) 665.0651, ob-
3
previously reported.22 Benzenesulfonic acid was purchased as
the dry acid (not as the monohydrate) and dried under vacuum
for 48 h. Iminium salt (imine PhSO3H) hydrolysis was tested by
3
1H NMR to ensure dryness. Deuterated acetonitrile was stirred
˚
with CaH2, vacuum transferred, degassed, and stored over 4 A
molecular sieves.
Nuclear magnetic resonance (NMR) characterization was
1
realized at 200, 300, 400, and 500 MHz for H NMR and at
75, 100, and 125 MHz for 13C NMR. 1H and 13C NMR chemical
shifts were referenced to residual solvent. 13C NMR spectra had
no signals in the regions not recorded (0-20 ppm). Mass spectra
were recorded on a high-resolution electrospray ionization
quadrupole mass spectrometer. Compounds 4a-c and 12 were
characterized by comparison to previous reports.20,33
served 665.0652. IR: νCO 1630, 1568 cm-1
.
(iii) 4,5-Bisbenzo[1,3]dioxol-5-yl-1,3-dibenzyl-2-p-tolyl-2-imid-
azolinium-4-carboxylate (4f). Yield of 70%. 1H NMR (400 MHz,
CD3OD): δ 7.41 (s, 2H), 7.35-6.61 (m, 18H), 6.05 (s, 2H), 5.95
(d, J=14.1 Hz, 2H), 5.45 (s, 1H), 4.89 (d, J=14.9 Hz, 1H), 4.45 (m,
2H), 4.05 (d, J=14.9 Hz, 1H), 2.40 (s, 3H). 13C NMR (100.62
MHz, DMSO): δ 165.7, 164.6, 148.2, 147.4, 147.3, 142.7, 136.3,
134.4, 133.5, 130.4, 130.3, 130.2, 128.8, 128.6, 129.4, 128.4, 128.0,
123.7, 123.7, 122.4, 120.6, 109.7, 109.3, 108.0, 101.6, 101.5, 73.7,
83.0, 50.3, 49.2, 21.5. HRMS (C39H32N2O6): calcd (M þ 1)
Ligand Screening. Reactions were set up in J. Young NMR
tubes fitted with PTFE valves. (4-CH3C6H4)HCdNCH2C6H5
(52.3 mg, 0.25 mmol), benzoyl chloride (17.0 mg, 0.12 mmol),
palladium catalyst (0.007 mmol), ligand (0.018 mmol), and benzyl
benzoate NMR standard (0.25 mmol) were combined in 800 μL of
CD3CN, stirred until the mixture was homogeneous, and trans-
ferred to the NMR tube. One freeze-pump-thaw cycle was con-
ducted before the tube’s contents were pressurized with 4.0 atm of
CO. The conversion to product was determined by 1H NMR
analysis by comparison to the benzyl benzoate standard.
625.23389, observed 625.2334. IR: νCO 1639, 1556 cm-1
.
(iv) 1,3-Dibenzyl-2-isopropyl-4,5-di-p-tolyl-2-imidazolinium-
4-carboxylate (4g). Yield of 93%. 1H NMR (300 MHz, CDCl3):
δ 7.50-7.00 (m, 16H), 6.69-6.92 (m, 2H), 5.20 (d, J = 17.6 Hz,
1H), 5.17 (s, 1H), 4.95 (d, J = 14.7 Hz, 1H), 4.90 (d, J = 17.2 Hz,
1H), 4.05 (d, J = 14.7 Hz, 1H), 3.25 (m, 1H), 2.35 (s, 3H), 2.29 (s,
3H), 1.50-1.39 (d, J = 7.3 Hz, 3H), 1.15-1.03 (d, J = 7.2 Hz,
3H). 13C NMR (75.46 MHz, CDCl3): δ 169.3, 166.6, 139.4,
138.8, 137.5, 136.9, 132.0, 131.3, 129.8, 129.7, 129.5, 129.1,
128.9, 128.5, 128.0, 127.4, 83.6, 72.7, 51.5, 49.3, 27.2, 21.7, 21.3,
18.3, 18.2. HRMS (C35H36N2O2):calcd(Mþ 1) 517.2855, observed
Typical Synthesis of Homocoupled Imidazolinium Carboxy-
lates (4a). In a 50 mL sealed glass reaction bomb equipped with a
magnetic stir bar, (4-CH3C6H4)HCdNCH2C6H5 (102 mg, 0.49
mmol), benzoyl chloride (38 mg, 0.27 mmol), Pd2(dba)3 CHCl3
3
5 (26 mg, 0.025 mmol), and di-tert-butyl-2-biphenylphosphine 7
(22 mg, 0.75 mmol) were combined in 15 mL of acetonitrile and
stirred for 15 min until the mixture was homogeneous. One
freeze-pump-thaw cycle was conducted before the bomb’s
contents were pressurized with 4.0 atm of CO. The reaction
mixtures were left for 16 h at 45 °C; the solvent was removed in
vacuo and the residue dissolved in CH2Cl2 and filtered through
Celite.36 The organic phase was washed sequentially with brine,
0.1 M HCl, and concentrated Na2CO3. The organic phase was
dried over Mg2SO4, filtered, concentrated to ca. 0.5 mL, and
then diethyl ether was added. Precipitation at -35 °C afforded
4a as a solid (0.23 mmol, 92%).37
517.2850. IR: νCO 1635, 1557 cm-1
.
(v) 1,3-Dibenzyl-2-isobutyl-4,5-di-p-tolyl-2-imidazolinium-4-car-
boxylate (4h). Yield of 49%. 1H NMR (400 MHz, CDCl3): δ
7.45-6.56 (m, 16H), 5.25 (s, 1H), 5.09 (d, J=17.0 Hz, 1H), 4.80
(d, J=15.4 Hz, 1H), 4.65 (d, J=16.7 Hz, 1H), 4.00 (d, J=15.2 Hz,
1H), 2.50 (m, 1H), 2.38-2.30(m,2H),2.29(s,3H),2.23(s,3H),1.05
(m, 6H). 13C NMR (100.62 MHz, CDCl3): δ 166.1, 165.5, 138.9,
138.4, 135.4, 132.4, 131.1, 129.5, 129.4, 129.3, 129.2, 129.1, 128.8,
128.2, 127.8, 127.0, 126.7, 83.4, 77.4, 72.9, 50.7, 48.9, 33.6, 27.5, 23.1,
22.6, 21.4, 20.9. HRMS (C36H38N2O2): calcd (M þ 1) 531.3006,
observed 531.3009. IR: νCO 1637, 1566 cm-1
.
(i) 1,3-Dibenzyl-2-thiophen-2-yl-4,5-di-p-tolyl-2-imidazolinium-
4-carboxylate (4d). Yield of 86%. 1H NMR (300 MHz, CD3OD):
δ 7.89 (d, J = 4.7 Hz, 1H), 7.53-6.92 (m, 18H), 6.63 (d, J = 7.4
Hz, 2H), 5.55 (s, 1H), 5.06 (d, J = 15.9 Hz, 1H), 4.71 (d, J = 16.0
Hz, 1H), 4.58 (d, J = 14.7 Hz, 1H), 4.02 (d, J = 14.8 Hz, 1H), 2.45
(s, 3H), 2.25 (s, 3H). 13C NMR (75.46 MHz, CD3OD): δ 168.8,
160.5, 139.60, 139.5, 136.5, 135.3, 133.7, 133.1, 132.3, 130.6, 129.4,
129.3, 129.1, 128.8, 128.6, 128.3, 127.9, 127.7, 127.4, 127.0, 120.3,
83.0, 71.9, 50.6, 49.5, 20.0, 19.7. HRMS (C36H32N2O2S): calcd
Typical Procedure for the Synthesis of Heterocoupled Imidazoline
Carboxylates (8a). In a 50 mL reaction bomb under nitrogen,
(4-CH3SC6H4)HCdN(CH2Ph) (53 mg, 0.22 mmol) and benzoyl
chloride (44 mg, 0.31 mmol) were dissolved in 3 mL of acetonitrile
andstirredforca.10min.[Pd(Cl)[η2-CH(4-CH3SC6H4)N(CH2Ph)-
COPh]] (9.8 mg, 0.01 mmol) and P(t-Bu)2(2-biphenyl) 2.7 (10 mg,
0.03 mmol) were then added as a solution in 3 mL of THF and
stirred for 5 min. Diisopropylethylamine (50 μL, 0.31 mmol) was
added via microsyringe, and the vessel was removed from the
glovebox. One freeze-pump-thaw cycle was performed before
the vessel was pressurized with 4.0 atm of CO. The reaction mixture
was allowed to stir at 45 °C for 16 h. CO was removed under
vacuum, and the reaction bomb was brought back into the drybox.
PhHCdN(CH2CHdCH2) (64 mg 0.44 mmol) and PhSO3H (28
mg, 0.18 mmol) were added as a solution in 2 mL of acetonitrile.
(M þ 1) 557.2257, observed 557.2256. IR: νCO 1637, 1533 cm-1
.
(34) Ukai, T.; Kawazura, H.; Ishii, Y.; Bonnet, J. J.; Ibers, J. A. J.
Organomet. Chem. 1974, 65, 253.
(35) Giumanini, A. G.; Toniutti, N.; Verardo, G.; Merli, M. Eur. J. Org.
Chem. 1999, 141.
(36) Celite filtration was performed when palladium black formed in the
crude solution. If the brine wash is neglected, unidentified phosphine species
contaminate the products and are very difficult to remove.
(37) To ensure the stability of these products during isolation, care must
be taken to avoid prolonged contact with CHCl3 or wet organic solvents.
Decarboxylation to 4,5-dihydroimidazolinium salts is commonly observed
when these precautions are not taken. Similarly, precipitation at -35 °C and
collection of the precipitate should be conducted with care under a dry
atmosphere as condensation of water vapor from the air can elicit the same
decomposition.
The reaction mixture was stirred at room temperature until the
€
1
Munchnone was completely consumed as observed by H NMR (3
h). The product was purified as described above to give imidazoline
carboxylate 8a (0.17 mmol, 75%). 1H NMR (400 MHz, CD3OD):
δ 7.65-7.60 (m, 2H), 7.47-7.41 (m, 6H), 7.32 (d, J=8.0 Hz, 2H),
7.00 (t, J = 7.3 Hz, 2H), 6.95-6.88 (m, 3H), 6.49-6.33 (m, 2H),
5.91 (s, 1H), 5.91-5.76 (m, 1H), 5.28 (d, J = 10.1 Hz, 1H), 4.97
J. Org. Chem. Vol. 76, No. 1, 2011 177

Worrall et al.
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(d, J = 17.0 Hz, 1H), 4.91 (d, J = 15.8 Hz, 1H), 4.46 (d, J =
15.8 Hz, 1H), 3.88 (dd, J= 15.5, 5.0 Hz, 1H), 3.48 (dd, J= 15.3, 8.1
Hz, 1H), 2.34 (s, 3H). 13C NMR (100.62 MHz, CD3OD): δ 168.7,
165.7, 141.2, 135.3, 135.1, 133.8, 132.1, 129.5, 129.3, 129.3, 129.1,
128.9, 128.5, 127.8, 127.7, 127.6, 127.2, 127.0, 126.1, 123.1, 121.3,
83.4, 72.8, 50.2, 13.8. HRMS (C33H30N2O2S): calcd (M þ 1)
162.8, 139.5, 139.1, 138.4, 136.1, 135.8, 134.3, 130.0, 129.6, 129.5,
128.9, 128.6, 127.8, 127.0, 125.6, 115.1, 114.9, 83.7, 74.9, 55.0, 50.2,
32.4, 20.3, 20.0. HRMS (C33H32N2O3): calcd (M þ 1) 505.2491,
observed 505.2486. IR: νCO 1639, 1548 cm-1
.
(vii) 1-Benzyl-3-(3,4-dimethoxybenzyl)-2,4,5-2-imidazolinium-
4-carboxylate (8h). Yield of 44%. 1H NMR (400 MHz, CD3OD):
δ 7.61-7.38 (m, 19H), 7.14 (d, J=7.6 Hz, 1H), 7.03 (m, 2H), 6.45
(d, J = 8.3 Hz, 1H), 6.39 (s, 1H), 5.99 (d, J=8.0 Hz, 1H), 5.58 (s,
1H), 4.95 (d, J=15.2 Hz, 1H), 4.42 (d, J=14.8 Hz, 1H), 4.30 (d,
J=15.1 Hz, 1H), 3.92 (d, J = 14.8 Hz, 1H), 3.71 (s, 3H), 3.61 (s,
3H). 13CNMR(100.62MHz,CD3OD): δ168.7, 165.1, 148.7, 148.4,
140.1, 132.2, 132.0, 129.6, 129.5, 129.3, 129.2, 129.1, 129.0, 128.98,
128.95, 128.6, 127.9, 127.7, 127.5, 127.1, 123.3, 121.1, 111.5, 110.9,
83.2, 82.2, 54.99, 54.98, 50.0, 49.1. HRMS (C38H34N2O4): calcd
519.2106, observed 519.2094. IR: νCO 1638, 1549 cm-1
.
(i) 5-Benzo[1,3]dioxol-5-yl-3-benzyl-1-ethyl-2-(4-methoxyphenyl)-
4-p-tolyl-2-imidazolinium-4-carboxylate (8b). Yield of 86%. 1H
NMR (400 MHz, CD3OD): δ 7.65 (d, J = 8.2 Hz, 2H), 7.30 (d,
J= 8.1 Hz, 1H), 7.03-6.82(m, 12H), 6.42(d, J= 7.4 Hz, 2H), 4.85
(d, J = 15.8 Hz, 1H), 4.40 (d, J = 15.8 Hz, 1H), 3.35-3.24 (m, 1H),
3.10-2.97 (m, 1H), 2.38 (s, 3H), 1.18-1.10 (m, 3H). 13C NMR
(100.62 MHz, CD3OD): δ 169.5, 165.8, 162.8, 149.1, 148.3, 139.7,
136.8, 135.7, 129.7, 129.4, 129.0, 128.4, 128.0, 127.9, 127.8, 127.1,
123.2, 115.1, 115.0, 107.1, 101.7, 83.2, 72.3, 55.0, 50.3, 40.8,
20.0, 11.8. HRMS (C34H32N2O5):calcd(Mþ 1) 549.2390, observed
(M þ 1) 583.2597, observed 583.2597. IR: νCO 1642, 1551 cm-1
.
(viii) 2-Benzyl-1,3-di-p-tolyl-1,5,6,10b-tetrahydroimidazolinium-
[5,1-a]isoquinoline-1-carboxylate (8i). Yield of 93%. 1H NMR
(300 MHz, CDCl3): δ 8.11 (d, J=7.3 Hz, 1H), 7.99 (d, J=8.3 Hz,
2H), 7.45 (d, J=7.7 Hz, 1H), 7.15-6.83 (m, 10H), 6.40 (d, J=
7.3 Hz, 1H), 6.05 (s, 1H), 4.75 (d, J=15.7 Hz, 1H), 4.20 (d, J=
15.7 Hz, 1H), 3.65 (m, 1H), 3.18-3.41 (m, 2H), 2.63 (d, J=14.8 Hz,
1H), 2.41 (s, 3H), 2.35 (s, 3H). 13C NMR (75.46 MHz, CDCl3): δ
166.0, 165.4, 143.4, 138.9, 135.8, 132.8, 132.2, 131.4, 129.9, 129.7,
129.4, 129.2, 129.0, 128.1, 128.0, 127.9, 127.89, 127.3, 126.9, 120.9,
86.8, 68.2, 49.6, 43.2, 29.9, 21.9, 21.3. HRMS (C33H30N2O2): calcd
549.2369. IR: νCO 1641, 1552 cm-1
.
(ii) 3-Benzyl-5-(4-bromophenyl)-2-(4-methoxyphenyl)-1-phenyl-4-
p-tolyl-2-imidazolinium-4-carboxylate (8c). Yield of 67%. 1H NMR
(400 MHz, CD3OD): δ 7.89-7.80 (d, J=8.5 Hz, 2H), 7.46-6.79
(m, 10H), 6.67 (s, 1H), 6.45-6.32 (d, J=7.4 Hz, 2H), 5.05 (d, J=
15.8 Hz, 1H), 4.55 (d, J = 15.8 Hz, 1H), 3.70 (s, 3H), 2.35 (s, 3H).
13C NMR (100.62 MHz, CD3OD): δ 168.9, 165.3, 162.8, 139.9,
135.6, 134.9, 134.3, 133.3, 131.2, 130.9, 130.6, 129.8, 129.6, 129.2,
128.5, 127.8, 127.7, 127.1, 127.0, 123.0, 115.2, 114.6, 84.4, 75.5, 54.9,
50.3, 20.0. HRMS (C37H31BrN2O3): calcd (M þ 1) 631.1596, ob-
(M þ 1) 487.2386, observed 487.2382. IR: νCO 1616, 1545 cm-1
.
(ix) 2-Benzyl-1-phenyl-3-thiophen-2-yl-1,5,6,10b-tetrahydroimi-
1
dazolinium[5,1-a]isoquinoline-1-carboxylate (8j). Yield of 71%. H
served 631.1586. IR: νCO 1635, 1567 cm-1
.
NMR (200 MHz, CDCl3): δ 8.09 (d, J = 6.6 Hz, 2H), 7.71 (m, 2H),
7.40-6.75 (m, 11H), 6.49 (d, J = 7.3 Hz, 2H), 6.09 (s, 1H), 4.91 (d,
J = 15.9 Hz, 1H), 4.22 (d, J = 15.9 Hz, 1H), 3.85 (m, 1H), 3.50-
3.12 (m, 2H), 2.63 (d, J = 15.0 Hz, 1H). 13C NMR (100.62 MHz,
CDCl3):δ165.0, 161.3, 135.1, 134.6, 134.0, 132.8, 132.7, 131.3, 129.3,
129.0, 128.8, 128.6, 128.2, 128.1, 127.8, 127.6, 127.5, 127.3, 126.7,
121.1, 86.6, 68.0, 49.7, 43.6, 29.7. HRMS (C29H24N2O2S): calcd
(iii) 3-Benzyl-1-(4-methoxybenzyl)-5-(4-methoxyphenyl)-4-(4-
methylsulfanylphenyl)-2-phenyl-2-imidazolinium-4-carboxylate (8d).
Yield of 75%. H NMR (300 MHz, CD3OD): δ 7.63-7.16 (m,
1
11H), 7.05-6.83 (m, 9H), 6.67-6.58 (d, J = 7.4 Hz, 2H), 5.47 (s,
1H), 4.95 (m, 1H), 4.44-4.33 (m, 2H), 3.95-3.72 (m, 7H), 2.45 (s,
3H). 13C NMR (75.46 MHz, CD3OD): δ 169.2, 165.2, 161.1, 160.7,
141.2, 136.3, 135.6, 132.3, 130.5, 129.9, 129.5, 128.4, 128.2, 128.1,
128.0, 127.4, 127.2, 126.3, 125.5, 124.1, 123.4, 114.5, 114.2, 83.0,
72.0, 54.7, 54.7, 54.7, 50.5, 48.8, 48.7. HRMS (C39H36N2O4S): calcd
(M þ 1) 465.1631, observed 465.1645. IR: νCO 1639, 1555 cm-1
.
(x) 3-Ethyl-1-methyl-2-phenyl-5-pyridin-4-yl-4-p-tolyl-2-imid-
azolinium-4-carboxylate (8k). Yield of 77%. 1H NMR (400
MHz, CDCl3): δ 8.61 (m, 2H), 7.85-7.52 (m, 8H), 7.34-7.18
(m, 8H), 5.44 (s, 1H), 3.58 (m, 2H), 2.74 (s, 3H), 2.36 (s, 3H), 0.54
(t, J = 7.0 Hz, 3H). 13C NMR (125.71 MHz, CDCl3): δ 166.0,
164.8, 150.1, 143.7, 139.2, 136.4, 133.0, 130.1, 129.6, 129.3,
128.1, 123.6, 123.3, 84.8, 76.3, 43.0, 33.6, 21.0, 14.8. HRMS
(C25H25N3O2): calcd (M þ 1) 400.2025, observed 400.2017.
(xi) 1,3-Dibenzyl-5-furan-2-yl-4-(4-methylsulfanylphenyl)-2-
phenyl-2-imidazolinium-4-carboxylate (8l). Yield of 53%. 1H
NMR (500 MHz, CD3OD): δ 7.68 (s, 1H), 7.57-7.51 (m, 1H),
7.48-7.33 (m, 10H), 7.25 (d, J = 8.2 Hz, 4H), 7.10-6.90 (m,
6H), 6.67 (m, 4H), 6.53 (s, 1H), 5.72 (s, 1H), 5.14 (d, J = 15.6 Hz,
1H), 4.45 (m, 1H), 4.35 (m, 1H), 3.97 (d, J = 14.9 Hz, 1H), 2.45
(3s, H). 13C NMR (125.71 MHz, CD3OD): δ 167.7, 164.4, 145.1,
143.1, 140.0, 134.3, 134.2, 131.4, 131.0, 128.4, 128.2, 127.8,
127.7, 127.5, 126.8, 126.7, 126.6, 125.9, 125.0, 121.9, 112.1,
109.6, 79.3, 65.2, 49.0, 48.2, 12.7. HRMS (C35H30N2O3S): calcd
(M þ 1) 629.2474, observed 629.2473. IR: νCO 1638, 1547 cm-1
.
(iv) 1,3-Dibenzyl-4-(4-methylsulfanylphenyl)-2-phenyl-5-(4-phenyl-
ethynylphenyl)-2-imidazolinium-4-carboxylate (8e). Yield of 95%.
1H NMR (400 MHz, CD3OD): δ 7.63-7.35 (m, 17H), 7.28-7.21
(m, 2H), 7.09-7.02 (m, 2H), 6.99-6.93 (m, 2H), 6.60 (m, 2H),
5.58 (s, H), 4.9 (d, J=15.6 Hz, 1H), 4.50 (d, J=14.8 Hz, 1H),
4.45 (d, J = 15.5 Hz, 1H), 4.02 (d, J = 14.9 Hz, 1H), 2.47 (s,
3H). 13C NMR (100.62 MHz, CD3OD): δ 168.6, 165.8, 141.4,
135.8, 135.4, 134.0, 132.4, 132.3, 131.8, 131.4, 129.9, 129.6,
129.3, 129.1, 128.5, 128.47, 128.4, 128.2, 128.1, 127.5, 127.3,
126.3, 124.9, 123.2, 123.1, 90.3, 88.4, 83.5, 72.3, 53.6, 50.6,
49.7, 14.0. HRMS (C45H36N2O2S): calcd (M þ 1) 669.2576,
observed 669.2568. IR: νCO 1637, 1567 cm-1
.
(v) 3-Benzyl-5-(3-bromophenyl)-1-(4-methoxybenzyl)-2-(4-me-
thoxyphenyl)-4-p-tolyl-2-imidazolinium-4-carboxylate (8f). Yield
1
of 73%. H NMR (200 MHz, CD3OD): δ 7.62-7.53 (m, 2H),
7.50-6.83 (m, 21H), 6.65 (d, J = 7.4 Hz, 2H), 5.55 (s, 1H), 5.01 (d,
J = 15.4 Hz, 1H), 4.49 (d, J = 14.8 Hz, 1H), 4.36 (d, J = 14.8 Hz,
1H), 3.91 (d, J = 14.9 Hz, 1H), 3.73 (s, 3H), 3.72 (s, 3H), 2.36
(s, 3H). 13C NMR (75.46 MHz, CD3OD): δ 168.9, 165.7, 163.0,
160.7, 139.7, 139.1, 136.9, 136.8, 135.8, 132.6, 130.5, 129.9, 129.7,
129.2, 128.1, 128.0, 127.7, 127.2, 124.1, 122.5, 115.3, 115.1, 114.6,
114.5, 83.5, 71.2, 55.0, 54.7, 50.3, 49.1, 19.9. HRMS (C39H35Br-
N2O4): calcd (M þ 1) 675.1853, observed 675.1846. IR: νCO 1640,
(M þ 1) 559.2055, observed 559.2051. IR: νCO 1640, 1567 cm-1
.
(xii) 3-Benzyl-1-(2-methoxyethyl)-2-(4-methoxyphenyl)-4-
1
p-tolyl-2-imidazolinium-4-carboxylate (8m). Yield of 93%. H
NMR (400 MHz, CD3OD): δ 7.60-6.85 (m, 11H), 6.51-6.42
(d, J = 7.4 Hz, 2H), 4.83-4.72 (m, 2H), 4.60 (d, J = 12.4 Hz,
1H), 4.45 (d, J = 16.2 Hz, 1H), 3.85 (s, 3H), 3.55 (m, 2H), 3.39-
3.27 (m, 5H), 2.31 (s, 3H). 13C NMR (100.62 MHz, CD3OD):
δ 174.0, 165.6, 162.9, 139.5, 135.8, 133.5, 130.3, 130.5, 129.4,
129.0, 127.8, 127.5, 127.0, 114.7, 77.6, 68.1, 59.5, 58.1, 55.0, 49.4,
48.4, 19.9. HRMS (C28H30N2O4): calcd (M þ 1) 459.2284,
1561 cm-1
.
(vi) 3-Benzyl-2-(4-methoxyphenyl)-1-methyl-5-m-tolyl-4-p-tolyl-
2-imidazolinium-4-carboxylate (8g). Yield of 87%. 1H NMR (200
MHz, CD3OD): δ 7.68 (d, J=8.2 Hz, 2H), 7.33-7.17 (m, 8H),
7.00-6.83 (m, 3H), 6.43 (d, J=7.5 Hz, 2H), 5.90 (s, 1H), 4.86 (d,
J=16.8 Hz, 1H), 4.40 (d, J=15.6 Hz, 1H), 3.80 (s, 3H), 2.79 (s,
3H), 2.35 (s, 6H). 13C NMR (75.46 MHz, CD3OD): δ 169.5, 166.2,
observed 459.2278. IR: νCO 1628, 1551 cm-1
.
(xiii) 3-Benzyl-1-(4-methoxyphenyl)-4-(4-methylsulfanylphenyl)-
2-phenyl-2-imidazolinium-4-carboxylate (8n). Yield of 80%. 1H
NMR (400 MHz, CDCl3): δ 7.61 (d, J = 8.5 Hz, 2H), 7.41-7.21
178 J. Org. Chem. Vol. 76, No. 1, 2011

Worrall et al.
JOCArticle
(m, 6H), 7.11 (m, 2H), 6.99-6.81 (m, 6H), 6.63 (d, J = 8.9 Hz, 2H),
6.40 (d, J = 7.2 Hz, 2H), 5.22 (d, J = 11.8 Hz, 1H), 5.00 (d, J = 16.2
Hz, 1H), 4.81-4.70 (m, 2H), 3.63 (s, 3H), 2.40 (s, 3H). 13C NMR
(125.71 MHz, CDCl3): δ 170.9, 163.2, 159.6, 140.5, 135.5, 132.3,
130.3, 129.5, 129.1, 128.9, 128.3, 128.1, 127.5, 126.8, 126.6, 126.5,
123.7, 115.0, 78.8, 64.5, 55.6, 50.6, 15.7. HRMS (C31H28N2O3S):
125.6, 77.9, 60.6, 53.0, 52.2. HRMS (C24H23O2N2): calcd (M þ 1)
371.1754, observed 371.1748. IR: νCO 1726 cm-1
.
Typical Protocol for Deallylation (10b). Imidazolinium-car-
boxylate (86 mg, 0.17 mmol) was charged into a 50 mL oven-dried
Schlenk flask under a positive atmosphere of nitrogen. Five milli-
liters of dry CH3CN was added by syringe. MeI (0.100 mL, 1.6
mmol) was then added by microsyringe. The resulting solution was
allowed to stir at 45 °C for 2 h. The solvent and MeI were then
removed in vacuo, and the resulting residue was placed under an
atmosphere of nitrogen. Pd(PPh3)4 (20.6 mg 0.017 mmol) was then
added by syringe as a solution in 2 mL of dry CH2Cl2 followed by
PhSiH3 (80 μL, 0.65 mmol) and glacial acetic acid (40 μL, 0.7
calcd (M þ 1) 509.1899, observed 509.1898. IR: νCO 1633, 1555 cm-1
.
(xiv) 1-Benzyl-3-ethyl-2-phenyl-4-p-tolyl-2-imidazolinium-
4-carboxylate (8o). Yield of 80%. 1H NMR (500 MHz, CDCl3):
δ 7.71-7.09 (m, 14H), 4.89 (d, J = 11.8 Hz, 1H), 4.47-4.33 (m,
4H), 4.09 (d, J = 11.7 Hz, 1H), 3.76-3.67 (m, 1H), 3.57-3.49
(m, 1H), 2.28 (s, 3H), 0.48 (m, 3H). 13C NMR (125.71 MHz,
CDCl3): δ 170.6, 163.4, 138.9, 135.2, 133.0, 132.9, 130.3, 130.0,
129.7, 129.6, 129.1, 128.9, 127.8, 123.4, 77.8, 61.2, 51.5, 42.1,
21.3, 15.4. HRMS (C26H26N2O2): calcd (M þ 1) 399.2073, ob-
1
mmol). Upon completion of the deallylation as observed by H
NMR (20 h), the solution was washed with saturated NaHCO3
followed by brine extraction. The combined organic layers were
dried with Na2SO4, filtered, and condensed to give a yellow oil
that was purified by silica gel chromatography (40% EtOAc in
hexanes) to give a yellow solid (0.15 mmol, 91%). 1H NMR (400
MHz, CDCl3): δ 7.59 (d, J = 6.4 Hz, 2H), 7.43-7.24 (m, 13H),
6.66 (d, J = 8.8 Hz, 2H), 6.54 (d, J = 8.8 Hz, 2H), 5.92 (s, 1H), 4.34
(d, J=16.0Hz,1H), 3.95(d,J= 16.0 Hz, 1H), 3.71 (s, 3H), 3.13 (s,
3H). 13C NMR (75.46 MHz, CDCl3): δ 171.0, 166.1, 158.1, 139.9,
139.5, 131.7, 130.3, 129.4, 128.8, 128.6, 128.4, 128.2, 128.11, 128.08,
128.0, 127.8, 127.6, 113.1, 83.0, 79.8, 55.2, 51.4, 48.2. HRMS
(C31H29O3N2): calcd (M þ 1) 477.2173, observed 477.2163. IR:
served 399.2063. IR: νCO 1628, 1568 cm-1
.
(xv) 4-(4-Methoxyphenyl)-1-methyl-3-phenyl-2-p-tolyl-2-imidazo-
linium-4-carboxylate (8p). Yield of 53%. 1H NMR (300 MHz,
DMSO-d6): δ 7.49 (d, J = 8.6 Hz, 2H), 7.40 (d, J = 7.2 Hz, 2H),
7.27 (t, J = 6.8 Hz, 4H), 6.98-6.90 (m, 3H), 6.72 (d, J = 8.7 Hz,
2H), 4.69 (d, J = 11.5 Hz, 1H), 4.46 (d, J = 11.3 Hz, 1H), 3.63 (s,
3H), 3.13 (s, 3H), 2.27 (s, 3H). 13C NMR (125.71 MHz, D2O): δ
176.1, 164.8, 159.5, 144.4, 135.7, 130.6, 129.9, 129.7, 129.5, 128.7,
128.6, 128.3, 119.5, 114.2, 78.8, 63.2, 55.5, 34.9, 20.9. HRMS
(C25H24N2O3): calcd (M þ 1) 401.1865, observed 401.1856.
CO 1733 cm-1
.
Typical Protocol for Removal of the Paramethoxybenzyl
(PMB) Group (9a). Imidazolinium-carboxylate 8q (111 mg,
0.2 mmol) was charged into a 50 mL oven-dried Schlenk flask
under a positive atmosphere of nitrogen. Five milliliters of dry
CH3CN was added by syringe. MeI (0.125 mL, 2.0 mmol) was then
added by microsyringe. The resulting solution was allowed to stir at
45 °C for 2 h. The solvent and MeI were then removed in vacuo, and
the resulting residue was dissolved with 5 mL of dry CH2Cl2 under
an atmosphere of nitrogen. The solution was then cooled to 0 °C,
and 1 M BBr3 in CH2Cl2 (2 mL, 2 mmol) was added dropwise. The
mixture was allowed to gradually warm to ambient temperature and
stirred for 2 h, after which it was rapidly added to a stirring 1 M
NaOH solution (20 mL). The product was extracted with additional
CH2Cl2, and the combined organic layers were dried with Na2SO4,
filtered, and condensed to give a yellow oil that was purified by silica
gel chromatography (40% EtOAc in hexanes) to give a yellow solid
(0.13 mmol, 66%). 1H NMR (300 MHz, CDCl3): δ 7.80 (m, 2H),
7.75 (d, J = 7.4 Hz, 2H), 7.49 (m, 3H), 7.41-7.28 (m, 8H), 7.09 (m,
3H), 6.75 (d, J = 7.2 Hz, 2H), 4.93 (s, 1H), 4.65 (d, J = 15.8 Hz,
1H), 3.85 (d, J = 15.8 Hz, 1H), 3.19 (s, 3H). 13C NMR (75.46 MHz,
CDCl3): δ 171.4, 165.7, 144.0, 137.8, 136.6, 130.5, 130.4, 128.9,
128.7, 128.5, 128.43, 128.36, 128.1, 128.0, 127.5, 127.4, 127.2, 126.8,
83.1, 73.9, 51.9, 48.7. HRMS (C30H27O2N2): calcd (M þ 1)
ν
Methyl 1-Benzyl-2,4,5-triphenyl-4,5-dihydro-1H-imidazole-5-
carboxylate (10a). Yield of 60%. 1H NMR (400 MHz, CDCl3): δ
7.59 (d, J = 6.8 Hz, 2H), 7.41 (d, J = 8.2 Hz), 7.37-7.25 (m,
11H), 7.01 (m, 3H), 6.80 (m, 2H), 5.96 (s, 1H), 4.44 (d, J = 16.3
Hz, 1H), 4.02 (d, J = 16.3 Hz, 1H), 3.13 (s, 3H). 13C NMR (75
MHz, CDCl3): δ 170.9, 166.1, 139.7, 139.5, 138.3, 131.6, 129.5,
128.6, 128.5, 128.2, 128.13, 128.10, 128.0, 127.9, 127.7 (two car-
bons), 127.5, 126.4, 83.1, 79.5, 51.4, 48.8. HRMS (C30H27-
O2N2): calcd (M þ 1) 447.2067, observed 447.2057. IR: νCO
1734 cm-1
.
Synthesis of 12. In a 50 mL round-bottom flask equipped with
a reflux condenser, compound 9a (59 mg, 0.13 mmol) was dissolved
in 20 mL of a 1:1 EtOH/2 M NaOH solution. This mixture was
heated at reflux until the ester was completely consumed as observed
by TLC (40% EtOAc in hexanes) (24 h). The solution was then
brought to pH 0 by HCl, and the product was extracted into CHCl3.
The combined organic layers were dried with Na2SO4, filtered, and
condensed, and the resulting off-white solid was purified by silica gel
chromatography (10% MeOH in CH2Cl2 with 1% acetic acid) to
afford the product 12 as an off-white solid (0.12 mmol, 91%). This
compound has been previously described.33
1-Benzyl-2,4,5-triphenyl-4,5-dihydro-1H-imidazole-5-carboxylic
Acid (120). Yield of 55%. 1H NMR (400 MHz, CD3OD): δ 7.83 (d,
J=7.1 Hz, 2H), 7.61-7.53 (m, 3H), 7.44-7.33 (m, 10H), 6.92-6.83
(m, 3H), 6.39 (d, J=7.1 Hz, 2H), 6.13 (s, 1H), 4.99 (d, J=16.4 Hz,
1H), 4.53 (d, J=16.4 Hz, 1H) (the CO2H signal is not observed due
to exchange with solvent). 13C NMR (125.71 MHz, CD3OD): δ
169.1, 166.0, 138.7, 136.6, 135.1, 132.3, 129.1, 129.0, 128.8, 128.7,
128.6, 128.0, 127.79, 127.6, 127.5, 127.3, 126.7, 124.4, 85.8, 69.5, 49.3.
HRMS (C29H24O2N2): calcd (M þ 1) 433.1911, observed 433.1901.
447.2067, observed 447.2061. IR: νCO 1732 cm-1
.
(i) Methyl 1-Allyl-5-(naphthalen-2-yl)-2,4-diphenyl-4,5-dihydro-
1H-imidazole-4-carboxylate (9b). Yield of 42%. 1H NMR (400
MHz, CDCl3): δ 7.94 (d, J=7.9 Hz, 2H), 7.87 (m, 4H), 7.79 (m,
2H), 7.58 (m, 1H), 7.51 (m, 5H), 7.44 (t, J=7.4 Hz, 2H), 7.34 (t, J=
7.3 Hz, 2H), 5.41 (m, 1H), 5.26 (s, 1H), 4.92 (d, J=10.2 Hz, 1H),
4.79 (d, J=17.1 Hz, 1H), 3.94 (dt, J = 16.1, 2.2 Hz, 1H), 3.36
(dd, J=16.3, 7.0 Hz, 1H), 3.15 (s, 3H). 13C NMR (75.46 MHz,
CDCl3): δ 171.4, 166.0, 144.3, 135.7, 133.3, 133.2, 133.0, 130.6,
130.4, 128.7, 128.5, 128.3, 128.2, 128.1, 127.7, 127.6, 127.5,
126.9, 126.3, 126.2, 125.4, 117.7, 83.0, 75.4, 52.0, 48.1. HRMS
(C30H27O2N2): calcd (M þ 1) 447.2067, observed 447.2057. IR:
IR: νCO 1624, 1559 cm-1
.
Synthesis of 11. In a 25 mL round-bottom flask, compound
10b (133 mg, 0.28 mmol) was dissolved in 4 mL of CH3CN along
with ca. 2 drops of distilled water. To this solution was added
cerium ammonium nitrate (765 mg, 1.4 mmol). The mixture was
stirred at ambient temperature for 24 h. Then 20 mL of 1 M NaOH
was added, and the resulting mixture was filtered over Celite. The
organic phase was extracted with CH2Cl2 and washed with
saturated NaHCO3 followed by brine. The combined organic
layers were dried with Na2SO4, filtered, and concentrated to give
a yellow oil, which was purified by silica gel chromatography
(40% EtOAc in hexanes) to give a white solid (0.18 mmol, 65%).
ν
CO 1734 cm-1
.
(ii) Methyl 1-Benzyl-2,4-diphenyl-4,5-dihydro-1H-imidazole-
4-carboxylate (9c). Yield of 47%. 1H NMR (400 MHz, CDCl3): δ
7.68 (d, J= 6.5 Hz, 2H), 7.44 (m, 5H), 7.31 (m, 6H), 7.19 (d, J=7.2
Hz, 2H), 4.59 (d, J = 10.1 Hz, 1H), 4.45 (d, J = 15.9 Hz, 1H), 4.23
(d, J = 15.9 Hz, 1H), 3.71 (s, 3H), 3.45 (d, J = 10.1 Hz, 1H). 13
C
NMR (75.46 MHz, CDCl3): δ 173.9, 167.0, 143.9, 137.1, 130.4,
130.3, 128.8, 128.64, 128.6 (two carbons), 127.48, 127.46, 126.9,
J. Org. Chem. Vol. 76, No. 1, 2011 179

Worrall et al.
JOCArticle
1H NMR (400 MHz, CD3OD): δ 8.00-7.98 (m, 2H), 7.77-7.74
(m, 2H), 7.57-7.47 (m, 3H), 7.36 (m, 8H), 5.47 (s, 1H), 3.14 (s, 3H)
(the NH signal not observed due to exchange with solvent). 13C
NMR (75.46 MHz, CD3OD): δ 171.3, 164.3, 143.0, 139.8, 131.2,
129.2, 128.3, 128.0, 127.85, 127.79, 127.6, 127.52, 127.50, 126.2,
80.6, 76.9, 50.9. HRMS (C23H20O2N2): calcd (M þ 1) 357.1598,
Acknowledgment. We thank NSERC, FQRNT, and CFI
ꢀ
for funding of this project. B.X. thanks Hydro-Quebec for a
graduate fellowship.
Supporting Information Available: 1H NMR and 13C NMR
spectra of all synthesized products. This material is available
free of charge via the Internet at http://pubs.acs.org.
observed 357.1590. IR: νCO 1733 cm-1
.
180 J. Org. Chem. Vol. 76, No. 1, 2011