Superacid-Catalyzed Reactions of Cinnamic Acids and the Role of Superelectrophiles

Article abstract of DOI:10.1021/jo030327t

The chemistry of cinnamic acids and related compounds has been studied. In superacid-catalyzed reactions with arenes, two competing reaction mechanisms are proposed. Both mechanisms involve the formation of dicationic intermediates (superelectrophiles), and the reactions can lead to either chalcone-type products or indanone products. The direct observation of a dicationic species (by low-temperature ¹³C NMR) is reported. We provide clear evidence that protonated carboxylic acid groups (or the corresponding acyl cation) can enhance the reactivity of an adjacent electrophilic center. Triflic acid is also found to be an effective acid catalyst for the direct synthesis of some electron-deficient chalcones and heterocyclic chalcones from cinnnamic acids.

Full text of DOI:10.1021/jo030327t

Su p er a cid -Ca ta lyzed Rea ction s of Cin n a m ic Acid s a n d th e Role of
Su p er electr op h iles1
Rendy Rendy,† Yun Zhang,† Aaron McElrea,† Alma Gomez,† and Douglas A. Klumpp*,‡
Department of Chemistry, California State Polytechnic University, 3801 West Temple Avenue,
Pomona, California 91768, and Department of Chemistry and Biochemistry,
Northern Illinois University, DeKalb, Illinois 60115
dklumpp@niu.edu
Received October 27, 2003
The chemistry of cinnamic acids and related compounds has been studied. In superacid-catalyzed
reactions with arenes, two competing reaction mechanisms are proposed. Both mechanisms involve
the formation of dicationic intermediates (superelectrophiles), and the reactions can lead to either
chalcone-type products or indanone products. The direct observation of a dicationic species (by low-
temperature 13C NMR) is reported. We provide clear evidence that protonated carboxylic acid groups
(or the corresponding acyl cation) can enhance the reactivity of an adjacent electrophilic center.
Triflic acid is also found to be an effective acid catalyst for the direct synthesis of some electron-
deficient chalcones and heterocyclic chalcones from cinnnamic acids.
In tr od u ction
studies of the superacid-catalyzed reactions of R-ketoacids
suggested the formation of dicationic intermediates from
the protonation of carboxylic acids and adjacent ketone
groups.6 In the present study, we examine the electro-
philic chemistry of cinnamic acids and related com-
pounds. In addition to several new synthetic reactions,
we also report the direct observation of a dicationic,
superelectrophilic species by low-temperature 13C NMR
and propose a general mechanistic scheme in which
diprotonated species are generated from cinnamic acids
in superacidic media. Moreover, the results from this
study provide further evidence that protonated carboxylic
acid groups can strongly activate adjacent electrophilic
sites.
The importance of superelectrophilic intermediates has
been recognized since Olah’s pioneering studies in the
1970s.2 Recent work has shown that superelectrophiles
and related dicationic electrophiles can be exceedingly
reactive and generally useful in synthetic chemistry.3 For
example, studies by Shudo and Ohwada demonstrated
that nitroolefins and R,â-unsaturated aldehydes (eqs 1
and 2) can form highly reactive electrophiles in the
Brønsted superacid, CF3SO3H (triflic acid, TfOH).4,5
Resu lts
Cinnamic acid (3a ) is a substance that was first
reported in the 1800s, and its reactions with benzene and
strong acids or superacids have been described.7 It has
been noted in these earlier reports that cinnamic acid
(3a ) gives 3,3-diphenylpropionic acid from strong acid (H2-
SO4 or AlCl3) reactions with benzene but gives 3-phe-
nylindan-1-one (4a ) from superacidic reactions (CF3SO3H
(1) Presented in part at the National Meeting of the American
Chemical Society: Rendy, R.; Zhang, Y.; McElrea, A.; Gomez, A.; Dang,
H.; Klumpp, D. A. Superacid-Catalyzed Reactions of Cinnamic Acids
and the Role of Superelectrophiles. In Abstracts of Papers, 225th
National Meeting of the American Chemical Society, New Orleans, LA,
March 2003; American Chemical Society: Washington, DC, 2003;
Abstract ORGN 503.
Diprotonated, superelectrophilic species 1 and 2 were
proposed as intermediates in the conversions. Our own
† California State Polytechnic University.
‡ Northern Illinois University.
(2) Olah, G. A.; Germain, A.; Lin, H. C.; Forsyth, D. J . Am. Chem.
Soc. 1975, 97, 2928.
10.1021/jo030327t CCC: $27.50 © 2004 American Chemical Society
Published on Web 03/06/2004
2340
J . Org. Chem. 2004, 69, 2340-2347

Superacid-Catalyzed Reactions of Cinnamic Acids
or >3 equiv of AlCl3). The 3-arylindan-1-ones are valuable
pharmaceutical intermediates, and the synthesis of these
products from cinnamic acids has been reported, both in
the patent literature7f and in published manuscripts.7e,g
In the case of the proprietary work, the synthesis of
indanones requires two steps: a reaction of the cinnamic
acid with H2SO4 and C6H6 to give a 3,3-diarylpropionic
acid and then a reaction with chlorosulfonic acid to yield
the cyclized product (an indanone).
When the cinnamic acid derivatives 3a -h react with
C6H6 in an excess of triflic acid, three types of products
are observed and the product distributions are similar
to those found in the above synthetic studies (Table 1).
For the para-substituted cinnamic acids (3a ,e-h ), the
3-arylindanones (4a ,e-h ) are the major products. Chal-
cones (5b-d ) are the only products in some cases (3b-
d ), and the propanones (6a ,e-h ) are also formed in
varying amounts. When the substituents are compared,
a consistent trend emerges: strongly electron-withdraw-
ing groups favor arylation at the acyl carbon to give
chalcones (5b-d ), while other groups tend to favor the
indanone cyclization products. A good correlation is seen
To explore the synthetic scope of the reactions of
cinnamic acids in superacid, a series of cinnamic acids
were reacted with CF3SO3H (triflic acid, TfOH) and C6H6
(Table 1). In general, two major types of reactions were
found to occur. Cinnamic acids with alkyl groups or
weakly electron-withdrawing groups give the indanone
products (4a ,h ,i,g,e) in good yields. With increased
substitution by electron-withdrawing groups, a mixture
of indanones and chalcones (4j/5j; 4k /5k ; 4l/5l) are
obtained.8 When the aryl ring of cinnamic acid is sub-
stituted by strong electron-withdrawing groups, the
chalcone products (5b,c,d ,m ,n ) are obtained by acylation.
In the cases of the heterocyclic derivatives 3p -q, the
heterocyclic ring is fully protonated in the TfOH and acts
like a strong electron-withdrawing group. Interestingly,
the nitro-substituted derivative (ortho regioisomer, 3o)
does not give product from the reaction, but instead the
starting material is recovered. While the methyl-substi-
tuted cinnamic acid (3r ) gives the indanone product (4r )
in almost quantitative yield, the indene derivatives 16
and 17 give acylation products (entries 18 and 19). A
series of 2-substituted cinnamic acids (3s-u ) were also
reacted with TfOH and benzene. Both 3s and 3t gave the
cyclization products (indanones) 4s and 4t, respectively.
However, the fluoro-substituted derivative (3u ) did not
react. This unexpected outcome is probably the result of
a strong inductive effect involving the fluorine atom. In
the case of 3v, acylation is apparently the major reaction
path, but the lactone 22 is formed in a secondary reaction.
When the fluorenylidene derivative (18) is reacted with
TfOH and C6H6, arylation and cyclization give the novel
ketone (23). The results shown above demonstrate that
cinnamic acids can be converted in superacid to either
indanones or chalcones, depending on the cinnamic acid
substituents.
+
between the relative product yields and the σp values
for the different substituents,9 suggesting that indanone
(4a -h ) product formation involves the generation of
positive charge adjacent to the aryl ring. Similar results
are obtained with ortho-substituted cinnamic acids.
In studying the effect of acid strength on the electro-
philic chemistry of cinnamic acids, a series of reactions
were done with cinnamic acid 3a and 3,3-diphenylpro-
pionic acid (Table 3). With varying quantities of TfOH,
it is seen that 1.1 equiv of TfOH acid gives a small
amount (20%) of addition product (7a ), but no indanone
(4a ) or propanone (6a ) products. With an increasing
amount of TfOH (3.0 equiv), cyclization product (4a ) is
observed, but the propanone (6a ) product is still not
formed. With increasing amounts of TfOH, the bulk
acidity of the solution rises to near Ho -14 (pure TfOH),
and the propanone (6a ) begins to be formed as a
significant product. The chalcone product (5a ) is not
observed as a product in any of the conversions, which
is consistent with the earlier report that 1,3-diphenyl-2-
propen-1-one (5a ) gives the addition product 6a from the
reaction with TfOH and C6H6.4 In a similar respect, the
acidity of the medium can be varied using the CF3SO3H/
CF3CO2H (TfOH/TFA) system designed by Shudo and
Ohwada.10 The addition product (7a ) is formed at low
acidity (Ho -2.7), while the indanone 4a begins to be
formed at higher acidities. The propanone product (6a )
is only formed when the solution is superacidic (Ho
-12).
<
These results suggest that the indanone product (4a )
arises from the cyclization of 7a , and 7a is an initial
product from the reaction of cinnamic acid 3a with TfOH
and C6H6. When compound 7a is reacted with TfOH (or
weaker acids, -14.1< Ho < -10) and C6H6, the indanone
4a is the sole product (Table 3). Other considerations
include: 7a does not generate product 6a ; product 6a is
formed by an addition reaction involving chalcone (5a );
product 4a is stable under these reaction conditions.
Thus, it is reasonable to conclude that cinnamic acid (3a )
reacts with TfOH and C6H6 by two competing reaction
paths. At high levels of acidity and at 25°C, cinnamic acid
acylates benzene to yield chalcone products 5a , while
cinnamic acid also can undergo an addition reaction to
yield 7a . Olah and co-workers provided evidence that
carboxylic acids may be diprotonated in superacid and
the resulting dicationic species can generate the acyl
The effects of substitutuents were further studied in
reactions of cinnamic acid derivatives (3a -h , Table 2).
(3) (a) Olah, G. A. Angew. Chem., Int. Ed. Engl. 1993, 32, 2, 767.
(b) Olah, G. A.; Laali, K. A.; Wang, Q.; Prakash, G. K. S. Onium Ions;
Wiley: New York, 1998; Chapter 10.
(4) Ohwada, T.; Okabe, K.; Ohta, T.; Shudo, K. Tetrahedron 1990,
46, 7539. (b) See also, Shildneck, P. R. Organic Syntheses; Wiley: New
York, 1943; Collect. Vol. II, p 236.
(5) Ohwada, T.; Ohta, T.; Shudo, K. J . Am. Chem. Soc. 1986, 108,
3092.
(6) Klumpp, D. A.; Garza, M.; Lau, S.; Shick, B.; Kantardjieff, K. J .
Org. Chem. 1999, 64, 7635.
(7) (a) Koncos, R.; Friedman, B. S. In Friedel-Crafts and Related
Reactions; Olah, G. A., Ed.; Wiley: New York, 1964; Vol 2, pp 318-
320 and references cited therewithin. (b) Liebermann, C.; Hartmann,
A. Chem. Ber. 1892, 25, 2124. (c) Simons, J . H.; Archer, S. J . Am. Chem.
Soc. 1939, 61, 1521. (d) Dippy, J . F.; Young, J . T. J . Chem. Soc. 1952,
1817. (e) Prakash, G. K. S.; Yan, P.; Torok, B.; Olah, G. A. Catal. Lett.
2003, 87(3-4), 109. (f) Moussa, A. M.; Haider, R.; Taft, H.; J urayj, J .;
Wang, W.; Suh, H. International Patent No. PCT/US99/00225, 1999,
International Publ. No. WO 99/35119. (g) Koelsch, C. F.; Hochmann,
H.; Le Claire, C. D. J . Am. Chem. Soc. 1943, 65, 1521. (h) See also:
Begitt, K.; Heesing, A. Chem. Ber. 1979, 112, 689.
(9) (a) Okamato, Y.; Inukai, T.; Brown, H. C. J . Am. Chem. Soc.
1958, 80, 4969. (b) March, J . Advanced Organic Chemistry, 4th Ed;
Wiley: New York, 1992; pp 279-280.
(10) Saito, S.; Saito, S.-i.; Ohwada, T.; Shudo, K. Chem. Pharm. Bull.
1991, 39, 2718.
(8) Trace quantities of the propanone products (6j-l) could also be
detected by GCMS, however these minor products could not be isolated.
J . Org. Chem, Vol. 69, No. 7, 2004 2341

Rendy et al.
TABLE 1. P r od u cts a n d Yield s fr om th e Rea ction s of Cin n a m ic Acid s a n d Rela ted com p ou n d s w ith CF 3SO3H (100
equ iv) a n d C6H6 a t 25 °Ca -c
a
b
Isolated yields of pure products. Product 5p isolated as the triflate salt; product 4t exists as a mixture of keto-enol forms. c Products
4a ,e were obtained from reaction at -15 °C.
2342 J . Org. Chem., Vol. 69, No. 7, 2004

Superacid-Catalyzed Reactions of Cinnamic Acids
TABLE 2. P r od u cts a n d Rela tive Yield sa fr om th e Rea ction s of P a r a -Su bstitu ted Cin n a m ic Acid s w ith C6H6 a n d
CF 3SO3H (100 equ iv; 12 h a t 25 °C)
a
b
Relative yields were determined by GC-FID analysis; the products are assumed to have FID response factors near unit. These
values are estimated from the value of 0.41 for the trimethylammonium group; starting materials (3c,d ) are the amino-substituted cinnamic
acids. c Cyclization produces exclusively 5-methyl-3-phenyl-1-indanone (4h ).
TABLE 3. P r od u cts a n d Rela tive Yield sa fr om th e Rea ction s of Cin n a m ic or 3,3-Dip h en ylp r op ion ic Acid w ith C6H6 a n d
Acid
a
Determined by GC-MS and GC-FID; TFA, CF3CO2H; TfOH, CF3SO3H.
J . Org. Chem, Vol. 69, No. 7, 2004 2343

Rendy et al.
SCHEME 1
cation at temperatures above -10 °C.11 When cinnamic
acids 3a or 3e are reacted with TfOH, C6H6, and CHCl3
(as an anti-freeze) at -15 °C, indanones 4a and 4e are
the only products formed (eqs 3 and 4). In contrast, both
conditions (130-180 °C) in large excess of acid (AlCl3-
NaCl or polyphosphoric acid). The reactions are thought
to occur by an electrocyclization mechanism involving the
protonated (or Lewis acid complexed) chalcone. The
cyclization is also similar to the superacid-catalyzed
reaction of 1-phenyl-2-propen-1-ones to give 2-phenyl-1-
indanone,13 which was studied recently by Shudo and
Ohwada. However, in the case of cinnamic acid 3a , the
indanone product 4a does not arise from cyclization of
the intermediate chalcone product (5a ). Chalcones 5a and
5j were reacted with a large excess (100 equiv) of TfOH
(60 h at 25 °C) and no indanone products were formed.
As noted previously, chalcone 5a is known to react
preferentially with benzene in superacidic medium and
yield 6a .4
Based on these considerations, we propose a mecha-
nism that invokes the formation of diprotonated, super-
electrophilic intermediates (Scheme 1; alternative mono-
cationic routes are also shown). The first protonation
occurs at the carboxyl group to give the carboxonium ion
(8). Arnett estimated the pKb of cinnamic acid to be about
-6,14 so it is reasonable to assume that cinnamic acid is
fully protonated in superacid. This suggests an equilib-
rium is established with the diprotonated species (9)
which cleaves to the acyl cation (10). The acyl cation then
acylates benzene and rapidly reacts with a second
benzene (via 11)4 to yield product 6a . Given the formation
of product 7a at relatively low acid strength (Ho ) -2.7),
it appears that some phenylation of cinnamic acid can
occur by reaction of the monoprotonated species (8).
However, arylation of cinnamic acid with o-dichloroben-
zene suggests a more reactive species is involved (in
superacidic reactions). It is proposed that arylation at the
olefinic site occurs through a diprotonated intermediate.
Two likely diprotonated species could lead to the in-
danone product (4a ): the O,O-diprotonated species (9)
or the C,O-diprotonated species (12). Protonation of the
carboxyl group is followed by protonation at the olefinic
3a and 3e give significant quantities of the propanone
(6a , e) products at 25 °C. This suggests that the chalcone
(5) products are formed by the reactions of the appropri-
ate acyl cations. When cinnamic acid is reacted with
o-dichloro benzene and excess of TfOH (25 °C), the
indanone product (4l) is formed as the major product in
92% yield (eq 5). Since o-dichlorobenzene is a significantly
deactivated arene, this indicates that cinnamic acid forms
a highly reactive electrophile in superacidic solution.
Products 4e and 4l also clearly show the preference for
cyclization toward the more electron-rich aryl ring.
Several earlier reports have described the acid-
catalyzed conversions of chalcone (5a ) to give the in-
danone product (4a ).12 These reactions employed forcing
(11) Prakash, G. K. S.; Rasul, G.; Liang, G.; Olah, G. A. J . Phys.
Chem. 1996, 100, 15805.
(12) Allen, J . M.; J ohnson, K. M.; J ones, J . F.; Shotter, R. G.
Tetrahedron 1977, 33, 2083.
(13) Suzuki, T.; Ohwada, T.; Shudo, K. J . Am. Chem. Soc. 1997, 119,
6774.
(14) Arnett, E. M. Prog. Phys. Org. Chem. 1963, 1, 233.
2344 J . Org. Chem., Vol. 69, No. 7, 2004

Superacid-Catalyzed Reactions of Cinnamic Acids
position to give dication 12 and reaction with benzene
gives the phenylated product which then cyclizes to 4a .
Alternatively, dication 9 could react with benzene at the
3-position by delocalization of the positive charge leading
to 4a (not shown). Ab initio calculations were done on
dications 9 and 12 at the B3LYP/6-311g (d,p)//B3LYP/6-
311g (d,p) level of theory15 and two stationary points were
found (see the Supporting Information). Structures 9 and
12 were characterized as true minima with 12 (the C,O-
diprotonated species) residing at the global energy mini-
or propanone (6h ) is produced (Table 2). The compounds
with intermediate σp+ values (0.15 > σp+ > -0.07; 3a ,e-
g) give products from both mechanistic pathways. Only
in the case of 3e (Br substituent) is there any chalcone
product (5e) detected, and the other cinnamic acids give
the respective propanones (6a ,f,g) as products. The
compounds having intermediate σp+ values should be able
to form intermediates such as 11, and thus react with
benzene to give the propanone products (6a ,f,g).
Using low temperature 13C NMR spectroscopy, an
effort was made to directly observe the diprotonated
species arising from cinnamic acid (3a ) in superacid,
however no cleanly formed species could be observed from
FSO3H/SbF5/SO2ClF (1:1:1) solution. When â-phenylcin-
namic acid is mixed with FSO3H/SbF5/SO2ClF (1:1:1) at
-80 °C, a reddish-orange solution is produced and a well
resolved 13C NMR spectrum is seen (Figure 1). Seven
resonance signals appear in the spectrum: 40.4, 132.0,
139.9, 143.4, 150.1, 186.8, and 201.2 ppm. The signals
are consistent with the C,O-diprotonated species (14, eq
6). The resonance signal at 201.2 ppm is assigned to the
mum and 28 kcal‚mol-1 more stable than
9 (the
O,O-diprotonated species). These calculated gas-phase
structures and energies suggest that the preferred reac-
tion pathway for cinnamic acid involves initial protona-
tion at the carboxylic acid group followed by protonation
at the C-2 to give dication 12. A recent report also
proposes the formation of dication 13 in this reaction.7e
While formation of the acyl-carbenium dication (13) is
plausible, intermediate 13 is not likely in the reactions
done at low temperatures (<-10 °C), due to the slow
formation of the acyl cation. Interestingly, cinnamic acid
(3a ) favors the C,O-diprotonated (12) structure, while the
analogous systems of cinnamaldehyde (eq 2) and â-ni-
trostyrene (eq 1), appear to prefer the O,O-diprotonated
structures (1 and 2).
When the results from Table 2 are considered, the
proposed mechanism (Scheme 1) offers an explanation
for the relationship between the σp+ values and relative
diphenylmethyl carbocation center, which suggests ex-
tensive delocalization of charge into the phenyl rings. The
signal at 186.8 ppm is assigned to the carboxylic carbon
of 14, which is comparable to the carboxonium signals
from protonated acetic acid (CH3CO2H2+, 191 ppm) and
benzoic acid (C6H5CO2H2+, 181 ppm).16 At -80 °C, the
signal at 143.4 ppm is significantly broadened, but upon
warming to -60 to -40 °C, the signal sharpens. This
suggests that there is restricted rotation about the phenyl
groups at low temperature. At the warmer temperatures,
new 13C signals (about 10-15 new signals) also begin to
appear, indicating that dication 14 decomposes at tem-
peratures warmer than -80 °C. According to calculations
done at the B3LYP/6-311G (d,p)//B3LYP/6-311G (d,p)
level of theory, the C,O-diprotonated species (14) is
considerably more stable (by 30 kcal‚mol-1) than the
corresponding O,O-diprotonated species (15, see Sup-
porting Information). Reaction of â-phenylcinnamic acid
with TfOH and C6H6 gives a nearly quantitative yield of
the indanone product (eq 7). The indanone product likely
arises from phenylation of the dication 14 at the benzylic
position and subsequent cyclization.6
+
product yields. The compounds with large positive σp
values (3b-d ) have strong electron-withdrawing sub-
stituents, and these starting materials give the chalcone
products (5b-d ) exclusively. The nitro and ammonium
substituents of compounds 3b-d would be expected to
destabilize intermediates generating benzylic, carboca-
tionic centers (similar to 12, Scheme 1), and this tends
to favor intermediates such as 9 and 10, which lead to
acylation reactions and the chalcones (5b-d ). Moreover,
the nitro and ammonium groups should destabilize
intermediates such as 11, so phenylation of the chalcones
(5b-d ) to give the propanones (6b-d ) does not occur.
With compound 3h , the methyl substituent is slightly
+
electron donating (large negative σp value) and the
benzylic intermediate (analogous to 12) is significantly
stabilized. The stabilization of the benzylic intermediate
leads to rapid phenylation and cyclization to 4h , while
the formation of the acyl cation (similar to 10) is a
considerably slower process so neither the chalcone (5h )
(15) (a) Frisch, M. J .; Trucks, G. W.; Schlegel, H. B.; Scuseria, G.
E.; Robb, M. A.; Cheeseman, J . R.; Zakrzewski, V. G.; Montgomery, J .
A.; Stratmann, R. E.; Burant, J . C.; Dapprich, S.; Millam, J . M.;
Daniels, R. E.; Kudin, K. N.; Strain, M. C.; Farkas, O.; Tomasi, J .;
Barone, V.; Cossi, M.; Cammi, R.; Mennucci, B.; Pomelli, C.; Adamo,
C.; Clifford, S.; Ochterski, J .; Petersson, G. A.; Ayala, P. Y.; Cui, Q.;
Morokuma, K.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.;
Foresman, J . B.; Cioslowski, J .; Ortiz, J . V.; Stefanov, B. B.; Liu, G.;
Liashenko, A.; Piskorz, P.; Komaromi, I.; Gomperts, R.; Martin, R. L.;
Fox, D. J .; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.;
Gonzalez, C.; Challacombe, M.; Gill, P. M. W.; J ohnson, B.; Chen, W.;
Wong, M. W.; Andres, J . L.; Gonzalez, C.; M. Head-Gordon, M.; Pople,
J . A. Gaussian 98, revision A.5; Gaussian, Inc.: Pittsburgh, PA, 1998.
(b) For details of the computational studies, see the Supporting
Information.
In addition to cinnamic acids, we examined the super-
acid-catalyzed reactions of related carboxylic acids with
benzene. Cyclopropanes are known to exhibit chemistry
(16) (a) Olah, G. A.; White, A. M. J . Am. Chem. Soc. 1967, 89, 7072.
(b) Other peak assignments: 40.4 ppm, methylene carbon; 132.0 ppm,
meta-position; 139.9 ppm, ortho-position; 143.4 ppm, ipso-position;
150.1 ppm, para-position. These assignments are made by comparison
to other related diphenylmethyl cations, see: Olah, G. A.; Prakash,
G. K. S.; Liang, G.; Westerman, P. W.; Kunde, K.; Chandrasekhar, J .;
Schleyer, P. v. R. J . Am. Chem. Soc. 1980, 102, 4485.
J . Org. Chem, Vol. 69, No. 7, 2004 2345

Rendy et al.
F IGURE 1. 13C NMR spectrum of superelectrophilic dication 14 in FSOH/SbF5/SO2CIF at -80 °C (b, acetone-d6 peak).
SCHEME 2
ment that 25 is not converted to 26 when mixed with
TfOH and C6H6.
Protonated carboxylic acids typically have pKa values
around -6 to -7, which roughly corresponds to the Ho
value at half-protonation. Pure triflic acid is estimated
to be Ho -14.1, so carboxylic acid 24 is fully protonated
in this superacid, and equilibration with the diprotonated
intermediates is plausible (Scheme 2). Protonation of the
acid group gives ion 27 and this species could conceivably
be protonated at the cyclopropyl ring (route a) to give
28, or a second protonation at the acid group could give
the ring opening reaction (route b) and yield the dication
29.20 Both ions (28 and 29) could undergo ring closure
and acylation reactions leading to product 25, while
phenylation of 28 would then yield 26 by intramolecular
acylation. When dication 28 is directly generated from
the reaction of compound 31 in TfOH and benzene,
product 26 is formed quantitatively (eq 9). Computational
studies also indicate that dication 28 is considerably more
stable than dication 29 (by more than 30 kcal‚mol-1),
suggesting that direct ring protonation may be favored
(route a, Scheme 2). Although the reaction of 24 in TfOH
is consistent with the formation of dications, the mono-
cationic species including acyl cations cannot be ruled
out as possible intermediates.18, 19
similar to olefins.17 When trans-2-phenyl-1-cyclopropan-
ecarboxylic acid (24) is mixed with triflic acid and
benzene, two products are observed (Scheme 2, eq 8). The
major product (25) has been prepared previously by the
reaction of trans-2-phenylcyclopropanecarbonyl chloride
with AlCl3,18 but to our knowledge, this is the first report
of a direct transformation of carboxylic acid 24 to the
product 25 via Brønsted acid catalysis. Additionally, a
small amount of 4-phenyl-1-tetralone (26) is formed in
the conversion. It was verified in a subsequent experi-
When phenylpropionic acid (31) is reacted with TfOH
and C6H6, 3,3-diphenylindanone (32) is formed quanti-
tatively (Scheme 3). This conversion also involves dipro-
tonated species such as 33 and 14. Theoretical studies
suggest that protonation occurs at the carboxyl group and
then at the C-2 position. Dication 33 is estimated to be
more than 30 kcal‚mol-1 more stable than the dication
(34; see the Supporting Information) arising from double
protonation of the carboxylic acid group. Intermediate 14
(17) Boche, G., Walborsky, H. M. In Cyclopropane Derived Reactive
Intermediates; Patai, S., Rappoport, Z., Eds.; Wiley: New York: 1990.
(18) Elling, G. R.; Hahn, R. C.; Schwab, G. J . Am. Chem. Soc. 1973,
95, 5659.
(19) A similar monocationic ring opening has been proposed recently,
see: Mohanta, P. K.; Peruncheralathan, S.; Ila, H.; J unjappa, H. J .
Org. Chem. 2001, 66, 1503.
(20) Ohwada, T.; Shudo, K. J . Am. Chem. Soc. 1988, 110, 1862.
2346 J . Org. Chem., Vol. 69, No. 7, 2004

Superacid-Catalyzed Reactions of Cinnamic Acids
SCHEME 3
equiv) and o-dichlorobenzene, little arylation-cyclization
product is formed. Even at elevated temperature, com-
pound 30 is recovered almost quantitatively. This is in
contrast to the chemistry of cinnamic acid (3a ), which
gives a good conversion to product 4l from TfOH and
o-dichlorobenzene (eq 5). We and others have noted that
the reactivities of dicationic systems can be influenced
by the proximity of the charge centers.25 In the case of
compound 30, reaction with superacid gives the 1,5-
dication (28, Scheme 2), while cinnamic acid forms the
1,4-dication (12, Scheme 1). The increased separation of
cationic charge centers renders the 1,5-dication (28)
unreactive toward the deactivated arene, o-dichloroben-
zene.
Su m m a r y
We have found that cinnamic acids and related com-
pounds form highly reactive electrophilic species in the
Brønsted superacid CF3SO3H. The cinnamic acids give
chalcone products when the aryl group is deactivated by
substituents or give indanone products when the aryl
group is not deactivated by substituents. Chalcone prod-
uct formation can also be suppressed by low temperatures
(-15 °C). Experimental evidence suggests two competing
reaction mechanisms.26 We propose that cinnamic acids
and related compounds form diprotonated species in CF3-
SO3H and the protonated carboxylic acid group can
activate adjacent electrophilic groups (like carbocations).
In some cases, diprotonated cinnamic acids can be
directly observed. Triflic acid is shown in the present
results to be an effective catalyst in the preparation of
either substituted indanones or chalcones from cinnamic
acids.27
is similar to dicationic species (i.e., 35) which are thought
to be involved in the reactions of R-ketoacids with
superacid and benzene,6 and 36 which is generated from
ionization of benzylic acid in superacid and undergoes
electrocyclization.20 Dications 14 and 35-36 all exhibit
significantly enhanced reactivity when compared to the
analogous monocation (37). In the cases of 14 and 35,
the dications are sufficiently electrophilic to react with
benzene, while under the same conditions (TfOH/C6H6)
cation 37 is stable.21 Clearly, the protonated carboxylic
acid group enhances the reactivity of the adjacent car-
bocation center in these dicationic species. This activation
is similar to that shown for ammonium groups,22 proto-
nated N-heteroaromatic groups,23 and phosphonium
groups,24 and it is consistent with Olah’s general concept
of superelectrophilic activation.3a
Ack n ow led gm en t. We are grateful to the NIH for
support of this work (SO6GM53933-0251). We are
indebted to Professors George A. Olah and G. K. Surya
Prakash for the use of their NMR instruments at the
University of Southern California. We also thank the
reviewers for their helpful comments.
Although the protonated carboxylic acid group can
enhance the reactivity of an adjacent carbocationic site,
it appears that this activation drops off with increasing
distance between the two cationic charge centers. When
compound 30 is reacted with a large excess of TfOH (500
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra for new compounds (4h , 4j, 5m , 19, 20, and 23),
general experimental procedures, and computation data for
dications 9, 12, 14, 15, 28, 30, 34, and 35. This material is
available free of charge via the Internet at http://pubs.acs.org.
(21) Klumpp, D. A.; Aguirre, S. L.; Sanchez, G. V., J r.; de Leon, S.
J . Org. Lett., 2001, 3, 2781.
(22) (a) Zhang, Y.; McElrea, A.; Sanchez, G. V., J r.; Do, D.; Gomez,
A.; Aguirre, S. L.; Rendy, R.; Klumpp, D. A. J . Org. Chem. 2003, 68,
5119. (b) Klumpp, D. A.; Beauchamp, P. S.; Sanchez, G. S., J r.; Aguirre,
S.; de Leon, S. Tetrahedron Lett. 2001, 42 (34), 5821. (c) Klumpp, D.
A.; Garza, M.; J ones, A.; Mendoza, S. J . Org. Chem. 1999, 64, 6702
(23) Klumpp, D. A.; Lau, S. J . Org. Chem., 1999, 64, 7309. (b)
Klumpp, D. A.; J ones, A.; Lau, S.; DeLeon, S.; Garza, M. Synthesis
2000, 1117. (c) Koltunov, K. Y.; Prakash, G. K. S.; Rasul, G.; Olah, G.
A. J . Org. Chem. 2002, 67, 8943.
J O030327T
(25) (a) Klumpp, D. A.; Garza, G.; Sanchez, G. V.; Lau, S.; DeLeon,
S. J . Org. Chem. 2000, 65, 8997. (b) Prakash, G. K. S.; Rawdah, T. N.;
Olah, G. A. Angew. Chem., Int. Ed. 1983, 22, 390.
(26) Competing mechanisms are also suggested in a report on the
chemistry of cinnamoyl chloride, see: Shotter, R. G.; J ohnston, K. M.;
J ones, J . F. Tetrahedron 1978, 34, 741.
(24) Zhang, Y.; Aguirre, S. A.; Klumpp, D. A. Tetrahedron Lett. 2002,
43, 6837.
(27) Triflic acid may be quantitatively recycled; see: Booth, B. L.;
El-Fekky, T. A. J . Chem. Soc., Perkin Trans. 1 1979, 2441.
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