Influence of Conformation and Proton-Transfer Dynamics in the Dibenzyl σ-Complex on Regioselectivity in Gattermann-Koch Formylation via Intracomplex Reaction

Article abstract of DOI:10.1021/jo980228t

The Gattermann-Koch formylations of diphenyl, diphenylmethane, dibenzyl, and 1,3-diphenyl- propane were studied in HF-SbF₅, -TaF₅, -BF₃, -NbF₅, and CF₃SO₃H-SbF₅. While usual high para regioselectivity was obtained for diphenyl, diphenylmethane, and 1,3-diphenylpropane, unprecedented ortho regioselectivity was observed for dibenzyl which increased with decreasing the SbF₅/dibenzyl molar ratio and with strength of Lewis acids used in HF. A sandwich-like complex for monoprotonated dibenzyl resulting in ortho regioselectivity via the intracomplex reaction was suggested; therefore, the conformations of protonated diphenylmethane, dibenzyl, and 1,3- diphenylpropane and their proton-transfer dynamics were probed by semiempirical calculation (PM3). The calculation predicted that ortho monoprotonation was slightly preferable for dibenzyl, and remarkable preference of dibenzyl over other aromatic compounds was observed in ortho- ortho intramolecular inter-ring proton transfer via a fan-shaped complex rather than a sandwich- like complex. The experimental and theoretical data for dibenzyl are compatible with the intracomplex reaction, whereby CO is protonated by the ortho σ-complex undergoing rapid inter- ring proton transfer to generate formyl cation in the vicinity of the ortho position leading to ortho regioselectivity.

Full text of DOI:10.1021/jo980228t

4408
J . Org. Chem. 1998, 63, 4408-4412
In flu en ce of Con for m a tion a n d P r oton -Tr a n sfer Dyn a m ics in th e
Diben zyl σ-Com p lex on Regioselectivity in Ga tter m a n n -Koch
F or m yla tion via In tr a com p lex Rea ction
Mutsuo Tanaka,*,† Masahiro Fujiwara,† Qiang Xu,† Hisanori Ando,† and Todd J . Raeker‡
Osaka National Research Institute, AIST, 1-8-31, Midorigaoka, Ikeda, Osaka 563, J apan, and
Department of Chemistry, Kent State University, Kent, Ohio 44242
Received February 6, 1998
The Gattermann-Koch formylations of diphenyl, diphenylmethane, dibenzyl, and 1,3-diphenyl-
propane were studied in HF-SbF5, -TaF5, -BF3, -NbF5, and CF3SO3H-SbF5. While usual high
para regioselectivity was obtained for diphenyl, diphenylmethane, and 1,3-diphenylpropane,
unprecedented ortho regioselectivity was observed for dibenzyl which increased with decreasing
the SbF5/dibenzyl molar ratio and with strength of Lewis acids used in HF. A sandwich-like complex
for monoprotonated dibenzyl resulting in ortho regioselectivity via the intracomplex reaction was
suggested; therefore, the conformations of protonated diphenylmethane, dibenzyl, and 1,3-
diphenylpropane and their proton-transfer dynamics were probed by semiempirical calculation
(PM3). The calculation predicted that ortho monoprotonation was slightly preferable for dibenzyl,
and remarkable preference of dibenzyl over other aromatic compounds was observed in ortho-
ortho intramolecular inter-ring proton transfer via a fan-shaped complex rather than a sandwich-
like complex. The experimental and theoretical data for dibenzyl are compatible with the
intracomplex reaction, whereby CO is protonated by the ortho σ-complex undergoing rapid inter-
ring proton transfer to generate formyl cation in the vicinity of the ortho position leading to ortho
regioselectivity.
In tr od u ction
(2)
Electrophilic aromatic substitution is a widely used
classical method to prepare various aromatic compounds.1
As shown in eq 1, the conventional aromatic substitution
is known to consist of four steps, which are (1) formation
of an electrophile (E+) from a proelectrophile (P) through
activation by a Brønsted or Lewis acid (A), (2) attack of
the electrophile on an aromatic compound (ArH) forming
a π-complex, (3) transition of the π-complex to a σ-com-
plex, and (4) loss of proton from the σ-complex to give
the product.
common factors such as electron density of the aromatic
substrate,3 reactivity of electrophiles,4 stability of the
reaction intermediates,5 and steric factors6 may influence
the regioselectivity.7
The Gattermann-Koch formylation8 has been consid-
ered as a typical electrophilic aromatic substitution with
high para regioselectivity.9 In previous work,10 it was
found, however, that the regioselectivity of 1-methyl-
naphthalene formylation in HF-SbF5 drastically changes
(1)
(3) (a) Pedersen, E. B.; Petersen, T. E.; Torssell, K.; Lawesson, S.
Tetrahedron 1973, 29, 579. (b) Kita, Y.; Tohma, H.; Hatanaka, K.;
Takeda, T.; Fujita, S.; Mitoh, S.; Sakurai, H.; Oka, S. J . Am. Chem.
Soc. 1994, 116, 3684.
In the conventional aromatic substitution, the forma-
tion and the attack of the electrophile are separate steps.
The electrophile is formed and dispersed in the reaction
medium before the attack on an aromatic compound.
However, Cacace et al. recently suggested that an
alternative route, the intracomplex reaction eq 2, is
possible, whereby the electrophilic substitution occurs
within the complex formed upon addition of a σ-complex
to the proelectrophile.2
(4) (a) Olah, G. A.; Kobayashi, S. J . Am. Chem. Soc. 1971, 93, 6964.
(b) Olah, G. A.; Kobayashi, S.; Tashiro, M. J . Am. Chem. Soc. 1972,
94, 7448. (c) Olah, G. A.; Kobayashi, S.; Nishimura, J . J . Am. Chem.
Soc. 1973, 95, 564.
(5) (a) J ensen, F. R.; Brown, H. C. J . Am. Chem. Soc. 1958, 80, 4046.
(b) Olah, G. A.; Lukas, J .; Lukas, E. J . Am. Chem. Soc. 1969, 91, 5319.
(c) Olah, G. A.; Tashiro, M.; Kobayashi, S. J . Am. Chem. Soc. 1970,
92, 6369. (d) Olah, G. A. Acc. Chem. Res. 1971, 4, 240. (e) Olah, G. A.;
Melby, E. G. J . Am. Chem. Soc. 1973, 95, 4971. (f) Olah, G. A.;
Nishimura, J . J . Org. Chem. 1974, 39, 1203. (g) Olah, G. A.; Hashimoto,
I.; Lin, H. C. Proc. Natl. Acad. Sci. U.S.A. 1977, 74, 4121.
(6) Brown, H. C.; Bolto, B. A.; J ensen, F. R. J . Org. Chem. 1958,
23, 414.
(7) On the other hand, the difference between meta and ortho-para
regioselectivity is considered to derive from the oxidation potential
difference. Fukuzumi, S.; Kochi, J . K. J . Am. Chem. Soc. 1981, 103,
7240.
(8) (a) Gattermann, L.; Koch, J . A. Chem. Ber. 1897, 30, 1622. (b)
de Rege, P. J . F.; Gladysz, J . A.; Horva´th, I. T. Science 1997, 276, 776.
(9) (a) Olah, G. A.; Pelizza, F.; Kobayashi, S.; Olah, J . A. J . Am.
Chem. Soc. 1976, 98, 296. (b) Olah, G. A.; Ohannesian, L.; Arvanaghi,
M. Chem. Rev. 1987, 87, 671. (c) Tanaka, M.; Iyoda, J .; Souma, Y. J .
Org. Chem. 1992, 57, 2677. (d) Tanaka, M.; Souma, Y. J . Chem. Soc.,
Chem. Commun. 1991, 1551. (e) Tanaka, M.; Fujiwara, M.; Ando, H.;
Souma, Y. J . Org. Chem. 1993, 58, 3213.
In eq 2, a protonated aromatic compound (ArH2+) acts
as an acid to activate proelectrophile P to electrophile
E+. On the other hand, it has been reported that the
† Osaka National Research Institute.
‡ Kent State University.
(1) Olah, G. A. Friedel-Crafts and Related Reactions; Wiley-
Interscience: New York, 1964.
(2) (a) Aschi, M.; Attina, M.; Cacace, F. Angew. Chem., Int. Ed. Engl.
1995, 34, 1589. (b) Aschi, M.; Attina, M.; Cacace, F. J . Am. Chem. Soc.
1995, 117, 12832. (c) Aschi, M.; Attina, M.; Cacace, F. Res. Chem.
Intermed. 1996, 22, 645.
S0022-3263(98)00228-X CCC: $15.00 © 1998 American Chemical Society
Published on Web 05/30/1998

Gattermann-Koch Formylation in Dibenzyl σ-Complex
J . Org. Chem., Vol. 63, No. 13, 1998 4409
a
a
Ta ble 1. F or m yla tion of Diben zyl in HF -SbF 5
Ta ble 2. F or m yla tion of Diben zyl in HF -SbF 5
yields (%) for
yields (%) for
regioselectivity
(%) for
regioselectivity
(%) for
SbF5/
dibenzyl
molar ratio
SbF5/
dibenzyl
mono-
HF
mono-
aldehydec
dialdehyded
ortho meta para
molar ratio (mmol) aldehydec dialdehyded ortho meta para
0.25b
0.5b
0.75b
1.0b
1.25b
1.5b
1.75b
2.0b
2.5
23 (72:2:26)
38 (60:2:38)
0
72
52
36
32
23
23
21
11
7
2
2
1
1
1
1
1
0
0
0
26
46
63
67
76
76
78
89
93
93
1.0b
1.0b
1.0b
1.25b
1.25b
1.25b
2.5
250 37 (36:2:62) 31 (12:9:79) 24
500 38 (48:2:50) 26 (15:9:76) 32
1000 46 (63:2:35) 23 (19:9:72) 43
250 39 (30:2:68) 41 (10:9:81) 19
500 45 (37:3:60) 37 (10:9:81) 23
1000 45 (54:2:44) 37 (13:8:79) 31
1
1
1
1
1
1
0
0
0
75
67
56
80
76
68
92
93
93
6 (24:9:67)
40 (50:2:48) 17 (14:9:77)
38 (48:2:50) 26 (15:9:76)
45 (37:3:60) 37 (10:9:81)
45 (39:3:58) 51 (11:10:79)
37 (39:3:58) 62 (11:11:78)
2 (44:0:56) 96 (7:8:85)
250
500
1000
0
0
0
97 (5:6:89)
97 (6:3:91)
97 (5:3:92)
8
7
7
2.5
2.5
0
0
97 (6:3:91)
95 (6:2:92)
3.0
7
a
The formylation was carried out with dibenzyl (10 mmol)
under 20 atm of CO pressure at 0 °C for 2 h. The regioselectivity
(%) presents the total of mono- and dialdehyde regioselectivity.
a
The formylation was carried out with HF (500 mmol) and
dibenzyl (10 mmol) under 20 atm of CO pressure at 0 °C for 2 h.
The regioselectivity (%) presents the total of mono- and dialdehyde
regioselectivity. b Unreacted dibenzyl was recovered. c Isomer ratio
Unreacted dibenzyl was recovered. c Isomer ratio of o-:m-:p-
b
d
formyldibenzyl. Isomer ratio of o,o′-:o,p′-:p,p′-diformyldibenzyl.
d
of o-:m-:p-formyldibenzyl. Isomer ratio of o,o′-:o,p′-:p,p′-diformyl-
dibenzyl.
mixture was heterogeneous. Therefore, to evaluate the
influence of heterogeneous conditions on the regioselec-
tivity, the formylation was conducted using various
amounts of HF as listed in Table 2. When the SbF5/
dibenzyl molar ratio was less than 2, ortho regioselec-
tivity increased with increasing the amount of HF,
namely, with the dissolution of dibenzyl into HF-SbF5.
On the other hand, such tendency was not observed
under the homogeneous conditions where the SbF5/
dibenzyl molar ratio was 2.5. These results indicate that
the ortho regioselectivity is enhanced by the low SbF5/
dibenzyl molar ratio, but not by the heterogeneous
conditions. When the SbF5/dibenzyl molar ratio is less
than 2, dibenzyl is mono- and diprotonated to be in an
equilibrium condition between mono- and dications. As
the ratio of monocation decreases with the SbF5/dibenzyl
molar ratio, the monocation seems to favor the ortho
regioselectivity. The kinetic study10 suggests that the
intracomplex reaction can be predominant when the
SbF5/dibenzyl molar ratio is less than 2 because dibenzyl
has two aromatic rings being almost chemically inde-
pendent of each other.9e Taking into account the three-
order equation containing two aromatic molecules for the
intracomplex formylation,10 two types of σ-complexes13
as a reaction precursor are conceivable in the case of
dibenzyl monocation, which are (1) the σ-complex com-
prised of two dibenzyls and one HF‚SbF5 and (2) the
σ-complex comprised of one dibenzyl and one HF‚SbF5
to form a sandwich-like complex. The former σ-complex
apparently will show high para regioselectivity, but the
latter one seems to show ortho regioselectivity because
the proton to produce formyl cation is located at the ortho
position of dibenzyl (eq 4).
depending on the SbF5/1-methylnaphthalene molar ratio.
The kinetic study10,11 showed that the change in regiose-
lectivity is caused by the reaction path transfer depend-
ing on the SbF5/1-methylnaphthalene molar ratio be-
tween the intracomplex and the conventional reactions,
where the intracomplex reaction reflecting the structure
of the σ-complex as a reaction precursor gives only
1-methyl-4-naphthaldehyde (eq 3).
(3)
This paper reports the regioselectivity of the intracom-
plex reaction in the Gattermann-Koch formylation re-
flecting not only the structure but also the proton-
transfer dynamics of the σ-complex as a reaction precursor.
Resu lts a n d Discu ssion
F or m yla tion Stu d ies. We previously reported that
the formylation of diphenyl, diphenylmethane, and di-
benzyl gives their corresponding dialdehydes with high
para regioselectivity in HF-SbF5.9d,e However, it was
found that the regioselectivity of dibenzyl formylation
changed from ortho to para with an increase in the SbF5/
dibenzyl molar ratio as shown in Table 1.12 When the
SbF5/dibenzyl molar ratio was less than 2, the reaction
The formation of such a sandwich-like complex has
been suggested in several papers.14 If the sandwich-like
complex for the monocation is formed, the regioselectivity
change in the dibenzyl formylation is explained by the
change in ratio between mono- and dications depending
on the SbF5/dibenzyl molar ratio resulting in ortho and
para regioselectivity, respectively (eq 4).15 However,
attempts to detect the sandwich-like complex by NMR
failed.16
(10) (a) Tanaka, M.; Fujiwara, M.; Ando, H.; Souma, Y. J . Chem.
Soc., Chem. Commun. 1996, 159. (b) Tanaka, M.; Fujiwara, M.; Xu,
Q.; Souma, Y.; Ando, H.; Laali, K. K. J . Am. Chem. Soc. 1997, 119,
5100.
(11) (a) Tanaka, M.; Fujiwara, M.; Ando, H. J . Org. Chem. 1995,
60, 2106. (b) Tanaka, M.; Fujiwara, M.; Ando, H. J . Org. Chem. 1995,
60, 3846.
(12) In control experiments, the elimination of the formyl group was
not observed under the same conditions, and the regioselectivity for
the formylation of monoformyldibenzyl was para about 90% in ratio.
(13) The σ-complex here is in equilibrium with the π-complex.
(14) (a) Cacace, F.; de Petris, G.; Fornarini, S.; Giacomello, P. J .
Am. Chem. Soc. 1986, 108, 7495. (b) Kuck, D.; Matthias, C. J . Am.
Chem. Soc. 1992, 114, 1901. (c) Cacace, F.; Crestoni, M. E.; Fornarini,
S.; Kuck, D. J . Am. Chem. Soc. 1993, 115, 1024. (d) Laali, K. K.;
Forsyth, D. A. J . Org. Chem. 1993, 58, 4673.

4410 J . Org. Chem., Vol. 63, No. 13, 1998
Tanaka et al.
Ta ble 3. In flu en ce of Ch a in Len gth betw een Ar om a tic
Rin gs on F or m yla tion Regioselectivitya
Ta ble 4. In flu en ce of Acid ity of F or m yla tion
Regioselectivitya
yields (%) for
yields (%) for
regioselectivity
(%) for
regioselectivity
(%) for
mono-
Lewis
acid
mono-
substrate
aldehyded dialdehydee ortho meta para
aldehydeb
dialdehydec
ortho
meta
para
diphenyl
97 (0:0:100)
15 (0:0:100) 77 (6:8:86)
15 (2:0:98) 2 (0:0:100)
0
0
9
2
0
0
0
1
1
100
91
98
67
95
SbF5
TaF5
BF3
38 (48:2:50)
45 (48:1:51)
34 (41:1:58)
28 (23:2:75)
26 (15:9:76)
26 (12:6:82)
18 (9:6:85)
7 (6:6:88)
32
30
26
18
1
1
1
1
67
69
73
81
diphenylb
diphenylmethanec
dibenzyl
1,3-diphenylpropane 50 (2:2:96) 24 (3:6:91)
38 (48:2:50) 26 (15:9:76) 32
NbF5
4
a
The formylation was carried out with HF (500 mmol), Lewis
acid (10 mmol), and dibenzyl (10 mmol) under 20 atm of CO
pressure at 0 °C for 2 h. The regioselectivity (%) presents the total
of mono- and dialdehyde regioselectivity. Unreacted dibenzyl was
a
The formylation was carried out with HF (500 mmol), SbF5
(10 mmol), and substrate (10 mmol) under 20 atm of CO pressure
at 0 °C for 2 h. The regioselectivity (%) presents the total of mono-
and dialdehyde regioselectivity. Unreacted substrate was recov-
b
recovered in all experiments. Isomer ratio of o-:m-:p-formyldi-
b
ered in all experiments. The formylation was carried out with
benzyl. c Isomer ratio of o,o′-:o,p′-:p,p′-diformyldibenzyl.
25 mmol of SbF5. c The cleavage of methylene chain occurred to
a
give benzaldehyde.9d,e Isomer ratio of o-:m-:p-formyldibenzyl.
d
Ta ble 5. F or m yla tion of Diben zyl in CF 3SO3H-SbF 5
e Isomer ratio of o,o′-:o,p′-:p,p′-diformyldibenzyl.
yields (%) for
regioselectivity
(%) for
SbF5/
dibenzyl
molar ratio
mono-
aldehydeb
dialdehydec ortho meta para
0.5
1.0
2.0
3.0
25 (14:1:85)
35 (12:1:87)
17 (20:1:79) 26 (5:4:91)
2 (34:0:66) 33 (10:4:86)
2 (0:0:100)
3 (4:5:91)
12
11
10
13
1
1
0
0
87
88
90
87
a
The formylation was carried out with CF3SO3H (200 mmol)
and dibenzyl (10 mmol) under 20 atm of CO pressure at 0 °C for
2 h. The regioselectivity (%) presents the total of mono- and
dialdehyde regioselectivity. Unreacted substrate was recovered
b
in all experiments. Isomer ratio of o-:m-:p-formyldibenzyl. c Iso-
mer ratio of o,o′-:o,p′-:p,p′-diformyldibenzyl.
To investigate the influence of acidity on the regiose-
lectivity, dibenzyl formylation was carried out using
various Lewis acids in HF. The results are tabulated in
Table 4. The order of acidities are SbF5 > TaF5 > BF3 >
NbF5.17 Ortho regioselectivity decreased with a decrease
in the acidity of the Lewis acids, namely, with a decrease
in the coordination ability of superacids to form the
sandwich-like complex. This tendency in regioselectivity
depending on the stability of the sandwich-like complex
is consistent with the notion that regioselectivity of the
intracomplex reaction reflects the structure of the σ-com-
plex as a reaction precursor.10
When dibenzyl formylation was carried out with
CF3SO3H-SbF5 instead of HF-SbF5, a regioselectivity
change was not observed as tabulated in Table 5.
CF3SO3H-SbF5 is well-known to be a far weaker acid
than HF-SbF5,17a,b but the acidity of CF3SO3H itself is
strong enough to make the Gattermann-Koch formyla-
tion occur.18 Therefore, the formylation in CF3SO3H-
SbF5 does not proceed via the sandwich-like complex
regardless of the SbF5/dibenzyl molar ratio.
Th eor etica l Stu d ies. To evaluate the preference of
dibenzyl over other aromatic compounds to form the
sandwich-like complex in view of experimental results,
the protonation energies and conformations were exam-
ined for diphenylmethane, dibenzyl, and 1,3-diphenyl-
propane by semiempirical calculations (PM3 in Hyper-
chem and GAMESS19). The calculation was performed
not only for ortho and para σ-complexes but also for the
ipso σ-complex because the ipso σ-complex can be another
(4)
To evaluate the existence of the sandwich-like complex,
the formylation of various polynuclear aromatic com-
pounds, in which the chain length between the aromatic
rings differed, was conducted in HF-SbF5. The results
are summarized in Table 3. Ortho regioselectivity was
observed only during dibenzyl formylation. This result
clearly shows that only the distance between two aro-
matic rings of dibenzyl is appropriate for the formation
of the sandwich-like complex leading to ortho regioselec-
tivity. For diphenyl, the reaction mixtures were hetero-
geneous similar to dibenzyl when the SbF5/diphenyl
molar ratio was less than 2. As shown in Table 3,
although only para formyldiphenyl was formed under
heterogeneous conditions, both ortho and para formyl-
diphenyl were produced under homogeneous conditions.
This result also supports that the heterogeneous condi-
tions do not favor the ortho regioselectivity as mentioned
before.
(15) Protonation usually occurs at the para position of a substituent.
(a) Olah, G. A.; Schlosberg, R. H.; Porter, R. D.; Mo, Y. K.; Kelly, D.
P.; Mateescu, G. D. J . Am. Chem. Soc. 1972, 94, 2034. (b) Olah, G. A.;
Mateescu, G. D.; Mo, Y. K. J . Am. Chem. Soc. 1973, 95, 1865. (c) Olah,
G. A.; Staral, J . S.; Asencio, G.; Liang, G.; Forsyth, D. A.; Mateescu,
G. D. J . Am. Chem. Soc. 1978, 100, 6299.
(16) Attempts to detect the sandwich-like complex in HF-SbF5 and
CF3SO3H-SbF5 at various temperatures by NMR resulted in the
observation of broad peaks which merged with baselines. This result
indicates that the sandwich-like complex is in protonation equilibrium
and has both π- and σ-complex natures.
(17) (a) Gillespie, R. J .; Liang, J . J . Am. Chem. Soc. 1988, 110, 6053.
(b) Olah, G. A.; Prakash, G. K. S.; Sommer. J . Superacids; Wiley-
Interscience: New York, 1985; Chapter 1. (c) Kramer, G. M. J . Org.
Chem. 1975, 40, 302.
(18) (a) Booth, B. L.; El-Fekky, T. A.; Noori, G. F. M. J . Chem. Soc.,
Perkin Trans. 1 1980, 181. (b) Olah, G. A.; Laali, K.; Farooq, O. J .
Org. Chem. 1985, 50, 1483.

Gattermann-Koch Formylation in Dibenzyl σ-Complex
J . Org. Chem., Vol. 63, No. 13, 1998 4411
F igu r e 3. Transition conformations for O+ f O′+ (left) and
P f P′ (right) inter-ring proton transfer.
F igu r e 1. Conformations of ortho diphenylmethane σ-com-
plexes (O+, left; O-, right).
plex was more favorable than para σ-complex with 0.8
kcal/mol difference in energy. The calculation results for
diprotonation of dibenzyl showed that para-para dipro-
tonation was favored over para-ortho (1.9 kcal/mol) and
ortho-ortho (4.0 kcal/mol) diprotonation. The calculation
results for protonation energies suggest that ortho mono-
protonation is slightly preferable for dibenzyl and 1,3-
diphenylpropane which is unusual in σ-complexes in
superacids.15 The interaction among proton and two
aromatic rings, namely, a kind of cation-π interaction,20
seems to favor the fan-shaped structure for coordination
with ortho protonation.
To evaluate the formation step of formyl cation, we
scrutinized the transition-state energies for proton trans-
fer at the PM3 level. Ortho-ortho and para-para inter-
ring proton transfers were considered. As ortho-para
inter- and intra-ring proton transfers were clearly unfa-
vorable intuitively in view of a long-distance proton
transfer, these processes were not considered. Transi-
tion-state modeling for diphenylmethane showed that the
transition barriers for ortho-ortho (O+ f O′+) and para-
para (P f P′) inter-ring proton transfer were 12.6 and
31.3 kcal/mol, respectively. The result suggests that the
proton transfer is unlikely to influence the formylation
in view of the protonation energy for the ipso σ-complex,
although ortho-ortho inter-ring proton transfer is sig-
nificantly favorable over para-para inter-ring proton
transfer. In the case of dibenzyl, the barriers for ortho-
ortho and para-para inter-ring proton transfer were 3.3
and 26.2 kcal/mol, respectively, where the transition
barrier for ortho-ortho inter-ring proton transfer was
F igu r e 2. Conformations of ortho dibenzyl σ-complexes
(O+, left; O-, right).
reaction precursor resulting in ortho regioselectivity in
the intracomplex formylation (eq 5).
(5)
For diphenylmethane, the calculation predicted that
para σ-complex was slightly favored over ortho σ-complex
(0.2 kcal/mol) and that formation of ipso σ-complex was
least favorable (10.1 kcal/mol). There were two minimum-
energy conformations for the ortho σ-complex both having
a 90° ring-ring torsional angle (perpendicular π-faces)
with the protonated site pointing toward the opposite ring
(O+) and away from it (O-), respectively (Figure 1), where
O+ was preferred by about 1.5 kcal/mol. For dibenzyl,
ortho σ-complex was slightly favored over para σ-complex
(1.0 kcal/mol) in contrast with diphenylmethane. Ipso
σ-complex again was least favorable (9.5 kcal/mol). There
were two minimum-energy conformations, O+ and O-, for
the ortho σ-complex (Figure 2) similar to diphenyl-
methane. This was at ca. (75° ring-ring dihedral angle,
again with the protonated site pointing toward the
opposite ring (O+) being favored by about 1.4 kcal/mol.
The cofacially constrained para σ-complex, a sandwich-
like complex, was about 4.2 kcal/mol higher in energy
compared to the unconstrained para σ-complex, a fan-
shaped complex. For 1,3-diphenylpropane, ortho σ-com-
remarkably low. The transition conformations for O+
f
O′+ and P f P′ inter-ring proton transfer are shown in
Figure 3, where the proton in ortho-ortho inter-ring
transfer is closer to aromatic rings compared with that
in para-para inter-ring transfer. The ortho-ortho inter-
ring proton transfer occurred within a fan-shaped com-
plex (ring-ring dihedral angle 75°) rather than a sand-
wich-like complex discussed before. To visually under-
stand the proton-transfer dynamics in the dibenzyl
σ-complex, a potential energy diagram is depicted in
Figure 4 for intra-ring, inter-ring, and intra-ring/inter-
ring proton-transfer pathways involving the ortho (O+
and O-) and ipso (I) σ-complexes. Proton transfers via
the ipso σ-complex, which was higher in energy than the
ortho σ-complex, were more energy demanding. On the
other hand, 1,3-diphenylpropane showed that the barrier
for ortho-ortho inter-ring proton transfer was 21.7 kcal/
mol, and that for para-para inter-ring proton transfer
was not available because of difficulty in convergence,
(19) Schmidt, M. W.; Baldridge, K. K.; Boatz, J . A.; Elbert, S. L.;
Gordon, M. S.; J ensen, J . J .; Koseki, S.; Matsunaga, M.; Nguyen, K.
A.; Su, S.; Windus, T. L.; Dupuis, M.; Montgomery, J . A. J . Comput.
Chem. 1993, 14, 1347.
(20) Dougherty, D. A. Science 1996, 271, 163.

4412 J . Org. Chem., Vol. 63, No. 13, 1998
Tanaka et al.
Con clu sion s
Taking together the experimental and theoretical
results, it seems quite probable that in accord with eq 4,
CO is protonated by the ortho dibenzyl σ-complex un-
dergoing rapid inter-ring proton transfer to generate a
formyl cation in the vicinity of the ortho position, leading
to high ortho regioselectivity through the intracomplex
mechanism. While the experimental study suggests
influence of the conformation of the σ-complex as a
reaction precursor on the regioselectivity, the theoretical
study points that the crucial step to determine the
regioselectivity is in the proton-transfer dynamics to
produce the formyl cation. These results show that the
specific features of the intracomplex reaction are in the
proton-transfer dynamics itself being consistent with
Cacace’s concept.2
F igu r e 4. Potential energy profile for various proton-transfer
processes in ortho and ipso dibenzyl σ-complexes.
Exp er im en ta l Section
All materials were of the highest available purity and used
without further purification. HF and CF3SO3H contained 0.1
and 5 mol % H2O, respectively. H2O was considered to form
H2O‚SbF5 quantitatively as an inert additive. The identifica-
tion of products was performed by NMR (1H and 13C NMR,
H-H COSY, C-H COSY, and COLOC) and MS after separa-
tion by distillation, recrystallization, and HPLC. The yields
were determined by GC, and the isomer distributions were
determined by GC and NMR.
Ga t t er m a n n -Koch F or m yla t ion P r oced u r es. Sub-
strate (10 mmol) was added to a solution of Lewis acids with
HF or CF3SO3H in a Hastelloy autoclave (100 mL) equipped
with a Hastelloy magnetic stir bar under temperature control.
The autoclave was sealed, and CO (20 atm) was introduced
with vigorous stirring. After the reaction was over, the
autoclave was depressurized and opened. The reaction was
quenched with ice-water and extracted with benzene.
1,3-Dip h en ylp r op a n e P r ep a r a tion P r oced u r es. 1,3-
Dichloropropane (50 mmol, 5.65 g) was slowly added to a slurry
of AlCl3 (100 mmol, 13.3 g) in benzene (150 mL) at room
temperature. After 2 h, the reaction mixture formed two liquid
phases. The supernatant fraction was separated and washed
with water. After evaporation of benzene, 1,3-diphenylpropane
was separated by vacuum distillation.
F igu r e 5. Potential energy profile for O+ f O′+ and P f P′
inter-ring proton transfer. O* and P* represent transition
states for O+ f O′+ and P f P′ inter-ring proton transfer,
respectively.
NMR Stu d y P r oced u r es. Dibenzyl (10 mmol, 1.82 g) was
added to a solution of various amounts of SbF5 in HF (500
mmol, 10.0 g) or CF3SO3H (200 mmol, 30.0 g) in a Teflon
round-bottom flask (300 mL) at 0 °C with stirring. A portion
of the solution was transferred to a 5-mm Teflon NMR sample
tube with a Teflon pipet, and then, the tube was sealed with
a Teflon stopper. The NMR measurements were performed
according to the procedures in ref 11a.
namely, a high barrier. The calculation results for the
proton-transfer barriers summarized in Figure 5 show
that only ortho-ortho inter-ring proton transfer for
dibenzyl is a likely path. The mobility of the proton
between two rings in the ortho dibenzyl σ-complex can
make the ortho σ-complex more reactive to form formyl
cation than the para σ-complex according to the intra-
complex features.2
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