Synthesis and rearrangement of dewar benzenes into biaryls: Experimental evidence for conrotatory ring opening

Article abstract of DOI:10.1002/ejoc.200700916

Rearrangement of aryl-substituted Dewar benzenes into the corresponding biaryls may serve as an alternative pathway for synthesis of sterically hindered biaryls. The kinetic data obtained from thermal rearrangements of Dewar benzenes provide experimental

Full text of DOI:10.1002/ejoc.200700916

SHORT COMMUNICATION
DOI: 10.1002/ejoc.200700916
Synthesis and Rearrangement of Dewar Benzenes Into Biaryls: Experimental
Evidence for Conrotatory Ring Opening
[a]
[b]
[c]
[a,b]
ˇ
ˇ
ˇ
ˇ
Stepánka Janková, Martin Dracínský, Ivana Císarová, and Martin Kotora*
Dedicated to Zbyneˇk Janousˇek on the occasion of his 60th birthday
Keywords: Dewar benzene / Biaryls / Alkynes / Hammett / Rearrangement
Rearrangement of aryl-substituted Dewar benzenes into the
corresponding biaryls may serve as an alternative pathway
for synthesis of sterically hindered biaryls. The kinetic data
obtained from thermal rearrangements of Dewar benzenes
provide experimental evidence for the proposed orbital-sym-
metry-controlled electrocyclic ring opening.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2008)
During our studies on the Cu- and Ni-mediated reaction
of zirconacyclopentadienes with ortho-substituted phenyl-
propynoates, we observed the formation of DBs as side
products in relatively high yields.[13]
Introduction
Syntheses and rearrangements of strained carbocyclic
substances have been fertile ground for the discovery of new
reactions and compounds.[1,2] One of these compounds that
has attracted considerable synthetic and theoretical interest
is Dewar benzene (DB) Ϫ a benzene valence isomer.[3] Syn-
theses of the first Dewar benzenes were performed in the
1960s by a clever choice of conventional reactions and/or
UV irradiation of suitable precursors; they became the first
isolated valence-bond isomers of benzene.[4] Facile isomer-
ization of DBs into their more stable isomers Ϫ benzenes
Ϫ can be achieved cleanly and quantitatively under thermal
or photochemical conditions. Soon after these reports, a re-
markable trimerization reaction of 2-butyne in the presence
of AlCl3 for the preparation of hexamethyl[2.2.0]bicy-
clohexa-2,5-diene (hexamethyl-DB) in reasonable yields was
discovered.[5] This method also opened a simple pathway to
other DB derivatives.[6–9] Although DBs are in many in-
stances stable compounds, they have found interesting prac-
tical applications only recently, for example, in the synthesis
of oligophenylene macrocycles,[10] as a supramolecular pro-
tecting group,[11] in the synthesis of ladderanes, and high-
content DB polymers.[12]
Results and Discussion
The above-mentioned results brought us to an idea of
whether potentially atropoisomeric biaryls could be alterna-
tively prepared with the use of Dewar benzenes followed by
rearrangement. Because it was reported that alkynes react
with AlCl3 to give a stable “cyclobutadiene–AlCl3 com-
plex”,[14] we decided to check its reactivity with substituted
phenylpropynoates. Initially, the reactions were carried out
with the complexes of 2-butyne (1a) or 3-hexyne (1b) with
2-methoxynaphthylpropynoate (2a; Scheme 1). Addition of
a solution of 2a in a mixture of dichloromethane and
DMSO[15] into a preformed red solution of the cyclobutadi-
ene complex proceeded in both cases uneventfully to give
corresponding DB 3aa and 3ba in good isolated yields of
63 and 69%, respectively.
Both products were stable at room temperature. After
recrystallization of 3aa from MeOH, single-crystal X-ray
analysis unambiguously confirmed its DB skeleton (Fig-
ure 1). Encouraged by these results, diastereoselective for-
mation of DB was also attempted. Chiral (–)-menthyl 2-
methoxynaphthylpropynoate (2b) was taken into the reac-
tion with 1a according to the above-mentioned method and
corresponding DB 3ab was isolated in 45% yield as a 1:1
diastereoisomeric mixture, which indicates that no dia-
stereoselective discrimination took place. Both diastereoiso-
mers were separated by preparative HPLC (unfortunately,
attempts to determine the configuration of the separated
diastereoisomers were unsuccessful; crystallization did not
[a] Department of Organic and Nuclear Chemistry, Faculty of Sci-
ence, Charles University,
Hlavova 8, 128 43 Praha 2, Czech Republic
Fax: +420-220-951-326
E-mail: kotora@natur.cuni.cz
[b] Institute of Organic Chemistry and Biochemistry, Academy of
Science of the Czech Republic,
Flemingovo n. 2, 166 10 Praha 6, Czech Republic
[c] Department of Inorganic Chemistry, Faculty of Science,
Charles University,
Hlavova 8, 128 43 Praha 2, Czech Republic
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
Eur. J. Org. Chem. 2008, 47–51
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
47

ˇ
S. Janková, M. Dracˇínský, I. Císarˇová, M. Kotora
SHORT COMMUNICATION
of the formed arylnaphthalene remains, at the moment, un-
clear. Interestingly, attempts to rearrange DB 3aa by transi-
tion-metal complexes, such as, [IrCl(cod)]2, [RhCl(CO)2]2,
RhCl(PPh3)3, and PdCl2(MeCN)2 (at 20 or 40 °C) did not
take place, despite the fact that hexamethyl-DB could be
rearranged into hexamethylbenzene at 20 °C.[16]
Scheme 2. Rearrangement of 3aa and 3ab into benzenes 4.
Scheme 1. Formation 2-methoxy-1-naphthyl-substituted Dewar
benzenes 3.
afford suitable crystals for X-ray analysis, and NMR spec-
troscopic analysis did not give any clear-cut data).
Figure 2. X-ray structure of 4a. Displacement parameters are
shown at the 50% probability level.
Next, our attention shifted to the reaction of the cyclobu-
tadiene complex with ortho- and para-substituted phenyl-
propynoates. We assumed that the synthesis of a series of
DBs with variously substituted benzene rings attached, fol-
lowed by a study of substituent effects on their rearrange-
ment could provide further insight into its reaction mecha-
nism. The reaction was carried out under the above-men-
tioned conditions and the obtained results are presented in
Figure 1. X-ray structure of 3aa. Displacement parameters are
shown at the 50% probability level.
With a set of DBs in hand, we decided to proceed with Table 1. In all cases, the reaction proceeded uneventfully
the rearrangement into the corresponding benzenes under and corresponding DBs 5a–l were isolated in a broad range
thermal conditions (Scheme 2). Dewar benzene 3aa, a solid of yields (9–70%).
and stable compound, was cleanly and quantitatively re-
The rearrangements of para-phenyl-substituted DBs 5a–
arranged into corresponding benzene 4a only after it was g were carried out in DMSO at 135 °C in an NMR device
heated to its melting point (ca. Ͼ130 °C). Its structure was to monitor the course of the reaction and to collect reliable
again unambiguously confirmed by single-crystal X-ray data for calculation of rate constants. The results presented
analysis (Figure 2). Also, enantiomerically pure dia- in Table 2 clearly show that the rate constants strongly de-
stereoisomer 3ab was easily rearranged into corresponding pend on the nature of the substituent in the para position.
biaryl 4b; however, the stereochemical information intro- The difference in the rate constants for DB with a strongly
duced by the DB moiety was lost in the course of the reac- electron-donating substituent (OMe) and a strongly elec-
tion, which resulted in the formation of a 1:1 mixture of tron-accepting substituent (CN) is 6.5-fold. This indicates
diastereoisomers. Whether this was caused by the formation that electronic effects exerted by the para substituents are
of a highly distorted intermediate in which free rotation translated across the π system of the conjugated C–C bonds
around the bond connecting the naphthyl moiety and the to the Dewar ring backbone and influence its stability.
Dewar benzene backbone was allowed or by racemization Quite importantly, a Hammett-type correlation with a good
48
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 47–51

Synthesis and Rearrangement of Dewar Benzenes Into Biaryls
Table 1. Formation of Dewar benzenes.
of the reaction could be similar to those affecting the elec-
trocyclic ring opening of cyclobutenes. It has been shown
that substituents attached to the double bond of the cyclo-
butene ring affect the reaction rate depending on its elec-
tronic properties.[17] Thus electron-donating substituents in-
crease the activation energy and thus decrease the reaction
rate, whereas electron-accepting substituents exert the op-
posite effect. In this regard, the results presented in Table 2
follow the same trend: electron-donating substituents such
as Me and MeO decrease the reaction rate of the rearrange-
ment, whereas electron-accepting substituents increase it
(with respect to 5c, which was used as a standard).
The reaction mechanism of the rearrangement of DB
into benzene has for a long time been a target of many
studies and has led to the universal assumption that electro-
cyclic ring opening of DB must follow an orbital symmetry-
forbidden disrotatory path. However, contrary to this as-
sumption, recent calculations indicate that conrotatory
opening of DB to intermediate cis,cis,trans-cyclohexatriene,
which then rearranges into benzene, proceeds through a
slightly lower energy transition state than direct disrotatory
opening. Thus, despite formidable ring constraints and the
formation of an extraordinarily strained intermediate, or-
bital symmetry control triumphs in a case long maintained
as a paradigm for a symmetry-forbidden reaction.[18]
In this paper,[18] two modes of electrocyclic ring opening
of DB into benzene were studied: the commonly accepted
C2v transition state for the disrotatory pathway was found
to be a second-order saddle point. Instead, a Cs true transi-
tion state, positioned 3.7 kcalmol–1 below the C2v saddle
point, was identified, as expected for the thermally allowed
conrotatory electrocyclic ring opening of DB. Later, the dis-
rotatory and conrotatory pathway were studied at the
CASSCF(10,10) level.[19]
Propynoate Ar
Dewar benzene 5
Isolated yield [%]
4-MeOC6H4
4-MeC6H4
C6H5
5a
5b
5c
5d
5e
5f
5g
5h
5i
49
53
70
50
39
27
51
50
70
37
9
4-ClC6H4
4-MeOOCC6H4
4-CF3C6H4
4-CNC6H4
2-MeOC6H4
2-MeC6H4
2-ClC6H4
5j
5k
5l
2-MeOOCC6H4
2-CF3C6H4
18
fit (R2 = 0.987) was obtained between lnkexp and the σp
substituent constants with a slope of 1.79, which indicates
a strong dependence on electronic effects (Figure 3).
Table 2. Rearrangement of Dewar benzenes 5 into benzenes 6.
Dewar benzene
X
Benzene 6
k [s–1] at 135.1 °C
5a
5b
5c
5d
5e
5f
OMe
Me
H
6a
6b
6c
6d
6e
6f
0.44ϫ10–4
0.63ϫ10–4
0.71ϫ10–4
1.03ϫ10–4
1.70ϫ10–4
1.72ϫ10–4
2.86ϫ10–4
True transition states (with one imaginary frequency)
were found for both modes of the ring-opening reaction;
the conrotatory transition state was 6.6 kcalmol–1 below
the disrotatory transition state. Furthermore, an IRC calcu-
lation showed that the conrotatory transition state connects
DB directly with benzene without passing through the cis,-
cis,trans-cyclohexa-1,3,5-triene. In another work,[20] it was
found that the potential energy surface of hexamethyl-DB
is slightly different from that of DB. The ring opening of
hexamethyl-DB leads to the strained trans conformation of
hexamethylbenzene.
Cl
COOMe
CF3
CN
5g
6g
To shed further light on the reaction mechanism of the
rearrangement, calculations were carried out by using the
Gaussian 03 software package and DFT calculations were
performed by using the Becke3LYP functional with the 6-
311+G(d,p) basis set. A conrotatory transition state was
found for all derivatives. The relative energies for the calcu-
lated structures and the free energies are listed in Table 3.
The calculated free energies of activation can be compared
with the experimentally obtained value of ∆G# from the
Eyring equation ∆G# = RT[23.76 – ln(k/T)]. The calculated
Figure 3. Correlation of para-σ Hammett constants with ln of re-
arrangement rate constants k.
As it has been proposed that electrocyclic ring opening free energies of activation are slightly lower than the experi-
of DB benzene is controlled by orbital symmetry, it is rea- mental (up to 0.9 kcalmol–1) but the change in the experi-
sonable to assume that the substituent effects on the course mental free energy depending on the substituent in the para
Eur. J. Org. Chem. 2008, 47–51
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
49

ˇ
S. Janková, M. Dracˇínský, I. Císarˇová, M. Kotora
SHORT COMMUNICATION
was poured onto crushed ice and extracted with hexane
(3ϫ10 mL). The combined organic layer was dried with MgSO4.
The solvent was evaporated, and column chromatography afforded
the desired products.
position is very well reproduced by the theoretical calcula-
tions. The correlation between the calculated and experi-
mental free energies of activation is shown in Figure 4.
Table 3. Calculated relative energies (referenced to biaryl deriva-
tives, Erel = 0), energies of activation in vacuo and in DMSO, dipole
moments and calculated and experimental free energies of acti-
vation for the rearrangement of Dewar benzene derivatives.[a]
Supporting Information (see footnote on the first page of this arti-
cle): Experimental details, kinetic measurements, and spectral and
crystallographic data.
DB
ERel
DB
ERel
TS
∆E#[b]
∆µ#
∆E#[c] ∆G#[c] ∆G#
exp.
Acknowledgments
6a
6b
6c
6d
6e
6f
54.28 87.44 33.17
54.95 87.66 32.71
55.39 87.77 32.38
55.24 87.59 32.35
55.73 87.47 31.74 –1.32 30.50 30.27 31.19
55.83 87.34 31.72 –0.26 30.35 30.37 31.18
55.64 87.34 31.70 –0.42 30.02 29.83 30.77
0.85
1.20
0.90
0.13
32.29 31.89 32.28
31.89 31.57 32.00
31.42 31.03 31.90
31.04 30.74 31.60
This project was supported by the Centre for New Antivirals and
Antineoplastics (project No. 1M0508) and a project from the Min-
istry of Education of the Czech Republic (MSM0021620857).
6g
[a] All energies in kcalmol–1, dipole moments in Debye. [b] In vac-
uum. [c] In DMSO.
[1] a) H. Hopf, Classics in Hydrocarbon Chemistry, Syntheses,
Concepts, Perspectives, Wiley-VCH, Weinheim, 2000; b) J. F. Li-
ebman, A. Greenberg (Eds.), Molecular Structure and Ener-
getics Vol. 2: Studies of Organic Molecules, John Wiley & Sons,
New York, 1986; c) R. A. Moss, M. S. Platz, M. Jones Jr. in
Reactive Intermediate Chemistry, Wiley-Interscience, Hoboken,
2004, ch. 15, pp. 717–740.
[2] a) L. T. Scott, M. Jones Jr., Chem. Rev. 1972, 72, 181–201; b)
J. L. Liebman, A. Greenberg, Chem. Rev. 1976, 76, 311–365.
[3] The description of bridged formula of benzene is usually attrib-
uted to Dewar, see: J. Dewar, Proc. Roy. Soc. Edinburgh 1867,
6, 82–86. For further discussion on this issue, see: L. Se-
mentsov, J. Chem. Educ. 1966, 43, 151.
[4] a) E. E. van Tamelen, S. P. Pappas, J. Am. Chem. Soc. 1962, 84,
3789–3791; b) E. E. van Tamelen, S. P. Pappas, J. Am. Chem.
Soc. 1963, 85, 3297–3298; c) E. E. van Tamelen, S. P. Pappas,
K. L. Kirk, J. Am. Chem. Soc. 1971, 93, 6092–6101.
[5] a) W. Schaefer, Angew. Chem. 1966, 78, 716; b) W. Schaefer, R.
Criegee, R. Askani, H. Gruener, Angew. Chem. 1967, 79, 54–
55.
[6] a) J. B. Koster, G. J. Timmermans, H. van Bekkum, Synthesis
1971, 139–140; b) F. van Rantwijk, G. J. Timmermans, H.
van Bekkum, Recueil Trav. Chim. Pays-Bas 1976, 95, 39–42.
[7] a) J. H. Dopper, B. Greijdanus, H. Wynberg, Tetrahedron Lett.
1975, 16, 4297–4300; b) J. H. Dopper, B. Greijdanus, H. Wyn-
berg, J. Am. Chem. Soc. 1975, 97, 216–218.
Figure 4. Correlation between calculated and experimental free en-
ergies of activation of Dewar benzene derivatives rearrangement.
Conclusions
The obtained results could be summarized into the fol-
lowing points. Firstly, the aryl-substituted DBs and their
easy thermal rearrangement into the corresponding ben-
zenes may serve as an alternative pathway for synthesis of
sterically hindered biaryls. Secondly, the data obtained from
thermal rearrangements of DBs provide further experimen-
tal evidence for the proposed orbital-symmetry-controlled
electrocyclic ring opening. Thirdly, the theoretical calcula-
tions concerning the transition states and the thermochemi-
cal data are in good agreement with values obtained from
the experimental measurements, and they support the pro-
posed conrotatory Dewar benzene ring opening.
[8] a) P. B. J. Driessen, H. Hogeveen, J. Organomet. Chem. 1978,
156, 265–278; b) P. B. J. Driessen, H. Hogeveen, J. Am. Chem.
Soc. 1978, 100, 1193–1200.
[9] a) R. Gleiter, F. Ohlbach, J. Chem. Soc. Chem. Commun. 1994,
2049–2050; b) R. Gleiter, F. Ohlbach, T. Oeser, H. Irngartinger,
Liebigs Ann. 1996, 785–790.
[10] a) M. Ohkita, K. Ando, K. Yamamoto, T. Suzuki, T. Tsuji,
Chem. Commun. 2000, 83–84; b) M. Ohkita, K. Ando, T. Su-
zuki, T. Tsuji, J. Org. Chem. 2000, 65, 4385–4390; c) M. Ohkita,
K. Ando, T. Tsuji, Chem. Commun. 2001, 2570–2571.
[11] M. J. Marsella, M. M. Meyer, F. S. Tham, Org. Lett. 2001, 3,
3847–3849.
[12] M. J. Marsella, S. Estassi, L.-S. Wang, K. Yoon, Synlett 2004,
192–194.
[13] a) L. Dufková, M. Kotora, I. Císarˇová, Eur. J. Org. Chem.
2005, 2491–2499. For previous reports, see: b) T. Takahashi,
Z. F. Xi, M. Kotora, J. Chem. Soc. Chem. Commun. 1995, 361–
362; c) T. Takahashi, Z. F. Xi, A. Yamazaki, Y. H. Liu, K.
Nakajima, M. Kotora, J. Am. Chem. Soc. 1998, 120, 1672–
1680; d) T. Takahashi, F. Y. Tsai, Y. Li, K. Nakajima, M. Ko-
tora, J. Am. Chem. Soc. 1999, 121, 11093–11100.
Experimental Section
A Typical Procedure for the Preparation of Dewar Benzenes: A solu-
tion of 2-butyne (196 µL, 2.5 mmol) was added to a stirred suspen-
sion of powdered anhydrous AlCl3 (166 mg, 1.25 mmol) in dry
dichloromethane (3 mL) at –10 °C. To the resulting complex was
added the substituted arylpropynoate (1.25 mmol) at –15 °C. After
stirring for 1 h at –15 °C, DMSO (450 µL) was added. The mixture
[14] For cyclobutadiene generation and reactions, see: a) T. Bally,
S. Masamune, Tetrahedron 1980, 36, 343–370; b) G. Maier, An-
gew. Chem. Int. Ed. Engl. 1988, 27, 309–332.
[15] For discussion on the role of DMSO see ref.[6a]
50
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 47–51

Synthesis and Rearrangement of Dewar Benzenes Into Biaryls
[16] a) H. Dietl, P. M. Maitlis, Chem. Commun. (London) 1967, [18] R. P. Johnson, K. J. Daoust, J. Am. Chem. Soc. 1996, 118,
759–760; b) H. C. Volger, M. M. Gaasbeek, Recueil Trav.
7381–7385.
Chim. Pays-Bas 1968, 87, 1290–1292; c) H. C. Volger, H. Hoge- [19] R. W. A. Havenith, L. W. Jenneskensm, J. H. Lenthe, J. Mol.
veen, Recueil Trav. Chim. Pays-Bas 1967, 86, 830–832.
[17] a) S. Niwayama, E. A. Kallel, D. C. Spellmeyer, C. Sudu, K. N.
Houk, J. Org. Chem. 1996, 61, 2813–2825; b) W. R. Dolbier Jr.,
H. Koroniak, K. N. Houk, C. Sheu, Acc. Chem. Res. 1996, 29,
471–477.
Struct. (Theochem) 1999, 492, 217–224.
[20] J. E. Norton, L. P. Olson, K. N. Houk, J. Am. Chem. Soc. 2006,
128, 7835–7845.
Received: September 27, 2007
Published Online: November 12, 2007
Eur. J. Org. Chem. 2008, 47–51
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
51