Electrochemical generation and reaction of o-quinodimethanes from {[[2-(2,2-dibutyl-2-stannahexyl)phenyl]-methyl]thio} benzenes

Article abstract of DOI:10.1021/ol990647s

(equation presented) The anodic oxidation of {[[2-(2,2-dibutyl-2-stannahexyl)phenyl]methyl]thio}benzenes gave o-quinodimethanes which were trapped in situ by dienophiles to give the corresponding cycloadducts in excellent yields. The electron transfer and succeeding 1,4-elimination reaction was efficiently completed in a solution of lithium perchlorate/nitromethane in the presence of acetic acid. The reaction progress was quantitatively controlled by the passage of charge. By using this new method, an aryltetralin lignan skeleton was also synthesized.

Full text of DOI:10.1021/ol990647s

ORGANIC
LETTERS
1999
Vol. 1, No. 3
435-437
Electrochemical Generation and
Reaction of o-Quinodimethanes from
{[[2-(2,2-Dibutyl-2-stannahexyl)phenyl]-
methyl]thio}benzenes
Madoka Jinno, Yoshikazu Kitano, Masahiro Tada, and Kazuhiro Chiba*
Laboratory of Bio-organic Chemistry, Tokyo UniVersity of Agriculture and Technology,
3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan
chiba@cc.tuat.ac.jp
Received May 7, 1999
ABSTRACT
The anodic oxidation of {[[2-(2,2-dibutyl-2-stannahexyl)phenyl]methyl]thio}benzenes gave o-quinodimethanes which were trapped in situ by
dienophiles to give the corresponding cycloadducts in excellent yields. The electron transfer and succeeding 1,4-elimination reaction was
efficiently completed in a solution of lithium perchlorate/nitromethane in the presence of acetic acid. The reaction progress was quantitatively
controlled by the passage of charge. By using this new method, an aryltetralin lignan skeleton was also synthesized.
It has recently been demonstrated that electrochemical
oxidation provides a relatively efficient means of effecting
intermolecular carbon-carbon bond formation. The potential
of this electrochemical method is highlighted by the general
way in which electrochemistry can be used to generate
reactive intermediates to construct varied cycloadducts under
mild conditions. In this study, we aimed at accomplishing
the electrochemical generation and reaction of o-quino-
dimethanes, a goal which has been of great interest in the
synthesis of polycyclic compounds.1
the other hand, we anticipate that the electrochemical method
also has the potential to play an important role in the
generation of unstable o-quinodimethanes followed by their
cycloaddition with dienophiles. The method is further
expected to proceed under the quantitative control of the
chemical reaction by regulating the passed charge. Previ-
ously, a cathodic generation and Diels-Alder reaction of
o-quinodimethanes has been accomplished by using 1,2-bis-
(bromomethyl)benzene.6 Recently, we accomplished some
cycloaddition reactions by using an electrooxidative reaction
To date, various methods have been reported for the
generation of o-quinodimethane intermediates, including the
metal-,2 anion-,3 or acid-induced,4 thermal, or photochemical
elimination reaction5 of the corresponding precursors. On
(3) Ito, Y.; Nakatsuka, M.; Saegusa, T. J. Am. Chem. Soc. 1980, 102,
863. Ito, Y.; Nakatsuka, M.; Saegusa, T. J. Am. Chem. Soc. 1982, 104,
7609. Kerdesky, F. A.; Ardecky, R. J.; Lakshmikanthan, M. V.; Cava, P.
J. Am. Chem. Soc. 1981, 103, 1992. Trahanovsky, W. S.; Macias, J. R. J.
Am. Chem. Soc. 1986, 108, 6820. McOmie, F. W.; Perry, D. H. Synthesis
1973, 416; 1974, 39, 2769. Nozaki, H.; Noyori, R. Tetrahedron 1966, 22,
2163. Sisido, K.; Kusano, N.; Noyori, R.; Nozaki, Y.; Simosaka, M.; Nozaki,
H. J. Polym. Sci., Part A 1963, 1, 2101.
(4) Sano, H.; Ohtsuka, H.; Migita, T. J. Am. Chem. Soc. 1988, 110, 2014.
(5) Cava, M. P.; Deana, A. A. J. Am. Chem. Soc. 1959, 81, 4266. Cava,
M. P.; Mitchell, M. J.; Deana, A. A. J. Org. Chem. 1960, 25, 1481. Errede,
L. A. J. Am. Chem. Soc. 1961, 83, 949. Flynn, C. R.; Michl, J. J. Am.
Chem. Soc. 1974, 96, 3280. Ouchi, A.; Koga, Y. J. Org. Chem. 1998, 63,
6780. Quinkert, G.; Opitz, K.; Wiersdorff, W.-W.; Weinlich, J. Tetrahedron
Lett. 1963, 1863. Sisido, K.; Noyori, R.; Nozaki, H. J. Am. Chem. Soc.
1962, 84, 3562.
(1) Kshirsagar, T. A.; Portoghese, P. S. J. Org. Chem. 1998, 63, 1706.
Lenihan, B. D.; Shechter, H. Tetrahedron Lett. 1994, 35, 7507. Lenihan,
B. D.; Shechter, H. J. Org. Chem. 1998, 63, 2086. Lenihan, B. D.; Shechter,
H. J. Org. Chem. 1998, 63, 2086. Maeda, Y.; Sato, Y. Chem. Pharm. Bull.
1998, 46, 508.
(2) Alder, K.; Fremery, M. Tetrahedron 1961, 14, 190. Cava, M. P.;
Napier, D. R. J. Am. Chem. Soc. 1957, 79, 1701. Cava, M. P.; Deana, A.
A.; Muth, K. J. Am. Chem. Soc. 1959, 81, 6458. Han, B. H.; Boudjouk, P.
J. Org. Chem. 1982, 47, 751. Ito, Y.; Nakatsuka, M.; Saegusa, T. J. Am.
Chem. Soc. 1982, 104, 7609.
10.1021/ol990647s CCC: $18.00 © 1999 American Chemical Society
Published on Web 06/25/1999

system composed of lithium perchlorate-nitromethane solu-
tion.7 The reaction media have been found to promote the
oxidative fission of carbon-sulfur bonds and to show the
marked acceleration property of following intermolecular
cycloaddition between unactivated alkenes and electrogen-
erated o-quinone methides.8 It is presumed that the polar ionic
solvent system promotes the oxidative fission of C-S bonds
and gives an appropriate environment to generate a dipolar
compound such as o-quinone methide. It is therefore
envisioned that o-quinodimethanes could be obtained by
using the electrochemical induction of the C-S bond fission
by the assist of the effective polar, ionic solvent system. We
herein report a new method for the electrochemical genera-
tion of o-quinodimethane intermediates by the oxidative 1,4-
elimination of {[[2-(2,2-dibutyl-2-stannahexyl)phenyl]methyl]-
thio}benzenes.
dimethyl fumarate (7), using glassy carbon as an anode and
Pt as a cathode. Electrooxidation of compound 1 or 2 gave
a small amount of the corresponding sulfoxide and messy
products with no desired cycloadduct. Trimethylsilyl and
phenylsulfanyl groups of 2 did not eliminate under these
conditions. On the other hand, the electrooxidation of
compound 3 at 70 °C gave the desired cycloadduct 8 in 93%
yield (Scheme 1). Compound 5 also showed an oxidation
Scheme 1
First, to investigate the electrolytic precursor of o-
quinodimethane, the three sulfides 1-3 (Figure 1) were
Figure 1. Structures of the substrates for the electrogeneration of
o-quinodimethanes and related compounds.
synthesized from 4,5-dimethoxy-2-methylbenzophenone or
2-methylbenzaldehyde (See the Supporting Information and
refs 4 and 9). The oxidation potentials of sulfides 1-3 in
1.0 M lithium perchlorate-nitromethane were measured by
cyclic voltammetry to show clear oxidation potentials at 1.46,
1.15, and 1.17 V (vs SCE), respectively. On the other hand,
[o-(1-hydroxymethyl)benzyl]tributylstannane (4) showed no
oxidation peak below 1.8 V vs SCE. These results indicated
that the electron-releasing groups at the o-methyl group
decreased the oxidation potentials of sulfides. The elec-
trooxidation of these sulfides was performed in 1.0 M lithium
perchlorate-nitromethane, 0.1 M AcOH, in the presence of
peak at 1.10 V vs SCE; in contrast, such a peak was not
observed for compound 6 below 1.8 V vs SCE. The
electrooxidation of 5 at the peak potential with maleic
anhydride 10 successfully gave cycloadduct 12 at ambient
temperature in excellent yields. The oxidative cycloaddition
of 5 with methyl acrylate 13 gave a mixture of isomers
14a-c in moderate yields (14c is a single stereoisomer of
unknown stereoisomer). The stereochemistry of cycloadducts
9, 12, 14, and 16 was established by an 1H NMR study. The
difference in the reactivities between 3 and 5 should depend
on the stability of corresponding benzyl cation intermediates.
We also confirmed that these reactions did not proceed when
(6) Eru, E.; Hawkes, G. E.; Utley, J. H. P.; Wyatt, P. B. Tetrahedron
1995, 51, 3033. Oguntoye, E.; Szunerits, S.; Utley, J. H. P.; Wyatt, P. B.
Tetrahedron 1996, 52, 7771.
(7) Chiba, K. Tada., M. J. Chem. Soc., Chem. Commun. 1994, 2485.
Chiba, K. Arakawa, T.; Tada, M. Chem. Commun. 1996, 1763. Chiba, K.;
Arakawa, T.; Tada, M. J. Chem. Soc., Perkin Trans. 1 1998, 17, 2939.
Chiba, K.; Jinno, M.; Kuramoto, R.; Tada, M. Tetrahedron Lett. 1998, 39,
5527. Chiba, K.; Sonoyama, J.; Tada, M. J. Chem. Soc., Chem. Commun.
1995, 1381.
(8) Chiba, K. Sonoyama., J.; Tada, M. J. Chem. Soc., Perkin Trans. 1
1996, 1435. Chiba, K. Yamaguchi, Y.; Tada, M. Tetrahedron Lett. 1998,
39, 9035.
(9) Guindon, Y.; Frenette, R.; Fortin, R.; Rokach, J. J. Org. Chem. 1983,
48, 1357.
436
Org. Lett., Vol. 1, No. 3, 1999

binations of electrolyte and solvent such as in 0.1 M
tetraethylammonium p-toluenesulfonate-acetonitrile even in
the presence of 0.1 M AcOH. The results suggested that the
lithium perchlorate-nitromethane system is essential to
generate o-quinodimethane from the present substrates.
According to our data, the tributylstannyl group and the
reaction media might assist in the oxidative release of the
phenylsulfanyl radical, followed by the release of the
tributylstannyl group, to generate the o-quinodimethanes
(Figure 2).
In conclusion, a new, mild method for the generation of
o-quinodimethane intermediates initiated by electrooxidation
has been accomplished. Under the regulation of charge
transfer, the generation and Diels-Alder reaction of o-
quinodimethane was successfully controlled to give desired
cycloadducts in excellent yields, including those possessing
natural aryltetralin lignan skeletons.
Figure 2. Proposed mechanism of the electrochemical generation
and Diels-Alder reaction of o-quinodimethanes. It is presumed that
the electron-donative property of the tributylstannyl group, stabi-
lization of the benzyl carbocation by perchlorate ion, and the Lewis
acidity of the lithium ion assist the electrooxidative elimination of
phenylsulfanyl radical followed by the fission of the C-Sn bond
to generate the corresponding o-quinodimethanes.
Acknowledgment. This work was supported by a Grant-
in-Aid for Scientific Research on Priority Areas (No. 283,
“Innovative Synthetic Reactions”) from the Ministry of
Education, Science, Sports and Culture of Japan.
the reaction mixture was just allowed to stand in the solvent
system without the application of voltage, and the starting
materials were almost completely recovered. During the
electrolysis of 5, the yield of the product increased with the
amount of passed charge, and the reaction was completed
after ca. 1.2 faraday/mol of charge. In the presence of a small
amount of AcOH, the electrolysis proceeded efficiently in
higher current density. In addition, the electrolytic Diels-
Alder adducts were scarcely obtained in other usual com-
Supporting Information Available: General procedure
for the synthesis of 3, 5, the electrochemical synthesis of
cycloadducts, and selected NMR data for 3, 5, 9a, 9b, 12,
16a, and 16b. This material is available free of charge via
the Internet at http://pubs.acs.org.
OL990647S
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