Diels-Alder additions of benzynes within helicene skeletons

Article abstract of DOI:10.1021/jo048707h

Although the contortions required are unprecedented, the benzynes formed by the fluoride-induced elimination of TMSOTf from o-trimethylsilyl [6]- and [7]-helicenol triflates add to another ring of the helicenes rather than to an external fur an molecule.

Full text of DOI:10.1021/jo048707h

syntheses for 6 and 17, the precursors of benzyne
derivatives of two helicenes, and found that these un-
dergo novel transformations in which one ring of a
helicene adds to another. The products are bridged
derivatives of coronene.
Diels-Ald er Ad d ition s of Ben zyn es w ith in
Helicen e Sk eleton s
David Zhigang Wang,† Thomas J . Katz,*,†
J ames Golen,‡ and Arnold L. Rheingold‡
By silylating [7]-helicene 3, which is easy to prepare
in amounts greater than 10 g (by benzylating the inner
hydroxyl groups of 2 and then brominating with NBS),3
4 was obtained in 92% yield (Scheme 1). The benzyl
groups were then removed quantitatively5 and replaced
by triflate groups in 91% yield. Fluoride ion was expected
to eliminate the o-trimethylsilyl triflate functions from
6, giving benzynes,6 which, if the solvent contains furan,
were expected to add to the furan molecules. However,
this is not what happened when 6 was treated with Me4-
NF in a 3:1 furan-MeCN solvent mixture. After acid
hydrolysis, a 1:1 mixture of isomers 9 and 10 was
obtained in 90% yield. Not surprisingly, a different
precursor of the same benzyne (13, prepared from 123)
when treated with phenyllithium also gave 9 and 10,
albeit in a lower yield (67%).
Department of Chemistry, Columbia University,
New York, New York 10027, and Department of Chemistry
and Biochemistry, University of California, San Diego,
9500 Gilman Drive, La J olla, California 92093
tjk1@columbia.edu
Received J uly 27, 2004
Abstr a ct: Although the contortions required are unprec-
edented, the benzynes formed by the fluoride-induced elimi-
nation of TMSOTf from o-trimethylsilyl [6]- and [7]-helicenol
triflates add to another ring of the helicenes rather than to
an external furan molecule.
The presumed intermediate, 7, probably a mixture of
endo and exo isomers, was too unstable to isolate. Ketone
8, formed from it by brief acid hydrolysis, was more
stable. However, although it could not be isolated pure,
the ketone function was recognizable both by its 13C NMR
(a peak at δ 202 ppm) and its IR absorption (at 1724
cm-1), and after being combined with t-BuOK and PhCH2-
Br, 8 gave the C-benzylated product 11 (in 83% yield).
The structure of 11, determined by X-ray diffraction
analysis of a single crystal, implies that the structures
of 8, 9, and 10 are those pictured. The latter two are
obtained when 8 is hydrolyzed more extensively in acid.
(Their masses were analyzed by mass spectrometry.)
The combination of enol ethers of bis(aryl methyl
ketones) and 1,4-benzoquinone makes it possible to
prepare helicenebisquinones in multigram quantities and
enantiopure form.1 A subsequent Na2S2O4 reduction/
Russig-Laatsch methylation sequence applied to ex-
amples of such [6]- and [7]-helicenebisquinones leads to
dihydroxyhelicenes 1 and 2.1d,2 In turn, electrophilic
substitutions (bromination, acetylation, and formylation)
and some rearrangement reactions have allowed these
molecules to be elaborated regioselectively into deriva-
tives that, notably, are functionalized at the inner, most
sterically hindered positions (positions 1, 2, 15, 16 in 1
and 1, 2, 17, 18 in 2).3
Similarly (Scheme 2), [6]-helicene 14, prepared in high
yield from 1,3 gave the double benzyne precursor 17,
which, after fluoride-induced 1, 2-elimination in furan
and acid hydrolysis, gave 18. The 1, 4-endo oxide moiety
appears to be considerably more stable in this molecule
than in 8, for 18 does not rearrange to a phenol even after
prolonged (2 h) exposure to aqueous HCl.
Since in these transformations the two generated
benzynes behave differently-one adding internally to
another helicene ring, the other externally to a furan
These discoveries suggest that the functionalized he-
licenes might be used to synthesize higher [n]-helicenes
in which n g 8.4 In pursuing this goal, we developed
(4) For the conversion of a [6]-helicene into an [8]-helicene, see: Fox,
J . M.; Katz, T. J . J . Org. Chem. 1999, 64, 302.
(5) Martinborough, E.; Denti, T. M.; Castero, P. P.; Wyman, T. B.;
Knobler, C. B.; Diederich, F. Helv. Chim. Acta 1995, 78, 1037.
(6) For the use of o-trimethylsilyl aryl triflates as precursors of
arynes under neutral conditions, see: (a) Himeshima, Y.; Sonoda, T.;
Kobayashi, H. Chem. Lett. 1983, 1211. (b) Yoshikawa, E.; Radhakrish-
nan, K. V.; Yamamoto, Y. J . Am. Chem. Soc. 2000, 122, 7280. (c)
Yoshikawa, E.; Yamamoto, Y. Angew. Chem., Int. Ed. 2000, 39, 173.
(d) Pena, D.; Perez, D.; Guitian, E.; Castero, L. J . Org. Chem. 2000,
65, 6944. (e) Pena, D.; Perez, D.; Guitian, E.; Castero, L. Synlett 2000,
7, 1061. (f) Yoshikawa, E.; Radhakrishnan, K. V.; Yamamoto, Y.
Tetrahedron Lett. 2000, 41, 729. (g) Radhakrishnan, K. V.; Yoshikawa,
E.; Yamamoto, Y. Tetrahedron Lett. 1999, 40, 7533. (h) Pena, D.; Perez,
D.; Guitian, E.; Castero, L. Org. Lett. 1999, 1, 1555. (i) Pena, D.; Perez,
D.; Guitian, E.; Castero, L. J . Am. Chem. Soc. 1999, 121, 5827. For
recent reviews on arynes chemistry, see: (j) Pellissier, H.; Santelli,
M. Tetrahedron 2003, 59, 701. (k) Wenk, H. H.; Winkler, M.; Sander,
W. Angew. Chem., Int. Ed. 2003, 42, 502.
† Columbia University.
‡ University of California, San Diego.
(1) (a) Katz, T. J .; Liu, L.; Willmore, N. D.; Fox, J . M.; Rheingold,
A. L.; Shi, S.; Nuckolls, C.; Rickman, B. H. J . Am. Chem. Soc. 1997,
119, 10054. (b) Fox, J . M.; Goldberg, N. R.; Katz, T. J . J . Org. Chem.
1998, 63, 7456. (c) Dreher, S. D.; Weix, D. J .; Katz, T. J . J . Org. Chem.
1999, 64, 3671. (d) Paruch, K.; Katz, T. J .; Incarvito, C.; Lam, K. C.;
Rhatigan, B.; Rheingold, A. L. J . Org. Chem. 2000, 65, 7602. (e) Paruch,
K.; Vyklicky, L.; Katz, T. J .; Incarvito, C. D.; Rheingold, A. L. J . Org.
Chem. 2000, 65, 8774.
(2) Dreher, S. D.; Paruch, K.; Katz, T. J . J . Org. Chem. 2000, 65,
806.
(3) Paruch, K.; Vyklicky, L.; Wang, D. Z.; Katz, T. J .; Incarvito, C.;
Zakharov, L.; Rheingold, A. L. J . Org. Chem. 2003, 68, 8539.
10.1021/jo048707h CCC: $27.50 © 2004 American Chemical Society
Published on Web 09/30/2004
J . Org. Chem. 2004, 69, 7769-7771
7769

SCHEME 1a
a
For clarity hydrogen atoms have been omitted from the drawing of the structure according to X-ray diffraction analysis, at the lower
right. Reagents and conditions: (a) BuLi, TMSCl, Et2O, -50 to 25 °C, 10 h; (b) 10% Pd/C, HCO2NH4, 1:1 THF-MeOH, 25 °C, 2 h;
(c) BuLi, Tf2O, -78 to 25 °C, 1 h; (d) Me4NF, furan-MeCN (3:1), 0 °C, 2 h; (e) HCl in 1:1 MeOH-CH2Cl2, 5 min, 25 °C; (f) HCl in
1:1 MeOH-CH2Cl2, 15 min, 25 °C; (g) endo isomer, t-BuOK, THF, 30 min, then PhCH2Br, 25 °C, 3 h; (h) NaH, THF, 30 min, then TsCl,
25 °C, 5 h; (i) PhLi, furan-THF (1:3), -78 to 25 °C, 4 h, then concd HCl, 25 °C, 30 min.
ring-experiments were carried out to see whether the
former reaction can occur before the latter. Accordingly
(Scheme 3), the precursor, 21, of a monobenzyne was
synthesized by monosilylating 3. This was achieved by
treating 3 with only limited amounts of BuLi before
TMSCl was added and then debenzylating and triflating
as before. This sequence gave 21 in 46% yield. Its
exposure to fluoride in a 1:1 furan-acetonitrile mixture
and then to methanolic HCl led only to 22, implying that
a benzyne function preferentially adds to the internal
ring rather than to the external furan.
previously been seen to add internally to another ring of
helicenes (usually to the carbon atom 5 or 6 away) and,
in the case of the vinyl substituent, in a Diels-Alder
reaction, but in all of these cases the substituent’s
unsaturation was perpendicular to the plane of its
attached benzene ring. Moreover, the unsaturated sub-
stituents have never been part of a ring, where their
rotational flexibility would be constrained. The remark-
able observation here is that the benzyne adds to another
ring of its own skeleton, even though the former’s reactive
unsaturation is parallel to a benzene ring and the
transformation must distort the structures much more
Unsaturated carbon substituents (carbocations,7 vinyl
groups,8 carbenes,9 and methylenes10) at 1-positions have
(8) Martin, R. H.; J espers, J .; Defay, N. Helv. Chim. Acta 1975, 58,
776.
(7) (a) Martin, R. H.; J espers, J .; Defay, N. Tetrahedron Lett. 1975,
1093. (b) Numan, H.; Wynberg, H. Tetrahedron Lett. 1975, 1097. (c)
Puls, C.; Stolle, A.; de Meijere, A. Chem. Ber. 1993, 126, 1635.
(9) J espers, J .; Defay, N.; Martin, R. H. Tetrahedron 1977, 33, 2141.
(10) Borkent, J . H.; Rouwette, P. H. F. M.; Laarhoven, W. H.
Tetrahedron 1978, 34, 2569.
7770 J . Org. Chem., Vol. 69, No. 22, 2004

SCHEME 2a
SCHEME 3a
a
Reagents and conditions: (a) BuLi, Et2O, -78 to 25 °C,
30 min, then TMSCl, 0 to 25 °C, 6 h; (b) 10% Pd/C, HCO2NH4, 1:1
THF-MeOH, 25 °C, 7 h; (c) BuLi, Et2O, -78 to 25 °C, 20 min,
then Tf2O, -78 to 25 °C, 1.5 h; (d) Me4NF, furan-MeCN (1:1),
0 °C, 3 h; then MeOH saturated with HCl (g), CH2Cl2, 25 °C,
20 min.
studied as a way to increase by two the number of rings
of a helicene.
Ack n ow led gm en t. This material is based upon
work supported by the National Science Foundation
under Grant CHE00-94723.
a
Reagents and conditions: (a) BuLi, Et2O, -78 to 0 °C, 30 min,
then TMSCl, 0 to 25 °C, overnight; (b) 10% Pd/C, HCO2NH4, 1:1
THF-MeOH, 25 °C, 4 h; (c) BuLi, Et2O, -78 to 25 °C, 10 min,
then Tf2O, -78 to 25 °C, 2 h; (d) TBAF, furan, 0 to 25 °C, 2 h,
then concd HCl, 25 °C, 30 min.
Su p p or tin g In for m a tion Ava ila ble: Experimental de-
tails; X-ray diffraction data for 11; and 1H NMR, 13C NMR,
and IR spectra of compounds 4-6, 9-11, 13, and 15-22. This
material is available free of charge via the Internet at
http://pubs.acs.org.
than in previous examples. It was in the hope that
addition to the internal ring would be disfavored by this
distortion while addition to the furan would be favored
by its electron richness that the process described was
J O048707H
J . Org. Chem, Vol. 69, No. 22, 2004 7771