6πe- versus 8πe- electrocyclization of 1-aryl-And heteroaryl-substituted

Article abstract of DOI:10.1021/ol802925q

Peri selectivity of the electrocyclization of 1-aryl- and heteroaryl-substituted (1Z,3Z)-1,3,5-hexatrienes, obtained by Ru-catalyzed linear coupling of 1,6-diynes to Z-propenyl(hetero)arenes, can be efficiently modulated depending on the aromaticity of th

Full text of DOI:10.1021/ol802925q

ORGANIC
LETTERS
6πe- versus 8πe- Electrocyclization of
1-Aryl- and Heteroaryl-Substituted
(1Z,3Z)-1,3,5-Hexatrienes: A Matter of
Aromaticity†
2009
Vol. 11, No. 4
983-986
Silvia Garc´ıa-Rub´ın, Jesu´s A. Varela, Luis Castedo, and Carlos Saa´*
Departamento de Qu´ımica Orga´nica, Facultad de Qu´ımica, UniVersidad de Santiago
de Compostela, 15782 Santiago de Compostela, Spain
carlos.saa@usc.es
Received December 19, 2008
ABSTRACT
Peri selectivity of the electrocyclization of 1-aryl- and heteroaryl-substituted (1Z,3Z)-1,3,5-hexatrienes, obtained by Ru-catalyzed linear cou-
pling of 1,6-diynes to Z-propenyl(hetero)arenes, can be efficiently modulated depending on the aromaticity of the (hetero)arene: 1,3,5-
hexatrienyl(hetero)arenes give 8πe- electrocyclization with the exception of 1,3,5-hexatrienylbenzenes, which give 6πe- electrocyclization.
Electrocyclizations are an important type of pericyclic
reaction from both a theoretical1 and an experimental
standpoint2 as they allow the formation of complex poly-
cyclic molecules from simple polyenic compounds. Accord-
ing to the Woodward and Hoffmann rules,3 1,3-cyclohexa-
dienes can be obtained by thermal disrotatory 6πe-
electrocyclization of (3Z)-1,3,5-hexatrienes, whereas 1,3,5-
cyclooctatrienes can be prepared by thermal conrotatory 8πe-
electrocyclization of (3Z,5Z)-1,3,5,7-octatetraenes. We report
here an interesting dichotomy showing that (3Z,5Z)-1,3,5,7-
octatetraenes, in which one of the terminal double bonds of
the system forms part of an (hetero)aromatic ring, selectively
undergo thermal 6πe- or 8πe- electrocyclizations depending
on the nature of the arene.4
Besides the 8πe- electrocyclization, at least three other
electrocyclic processes are also conceivable for (3Z,5Z)-
1,3,5,7-octatetraenes: one 6πe- and two 4πe- electrocy-
clizations. According to Coss´ıo’s calculations,5 the transition
states for these processes would be associated with activation
energies larger than those found for the 8πe- electrocycliza-
tion, and therefore, (3Z,5Z)-1,3,5,7-octatetraene would be
† Dedicated to professor Josep Font on the occasion of his 70th
birthday.
(1) (a) Fukui, K. Acc. Chem. Res. 1971, 4, 57. (b) Woodward, R. B.;
Hoffmann, R. The ConserVation of Orbital Symmetry; Verlag Chemie
International: Deerfield Beach, FL, 1970.
(4) (3Z)-1,3,5-Hexatrienes and (3Z,5Z)-1,3,5,7-octatetraenes can be
efficiently prepared by Ru-catalyzed linear coupling of 1,6-diynes to alkenes
and 1,3-dienes, respectively. (a) Garc´ıa-Rub´ın, S.; Varela, J. A.; Castedo,
L.; Saa´, C. Chem. Eur. J. 2008, 14, 9772. (b) Varela, J. A.; Rub´ın, S. G.;
Gonza´lez-Rodr´ıguez, C.; Castedo, L.; Saa´, C. J. Am. Chem. Soc. 2006, 128,
9262. (c) Varela, J. A.; Castedo, L.; Saa´, C. Org. Lett. 2003, 5, 2841.
(5) Lecea, B.; Arrieta, A.; Cossio, F. P. J. Org. Chem. 2005, 70, 1035.
(2) (a) Pindur, U.; Schneider, G. H. Chem. Soc. ReV. 1994, 409. (b)
Trost, B. M.; Fleming, I.; Paquette, L. A. ComprehensiVe Organic Synthesis;
Pergamon: Oxford, U.K., 1991; Vol. 5, pp 675-784. (c) Marvell, E. N.
Thermal Electrocyclic Reactions; Academic Press: New York, 1980.
(3) Woodward, R. B.; Hoffmann, R. J. Am. Chem. Soc. 1965, 87, 395.
10.1021/ol802925q CCC: $40.75
Published on Web 01/21/2009
2009 American Chemical Society

Scheme 1
.
Ru-Catalyzed Synthesis and 6πe- Electrocyclization
of 1,3,5-Hexatrienylbenzenes 3
Scheme 2. Thermal [1,5]-Hydrogen Shift of
1,3,5-Cyclooctatrienes 5g and 9f to 1,3,6-Cyclooctatrienes 6g
and 10f
Table 1. Ru-Catalyzed Cascade Reaction of 1,6-Diyne 1a with
[(Z)-1-Propenyl]arenes 2
cyclohexadiene 4a was obtained selectively and quantita-
tively as the product of the thermal 6πe- electrocyclization
(Scheme 1). Not unexpectedly, the same reactivity was
observed when an electron-rich (3b) or an electron-poor (3c)
hexatrienylbenzene was heated, thus showing that the
electronic richness of the aromatic moiety does not affect
the peri selectivity of the electrocyclization reaction.
Interestingly, the electrocyclic peri selectivity changed
when other aromatic nuclei were present in the starting
polyene. For example, when 1-(hexatrienyl)naphthalene 3d6
was heated under reflux in toluene, 1,3,6-cyclooctatriene 6d
was selectively obtained in quantitative yield (56% overall
yield, entry 1, Table 1).7 The cyclooctatriene most probably
arises from a thermal conrotatory 8πe- electrocyclization,
followed by a [1,5]-hydrogen shift to allow the aromaticity
of the naphthalene ring to be recovered.8 When isomeric
2-(propenyl)naphthalene 2e and 2-(propenyl)anthracene 2f9
were used in the Ru-catalyzed linear coupling with 1a, the
(6) 1,3,5-Hexatrienylarenes 3 were obtained by Ru-catalyzed linear
coupling of diynes 1 and (Z)-1,3-dienes 2, while (E)-1,3-dienes 2 failed to
give the linear coupling reaction. See ref 4 for more details and Supporting
Information for X-ray data for compound 3a.
(7) For reviews on metal-mediated cyclooctanoid construction, see: (a)
Yet, L. Chem. ReV. 2000, 100, 2963. (b) Mehta, G.; Singh, V. Chem. ReV.
1999, 99, 881. For [2 + 2 + 2 + 2] cycloadditions, see: (c) Wender, P. A.;
Christy, J. P. J. Am. Chem. Soc. 2007, 129, 13402. (d) Bouissie, T. R.;
Streitwieser, A. J. Org. Chem. 1993, 58, 2377. (e) Walther, D.; Braun, D.;
Schulz, W.; Rosenthal, U. Z. Anorg. Allg. Chem. 1998, 577, 270. (f) Diercks,
R.; Stamp, L.; tom Dieck, H. Chem. Ber. 1984, 117, 1913. For [4 + 2 +
2] cycloadditions, see: (g) DeBoef, B.; Counts, W. R.; Gilbertson, S. R. J.
Org. Chem. 2007, 72, 799. (h) Wender, P. A.; Christy, J. P. J. Am. Chem.
Soc. 2006, 128, 5354. (i) Murakami, M.; Ashida, S.; Matsuda, T. J. Am.
Chem. Soc. 2006, 128, 2166. (j) Baik, M. H.; Baum, E. W.; Burland, M. C.;
Evans, P. A. J. Am. Chem. Soc. 2005, 127, 1602. For [5 + 2+1]
cycloadditions, see: (k) Wang, Y.; Wang, J.; Su, J.; Huang, F.; Jiao, L.;
Liang, Y.; Yang, D.; Zhang, S.; Wender, P. A.; Yu, Z. X., J. Am. Chem.
Soc. 2007, 129, 10060. For [4 + 4] cycloadditions, see: (l) Murakami, M.;
Itami, K.; Ito, Y. Synlett 1999, 951. (m) Sieburth, S. M.; Cunard, N. T.
Tetrahedron 1996, 52, 6251. (n) Baldenius, K.-U.; tom Dieck, H.; Ko¨ning,
W. A.; Icheln, D.; Runge, T. Angew. Chem., Int. Ed. Engl. 1992, 31, 305.
(o) Wender, P. A.; Ihle, N. C. J. Am. Chem. Soc. 1986, 108, 4678. For [6
+ 2] cycloadditions, see: (p) Tenaglia, A.; Gaillard, S. Angew. Chem., Int.
Ed. 2008, 47, 2454. (q) Wender, P. A.; Correa, A. G.; Sato, Y.; Sun, R.
J. Am. Chem. Soc. 2000, 122, 7815. (r) Achard, M.; Mosrin, M.; Tenaglia,
A.; Buono, G. J. Org. Chem. 2006, 71, 2907.
a Isolated yields from reactions performed at 80 °C by slow addition,
over 4 h, of 0.5 mmol of 1a in DMF to a mixture of 3 equiv of 2, 10%
Et4NCl, and 10% [Cp*Ru(CH3CN)3]PF6 in DMF. X ) C(CO2Me)2.
expected to cyclize to 1,3,5-cyclooctatriene with complete
peri selectivity.
However, we found that when (1Z,3Z)-1,3,5-hexatrienyl-
benzene 3a6 (which can be seen as an (3Z,5Z)-1,3,5,7-
octatetraene being one of the terminal double bonds part of
the benzene ring) was heated under reflux in toluene,
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Org. Lett., Vol. 11, No. 4, 2009

Table 2. Ru-Catalyzed Cascade Reaction of 1,6-Diyne 1a with
[(Z)-1-Propenyl]heteroarenes 7
Scheme 3. Double Ru-Catalyzed Cascade Reaction of 1,6-Diyne
1b with Bis(Z-propenyl)pyrrole 11
cyclooctatrienes 6e and 6f in 79% and 75% yields, respec-
tively (entries 2 and 3, Table 1). Curiously, a Ru-catalyzed
linear coupling reaction of 9-(propenyl)phenanthrene 2g and
1a enabled the isolation of 1,3,5-cyclooctatriene 5g in 66%
yield (entry 4, Table 1). Further heating at 120 °C afforded
6g quantitatively through a [1,5]-H shift (Scheme 2). Non-
propenyl arenes such as silylated vinylnaphthalene 2h also
participate in the cascade reaction to give the expected
cyclooctatriene 6h in 58% yield (entry 5, Table 1).
We then turned our attention to [(Z)-1-propenyl]heteroare-
nes 7. In all of the examples tested, i.e., 2-(propenyl)furan
7a, 2- and 3-(propenyl)pyrroles 7b and 7d, 2-(propenyl)ben-
zofuran 7c, and 3-(propenyl)indole 7e, the corresponding
1,3,6-cyclooctatrienes 10a-e10 were obtained peri selectively
from 8πe- electrocyclizations followed by [1,5]-H shifts
(entries 1-5, Table 2). The exception was the case of
2-(propenyl)indole (7f), from which 1,3,5-cyclooctatriene 9f
was obtained (entry 6, Table 2). Further heating at 120 °C
afforded 10f quantitatively through a [1,5]-H shift (Scheme
2).
To gain further insights into the influence of the arene in
the electrocyclization of 1,3,5-hexatrienylarenes, DFT cal-
culations were performed for the 6πe- and 8πe- electrocy-
clizations of compounds 3a′ and 8f′ (Figure 1). The results
clearly show that 8πe- electrocyclizations are kinetically
favored, whereas 6πe- electrocyclizations are thermody-
namically favored. In the case of benzene derivative 3a′, the
loss of aromaticity of the benzene ring involved in the 8πe-
electrocyclization makes this process highly endothermic
a Isolated yields following the same reaction conditions as in Table 1.
b 10c was obtained by further heating at 120 °C of the initially isolated
mixture of 9c and 10c. X ) C(CO2Me)2.
electrocyclization of the putative intermediates 3e and 3f took
place in a regio- and peri-selective manner to afford
Figure 1. Energy profile (G in Kcal mol-1 at 298 K and 1 atm) for the 6e- and 8πe- electrocyclizations followed by a [1,5]-H shift in the
latter of compounds 3a′ and 8f′.
Org. Lett., Vol. 11, No. 4, 2009
985

(14.6 Kcal mol-1), with the competitive 6πe- electrocycliza-
tion more favored. Conversely, if the 8πe- electrocyclization
involves an heteroaryl ring, e.g., indole 8f′, the process
becomes exothermic (-1.8 Kcal mol-1) with an activation
barrier of 14.4 Kcal mol-1, therefore making this process
more favorable. The final [1,5]-H shift of 9f′, which allows
to recover the aromaticity of the indole nucleus 10f′, has to
overcome the activation barrier ∆Gq ) 28.0 Kcal mol-1 with
∆G° ) -9.3 Kcal mol-1.
Interestingly, the double Ru-catalyzed cascade reaction of
diyne 1b with bis-propenylpyrrole 11 gave rise to the
pentacyclic pyrrole derivative 13, in which pyrrole units are
fused to cyclooctene rings (Scheme 3).
of 1,6-diynes to Z-propenyl(hetero)arenes, undergo thermal
8πe- electrocyclizations followed by [1,5]-H shifts to afford
the corresponding 1,3,6-cyclooctatrienes. The exceptions are
1,3,5-hexatrienylbenzenes, which gave 1,3-cyclohexadienes
derived from 6πe- electrocyclizations.
Acknowledgment. This work was supported by the
MICINN (CTQ2005-08613 and CTQ2008-06557), Con-
solider Ingenio 2010 (CSD2007-00006), and the Xunta de
Galicia (2007/XA084 and INCITE08PXIB209024PR). S.G-
R. thanks the MEC for a FPU fellowship. We are also
grateful to the CESGA for computational time.
In conclusion, 1-aryl- and heteroaryl-substituted (1Z,3Z)-
1,3,5-hexatrienes, obtained by Ru-catalyzed linear coupling
Supporting Information Available: A typical procedure
for the Ru-catalyzed cascade reaction, spectral data for all
new compounds, X-ray structures, and optimized geometric
parameters for all the calculated structures. This material is
available free of charge via the Internet at http://pubs.acs.org.
(8) For a computational study involving a [1,5]-H shift and 8pe-
electrocyclization, see: (a) Zhu, Y.; Guo, Y.; Zhang, L.; Xie, D. J. Comput.
Chem. 2007, 28, 2164. For a computational study of 8πe- electrocyclic
reactions, see ref 5. For other examples of cascade metal-mediated reactions/
electrocyclization, see: (c) Kan, S. B. J.; Anderson, E. A. Org. Lett. 2008,
10, 2323. (d) Salem, B.; Suffert, J. Angew. Chem., Int. Ed. 2004, 43, 2826.
(e) von Zezschwitz, P.; Petry, F.; de Meijere, A. Chem. Eur. J. 2001, 7,
4035. (f) de Meijere, A.; Bra¨se, S. J. Organomet. Chem. 1999, 576, 88.
(9) The isomeric 9-(propenyl)anthracene did not participate in the
reaction, probably due to steric hindrance caused by the anthracene ring.
OL802925Q
(10) See Supporting Information for X-ray data for compounds 10c and
9f.
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Org. Lett., Vol. 11, No. 4, 2009