GaCl3-catalyzed formation of eight-membered rings from enynes bearing a cyclic olefin

Article abstract of DOI:10.1021/ol061801v

GaCl₃-catalyzed cycloisomerization of enynes having a cyclic olefin led to isolation of eight-membered ring compounds.

Full text of DOI:10.1021/ol061801v

ORGANIC
LETTERS
2006
Vol. 8, No. 24
5425-5427
GaCl3-Catalyzed Formation of
Eight-Membered Rings from Enynes
Bearing a Cyclic Olefin
Soo Min Kim, Sang Ick Lee, and Young Keun Chung*
Intelligent Textile System Research Center and Department of Chemistry,
College of Natural Sciences, Seoul National UniVersity, Seoul 151-747, Korea
ykchung@snu.ac.kr
Received July 21, 2006 (Revised Manuscript Received September 26, 2006 )
ABSTRACT
GaCl3-catalyzed cycloisomerization of enynes having a cyclic olefin led to isolation of eight-membered ring compounds.
The development of organometallic transformations1 offers
exciting opportunities for the rapid access to structurally
complex targets. Ring synthesis through modular, complex-
ity-building reactions in a catalytic manner is a tremendous
challenge.2 Recently, many research groups have demon-
strated that treatment of enynes bearing an olefinic cycle with
a catalytic amount of Pd,3 Pt,4 Ga,5 and Fe6 complexes leads
diate in the process. Depending upon the circumstances,
liberation of metal from the butene intermediate will lead to
the formation of bicyclic compounds. For example, six-,
seven-, and ten-membered bicyclic compounds have been
generated. We are not aware, however, of any precedent of
cyclobutene intermediates generating eight-membered ring
compounds from the reaction. Many strategies toward
cyclooctanoids have been developed in the context of specific
targets, but their generality, operational simplicity, and regio-
and stereocontrol elements still remain to be fully delineated.7
In this Communication, we establish that gallium chloride
(GaCl3) catalyzes a novel cycloisomerization of enynes
having an olefinic cycle to generate eight-membered ring
compounds (eq 1). Our recent investigation on the gold(I)-
to a cycloisomerized reaction product. In some cases,3-5
a
highly strained cyclobutene was proposed as a key interme-
(1) For selected reviews, see: (a) Dyker, G., Ed. Handbook of C-H
Transformations; Wiley-VCH: Weinheim, 2005. (b) Evans, P. A., Ed.
Modern Rhodium-Catalyzed Organic Reactions; Wiley-VCH: Weinheim,
2005. (c) Tamaru, Y., Ed. Modern Organonickel Chemistry; Wiley-VCH:
Weinheim, 2005. (d) Shibasaki, M.; Yamamoto, Y., Ed. Multimetallic
Catalysts in Organic Synthesis; Wiley-VCH: Weinheim, 2004.
(2) For selective reviews, see: (a) Wasilke, J.-C.; Obrey, S. J.; Baker,
R. T.; Bazan, G. C. Chem. ReV. 2005, 105, 1001-1020. (b) McManus, H.
A.; Guiry, P. J. Chem. ReV. 2004, 104, 4151-4202. (c) Skda-Foldes, R.;
Kollar, L. Chem. ReV. 2003, 103, 4095-4130. (d) Widenhoefer, R. A. Acc.
Chem. Res. 2002, 35, 905-913. (e) Aubert, C.; Buisine, O.; Malacria, M.
Chem. ReV. 2002, 102, 813-834. (f) Trnka, T. M.; Grubbs, R. H. Acc.
Chem. Res. 2001, 34, 18-29. (g) Montgomery, J. Acc. Chem. Res. 2000,
33, 467-473. (h) Malacria, M. Chem. ReV. 1996, 96, 289-306. (i) Lautens,
M.; Klute, W.; Tam, W. Chem. ReV. 1996, 96, 49-92.
(3) Trost, B. M.; Yanai, M.; Hoogsteen, K. J. Am. Chem. Soc. 1993,
115, 5294-5295.
(4) (a) Fu¨rstner, A.; Szillat, H.; Stelzer, F. J. Am. Chem. Soc. 2001, 123,
6785-6786. (b) Fu¨rstner, A.; Stelzer, F.; Szillat, H. J. Am. Chem. Soc.
2001, 123, 11863-11869.
catalyzed cycloisomerization of enynes showed that the
introduction of an olefinic group to the enyne substrates
dramatically increased the yield.8
(5) Chatani, N.; Inoue, H.; Kotsuma, T.; Murai, J. J. Am. Chem. Soc.
2002, 124, 10294-10295.
(6) Fu¨rstner, A.; Martin, R.; Majima, K. J. Am. Chem. Soc. 2005, 127,
12236-12237.
(7) Mehta, G.; Singh, V. Chem. ReV. 1999, 99, 881-930.
10.1021/ol061801v CCC: $33.50
© 2006 American Chemical Society
Published on Web 10/24/2006

Thus, we chose enynes bearing a cyclic olefin as substrates
for our study and screened Lewis acids such as [Au(PPh3)]-
Table 2. GaCl3-Catalyzed Ring-Opening Metathesis of Cyclic
Enyne to an Eight-Membered Ringa
5
OTf, PtCl2,4 FeCl3,6 and GaCl3 (Table 1).
Table 1. Various Lewis Acid Catalyzed Metathesesa
yield
(%)b
temp
entry
1
catalyst
5 mol % of
AuCl(PPh3)/AgOTf
5 mol % of PtCl2
5 mol % of FeCl3
10 mol % of GaCl3
solvent
(°C)
time 1b 1c
CH2Cl2 15∼20 1 h
-
30
2
3
4
toluene 80
toluene 90
toluene 60
6 h
-
39
24 h
12 10
30 min 91
-
a 0.5 mmol of 1a (0.165 g) in 3 mL of toluene was used. b Isolated yield.
c 5 mL of Et2NH was used.
When the gold compound was used as a catalyst, a
cyclopropanated compound was obtained in 30% yield with
the concomitant formation of polymerized compounds. When
PtCl2 was used as a catalyst, a cyclopropanated compound
(39%) with an unidentifiable compound was obtained. Use
of FeCl3 as a catalyst gave a mixture of a cyclopropanated
and an eight-membered compound in 10% and 13% yields,
respectively, with 57% recovery of the reactant. However,
fortunately, treatment of enyne with GaCl3 afforded an eight-
membered ring compound in 91% yield. Formation of eight-
membered ring compounds was confirmed by an X-ray
diffraction study of one of the reaction products.9 The
reaction provides a simple and rapid synthesis of eight-
membered rings.
a 0.5 mmol of enyne in 3 mL of toluene was used. b Isolated yield. c 14%
of reactant was recovered. d 72% of reactant was recovered. e The reaction
was run at 0 °C.
Encouraged by this result, we investigated the GaCl3-
catalyzed cycloisomerization of various enynes bearing a
cyclic olefin (Table 2). Enynes bearing a cyclic diene with
an NTs tether group (entries 1-5) were quite viable
substrates for the cycloisomerization. In entry 3, a mixture
of two isomers in a ratio of 2:1 was used as a substrate and
the same ratio of two isomeric products was obtained.
However, in the case of entry 4, one of the isomers was
completely aromatized. Compared to the substrates with a
cyclic diene, an enyne with a cyclic monoene with an NTs
tether group (entry 6) is inferior. Interestingly, an enyne with
no spacer between an N atom and cyclohexene (entry 7) did
not give the expected product.
was introduced at the carbon atom between an alkyne and a
nitrogen atom (entry 8), the yield was poor presumably due
to the steric congestion. An enyne having oxygen in a tether
(entry 9) was found to serve as a good substrate. When the
tether atom was carbon (entry 10), the reaction at 0 °C went
to completion within 10 min. However, the yield was poor
(33%). Interestingly, the lowering of the reaction temperature
or the lengthening of the reaction time did not improve the
reaction yield. When the reaction was conducted at -15 °C,
29% of the reaction product was obtained with recovery of
the same amount (29%) of the reactant. Interestingly, no
reaction was observed at 80 °C for an enyne having a
nobornadienyl group (entry 11). However, when the reaction
temperature increased to 100 °C, a seven-membered com-
pound was obtained in 19% yield. Furthermore, a substrate
with a cyclopentene moiety gave a seven-membered com-
pound in 76% yield (entry 12). Thus, the methodology
Instead, a cyclopropanated compound was obtained in 12%
yield with 72% recovery of the reactant. When an alkyl group
(8) Lee, S. I.; Kim, S. M.; Choi, M. R.; Kim, S. Y.; Chung, Y. K.; Han,
W.-S.; Kang, S. O. J. Org. Chem. 2006, in press.
(9) See the Supporting Information: Crystal data for 1b: C19H23S1O2N1,
MW ) 329.46, triclinic, space group P-1, a ) 5.0300(4) Å, b ) 12.3658-
(9) Å, c ) 14.0720(10) Å, R) 102.516(1)°, â) 95.968(1)°, γ) 95.375-
(1)°, V ) 843.74(3) Å3, Z ) 2, final R indices [I > 2σ(I)], R1 ) 0.0236,
wR2 ) 0.0339. CCDC reference number: 614687.
5426
Org. Lett., Vol. 8, No. 24, 2006

developed in this study can be extended to a synthesis of
seven-membered ring compounds. We also investigated the
cycloisomerization of enynes with an internal alkyne (eq 2).
and Szillat4b and a transformation of a 6.5.4-tricyclic
compound to an 8.5-bicyclic compound were reported by
Paquette and Wang.11 Thus, the ring opening seemed to be
highly dependent upon the fused rings and there should be
substantial ring strain for a ring to be opened during the
reaction. In our study, the substrates in Table 2 were designed
to give a 6.5.4-tricyclic intermediate, eventually resulting in
an eight-membered ring compound.
As already mentioned, the GaCl3-catalyzed cycloisomer-
ization of enynes has been reported by Chatani’s group.5
They also proposed a plausible reaction mechanism. We
expected that the formation of an eight-membered ring would
follow a mechanism similar to that suggested by Chatani’s
group except in the ring opening (Scheme 1).
However, the well-known cyclopropanated compound was
isolated in low yields.
To gain some insight on the reaction mechanism, the
following substrates were tested (Figure 1).
Scheme 1
In conclusion, we have demonstrated that the GaCl3-
catalyzed reactions of enynes bearing an olefinic cycle
represent a versatile new catalytic method for the synthesis
of bicyclic eight-membered ring compounds. The reaction
is highly sensitive to the distance between a tether atom and
an olefinic cycle and between a tether atom and an alkyne
moiety, and an olefinic cycle with a diene is more favorable
than that with a monoene. This method compares favorably
with other approaches to the construction of this important
family of compounds. Additional synthetic investigations of
this ring-forming process are underway.
Figure 1. Different types of cyclic enynes tested for GaCl3-
catalyzed ring-opening metathesis.
When a substrate (15a, 16a) expecting a 6.6.4-tricyclic
intermediate was reacted, a ring-opened product was not
obtained. Moreover, the increase of the reaction time led to
decomposition. Other cyclic enynes such as 17a, 18a, and
19a were also reacted. However, in those cases, no reaction
proceeded.
Many research groups reported10 the formation of 8.6.4-
and/or 6.6.4-tricycles and their attempts to open the cyclo-
butene ring. However, their endeavor was unsuccessful. On
the contrary, a transformation of an 8.5.4-tricyclic intermedi-
ate to a 10.5-bicyclic compound was reported by Fu¨rstner
Acknowledgment. This work was supported by the Korea
Research Foundation Grant funded by the Korean Govern-
ment (MOEHRD) (R02-2004-000-10005-0) and the Korea
Science and Engineering Foundation (KOSEF) through the
SRC/ERC Program of MOST/KOSEF (R11-2005-065).
Supporting Information Available: Procedures, spectral
data for new compounds, and details for the crystal structure
of 1b. This material is available free of charge via the Internet
at http://pubs.acs.org.
(10) (a) Trost, B. M.; Yani, M.; Hoogsteen, K. J. Am. Chem. Soc. 1993,
115, 5294-5295. (b) Nieto-Oberhuber, C.; Lo´pez, S.; Mun˜oz, M. P.;
Ca´rdenas, D. J.; Bun˜uel, E.; Nevado, C.; Echavarren, A. M. Angew. Chem.,
Int. Ed. 2005, 44, 6146-6148.
OL061801V
(11) Wang, T.-Z.; Paquette, L. A. J. Org. Chem. 1986, 51, 5232-5234.
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