Acids direct 2-styrylcyclobutanone into two distinctly different reaction pathways

Article abstract of DOI:10.1021/ol0506922

(Chemical Equation Presented) Two structurally distinct carbocycles were selectively obtained by the reactions of 2-(o-styryl)cyclobutanones promoted by ytterbium salts. Treatment of the cyclobutanones with YbCl₃ in 1,4-dioxane at 100°C afforde

Full text of DOI:10.1021/ol0506922

ORGANIC
LETTERS
2005
Vol. 7, No. 10
2059-2061
Acids Direct 2-Styrylcyclobutanone into
Two Distinctly Different Reaction
Pathways
Masahiro Murakami,* Sho Kadowaki, Atsushi Fujimoto, Mitsuru Ishibashi, and
Takanori Matsuda
Department of Synthetic Chemistry and Biological Chemistry, Kyoto UniVersity,
Katsura, Kyoto 615-8510, Japan
murakami@sbchem.kyoto-u.ac.jp
Received April 1, 2005
ABSTRACT
Two structurally distinct carbocycles were selectively obtained by the reactions of 2-(o-styryl)cyclobutanones promoted by ytterbium salts.
Treatment of the cyclobutanones with YbCl3 in 1,4-dioxane at 100 C afforded 2-(2-chloroethyl)naphthalenes. On the other hand, the reaction
with Yb(OTf)3 in chlorobenzene at 130 C gave 9,10-dihydrobenzocycloocten-7(8H)-ones.
°
°
The acid-promoted addition of an olefin to a carbonyl com-
pound, as in the Prins reaction and the carbonyl-ene reaction,
provides a valuable method for carbon-carbon bond forma-
tion.1 In this context, cyclization reactions have been exten-
sively studied because carbo- and heterocyclic motifs con-
tained in a wide array of biologically active natural products
can be efficiently constructed in a stereoselective manner.
We previously reported that treatment of 2-(o-styryl)-
cyclobutanones with a catalytic amount of rhodium produces
eight-membered ring ketones.2 The reaction takes place
through insertion of rhodium(I) between the carbonyl carbon
and the adjacent R-carbon3 and subsequent intramolecular
olefin insertion process.3c During the course of careful
investigation of the reaction conditions, we found that two
distinctly different reaction pathways, both promoted by
simple Brønsted and Lewis acids, can operate with 2-(o-
styryl)cyclobutanone.
First, HCl gas was bubbled into an ethanol solution of
2-methyl-2-(o-styryl)cyclobutanone (1a) at 75 °C for 3 h
(Scheme 1). Formation of a much less polar substance was
observed by a TLC analysis. Chromatographic isolation
Scheme 1
(1) (a) Snider, B. B. In ComprehensiVe Organic Synthesis; Trost, B. M.,
Fleming, I. Eds.; Pergamon: Oxford, 1991; Vol. 2, p 527. (b) Mikami, K.;
Terada, M.; Narisawa, S.; Nakai, T. Synlett 1992, 255.
(2) Matsuda, T.; Fujimoto, A.; Ishibashi, M.; Murakami, M. Chem. Lett.
2004, 33, 876.
(3) (a) Suggs, J. W.; Jun, C.-H. J. Am. Chem. Soc. 1984, 106, 3054. (b)
Murakami, M.; Amii, H.; Ito, Y. Nature 1994, 370, 540. (c) Murakami,
M.; Itahashi, T.; Ito, Y. J. Am. Chem. Soc. 2002, 124, 13976.
10.1021/ol0506922 CCC: $30.25
© 2005 American Chemical Society
Published on Web 04/21/2005

afforded 2-(â-naphthyl)ethyl chloride 2a-Cl in 73% yield.
The formation of 2a-Cl is explained by assuming the
following sequence. Protonation of the carbonyl group
induces an intramolecular electrophilic attack on the pendant
vinyl group.4 Elimination of the â-proton quenches the
resultant benzylic cation, yielding tertiary alcohol 3. Proto-
nation of the hydroxy group then assists the removal of water,
setting up an equilibrium with the nonclassical cyclobutyl
cation 4.5 A chloride anion attacks the cation in such a way
to accompany concomitant aromatization, furnishing the
naphthalene derivative 2a-Cl.6 Release of the ring strain
together with aromatic stabilization provides the driving force
for this transformation.
cyclohexadiene moiety with disrotatory motion of the sub-
stituents to furnish the eight-membered ring intermediate
7.9,10 The strain of the four-membered ring is released by
this sequence. Protonation at the benzylic position results in
rearomatization to furnish the eight-membered ring ketone
5a.
Encouraged by these distinctly contrasting results, a variety
of Lewis acids were examined, with the selected results listed
in Table 1. The use of ZnBr2 afforded a mixture of products
Table 1. Effect of Reaction Conditions on the Reaction of
2-(o-Styryl)cyclobutanone 1a
On the other hand, when 1a was heated in m-xylene at
140 °C for 18 h in the presence of molecular sieves (4 Å),
the benzene-fused eight-membered ring ketone 5a was
produced in 25% yield (Scheme 2).7,8 It is likely that the
conditions
solvent temp time
% yielda
Lewis acid
(equiv)
entry
2a (X)
5a
Scheme 2
1
2
3
4
5
6
7
ZnBr2 (1.05)
YbCl3 (2.0)
YbCl3 (2.0)
YbCl3 (2.0)
m-xylene 140 °C 6 h
m-xylene 140 °C 3 h
40 (Br)
14 (Cl)
44 (Cl)
90 (Cl)
27
72
48
b
PhCl
dioxane
130 °C 1 h
100 °C 1 h
Yb(OTf)3 (0.2) m-xylene 140 °C 3 h
<5 (OH) 73
87
24 (OH) 38
Yb(OTf)3 (0.2) PhCl
Yb(OTf)3 (0.2) dioxane
130 °C 0.5 h
100 °C 3 h
b
a Determined by 1H NMR of the crude reaction mixture. b Not detected.
2a-Br (40%) and 5a (27%) (entry 1). The reactions with
AlCl3 (-10 °C) and Cu(OTf)2 (140 °C) resulted in lower
conversion. With SnCl4 (-78 °C) and BF3‚OEt2 (-78 °C),
a complex mixture of products was obtained. Gratifying
activities were finally found with ytterbium(III) salts. In the
case of YbCl3, the product distribution was largely influenced
by the solvent employed (entries 2-4).11 Whereas a mixture
of 2a-Cl and 5a was obtained in m-xylene and in chloroben-
zene, 2a-Cl was produced exclusively in 90% yield using
1,4-dioxane. On the other hand, the use of Yb(OTf)3 as the
catalyst (20 mol %) favored the formation of the eight-
membered ring ketone 5a. In particular, 5a was obtained as
the sole product when the reaction was carried out in
chlorobenzene at 130 °C (entry 6).
Thus, appropriate selection of Lewis acid and solvent
dramatically alters the reaction pathway. A polar solvent
favors the formation of a nonclassical cation, and opening
of the four-membered ring predominates in the presence of
a nucleophilic halide anion. On the other hand, the use of a
less polar solvent disfavors the ionic pathway, and the
absence of a suitable nucleophile steers the reaction course
to an alternative electrocyclic pathway to open the six-
membered ring.
Lewis acidic character of the molecular sieves was respon-
sible for activating the carbonyl group and promoting
electrophilic cyclization, since no thermal reaction occurred
in their absence. Loss of a proton then generates tricyclic
intermediate 6, as is the case with the HCl-promoted reaction.
Intermediate 6, in the absence of an appropriate nucleophile,
undergoes thermal electrocyclic ring-opening of the 1,3-
(4) For a related electrophilic aromatic substitution, see: Bernard, A.
M.; Floris, C.; Frongia, A.; Piras, P. P. Synlett 2002, 796.
(5) (a) Koch, W.; Liu, B.; DeFrees, D. J. J. Am. Chem. Soc. 1988, 110,
7325. (b) Saunders, M.; Laidig, K. E.; Wiberg, K. B.; Schleyer, P. v. R. J.
Am. Chem. Soc. 1988, 110, 7652. (c) Holman, R. W.; Plocica, J.; Blair, L.;
Giblin, D.; Gross, M. L. J. Phys. Org. Chem. 2001, 14, 17.
(6) For recent examples of acid-promoted dehydrative aromatization
reactions, see: (a) Kumar, S. J. Chem. Soc., Perkin Trans. 1 1998, 3157.
(b) Kabalka, G. W.; Ju, Y.; Wu, Z. J. Org. Chem. 2003, 68, 7915. For a
review, see: (c) Bradsher, C. K. Chem. ReV. 1987, 87, 1277.
(7) For the syntheses of eight-membered ring ketones from cyclobu-
tanones, see: (a) Wender, P. A.; Correa, A. G.; Sato, Y.; Sun, R. J. Am.
Chem. Soc. 2000, 122, 7815. (b) Oh, H.-S.; Lee, H.-I.; Cha, J. K. Org.
Lett. 2002, 4, 3707. (c) Dowd, P.; Zhang, W. Chem. ReV. 1993, 93, 2091.
(d) Mehta, G.; Singh, V. Chem. ReV. 1999, 99, 881. See also: (e) Paquette,
L. A. Eur. J. Org. Chem. 1998, 1709. (f) Hamura, T.; Kawano, N.; Tsuji,
S.; Matsumoto, T.; Suzuki, K. Chem. Lett. 2002, 1042.
(9) For the disrotatory 6π electrocyclic ring-opening of bicyclo[4.2.0]-
octane ring system, see: (a) Wang, T.-Z.; Paquette, L. A. J. Org. Chem.
1986, 51, 5232. (b) Takeda, T.; Fujiwara, T. Synlett 1996, 481.
(10) For a related ring-expansion, see: Suginome, H.; Itoh, M.; Koba-
yashi, K. J. Chem. Soc., Perkin Trans. 1 1988, 491.
(11) Use of other lanthanide salts such as SmCl3 and CeCl3 led to poor
reactivities compared with YbCl3.
(8) 9,10-Dihydrobenzocycloocten-7(8H)-one skeleton is similar to that
obtained by the rhodium-catalyzed reaction of 2-(o-styryl)cyclobutanone
(ref 2). Under rhodium catalysis, however, no reaction occurred with 1a
having an additional methyl group at the R-position, presumably because
the rhodium insertion was hampered due to the increased steric congestion.
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Org. Lett., Vol. 7, No. 10, 2005

Other examples of the selective synthesis of either 2 or 5
from 1 using the corresponding optimized reaction conditions
A or B are given in Table 2. Cyclobutanones 1a and 1b
to the chlorides, bromides 2a-Br and 2b-Br were successfully
prepared using YbBr3 in place of YbCl3. The reactions of
cyclobutanones 1c and 1d having a hydrogen at the 2-posi-
tion also worked well to give the corresponding products
with a high selectivity by simply choosing the reaction
conditions. Cyclobutanone 1e with an isopropenyl group
afforded the corresponding chloride 2e-Cl on treatment with
YbCl3. On the other hand, the reaction under conditions B
also gave the naphthalene derivative 2e-OH instead of an
eight-membered ring ketone. We assume that 2e-OH was
produced by hydrolysis of 2-(â-naphthyl)ethyl triflate,
initially formed via a nonclassical cation corresponding to
4. The different reactivity of 1e relative to 1a under con-
ditions B is explained by assuming that the additional methyl
group renders the cation stable enough to induce the attack
even by the less nucleophilic triflate anion. A phenyl group
could also participate in the YbCl3-promoted reaction as the
electrophilic site, although less efficiently. However, the
attempted cyclization of 1f with Yb(OTf)3 gave a complex
mixture. The thermal electrocyclic ring-opening process is
likely to be energetically disfavored because the two phenyl
rings need to be dearomatized simultaneously.
Table 2. Lewis Acid-Promoted Reactions of 1a
In summary, two structurally distinct carbocycles 2 and 5
have been selectively synthesized from 2-(o-styryl)cyclobu-
tanones 1 by simply choosing the acidic reaction conditions.
These results demonstrate that cyclobutanones having a
pendant unsaturated functionality are highly versatile com-
pounds that are amenable to Lewis acids as well as to
transition metal catalysts.13
Acknowledgment. S.K. thanks fellowship support from
the Japan Society of Promotion of Science for Young
Scientists.
a Conditions A: 1 and 2.0 equiv of YbX3 (X ) Cl or Br) were heated
in refluxing 1,4-dioxane. Conditions B: 1 and 0.2 equiv of Yb(OTf)3 were
heated in refluxing PhCl. b Isolated yield by preparative TLC. c Reaction
was carried out in refluxing Bu2O.
Supporting Information Available: Experimental pro-
cedures and characterization data for new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
having a substituent at the 2-position furnished naphthalenes
2-Cl and ketones 5, respectively, in high yield.12 In addition
OL0506922
(13) For synthetic applications of cyclobutane derivatives, see: (a) Lee-
Ruff, E.; Mladenova, G. Chem. ReV. 2003, 103, 1449. (b) Namyslo, J. C.;
Kaufmann, D. E. Chem. ReV. 2003, 103, 1485.
(12) 2a-Cl was obtained in 81% yield with 1.0 equiv of YbCl3, and 4a
was obtained in 80% yield with 0.1 equiv of Yb(OTf)3.
Org. Lett., Vol. 7, No. 10, 2005
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