Single step synthesis of cyclooctadienone derivatives by reaction of cyclobutenones with dienyllithium

Article abstract of DOI:10.1246/cl.2002.750

Various functionalized cyclooctadienones are accessible in high yields by the reaction of cyclobutenones with dienyllithium.

Full text of DOI:10.1246/cl.2002.750

750
Chemistry Letters 2002
Single Step Synthesis of Cyclooctadienone Derivatives
by Reaction of Cyclobutenones with Dienyllithium
Toshiyuki Hamura, Shinsuke Tsuji, Takashi Matsumoto, and Keisuke Suzukiꢀ
Department of Chemistry, Tokyo Institute of Technology and
CREST, Japan Science and Technology Corporation (JST), O-okayama, Meguro-ku, Tokyo 152-8551
(Received April 26, 2002; CL-020366)
Various functionalized cyclooctadienones are accessible in
high yields by the reaction of cyclobutenones with dienyllithium.
Eq 1 shows the preliminary experiments on cyclobutenone 2.
Upon treatment of 2 with dienyllithium 67 (1.3 equiv) in Et2O at
ꢁ78 ꢂC, the starting material 2 was quickly consumed. Immediate
quenching with H2O gave a mixture of alcohol 7 and
cyclooctadienone 8 (entry 1), suggesting that the ring expansion
could be executed in one pot, simply by warming the reaction.
Indeed, we were pleased to find that when the identical reaction
was gradually warmed to room temperature, the ring-enlarged
product 8 was obtained as a sole product in 89% yield (entry 2).8
The formation of 8 implies that the intermediary enolate 9
underwent protonation selectively at the ꢀ position.
We recently reported an approach to benzocyclooctenone III
via the thermal ring expansion of dienylbenzocyclobutenol
derivative II, prepared by the dienylation–silylation of benzocy-
clobutenone I (Scheme 1).1;2
By analogy, we became interested in the corresponding
reactions of the simpler, ‘‘non-benzo’’ series of compounds,
which is reported in this communication. Particularly notable in
the latter series was that the rearrangement proceeded quite easily
in one pot, i.e. without isolation and derivation of intermediates
(cf. II). Thus, the alkoxide V, formed by the reaction of IV with
dienyllithium, directly underwent the ring enlargement, provid-
ing a facile access to cyclooctadienone VI.4
The application of this protocol to other substrate combina-
tions is summarized in Table 1.10 Upon treatment of 2 with ꢁ-
substituted dienyllithiums 12 and 13 at ꢁ78 ꢂC followed by
warming to room temperature, the ring expansion smoothly
occurred to give ketones 15 and 16 in high yield, respectively
(entries 1 and 2). Likewise, the procedure was applied to
dienyllithium 14 with ꢂ; ꢁ-dimethyl groups, which was treated
with 2 (ꢁ78 ꢂC ! room temperature) to give ketone 17 in 81%
yield. Clean ring expansion was also achieved for the cyclobu-
tenones 10 and 11, having a butyl group or two propyl groups on
the four-membered ring (entries 4 and 5).11
Also examined were reactions of the chlorinated cyclo-
butenone 5 (eq 2). When 5 was treated with dienyllithium 6 in
Et2O at ꢁ78 ꢂC followed by warming to room temperature,
cyclooctadienone 20 was obtained in 77% yield (entry 1).
Bicyclic compound 21 was obtained as a side product,12 which
was possibly formed by the 6ꢃ electrocyclization of the
intermediary enolate 22.13 This side reaction, though interesting
in its own right, was suppressed by keeping the reaction
temperature at 0 ꢂC, and cyclooctadienone 20 was obtained in
89% yield (eq 2, entry 2).
Scheme 1.
Ketone 2 was prepared from 1 by known methods (Scheme
2).5 Chloroketone 5 was obtained via the selective SN2’ reaction
of the acetal 3 with MeLi as reported previously,6 and subsequent
acid hydrolysis.
Scheme 2.
Copyright Ó 2002 The Chemical Society of Japan

Chemistry Letters 2002
751
Table 1.a
dienone derivatives starting from cyclobutenes and dienes would
find utility in natural product synthesis, and further studies are
currently underway in our laboratories.
References and Notes
1
T. Hamura, S. Tsuji, T. Matsumoto, and K. Suzuki, Chem. Lett.,
2002, 280.
2
T. Hosoya, T. Hasegawa, Y. Kuriyama, T. Matsumoto, and K.
Suzuki, Synlett, 1995, 177; T. Hosoya, T. Hasegawa, Y.
Kuriyama, and K. Suzuki, Tetrahedron Lett., 36, 3377 (1995);
T. Hosoya, T. Hamura, Y. Kuriyama, M. Miyamoto, T.
Matsumoto, and K. Suzuki, Synlett, 2000, 520.
3
For a discussion of the difficulty in forming eight-membered
rings, due to the inherent strain, see: a) G. Mehta and V. Singh,
Chem. Rev., 99, 881 (1999). b) N. A. Petasis and M. A. Patane,
Tetrahedron, 48, 5757 (1992).
4
5
For related [4 þ 2 þ 2] approaches, see: a) L. A. Paquette and J.
Tae, Tetrahedron Lett., 38, 3151 (1997). b) L. A. Paquette and
T. M. Morwick, J. Am. Chem. Soc., 119, 1230(1997).
a) R. L. Danheiser and H. Sard, Tetrahedron Lett., 24, 23 (1983).
b) R. L. Danheiser and S. Savariar, Tetrahedron Lett., 28, 3299
(1987). c) R. L. Danheiser, S. Savariar, and D. D. Cha, ‘‘Organic
Synthesis,’’ Wiley, New York (1993), Collect. Vol. VIII,
pp 82–86. d) A. Hassner and J. L. Dillon, Jr., J. Org. Chem.,
48, 3382 (1983).
6
7
T. Hamura, M. Kakinuma, S. Tsuji, T. Matsumoto, and K.
Suzuki, Chem. Lett., 2002, 748.
Dienyllithium was generated by halogen–lithium exchange of
the corresponding dienyl bromide and t-BuLi. For the synthesis
of dienyl bromides, see: J. Uenishi, R. Kawahama, O.
Yonemitsu, and J. Tsuji, J. Org. Chem., 63, 8965 (1998).
A typical procedure: To a solution of cis-1-bromo-3-butylbuta-
1,3-diene9 (425 mg, 2.21 mmol) in Et2O (4.0mL) was added t-
BuLi (1.64 M in pentane, 2.3 ml, 3.8 mmol) at ꢁ78 ꢂC, and the
reaction was further stirred for 1 h, to which was added ketone 2
(212 mg, 1.47 mmol) in Et2O (3.0mL). After warmed to room
temperature over 2 h, and further stirred for 30min, the reaction
was quenched with water. The products were extracted with
EtOAc (X3), dried (Na2SO4), and concentrated in vacuo. The
residue was purified by silica-gel flash column chromatography
(hexane/EtOAc ¼ 92=8) to give cyclooctadienone 8 (331 mg,
89%) as a colorless oil. 1H NMR (CDCl3) ꢁ 0.84 (t, 3H,
J ¼ 7:1 Hz), 1.16–1.35 (m, 4H), 1.94 (t, 2H, J ¼ 7:6 Hz), 2.44
(t, 2H, J ¼ 6:8 Hz), 3.22 (t, 2H, J ¼ 6:8 Hz), 3.45 (d, 2H,
J ¼ 8:3 Hz), 5.42 (t, 1H, J ¼ 8:3 Hz), 6.27 (s, 1H), 7.35–7.46
(m, 5H); 13C NMR (CDCl3) ꢁ 13.8, 22.2, 30.4, 30.9, 31.0, 39.9,
44.0, 116.3, 126.7, 128.6, 128.8, 129.0, 142.0, 142.3, 153.0,
202.3; IR (neat) 3028, 2957, 2871, 1669, 1652, 1574, 1485,
1378, 1267, 1186, 1000, 968, 795 cmꢁ1; Anal. Calcd for
C18H22O: C, 84.99; H, 8.72. Found: C, 84.76; H, 8.81.
cis-1-Bromo-3-butylbuta-1,3-diene was prepared by dibromo-
olefination of 2-butylpropenal, and subsequent stereoselective
reduction of the resulting 1,1-dibromo-1-alkene, see Ref. 7.
8
Similarly, chlorocyclobutenones 23a and 23b14 reacted with
dienyllithium 6, where the addition and ring expansion sequence
again proceeded smoothly to give ketones 24a and 24b in high
yield, respectively (eq 3). In contrast to the case in eq 2, no four-
membered ring compounds were obtained.
9
10All new compounds were fully characterized by spectroscopic
means and combustion analysis.
11 Cyclobutene 11 was prepared by the [2 þ 2] cycloaddition of 4-
octyne and dichloroketene, followed by reduction of two
chlorine atom, see Ref. 5c.
12 The stereochemistry of 21 was determined by an NOE study.
13 For related reaction, see: K. C. Nicolaou, N. A. Petasis, R. E.
Zipkin, and J. Uenishi, J. Am. Chem. Soc., 104, 5555 (1982).
14 Cyclobutenones 23a and 23b were prepared by the SN2’
reaction of the corresponding dichlorocyclobutenone acetals
with 4-methoxyphenyllithium, followed by acid hydrolysis
(Ref. 6).
In summary, the present [4 þ 4] approach to the cycloocta-