Chemistry Letters 2002
1043
Table 1.a
Scheme 2.
with respect to two alkenyl groups, as shown by NOE study.
These results are consistent with a mechanistic proposal
summarized in Scheme 3. There exists a seemingly opposite
tendency in the relative reactivities of the alkoxide vs the acetate
in the two electrocyclic processes: The initial ring opening of the
four-membered ring is faster with the lithium alkoxide 11,
whereas the subsequent 8ꢀ ring closure of tetraene is faster with
acetate 10 than the corresponding lithium alkoxide 12.8
In summary, the present [4 þ 2 þ 2] approach to the
cyclooctenone derivatives starting from cyclobutenes and dienes
should find utility in natural product synthesis, and further studies
are currently underway in our laboratories.
Scheme 3.
References and Notes
This finding was not only mechanistically interesting, but
allowed us to establish a rapid, high-yielding synthetic protocol
for constructing eight-membered ring compounds. Indeed, when
cyclobutenone 14, having a butyl group on the four-membered
ring, was treated with 2-propenyllithium (À78 ! 0 ꢁC) followed
by Ac2O (0 ! 25 ꢁC), the ring expansion occurred to give eight-
membered compound 16 in 83% yield (entry 1, Table 1). Under a
similar set of conditions with acetylation, reaction of 3 with cis-2-
butenyllithium and cyclopentenyllithium proceeded smoothly to
give cyclooctatrienes 17 and 18 in 88% and 91% yield,
respectively (entries 2 and 3). Alkenylcyclobutenone 15, with a
cyclic alkenyl moiety, was also a good substrate for the clean ring
expansion (entry 4).
Compounds 16–19 were hydrolyzed by either of two
procedures, (1) K2CO3, MeOH, 0 ! 25 ꢁC, 2–3 h (for 16 and
17), or (2) 2 M NaOH, MeOH, 0 ꢁC, 1 h (for 18 and 19)9 to give the
corresponding ketones 20–23 in high yields, respectively.
Compounds 21 and 22 were solely or mainly composed of the
cis isomers with respect to the relation of vicinal dialkyl groups as
evidenced by X-ray analysis.10
1
2
3
T. Hamura, S. Tsuji, T. Matsumoto, and K. Suzuki, Chem Lett., 2002, 280.
T. Hamura, S. Tsuji, T. Matsumoto, and K. Suzuki, Chem Lett., 2002, 750.
For the difficulty in forming eight-membered rings, and the strain inherent in such
medium rings, 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). c) M. Zora, I. Koyuncu, and B. Yucel, Tetrahedron Lett., 41,
7111 (2000).
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, Org. Synth., Coll. Vol. VIII, 82 (1993). 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.
We thank Ms. Sachiyo Kubo, this department, for X-ray analysis. Crystal-
lographic data reported in this paper have been deposited with Cambridge
Crystallographic Data Centre as supplementary publication no. CCDC-192410.
Copies of the data can be obtained free of charge on application to CCDC, 12
Unions Road, Cambridge, CB2 1EZ, UK (fax: (+44)1223-336-033; e-mail:
deposit@ccdc.cam.ac.uk).
8For a related precedent, see: K. C. Nicolaou, N. A. Petasis, R. E. Zipkin, and J.
Uenishi, J. Am. Chem. Soc., 104, 5555 (1982).
9
Hydrolysis of compounds 18 and 19 with K2CO3 in MeOH gave lower yields of
products.
10 The stereochemistry of 23 is currently under study, which will be reported in a full
paper.