Stereoselective ring expansion via bicyclooxonium ion. A novel approach to oxocanes

Article abstract of DOI:10.1021/ol016919k

(equation presented) The stereoselective 1,4-rearrangement-ring expansion of tetrahydrofurans via bicyclo[3.3.0]oxonium ions was developed to synthesize oxocanes. On the basis of this rearrangement, the stereoselective synthesis of 2,8-syn-2,8-dimethyloxo

Full text of DOI:10.1021/ol016919k

ORGANIC
LETTERS
2002
Vol. 4, No. 5
675-678
Stereoselective Ring Expansion via
Bicyclooxonium Ion. A Novel Approach
to Oxocanes
Yasuharu Sakamoto, Kyoko Tamegai, and Tadashi Nakata*
RIKEN (The Institute of Physical and Chemical Research),
Wako, Saitama 351-0198, Japan
nakata@postman.riken.go.jp
Received October 17, 2001 (Revised Manuscript Received January 22, 2002)
ABSTRACT
The stereoselective 1,4-rearrangement−ring expansion of tetrahydrofurans via bicyclo[3.3.0]oxonium ions was developed to synthesize oxocanes.
On the basis of this rearrangement, the stereoselective synthesis of 2,8-syn-2,8-dimethyloxocane was accomplished.
Medium-sized cyclic ethers are found as a part of the
structure of many natural products, such as brevetoxins1 and
lauroxanes,2 isolated mainly from marine organisms. In the
synthesis of these compounds, most of which have alkyl
substituents next to the oxygen atom on the cycle, the
stereoselective construction of the cyclic units is essential.
We already developed an efficient method for the stereo-
selective synthesis of tetrahydropyrans 3 (n ) 1) and
oxepanes 3 (n ) 2) based on a Zn(OAc)2-mediated 1,2-
rearrangement-ring expansion of tetrahydrofurans 1 (n )
1) and tetrahydropyrans 1 (n ) 2) having a C1′-mesylate,
respectively (Scheme 1).3 Recently, the present method was
Scheme 1. Rearrangement-Ring Expansion Reactions
(1) For reviews, see: (a) Shimizu, Y. Chem. ReV. 1993, 93, 1685. (b)
Yasumoto, T.; Murata, M. Chem. ReV. 1993, 93, 1897.
(2) For reviews, see: (a) Moore, R. E. In Marine Natural Products;
Scheuer, P. J., Ed.; Academic Press: New York, 1978; Vol. 1, pp 43-121.
(b) Erickson, K. L. In Marine Natural Products; Scheuer, P. J., Ed.;
Academic Press: New York, 1983; Vol V, pp 131-257. (c) Faulkner, D.
J. Nat. Prod. Rep. 2001, 18, 1. See also his previous reviews in Nat. Prod.
Rep.
(3) (a) Nakata, T.; Nomura, S.; Matsukura, H. Tetrahedron Lett. 1996,
37, 213. (b) Nakata, T.; Nomura, S.; Matsukura, H.; Morimoto, M.
Tetrahedron Lett. 1996, 37, 217. (c) Nakata, T.; Nomura, S.; Matsukura,
H. Chem. Pharm. Bull. 1996, 44, 627. (d) Nagasawa, K.; Hori, N.; Shiba,
R.; Nakata, T. Heterocycles 1997, 44, 105. (e) Nagasawa, K.; Hori, N.;
Koshino, H.; Nakata, T. Heterocycles 1999, 50, 919.
(4) (a) Hori, N.; Nagasawa, K.; Shimizu, T.; Nakata, T. Tetrahedron
Lett. 1999, 40, 2145. (b) Shimizu, T.; Hiranuma, S.; Nakata, T. Tetrahedron
Lett. 1996, 37, 6145. (c) Shimizu, T.; Ohzeki, T.; Hiramoto, K.; Hori, N.;
Nakata, T. Synthesis 1999, 1373.
(5) Morimoto, M.; Matsukura, H.; Nakata, T. Tetrahedron Lett. 1996,
37, 6365.
further improved by using a monochlate (OSO2CH2Cl )
OMc),4 instead of the mesylate, as an efficient leaving group
and was successfully applied to the synthesis of the CD-
ring of hemibrevetoxin B5 and the E-ring of brevetoxin B.6
These ring expansions would proceed through (1) stereo-
(6) Matsuo, G.; Hori, N.; Matsukura, H.; Nakata, T. Tetrahedron Lett.
2000, 41, 7677.
10.1021/ol016919k CCC: $22.00 © 2002 American Chemical Society
Published on Web 02/05/2002

selective formation of bicyclo[3.1.0] and [4.1.0]oxonium ions
2 (n ) 1, 2) as a reaction intermediate and (2) regio- and
stereoselective nucleophilic attack of H2O or AcOH at the
C2-position of 2. These results led us to investigate 1,n+3-
rearrangement-ring expansion via bicyclo[m+2.n+2.0]-
oxonium ion 5.7 We report here a stereoselective synthesis
of oxocanes by 1,4-rearrangement-ring expansion of tet-
rahydrofurans8 via bicyclo[3.3.0]oxonium ion 5 (m ) n )
1), which is known as a reaction intermediate for solvolysis9
and ring contraction.10
a slightly higher selectivity (9b:10b ) 5:1) than that of
AcOH (9a:10a ) 3.15:1). However, use of the THF-H2O
solvent system instead of AcOH-H2O resulted in almost
the same ratio (entry 2). The results also suggest that Zn-
(OAc)2 is a source of the OAc group as a nucleophile in
this reaction. The lower reaction temperature increased the
selectivity of ring expansion (entry 3, 9:10 ) 20.3:3.8 at
room temperature; entry 2, 9:10 ) 11:3 at 50 °C), although
the reaction required rather longer time for completion (entry
3).
First, the ring expansion of the simple substrate 7 having
Therefore, the use of monochlate as an efficient leaving
group was next investigated for this expansion. The reaction
of monochlate 11, prepared from alcohol 10b12 with chlo-
romethanesulfonyl chloride (McCl) and 2,6-lutidine in CH2-
Cl2, was examined in several aqueous solvent systems (Table
2). To our surprise, even in the absence of a Lewis acid, the
a mesylate11 was examined (Table 1). Treatment of 7 under
a
Table 1. Reaction of Mesylate 7 with Zn(OAc)2
Table 2. Reaction of Monochlate 11 without Lewis Acid
temp time yieldb
entry
solvent
(°C)
(h)
(%)
9a :9b:10a :10bc
1
2
3
AcOH-H2O, 1:1
THF-H2O, 1:1
THF-H2O, 1:1
50
50
rt
1.5
5
48
83
91
93
6.3:5.0:2.0:1
6.0:5.0:2.0:1
11.7:8.6:2.8:1
time
(h)
yielda
(%)
entry
solvent
temp
9b:10bb
a All reactions were carried out with 4 equiv of Zn(OAc)2. b Combined
1
2
3
4
5
THF-H2O, 1:1
THF-H2O, 4:1
MeCN-H2O, 1:1
MeCN-H2O, 4:1
acetone-H2O, 1:1
rt
rt
rt
rt
rt
2
5
2
2
2
82
56
60
55
30
8.0:1
6.7:1
8.0:1
6.2:1
6.0:1
1
yield of 9a, 9b, 10a, and 10b. c Determined by H NMR spectroscopy.
the standard conditions, Zn(OAc)2 in AcOH-H2O at 50 °C,
for our 1,2-rearrangement, effected ring expansion to afford
5-acetoxy- and 5-hydroxyoxocanes (9a and 9b) along with
10a and 10b in 6.3:5:2:1 ratio (entry 1). The nucleophilic
attack of AcOH and H2O to the bicyclooxonium ion 8 by
the path a could afford the expanded products 9a and 9b,
respectively. This result showed that the attack of H2O has
a Combined yield of 9b and 10b in 2 steps from the starting 10b.
b Determined by H NMR spectroscopy.
1
rearrangement of monochlate 11 in aqueous solvent took
place very smoothly. The best result was obtained in THF-
H2O (1:1) at room temperature within 2 h to give the ring-
expanded 9b in good yield and high selectivity (entry 1).
(7) 1,4- and 1,5-Rearrangement-ring expansion of oxiranes via bicyclo-
[3.1.0] and [4.1.0]oxonium ions, respectively, were reported. (a) Hayashi,
N.; Fujiwara, K.; Murai, A. Chem. Lett. 1996, 341. (b) Hayashi, N.;
Fujiwara, K.; Murai, A. Tetrahedron Lett. 1996, 37, 6173. (c) Hayashi, N.;
Fujiwara, K.; Murai, A. Synlett 1997, 793. (d) Fujiwara, K.; Murai, A.
Tetrahedron 1997, 53, 12425. (e) Fujiwara, K.; Hayashi, N.; Tokiwano,
T.; Murai, A. Heterocycles 1999, 50, 561. (f) Hayashi, N.; Noguchi, H.;
Tsuboi, S. Tetrahedron 2000, 56, 7123.
Scheme 2
(8) (a) Kamada, T.; Ge-Qing; Abe, M.; Oku, A. J. Chem. Soc., Perkin
Trans. 1 1996, 413. (b) Mukai, C.; Yamashita, H.; Ichiryu, T.; Hanaoka,
M. Tetrahedron 2000, 56, 2203.
(9) Kwiatkowski, G. T.; Kavarnos, S. J.; Closson, W. D. J. Heterocycl.
Chem. 1965, 2, 11.
(10) (a) Paquette, L. A.; Scott, M. K. J. Am. Chem. Soc. 1972, 94, 6751.
(b) Paquette, L. A.; Scott, M. K. J. Am. Chem. Soc. 1972, 94, 6760. (c)
Blumenkopf, T. A.; Bratz, M.; Castan˜eda, A.; Look, G. C.; Overman, L.
E.; Rodriguez, D.; Thompson, A. S. J. Am. Chem. Soc. 1990, 112, 4386.
(11) Mesylate 7 was prepared from alcohol 10b with mesyl chloride and
triethylamine in CH2Cl2 at 0 °C. See ref 12 for preparation of 10b.
(12) Alcohol 10b was prepared by a known procedure; see: Hornberger,
C. S., Jr.; Heitmiller, R. F.; Gunsalus, I. C.; Schnakenberg, G. H. F.; Reed,
L. J. J. Am. Chem. Soc. 1953, 75, 1273.
676
Org. Lett., Vol. 4, No. 5, 2002

Scheme 3
To investigate the present rearrangement in more detail,
inversion via bicyclooxonium ion 16 and 19 in path c,
respectively, while 17d and 20d were provided by the direct
solvolysis with inversion and not via the bicyclooxonium
ion intermediate. The ring-migrated product 20b was ob-
tained via bicyclooxonium ion 19 in path b. As was expected,
the monochlate prepared from 20b also gave the expanded
oxocane 20a by this rearrangement via the same bicyclooxo-
nium ion 19, although it took 22 h for completion.
On the basis of this stereoselective ring expansion, the
synthesis of cis-2,8-dialkyloxocanes, which are the structures
found in brevetoxins and lauroxanes, was examined (Scheme
4). Treatment of an optically pure 2,5-anti-2,3′-syn-tetrahy-
drofuran 21 with McCl followed by treatment in THF-H2O
(1:1) stereoselectively afforded the desired 2,5-anti-2,8-syn-
2,8-dimethyl-5-hydroxyoxocane (23a)13 along with tetrahy-
drofuran 23b14 in 96% combined yield (23a:23b ) 6:1)
within 20 min. On the other hand, 2,5-syn-2,3′-anti-tetrahy-
drofuran 24 gave no ring-expanded ether but gave a 1.5:1
mixture of epimeric tetrahydrofurans 26. These results could
a deuterated substrate 12 was subjected to this reaction
(Scheme 2). The production of 14a and 14b confirmed the
existence of bicyclooxonium ion 13 as the reaction inter-
mediate. The preferred production of 14c to 14b would
suggest a contribution of the direct solvolysis of the starting
monochlate.
The stereoselectivity of the present rearrangement was
explored with a pair of diastereomers 15 and 18 having a
secondary monochlate (Scheme 3). Treatment of 2,3′-syn-
tetrahydrofuran 15 with McCl followed by treatment of the
resultant monochlate in THF-H2O (1:1) stereoselectively
afforded the expanded 2,5-anti-oxocane 17a13 in high yield
within 1 h along with 17c,d. The 2,3′-anti-tetrahydrofuran
18 under the same conditions produced 2,5-syn-oxocane
20a13 stereoselectively along with 20b-d. These results
revealed that the present rearrangement-ring expansion takes
place stereoselectively and stereospecifically. The byproducts
17c and 20c were given by the solvolysis with double
Scheme 4
Org. Lett., Vol. 4, No. 5, 2002
677

be explained by the ease of formation of the bicyclooxonium
ion. In the reaction of the monochlate derived from 24,
bicyclooxonium ion 25 would be hardly formed as a reaction
intermediate because the dimethyl groups directed to the
concave face have steric hindrance. Thus, 26 was provided
by the direct solvolysis. In contrast, the monochlate derived
from 21 can easily form bicyclooxonium ion 22, because
22 has the dimethyl groups in the convex face without severe
steric repulsion.
In summary, we have developed a stereoselective 1,4-
rearrangement-ring expansion of tetrahydrofurans via bicyclo-
[3.3.0]oxonium ions to afford oxocanes. On the basis of this
rearrangement, we have accomplished the synthesis of 2,8-
syn-2,8-dimethyloxocane. Applications of the present rear-
rangement to natural product synthesis are in progress in this
laboratory.
(13) 1H and 13C NMR Data for Oxocanes 17a, 20a, and 23a. 17a:
1H NMR (500 MHz, CDCl3) δ 4.19 (tt, J ) 7.9, 3.6 Hz, 1H), 3.72 (ddd, J
) 12.0, 8.3, 3.6 Hz, 1H), 3.62 (ddq, J ) 6.4, 3.0, 6.4(q) Hz, 1H), 3.48
(ddd, J ) 12.0, 6.4, 3.4 Hz, 1H), 1.48-1.92 (m, 8H), 1.14 (d, J ) 6.4 Hz,
3H); 13C NMR (125 MHz, CDCl3) δ 74.2, 70.8, 67.1, 34.2, 33.9, 31.5,
26.0, 21.3. 20a: 1H NMR (500 MHz, CDCl3) δ 4.07 (tt, J ) 5.5, 3.3 Hz,
1H), 3.73 (ddd, J ) 12.4, 8.1, 3.9 Hz, 1H), 3.60 (m, 1H), 3.49 (ddd, J )
12.4, 6.4, 3.8 Hz, 1H), 1.56-1.98 (m, 8H), 1.17 (d, J ) 6.4 Hz, 3H); 13C
NMR (150 MHz, acetone-d6) δ 74.5, 70.4, 67.9, 34.4, 32.3, 31.2, 26.0,
22.1. 23a: 1H NMR (500 MHz, CDCl3) δ 4.23 (tt, J ) 9.0, 3.4 Hz, 1H),
3.60 (ddq, J ) 6.4, 3.0, 6.4(q) Hz, 2H), 1.94 (m, 2H), 1.86 (m, 2H), 1.59
(m, 2H), 1.45 (m, 2H), 1.14 (d, J ) 6.4 Hz, 6H); 13C NMR (150 MHz,
CDCl3) δ 74.3, 71.7, 33.9, 32.7, 22.0.
Acknowledgment. This work was supported in part by
Special Project Funding for Basic Science (Essential Reac-
tion) from RIKEN and by a Grant-in-Aid for Scientific
Research (10750629) to Y.S. from the Ministry of Education,
Culture, Sports, Science and Technology of Japan. We thank
Dr. H. Koshino for the NMR spectral measurements and Ms.
K. Harata for the mass spectral measurements.
(14) The tetrahydrofuran 23b was a 1:1 mixture of 21 and ent-21. The
ratio was determined by 1H NMR spectrum analysis of the diastereomeric
mixture of their (R)-MTPA ester derivatives. This result indicates that 23b
was produced via meso-bicyclooxonium ion intermediate 22.
OL016919K
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Org. Lett., Vol. 4, No. 5, 2002