Synthesis of eleven-membered carbocycles by a new five-carbon ring expansion reaction

Article abstract of DOI:10.1016/S0040-4039(01)00020-X

3-Methylenecycloundeca-1,6-diene was synthesized by a homo-Cope ring expansion reaction of 2-(trimethylsilylmethyl)-3-(2-vinylcyclohexyl)prop-2-en-1-ol.

Full text of DOI:10.1016/S0040-4039(01)00020-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 1915–1917
Synthesis of eleven-membered carbocycles by a new five-carbon
ring expansion reaction
Hideyuki Suzuki, Akiko Monda and Chiaki Kuroda*
Department of Chemistry, Rikkyo University, Nishi-Ikebukuro, Toshima-ku, Tokyo 171-8501, Japan
Received 18 October 2000; revised 11 December 2000; accepted 28 December 2000
Abstract—3-Methylenecycloundeca-1,6-diene was synthesized by a homo-Cope ring expansion reaction of 2-(trimethylsilylmethyl)-
3-(2-vinylcyclohexyl)prop-2-en-1-ol. © 2001 Elsevier Science Ltd. All rights reserved.
Eleven-membered carbocycles are classified as medium-
membered rings and are found in natural terpenes such
as humulanes or lathylols.1,2 To synthesize medium-
membered carbocycles, ring expansion reaction is a
common method,3 in which a Cope rearrangement is
widely used as the four-carbon ring expansion reaction.4
This method is often applied to the synthesis of germa-
cranes.5 b-(Hydroxymethyl)allylsilanes are useful three-
carbon units in organic synthesis, and thus replacement
of the carbonꢀcarbon double bond in some organic
reactions with such a unit enables a one-carbon
homologous reaction. Giguere et al. reported the synthe-
sis of hydroazulene derivatives utilizing intramolecular
homo-Diels–Alder reaction using b-(hydroxymethyl)-
allylsilane as the dienophile.6 During the course of our
continuous study of b-functionalized allylsilanes,7 we
planned to perform a homo-Cope rearrangement by
replacing one of the two CꢁC bonds in the Cope
rearrangement with a b-(hydroxymethyl)allylsilane unit.
Here we report the synthesis of 11-membered carbocy-
cles from cyclohexane derivatives by a new homo-Cope
type of five-carbon ring expansion reaction.8,9
Scheme 1. Reagents: (a) PivCl, pyridine, CHCl3; (b) (COCl)2, DMSO, Et3N, CH2Cl2; (c) Ph3PꢁCH2, THF; (d) LiAlH4, THF; (e)
(EtO)2P(O)CH(CO2Et)CH2SiMe3, NaH, DME; (f) DIBAL-H, CH2Cl2.
Keywords: cycloalkenes; medium-ring carbocycles; ring transformations; silicon and compounds.
* Corresponding author. E-mail: kuroda@rikkyo.ac.jp
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00020-X

1916
H. Suzuki et al. / Tetrahedron Letters 42 (2001) 1915–1917
Scheme 2.
The substrates of the present study are the compounds
1a and 1b, which were synthesized in accordance with
Scheme 1. Namely, trans-1,2-cyclohexanedimethanol
(2), prepared from trans-1,2-cyclohexanedicarboxylic
acid, was first monoprotected with a pivaloyl group to
afford 3 (93%), which was then oxidized to the alde-
hyde followed by a Wittig reaction to obtain 4 (83%).
Reductive deprotection of 4 gave alcohol 5 (98%),
which was then subjected to the introduction of a silyl
group7c to afford an ester-conjugated allylsilane in 60%
yield. It was found that the product consisted of four
isomers, among which E-allylsilane 6a and Z-allylsilane
6b could be separated by repetition of silica gel column
chromatography; however, the isomers with respect to
the cyclohexane ring could not be separated. The ratio
of 6a to 6b was 6:5, and each consisted of trans- and
cis-substituted cyclohexanes in 3:2 and 9:2 ratios,
respectively. The geometry of the double bond was
determined from the chemical shifts of the olefinic
protons7e (e.g. trans-6a: l 5.41, trans-6b: l 6.40), while
the geometry on the cyclohexane ring was confirmed by
the coupling pattern of the allylic protons (e.g. cis-6a:
br dq, J=10, 5 Hz, trans-6a: ddt, J=3.5, 11.4, 10.1
Hz). The formation of the cis-isomer on the cyclohex-
ane ring is due to isomerization during the Horner–
Emmons reaction, which was confirmed by the
synthesis from cis-1,2-cyclohexanedimethanol resulting
in the same mixture of 6a,b. Finally, 1a and 1b were
obtained by DIBAL-H reduction of the ester group in
6a and 6b, respectively (1a: 95%, 1b: 93%).
Figure 1.
Table 1.
Entry
Isomer ratio in 1a (trans: cis)
Ratio of 7a and 7b
1
2
3
4
88:12
68:32
60:40a
44:56
93:7
78:22
75:25
63:37
a Original ratio.
pathway, since the direct cyclization of 1b is considered
to proceed through a seven-membered transition state
including the highly strained trans-substituted double
bond 8b, while the cis-substituted double bond is
included in 8a (Fig. 1).
To explore the stereochemistry of this reaction, three
mixtures of 1a with different cis/trans ratios were pre-
pared by repetition of column chromatography, how-
ever it was not possible to obtain pure trans- and
cis-1a. Each mixture was exposed to the same reaction
conditions, and the results are listed in Table 1. Extrap-
olation of these results showed that trans-1a produces
7a selectively, whereas cis-1a produces 7a and 7b in a
1:2 ratio.
The ring expansion reaction was carried out following
the report of Giguere et al.6a When 1a was treated with
1.5 equiv. of Tf2O in the presence of 2.5 equiv. of
2,6-lutidine in CH2Cl2 at −60°C, 11-membered hydro-
carbons 7a and 7b† were afforded as an inseparable
In conclusion, a new five-carbon ring expansion reac-
tion from six- to eleven-membered carbocycles was
established utilizing b-(hydroxymethyl)allylsilane as the
three-carbon unit. The reaction proceeded under mild
conditions and with easy of operation. The scope and
limitations of this reaction are currently under
investigation.
1
mixture in a 81% yield (7a:7b=3:1) (Scheme 2). The H
NMR spectrum showed that 7a and 7b are the isomers
with respect to the non-conjugated double bond (E for
the major isomer 7a), as determined from their J-val-
ues. On the other hand, the reaction of 1b under the
same conditions resulted in the formation of the same
3:1 mixture of 7a,b in a 24% yield. The isomerization
from 1b to 1a prior to the ring expansion is a plausible
References
† 1H NMR (CDCl3) assigned for 7a: l 4.81 (1H, d, J=2.0 Hz), 4.85
(1H, d, J=2.0 Hz), 5.11 (1H, dt, J=15.5, 7.7 Hz), 5.34 (1H, dt,
J=15.5, 7.6 Hz), 5.40 (1H, dt, J=15.8, 7.3 Hz), and 5.91 (1H, br d,
J=15.8 Hz); assigned for 7b: l 4.73 (2H, br s), 5.24–5.32 (1H, m),
5.49 (1H, dtt, J=10.6, 8.6, 1.7 Hz), 5.88 (1H, dt, J=15.8, 6.8 Hz),
and 6.03 (1H, br d, J=15.8 Hz); 13C NMR (CDCl3) assigned for
7a: l 27.55, 29.88, 32.27, 33.98, 34.76, 34.88, 112.64, 130.82, 130.92,
134.45, 137.83, and 148.78; assigned for 7b: l 25.56, 26.64, 26.80,
28.64, 29.69, 32.85, 111.21, 129.52, 130.18 (2C), 135.66, and 149.65.
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