New cyclization reaction of 2-(trimethylsilylmethyl)pentadienal. Synthesis of spiro[4.5]decane ring system

Article abstract of DOI:10.1246/cl.2000.962

4-Cyclohexylidene-2-(trimethylsilylmethyl)but-2-enal, allylsilane type of linearly conjugated pentadienal, underwent a new self-cyclization reaction to afford 2-methylspiro[4.5]-2-decen-1-one. The reaction of 4-(4-alkylcyclohexylidene)-2-(trimethylsilylme

Full text of DOI:10.1246/cl.2000.962

962
Chemistry Letters 2000
New Cyclization Reaction of 2-(Trimethylsilylmethyl)pentadienal.
Synthesis of Spiro[4.5]decane Ring System
Chiaki Kuroda* and Hiroyuki Koshio
Department of Chemistry, Rikkyo University, Nishi-Ikebukuro, Toshima-ku, Tokyo 171-8501
(Received May 31, 2000; CL-000523)
4-Cyclohexylidene-2-(trimethylsilylmethyl)but-2-enal,
allylsilane type of linearly conjugated pentadienal, underwent a
new self-cyclization reaction to afford 2-methylspiro[4.5]-2-
decen-1-one. The reaction of 4-(4-alkylcyclohexylidene)-2-
(trimethylsilylmethyl)-2-butenal proceeded stereoselectively.
The Nazarov cyclization of a cross-conjugated divinyl
ketone is a useful method to synthesize five-memberd carbocy-
cles.1 We reported the synthesis of spiro[4.5]decanes 1 by
Nazarov cyclization of α-(trimethylsilylmethyl)divinyl ketones
2 (Scheme 1),2 in which the reaction was activated by an allylic
trimethylsilyl group.3,4 In contrast, linearly conjugated dienal
is not a suitable substrate for the Nazarov or related type of
self-cyclization. We envisioned that this moiety would also be
useful if the double bond is activated by silyl group at allylic
position, since allylsilanes act as the carbanion equivalent and
thus easily react with aldehyde.5 Here we report a new cycliza-
tion reaction of linearly conjugated 2,4-pentadienal substituted
by trimethylsilylmethyl group at C(2)-position, by which
spiro[4.5]decane ring system,6 one of the major skeleton in nat-
ural sesquiterpenes such as acoranes or vetispiranes,7,8 was syn-
thesized.
The substrates of the present study are the compounds
3a–c, which were synthesized by the route illustrated in
Scheme 2. Namely, to the aldehyde 4a, prepared from cyclo-
hexanone, was introduced the β-(ethoxycarbonyl)allylsilane
moiety2 giving 5a in 51% yield. Compound 5a was obtained as
the only (Z)-isomer, and the geometry of which was determined
based on the chemical shift of the olefinic proton (δ 7.40;
CH=CCO2Et).9 DIBAL-H reduction of 5a (92%) followed by
MnO2 oxidation afforded aldehyde 3a (89%). Similarly, 3b
and 3c were prepared from 4-tert-butylcyclohexanone and 4-
methylcyclohexanone, respectively.
substrate, which afforded 6b13 as a single diastereomer in 80%
yield. The structure of 6b was determined from NOE signal
observed between allylic methylene and axial protons on cyclo-
hexane ring as shown in Figure 1. Compound 3c afforded 6c14
in 70% yield, which was again obtained as a single diastere-
omer, and its structure was determined independently in the
same way (Figure 1). The stereoselectivity of the cyclization
reaction can be rationalized by a preferential equatorial attack
to the exocyclic double bond.15
The cyclization reaction was carried out by the treatment of
10
3a with ca. 2 eq of FeCl3 in CH2Cl2 at room temperature11
giving spiro[4.5]decane compound 6a12 in 78% yield (Scheme
3). Some other Lewis acids, such as AlCl3, Et2AlCl and
BF3OEt2 were also used but without success. The stereochem-
istry of the cyclization reaction was then studied using 3b as the
Copyright © 2000 The Chemical Society of Japan

Chemistry Letters 2000
963
In order to clarify the role of the trimethylsilyl group, the
cyclization reaction of desilylated substrate 7, prepared in the
same way, was also examined. However, as expected, com-
pound 7 did not afford any cyclization product after treatment
under the same reaction conditions (Scheme 3). This indicates
that the cyclization of 3 proceeds through silicon-stabilized car-
bocation 10 (Scheme 4).5 It is interesting that the product was
not the expected alcohol 11 but enone 6. The reaction mecha-
nism is not clear as yet, however isomerization from 11 to 6 is a
plausible pathway. The double-bond isomerization from (Z)-3
to (E)-3 should occur prior to the cyclization, as observed previ-
ously,9 since the cyclization must be proceeded from (E)-3.
Another interesting aspect of the present cyclization is the
reaction mode, which is illustrated in Figure 2. We previously
References and Notes
1
2
3
S. E. Denmark, in “Comprehensive Organic Synthesis,” ed.
by B. M. Trost, Pergamon Press, Oxford (1991), Vol. 5, p.
751.
a) C. Kuroda and Y. Hirono, Tetrahedron Lett., 35, 6895
(1994). b) C. Kuroda, H. Sumiya, A. Murase, and A.
Koito, Chem. Commun., 1997, 1177.
For allylsilane promoted Nazarov cyclization: a) S. E.
Denmark and R. C. Klix, Tetrahedron, 44, 4043 (1988). b)
S. E. Denmark, M. A. Wallace, and C. B. Walker, Jr., J.
Org. Chem., 55, 5543 (1990). c) K.-T. Kang, S. S. Kim, J.
C. Lee, and J. S. U, Tetrahedron Lett., 33, 3495 (1992).
For related reaction of allylsilanes from our laboratory: C.
Kuroda, Recent Res. Dev. Pure Appl. Chem., 2, 189 (1998).
For review on the reaction of allylsilanes: a) A. Hosomi,
Acc. Chem. Res., 21, 200 (1988). b) Y. Yamamoto and N.
Asao, Chem. Rev., 93, 2207 (1993). c) E. Langkopf and D.
Schinzer, Chem. Rev., 95, 1375 (1995). d) I. Fleming, A.
Barbero, and D. Walter, Chem. Rev., 97, 2063 (1997).
For recent examples on the synthesis of spiro[4.5]decanes:
a) T. Sattelkau and P. Eilbracht, Tetrahedron Lett., 39,
1905 (1998). b) G. A. Molander and C. Alonso-Alija,
Tetrahedron, 53, 8067 (1997). c) Y. Takemoto, T. Ohra,
Y. Yonetoku, and C. Iwata, Chem. Pharm. Bull., 45, 459
(1997). d) P. J. Biju and G. S. R. S. Rao, Tetrahedron
Lett., 40, 2405 (1999). e) S. Kotha, E. Manivannan, T.
Ganesh, N. Sreenivasachary, and A. Deb, Synlett, 1999,
1618. f) M. Pohmakotr, T. Bunlaksananusorn, and P.
Tuchinda, Tetrahedron Lett., 41, 377 (2000).
4
5
6
7
8
9
T. K. Devon and A. I. Scott, “Handbook of Naturally
Occurring Compounds, Vol. II,” Academic Press, New
York (1972).
For recent reports on natural sesquiterpenes: B. M. Fraga,
Nat. Prod. Rep., 16, 711 (1999); 15, 73 (1998); 14, 145
(1997).
reported9 that 2-(trimethylsilylmethyl)pentadienoic acid or its
ester reacts with proton to afford lactone, where the reaction
proceeded through mode A (E = R3 = H, R4 = OH or OEt) but
not mode B. In contrast, the present reaction apparently pro-
ceeded via mode B (E = FeCl3, R1 = R4 = H).
C. Kuroda, N. Mitsumata, and C. Y. Tang, Bull. Chem.
Soc. Jpn., 69, 1409 (1996).
10 Anhydrous FeCl3 was used without careful handling.
11 FeCl3 was added to a solution of 3 at –60 °C, and the reac-
tion mixture was slowly warmed to room temperature; See
Ref. 2a.
1
12 6a: IR (neat) 1702 and 1640 cm–1; H NMR (CDCl3) δ
1.20–1.40 (6H, m) 1.52–1.77 (4H, m), 1.77 (3H, dt, J =
1.3, 2.3 Hz), 2.42 (2H, quint, J = 2.3 Hz), and 7.23 (1H, tq,
J = 2.3, 1.3 Hz).
1
13 6b: IR (neat) 1706 and 1637 cm–1; H NMR (CDCl3) δ
0.85 (9H, s), 1.00–1.11 (3H, m), 1.24–1.35 (2H, m),
1.53–1.66 (2H, m), 1.73–1.80 (2H, m), 1.77 (3H, dt, J =
1.4, 2.2 Hz), 2.39 (2H, quint, J = 2.2 Hz), and 7.23 (1H, tq,
J = 2.2, 1.4 Hz).
In conclusion, a new self-cyclization reaction of linearly
conjugated pentadienal assisted by allylic trimethylsilyl group
was established. Since the carbonyl position in the product is
different from that of the Nazarov cyclization, it is possible to
obtain both spiro[4.5]decan-1-one (6) and -2-one (1) derivatives
from cyclohexanone by two different types of spiroannulation
reaction, the present dienal cyclization and the Nazarov cycliza-
tion.
1
14 6c: IR (neat) 1703 and 1641 cm–1; H NMR (CDCl3) δ
0.90 (3H, d, J = 6.5 Hz), 0.93–1.05 (2H, m), 1.21–1.28
(2H, m), 1.36–1.49 (1H, m), 1.61 (2H, br dt, J = 3.5, 13
Hz), 1.66–1.72 (2H, m), 1.77 (3H, dt, J = 1.4, 2.3 Hz), 2.39
(2H, quint, J = 2.3 Hz), and 7.23 (1H, tq, J = 2.3, 1.4 Hz).
15 D. Caine, in “Comprehensive Organic Synthesis,” ed. by
B. M. Trost, Pergamon Press, Oxford (1991), Vol. 3, p. 1.