Cyclization into Hydrindanones Using Samarium Diiodide

Article abstract of DOI:10.1021/jo9918450

Samarium(II) iodide has been employed to promote vinylogous pinacol coupling reaction of aldehyde onto α,β-unsaturated ketones. The diastereoselectivity of 6-endo products was changed by addition of a proton source and/or HMPA and by the reaction temperature. The cyclization reactions described herein provide a general approach to the syntheses of 3,3-dimethylhydrindanes with a cis-relationship between the OH at C-4 and the proton at C-3a with good diastereoselectivity and under mild reaction conditions.

Full text of DOI:10.1021/jo9918450

J . Org. Chem. 2000, 65, 3099-3106
3099
Cycliza tion in to Hyd r in d a n on es Usin g Sa m a r iu m Diiod id e
Masakazu Sono, Yasuyo Nakashiba, Katsuyuki Nakashima, and Motoo Tori*
Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho,
Tokushima 770-8514, J apan
Received November 30, 1999
Samarium(II) iodide has been employed to promote vinylogous pinacol coupling reaction of aldehyde
onto R,â-unsaturated ketones. The diastereoselectivity of 6-endo products was changed by addition
of a proton source and/or HMPA and by the reaction temperature. The cyclization reactions described
herein provide a general approach to the syntheses of 3,3-dimethylhydrindanes with a cis-
relationship between the OH at C-4 and the proton at C-3a with good diastereoselectivity and
under mild reaction conditions.
Sch em e 1
In tr od u ction
Samarium (II) diiodide (SmI2) is an exceptional reagent
for promoting intramolecular reductive cyclization reac-
tions, and the chemistry of this reagent has been well
documented in several reviews.1 Among many synthetic
reactions and strategies, carbon-carbon bond formations
between aldehydes or ketones and R,â-unsaturated esters
are of extreme interest. Most cases are classified as
4-exo,2 5-exo-,3 6-exo,4 or 7-exo-Trig5 type cyclizations.
Thus, our interest has been focused on the 6-endo-Trig-
type cyclization between aldehydes and enones.
At the same time, we have been interested in total
syntheses of compounds having a hydrindane system,
such as tamariscol,6 conocephalenol,7 isovalerenenol,8
chiloscyphone,9 and so on. Botrydial (1) is a secondary
metabolite of Botrytis cinerea and possesses six chiral
centers in a hydrindane system.10 Reductive cyclization
using SmI2 has been a promising method to construct the
hydrindane system, although the cis and trans stereo-
chemistry depends on the reaction conditions.11 Because
hydrindanone systems such as 2 could be derived from
the corresponding enone aldehyde 3 by an intramolecular
reductive cyclization, we have prepared substrates and
tested the scope and limitation of this process. This enone
aldehyde may be obtained from mono-alcohol 6 and
bromide 5 (Scheme 1).
In electrochemistry, comparison of the half-wave po-
tential of R,â-unsaturated carbonyls with those of the
corresponding saturated carbonyls has been extensively
studied.12 The first waves of carbonyl groups, referred to
as SCE, are 2.45 V (cyclohexanone), 2.25 V (methyl ethyl
ketone), 1.8 V (propionaldehyde), 1.55 V (2-cyclohexen-
1-one), 1.5 V (acrolein), and 1.42 V (methyl vinyl ketone),
respectively. On the other hand, the reducing character-
istics of SmI2 can be modulated by the addition of
catalysts13 and solvent additives.14 For example, the
oxidation potential of SmI2, referred to as Ag/AgNO3
electrode, can be changed to between -1.33 V (non
* To whom correspondence should be addressed. Phone +81-88-622-
9611 ext 5631. Fax +81-88-655-3051. E-mail: tori@ph.bunri-u.ac.jp.
(1) (a) Molander, G. A. Chem. Rev. 1992, 92, 29. (b) Molander, G.
A.; Harris, C. R. Chem. Rev. 1996, 96, 307. (c) Molander, G. A. Acc.
Chem. Res. 1998, 31, 603. (d) Molander, G. A.; Harris, C. R. Tetrahe-
dron 1998, 54, 3321.
(2) J ohnston, D.; McCusker, C. M.; Procter, D. J . Tetrahedron Lett.
1999, 40, 4913.
(3) (a) Enholm, E. J .; Trivellas, A. Tetrahedron Lett. 1989, 30, 1063.
(b) Kan, T.; Hosokawa, S.; Nara, S.; Oikawa, M.; Ito, S.; Matsuda, F.;
Shirahama, H. J . Org. Chem. 1994, 59, 5532. (c) Kan, T.; Nara, S.;
Ito, S.; Matsuda, F.; Shirahama, H. J . Org. Chem. 1994, 59, 5111. (d)
Sakai, H.; Hagiwara, H.; Ito, Y.; Hoshi, T.; Suzuki, T.; Ando, M.
Tetrahedron Lett. 1999, 40, 2965.
(4) Kito, M.; Sakai, T.; Yamada, K.; Matsuda, F.; Shirahama, H.
Synlett. 1993, 158.
(5) (a) Fukuzawa, S.; Iida, M.; Nakanishi, A.; Fujinami, T.; Sakai,
S. J . Chem. Soc., Chem. Commun. 1987, 920. (b) Fukuzawa, S.;
Nakanishi, A.; Fujinami, T.; Sakai, S. J . Chem. Soc., Perkin Trans. 1
1988, 1669.
(6) (a) Tori, M.; Sono, M.; Asakawa, Y. J . Chem. Soc., Perkin Trans.
1 1990, 2849. (b) Tori, M.; Sono, M.; Nishigaki, Y.; Nakashima, K.;
Asakawa, Y. J . Chem. Soc., Perkin Trans. 1 1991, 435.
(7) (a) Tori, M.; Sono, M.; Nakashima, K.; Nakaki, Y.; Asakawa, Y.
J . Chem. Soc., Perkin Trans. 1 1991, 447. (b) Tori, M.; Nakashima,
K.; Asakawa, Y.; Connolly, J . D.; Harrison, L. J .; Rycroft, D. S.; Singh,
J .; Woods, N. J . Chem. Soc. Perkin Trans. 1 1995, 593.
(8) Tori, M.; Ikawa, M.; Sagawa, T.; Furuta, H.; Sono, M.; Asakawa,
Y. Tetrahedron 1996, 52, 9999.
(9) (a) Tori, M.; Hasebe, T.; Asakawa, Y. J . Chem. Soc., Perkin Trans.
1 1989, 1552. (b) Tori, M.; Hasebe, T.; Asakawa, Y. Bull. Chem. Soc.
J pn. 1990, 63, 1706. (c) Tori, M.; Hasebe, T.; Asakawa, Y., Ogawa, K.;
Yoshimura, S. Bull. Chem. Soc. J pn. 1991, 64, 2303.
(10) (a) Fehlhaber, H. W.; Geipel, R.; Mercker, H. J .; Tschesche, R.;
Welmar, K. Chem. Ber. 1974, 107, 1720. (b) Cuevas, O.; Hanson, J . R.
Phytochemistry 1977, 16, 1061. (c) Peter, A.; Bradshaw, W.; Hanson,
J . R. J . Chem. Soc., Perkin Trans. 1 1980, 741. (d) Kimura, Y.; Fujioka,
H.; Nakajima, H.; Hamasaki, T.; Irie, M.; Fukuyama, K.; Isogai, A.
Agric. Biol. Chem. 1986, 50, 2123. (e) Kimura, Y.; Fujioka, H.;
Nakajima, H.; Hamasaki, K.; Isogai, A. Agric. Biol. Chem. 1988, 52,
1845. (f) Collado, I. G.; Hernandez-Galan, R.; Prieto, V.; Hanson, J .;
Rebordinos, L. G. Phytochemistry 1996, 41, 513.
(11) (a) Molander, G. A.; Etter, J . B. Tetrahedron Lett. 1984, 25,
3281. (b) Molander, G. A.; Etter, J . B. J . Org. Chem. 1986, 51, 1778.
(12) Lund, H.; Baizer, M. M. Organic Electrochemistry; 3rd ed.;
Marcel Dekker, Inc.: New York, 1991; p 453.
(13) Machrouhi, F.; Hamann, B.; Namy, J .-L.; Kagan, H. B. Synlett
1996, 633.
10.1021/jo9918450 CCC: $19.00 © 2000 American Chemical Society
Published on Web 04/25/2000

3100 J . Org. Chem., Vol. 65, No. 10, 2000
Sono et al.
Sch em e 2
additive) and -2.05 V (HMPA 4.0 equiv and more). We
are interested in the trend of diastereoselectivity of the
reductive cyclization reaction using SmI2 with various
additives.
Ta ble 1. Red u ctive Cycliza tion of 13a
We now report the results on the cyclization processes
of compounds having the general structure 3. Three
continuous stereocenters were newly constructed in the
reductive annulation. The cis arrangement for the hy-
droxyl group at C-4 and the juncture proton at C-3a is
predominant when the reaction is performed without any
additive or in the presence of HMPA. However, addition
of a proton source such as MeOH and/or HMPA dramati-
cally changes the product configuration in some cases.
The thermodynamic stability between cis and trans
hydrindanes has also been studied.
temp recovery (%) yield (%) [ratioa]
entry additives (equiv)
(°C)
of 13a
14:15a :19a
1
2
3
4
5
6
7
8
-
0
-78
0
12
33
-
-
-
9
77 [47:48:5]
38 [37:33:30]
87 [40:52:8]
78 [48:46:6]
96 [59:14:27]
63 [43:11:46]
61 [37:28:35]
93 [19:9:72]
-
Resu lts a n d Discu ssion
HMPA
HMPA
MeOH (2.0)
MeOH (2.0)
HMPA/MeOH (2.0)
-78
Syn th esis of Ald eh yd e 13a , 13b, 13c, a n d 13d . We
chose the simple model 13a , which was prepared from
1,6-hexanediol via aldehyde 7a (eight steps, 16% overall
yield) as summarized in Scheme 2.15 Compound 13b
having a â-methyl group was prepared from S-(-)-
citronellol via aldehyde 7b (eight steps, 28% overall yield)
in a similar way. The vinyl group substituted aldehydes
13c and 13d were derived from aldehydes 7c (15 steps,
5% overall yield) and 7d (15 steps, 1.3% overall yield),
respectively (Scheme 2), which were prepared from
S-(-)-citronellol.15
Cycliza t ion w it h Sm I2. Cyclization reactions were
performed in 0.1 mmol scale of the starting material. The
amount of SmI2 employed was 4.0 equiv for simple enone-
aldehyde 13a and 3.0 equiv for methylated enone-
aldehyde 13b. A large amount of SmI2 (6.0 equiv) was
used for vinylated enone-aldehyde 13c and 13d consider-
ing the reactivity of vinyl group. After the cyclizaton
reaction, the cyclyzation products were separated as a
mixture of diastereoisomers on silica gel column chro-
matography. Each diastereoisomer was purified by HPLC,
and the structure was determined by mainly using 2D-
NMR experiments. The yields were calculated from the
mixture of the cyclization products, and the ratios of
diastereoisomers were determined on GC-MS analysis
(identified on the retention time and the mass fragment
pattern).
0
-78
0
-
2
HMPA/MeOH (2.0) -78
a
Ratios were determined by GC analyses.
The results of the reductive cyclization of aldehyde 13a
are shown in Table 1. Without any additive at 0 °C,
alcohols 14a and 15a were the main products (entry 1).
Compound 14a was purified by recrystallization, but the
purification of 15a from 14a was not effective. Therefore,
the mixture was converted into the corresponding ac-
etates 22 and 23, which were separated by HPLC, and
their stereochemistries were also established by the
NOESY experiments.16 The hydroxyl group at C-4 and
the juncture proton at C-3a were cis to each other as
revealed by the NOESY spectrum.16 At -78 °C, the
recovery of 13a increased and the yield of the cyclization
products was as low as 38% (entry 2), and the addition
of HMPA forced an efficient reaction even at -78 °C
(entries 3, 4). However, if a proton source is present, the
yield of trans alcohol 19a 16 was raised (entries 5, 6). In
the presence of HMPA and MeOH at -78 °C, 19a was
the main product (entry 8). Although we do not postulate
equilibration in the reaction mixture, compound 15a was
subjected to isomerization conditions (K2CO3, MeOH),
and the equilibration ratio was found to be 14a :15a )
93:7 by GC.15 Under the equilibration conditions com-
(14) (a) Inanaga, J .; Ishikawa, M.; Yamaguchi, M. Chem. Lett. 1987,
1485. (b) Shabangi, M.; Flowers, R. A., II Tetrahedron Lett. 1997, 38,
1137. (c) Shabangi, M.; Sealy, J . M.; Fuchs, J . R.; Flowers, R. A., II.
Tetrahedron Lett. 1998, 39, 4429.
(16) The full structure was established by the combination of the
2D NMR and NOESY spectroscopy, and the summary of the observed
NOE’s are shown in the Supporting Information.
(15) The details are available as Supporting Information.

Cyclization into Hydrindanones Using SmI2
J . Org. Chem., Vol. 65, No. 10, 2000 3101
Sch em e 3
pound 19a afforded the isomer 18a (18a :19a ) 21:79),15
which was not isolated in this cyclization reaction.
Samarium(II) reduces the aldehyde, and the samarium-
coordinated species is sterically bulky. Thus, if a proton
source is not present, conformation 13a -A is predominant
and the cyclization occurs to lead to cis arrangement for
the hydroxyl group at C-4 and the juncture hydrogen at
C-3a as observed in compounds 14a and 15a (Scheme
3). The reduction of carbonyl groups by SmI2 proceeds
under equilibrium conditions, and the radical coupling
and the protonation of samarium enolates are competi-
tive. R,â-Unsaturated ketones are reduced more easily
than saturated aldehydes electrochemically. Therefore,
if a proton source is present, the reduction of the enone
moiety of 13a may be faster. After the enolate 13a -I is
protonated, the samarium(III) attached to the intermedi-
ate 13a -K may interact with the other carbonyl group to
provide the trans arrangement between the hydroxyl
group at C-4 and the juncture proton at C-3a. This
process may be slow, and therefore, in the presence of
the proton source, the trans product 19a predominates
at the lower temperature compared to the case at the
higher temperature, presumably because of the energetic
stability by coordination to both oxygen atoms.
Ta ble 2. Red u ctive Cycliza tion of 13b
additives
(equiv)
temp
(°C)
recovery (%) yield (%) [ratioa]
entry
of 13b
14b:24:15b:19b
1
2
3
4
-
0
0
0
11
0
28
18
60 [23:4:60:13]
81 [26:11:47:16]
56 [42:5:36:17]
57 [0:0:0:100]
HMPA
MeOH (2.0)
MeOH (25)
-78
a
Ratios were determined by GC analyses.
arrangement for the hydroxyl group at C-4 and the
juncture proton at C-3a is also seen in 14b16 and 15b,16
which were the major products (entries 1, 2). If MeOH
(2.0 equiv) was added at 0 °C, the trans-arranged product
19b16 was produced in 17% ratio (entry 3). When excess
MeOH (25 equiv) as a proton source was added at -78
°C, the stereoselectivity was changed to give 19b as the
sole product, although the total yield was as rather low
as 57% (entry 4). Compounds 19b and 15b were treated
with K2CO3 in MeOH to see if there are isomers in the
mixture. Compound 19b afforded the isomer 18b (19b:
18b ) 64:36),15 which was not produced in the cyclization
reaction. Compounds 15b and 14b were isomers to each
other and the ratio was 17:83.15 Compound 2415 was the
Formation of trans-fused 3,3-dimethylhydrindanes with
a cis relationship between the OH at C-4 and the proton
at C-3a (e.g., 14a ) should be accessible in yields of
approximately 80% by cyclization with Sml2 (4 equiv) and
HMPA (5 equiv) at 0 °C followed by equilibration under
basic conditions (K2CO3, MeOH) and separation from
their cis-fused analogues (e.g., 15a ) and other diastere-
oisomers present in minute quantities (e.g., 18a and 19a ,
less than 8%).
The reaction of aldehyde 13b was next investigated
and the results are summarized in Table 2. The cis

3102 J . Org. Chem., Vol. 65, No. 10, 2000
Sono et al.
Ta ble 4. Red u ctive Cycliza tion of 13d
Ta ble 3. Red u ctive Cycliza tion of 13c
additives
(equiv)
temp recovery (%)
yield (%) [ratioa]
14c:15c:16c:18c:19c
additives
(equiv)
temp recovery (%)
yield (%) [ratioa]
16d :17d :19d :20d :25
entry
(°C)
of 13c
entry
(°C)
of 13d
1
2
3
4
5
6
-
0
-78
0
10
4
-
6
-
58
55 [84:10:6:0:0]
66 [85:15:0:0:0]
73 [94:6:0:0:0]
59 [91:4:5:0:0]
70 [31:2:5:6:56]
30 [17:0:4:3:76]
1
2
3
4
5
6
-
0
-78
0
-
-
-
-
-
3
68 [58:19:16:7:0]
86 [53:16:21:10:0]
52 [30:9:26:21:14]
76 [31:8:32:14:15]
83 [49:16:20:15:0]
76 [43:12:38:7:0]
-
-
HMPA
HMPA
MeOH (25)
HMPA
HMPA
MeOH (25)
-78
-78
0
0
MeOH (25) -78
MeOH (25) -78
a
a
Ratios were determined by GC analyses.
Ratios were determined by GC analyses.
over-reduction product, whose structure was confirmed
by the NaBH4 reduction of 14b.
Finally, the diastereoisomer 13d was subjected to
reaction with SmI2. As shown in Table 4, under any
reaction conditions almost the same stereoselectivity was
obtained regardless of the presence or absence of a proton
source. Thus, compounds 16d 16 and/or 19d 16 were ob-
tained as major products. The structures of 17d and 20d
were completely established by X-ray crystallographic
analyses,13 and the others were determined by the
NOESY spectra.16
These results may be due to the fact that aldehyde 13d
is conformationally inflexible, and the difference in the
conditions did not affect the results (Scheme 3). Actually,
there is no product from conformation 13d -A, which was
predominant in three other cases. Only in this case both
the carbonyl groups reacted leading to diol 25.16 This also
shows that the reaction route is diverse in this case,
presumably because the stability of each intermediate
is almost the same as others.
As shown in Scheme 3, in case no additive is present
or only HMPA is present, the samarium-coordinated
species is much bulkier to adopt the conformation outside
the cyclopentane ring to lead to cis stereochemistry for
the hydroxyl group at C-4 and the juncture proton at
C-3a. The conformation 13b-A is the most stable due to
the equatorial orientation of the methyl substituent.
When excess MeOH was added, the reduction of the
enone system may be faster, and consequently, interme-
diate 13b-K was formed to change the conformation such
that the same samarium(III) as a Lewis acid coordinates
both the carbonyl groups to lead to trans stereochemistry
as in the case of 19b. Therefore, intermediate 13b-J or
its further reduced species 13b-K may play an important
role under these reaction conditions. These results were
almost in accordance with those shown in Table 1.
The vinyl group substituted aldehyde 13c was next
studied (Table 3). Compound 14c was the major product
in entries 1-4, the structure being established by the
X-ray analysis,17 while by addition of excess MeOH (25
equiv) as a proton source, compound 19c16 became the
major product in entries 5 and 6. Compound 18c, whose
structure was established by X-ray crystallography,13 was
also obtained in minute quantity because of the confor-
mational unstability.
The same mechanism as above can be applied as
follows. When no additive is present or only HMPA is
present, the samarium-coordinated species is much bulkier
to adopt the conformation such that this part protrudes
outside the cyclopentane ring to lead to cis stereochem-
istry for the hydroxyl group at C-4 and the juncture
proton at C-3a (Scheme 3). Thus, conformation 13c-A is
more stable due to the methyl and vinyl substitutions.
When MeOH was added, the reduction of the enone
system may be faster to change the conformation to lead
to trans stereochemistry as in the case of 19c through
13c-J . The cis product 15c16 and the cis but reversed-
face selected compound 16c16 were produced in minute
amounts.
Con clu sion
These results show that 6-endo-Trig type reactions may
smoothly proceed to cyclize into hydrindanones by the
action of SmI2, depending on the predominant conforma-
tion of the substrate. Unfortunately, the configuration
at the C-4 position of compound 19d differs from that of
botrydial (1). However, compound 14c must be a good
candidate for construction of botrydial, because the C-7
position could be inverted at a later stage. Therefore, we
are currently working along this line to prepare the
hydrindane system.
Exp er im en ta l Section
Gen er a l. Tetrahydrofuran (THF) was distilled from LiAlH4
under Ar and then redistilled from sodium-benzophenone
ketyl prior to use. Samarium metal was purchased from Strem,
Inc. and stored under Ar. Iodine was purchased from Aldrich.
HMPA was purchased from Aldrich, distilled from CaH2, and
stored over 4 Å molecular sieves under Ar. t-BuOH was
purchased from Aldrich and was distilled from magnesium and
stored over 4 Å molecular sieves under Ar. Commercially
available reagents were used without further purification.
(17) The structure was analyzed by X-ray crystallography. The X-ray
data are available in the Supporting Information.

Cyclization into Hydrindanones Using SmI2
J . Org. Chem., Vol. 65, No. 10, 2000 3103
Standard benchtop techniques were employed for handling air-
sensitive reagents, and all reactions were performed under Ar.
P r ep a r a tion of th e Sm I2 Solu tion . Samarium metal
(496.3 mg, 3.3 mmol) was added under a flow of Ar to an oven-
dried, round-bottomed two-necked flask containing a magnetic
stirring bar and septum inlet. Diiodomethane (803.5 mg, 3.0
mmol) was added to a vigorously stirred suspension of sa-
marium metal in THF (30 mL). The mixture was stirred
vigorously for 3 h at room temperature. The resultant deep
blue-green solution was used directly to effect the following
reactions.
Gen er a l P r oced u r e for t h e Syn t h esis of H yd r in -
d a n on es. A solution of SmI2 in THF was cooled to a fixed
temperature, and an enone-aldehyde and an additive in THF
were added dropwise slowly. The mixture was stirred at the
temperature for 30 min. The reaction was quenched with a
saturated aq solution of Rochelle’s salt. Organic materials were
extracted with diethyl ether, washed with brine, and dried over
anhydrous magnesium sulfate. The products were purified by
silica gel flash chromatography and HPLC. Gas chromato-
graphic analyses were carried out on a capillary column [HP-
20M 25 m × 0.2 mm × 0.2 µm, 50-100 °C (20 °C/min) followed
by 100-200 °C (5 °C/min)].
Sm I2 Red u ction of 13a . Entry 1: A solution of 13a (20
mg, 0.11 mmol) in THF (0.8 mL) was treated with SmI2 (0.1
M, 4.4 mL, 0.44 mmol) at 0 °C according to the general
procedure to afford 13a (2.3 mg) and a mixture (15.6 mg) of
14a , 15a , and 19a after flash chromatography (SiO2, 0-40%
AcOEt/hexane).
Entry 2: A solution of 13a (20 mg, 0.11 mmol) in THF (0.8
mL) was treated with SmI2 (0.1 M, 4.4 mL, 0.44 mmol) at -78
°C according to the general procedure to afford 13a (6.5 mg)
and a mixture (7.7 mg) of 14a , 15a , and 19a after flash
chromatography (SiO2, 0-40% AcOEt/hexane).
13.7, 9.9 Hz), 1.83-1.88 (1H, m), 1.95 (1H, dddd, J ) 13.7,
11.3, 3.3, 1.4 Hz), 1.99-2.06 (2H, m), 2.03 (1H, brd, J ) 19.2
Hz), 2.19 (1H, dd, J ) 19.2, 1.4 Hz), 3.74 (1H, tt, J ) 9.9, 4.7
Hz); 13C NMR (50 MHz, CDCl3) δ 22.3 (CH3), 24.5 (CH2), 24.7
(CH2), 30.8 (CH3), 36.2 (C), 36.8 (CH2), 51.7 (CH), 53.8 (CH2),
57.8 (CH), 72.7 (CH), 217.2 (C); MS (EI) m/z 182 (M+), (base);
HRMS (EI) Calcd for C11H18O2 182.1307. Found: 182.1279
(M+).
(3a R,4S,7a S)-4-Hyd r oxy-3,3-d im eth ylp er h yd r o-1-in d e-
n on e (15a ): (mixture with 14a , 14a :15a ) 1:2). Retention
time on GC: 24.4 min; 1H NMR (200 MHz, CDCl3) (major
peak) δ 1.00-1.40 (3H, m), 1.19 (3H, s), 1.33 (3H, s), 1.51-
1.64 (1H, m), 1.80-2.20 (4H, m), 2.13 (2H, br s), 2.78 (1H, brt,
J ) 7.4 Hz), 3.43 (1H, td, J ) 10.5, 4.2 Hz).
(3a R,4R,7a S)-4-Hyd r oxy-3,3-d im eth ylp er h yd r o-1-in d e-
n on e (19a ). Retention time on GC: 27.2 min; mp 127-129
°C (hexane-AcOEt); FTIR: 3480, 1720 cm-1 1H NMR (600
;
MHz, CDCl3) δ 0.83 (1H, br s), 1.17 (3H, s), 1.29-1.35 (1H,
m), 1.32 (3H, s), 1.42-1.46 (1H, m), 1.47 (1H, ddd, J ) 13.5,
3.8, 1.6 Hz), 1.55-1.64 (1H, m), 1.68-1.74 (1H, m), 1.75 (1H,
dd, J ) 7.2, 2.7 Hz), 1.98 (1H, dt, J ) 18.4, 1.4 Hz), 2.20-2.25
(1H, m), 2.40 (1H, dd, J ) 18.4, 0.5 Hz), 2.56 (1H, brt, J ) 7.2
Hz), 4.21 (1H, br s); 13C NMR (50 MHz, CDCl3) δ 15.1 (CH2),
20.7 (CH2), 24.2 (CH3), 31.4 (CH3), 32.5 (CH2), 35.8 (C), 45.5
(CH), 50.0 (CH), 51.3 (CH2), 66.6 (CH), 207.7 (C); MS (EI) m/z
182 (M+), 122 (base); HRMS (EI) Calcd for C11H18O2 182.1307.
Found: 182.1258 (M+).
Acetyla tion of 14a a n d 15a . The mixture (7.3 mg) of 14a
and 15a (14a :15a ) 1:2)were acetylated using acetic anhy-
dride, DMAP, and pyridine to afford 22 (1.7 mg) and 23 (5.0
mg) after flash chromatography (SiO2, 15% AcOEt/hexane) and
HPLC (Nucleosil 50-5, 4.6φ × 250 mm, 10% AcOEt/hexane).
(3a R,4S,7a R)-4-Acetoxy-3,3-d im eth ylp er h yd r o-1-in d e-
1
n on e (22). FTIR: 1640 cm-1; H NMR (600 MHz, CDCl3) δ
Entry 3: A solution of 13a (20 mg, 0.11 mmol) and HMPA
(0.1 mL, 0.55 mmol) in THF (0.8 mL) was treated with SmI2
(0.1 M, 4.4 mL, 0.44 mmol) at 0 °C according to the general
procedure to afford a mixture (17.6 mg) of 14a , 15a , and 19a
after flash chromatography (SiO2, 0-40% AcOEt/hexane).
Entry 4: A solution of 13a (20 mg, 0.11 mmol) and HMPA
(0.1 mL, 0.55 mmol) in THF (0.8 mL) was treated with SmI2
(0.1 M, 4.4 mL, 0.44 mmol) at -78 °C according to the general
procedure to afford a mixture (15.8 mg) of 14a , 15a , and 19a
after flash chromatography (SiO2, 0-40% AcOEt/hexane).
Entry 5: A solution of 13a (20 mg, 0.11 mmol) and MeOH
(7.1 mg, 0.22 mmol) in THF (0.8 mL) was treated with SmI2
(0.1 M, 4.4 mL, 0.44 mmol) at 0 °C according to the general
procedure to afford a mixture (19.4 mg) of 14a , 15a , and 19a
after flash chromatography (SiO2, 0-40% AcOEt/hexane).
Entry 6: A solution of 13a (20 mg, 0.11 mmol) and MeOH
(7.1 mg, 0.22 mmol) in THF (0.8 mL) was treated with SmI2
(0.1 M, 4.4 mL, 0.44 mmol) at -78 °C according to the general
procedure to afford 13a (1.8 mg) and a mixture (12.7 mg) of
14a , 15a , and 19a after flash chromatography (SiO2, 0-40%
AcOEt/hexane).
Entry 7: A solution of 13a (20 mg, 0.11 mmol), HMPA (0.1
mL, 0.55 mmol), and MeOH (7.1 mg, 0.22 mmol) in THF (0.8
mL) was treated with SmI2 (0.1 M, 4.4 mL, 0.44 mmol) at 0
°C according to the general procedure to afford a mixture (12.3
mg) of 14a , 15a , and 19a after flash chromatography (SiO2,
0-40% AcOEt/hexane).
Entry 8: A solution of 13a (20 mg, 0.11 mmol), HMPA (0.1
mL, 0.55 mmol), and MeOH (7.1 mg, 0.22 mmol) in THF (0.8
mL) was treated with SmI2 (0.1 M, 4.4 mL, 0.44 mmol) at -78
°C according to the general procedure to afford 13a (0.3 mg)
and a mixture (18.8 mg) of 14a , 15a , and 19a after flash
chromatography (SiO2, 0-40% AcOEt/hexane).
1.05 (3H, s), 1.08-1.12 (1H, m), 1.23 (3H, s), 1.20-1.28 (1H,
m), 1.34 (1H, qt, J ) 13.7, 3.8 Hz), 1.64 (1H, dd, J ) 13.7,
10.4 Hz), 1.86 (1H, dtt, J ) 13.7, 3.8, 2.7 Hz), 2.00-2.14 (3H,
m), 2.04 (1H, d, J ) 19.2 Hz), 2.07 (3H, s), 2.20 (1H, dd, J )
19.2, 1.4 Hz), 4.91 (1H, td, J ) 10.4, 4.4 Hz); MS (EI) m/z 224
(M+), 164 (base); HRMS (EI) Calcd for C13H20O3 224.1412.
Found: 224.1385 (M+).
(3a R,4S,7a S)-4-Acetoxy-3, 3-d im eth ylp er h yd r o-1-in d e-
1
n on e (23). FTIR: 1740 cm-1; H NMR (600 MHz, CDCl3) δ
1.07-1.21 (2H, m), 1.09 (3H, s), 1.17 (3H, s), 1.39 (1H, dddd,
J ) 13.7, 12.6, 6.5, 4.4 Hz), 1.53-1.59 (1H, m), 1.94-1.98 (1H,
m), 2.04 (3H, s), 2.09-2.17 (4H, m), 2.84 (1H, brt, J ) 6.5 Hz),
4.57 (1H, td, J ) 10.2, 4.4 Hz); MS (EI) m/z 224 (M+), 164
(base); HRMS (EI) Calcd for
C13H20O3 224.1412. Found:
224.1417 (M+).
Isom er iza tion of 14a a n d 15a . K2CO3(12 mg) was added
to a MeOH solution of 14a and 15a (14a :15a ) 1:1, 1.9 mg,
0.01 mmol), and the mixture was stirred vigorously and
refluxed for 19 h. The organic materials were extracted with
diethyl ether, washed with brine, and dried over anhydrous
magnesium sulfate. After filtration and evaporation of solvent
in vacuo, the mixture (1.8 mg) of 14a and 15a (93:7 on GC)
was prepared.
Isom er iza tion of 19a . K2CO3 (12 mg) was added to a
MeOH (3 mL) solution of 19a (2.1 mg, 0.012 mmol), and the
mixture was stirred vigorously and refluxed for 24 h. The
organic materials were extracted with diethyl ether, washed
with brine, and dried over anhydrous magnesium sulfate. After
filtration and evaporation of solvent in vacuo, the mixture (1.9
mg) of 18a and 19a (21:79) was prepared.
Sm I2 Red u ction of 13b. Entry 1: A solution of13b (20 mg,
0.1 mmol) in THF (1.0 mL) was treated with SmI2 (0.1 M, 3.0
mL, 0.30 mmol) at 0 °C according to the general procedure to
afford 13b (2.2 mg) and a mixture (12.1 mg) of 14b, 15b, 19b,
and 24 after flash chromatography (SiO2, 0-40% AcOEt/
hexane).
Entry 2: A solution of 13b (20 mg, 0.1 mmol) and HMPA
(0.09 mL, 0.50 mmol) in THF (1.0 mL) was treated with SmI2
(0.1 M, 3.0 mL, 0.30 mmol) at 0 °C according to the general
procedure to afford a mixture (16.4 mg) of 14b, 15b, 19b, and
24 after flash chromatography (SiO2, 0-40% AcOEt/hexane).
14a and 19a were purified on HPLC (Nucleosil 50-5, 10φ
× 250 mm, 30% AcOEt/hexane) and recrystalyzation (hexane-
AcOEt). 15a could not be separated from 14a (14a :15a ) 1:2).
(3a R,4S,7a R)-4-Hyd r oxy-3,3-d im eth ylp er h yd r o-1-in d e-
n on e (14a ). Retention time on GC: 24.7 min; mp 156-159
°C (hexane-AcOEt); FTIR: 3430, 1720 cm-1 1H NMR (600
;
MHz, CDCl3) δ 1.02-1.10 (1H, m), 1.15 (3H, s), 1.21-1.34 (2H,
m), 1.35 (3H, s), 1.37(1H, brd, J ) 4.9 Hz), 1.38 (1H, dd, J )

3104 J . Org. Chem., Vol. 65, No. 10, 2000
Sono et al.
Entry 3: A solution of 13b (20 mg, 0.1 mmol) and MeOH
(6.5 mg, 0.2 mmol) in THF (1.0 mL) was treated with SmI2
(0.1 M, 3.0 mL, 0.30 mmol) at 0 °C according to the general
procedure to afford 13b (4.6 mg) and a mixture (11.3 mg) of
14b, 15b, 19b, and 24 after flash chromatography (SiO2,
0-40% AcOEt/hexane).
Entry 4: A solution of 13b (20 mg, 0.1 mmol) and MeOH
(79.1 mg, 2.5 mmol) in THF (1.0 mL) was treated with SmI2
(0.1 M, 3.0 mL, 0.30 mmol) at -78 °C according to the general
procedure to afford 13b (3.5 mg) and 19b (11.5 mg) after flash
chromatography (SiO2, 0-40% AcOEt/hexane).
mg) of 18b and 19b (36:64) was prepared. 18b and 19b were
purified by flash chromatography (SiO2, 0-40% AcOEt/hex-
ane).
(3a R,4R,6S,7a R)-4-Hyd r oxy-3,3,6-t r im et h ylp er h yd r o-
1-in d en on e (18b). mp 90-92 °C (hexane-CHCl3); [R]D19 -160°
1
(c 0.64, CHCl3); FTIR: 3500, 1730 cm-1; H NMR (600 MHz,
CDCl3) δ 0.82 (1H, q, J ) 11.6 Hz), 0.94 (3H, d, J ) 6.6 Hz),
1.13 (1H, ddd, J ) 13.7, 12.6, 2.5 Hz), 1.16 (3H, s), 1.21 (3H,
s), 1.28 (1H, br s), 1.38 (1H, dd, J ) 14.3, 1.5 Hz), 1.80 (1H,
dtd, J ) 14.3, 3.6, 1.6 Hz), 1.84-1.93 (1H, m), 2.03 (1H, d, J
) 18.6 Hz), 2.14 (1H, dtd, J ) 12.9, 3.8, 1.6 Hz), 2.18 (1H, dd,
J ) 18.6, 1.4 Hz), 2.60 (1H, dddd, J ) 14.3, 11.6, 3.8, 1.5 Hz),
4.43 (1H, s); 13C NMR (50 MHz, CDCl3) δ 21.8 (CH3), 24.6
(CH3), 26.2 (CH), 28.6 (CH3), 34.7 (CH2), 36.6 (C), 43.8 (CH2),
45.0 (CH), 55.3 (CH2), 55.5 (CH), 65.8 (CH), 218.7 (C); MS (EI)
m/z 196 (M+), 163 (base); HRMS (EI) Calcd for C12H20O2
196.1463. Found 196.1460 (M+).
Isom er iza tion of 14b. K2CO3 (12 mg) was added to a
MeOH (3 mL) solution of 14b (5.5 mg, 0.01 mmol), and the
mixture was stirred vigorously and refluxed for 24 h. The
organic materials were extracted with diethyl ether, washed
with brine, and dried over anhydrous magnesium sulfate. After
filtration and evaporation of solvent in vacuo, the mixture (4.5
mg) of 14b and 15b (83:17) was prepared.
Sm I2 Red u ction of 13c. Entry 1: A solution of 13c (20
mg, 0.09 mmol) in THF (1.0 mL) was treated with SmI2 (0.1
M, 5.4 mL, 0.54 mmol) at 0 °C according to the general
procedure to afford 13c (2.0 mg) and a mixture (11.1 mg) of
14c, 15c, and 16c after flash chromatography (SiO2, 0-40%
AcOEt/hexane).
Entry 2: A solution of 13c (20 mg, 0.09 mmol) in THF (1.0
mL) was treated with SmI2 (0.1 M, 5.4 mL, 0.54 mmol) at -78
°C according to the general procedure to afford 13c (0.9 mg)
and a mixture (13.3 mg) of 14c and 15c after flash chroma-
tography (SiO2, 0-40% AcOEt/hexane).
Entry 3: A solution of 13c (20 mg, 0.09 mmol) and HMPA
(0.08 mL, 0.45 mmol) in THF (1.0 mL) was treated with SmI2
(0.1 M, 5.4 mL, 0.54 mmol) at 0 °C according to the general
procedure to afford a mixture (14.7 mg) of 14c and 15c after
flash chromatography (SiO2, 0-40% AcOEt/hexane).
Entry 4: A solution of 13c (20 mg, 0.09 mmol) and HMPA
(0.08 mL, 0.45 mmol) in THF (1.0 mL) was treated with SmI2
(0.1 M, 5.4 mL, 0.54 mmol) at -78 °C according to the general
procedure to afford 13c (1.1 mg) and a mixture (11.9 mg) of
14c, 15c, and 16c after flash chromatography (SiO2, 0-40%
AcOEt/hexane).
Entry 5: A solution of 13c (20 mg, 0.09 mmol) and MeOH
(79.1 mg, 2.47 mmol) in THF (1.0 mL) was treated with SmI2
(0.1 M, 5.4 mL, 0.54 mmol) at 0 °C according to the general
procedure to afford a mixture (14.1 mg) of 14c, 15c, 16c, 18c,
and 19c after flash chromatography (SiO2, 0-40% AcOEt/
hexane).
The mixture of 14b , 15b , 19b , and 24 was separated by
HPLC (Nucleosil 50-5, 4.6φx250 mm, 30% AcOEt/hexane) and
(Cosmosil 50-5, 4.6φ × 250 mm, 40% MeOH/H2O).
(3a R,4S,6S,7a R)-4-Hyd r oxy-3,3,6-tr im eth ylp er h yd r o-1-
in d en on e (14b). Retention time on GC: 25.3 min; mp 132-
134 °C (hexane-CHCl3); [R]19 -78° (c 0.84, CHCl3); FTIR:
D
3450, 1720 cm-1; 1H NMR (600 MHz, CDCl3) δ 0.79 (1H, br q,
J ) 12.1 Hz), 0.98 (3H, d, J ) 6.6 Hz), 1.01 (1H, td, J ) 12.4,
10.4 Hz), 1.14 (3H, s), 1.34 (1H, br s), 1.34 (3H, s), 1.36 (1H,
dd, J ) 13.7, 10.4 Hz), 1.49-1.58 (1H, m), 1.97-2.05 (3H, m),
2.05 (1H, dd, J ) 19.2, 0.5 Hz), 2.21 (1H, dd, J ) 19.2, 1.4
Hz), 3.76 (1H, td, J ) 10.4, 4.1 Hz); 13C NMR (50 MHz, CDCl3)
δ 21.6 (CH3), 22.3 (CH3), 30.8 (CH3), 31.7 (CH), 33.1 (CH2),
36.0 (C), 45.8 (CH2), 51.5 (CH), 54.3 (CH2), 57.7 (CH), 72.0
(CH), 216.7 (C); MS (EI) m/z 196 (M+), 111 (base); HRMS (EI)
Calcd for C12H20O2 196.1463. Found 196.1467 (M+).
(3a R,4S,6S,7a S)-4-Hyd r oxy-3,3,6-tr im eth ylp er h yd r o-1-
in d en on e (15b). Retention time on GC: 24.4 min; mp 91-
93 °C (hexane-CHCl3); [R]21 +106° (c 1.6, CHCl3); FTIR:
D
3450, 1740 cm-1; H NMR (600 MHz, CDCl3) δ 0.93 (3H, d, J
1
) 6.6 Hz), 0.93-1.03 (2H, m), 1.18 (3H, s), 1.20-1.26 (1H, m),
1.34 (3H, s), 1.59 (1H, br s), 1.80 (1H, dd, J ) 10.0, 7.8 Hz),
1.83 (1H,ddt, J ) 12.4, 4.7, 2.2 Hz), 2.11 (2H, s), 2.15 (1H,
ddt, J ) 13.7, 3.8, 1.9 Hz), 2.80 (1H, td, J ) 7.8, 0.8 Hz), 3.45
(1H, td, J ) 10.0, 4.0 Hz); 13C NMR (50 MHz, CDCl3) δ 21.9
(CH3), 27.0 (CH3), 27.6 (CH), 30.0 (CH3), 31.2 (CH2), 36.2 (C),
43.1 (CH2), 49.7 (CH), 50.4 (CH2), 53.4 (CH), 69.3 (CH), 218.9
(C); MS (EI) m/z 196 (M+), 111 (base); HRMS (EI) Calcd for
C
12H20O2 196.1463. Found 196.1469 (M+).
(3a R,4R,6S,7a S)-4-Hyd r oxy-3,3,6-tr im eth ylp er h yd r o-1-
in d en on e (19b). Retention time on GC: 26.8 min; mp 128-
130 °C (hexane-CHCl3); [R]19D +63° (c 1.0, CHCl3); FTIR: 3400,
1
1725 cm-1; H NMR (600 MHz, CDCl3) δ 0.90 (3H, d, J ) 6.6
Hz), 0.99 (1H, br s), 1.02 (1H, ddd, J ) 14.0, 12.4, 6.9 Hz),
1.13 (1H, ddd, J ) 13.7, 12.9, 1.6 Hz), 1.17 (3H, s), 1.33 (3H,
s), 1.67-1.73 (2H, m), 1.75-1.83 (1H, m), 1.97 (1H, dt, J )
18.0, 1.1 Hz), 2.26 (1H, ddt, J ) 14.0, 4.7, 1.6 Hz), 2.40 (1H, d,
J ) 18.0 Hz), 2.60 (1H, brt, J ) 7.4 Hz), 4.21 (1H, br s); 13C
NMR (50 MHz, CDCl3) δ 21.0 (CH), 22.2 (CH3), 24.3 (CH3),
29.7 (CH2), 31.5 (CH3), 35.6 (C), 41.4 (CH2), 46.3 (CH), 49.9
(CH), 51.5 (CH2), 67.4 (CH), 218.5 (C); MS (EI) m/z 196 (M+),
136 (base); HRMS (EI) Calcd for C12H20O2 196.1463. Found
196.1444 (M+).
Entry 6: A solution of 13c (20 mg, 0.09 mmol) and MeOH
(79.1 mg, 2.47 mmol) in THF (1.0 mL) was treated with SmI2
(0.1 M, 5.4 mL, 0.54 mmol) at -78 °C according to the general
procedure to afford 13c (11.6 mg) and a mixture (6.1 mg) of
14c, 16c, 18c, and 19c after flash chromatography (SiO2,
0-40% AcOEt/hexane).
(1R,3a R,4S,6S,7a R)-1,4-Dih yd r oxy-3,3,6-tr im eth ylp er -
h yd r oin d en e (24). Retention time on GC: 27.0 min; mp 150-
152 °C (hexane-CHCl3); [R]19 -13° (c 0.96, CHCl3); FTIR:
D
3300 cm-1; 1H NMR (600 MHz, CDCl3) δ 0.67 (1H, q, J ) 11.8
Hz), 0.91 (1H, td, J ) 12.4, 10.4 Hz), 0.96 (3H, d, J ) 6.6 Hz),
0.98 (1H, dd, J ) 12.4, 10.4 Hz), 1.11 (3H, s), 1.17 (3H, s),
1.37 (1H, dd, J ) 13.6, 7.4 Hz), 1.45-1.53 (2H, m), 1.64 (2H,
br s), 1.89-1.95 (2H, m), 1.97 (1H, dd, J ) 13.6, 9.0 Hz), 3.66
(1H, td, J ) 10.4, 4.4 Hz), 3.80 (1H, td, J ) 9.0, 7.4 Hz); 13C
NMR (50 MHz, CDCl3) δ 21.9 (CH3), 25.8 (CH3), 31.6 (CH),
32.5 (CH3), 37.4 (C), 37.5 (CH2), 45.6 (CH2), 49.7 (CH), 51.0
(CH2), 58.3 (CH), 71.6 (CH), 76.3 (CH); MS (EI) m/z 198 (M+),
125 (base); HRMS (EI) Calcd for C12H22O2 198.1620. Found
198.1637 (M+).
Isom er iza tion of 19b. K2CO3 (12 mg) was added to a
MeOH (3 mL) solution of 19b (21.0 mg, 0.012 mmol), and the
mixture was stirred vigorously and refluxed for 19 h. The
organic materials were extracted with diethyl ether, washed
with brine, and dried over anhydrous magnesium sulfate. After
filtration and evaporation of solvent in vacuo, the mixture (20.9
The mixture of 14c, 15c, 16c, 18c, and 19c was separated
by HPLC (Develosil 60-10, 20φx250 mm, 30% AcOEt/hexane)
and recrystalyzation.
(3aR,4S,6R,7R,7aR)-4-Hydr oxy-3,3,6-tr im eth yl-7-vin ylp-
er h yd r o-1-in d en on e (14c). Retention time on GC: 31.8 min;
mp 113-116 °C (hexane-CHCl3); [R]21 -107° (c 1.6, CHCl3);
D
FTIR: 3450, 1720, 1640 cm-1; 1H NMR (600 MHz, C6D6) δ 0.75
(3H, d, J ) 6.9 Hz), 0.80 (3H, s), 0.89 (1H, br s), 0.99 (1H, td,
J ) 12.6, 10.7 Hz), 1.14-1.20 (1H, m), 1.20 (3H, s), 1.33 (1H,
dt, J ) 10.2, 4.2 Hz), 1.53 (1H, dd, J ) 14.3, 10.2 Hz), 1.72
(1H, dd, J ) 18.3, 0.5 Hz), 1.72 (1H, dd, J ) 10.2, 1.1 Hz),
1.91 (1H, dd, J ) 18.3, 1.4 Hz), 2.63 (1H, dt, J ) 9.3, 4.1 Hz),
3.25 (1H, td, J ) 10.2, 4.2 Hz), 5.14 (1H, dd, J ) 10.2, 4.2 Hz),
5.33 (1H, dd, J ) 17.0, 2.5 Hz), 5.51 (1H, dt, J ) 17.0, 10.2
Hz); 13C NMR (100 MHz, CDCl3) δ 19.1 (CH3), 21.7 (CH3), 30.6
(CH3), 34.8 (CH), 36.0 (C), 41.1 (CH2), 43.0 (CH), 41.1 (CH2),
43.0 (CH), 51.3 (CH), 55.3 (CH2), 55.7 (CH), 72.4 (CH), 120.0

Cyclization into Hydrindanones Using SmI2
J . Org. Chem., Vol. 65, No. 10, 2000 3105
(CH2), 132.4 (CH), 215.3 (C); MS (EI) m/z 222 (M+), 121 (base);
HRMS (EI) Calcd for C14H22O2 222.1620. Found 222.1644 (M+).
(3aR,4S,6R,7R,7aS)-4-Hydr oxy-3,3,6-tr im eth yl-7-vin ylp-
er h yd r o-1-in d en on e (15c). Retention time on GC: 28.8 min;
(0.1 M, 5.4 mL, 0.54 mmol) at 0 °C according to the general
procedure to afford a mixture (10.5 mg) of 16d , 17d , 19d , 20d ,
and 25 after flash chromatography (SiO2, 0-40% AcOEt/
hexane).
Entry 4: A solution of 13d (20 mg, 0.09 mmol) and HMPA
(0.08 mL, 0.45 mmol) in THF (1.0 mL) was treated with SmI2
(0.1 M, 5.4 mL, 0.54 mmol) at -78 °C according to the general
procedure to afford a mixture (15.3 mg) of 16d , 17d , 19d , 20d ,
and 25 after flash chromatography (SiO2, 0-40% AcOEt/
hexane).
Entry 5: A solution of 13d (20 mg, 0.09 mmol) and MeOH
(79.1 mg, 2.47 mmol) in THF (1.0 mL) was treated with SmI2
(0.1 M, 5.4 mL, 0.54 mmol) at 0 °C according to the general
procedure to afford a mixture (16.8 mg) of 16d , 17d , 19d , and
20d after flash chromatography (SiO2, 0-40% AcOEt/hexane).
Entry 6: A solution of 13d (20 mg, 0.09 mmol) and MeOH
(79.1 mg, 2.47 mmol) in THF (1.0 mL) was treated with SmI2
(0.1 M, 5.4 mL, 0.54 mmol) at -78 °C according to the general
procedure to afford 13d (0.6 mg) and a mixture (15.4 mg) of
16d , 17d , 19d , and 20d after flash chromatography (SiO2,
0-40% AcOEt/hexane).
[R]20 +129° (c 1.2, CHCl3); FTIR: 3400, 1740, 1640 cm-1; 1H
D
NMR (600 MHz, CDCl3) δ 0.87 (3H, d, J ) 6.9 Hz), 1.18 (3H,
s), 1.27 (1H, td, J ) 12.9, 11.0 Hz), 1.34 (3H, s), 1.39-1.46
(1H, m), 1.54 (1H, br s), 1.56-1.60 (1H, m), 1.93 (1H, dd, J )
10.0, 8.2 Hz), 2.12 (2H, s), 2.75 (1H, dd, J ) 8.2, 0.8 Hz), 2.79
(1H, dd, J ) 9.1, 4.4 Hz), 3.47 (1H, td, J ) 11.0, 5.2 Hz), 5.10-
5.13 (2H, m), 5.89 (1H, ddd, J ) 15.7, 11.5, 8.8 Hz); 13C NMR
(50 MHz, CDCl3) δ 19.3 (CH3), 27.0 (CH3), 29.9 (CH), 29.9
(CH3), 36.2 (C), 38.0 (CH2), 41.5 (CH), 50.1 (CH2), 51.1 (CH),
55.3 (CH), 69.6 (CH), 116.8 (CH2), 136.3 (CH), 217.5 (C); MS
(EI) m/z 222 (M+), 121 (base); HRMS (EI) Calcd for C14H22O2
222.1620. Found 222.1622 (M+).
(3aS,4R,6R,7R,7aR)-4-Hydr oxy-3,3,6-tr im eth yl-7-vin ylp-
er h yd r o-1-in d en on e (16c). Retention time on GC: 32.0 min;
[R]20 -71° (c 0.97, CHCl3); FTIR: 3450, 1730, 1640 cm-1; 1H
D
NMR (600 MHz, CDCl3) δ 0.88 (3H, d, J ) 7.1 Hz), 1.21 (3H,
s), 1.23 (3H, s), 1.41 (1H, br s), 1.54 (1H, ddd, J ) 13.7, 7.4,
4.1 Hz), 1.69 (1H, ddd, J ) 13.7, 11.5, 4.1 Hz), 1.78-1.83 (1H,
m), 2.06 (1H, dd, J ) 9.1, 6.5 Hz), 2.16 (1H, dd, J ) 18.7, 0.5
Hz), 2.23 (1H, d, J ) 18.7 Hz), 2.31 (1H, q, J ) 6.6 Hz), 2.57
(1H, dd, J ) 9.1, 6.6 Hz), 3.95 (1H, dt, J ) 6.5, 4.1 Hz), 5.01
(1H, dt, J ) 17.1, 1.4 Hz), 5.10 (1H, ddd, J ) 10.2, 1.4, 0.8
Hz), 5.76 (1H, ddd, J ) 17.1, 10.2, 7.7 Hz); 13C NMR (50 MHz,
CDCl3) δ 20.0 (CH3), 26.7 (CH3), 29.8 (CH3), 30.7 (CH), 36.8
(C), 37.5 (CH2), 44.6 (CH), 50.7 (CH), 52.1 (CH), 52.6 (CH2),
64.9 (CH), 115.0 (CH2), 141.5 (CH), 218.2 (C); MS (EI) m/z 222
(M+), 120 (base); HRMS (EI) Calcd for C14H22O2 222.1620.
Found 222.1612 (M+).
The mixture of 16d , 17d , 19d , 20d , and 25 was separated
by HPLC (Develosil 60-10, 20φ × 250 mm, 30% AcOEt/
hexane) and recrystalyzation.
(3aS,4R,6R,7S,7aR)-4-Hydr oxy-3,3,6-tr im eth yl-7-vin ylp-
er h yd r o-1-in d en on e (16d ). Retention time on GC: 31.1 min;
1
[R]20 -91° (c 1.1, CHCl3); FTIR: 3400, 1730, 1640 cm-1; H
D
NMR (600 MHz, CDCl3) δ 0.87 (3H, d, J ) 7.1 Hz), 1.20 (3H,
s), 1.22 (3H, s), 1.53 (1H, ddd, J ) 13.7, 7.4, 4.0 Hz), 1.70 (1H,
ddd, J ) 13.7, 7.7, 4.0 Hz), 1.71 (1H, br s), 1.77-1.84 (1H, m),
2.07 (1H, dd, J ) 9. 1, 6.0 Hz), 2.16 (1H, dd, J ) 18.7, 0.6 Hz),
2.23 (1H, d, J ) 18.7 Hz), 2.29 (1H, dt, J ) 13.7, 6.6 Hz), 2.57
(1H, dd, J ) 9.1, 7.2 Hz), 3.95 (1H, ddd, J ) 7.4, 6.0, 4.0 Hz),
5.01 (1H, dt, J ) 17.3, 1.4 Hz), 5.09 (1H, ddd, J ) 10.3, 1.4,
0.8 Hz), 5.76 (1H, ddd, J ) 17.3, 10.3, 7.2 Hz); 13C NMR (50
MHz, CDCl3) δ 20.0 (CH3), 26.6 (CH3), 29.7 (CH3), 30.6 (CH),
36.8 (C), 37.5 (CH2), 44.7 (CH), 50.6 (CH), 52.2 (CH), 52.6
(CH2), 64.7 (CH), 144.9 (CH2), 141.4 (CH), 218.4 (C); MS (EI)
m/z 222 (M+), 120 (base); HRMS (EI) Calcd for C14H22O2
222.1620. Found 222.1612 (M+).
(3aR,4R,6R,7R,7aR)-4-Hydr oxy-3,3,6-tr im eth yl-7-vin ylp-
er h yd r o-1-in d en on e (18c). Retention time on GC: 31.6 min;
mp 162-170 °C (hexane-AcOEt); [R]20D -129° (c 1.3, CHCl3);
1
FTIR: 3430, 1730, 1645 cm-1; H NMR (600 MHz, CDCl3) δ
0.85 (3H, d, J ) 7.1 Hz), 1.11 (3H, s), 1.23 (3H, s), 1.33 (1H, br
s), 1.45 (1H, ddd, J ) 14.8, 13.2, 2.5 Hz), 1.62 (1H, dt, J )
14.8, 4.0 Hz), 1.78 (1H, dd, J ) 14.0, 1.8 Hz), 1.90 (1H, dd, J
) 18.1, 0.6 Hz), 2.05-2.13 (1H, m), 2.11 (1H, dd, J ) 18.1, 1.6
Hz), 2.78-2.83 (2H, m), 4.44 (1H, br q, J ) 2.5 Hz), 5.14 (1H,
dd, J ) 10.3, 2.2 Hz), 5.18 (1H, ddd, J ) 17.0, 2.2, 0.8 Hz),
5.63 (1H, ddd, J ) 17.0, 10.3, 9.6 Hz); 13C NMR (50 MHz,
CDCl3) δ 19.2 (CH3), 24.0 (CH3), 28.2 (CH3), 28.8 (CH), 36.6
(C), 39.4 (CH2), 44.3 (CH), 48.9 (CH), 49.0 (CH), 55.7 (CH2),
65.7 (CH), 120.0 (CH2), 132.1 (CH), 217.5 (C); MS (EI) m/z 222
(M+), 189 (base); HRMS (EI) Calcd for C14H22O2 222.1620.
Found 222.1611 (M+).
(3aS,4R,6R,7S,7aS)-4-Hydr oxy-3,3,6-tr im eth yl-7-vin ylp-
er h yd r o-1-in d en on e (17d ). Retention time on GC: 30.3 min;
mp 93-98 °C (hexane-CHCl3); [R]20 +177° (c 0.97, CHCl3);
D
1
FTIR: 3450, 1730, 1640 cm-1; H NMR (600 MHz, CDCl3) δ
1.06 (3H, d, J ) 7.4 Hz), 1.12 (3H, s), 1.34 (3H, s), 1.63-1.71
(3H, m), 1.73 (1H, dd, J ) 14.0, 10.2 Hz), 1.97 (1H, d, J ) 19.5
Hz), 2.12-2.17 (1H, m), 2.17 (1H, dd, J ) 19.5, 1.6 Hz), 2.34
(1H, ddd, J ) 14.3, 4.5, 1.4 Hz), 2.62 (1H, brt, J ) 4.5 Hz),
3.95 (1H, td, J ) 10.3, 4.5 Hz), 5.11 (1H, dt, J ) 10.7, 1.4 Hz),
5.14 (1H, dt, J ) 17.3, 1.4 Hz), 5.79 (1H, ddd, J ) 17.3, 10.7,
6.5 Hz); 13C NMR (50 MHz, CDCl3) δ 19.9 (CH3), 21.1 (CH3),
30.6 (CH3), 33.7 (CH), 36.2 (C), 38.7 (CH2), 42.0 (CH), 50.2
(CH), 52.4 (CH), 55.1 (CH2), 69.3 (CH), 116.8 (CH2), 137.1 (CH),
217.2 (C); MS (EI) m/z 222 (M+), 93 (base); HRMS (EI) Calcd
for C14H22O2 222.1620. Found 222.1622 (M+).
(3aR,4R,6R,7R,7aS)-4-Hydr oxy-3,3,6-tr im eth yl-7-vin ylp-
er h yd r o-1-in d en on e (19c). Retention time on GC: 32.9 min;
[R]20 +52.6° (c 1.7, CHCl3); FTIR: 3500, 1740, 1650 cm-1; 1H
D
NMR (600 MHz, CDCl3) δ 0.84 (3H, d, J ) 6.9 Hz), 0.95 (1H,
br s), 1.18 (3H, s), 1.34 (3H, s), 1.41-1.45 (2H, m), 1.82 (1H,
dd, J ) 7.7, 3.0 Hz), 1.98 (1H, dt, J ) 18.5, 1.4 Hz), 2.00-2.08
(1H, m), 2.42 (1H, d, J ) 18.5 Hz), 2.54 (1H, br d, J ) 7.7 Hz),
2.86 (1H, dd, J ) 9.2, 4.9 Hz), 4.21 (1H, br t, J ) 3.0 Hz), 5.08
(1H, dd, J ) 10.2, 1.8, 1.4 Hz), 5.10 (1H, ddd, J ) 16.9, 1.8,
0.8 Hz), 5.86 (1H, ddd, J ) 16.9, 10.2, 9.2 Hz); 13C NMR (50
MHz, CDCl3) δ 19.4 (CH3), 23.0 (CH), 24.3 (CH3), 31.5 (CH3),
35.6 (C), 36.9 (CH2), 40.2 (CH), 47.4 (CH), 50.9 (CH2), 52.2
(CH), 67.5 (CH), 116.1 (CH2), 137.2 (CH), 217.1 (C); MS (CI)
m/z 223 (M + 1)+, 163 (base), 135, 121, 109, 93, 81; HRMS
(CI) Calcd for C14H23O2 223.1698. Found 223.1705 (M + H)+.
Sm I2 Red u ction of 13d . Entry 1: A solution of 13d (20
mg, 0.09 mmol) in THF (1.0 mL) was treated with SmI2 (0.1
M, 5.4 mL, 0.54 mmol) at 0 °C according to the general
procedure to afford a mixture (13.7 mg) of 16d , 17d , 19d , and
20d after flash chromatography (SiO2, 0-40% AcOEt/hexane).
Entry 2: A solution of 13d (20 mg, 0.09 mmol) in THF (1.0
mL) was treated with SmI2 (0.1 M, 5.4 mL, 0.54 mmol) at -78
°C according to the general procedure to afford a mixture (17.4
mg) of 16d , 17d , 19d , and 20d after flash chromatography
(SiO2, 0-40% AcOEt/hexane).
(3aR,4R,6R,7S,7aS)-4-Hydr oxy-3,3,6-tr im eth yl-7-vin ylp-
er h yd r o-1-in d en on e (19d ). Retention time on GC: 31.8 min;
[R]19 -32° (c 0.26, CHCl3); FTIR: 3500, 1720, 1640 cm-1; 1H
D
NMR (600 MHz, CDCl3) δ 0.84 (3H, d, J ) 6.3 Hz), 0.96 (1H,
br s), 1.20 (3H, s), 1.23 (1H, ddd, J ) 14.0, 11.8, 1.6 Hz), 1.29
(3H, s), 1.67 (1H, dd, J ) 7.1, 2.2 Hz), 1.79 (1H, ddd, J ) 14.0,
4.1, 3.0 Hz), 1.84-1.93 (2H, m), 1.95 (1H, dt, J ) 18.4, 1.4
Hz), 2.31 (1H, d, J ) 18.4 Hz), 2.76 (1H, ddd, J ) 6.9, 5.8, 1.1
Hz), 4.19 (1H, br s), 5.01 (1H, ddd, J ) 17.0, 2.4, 1.1 Hz), 5.03
(1H, dd, J ) 10.2, 2.4 Hz), 6.58 (1H, ddd, J ) 17.0, 10.2, 9.6
Hz); 13C NMR (100 MHz, CDCl3) δ 20.3 (CH3), 24.6 (CH3), 31.7
(CH), 35.3 (C), 42.4 (CH2), 50.0 (CH), 51.6 (CH), 52.0 (CH2),
52.2 (CH), 67.5 (CH), 114.9 (CH2), 141.0 (CH), 216.4 (C); MS
(EI) m/z 222 (M+), 121 (base); HRMS (EI) Calcd for C14H22O2
222.1620. Found 222.1612. (M+).
(3aS,4S,6R,7S,7aR)-4-Hydr oxy-3,3,6-tr im eth yl-7-vin ylp-
er h yd r o-1-in d en on e (20d ). Retention time on GC: 35.6 min;
mp 93-98 °C (hexane-CHCl3); [R]19 -34° (c 0.75, CHCl3);
D
1
Entry 3: A solution of 13d (20 mg, 0.09 mmol) and HMPA
(0.08 mL, 0.45 mmol) in THF (1.0 mL) was treated with SmI2
FTIR: 3450, 1730, 1640 cm-1; H NMR (600 MHz, CDCl3) δ
0.90 (3H, d, J ) 6.6 Hz), 1.05 (1H, br s), 1.15 (1H, ddd, J )

3106 J . Org. Chem., Vol. 65, No. 10, 2000
Sono et al.
15.0, 9.6, 1.7 Hz), 1.16 (3H, s), 1.26 (3H, s), 1.40-1.47 (1H,
m), 1.86 (1H, dd, J ) 9.1, 1.7 Hz), 2.00 (1H, dt, J ) 18.6, 1.1
Hz), 2.12 (1H, ddd, J ) 15.0, 7.8, 5.8 Hz), 2.26 (1H, dt, J )
11.5, 8.8 Hz), 2.40 (1H, d, J ) 18.6 Hz), 2.47 (1H, td, J ) 8.8,
1.7 Hz), 4.28 (1H, dt, J ) 5.7, 1.7 Hz), 5.11 (1H, dd, J ) 10.2,
1.9 Hz), 5.18 (1H, ddd, J ) 17.2, 1.9, 0.8 Hz), 5.59 (1H, ddd, J
) 17.2, 10.2, 8.8 Hz); 13C NMR (50 MHz, CDCl3) δ 20.7 (CH3),
25.2 (CH3), 30.3 (CH), 31.7 (CH3), 35.8 (C), 42.0 (CH2), 45.0
(CH2), 48.6 (CH), 51.2 (CH), 52.2 (CH2), 67.8 (CH), 115.7 (CH2),
142.0 (CH), 220.2 (C); MS (EI) m/z 222 (M+), 163 (base); HRMS
(EI) Calcd for C14H22O2 222.1620. Found 222.1638 (M+).
(4S,5R,7R,7aR,)-7,7a-Dih ydr oxy-2,2,5-tr im eth yl-4-vin yl-
1,4,5,6,7,7a -h exa h yd r o-2H-in d en e (25). Retention time on
2.1 Hz), 5.32 (1H, d, J ) 1.9 Hz), 5.64 (1H, ddd, J ) 17.0, 10.2,
9.2 Hz); 13C NMR (50 MHz, CDCl3) δ 20.0 (CH3), 29.1 (CH3),
30.6 (CH), 31.4 (CH3), 37.0 (CH2), 42.8 (C), 47.6 (CH), 49.9
(CH2), 71.3 (CH), 85.6 (C), 116.8 (CH2), 138.9 (CH), 139.1 (CH),
141.9 (C); MS (EI) m/z 222 (M+), 189 (base); HRMS (EI) Calcd
for C14H22O2 222.1620. Found 222.1612 (M+).
Ack n ow led gm en t. We thank Dr. M. Tanaka and
Miss Y. Okamoto (this University) for measurements
of 600 MHz NMR and mass spectra, respectively. X-ray
analysis was carried out by Mr. S. Takaoka (this
University), to whom many thanks are due.
GC: 24.9 min; [R]20 -54° (c 0.58, CHCl3); FTIR: 3400, 1720,
D
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedure for compounds 13a , 13b, 13c, 13d , and 26-35, data of
X-ray crystallography, and photocopies of 1H NMR spectra for
7a -35. This material is available free of charge via the
Internet at http://pubs.acs.org.
1
1690, 1940 cm-1; H NMR (600 MHz, CDCl3) δ 0.92 (3H, d, J
) 6.6 Hz), 1.08 (3H, s), 1.15 (3H, s), 1.37 (1H, br s), 1.50-1.58
(2H, m), 1.63 (1H, d, J ) 14.3 Hz), 1.76 (1H, dt, J ) 14.6, 3.6
Hz), 1.90 (1H, ddd, J ) 14.6, 12.6, 2.2 Hz), 2.35 (1H, d, J )
14.3 Hz), 2.49 (1H, ddd, J ) 11.0, 9.2, 1.9 Hz), 3.70 (1H, br s),
5.08 (1H, ddd, J ) 17.0, 2.1, 0.5 Hz), 5.15 (1H, dd, J ) 10.2,
J O9918450