Expeditious copper-catalyzed conjugate 1,4-addition of bromo[2-(1,3-dioxolan-2-yl)ethyl]magnesium to α,β-cycloalkenones and subsequent transformations

Article abstract of DOI:10.1021/jo034350q

Expeditious CuI-catalyzed conjugate 1,4-addition of bromo [2-(1,3-dioxolan-2-yl)ethyl] magnesium to the five-, six-, seven-, and eight-membered α,β-cycloalkenones is described. The reaction times are decreased dramatically compared to CuBr-(CH₃

Full text of DOI:10.1021/jo034350q

SCHEME 1. Cu I-Ca ta lyzed 1,4-Ad d ition of 1 to 2
a n d Su bsequ en t Cycliza tion
Exp ed itiou s Cop p er -Ca ta lyzed Con ju ga te
1,4-Ad d ition of
Br om o[2-(1,3-d ioxola n -2-yl)eth yl]m a gn esiu m
to r,â-Cycloa lk en on es a n d Su bsequ en t
Tr a n sfor m a tion s
Georgia G. Tsantali and Ioannis M. Takakis*
Department of Chemistry, University of Thessaloniki,
Thessaloniki 541 24, Greece
itakakis@chem.auth.gr
Received March 17, 2003
Abstr a ct: Expeditious CuI-catalyzed conjugate 1,4-addition
of bromo[2-(1,3-dioxolan-2-yl)ethyl]magnesium to the five-,
six-, seven-, and eight-membered R,â-cycloalkenones is
described. The reaction times are decreased dramatically
compared to CuBr-(CH3)2S catalysis. The resulting keto-
acetals were subsequently cyclized to bicyclic â-hydroxy
ketones and R,â-enones, followed by further transformations.
Conjugate 1,4-addition of bromo[2-(1,3-dioxolan-2-yl)-
ethyl]magnesium (1) to the R,â-cycloalkenones 2a -c
under CuBr-(CH3)2S catalysis has been previously re-
ported by Helquist and associates.3 The experimental
procedures are, however, unnecessarily time-consuming,
with the addition of 1 to 2 requiring 4 h followed by
stirring at -78 °C for an additional 15 h.
Conjugate 1,4-addition of acetal-containing Grignard
reagents to R,â-unsaturated ketones followed by annu-
lation1-5 comprises an important class of reactions be-
cause the resulting ring systems intervene in the syn-
thesis of many natural products and useful compounds
as, for example, in the total synthesis of hymenolin,6a
parthenin,6a,b ceroplastin sesterterpenes,6c pentacyclic
triterpenes,6d axanes,6e 7,8-epoxy-2-basmen-6-one,6f ptilo-
caulin,6g,h retigeranic acid A,6i senoxydene,6j dehydrocos-
tus lactone,6k estafiatin,6k silphiperfol-6-ene,6l oxosilphip-
erfol-6-ene,6l silphinene,6m isocomene,6n modhephene,6o
and others.5,6p,q,r
We report herein the conjugate 1,4-addition of Grig-
nard reagent 1 to the R,â-cycloalkenones 2 under CuI
catalysis. The reaction of 1 with 2d is unprecedented.
The enones 2 were converted smoothly into the corre-
sponding ketoacetals 3 with the exception of 2a , “a
notoriously difficult case for conjugate additions”,3 which
afforded a moderate yield of ketoacetal 3a (Scheme 1).
6d
The use of CeCl3 in place of CuI did not improve the
yield. Our results are in part comparable to those of
Helquist; however, the overall reaction times are de-
creased dramatically.
Prior to the use of CuI, we employed the conditions
reported by Helquist,3 with the modification that the
addition of the enone to the reaction mixture took place
within 5 min instead of 4 h. The yield in ketoacetal was
satisfactory with enone 2b, but not with 2a ,c,d . We have
also carried out addition of 1 to enone 2b at -78 °C in
the absence of CuI, according to conditions reported by
Sworin.2 The yield in ketoacetal 3b was less satisfactory,
and the reaction mixture was complicated by the pres-
ence of the 1,2-addition product and by heavier products
resulting from consecutive 1,4- and 1,2-additions.
The ketoacetals 3 were isolated and hydrolyzed with
aq HCl. Thus, 3b,c afforded the bicyclic enones 4b,c, as
reported by Helquist.3 The ketoacetal 3d furnished a
mixture of the enone 4d and the trans-diastereomeric
â-hydroxy ketones 7a ,b. Apparently, the trans isomers
are thermodynamically more stable relative to the cis.
Interestingly, 3a gave, in addition to 5a , the three
diastereomeric â-hydroxy ketones 5b and 6a ,b, not
previously observed. Yields are presented in Table 1.
* To whom correspondence should be addressed. Tel: +2310-997853.
Fax: +2310-997679.
(1) (a) Hudlicky, T.; Price, J . D. Chem. Rev. 1989, 89, 1467-1486.
(b) Stowell, J . C. Chem. Rev. 1984, 84, 409-435.
(2) Sworin, M.; Neumann, W. L. Tetrahedron Lett. 1987, 28, 3217-
3220.
(3) Bal, S. A.; Marfat, A.; Helquist, P. J . Org. Chem. 1982, 47, 5045-
5050.
(4) Abbott, R. E.; Spencer, T. A. J . Org. Chem. 1980, 45, 5398-5399.
(5) Alexakis, A.; Chapdelaine, M. J .; Posner, G. H.; Runquist, A. W.
Tetrahedron Lett. 1978, 4205-4208.
(6) (a) Shimoma, F.; Kusaka, H.; Azami, H.; Wada, K.; Suzuki, T.;
Hagiwara, H.; Ando, M. J . Org. Chem. 1998, 63, 3758-3763. (b)
Heathcock, C. H.; Tice, C. M.; Germroth, T. C. J . Am. Chem. Soc. 1982,
104, 6081-6091. (c) Paquette, L. A.; Liang, S.; Wang, H.-L. J . Org.
Chem. 1996, 61, 3268-3279. (d) Arseniyadis, S.; Rodriguez, R.;
Camara, J .; Gallard, J . F.; Guittet, E.; Toupet, L.; Ourisson, G.
Tetrahedron 1995, 51, 9947-9972. (e) Ohkubo, T.; Akino, H.; Asaoka,
M.; Takei, H. Tetrahedron Lett. 1995, 36, 3365-3368. (f) Paquette, L.
A.; Kang, H.-J . J . Am. Chem. Soc. 1991, 113, 2610-2621. (g) Asaoka,
M.; Sakurai, M.; Takei, H. Tetrahedron Lett. 1990, 31, 4759-4760.
(h) Snider, B. B.; Faith, W. C. J . Am. Chem. Soc. 1984, 106, 1443-
1445. (i) Wright, J .; Drtina, G. J .; Roberts, R. A.; Paquette, L. A. J .
Am. Chem. Soc. 1988, 110, 5806-5817. (j) Paquette, L. A.; Galemmo,
R. A., J r.; Caille, J .-C.; Valpey, R. S. J . Org. Chem. 1986, 51, 686-
695. (k) Rigby, J . H.; Wilson, J . Z. J . Am. Chem. Soc. 1984, 106, 8217-
8224. (l) Paquette, L. A.; Roberts, R. A.; Drtina, G. J . J . Am. Chem.
Soc. 1984, 106, 6690-6693. (m) Paquette, L. A.; Leone-Bay, A. J . Am.
Chem. Soc. 1983, 105, 7352-7358. (n) Paquette, L. A.; Han, Y.-K. J .
Am. Chem. Soc. 1981, 103, 1835-1838. (o) Oppolzer, W.; Marazza, F.
Helv. Chim. Acta 1981, 64, 1575-1578. (p) Brattesani, D. N.; Heath-
cock, C. H. J . Org. Chem. 1975, 40, 2165-2170. (q) Overman, L. E.
Tetrahedron Lett. 1975, 1149-1152. (r) Matlin, A. R.; Agosta, W. C.
J . Chem. Soc., Perkin Trans. 1 1987, 365-368.
Structural assignments were based on NMR experi-
ments (including NOE, paramagnetic shifts reagents, and
COSY), on conversion of the reaction products to known
compounds, and on the preparation of authentic samples.
Thus, an NOE was observed with 6a but not with 6b.
With the use of Eu(fod)3,7 we have accomplished resolu-
10.1021/jo034350q CCC: $25.00 © 2003 American Chemical Society
Published on Web 07/09/2003
J . Org. Chem. 2003, 68, 6455-6458
6455

SCHEME 2. Con ver sion of 7a a n d 7b to 14a
TABLE 1. Ketoa ceta ls a n d An n u la tion P r od u cts
enone ketoacetal (yield, %)a annulation product (yield, %)a
4b (93)
2bb
2cb
2d b
2a c
3b (92)
3c (88)
3d (89)
3a (43)
4c (90)
4d (15) +7a (38) + 7b (31)
5a (53) + 5b (9) + 6a (20) + 6b (3)
a
b
Isolated. Two equiv of Grignard reagent 1 were used. c Four
equiv of 1 were used.
TABLE 2. NMR P seu d o-Con ta ct Sh ifts in 6a a n d 6b
In d u ced by Eu (fod )3
∆δ 1Ha
∆δ 13Ca
H
6a
6b
C
6a
6b
1
0.22
0.23
0.23
0.53
0.84
0.73
0.81
0.35
0.62
0.38
0.76
0.55
1.48
1.08
1
2
0.41
0.23
0.58
0.65
2exo
2endo
3exo
3endo
4
3
0.32
0.63
a
Reagents and conditions: (a) p-TsNHNH2, CH3OH, 25 °C, 15-
4
5
6
7
2.46
0.84
1.69
0.32
2.65
0.70
1.53
0.60
20 h; (b) BuLi, TMEDA, THF, 25 °C, 17-21 h; (c) Swern oxidation.
5
6
SCHEME 3. P r ep a r a tion of Au th en tic 14a
7exo
7endo
8exo
8endo
0.42
0.49
0.25
0.22
0.56
0.56
0.48
0.82
8
0.39
0.80
a
Chemical shift difference estimated at [Eu(fod)3]/[compd] )
0.070 for 6a and 6b.
tion of all the protons in 6a and 6b. A total of three
additions of Eu(fod)3 were performed (see Tables S1 and
S2, Supporting Information), and after each addition,
(H,H)- and (H,C)-COSY were obtained to identify proton
and carbon atoms. Plots were constructed next (the
relationships were linear, or nearly linear) in order to
compare the lanthanide induced shifts (LIS) in 6a and
6b at the same [Eu(fod)3]/[compound] ratio. The results
(Table 2) confirm the stereochemistry assigned to 6a and
6b. Noticeable are the H2exo, H3exo, H8endo, and C8 LIS
which are greater in 6b (exo-OH), compared to the
corresponding LIS in 6a (endo-OH). The reverse is
a
Reagents and conditions: (a) THF, 25 °C, 1 h; (b) POCl3,
observed with the LIS of H3endo
.
pyridine, 25 °C, 21 h; (c) AcOH-H2O (1:1), 25 °C, 77 h; (d) MeAlCl2,
CH2Cl2, 5-25 °C, 21 h; (e) DIBAL-H.
The â-hydroxy ketones 7a ,b were partially converted
to the same enone 4d with 20% aq H2SO4, the rate of
elimination of 7a being greater than that of 7b. Oxidation
of 5a ,b and 6a ,b with PCC furnished the known 1,3-
diones 88 and 9,9 respectively. The â-hydroxy ketone 5a
was converted to the olefinic alcohol 10 via its p-
tosylhydrazone derivative followed by reaction with me-
thyllithium and found to be identical with an authentic
sample.10 Oxidation of alcohol 10 with CrO3-pyridine
complex11 gave the known10 enone 11.
Scheme 2. Elimination of these with butyllithium (BuLi)
to the alkene alcohols 13a ,b followed by Swern12 oxida-
tion afforded the same enone 14. An authentic sample
of 14 was prepared as shown in Scheme 3. Thus,
conjugate 1,2-addition of the Grignard reagent 1 to
3-cycloocten-1-one10 furnished cyclooctanol 15, which was
eliminated with POCl3 affording diene 16, as the major
product, and the other two possible isomeric dienes 16a
and 16b (see the Supporting Information). Hydrolysis of
16 was carried out with AcOH-H2O (1:1) and gave dienal
17, which was cyclized with MeAlCl2 to enone 14 accord-
ing to a procedure described in the literature.13 Reduction
of the latter with DIBAL-H furnished the diastereomeric
alcohols 13a ,b. This is an alternative route for preparing
these two alcohols.
The â-hydroxy ketones 7a ,b were converted to the
corresponding p-tosylhydrazones 12a ,b as depicted in
(10) Crandall, J . K.; Chang, L.-H. J . Org. Chem. 1967, 32, 532-
536.
(7) Cockerill, A. F.; Davis, G. L. O.; Harden, R. C.; Rackham, D. M.
Chem. Rev. 1973, 73, 553-588.
(11) Ratcliffe, R.; Rodehorst, R. J . Org. Chem. 1970, 35, 4000-4002.
(12) Mancuso, A. J .; Huang, S.-L.; Swern, D. J . Org. Chem. 1978,
43, 2480-2482.
(13) Snider, B. B.; Cartaya-Marin, C. P. J . Org. Chem. 1984, 49,
153-157; Snider, B. B.; Kirk, T. C. J . Am. Chem. Soc. 1983, 105, 2364-
2368.
(8) Eaton, P. E.; Mueller, R. H.; Carlson, G. R.; Cullison, D. A.;
Cooper, G. F.; Chou, T.-C.; Krebs, E.-P. J . Am. Chem. Soc. 1977, 99,
2751-2767.
(9) Rigby, J . H.; Kotnis, A. S. Tetrahedron Lett. 1987, 28, 4943-
4946.
6456 J . Org. Chem., Vol. 68, No. 16, 2003

with 30% NH4Cl (adjusted to pH 8).3 The mixture was extracted
with CH2Cl2, dried, and concentrated. Column chromatography
(column A, x/y: 10/1, then 5/1) afforded the Wurtz-type coupling
product (250 mg) and the ketoacetal 3b3 (5.68 g, 92%, colorless
oil). Hydrolysis of 3b (5.68 g, 28.6 mmol) was accomplished by
refluxing with 2.5% aq HCl (50 mL) in THF (50 mL) for 1 h.
Neutralization with 5% aq NaHCO3, extraction with CH2Cl2,
drying, concentration, and column chromatography (column A,
x/y: 10/1) furnished the enone 4b3 (3.62 g, 93%, colorless oil).
SCHEME 4. Ald ol Con d en sa tion of 3a
1,2,5,6,7,8,9,9a -Octa h yd r o-4H-cyclop en ta [a ]cycloocten -
4-on e (4d ), r a c-(3R,3a S,9a R)-3-Hyd r oxyd eca h yd r o-4H-cy-
clop en ta [a ]cycloocten -4-on e (7a ), a n d r a c-(3S,3a S,9a R)-3-
Hydr oxydecah ydr o-4H-cyclopen ta[a ]cycloocten -4-on e (7b).
Reagents: Mg (5.90 g, 243 mmol), 2-(2-bromoethyl)-1,3-dioxolane
(14.6 g, 80.7 mmol), CuI (1.55 g, 8.1 mmol), 2d (5.00 g, 40.3
mmol). Column chromatography (column A, x/y: 10/1, then 5/1)
afforded 3-[2-(1,3-dioxolan-2-yl)ethyl]cyclooctanone (3d ) (8.13 g,
89%, pale-yellow oil). Hydrolysis of 3d (8.13 g, 35.9 mmol)
followed by column chromatography (column A, x/y: 10/1, then
5/1) furnished the enone 4d (0.879 g, 15%, first fraction, colorless
oil), and the keto alcohols 7a (2.49 g, 38%, second fraction, pale-
yellow oil) and 7b (2.02 g, 31%, third fraction, white crystalline
solid). In a different hydrolysis experiment, 4d (31.54 g, 139.4
mmol) was heated at reflux with 20% aq H2SO4 (150 mL) in THF
(200 mL) for 2 h. Workup and column chromatography as above
gave 4d (9.12 g, 40%), 7a (3.17 g, 12%), and 7b (7.76 g, 31%).
Compound 3d : IR ν 1734, 1696, 1142, 1088, 1039 cm-1; 1H NMR
δ 1.13-1.28 (m, 1H), 1.31-1.52 (m, 4H), 1.59-1.78 (m, 4H),
1.79-2.08 (m, 4H), 2.28-2.52 (m, 4H), 3.82-4.02 (m, 4H), 4.85
(t, J ) 4.7 Hz, 1H); 13C NMR δ 23.7, 24.8, 27.6, 31.3, 31.5, 33.3,
37.7, 42.9, 47.2, 64.88, 64.90, 104.5, 217.0; MS (EI) m/z (%
relative abundance) 226 (M+, 60), 182 (21), 152 (10), 135 (100),
NMR experiments with 13a , 13b, and Eu(fod)3 followed
by analysis of the data as described above, albeit less
elaborate (see Table S3, Supporting Information), indi-
cated that the proton at the 3a-position in 13a (cis to the
OH) was shifting downfield more rapidly than the cor-
responding in 13b (trans to the OH), estimated at [Eu-
(fod)3]/[compound] ) 0.070 (∆δ3a ) 1.32 for 13a vs 0.30
for 13b). The reverse was observed with the proton at
9a
the 9a-position (∆δ
) 0.70 for 13a vs 0.84 for 13b),
even though the shift difference in this case was less
pronounced.
99 (57), 87 (31), 73 (89). Anal. Calcd for
C13H22O3 (MW
Mechanistically, it is apparent that the alcohols 5a ,b
are obtained as a result of intramolecular aldol conden-
sation at the 2-position, whereas 6a ,b come from con-
densation at the 5-position of the keto aldehyde 18 via
the two different enol intermediates, as shown in Scheme
4. Analogous examples are cited in the literature.14 This
was not observed in any other case studied.
In conclusion, we have shortened dramatically the
reaction times for the addition of the Grignard reagent
1 to the cycloalkenones 2 by the use of CuI instead of
CuBr-(CH3)2S catalysis,3 also avoiding the unpleasant
odor of (CH3)2S. In addition, we have identified three
more isomeric annulation products in the case of enone
2a , and placed the eight-membered enone 2d under the
aegis of this important class of reactions.
226.312): C, 68.99; H, 9.80. Found: C, 69.10; H, 9.71. Compound
4d : UV λmax (ꢀ) 257 (2550) nm; IR ν 1702, 1600, 1454, 1324 cm-1
1H NMR δ 1.17-2.07 (m, 9H), 2.08-2.67 (m, 4H), 2.83 (ddd, J
) 11.0, 8.8, 8.8 Hz, 1H), 3.10 (m, 1H), 6.71 (m, 1H); 13C NMR δ
25.88, 25.93, 28.6, 31.0, 33.5, 37.0, 39.7, 44.1, 141.5, 148.6, 203.6;
MS (EI) m/z (% relative abundance) 165 (M+ + 1, 100) 164 (M+,
47), 146 (5), 136 (9), 121 (23), 108 (14), 107 (14), 93 (45), 80 (32),
79 (19). Anal. Calcd for C11H16O (MW 164.244): C, 80.44; H,
9.82. Found: C, 80.19; H, 9.58. Compound 7a : IR ν 3620, 3455,
1670, 1172, 1073, 1042, 983 cm-1; 1H NMR δ 1.02-1.38 (m, 3H),
1.44-2.17 (m, 9H), 2.37-2.62 (m, 4H), 4.05 (br s, 1H, OH), 4.41
(t, J ) 4.0 Hz, 1H); 13C NMR δ 22.9, 24.9, 28.2, 30.9, 31.4, 33.6,
44.3, 46.4, 58.0, 75.8, 221.6; MS (EI) m/z (% relative abundance)
183 (M+ + 1, 93), 182 (M+, 4), 165 (55), 164 (11), 154 (31), 153
(9), 147 (10), 138 (100), 125 (25), 111 (14). Anal. Calcd for
C11H18O2 (MW 182.259): C, 72.49; H, 9.95. Found: C, 72.49; H,
10.07. Compound 7b: mp (white needles from ethyl ether) 64-
;
1
65 °C; IR ν 3615, 3450, 1688, 1082 cm-1; H NMR δ 1.05-1.19
(m, 1H), 1.19-1.34 (m, 1H), 1.44-1.75 (m, 5H), 1.75-1.97 (m,
4H), 2.03-2.20 (m, 2H), 2.43 (m, 2H), 2.75 (dd, J ) 11.1, 8.4
Hz, 1H), 2.99 (br s, 1H, OH), 4.51 (ddd, J ) 8.4, 8.4, 6.5 Hz,
1H); 13C NMR δ 23.3, 24.8, 28.0, 30.8, 32.0, 32.2, 43.4, 47.1, 63.9,
75.6, 217.7; MS (EI) m/z (% relative abundance) 183 (M+ + 1,
41), 182 (M+, 3), 165 (51), 164 (100), 149 (13), 138 (18), 136 (33),
125 (24), 122 (24), 121 (29), 111 (19). Anal. Calcd for C11H18O2
(MW 182.259): C, 72.49; H, 9.95. Found: C, 72.60; H, 10.16.
r a c-(3a R,6R,6a S)-6-H yd r oxyh exa h yd r o-1(2H )-p en t a le-
n on e (5a ), r a c-(3a R,6S,6a S)-6-Hyd r oxyh exa h yd r o-1(2H)-
p en ta len on e (5b), r a c-(4R)-4-Hyd r oxybicyclo[3.2.1]octa n -
6-on e, (6a ), a n d r a c-(4S)-4-Hyd r oxybicyclo[3.2.1]octa n -6-
on e (6b). Reagents: Mg (2.41 g, 99.1 mmol), 2-(2-bromoethyl)-
1,3-dioxolane (8.95 g, 49.4 mmol), CuI (0.942 g, 4.95 mmol), 2a
(1.01 g, 12.3 mmol). Column chromatography (column A, x/y: 10/
1, then 5/1) afforded 3a 3 (0.972 g, 43%, pale-yellow oil). The yield
was inferior under CeCl3 catalysis.6d Hydrolysis of 3a (972 mg,
5.3 mmol) followed by column chromatography (column A, x/y:
10/1, then 5/1) furnished 5a 3 (391 mg, 53%, first fraction, whitish
semisolid), 6b (23 mg, 3%, second fraction, white solid), 5b (64
mg, 9%, third fraction, whitish semisolid), 6a (149 mg, 20%,
fourth fraction, white solid). Compound 5a : IR ν 3590, 3470,
1720, 1153, 1113, 1077 cm-1; 1H NMR δ 1.62-1.90 (m, 4H), 1.97
Exp er im en ta l Section
Column chromatography was performed with columns con-
taining silica gel (70-270 mesh). Columns used: A (85 × 2.5
cm, filled with 180 g), B (26 × 2.0 cm, 32 g), C (46 × 1.6 cm, 33
g), D (60 × 2.0 cm, 75 g), E (70 × 2.0 cm, 82 g). The columns
were eluted with petroleum ether (bp 65-69 °C)/ethyl acetate
x:y (v/v). The cycloalkenones 2 were prepared as described in
the literature.15
Gen er a l P r oced u r e for Con ju ga te Ad d ition a n d Su bse-
qu en t An n u la tion , by Exa m p le. 1,2,5,6,7,7a -Hexa h yd r o-4H-
in d en -4-on e (4b). To ground Mg turnings2,3 (3.09 g, 127 mmol)
in THF (25 mL) was added 2-(2-bromoethyl)-1,3-dioxolane (11.37
g, 62.8 mmol) in THF (25 mL) at 22-24 °C2 over a period of 15
min. After being stirred for 30 min, the mixture was cooled to
-30 °C, CuI (1.19 g, 6.2 mmol) was added all at once, the mixture
was stirred for 15 min and cooled to -78 °C, a solution of 2b
(3.00 g, 31.2 mmol) in THF (25 mL) was added within 5 min,
and the mixture was warmed to 0 °C within 1 h and quenched
(14) Filippini, M.-H.; M.; Rodriguez, J . Chem. Rev. 1999, 99, 27-
76.
(15) Garbisch, E. W., J r. J . Org. Chem. 1965, 30, 2109-2120.
J . Org. Chem, Vol. 68, No. 16, 2003 6457

(m, 1H), 2.14 (dddd, J ) 13.0, 8.3, 8.3, 8.3 Hz, 1H), 2.22-2.46
(m, 2H), 2.70 (dd, J ) 8.4, 8.4, Hz, 1H), 2.84 (m, 1H), 2.91 (br s,
1H, OH), 4.49 (ddd, J ) 7.4, 4.5, 4.5 Hz, 1H); 13C NMR δ 27.3,
30.6, 36.2, 39.9, 40.8, 56.9, 74.7, 222.1; MS (EI) m/z (% relative
abundance) 140 (M+, 8), 122 (26), 112 (7), 111 (14), 96 (61), 94
(13), 83 (100), 81 (47), 80 (73). Anal. Calcd for C8H12O2 (MW
140.180): C, 68.54; H, 8.63. Found: C, 68.56; H, 8.79. Compound
3H), 2.02 (dddd, J ) 12.9, 12.9, 6.2, 2.3 Hz, 1H), 2.17 (dd, J )
18.5, 3.4 Hz, 1H), 2.29 (dd, J ) 18.5, 6.5 Hz, 1H), 2.32 (ddd, J )
11.8, 3.4, 3.0 Hz, 1H), 2.37 (br s, 1H, OH), 2.50 (t, J ) 4.9 Hz,
1H), 2.62 (m, 1H), 4.06 (m, 1H); 13C NMR δ 26.5, 26.8, 30.0, 32.1,
42.6, 53.4, 67.5, 218.3; MS (EI) m/z (% relative abundance) 141
(M+ + 1, 7), 140 (M+, 13), 123 (9), 122 (4), 96 (59), 94 (11), 83
(100), 80 (30). Anal. Calcd for C8H12O2 (MW 140.180): C, 68.54;
H, 8.63. Found: C, 68.15; H, 8.67.
5b: IR ν 3600, 3410, 1716, 1146, 1040, 1022, 1006, 970 cm-1
;
1H NMR δ 1.43 (m, 1H), 1.56-1.89 (m, 3H), 2.06-2.22 (m, 2H),
2.23-2.33 (m, 2H), 2.58 (d, J ) 8.8 Hz, 1H), 3.01 (m, 1H), 3.19
(br s, 1H, OH), 4.33 (m, 1H); 13C NMR δ 26.6, 30.9, 35.4, 38.0,
39.5, 61.9, 76.7, 220.9; MS (EI) m/z (% relative abundance) 140
(M+, 57), 122 (64), 112 (69), 111 (60), 96 (84), 94 (52), 83 (96), 81
(72), 80 (79), 55 (100). Anal. Calcd for C8H12O2 (MW 140.180):
C, 68.54; H, 8.63. Found: C, 68.50; H, 8.78. Compound 6a : mp
Ack n ow led gm en t. We thank Mr. D. Rigas for
obtaining the mass spectra. G.G.T. thanks the “Leonidas
Zervas Foundation” for a two-year (1994-1996) scholar-
ship during her Ph.D. work.
1
157-160 °C; IR ν 3560, 3445, 1732, 1160, 1070 cm-1; H NMR
Su p p or tin g In for m a tion Ava ila ble: General experimen-
tal procedures; 13C NMR for 3b, 4b, and 3a ; MS for 3b;
preparation and data for 4c, 8, 9, rac-N′-[(3aS,6R,6aR)-6-
hydroxyhexahydro-1(2H)-pentalenylidene]-4-methylbenzene-
sulfonohydrazide, 10, 11, 12a ,b, 13a ,b, and 14-17; reduction
of 14; NMR Eu(fod)3 data for 6a ,b and 13a ,b (Tables S1-S3).
This material is available free of charge via the Internet at
http://pubs.acs.org.
δ 1.36 (m, 1H), 1.63 (dd, J ) 12.2, 3.2 Hz, 1H), 1.71 (m, 1H),
1.74 (m, 1H), 2.01-2.14 (m, 2H), 2.05 (dd, J ) 18.5, 3.4, Hz,
1H), 2.27 (br s, 1H, OH), 2.26 (dd, J ) 18.5, 6.8 Hz, 1H), 2.49
(m, 1H), 2.55 (m, 1H), 3.87 (m, 1H); 13C NMR δ 29.1, 29.2, 31.5,
35.2, 43.8, 53.5, 71.9, 219.9; MS (EI) m/z (% relative abundance)
141 (M+ + 1, 58), 140 (M+, 62), 123 (72), 122 (74), 112 (27), 111
(41), 96 (81), 94 (63), 83 (97), 81 (89), 80 (100). Anal. Calcd for
C8H12O2 (MW 140.180): C, 68.54; H, 8.63. Found: C, 68.32; H,
8.67. Compound 6b: mp 140-142 °C; IR ν 3605, 3430, 1730,
1156, 1012, 963 cm-1
;
1H NMR δ 1.54 (m, 1H), 1.59-1.80 (m,
J O034350Q
6458 J . Org. Chem., Vol. 68, No. 16, 2003