Anomalous products from the thermal diels-alder reaction of a (E)-2- thiophenyl butadiene tethered to 3-methallyl cyclohexenone

Full text of DOI:10.1021/jo9824192

2590
J . Org. Chem. 1999, 64, 2590-2594
Sch em e 1a
An om a lou s P r od u cts fr om th e Th er m a l
Diels-Ald er Rea ction of a (E)-2-Th iop h en yl
Bu ta d ien e Teth er ed to 3-Meth a llyl
Cycloh exen on e
Paul A. Grieco*,1 and Michael D. Kaufman
Department of Chemistry and Biochemistry, Montana State
University, Bozeman, Montana 59717, and Department of
Chemistry, Indiana University, Bloomington, Indiana 47405
Received December 10, 1998
In connection with our interest in the intramolecular
Diels-Alder reaction of in situ-generated, heteroatom-
stabilized allyl cations in polar media,2 we set out to
extend this chemistry by employing a terminal (E)-2-
thiophenyl group on the terminal butadiene unit and
incorporating a methallyl group at the γ carbon of the
intermediate allyl cation (cf. 2) so as to generate a
quaternary carbon atom within a carbocyclic array (cf. 1
f 4).
biguously established by single-crystal X-ray analysis.4
The structures of 12 and 13 were derived from their
1
respective H NMR spectra and by comparison with the
spectrum of 11.
On the basis of previous work from our laboratory,2 it
was anticipated that substrate 1 would undergo facile
cycloaddition with formation of 3 via an exo transition
state followed by equilibration3 adjacent to the carbonyl
leading exclusively to 4. Upon exposure (1 h, ambient
temperature) of 1 (for the synthesis of 1, see Scheme 1)
to 2.0 M lithium perchlorate in diethyl ether containing
10 mol % trifluoroacetic acid, neither the expected
product 4 nor 3 could be detected. Workup provided four
cycloadducts 10-13 in a combined yield of 78%. The
structure of tricyclic ketone 10, which presumably arises
via a stepwise, endo-like transition state, was readily
1
1
confirmed by H NMR and NOE measurements. The H
NMR spectra of 11-13 were strikingly similar in that
they all possessed an isobutyl group and had lost the
methallyl functionality. The structure of 11 was unam-
Extensive experimentation was undertaken in an effort
to obtain tricyclic ketone 4 by modifying the conditions
(4) Cycloadduct 11, mp 74.5-76.5 °C, crystallizes in space group
Pcan with cell dimensions at -172 °C of a ) 14.120(11) Å, b ) 14.598-
(15) Å, c ) 21.349(11) Å, and Z ) 8. The volume of the crystal was
(1) Address correspondence to this author at Montana State Uni-
versity.
(2) Grieco, P. A.; Kaufman, M. D.; Daeuble, J . F.; Saito, N. J . Am.
Chem. Soc. 1996, 118, 2095. Grieco, P. A.; Dai, Y. J . Am. Chem. Soc.
1998, 120, 5128.
(3) Complete equilibration of 3 to 4 was anticipated because MMX
calculations indicated 4 is more stable than 3 by 2.1 kcal.
4400.50 Å3 with density of 1.191 g cm-3. All atoms, including
a
hydrogens, were located and refined to final residuals of R(F) ) 0.0571
and Rw(F) ) 0.0472. Complete crystallographic data can be obtained
from the Molecular Structure Center, Indiana University, Bloomington,
IN 47405 (report 96072).
10.1021/jo9824192 CCC: $18.00 © 1999 American Chemical Society
Published on Web 03/05/1999

Notes
J . Org. Chem., Vol. 64, No. 7, 1999 2591
Ta ble 1. P r od u ct Distr ibu tion in th e Cycloa d d ition of Su bstr a te 1a
yield (%)b
entry
solvent
catalyst
T (°C)
time (min)
10
11
12
13
14
1
2
3
4
5
6
2.0 M LiClO4-Et2O
2.0 M LiClO4-Et2O
1.0 M LiClO4-Et2O
1.0 M LiClO4-Et2O
0.5 M LiClO4-Et2O
1.0 M LiClO4-EtOAc
1.0 M LiClO4-EtOAc
CH2Cl2
10 mol % TFA
10 mol % TFA
20 mol % TFA
15 mol % HOAc
10 mol % TFA
10 mol % TFA
10 mol % HOAc
BF3‚Et2O
rt
0
0
rt
0
60
25
60
40
60
60
120
90
25
21
21
14
13
9
21
24
22
17
13
4
24
31
25
20
16
5
8
10
5
6
5
30
32
49
80
66
71
0
0
1
7
8c
9d
-78
CH2Cl2
TMSOTf
0
60
a
b
d
All of reactions were carried out at 0.01 M in the indicated solvent. Isolated yields. c 1.1 equiv of BF3‚Et2O was employed. Reaction
was conducted initially at -78 °C employing 1.1 equiv of 2,6-lutidine and 2.0 equiv of TMSOTf.
for the cycloaddition of substrate 1 (see Table 1). When
various acidic polar media were employed, neither adduct
3 nor 4 could be detected. The table reveals that reducing
the polar nature of the medium serves to promote
hydrolysis of the intermediate heteroatom-stabilized allyl
cation 2, at the expense of cycloaddition, thus leading to
the formation of cyclohexenone 14. Attempts to promote
the Diels-Alder reaction with Lewis acids led exclusively
to cyclohexenone formation.
tube which had been pretreated with N,O-bis(trimeth-
ylsilyl)acetamide. As anticipated, the stronger base in-
hibited migration of the enol phenylthioether in all of the
cycloadducts (10, 17, and 18). We were surprised to find,
however, that tricyclic ketone 10, mp 96.5-97.5 °C, was
isolated in only 15% yield, with no trace of the endo-
derived product 3 or the more stable equilibrated adduct
4. Remarkably, the anomalous Diels-Alder adducts 17
and 18 were isolated in a ratio of ca. 2.5:1, respectively,
in a combined yield of 74%. The structures of 17 and 18
Having been unsuccessful in our attempts to prepare
tricyclic ketone 4 from 1, we directed our attention to the
thermal cycloaddition of enone 14.5 In an initial experi-
ment, a 0.02 M solution of 14 in 1,2-dichlorobenzene
containing 1.0 equiv of diethylaniline was heated at 180
°C in a sealed tube [presilylated with N,O-bis(trimeth-
ylsilyl)acetamide] for 18 h. Workup provided a 69% yield
of tricyclic ketone 15, wherein the enol phenylthioether
of the originally formed cycloadduct had migrated, and
a 17% yield of crystalline octahydroanthracenone 16, mp
164.5-165.0 °C, whose structure was established by
single-crystal X-ray analysis.6 Once again, the equili-
brated tricyclic ketone 4 or the all-cis cycloadduct 3 could
not be detected. The isolation of both 15 and 16 was
surprising and raised a number of questions. Of particu-
lar concern was the origin of these cycloadducts.
1
follow from their respective H NMR spectra and differ-
ence NOE spectroscopy.
The formation of cycloadduct 15 presumably arises
from either 10 or the elusive cycloadduct 3 via isomer-
ization of the enol phenylthioether. To address this issue,
the cycloaddition was repeated in the presence of the
more basic diisopropylethylamine (DIPEA). Thus, a 0.02
M solution of 14 in 1,2-dichlorobenzene containing 2.0
equiv of DIPEA was heated at 180 °C for 18 h in a sealed
(5) Enone 14 can be prepared in 80% yield employing 1.0 M LiClO4‚
EtOAc containing 10 mol % acetic acid at 0 °C for 2 h (see Experimental
Section).
The above results reveal the difficulties associated with
the use of (E)-thiophenyl butadienes such as 14 in
thermal Diels-Alder reactions.7 It would appear that the
(6) Cycloadduct 16 crystallizes in space group P21/c with cell
dimensions at -169 °C of a ) 11.776(2) Å, b ) 11.812(2) Å, c ) 13.535-
(3) Å, â ) 107.10(1)°, and Z ) 4. The volume of the crystal was 1799.37
Å3 with a density of 1.250 g cm-3. All atoms, including hydrogens, were
located and refined to final residuals of R(F) ) 0.0409 and Rw(F) )
0.0364. Complete crystallographic data can be obtained from the
Molecular Structure Center, Indiana University, Bloomington, IN
47405 (report 96116).
(7) The thermal isomerization of thiophenyl-substituted butadienes
has been noted previously: Voyle, M.; Kyler, K. S.; Arseniyadis, S.;
Dunlap, N. K.; Watt, D. S. J . Org. Chem. 1983, 48, 470. Grieco, P. A.;
Lis, R.; Zelle, R. E.; Finn, J . J . Am. Chem. Soc. 1986, 108, 5908.

2592 J . Org. Chem., Vol. 64, No. 7, 1999
Notes
63.3, 44.9, 30.3, 27.8, 27.7, 26.2, 25.9, 25.8, 19.0, 18.3, -5.3;
HRMS (CI) calcd for C19H37O3Si (M + 1) m/e 341.25131, found
341.25157.
activation energy for the cycloaddition of 14 is sufficiently
high that diene isomerization occurs leading to the
formation of 19, the precursor to 10, and 20, which gives
rise to the octahydroanthracenones 17 and 18. Further
studies are underway to examine the scope of this novel
Diels-Alder reaction.
6-(3-Hydr oxy-pr opyl)-3-isobu toxy-2-cycloh exen -1-on e (7).
To a solution of silyl ether 6 (6.30 g, 18.5 mmol) in 20 mL of
THF cooled to 0 °C was added a 1.0 M solution of TBAF in THF
(28 mL, 28 mmol). The resultant solution was allowed to warm
to ambient temperature overnight. The reaction mixture was
poured into 75 mL of H2O. The aqueous layer was extracted with
Et2O. The combined organic extracts were washed with H2O and
saturated aqueous brine solution, dried over anhydrous MgSO4,
and concentrated under reduced pressure. The residue was
chromatographed on 150 g of silica gel. Elution with ethyl
acetate-hexanes (3:1) containing 0.1% triethylamine afforded
4.14 g (99%) of alcohol 7 as a colorless oil: Rf 0.42 (ethyl acetate);
IR (CHCl3) 3640, 3430, 1650, 1615 cm-1 1H NMR (400 MHz,
;
CDCl3) δ 5.31 (s, 1 H), 3.63 (q, J ) 6.0 Hz, 2 H), 3.58 (d, J ) 6.6
Hz, 2 H), 2.45 (dd, J ) 7.2, 5.4 Hz, 2 H), 2.24 (m, 1 H), 2.11-
1.97 (m, 3 H), 1.87 (m, 1 H), 1.76 (m, 1 H), 1.71-1.49 (m, 3 H),
0.97 (d, J ) 6.4 Hz, 6 H); 13C NMR (100 MHz, CDCl3) δ 201.9,
177.3, 102.1, 74.7, 62.3, 44.7, 30.1, 28.0, 27.7, 26.5, 25.5, 19.0;
HRMS (CI) calcd for C13H23O3 (M + 1) m/e 227.16483, found
227.16431.
3-(4-Isob u t oxy-2-oxo-cycloh e x-3-e n yl)-p r op ion a ld e -
h yd e (8). A solution of alcohol 7 (1.79 g, 7.90 mmol) in 30 mL
of THF was cooled to -78 °C and degassed, back-filling with
argon. To this solution was added a 1.0 M solution of vinylmag-
nesium bromide (8.5 mL, 8.5 mmol) in THF. After 30 min at
-78 °C, 1,1′-(azodicarbonyl)dipiperidine11 (2.16 g, 8.56 mmol)
was added in 30 mL of THF. The resultant deep red solution
was allowed to slowly warm to 0 °C over 3 h. The reaction was
quenched with H2O (5.0 mL) and acidified with 1 N HCl (6 mL).
The resultant mixture was partitioned between hexanes (100
mL) and H2O (50 mL). The aqueous layer was extracted with
ethyl acetate, and the combined organic extracts were washed
with saturated aqueous brine, dried over anhydrous MgSO4, and
concentrated in vacuo. The product was purified by chromatog-
raphy on 150 g of silica gel. Elution with hexanes-ethyl acetate
(2:1) afforded 1.40 g (79%) of aldehyde 8 as a colorless oil: Rf
Exp er im en ta l Section 8
6-[3-ter t-Bu tyld im eth ylsilyloxy)-p r op yl)]-3-isobu toxy-2-
cycloh exen -1-on e (6). A 2.5 M solution of n-butyllithium in
hexanes (24.0 mL, 60.0 mmol) was slowly added over 6 min to
a solution of diisopropylamine (8.41 mL, 60.0 mmol) in 120 mL
of THF cooled to -20 °C. After 25 min, the resultant solution
was cooled to -78 °C. A solution of vinylogous ester 59 (8.41 g,
50.0 mmol) in 10 mL of THF was added, and the reaction
mixture was stirred at -78 °C. After 30 min, HMPA (21.0 mL,
121 mmol) was added. After an additional 5 min, a solution of
3-iodo-tert-butyldimethylsilyloxy propane10 (15.5 g, 51.7 mmol)
in 20 mL of THF was added. The reaction mixture was allowed
to warm to -20 °C. After 10 h at -20 °C, the reaction mixture
was quenched with 5 mL of H2O and was concentrated to about
1/3 volume. The remaining solution was partitioned between 200
mL of hexanes and 100 mL of H2O. The aqueous layer was
extracted with hexanes, and the combined organic extracts were
washed with saturated aqueous brine solution, dried over
anhydrous MgSO4, and concentrated in vacuo. The residue was
chromatographed on 400 g of silica gel. Elution with hexanes-
ethyl acetate (9:1) afforded 9.50 g (56%) of 6 as a colorless oil:
0.60 (ether); IR (CHCl3) 1730, 1650, 1615 cm-1 1H NMR (400
;
MHz, CDCl3) δ 9.77 (t, J ) 1.6 Hz, 1 H), 5.28 (s, 1 H), 3.56 (m,
2 H), 2.57 (td, J ) 7.6, 1.6 Hz, 2 H), 2.44 (m, 2 H), 2.22 (m, 1 H),
2.13-1.96 (m, 3 H), 1.80-1.68 (m, 2 H), 0.97 (d, J ) 6.6 Hz, 3
H), 0.95 (d, J ) 6.6 Hz, 3 H); 13C NMR (100 MHz, CDCl3) δ 202.2,
200.5, 177.0, 102.1, 74.7, 44.2, 41.6, 28.0, 27.6, 26.8, 22.3, 19.0;
HRMS (EI) calcd for C13H20O3 (M+) m/e 224.1413, found
224.1414.
3-Isob u t oxy-6-(4-p h en ylsu lfa n yl-h exa -3(E),5-d ien yl)-2-
cycloh exen -1-on e (9). A solution of freshly distilled 1-phe-
nylthio-1-trimethylsilyl allene (1.54 g, 7.00 mmol) in 7.0 mL of
THF was treated with a 0.5 M solution of 9-borabicyclo[3.3.1]-
nonane in THF (9.75 mmol, 4.88 mmol).12 The resultant solution
was heated in an oil bath for 12 h at 35 °C. After the mixture
cooled to 0 °C, a solution of aldehyde 8 (1.51 g, 6.72 mmol) in 12
mL of THF was added, and stirring was continued at 0 °C. After
3 h, 5.0 N aqueous sodium hydroxide solution (3.0 mL) was
added, and the reaction mixture was warmed to ambient
temperature. After an additional 3.5 h, the reaction was poured
into 150 mL of pentane and washed with water and saturated
aqueous brine solution. The organic layer was dried over
anhydrous MgSO4 and concentrated in vacuo. The residue was
chromatographed on 200 g of silica gel. Elution with hexanes-
dichloromethane-ethyl acetate (15:4:1) afforded 1.90 g (79%) of
(E)-diene 9 as a colorless oil: Rf 0.48 (hexanes-ethyl acetate,
Rf 0.59 (hexanes-ethyl acetate, 3:1); IR (CHCl3) 1635, 1605 cm-1
;
1H NMR (400 MHz, CDCl3) δ 5.28 (s, 1 H), 3.61 (m, 2 H), 3.56
(d, J ) 6.6 Hz, 2 H), 2.46-2.39 (m, 2 H), 2.17 (m, 1 H), 2.06 (m,
1 H), 2.00 (m, 1 H), 1.84 (m, 1 H), 1.72 (m, 1 H), 1.65-1.46 (m,
2 H), 1.40 (m, 1 H), 0.95 (d, J ) 6.9 Hz, 6 H), 0.87 (s, 9 H), 0.03
(s, 6 H); 13C NMR (100 MHz, CDCl3) δ 201.5, 176.8, 102.1, 74.6,
(8) Proton and carbon nuclear magnetic resonance spectra were
recorded on Varian VXR 400 MHz or Bruker DPX 300 MHz spectrom-
eters. Chemical shifts are reported in parts per million (δ) relative to
tetramethylsilane (δ 0.0). Infrared spectra were taken on a Perkin-
Elmer Model 298 spectrophotometer, a Mattson Galaxy 4020 series
FTIR spectrometer, or
a Perkin-Elmer model 1600 FTIR. High-
resolution mass spectra were obtained on a VG Instuments 70E-HF
mass spectrometer. Elemental analyses were performed by Robertson
Microlit Laboratories, Inc., Madison, NJ . Melting points were obtained
on a Fisher-J ohns hot-stage or a MEL-TEMP capillary melting point
apparatus and are uncorrected. Reactions were monitored by thin-layer
chromatography using E. Merck precoated silica gel 60 F-254 (0.25
mm) plates. Plates were visualized by immersion in p-anisaldehyde
solution or phosphomolybdic acid solution. E. Merck precoated silica
gel 60 F-254 (0.50 mm) plates were used for preparative plate
chromatography. E. Merck silica gel 60 (230-400 mesh) was used for
chromatography. Anhydrous lithium perchlorate was purchased and
was further dried at 180 °C under high vacuum for 24 h prior to use.
(9) Cf. Stork, G.; Danheiser, R. L. J . Org. Chem. 1973, 38, 1775.
(10) Poleschner, H.; Heydenreich, M.; Martin, D. Synthesis 1991,
1231.
1
3:1); IR(CHCl3) 1645, 1610 cm-1; H NMR (400 MHz, CDCl3) δ
7.24-7.21 (m, 4 H), 7.15 (m, 1 H), 6.72 (ddd, J ) 16.7, 10.7, 0.8
Hz, 1 H), 6.17 (t, J ) 7.2 Hz, 1 H), 5.65 (br d, J ) 16.7 Hz, 1 H),
5.31 (s, 1 H), 5.21 (br d, J ) 10.7 Hz, 1 H), 3.58 (m, 2 H), 2.48-
2.38 (m, 4 H), 2.22 (m, 1 H), 2.12-1.97 (m, 3 H), 1.75 (m, 1 H),
1.51 (m, 1 H), 0.97 (d, J ) 6.6 Hz, 6 H); 13C NMR (100 MHz,
CDCl3) δ 200.9, 176.9, 141.9, 130.2, 128.7, 128.1, 125.6, 118.8,
(11) Narasaki, K.; Morikawa, A.; Saigo, K.; Mukaiyama, T. Bull.
Chem. Soc. J pn. 1997, 500, 2773.
(12) Pearson, W. H.; Lin, K.-C.; Poon, Y.-F. J . Org. Chem. 1989, 54,
5814.

Notes
J . Org. Chem., Vol. 64, No. 7, 1999 2593
102.3, 74.8, 44.5, 29.3, 28.1, 27.7, 26.6, 26.6, 19.1; HRMS (EI)
calcd for C22H28O2S (M+) m/e 356.18114, found, 356.18096.
from pentane, mp 58.5-59.5 °C. Anal. Calcd for C26H34OS: C,
79.14; H, 8.68. Found: C, 79.18; H, 8.69.
13: IR (CHCl3) 1590, 1460 cm-1; 1H NMR (400 MHz, CDCl3)
δ 7.34 (d, J ) 7.6 Hz, 2 H), 7.28 (t, J ) 7.6 Hz, 2 H), 7.18 (t, J
) 7.6 Hz, 1 H), 6.20 (br d, J ) 6.0 Hz, 1 H), 4.76 (s, 1 H), 4.67
(s, 1 H), 3.17 (m, 2 H), 2.48 (dt, J ) 18.9, 6.0 Hz, 1 H), 2.32 (br
d, J ) 7.6 Hz, 1 H), 2.30 (ABquartet, J ) 12.3 Hz, ∆ν ) 36.7
Hz, 2 H), 2.12 (dd, J ) 18.9, 11.3 Hz, 1 H), 2.04 (dd, J ) 12.6,
5.4 Hz, 1 H), 1.97 (ABquartet, J ) 12.6 Hz, ∆ν ) 14.5 Hz, 1 H),
1.86 (dd, J ) 11.3, 6.0 Hz, 1 H), 1.80-1.49 (m, 7 H), 1.39 (m, 1
H), 0.92 (d, J ) 6.6 Hz, 3 H), 0.91 (d, J ) 6.6 Hz, 3 H); 13C NMR
(100 MHz, CDCl3) δ 144.5, 135.7, 134.9, 134.5, 129.9, 128.9,
126.2, 111.8, 77.0, 67.3, 52.1, 50.3, 48.0, 46.1, 44.2, 42.4, 34.6,
30.9, 30.1, 29.3, 26.7, 25.4, 19.7, 19.6; HRMS (EI) calcd for
C26H34OS (M+) m/e 394.23322, found, 394.23409.
3-(2-Meth yl-allyl)-4-(4-ph en ylsu lfan yl-h exa-3(E),5-dien yl)-
2-cycloh exen -1-on e (14). To a solution of substrate 1 (80 mg,
0.19 mmol) in anhydrous EtOAc (12.0 mL) cooled to 0 °C was
added 3.0 M LiClO4-EtOAc (6.0 mL) followed by glacial acetic
acid (1.1 mL). After 2 h at 0 °C, the reaction was quenched with
Et3N (15 mL). The reaction mixture was poured into H2O, and
the product was isolated by extraction with CH2Cl2. The
combined organic extracts were washed with brine, dried over
anhydrous MgSO4, and concentrated in vacuo. The crude enone
was chromatographed on silica gel. Elution with hexanes-ether
(2:1) afforded 53 mg (80%) of pure 14 as an oil: Rf 0.31(hexanes-
ethyl acetate, 4:1); IR (CHCl3) 1670, 1625, 1590 cm-1; 1H NMR
(400 MHz, CDCl3) δ 7.26-7.23 (m, 4 H), 7.15 (m, 1 H), 6.67 (ddd,
J ) 16.7, 10.7, 0.6 Hz, 1 H), 6.11 (t, J ) 7.6 Hz, 1 H), 5.90 (d, J
) 16.7 Hz, 1 H), 5.86 (s, 1 H), 5.26 (d, J ) 10.7 Hz, 1 H), 4.90 (s,
1 H), 4.78 (s, 1 H), 2.96 (d, J ) 15.1 Hz, 2 H), 2.86 (d, J ) 15.1
Hz, 2 H), 2.53-2.29 (m, 5 H), 2.09-1.94 (m, 2 H), 1.77-1.59
(m, 2 H), 1.68 (s, 3 H); 13C NMR (100 MHz, CDCl3) δ 199.2, 166.4,
141.1, 140.0, 136.1, 131.8, 129.9, 128.8, 128.5, 127.1, 125.9, 119.5,
114.4, 44.7, 36.6, 33.2, 29.8, 27.2, 25.6, 22.2; HRMS (EI) calcd
for C22H26OS (M+) m/e 338.17058, found 338.17111.
8b â-(2-Met h yl-a llyl)-8-p h en ylsu lfa n yl-2,2a â,3,4,5a â,6,-
8a r,8bâ-octa h yd r o-1H-a cen a p h th ylen e-5-on e (10), 5r-Iso-
bu toxy-10-m eth yl-8-p h en ylsu lfa n yl-2,2aâ,3,4,5aâ,6,8ar,8bâ-
octa h yd r o-1H-5â,8bâ-p r op -9-en oa cen a p h th ylen e (11), 5r-
Isobu toxy-10-m eth yl-8-p h en ylsu lfa n yl-2,2aâ,3,4,5a â,6, 8a r,-
8bâ-octa h yd r o-1H-5â,8bâ-p r op -10-en oa cen a p h th ylen e (12),
a n d 5r-Isobu toxy-8-p h en ylsu lfa n yl-2,2aâ,3,4,5a â,6,8a r,8bâ-
oct a h yd r o-1H -5â,8b â-p r op a n oa cen a p h t h ylen -10-ylid en e
(13). A 25 mL round-bottom flask was charged with magnesium
turnings (82 mg, 3.3 mmol). THF (3.0 mL) was added, and the
mixture was chilled to 0 °C. Freshly distilled 3-chloro-2-
methylpropene (0.30 mL, 3.04 mmol) was added portionwise over
90 min, and the resultant solution was allowed to stir at 0 °C.
After 1 h, the Grignard solution was cooled to -78 °C. TMEDA
(1.0 mL, 6.62 mmol) was added, and the resultant slurry was
stirred 30 min at -78 °C followed by the addition of a solution
of vinylogous ester 9 (200 mg, 0.56 mmol) in 7.1 mL of THF.
After 15 min, the bright yellow reaction mixture was quenched
with H2O and poured into 40 mL of Et2O. The organic layer was
washed with H2O, dried over anhydrous Na2SO4, and concen-
trated in vacuo. The residue was taken up in pentane and
washed with H2O and saturated aqueous brine solution. The
organic layer was dried over anhydrous Na2SO4 and concen-
trated under reduced pressure to afford 224 mg (96%) of alcohol
1 as a colorless oil, which was used directly in the next reaction.
A solution of the above alcohol 1 (109 mg, 0.264 mmol) in
anhydrous Et2O (1.3 mL) was added dropwise via syringe pump
over 9 min to 2.0 M LiClO4-Et2O (13.0 mL) containing TFA (2.0
mL, 0.026 mmol). After a total of 1 h, the reaction was quenched
by the addition of Et3N (25 mL). The reaction mixture was
diluted with H2O, and the product was extracted with CH2Cl2.
The combined organic extracts were dried over anhydrous
MgSO4 and concentrated in vacuo. The residue was chromato-
graphed on 25 g of silica gel. Elution with hexanes-ether (9:1)
afforded 59 mg of a mixture of 11-13. Further elution afforded
25 mg (25%) of cycloadduct 10. Separation of 11-13 by prepara-
tive thin-layer chromatography (hexanes-ether, 49:1) afforded
22.1 mg (21%) of 11, 24.5 mg (24%) of 12, and 7.9 mg (8%) of
13.
8bâ-(2-Meth yl-a llyl)-8-p h en ylsu lfa n yl-2,2a â,3,4,5a â,6,7,-
8b â-oct a h yd r o-1H-a cen a p h t h ylen e-5-on e (15) a n d 7,8a â-
Dim eth yl-6-p h en ylsu lfa n yl-4,4a r,5,8,8a â,9,10,10a r-octa h y-
d r o-3H-a n th r a cen -2-on e (16). A 10 mL culture tube with a
Teflon-lined cap was charged with 1 mL of N,O-bis-(trimethyl-
silyl)acetamide and heated to 180 °C for 2 h. The cooled tube
was rinsed thoroughly with CH2Cl2 and dried in vacuo. A
solution of enone 14 (34.5 mg, 0.102 mmol) in 5.1 mL of
anhydrous 1,2-dichlorobenzene was added followed by the ad-
dition of diethylaniline (18.0 µL, 0.114 mmol). The tube was
sealed and heated to 180 °C. After 18 h, the reaction mixture
was cooled to room temperature and applied directly to 45 g of
silica gel. Elution with hexanes afforded a forerun of 1,2-
dichlorobenzene. Further elution with hexanes-ethyl acetate (8:
1) afforded 24.0 mg (69%) of cycloadduct 15 as a colorless film:
10: Rf 0.45 (hexanes-ether, 3:1); IR (CHCl3) 1710, 1640, 1590
cm-1 1H NMR (500 MHz, CDCl3) δ 7.31-7.24 (m, 4 H), 7.18
;
(m, 1 H), 5.83 (q, J ) 3.5 Hz, 1 H), 4.97 (s, 1 H), 4.75 (s, 1 H),
3.05 (dt, J ) 19.7, 3.2 Hz, 1 H), 2.89 (d, J ) 7.8 Hz, 1 H), 2.60
(m, 1 H), 2.52 (dt, J ) 10.9, 7.0 Hz, 1 H), 2.39 (td, J ) 13.0, 5.6
Hz, 1 H), 2.27 (dt, J ) 13.0, 3.7 Hz, 1 H), 2.14 (d, J ) 14.1 Hz,
1H), 2.13 (m, 1 H), 2.04-1.95 (m, 2 H), 1.93 (d, J ) 14.2 Hz, 1
H), 1.92 (s, 3 H), 1.65-1.54 (m, 3 H), 1.27 (m, 1 H); 13C NMR
(100 MHz, CDCl3) δ 212.0, 143.0, 135.3, 131.0, 130.1, 130.0,
128.9, 126.4, 115.7, 53.0, 48.2, 44.4, 39.9, 38.8, 38.3, 31.9, 27.6,
25.5, 23.8, 23.3. An analytical sample was prepared by recrys-
tallization from hexanes, mp 96.5-97.5 °C. Anal. Calcd for
Rf 0.45 (hexanes-ether, 3:1); IR (CHCl3) 1705, 1645, 1590 cm-1
;
1H NMR (400 MHz, CDCl3) δ 7.27-7.23 (m, 2 H), 7.17-7.13 (m,
3 H), 4.98 (s, 1 H), 4.78 (s, 1 H), 2.74 (dd, J ) 4.3, 3.2 Hz, 1 H),
2.68 (m, 1 H), 2.57-2.29 (m, 5 H), 2.29-2.21 (m, 3 H), 2.11 (m,
1 H), 2.00 (m, 1 H), 1.91-1.72 (m, 2 H), 1.88 (s, 3 H), 1.45 (m, 1
H), 1.36 (m, 1 H); 13C NMR (100 MHz, CDCl3) δ 211.5, 149.7,
142.5, 135.0, 129.3, 128.8, 125.9, 123.4, 116.0, 53.9, 46.7, 44.5,
41.4, 40.5, 29.6, 27.3, 26.9, 25.2, 18.9; HRMS (EI) calcd for
C22H26OS (M+) m/e 338.17058, found 338.17048.
C
22H26OS: C, 78.06; H, 7.74. Found: C, 77.91; H, 7.64.
11: IR (CHCl3) 1590, 1465 cm-1; 1H NMR (400 MHz, CDCl3)
δ 7.33-7.24 (m, 4 H), 7.17 (m, 1 H), 6.21 (dd, J ) 6.8, 1.7 Hz, 1
H), 5.28 (s, 1 H), 3.20 (m, 2 H), 2.50-2.42 (m, 2 H), 2.26-2.14
(m, 2 H), 2.05-1.98 (m, 3 H), 1.90 (dd, J ) 12.3, 5.0 Hz, 1 H),
1.82 (m, 9 H), 1.47 (m, 1 H), 1.18 (m, 1 H), 0.92(d, J ) 6.6 Hz,
3 H), 0.91(d, J ) 6.6 Hz, 3 H); 13C NMR (100 MHz, CDCl3) δ
136.4, 136.3, 135.8, 135.7, 129.5, 128.9, 127.2, 126.8, 75.1, 67.4,
49.6, 47.2, 46.8, 45.3, 43.3, 32.8, 31.4, 29.3, 26.0, 23.1, 23.0, 19.6,
19.5. An analytical sample was prepared by recrystallization
from hexanes, mp 74.5-76.5 C. Anal. Calcd for C26H34OS: C,
79.14; H, 8.68. Found: C, 79.15; H, 8.67.
12: IR (CHCl3) 1590, 1470 cm-1; 1H NMR (500 MHz, CDCl3)
δ 7.34 (br d, J ) 8.1 Hz, 2 H), 7.30 (br t, J ) 8.1 Hz, 2 H), 7.20
(br t, J ) 7.0 Hz, 1 H), 6.16 (dd, J ) 6.3, 2.1 Hz, 1 H), 5.26 (s,
1 H), 3.09 (m, 2 H), 2.34 (br d, J ) 8.1 Hz, 1 H), 2.22 (dt, J )
18.0, 6.0 Hz, 1 H), 2.11 (m, 1 H), 2.08 (br d, J ) 16.9 Hz, 1 H),
1.97 (dd, J ) 11.3, 6.0 Hz, 1 H), 1.94 (m, 1 H), 1.85-1.63 (m, 7
H), 1.66 (s, 3 H), 1.48 (m, 2 H), 1.27 (m, 1 H), 0.92 (d, J ) 6.5
Hz, 3 H), 0.91 (d, J ) 6.5 Hz, 3 H); 13C NMR (100 MHz, CDCl3)
δ 136.2, 135.5, 135.4, 133.2, 130.2, 130.1, 128.9, 126.3, 78.7, 68.3,
49.8, 49.7, 46.1, 45.0, 39.2, 34.4, 33.1, 29.6, 29.1, 25.5, 25.3, 23.1,
19.7 (2C). An analytical sample was prepared by recrystallization
Further elution with hexanes-ethyl acetate (3:1) afforded 6.0
mg of 16 as a crystalline solid: Rf 0.30 (hexanes-ethyl acetate,
3:1); IR (CHCl3) 1665, 1640, 1590 cm-1 1H NMR (400 MHz,
;
CDCl3) δ 7.28-7.19 (m, 4 H), 7.15 (br t, J ) 7.3 Hz, 1 H), 5.84
(s, 1 H), 2.39 (dt, J ) 16.4, 4.6 Hz, 1 H), 2.37-2.24 (m, 3 H),
2.23-1.98 (m, 5 H), 1.97 (s, 3 H), 1.94-1.76 (m, 2 H), 1.71 (m,
1 H), 1.61 (m, 1 H), 1.06 (dt, J ) 13.1, 12.0 Hz, 1 H), 0.77 (s, 3
H); 13C NMR (100 MHz, CDCl3) δ 199.7, 164.5, 139.7, 136.4,
128.9, 128.4, 126.0, 125.5, 121.8, 49.7, 48.7, 40.3, 37.4, 36.6, 36.2,
35.7, 35.0, 29.0, 21.7, 17.3. An analytical sample was prepared
by recrystallization from ether, mp 164.5-166.0 °C. Anal. Calcd
for C22H26SO: C, 78.06; H, 7.74. Found: C, 77.97; H, 7.82.
8b â-(2-Met h yl-a llyl)-8-p h en ylsu lfa n yl-2,2a â,3,4,5a â,6,-
8a r,8bâ-octa h yd r o-1H-a cen a p h th ylen e-5-on e (10), 7â,8a â-
Dim eth yl-6-p h en ylsu lfa n yl-4,4a r,7,8,8a â,9,10,10a r-octa h y-
d r o-3H-a n th r a cen -2-on e (17), a n d 7r,8a â-Dim eth yl-6-
p h e n y lsu lfa n y l-4,4a r,7,8,8a â,9,10,10a â-o c t a h y d r o-3H -

2594 J . Org. Chem., Vol. 64, No. 7, 1999
Notes
a n th r a cen -2-on e (18). A 20 mL culture tube with a Teflon-
lined cap was charged with 4.0 mL of N,O-bis(trimethyl-
silyl)acetamide and heated to 180 °C for 2 h. The cooled tube
was rinsed thoroughly with CH2Cl2 and dried in vacuo. A
solution of enone 14 (22 mg, 0.065 mmol) in 6.5 mL of anhydrous
1,2-dichlorobenzene was added to the culture tube followed by
diisopropylethylamine (23 µL, 0.13 mmol). The tube was sealed
and heated to 180 °C. After 18 h, the reaction mixture was cooled
to ambient temperature, and the solvent was removed in vacuo
with gentle heating (40-45 °C). The residue was purified by
preparative thin-layer chromatography. Elution with hexanes-
ethyl acetate (4:1) afforded 3.3 mg (15%) of 10, which was
identical in all respects with the sample of 10 prepared above,
4.7 mg (21%) of 18, and 11.7 mg (53%) of 17.
18: Rf 0.35 (hexanes-ethyl acetate, 3:1); IR (CHCl3) 1660,
1630, 1590 cm-1 1H NMR (500 MHz, C6D6) δ 7.41 (d, J ) 7.4
;
Hz, 2 H), 7.05 (t, J ) 7.7 Hz, 2 H), 6.94 (t, J ) 7.4 Hz, 1 H), 5.86
(s, 1 H), 5.76 (dd, J ) 3.5, 2.1 Hz, 1 H), 2.31 (dt, J ) 15.7, 3.7
Hz, 1 H), 2.30 (m, 1 H), 1.98 (ddd, J ) 15.5, 14.1, 5.1 Hz, 1 H),
1.90 (br d, J ) 13.4 Hz, 1 H), 1.75 (m, 1 H), 1.52 (m, 1 H), 1.42
(br, d, J ) 13.0 Hz, 1 H), 1.30-1.12 (m, 4 H), 1.14 (d, J ) 6.4
Hz, 3 H), 1.04 (dd, J ) 13.4, 6.8 Hz, 1 H), 0.95 (ddd, J ) 13.7,
6.0, 3.9 Hz, 1 H), 0.63 (s, 3 H); 13C NMR (100 MHz, CDCl3) δ
199.6, 166.8, 137.5, 135.2 (2 C), 130.6, 129.0, 126.6, 126.1, 44.9,
43.5, 41.8, 37.3, 35.4, 34.8, 34.5, 30.9, 29.2, 26.3, 20.5. An
analytical sample was prepared by recrystallization from pen-
tane-ether, mp 175.0-177.0 °C. Anal. Calcd for C22H26SO: C,
78.06; H, 7.74. Found: C, 77.80; H, 7.75.
17: Rf 0.30 (hexanes-ethyl acetate, 3:1); IR (CHCl3) 1660,
1630, 1590 cm-1 1H NMR (500 MHz, C6D6) δ 7.44 (d, J ) 7.8
;
Hz, 2 H), 7.06 (t, J ) 7.7 Hz, 2 H), 6.96 (t, J ) 7.8 Hz, 1 H), 5.87
(s, 1 H), 5.65 (s, 1 H), 2.43 (m, 1 H), 2.31 (dt, J ) 16.2, 3.7 Hz,
1 H), 1.96 (td, J ) 16.2, 5.3 Hz, 1 H), 1.76 (br d, J ) 13.4 Hz, 1
H), 1.69 (d, J ) 14.1 Hz, 1 H), 1.60 (m, 1 H), 1.45 (d, J ) 14.1
Hz, 1 H), 1.41 (dq, J ) 13.4, 4.9 Hz, 1 H), 1.34 (dd, J ) 13.7, 8.2
Hz, 1 H), 1.23 (d, J ) 7.4 Hz, 3 H), 1.17-1.04 (m, 3 H), 0.66 (dt,
J ) 11.6, 13.4 Hz, 1 H), 0.53 (s, 3 H); 13C NMR (100 MHz, CDCl3)
δ 199.6, 164.9, 137.1, 135.0, 134.3, 130.8, 128.9, 127.4, 126.7,
49.5, 44.9 (2 C), 37.9, 37.2, 34.7, 34.3, 32.1, 29.4, 21.2, 18.9. An
analytical sample was prepared by recrystallization from pen-
Ack n ow led gm en t . This investigation was sup-
ported by a Public Health Service Research Grant from
the National Institute of General Medical Sciences (GM
33605).
Su p p or tin g In for m a tion Ava ila ble: Photocopies of the
1H and 13C NMR spectra for compounds 6-9, 13, and 14. This
material is available free of charge via the Internet at
http://pubs.acs.org.
tane-ether, mp 134.0-136.0 °C (dec). Anal. Calcd for C22H26
-
SO: C, 78.06; H, 7.74. Found: C, 77.97; H, 7.70.
J O9824192