Radical Annulation vs the 3-Exo-Trig Cyclization via Fine Tuning of the Substrate Structure

Full text of DOI:10.1021/jo9703360

J . Org. Chem. 1997, 62, 7863-7865
7863
Notes
Ra d ica l An n u la tion vs th e 3-Exo-Tr ig
Cycliza tion via F in e Tu n in g of th e
Su bstr a te Str u ctu r e1
A. Srikrishna* and S. Danieldoss
Department of Organic Chemistry, Indian Institute of
Science, Bangalore 560 012, India
crowding between the peri-hydrogen of the naphthyl
group with the olefinic proton on one side and with the
bridgehead methyl group on the other side, the olefin and
the naphthyl moieties lie orthogonal to each other, and
hence the electrophilicity of the olefin in 3 will be much
less than that of the phenyl derivative 1. An analysis of
these radical reactions revealed that only the peri-
hydrogen present in the naphthyl group is responsible
for the generation of the isotwistane from naphthyl
derivative 3. Hence, it could be reasoned that an
o-methyl group on a phenyl ring in the place of the second
ring of the naphthyl group is good enough to bring about
the radical annulation reaction to generate the isotwis-
tane. To substantiate our hypothesis, we have investi-
gated the radical annulation reactions of the o-meth-
ylphenyl substituted derivative 5, and herein we describe
our results.
Received February 24, 1997
The marine sesquiterpenes 9- and 2-isocyanopupukea-
nanes, containing the unique tricyclo[4.3.1.03,7]decane
(isotwistane) carbon framework, were first isolated by
Scheuer et al. from Phyllidia varicosa and also from its
prey, a sponge Hymeniacidon sp. The structures of these
metabolites, which protects the delicate shell-less, brightly
colored opisthobranch mollusk from its predators, were
established by a combination of degradative and single-
crystal X-ray diffraction studies.2 The presence of a novel
isotwistane carbon framework and the thermodynami-
cally unfavorable endo orientation of the isopropyl group
made isocyanopupukeananes and the corresponding ke-
tones 9- and 2-pupukeanones as challenging synthetic
targets.3 Earlier, we have developed a radical annula-
tion-based methodology4 for the construction of chiral
isotwistane, in which the key concept was the intermo-
lecular Michael addition of a bicyclo[2.2.2]oct-5-en-2-yl
radical onto a radicophile followed by 5-exo-trig cycliza-
tion of the resulting radical to generate the tricyclo-
[4.3.1.03,7]decane system. Interestingly, the phenyl de-
rivative 1 resulted only in the formation of the cyclo-
propane compound 2 via a 3-exo-trig cyclization without
incorporation of the radicophile, whereas the correspond-
ing 1-naphthyl derivative 3 resulted in the formation of
the isotwistane derivative 4 via radical annulation. The
For the preparation of the radical precursor 5, the
methoxy enone 6, readily available5 from (R)-carvone in
four steps, was chosen as the starting material. The
reaction of an epimeric mixture of the methoxy enone 6
with boron tribromide in methylene chloride at low
temperature furnished the bromoenone 5, mp 68 °C, in
68% yield, as a single diastereomer whose structure was
delineated from its spectral data. Reaction of the bromo
enone 5 with 1.1 equiv of tri-n-butyltin hydride in the
presence of an excess of methyl acrylate (20 equiv) and
a catalytic amount of AIBN in refluxing benzene fur-
nished, as anticipated, the annulation product 7, mp 118
°C, in 39% yield in a regio- and stereospecific manner.6
The structure of the annulated product 7 was established
(3) For 9-isocyanopupukeanane and 9-pupukeanone, see: Corey, E.
J .; Behforouz, M.; Ishiguro, M. J . Am. Chem. Soc. 1979, 101, 1608.
Yamamoto, H.; Sham, H. L. J . Am. Chem. Soc. 1979, 101, 1609. White,
J . D.; Schiesher, G. A. J . Org. Chem. 1980, 45, 1864. Piers, E.; Winter,
M. J ustus Liebigs Ann. Chem. 1982, 973. Hsieh, S.-L.; Chiu, C.-T.;
Chang, N.-C. J . Org. Chem. 1989, 54, 3820. For 2-isocyanopu-
pukeanane and 2-pupukeanone, see: Corey, E. J .; Ishiguro, M.
Tetrahedron Lett. 1979, 2745. Frater, G.; Wenger, J . Helv. Chim. Acta
1984, 67, 1702. Chang, N.-C.; Chang, C.-K. J . Org. Chem. 1996, 61,
4967. Srikrishna, A.; Vijaykumar, D.; Sharma, G. V. R. Tetrahedron
Lett. 1997, 38, 2003. Subba Rao, G. S. R.; Kaliappan,K. Tetrahedron
Lett. 1997, 38, 2185.
difference in reactivity of the two substrates 1 and 3 can
be visualized as follows: The phenyl substitution, due
to the styrenic nature, made the olefin in 1 electrophilic
enough to promote the 3-exo-trig radical cyclization.
Whereas, in the compound 3, due to the presence of steric
(4) Srikrishna, A.; Hemamalini, P.; Sharma, G. V. R., J . Org. Chem.
1993, 58, 2509.
(1) Chiral synthons from carvone, Part 27. For part 26, see:
Srikrishna, A.; Reddy, T. J .; Kumar, P. P. Synlett 1997, 663.
(2) (a) Burreson, B. J .; Scheuer, P. J .; Finer, J .; Clardy, J . J . Am.
Chem. Soc. 1975, 97, 4763. (b) Hagadone, M. R.; Burreson, B. J .;
Scheuer, P. J .; Finer, J . S.;Clardy, J . Helv. Chim. Acta 1979, 62, 2484.
(5) Srikrishna, A.; Sharma, G. V. R.; Danieldoss, S.; Hemamalini,P.
J . Chem. Soc., Perkin Trans. 1 1996, 1305.
(6) In addition, as earlier,5 varying amounts of minor products
derived from simple Michael addition of the initial radical were also
formed, but no attempt was made to either purify or characterize them.
S0022-3263(97)00336-8 CCC: $14.00 © 1997 American Chemical Society

7864 J . Org. Chem., Vol. 62, No. 22, 1997
Notes
from its spectral data (see the Experimental Section). The
exo,exo stereochemistry at the carbons C-4 and C-2
bearing the methoxycarbonyl and aryl groups was as-
signed on the basis of the weak coupling (2.6 and 0 Hz)
of the C-2 and C-4 endo protons with the bridgehead
proton at C-3.7 The generation of the isotwistane 7 is
totally in agreement with our reasoning that only an
o-methyl group is enough (instead of the naphthyl group)
to change the course of the reaction and to bring about
the radical annulation reaction. To substantiate further,
radical annulation reaction of the bromo enone 5 with
methyl vinyl ketone as radicophile was also carried out.
Thus, reaction of the bromo enone 5 with tri-n-butyltin
hydride (1.1 equiv), excess of methyl vinyl ketone, and
AIBN (catalytic) in refluxing benzene (0.01 M) furnished
the diketone 8, mp 125 °C, in 40% yield, whose structure
was delineated from its spectral data in comparison with
that of the keto ester 7.
in contrast to the corresponding phenyl derivative 1,
demonstrated the possibility of fine tuning, by slight
variation in substrate structure, to alter the course of an
organic reaction and to bring about a reaction of choice.
Exp er im en ta l Section
Melting points were recorded in capillaries and not corrected.
In 1H and 13C NMR spectra, chemical shifts (δ) and coupling
constants (Hz) are reported in the standard fashion with
reference to either internal tetramethylsilane (for 1H) or the
central line (77.1 ppm) of CDCl3 (for 13C). In 13C NMR spectra,
the nature of the individual carbons were identified by either
off-resonance decoupling or SEFT experiments and are given
in parentheses. Dry benzene was obtained by distillation over
sodium. Dry ether was obtained by washing with ferrous sulfate
followed by distillation over sodium. BBr3, nBu3SnH, 10% Pd/
C, and p-TSA were obtained from Fluka and were used without
further purification. AIBN was recrystallized from methanol
and stored in dark.
(-)-(1R,4R,8S)-8-Br om o-1,8-d im et h yl-6-(2-m et h ylp h en -
yl)bicyclo[2.2.2]oct-5-en -2-on e (5). To a cold (-78 °C), mag-
netically stirred, methylene chloride solution of an epimeric
mixture of the enone 65 (3.0 g, 11.1 mmol) was added boron
tribromide (1.4 mL, 3.71 g, 14.8 mmol). The reaction mixture
was stirred at -30 °C for 1.5 h and then quenched with
saturated aqueous NaHCO3 solution (5 mL). The organic layer
was separated, and the aqueous layer was extracted with
methylene chloride (2 × 10 mL). The combined organic layer
was washed with water and brine and dried over anhydrous
Na2SO4. Evaporation of the solvent and purification of the
product on a silica gel (25 g) column using ethyl acetate-hexane
(1:4) as eluent furnished the bromo enone 5 (2.4 g, 67.7%) which
was recrystallized from hexanes: mp 68 °C; [R]25D -164.2 (c 0.14;
CHCl3); IR (neat) 1722 cm-1; 1H NMR (200 MHz, CDCl3) δ 7.20-
7.0 (3 H, m), 6.8 (1 H, br s), 6.31 (1 H, d, J ) 6.7 Hz), 3.28 (1 H,
m), 3.14 (1 H, d of 1/2 AB q, J ) 18.7 and 2 Hz), 2.62 (1 H, 1/2 AB
With the ready availability of the annulated products
7 and 8, attention was turned to their elaboration into
pupukeanones exploiting the steric crowding of the C-9
keto group. Thus, reaction of the tricyclic diketone 8 with
methylenetriphenylphosphorane furnished the keto olefin
9, mp 117 °C, in 56% yield in a highly regioselective
manner. Catalytic hydrogenation of the keto olefin 9
using 10% Pd-C in ethyl acetate at one atmosphere
pressure of hydrogen (balloon) furnished 10-(2-meth-
ylphenyl)-5-epipupukean-9-one (10), mp 84 °C, in 90%
yield. Whereas treatment of the ester 7 with an excess
of methylmagnesium iodide furnished the tertiary alcohol
12, which on dehydration with p-toluenesulfonic acid in
refluxing benzene using a Dean-Stark apparatus fur-
nished the olefin 11. Finally, stereoselective hydrogena-
tion of the olefin 11 using 10% Pd-C in ethanol at 40
psi of hydrogen pressure furnished 10-(exo-2-methylphen-
yl)pupukean-9-one 13, mp 86 °C, containing traces of the
epimer 10, in 92% yield.
1
q, J ) 15.2 Hz), 2.39 (1 H, d of /2 AB q, J ) 18.7 and 3.3 Hz),
2.3-2.0 (7 H, m), 0.85 (3 H, s); 13C NMR (22.5 MHz, CDCl3) δ
209.9 (s), 144.5 (s), 137.3 (s), 135.4 (s), 131.5 (d), 129.8 (d), 128.6
(d), 127.7 (d), 125.4 (d), 67.6 (s), 53.4 (s), 50.7 (t), 47.2 (d), 38.9
(t), 36.7 (q), 20.4 (q), 15.2 (q); mass, m/ z 320 (M+ for C17H1981BrO,
20), 318 (M+ for C17H1979BrO 20); HRMS m/ z calcd for C17H19BrO
318.0619, found 318.0625. Anal. Calcd for C17H19BrO: C, 63.96;
H, 6.00. Found: C, 64.16; H, 5.95.
(+)-Meth yl (1R,2R,3R,4S,6R,7R)-1,6-Dim eth yl-2-(2-m eth -
ylp h en yl)-9-oxotr icyclo[4.3.1.03,7]d eca n e-4-ca r boxyla te (7).
A solution of the bicyclic bromo enone 5 (354 mg, 1.11 mmol),
nBu3SnH (0.35 mL, 1.21 mmol), freshly distilled methyl acrylate
(2.0 mL, 20 mmol), and AIBN (∼10 mg) in dry benzene (55 mL)
was refluxed for 1 h. The reaction mixture was cooled, washed
with 1% aqueous NH4OH solution and brine, and dried over
anhydrous Na2SO4. Evaporation of the solvent and purification
of the residue on a silica gel (15 g) column using ethyl acetate-
hexane (1:9) as eluent furnished the annulated product 7 (140
mg, 38%), which was recrystallized from hexanes: mp 118 °C;
[R]24D +22.2 (c 0.045, CHCl3); IR (neat) 1722, 1700 cm-1; 1H NMR
(200 MHz, CDCl3) δ 7.15-7.0 (3 H, m), 6.83-6.79 (1 H, m), 3.63
(3 H, s), 2.94 (1 H, d, J ) 2.6 Hz), 2.89 (1 H, dd, J ) 9.2 and 5.3
Hz), 2.6 (2 H, d of AB q, J ) 16.0 and 2.0 Hz), 2.6 (1 H, m), 2.35
1
(3 H, s), 2.16 (1 H, d of /2 AB q, J ) 14 and 9.2 Hz), 2.04 (1 H,
d of 1/2 AB q, J ) 14 and 5.3 Hz), 1.95-2.25 (1 H, m), 1.66 (2 H,
AB q, J ) 15.2 Hz), 1.17 (3 H, s), 0.75 (3 H, s); 13C NMR (100
MHz, CDCl3) δ 215.9 (C), 176.2 (C), 141.8 (C), 136.0 (C), 130.5
(CH), 126.6 (CH), 126.3 (2 C, CH), 52.9 (CH3), 51.8 (CH), 50.9
(CH2), 50.5 (CH), 49.5 (CH), 48.1 (C), 45.4 (CH2), 43.3 (CH), 39.5
(C), 35.5 (CH2), 26.0 (CH3), 20.8 (CH3), 17.9 (CH3); mass, m/ z
326 (M+, 45); HRMS m/ z calcd for C21H26O3 326.1882, found
326.1871. Anal. Calcd for
Found: C, 77.04; H, 8.11.
C21H26O3: C, 77.27; H, 8.03.
(+)-(1R ,2R ,3R ,4S ,6R ,7R )-1,6-Dim e t h y l-4-a c e t y l-2-(2-
m eth ylp h en yl)tr icyclo[4.3.1.03,7]d eca n -9-on e (8). A solution
of the bicyclic bromo enone 5 (432 mg, 1.34 mmol), nBu3SnH (0.4
mL, 1.47 mmol), freshly distilled methyl vinyl ketone (2.2 mL,
26 mmol) and AIBN (∼10 mg) in dry benzene (73 mL) was
refluxed for 1 h. The reaction mixture was cooled to room
temperature, washed with 1% aqueous NH4OH solution and
In conclusion, the radical annulation mediated forma-
tion of the isotwistanes 7 and 8 from the bromo enone 5,
(7) Greuter, H.; Schmid, H. Helv. Chim. Acta 1972, 55, 2382.

Notes
J . Org. Chem., Vol. 62, No. 22, 1997 7865
brine, and dried over anhydrous Na2SO4. Evaporation of the
solvent and purification of the residue on a silica gel (15 g)
column using ethyl acetate-hexane (1:9) as eluent furnished the
annulated product 8 (166 mg, 40%), which was recrystallized
anhydrous Na2SO4. The solvent was evaporated, and the
residue was purified on a silica gel (5 g) column using ethyl
acetate-hexane (1:9) as eluent to furnish the tertiary alcohol
12 (30 mg, 60%) which was recrystallized from hexanes: mp
from hexanes: mp 125 °C; [R]24 +90 (c 0.1, CHCl3); IR (neat)
121 °C; [R]24 -28 (c 0.25, CHCl3); IR (neat) 3450, 1710 cm-1
;
D
D
1710 cm-1; 1H NMR (200 MHz, CDCl3) δ 7.2-7.0 (3 H, m), 6.85-
6.75 (1 H, m), 2.99 (1 H, dd, J ) 9.5 and 5.3 Hz), 2.97 (1 H, d,
J ) 3.0 Hz), 2.66 and 2.49 (2 H, d of AB q, J ) 20.1 and 3.1 Hz),
2.58 (1 H, m), 2.34 (3 H, s), 2.13 (3 H, s), 2.1 (1 H, d of 1/2 AB q,
J ) 13.5 and 9.5 Hz), 1.90 (1 H, m), 1.92 (1 H, d of 1/2 AB q, J )
13.5 and 5.3 Hz), 1.71 and 1.62 (2 H, AB q, J ) 14.5 Hz), 1.14
(3 H, s), 0.75 (3 H, s); 13C NMR (100 MHz, SEFT, CDCl3) δ 215.8
(C), 209.1 (C), 141.9 (C), 135.8 (C), 130.5 (CH), 126.7 (CH), 126.4
(CH), 126.3 (CH), 58.9 (CH), 53.0 (CH), 50.8 (CH2), 48.3 (C), 47.6
(CH), 44.1 (CH2), 43.0 (CH), 39.9 (C), 35.6 (CH2), 28.7 (CH3),
26.0 (CH3), 20.9 (CH3), 17.9 (CH3); mass, m/ z 310 (M+, 100);
HRMS m/ z calcd for C21H26O2 310.1933, found 310.1944.
(+)-(1R,2R,3S,4S,6R,7R)-1,6-Dim et h yl-4-isop r op en yl-2-
(2-m eth ylp h en yl)tr icyclo[4.3.1.03,7]d eca n -9-on e (9). To a
magnetically stirred suspension of methyltriphenylphosphonium
bromide (85 mg, 0.24 mmol) in dry benzene (1 mL) was added a
1 M solution of potassium tert-amyloxide in dry tert-amyl alcohol
(0.16 mL, 0.16 mmol), and the resultant yellow solution was
stirred at room temperature for 30 min. The Wittig reagent was
cooled to 0 °C, a benzene (0.5 mL) solution of the tricyclic ketone
8 (25 mg, 0.08 mmol) was added, and the mixture stirred at room
temperature for 5 h. The reaction mixture was diluted with
ether (5 mL), washed with aqueous 0.5 N HCl and brine, and
dried over anhydrous Na2SO4. Evaporation of the solvent and
purification of the residue on a silica gel (5 g) column using ethyl
acetate-hexane (1:9) as eluent furnished the tricyclic olefin 9
(14 mg, 56%) which was recrystallized from hexanes: mp 117
1H NMR (200 MHz, CDCl3) δ 7.2-7.0 (3 H, m), 6.86-6.81 (1 H,
m), 3.03 (1 H, d, J ) 2.4 Hz), 2.7 and 2.51 (2 H, d of AB q, J )
1
20.1 and 3.0 Hz), 2.36 (3 H, s), 2.28 (1 H, m), 2.10 (1 H, d of /2
AB q, J ) 13.4 and 8 Hz, H-5a), 1.95 (1 H, m), 1.84 (1 H, d, J )
13.4 Hz), 1.71 and 1.59 (2 H, AB q, J ) 14.2 Hz), 1.54 (1 H, m),
1.16 (9 H, s), 0.73 (3 H, s); mass, m/ z 326 (M+, 4); HRMS m/ z
calcd for C22H30O2 326.2246, found 326.2222.
Deh yd r a tion . A solution of the tertiary alcohol 12 (30 mg,
0.09 mmol) and p-toluenesulfonic acid (catalytic) in dry benzene
(5 mL) was refluxed using a Dean-Stark apparatus for 30 min.
The reaction mixture was cooled, washed with aqueous saturated
NaHCO3 solution and brine, and dried over anhydrous Na2SO4.
The solvent was evaporated under reduced pressure, and the
residue was purified on a silica gel (5 g) column using ethyl
acetate-hexane (1:9) as eluent to furnish the tricyclic olefin 11
(24 mg, 85%) as an oil: [R]26 +76 (c 0.72, CHCl3); IR (neat)
D
1715 cm-1; 1H NMR (270 MHz, CDCl3) δ 7.2-7.0 (3 H, m), 6.86
(1 H, d, J ) 7.5 Hz), 3.06 (1 H, d, J ) 1.9 Hz), 2.94 (1 H, br s),
1
2.73 (1 H, d of /2 AB q, J ) 20.3 and 3.2 Hz), 2.59 (1 H, d of 1/2
AB q, J ) 20.3 and 2.5 Hz), 2.38 and 2.25 (2 H, AB q, J ) 15.6
Hz), 2.28 (3 H, s), 1.90 (1 H, br s), 1.71 and 1.62 (2 H, AB q, J
) 14.3 Hz), 1.61 (3 H, s), 1.45 (3 H, s), 1.19 (3 H, s), 0.68 (3 H,
s); 13C NMR (100 MHz, SEFT, CDCl3) δ 215.7 (C), 142.2 (C),
139.6 (C), 136.0 (C), 130.1 (CH), 126.7 (CH), 126.5 (CH), 126.0
(CH), 120.9 (C), 52.9 (CH), 49.6 (CH2), 49.2 (C), 48.6 (CH), 47.5
(CH2), 44.4 (CH), 39.1 (C), 36.3 (CH2), 26.2 (CH3), 21.0 (CH3),
20.7 (CH3), 20.5 (CH3), 17.8 (CH3); mass, m/ z 308 (M+, 60);
HRMS m/ z calcd for C22H28O 308.2140, found 308.2134.
°C; [R]24 +13.33 (c 0.15, CHCl3); IR (neat) 1700 cm-1; 1H NMR
D
(200 MHz, CDCl3) δ 7.2-7.0 (3 H, m), 6.82 (1 H, dd, J ) 7.1 and
2.3 Hz), 4.68 (2 H, s), 2.98 (1 H, d, J ) 2.4 Hz), 2.64 (1 H, dd, J
) 9 and 5.6 Hz), 2.57 (2 H, t, J ) 3.4 Hz), 2.35 (3 H, s), 2.24 (1
1
H, m), 2.09 (1 H, d of /2 AB q, J ) 13.0 and 9.2 Hz), 2.0 (1 H,
m), 1.77 (3 H, s), 1.73 and 1.60 (2 H, AB q, J ) 18.2 Hz), 1.73-
1.60 (1 H, m), 1.13 (3 H, s), 0.81 (3 H, s); 13C NMR (100 MHz,
CDCl3, SEFT) δ 217.3 (C), 148.9 (C), 142.6 (C), 136,.2 (C), 130.5
(CH), 126.4 (CH), 126.0 (2 C, CH), 108.2 (CH2), 54.4 (CH), 53.9
(CH), 51.3 (CH2), 50.0 (CH), 48.1 (C), 47.6 (CH2), 43.2 (CH), 39.8
(C), 35.9 (CH2), 26.2 (CH3), 22.0 (CH3), 20.9 (CH3), 18.2 (CH3);
mass, m/ z 308 (M+, 93); HRMS m/ z calcd for C22H28O 308.2140,
found 308.2149.
(+)-(1R,2R,3R,4S,6R,7R)-1,6-Dim eth yl-4-(p r op a n -2-yl)-2-
(2-m eth ylp h en yl)tr icyclo[4.3.1.03,7]d eca n -9-on e (10) [10-(2-
Meth ylp h en yl)-5-ep ip u p u k ea n -9-on e]. A suspension of the
tricyclic olefin 9 (5 mg, 0.02 mmol) and 10% Pd-C (catalytic) in
ethyl acetate (5 mL) was magnetically stirred under a H2
atmosphere (balloon) for 4 h. The reaction mixture was filtered
through a silica gel (2 g) column using ethyl acetate-hexane
(1:9) as eluent to furnish the hydrogenated product 10 (4 mg,
(+)-(1R,2R,3R,4R,6R,7R)-1,6-Dim eth yl-4-en d o-isop r op yl-
2-(2-m et h ylp h en yl)t r icyclo[4.3.1.03,7]d eca n -9-on e (13).
A
suspension of the tricyclic olefin 11 (70 mg, 0.22 mmol) and 10%
Pd-C (70 mg, 0.06 mmol) in dry ethanol (2 mL) was placed in
a 250 mL pressure bottle and hydrogenated at 40 psi for 5 h in
a Parr type hydrogenation apparatus for 20 h. The catalyst was
filtered off using a Buchner funnel. Evaporation of the solvent
furnished the pupukean-9-one 13 (65 mg, 92%) which was
recrystallized from hexanes: mp 86 °C; [R]25 +73.3 (c 0.6,
D
CHCl3); IR (Nujol) 1715 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.2-
7.0 (3 H, m), 6.78 (1 H, d, J ) 7.5 Hz), 3.17 (1 H, d, J ) 3.1 Hz),
2.67 (1 H, d of 1/2 AB q, J ) 20 and 3.5 Hz), 2.51 (1 H, d of 1/2 AB
q, J ) 20 and 2.5 Hz), 2.39 (1 H, q, J ) 3.6 Hz), 2.33 (3 H, s),
2.07 (1 H, d of d, J ) 13.5 and 9.8 Hz), 1.89 (1 H, q, J ) 3.2 Hz),
1.75-1.5 (2 H, m), 1.43 (1 H, dd, J ) 13.5 and 8.1 Hz), 1.12 (3
H, s), 0.91 (3 H, d, J ) 6.2 Hz), 0.56 (3 H, d, J ) 6.2 Hz), 0.66
(3 H, s); 13C NMR (100 MHz, CDCl3) δ 216.2 (C), 142.6 (C), 136.0
(C), 130.0 (CH), 127.4 (CH), 126.4 (CH), 125.9 (CH), 52.2 (CH2),
50.7 (CH), 48.6 (C), 48.5 (CH), 48.3 (CH2), 45.9 (CH), 43.0 (CH),
39.2 (C), 36.4 (CH2), 31.1 (CH), 27.0 (CH3), 21.7 (CH3), 21.6
(CH3), 20.4 (CH3), 17.6 (CH3); mass m/ z 310 (M+, 100); HRMS
m/ z calcd for C22H30O 310.2296, found, 310.2293.
80%), which was recrystallized from hexanes: mp 84 °C; [R]24
D
+84.6 (c 0.13, CHCl3); IR (neat) 1720 cm-1; 1H NMR (400 MHz,
CDCl3) δ 7.1-6.95 (3 H, m), 6.73 (1 H, d, J ) 7.04 Hz), 2.9 (1 H,
d, J ) 2.2 Hz), 2.55 and 2.45 (2 H, d of AB q, J ) 19.9 and 3.0
1
Hz), 2.28 (3 H, s), 2.08 (1 H, br s), 1.86 (1 H, d of /2 AB q, J )
13.3 and 8.7 Hz), 1.74 (1 H, m), 1.65-1.50 (3 H, m), 1.36 (1 H,
1
m), 1.34 (1 H, d of /2 AB q, J ) 13.0 and 4.6 Hz), 1.04 (3 H, s),
0.77 (3 H, d, J ) 6.5 Hz), 0.74 (3 H, d, J ) 6.5 Hz), 0.66 (3 H, s);
13C NMR (100 MHz, CDCl3, SEFT) δ 217.3 (C), 142.6 (C), 136.0
(C), 130.3 (CH), 126.5 (CH), 126.3 (CH), 125.9 (CH), 55.5 (CH),
54.8 (CH), 50.7 (CH2), 49.1 (CH), 48.4 (C), 46.5 (CH2), 42.7 (CH),
39.7 (C), 36.0 (CH2), 33.0 (CH), 26.6 (CH3), 21.7 (CH3), 20.9
(CH3), 20.2 (CH3), 18.1 (CH3); mass, m/ z 310 (M+, 100); HRMS
m/ z calcd for C22H30O 310.2296, found 310.2301.
(+)-(1R,2R,3R,6R,7R)-1,6-Dim et h yl-4-isop r op ylid en e-2-
(2-m eth ylp h en yl)tr icyclo[4.3.1.03,7]d eca n -9-on e (11): Gr ig-
n a r d Rea ction . To a freshly prepared, magnetically stirred,
ice-cold suspension of methylmagnesium iodide [prepared from
methyl iodide (0.56 mL, 8 mmol) and magnesium (190 mg, 8
mmol) in 5 mL of dry ether] was added a solution of the tricyclic
ester 7 (50 mg, 0.16 mmol) in dry benzene (5 mL). The reaction
mixture was refluxed for 4 h, cooled, and quenched with aqueous
NH4Cl solution (5 mL). The organic phase was separated, and
the aqueous phase was extracted with ether (3 × 10 mL). The
combined ether extract was washed with brine and dried over
Ack n ow led gm en t. We thank the CSIR, New Delhi,
for the award of a research fellowship to S.D., and
Sophisticated Instrumentation Facility for recording the
high-field NMR spectra.
Su p p or tin g In for m a tion Ava ila ble: 1H and 13C NMR
spectra for compounds 8, 9, 10, 11, and 13 (10 pages). This
material is contained in libraries on microfiche, immediately
follows this article in the microfilm version of the journal, and
can be ordered from the ACS; see any current masthead page
for ordering information.
J O9703360