Author's personal copy

Tetrahedron 66 (2010) 164–171

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Tetrahedron
journal homepage: www.elsevier.com/locate/tet

Wittig-selectivity in mixed ketones: exploring 1,3-interaction and enolization

Asitanga Ghosh, Indrajit Chakraborty, Nayarussery N. Adarsh, Saswati Lahiri *
Department of Organic Chemistry, Indian Association for the Cultivation of Science, Kolkata 700032, India

a r t i c l e i n f o a b s t r a c t

Article history: The present work explored the primary factors governing regioselectivity of Wittig olefination in bicy-
Received 17 September 2009 clo[2.2.2]oct-5-en-2-ones having 5-aroyl or acyl substitutions. In absence of steric congestion less eno-
Received in revised form 21 October 2009 lizable ketone kinetically favored the initial formation of the oxaphosphetane ring whereas, in presence
Accepted 3 November 2009
of 1,3-interaction between phosphonium ylide and ketone substitutions could switch over the selectivity
Available online 10 November 2009
in other direction.
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Mixed ketone
Selective intramolecular olefination
1,3-Interaction

1. Introduction 1,3

The Wittig reaction occupies a position of central importance in L3 P O H H

H H R
organic syntheses since it can convert a carbonyl group to a double R R' R'
PL 3 O 4
bond with high level of geometrical control.1,2 Extensive work on +
-780 3
syn
reaction mechanism using triphenylphosphonium ylides has R H H R'
1 2
shown presence of Li-ion containing salts and stability of the in- L3 P O H R'
termediate ylide determine the ratio of formation of resultant Z and H R'
R H R H
E-alkenes.3 A detailed analysis of the transition state energies for 1,2 4'
Wittig reactions of aldehydes under salt-free condition provided anti
3'
support for, (i) involvement of oxaphosphetane mechanism and
Scheme 1. A general Wittig reaction of an aldehyde.
ruled out intervention of any betaine mechanism; (ii) involvement
of both the initial addition and the subsequent elimination as key
steps in determining E/Z selectivity; (iii) involvement of primarily
containing more than one carbonyl groups, the selectivity of ole-
1,2 and 1,3 steric interactions between phosphonium ylides and
fination has not been much looked into. It has been stated that the
aldehydes to form a trans-planar or, cis-puckered transition state
overall structural details has more influence on the selectivity of
which in turn, decide the E/Z selectivity.4 Thus, oxaphosphetanes
Wittig olefination in ketones than in aldehydes.3a However, no
(3, 30 ) are formed as the intermediates for these reactions by formal
detailed work on structure-reactivity relationship in molecules
[2þ2] cycloaddition (Scheme 1), which then, depending on the
with multiple carbonyl groups has yet been reported in the litera-
nature of interaction, decompose to yield syn or anti olefin and
ture. In this present work we tried to bridge this gap using mole-
phosphine oxide.5
cules containing enolizable cyclic ketone as well as an acyclic
While detailed work have been reported on mechanism and
ketone which, depending on the attached substituent may or may
selectivity of Wittig reactions with aldehydes, such data with ke-
not enolize.
tones are much inadequate.3a Furthermore, most of the mecha-
nistic details of carbonyl compounds are generally centered around
the correlation of the stabilities of the ylide and the ratio of E-Z
2. Results and discussion
geometries of the resulting alkenes whereas, in molecules
For the present work we selected 5-aroyl or acyl derivatives of
bicyclo[2.2.2]oct-5-en-2-ones, 5a–l as the model compounds most
* Corresponding author. Tel.: þ91 33 2473 4971; fax: þ91 33 2473 2805. of which were prepared following reported procedures.6 For
E-mail address: ocsl@iacs.res.in (S. Lahiri). identifying the primary factors governing regioselectivity in such

0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.11.006
 Author's personal copy

A. Ghosh et al. / Tetrahedron 66 (2010) 164–171 165

mixed carbonyl compounds Wittig reactions were carried out un- replacement of the iso-propyl group by a methyl resulted in re-
der the following limiting conditions: (a) the double bond was in- duction of steric congestion in 5h yielding a 1:1 mixture of 6h and
corporated in the rigid system to avoid E-Z isomerization of the 7h. In the case of 5i where both types of carbonyl experienced
enone; (b) to minimize 1,2-interaction and to avoid the possibility similar steric congestion, the nonenolizable acyclic ketone was
of E-Z isomerization in the products, methyltriphenylphosphonium preferentially olefinated to give 6i and 7i in 4:1 ratio however, the
iodide has been used for the present work; (c) to minimize the reaction became much sluggish here (Table 1).
probability of bis-olefination, 1 equiv of this reagent was slowly Depending on the molecular framework, even a remote sub-
added to THF solution of the ketones. stitution can interfere with the initial step of cycloaddition, Thus,
Dropwise addition of triphenyl phosphonium methylide to although 7d was the only product from 5d, from 5j only product
a THF solution of 5a under argon atmosphere at low temperature was 6j with w40% recovery of the starting material. Reaction with
followed by work-up of the reaction mixture after 0.5 h gave 6a as 5k was found to be an extremely unfavorable one and 67% of the
the exclusive product (Scheme 2). For ketones, risk of enolization is starting material was recovered from the reaction with 7k in only
expected to be one of the interfering factors in the initial addition 29% yield (Scheme 3, Table 2).
process of oxaphosphetane ring formation. In the present case, as
expected, olefination took place selectively at the non-enolizable
carbonyl group. When R was replaced by an iso-propyl group (5b), O O
reactivity of the acyl ketone was substantially reduced due to en- Ph 3P=CH 2
hanced enolizability. The less enolizability of the saturated acyl 2- or,
R (1 eq) R R
keto group in this case appeared to guide preferential olefination at
O O
this carbonyl under the same reaction condition to give 7b along 5j,k 6j 7k
with minor amount of the other olefin 6b (Scheme 2). The struc-
Scheme 3. Wittig reactions of 5j–k.
tures of the products were confirmed from their analytical and
spectral data.
Table 2
Yields from Wittig reactions of 5j and 5k
O O
Entry R 5(Rec) (%) 6 (%) 7 (%)
R2 R2 R2
Ph3 P=CH2 j Ph 40 48
+ d
R (1 eq) R R k CHMe2 67 d 29
R1 R1 R1
O O
5a-i 6a-i 7a-i
where,
a: R=Ph; R1 =R2 = H b: R=CHMe2 ; R 1=R2 = H The effect of steric congestion also explains the reported selec-
c: R=R 1 =Ph; R2 =H d: R=Ph; R 1=Me; R 2=H tive olefination of 8a–d where the enolizable but less sterically
e: R=Ph; R1 =OMe; R2 =H f : R=Ph; R1 =H; R 2=Me crowded cyclic ketone took part in the olefination (Scheme 4).8
g: R=CHMe 2;R 1=Me;R 2=H h: R=R 1=Me; R2 =H
i: R=Ph; R1 =R2 =Me
Scheme 2. Wittig reactions of 5a–i. O

R2 Ph3 P=CH 2 R2
Since steric hindrance in the reactants is also known to com-
plicate Wittig reactions of ketones3a,7 we wished to compare its O R1 Toluene, 700 O R1
effect with that of enolization. When the reaction was carried out 8a-d 9a-d
with 5c–e, enolizable 2-keto group was found to be preferentially where, a: R1 =CO 2 Et; R2 =H; 42%
olefinated giving 7c–e as exclusive/major products (Scheme 2, b: R 1 =R 2=CO 2 Me; 25%
Table 1). Similarly, in the case of 5f the only product obtained was c: R1 =Ph; R 2=H; 90%
6f. In all cases 1,3-interaction between the carbonyl substituents d: R 1 =R 2=Ph; 96%
and phenyl ring of the PPh3 ylide appeared to guide the preferential
Scheme 4. Selective Wittig reaction of 8a–d.
regioselectivity of initial oxaphosphetane ring formation.

Table 1 In Wittig reaction, enhanced electronic and steric 1,3-intractions

Yields from Wittig reactions of 5a–i
between the ketone substituents and the phenyl groups attached to
Entry R R1 R2 5 (%) 6 (%) 7 (%) phosphorous atom tend to destabilize the first step of cycloaddition
(Rec) and puckering of the transition structure is expected to decrease
a Ph H H 9 78 d this destabilizing effect specially for non-stabilized ylides.4,5 From
b CHMe2 H H 5 15 74 all the examples it appeared the first step of oxaphophetane for-
c Ph Ph H 21 d 73
d Ph Me H 15 d 79
mation is kinetically guided by these two effects. This was evident
e Ph OMe H 23 9 62 from the observations that while 5l9 under similar reaction con-
f Ph H Me 18 76 d dition exclusively yielded 7l with 12% recovery of the starting
g CHMe2 Me H 38 d 58 material, use of excess of the ylide now olefinated the sterically
h Me Me H 46 52
d
congested acyclic ketone to give 10 (Scheme 5). Also, when the
i Ph Me Me 46 41 11
cyclic ketone was protected, the ketal 1110 under similar condition
yielded the olefin 12 in 85% yields.
Since betaines are reported to be stabilized in presence of strong
That the steric factor often plays a more dominant role than the co-ordinating ions like Li-salt11 we wished to compare our results
enolizability of the ketone in this initial step was evident from the under Li-free condition to understand if betaines are involved in
reaction of 5g where the olefination was totally retarded at the these reactions. The base used for this purpose was potassium t-
acyclic ketone and 7g became the sole product. On the other hand, butoxide and the product 7d obtained from 5d was 76% ,which was
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166 A. Ghosh et al. / Tetrahedron 66 (2010) 164–171

comparable with the yield using BuLi as base (79%). Such an ob-
servation along with the report that increasing bulk of the carbonyl
substituents disfavors betaine formation4 favored oxaphosphetane
as intermediates in these reactions.

Ph3 P=CH 2
(1 eq), 73% Ph
H O
7l

Ph3 P=CH 2
Ph (2.5 eq), 82% Ph
H O H
5l 10
Ethylene glycol, D-CSA,
Toluene, 3h
O O
O O
Ph 3P=CH2 Figure 1. Thermal ellipsoid plot of 5aH0 (color code Cdgray, Odblack, Hdwhite).
Ph (1 eq), 85% Ph
H O H O
11 12
a molecule having mixed ketones and even a remote substitution in
Scheme 5. Wittig reactions of 5l and 11. such cases can interfere in selecting the site of olefination. In ab-
sence of appreciable steric congestion the preference is guided by
At this stage we wished to investigate if the influence of the the enolizability of the ketone. Since salt-effect was not observed in
endocyclic double bond on the regioselectivity of the reaction. On these reactions, involvement of oxaphosphetanes has been pre-
catalytic hydrogenation, 5a gave two diastereomeric products 5aH ferred as intermediates.
(73%) and 5aH0 (22%) (Scheme 6). While from analytical and
spectral analyses the stereochemistry of the products could not be 4. Experimental
ascertained.
4.1. General
O O O
All melting points were measured in a Gallenkamp melting
H2 /Pd-C point apparatus. UV absorption spectra were recorded on a Shi-
Ph 1h COPh + H
madzu UV-2401PC spectrophotometer. The IR spectra were recor-
R1 R1 COPh
O H ded on an FTIR-8300 Shimadzu spectrometer. The NMR spectra
5aH, 5dH 5aH'
5a,5d
(73%), (64%) (22%)
were recorded in CDCl3 solution at 300 MHz for 1H and at 75 MHz
where, a: R1 = H for 13C on a Brucker AC-300 spectrometer using tetramethylsilane
b: R 1= Me Ph3 P=CH2 as an internal standard. Elemental analyses were performed on
(1 eq.)
a 2400 series-II Perkin–Elmer CHN analyzer. High Resolution Mass
O Spectra were recorded on a Qtof Micro YA263 spectrometer. Flash
Column Chromatography was performed using silica gel (230–400
Ph mesh) under medium pressure and ordinary column chromatog-
COPh
7dH H 6aH H raphy was performed using silica gel (60–120 mesh). Petroleum
(89%) (87%) ether used was of the boiling range 60–80  C and is referred as PE.
Ether refers to diethyl ether. EA refers to ethyl acetate. 1-phenyl-
Scheme 6. Catalytic reductions of 5a, 5d and Wittig reactions of 5aH, 5dH.
prop-2-yn-1-one (monobenzoyl acetylene, MBA),13 4-methylpent-
1-yn-3-one,13 bicyclo[2.2.2]oct-5-en-2-ones (5a–b, 5d, 5f–g,
X-ray crystallographic data confirmed the structure of one of the
5i–k)6, 11-benzoyltricyclo[6.2.2.01,6]dodec-11-en-9-one (5l)9 were
diastereomersd5aH0 (Fig. 1).12 Wittig reaction of 5aH using 1 equiv
prepared according to reported methods. 1,5-dimethoxy-1,4-
of methyltriphenylphosphonium iodide yielded 6aH (87%) exclu-
cyclohexadiene14 and the trimethylsilyloxy-1,3-dienes15 were
sively. On the other hand 5dH, the sole hydrogenated product
prepared following the literature procedures.
obtained from 5d, under similar reaction condition yielded only
7dH (89%) (Scheme 6). Since similar selectivities were observed
4.2. Syntheses of 5c, 5e, 5h and 5k
from reactions of 5a, 5aH as well as from 5d, 5dH, the present work
confirmed that the endocyclic conjugation did not have any role in
4.2.1. 5-Benzoyl-4-phenylbicyclo[2.2.2]oct-5-en-2-one (5c). To a so-
guiding the regioselectivity of olefination in these cases.
lution of freshly distilled di-isopropylamine (2.3 mL, 16.5 mmol) in
dry THF (20 mL) n-butyllithium (8.8 mL of 1.5 M solution in hexane,
3. Conclusion 13.2 mmol) was added dropwise under argon atmosphere at
78  C. Temperature of the reaction bath was then slowly raised to
From the above results it was evident that simple Wittig 10  C and then again cooled to 78  C after 30 min. A solution of
reactions of ketones are dependent on the ease of oxaphosphetane 3-phenylcyclohexenone (1.9 g, 11.0 mmol) in dry THF (5 mL) was
ring formation in the initial step. The 1,3-interaction between the added in drops to the reaction mixture for a period of 2–3 min via
phosphonuim ylide and any of the nearby ketone substituent in syringe when the color of the solution turned deep orange. Stirring
particular plays a very important role for site-selectivity in was continued for additional 5 min at 78  C, and then the reaction
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A. Ghosh et al. / Tetrahedron 66 (2010) 164–171
mixture was quenched rapidly with freshly distilled chloro-
trimethyl silane (2.1 mL, 16.5 mmol). The stirred solution was
brought to room temperature during next 2 h. The solvent was
removed reduced pressure followed by immediate flushing of the
reaction vessel with argon. The residue was stirred three times with
dry n-pentane (315 mL) under inert atmosphere and the super-
natant liquid was transferred very carefully via a cannula to an oven
dried thoroughly argon flushed flask. The total solvent (w45 mL)
was then removed in vacuo to get the yellow liquid of trimethyl(5-
phenylcyclohexa-1,5-dienyloxy)silaney. Dry benzene (5 mL) and
a solution of MBA (1.3 gm, 10 mmol) in dry benzene (5 mL) was
immediately added to the diene and the mixture was stirred for 6 h
under inert atmosphere. A solution of 5% methanol–HCl (5 mL) was
added to it and the mixture was stirred for additional 20 min. After
removal of MeOH the mixture was extracted with ether (325 mL).
The organic phases were combined, dried over anhydrous Na2SO4,
and evaporated in vacuo. The residue was chromatographed over
a silica gel column. Elution of the column with 10% EA in PE gave
a solid of 5c (1.20 g, 40%), mp 97–98  C, as colorless crystals after
recrystallization from ether–PE (1:7) mixture. Anal. Calcd for
C21H18O2: C, 83.42; H, 6.00. Found: C, 83.31; H, 6.15. UV (CH3CN):
259 nm (log 3 4.01), 283 (3.6), 345 (2.4). IR: 1724, 1660 cm1. 1H
NMR: d 1.95–2.04 (m, 1H), 2.12–2.32 (m, 3H), 2.48 (d, J 18.4, 1H),
2.77 (dd, J 18.4 and 3 Hz, 1H), 3.49 (br m, 1H), 6.66 (d, J 6.6 Hz, 1H),
7.17–7.30 (m, 5H), 7.41–7.59 (m, 3H), 7.76–7.78 (m, 2H). 13C NMR:
d 23.9 (CH2), 31.4 (CH2), 46.5 (CH2), 47.7 (C), 49.4 (CH), 125.9
(C),126.1 (CH), 126.6 (CH) 126.28 (CH), 128.31 (CH), 129.5 (CH), 132.9
(CH), 134.8 (CH), 136.7(C), 142.4 (C), 150.9 (C) 193.7 (CO), 209.5 (CO).
HRMS (ES1) calcd for C21H18O2Na: 325.1205; found [MþNa]þ
325.1208.
4 . 2 . 2 . 5 - B e n z o yl - 4 - m e t h o x y b i c yc l o [ 2 . 2 . 2 ] o c t - 5 - e n - 2 - o n e
(5e). Mixture of 1,5-dimethoxycyclohexa-1,4-diene (5.5 g,
39.0 mmol), MBA (1.7 g, 13.0 mmol), and dichloromaleic anhydride
(5 mg) in dry benzene (20 ml) was refluxed with stirring for 8 h
under argon atmosphere. The solvent was removed in vacuo and
the residue was refluxed with 30 mL of 1,2-dimethoxyethane and
water (1:5) for another 8 h. After cooling it was extracted with
ether and the solvent was removed. Elution of the column with 10%
EA in PE gave a colorless solid of 5e (1.20 g, 36%), mp 81–82  C, as
colorless crystals after recrystallization from ether–PE (1:4) mix-
ture. Anal. Calcd for C16H16O3: C, 74.98; H, 6.29; Found: C, 75.23; H,
6.00. UV (MeCN): 253 nm (log 3 4.16). IR: 1728, 1656 cm1. 1H NMR:
d 1.78–1.87 (m, 1H), 1.95–2.08 (m, 3H), 2.39 (d, J 18 Hz, 1H), 2.65 (dd,
J 18 and 2.5 Hz, 1H), 3.26 (s, 3H), 3.30–3.33 (m,1H), 6.39 (d, J 6.6 Hz,
1H), 7.44–7.62 (m, 4H), 7.84–7.86 (m, 1H). 13C NMR: 22.0 (CH2), 29.4
(CH2), 44.0 (CH2), 48.7 (CH), 52.5 (CH3), 80.3(C), 128.6 (CH),
129.9(CH), 131.4 (CH), 133.5 (CH), 136.8 (C). 149.1 (C), 193.2 (CO),
206.8(CO). HRMS (ES1) calcd for C16H16O3Na 279.0997, found
([MþNa]þ) 279.0996.
4.2.3. 5-Acetyl-4-methylbicyclo[2.2.2]oct-5-en-2-one (5h). Mixture
of trimethyl(5-methyl-cyclohexa-1,5-dienyloxy)silane (3.5 g,
19.8 mmol) and 3-butyn-2-one (600 mg, 8.82 mmol) was stirred
under argon atmosphere for 2.5 h. A solution of 5% methanol–HCl
(5 mL) was added to it and the mixture was stirred for additional
20 min. The residue obtained after usual work-up and removal of
solvent was chromatographed over a silica gel column. Elution of
the column with 10% EA in PE gave a colorless oil of 5 h (900 mg,
57%). Anal. Calcd for C11H14O2: C, 74.13; H, 7.92. Found: C, 73.67; H,
8.07. UV (EtOH): 239 nm (log 3 3.73), 292 (3.27). IR: 1730,
1675 cm1. 1H NMR: d 1.49 (s, 3H), 1.49–1.58 (m, 2H), 1.88–2.06
y
This diene is highly susceptible towards even trace amount of moisture and
maintaining the inert atmosphere throughout the process is very important
167
(m, 4H), 2.30 (s, 3H), 3.29–3.31 (m, 1H), 7.01 (d, J 6 Hz, 1H). 13C NMR:
d 22.3, 22.9, 26.9, 32.4, 39.0, 46.9, 48.9, 137.4, 149.1, 196.4, 211.9.
4.2.4. 5-(2-Methylpropanoyl)-4,7,7-trimethylbicyclo[2.2.2]oct-5-en-
2-one (5k). Mixture of trimethyl(3,3,5-trimethylcyclohexa-1,5-
dienyloxy)silane (9.45 g, 45.0 mmol) and 4-methylpent-1-yn-3-
one (2.88 g, 30.0 mmol) was stirred under argon atmosphere for
6 h. A solution of 5% methanol–HCl (5 mL) was added to it and the
mixture was stirred for additional 20 min. The residue obtained
after usual work-up and removal of solvent was chromatographed
over a silica gel column. Elution of the column with 10% EA in PE
gave a colorless oil of 5k (4.93 g, 70%). Anal. Calcd for C15H22O2: C,
76.88; H, 9.46. Found: C, 76.83; H, 9.36. UV (CH3CN): 256 nm (log 3
3.70), 323 (1.90). IR: 1732, 1681 cm1. 1H NMR: d 0.96 (s, 3H), 1.05–
1.12 (m, 12H), 1.35 (s, 3H), 1.45 (s, 2H), 1.89 (d, J 18.7 Hz, 1H), 2.03 (d,
J 18.7 Hz, 1H), 2.89 (d, 1H, J 6.7 Hz), 3.07 (h, 1H, J 6.7 Hz), 6.73 (d, 1H,
J 6.7 Hz). 13C NMR: d 18.67 (CH3), 18.74 (CH3), 22.9 (CH3), 30.3 (CH3),
31.1 (CH3), 37.1 (C), 38 (CH), 40.7 (C), 46.3 (CH2), 49.8 (CH2), 62.7
(CH), 134.2 (CH), 149.9 (C), 205.2 (CO), 211.3 (CO). HRMS (ES1) calcd
for C15H22O2Na: 257.1518; found [MþNa]þ 257.1530.
4.3. Syntheses of the 9-ketal of 11-benzoyltricyclo
[6.2.2.01,6]dodec-11-en-9-one (11)
Freshly distilled ethylene glycol (5 mL) and a catalytic amount
D()camphor-10-sulphonic acid (w10 mmol%) were successively
introduced into a well stirred solution of 5l (1.5 g., 5.35 mmol) in
dry toluene (25 mL). The reaction mixture was refluxed under ar-
gon for 3 h with removal of water. The residue obtained after usual
work-up and removal of solvent was chromatographed over a silica
gel column. Elution of the column with 4% EA in PE gave a solid of 11
(1.47 g, 85%), mp 69–71  C, as colorless crystals after re-
crystallization from ether–PE (1:6) mixture. Anal. Calcd for
C21H24O3: C, 77.75; H, 7.46. Found: C, 77.89; H, 7.49. UV (CH3CN):
248 nm (log 3 3.83), 286 (3.04), 343 (1.82). IR: 1653 cm1. 1H NMR:
d 1.53 (br d, J 15 Hz) superimposed with 1.21–1.56 (m, total 7H),
1.68–1.84 (m, 5H), 2.45 (d, J 15 Hz, 1H), 2.61–2.65 (m, 1H), 3.88–4.01
(m, 4H), 6.43 (d, J 6.0 Hz, 1H), 7.40–7.53 (m, 3H), 7.84–7.87 (m, 2H).
13
C NMR: d 21.5 (CH2), 26.1 (CH2), 28.9 (CH2), 29.6 (CH2), 31.5 (CH2),
37.6 (CH), 38.9 (CH2), 39.3 (CH), 41.2 (C), 63.9 (CH2), 64.2 (CH2),
113.4 (C), 128.1 (CH), 130.0 (CH), 132.6 (CH), 138.2 (CH), 138.3 (CH),
149.7 (C), 195.9 (CO). HRMS (ES1) calcd for C21H25O3: 325.1804;
found [MþH]þ 325.1782.
4.4. Catalytic hydrogenation of 5a, 5d. General procedure
Solution of the substrate in dry ethanol was hydrogenated in
presence of active Pd–C (10 mol %) till the reaction was complete.
The reaction mixture was filtered through a pre-activated alumina
bed which was washed thoroughly with dichloromethane
(310 mL). The filtrate was evaporated to dryness in vacuo and the
crude residue was purified either by preparative TLC or by column
chromatography.
4.4.1. 5-endo-Benzoylbicyclo[2.2.2]octan-2-one (5aH0 ) and 5-exo-
benzoylbicyclo[2.2.2]octan-2-one (5aH). The crude reaction mixture
from hydrogenated 5a (452 mg, 2 mmol) was purified by several
preparative TLC with 15% EA in PE to get two isomeric solid
products:
5aH0 (99 mg, 22%), mp 102–104  C, as colorless crystals after
recrystallization from ether–PE (1:6) mixture Anal. Calcd for
C15H16O2: C, 78.92; H, 7.06. Found: C, 78.73; H, 7.19. UV (CH3CN):
240 nm (log 3 3.31), 278 (2.21), 320 (1.08). IR: 1710, 1679 cm1. 1H
NMR: d 1.43–1.49 (m, 1H), 1.60–2.02 (m, 5H), 2.38–2.47 (m, 2H),
2.51 (dt, J 13 and 2.8 Hz, 1H), 2.59 (ddd, J 13, 6 and 2.5 Hz, 1H), 3.64–
3.70 (m, 1H), 7.45–7.61 (m, 3H), 7.92–7.95 (m, 2H). 13C NMR: d 19.9
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168 A. Ghosh et al. / Tetrahedron 66 (2010) 164–171
(CH2), 22.2 (CH2), 24.3 (CH2), 31.9 (CH), 42.1 (CH), 43.6 (CH), 44.7
(CH2), 128.1 (CH), 128.6 (CH), 132.9 (CH), 135.9 (C), 200.4 (CO), 216.1
(CO). HRMS (ES1) calcd for C15H17O2: 229.1223; found [MþH]þ
229.1212.
5aH (329 mg, 73%), mp 59–61  C as colorless crystals after re-
crystallization from ether–PE (1:6) mixture Anal. Calcd for
C15H16O2: C, 78.92; H, 7.06. Found: C, 78.87; H, 7.15. UV (CH3CN):
242 nm (log 3 3.56), 278 (2.50), 323 (1.59). IR: 1726, 1674 cm1. 1H
NMR: d 1.62–1.73 (m, 1H), 1.90–2.10 (m, 5H), 2.38–2.46 (m, 4H),
3.69–3.75 (m, 1H), 7.43–7.60 (m, 3H), 7.88–8.01 (m, 2H). 13C NMR:
d 23.1 (CH2), 25.6 (CH2), 25.8 (CH2), 31.8 (CH), 40.4 (CH2), 42.34
(CH), 42.38 (CH), 128.3 (CH), 128.8 (CH), 133.2 (CH), 136.1 (C), 200.8
(CO), 215.3 (CO). HRMS (ES1) calcd for C15H17O2: 229.1223; found
[MþH]þ 229.1226.
4.4.2. 5-Benzoyl-4-methylbicyclo[2.2.2]octan-2-one (5dH). The crude
reaction mixture from hydrogenated 5d (240 mg, 1 mmol) was
chromatographed over silica gel. Elution of the column with 10% EA
in PE gave a solid of 5dH (155 mg, 64%), mp 63–65  C, as colorless
crystals after recrystallization from ether–PE (1:6) mixture. Anal.
Calcd for C16H18O2: C, 79.31; H, 7.49. Found: C, 79.43; H, 7.61. UV
(CH3CN): 243 nm (log 3 3.57), 280 (2.49), 328 (1.51). IR: 1722,
1674 cm1. 1H NMR: d 0.86 (s, 3H), 1.26 (dddd, J 12.2, 12.2, 4.5, and
1.5 Hz, 1H), 1.77–1.89 (m, 1H), 1.95–2.29 (m, 6H), 2.41 (p, J 2.7 Hz, 1H),
3.63 (ddd, J 10.7, 6.7 and 1.5 Hz, 1H), 7.45–7.61 (m, 3H), 7.92–7.96 (m,
2H). 13C NMR: d 23.3 (CH2), 25.6 (CH3), 26.9 (CH2), 28.4 (CH2), 36.7
(C), 42.5 (CH), 46.1 (CH), 52.7 (CH2), 128.2 (CH), 128.7 (CH), 133.2
(CH), 138.4 (C), 202.9 (CO), 216.2 (CO). HRMS (ES1) calcd for
C16H19O2: 243.1380; found [MþH]þ 243.1342.
4.5. General procedure for Wittig reactions
To a suspension of freshly prepared methyltriphenylphosphonium
iodide (1.1 equiv) in dry THF (10–15 mL) under argon atmosphere n-
BuLi solution (1 equiv) was slowly added via a syringe maintaining the
bath temperature in between 25 and 20  C. The solution was left
stirring for 5 min to ensure the complete production of the ylide. The
resulting orange colored ylide solution was then transferred via a sy-
ringe and was added dropwise to the well stirred solution of the ketone
(1 equiv) dissolved in a required amount of dry THF at 25 to 20  C
under argon atmosphere. The reaction mixture was then left stirring to
reach the room temperature gradually for next 0.5 h, then was rapidly
quenched by addition of 2–3 mL of water. The reaction mixture was
extracted with ether (325 mL) and the residue obtained after usual
work-up was chromatographed over a silica gel column.
4.5.1. 5-(1-Phenylvinyl)bicyclo[2.2.2]oct-5-en-2-one (6a). Prepared
from 5a (240 mg, 1 mmol), methyltriphenylphosphonium iodide
(445 mg, 1.1 mmol) and n-butyllithium (0.6 mL 1.8 M solution in
hexane, 1 mmol). Elution of the column with 5% EA in (PE) gave a pale
yellow thick liquid of 6a (188 mg, 78%). Anal. Calcd for C16H16O:
C, 85.68; H, 7.19. Found: C, 85.73; H, 7.26. UV (CH3CN): 243 nm (log 3
3.90), 306 (2.80), 367 (1.90). IR: 1728 cm1. 1H NMR: d 1.63–1.77
(m, 2H), 1.80–1.87 (m, 1H), 1.92–1.99 (m, 1H), 2.15 (br s, 2H), 3.15–3.18
(m, 1H), 3.29–3.33 (m, 1H), 5.16 (s, 1H), 5.39 (s, 1H), 5.95 (dd, J 6.7 and
1.7 Hz, 1H), 7.24–7.37 (m, 5H). 13C NMR: d 23.8 (CH2), 24.8 (CH2), 34.4
(CH), 40.8 (CH2), 49.6 (CH), 113.3 (CH2), 126.2 (CH), 128.0 (CH), 128.5
(CH), 129 (CH), 140.9 (C). 147.4 (C), 148.6 (C), 212.9(CO). HRMS (ES1)
calcd for C16H16ONa: 247.1099; found [MþNa]þ 247.1076.
Further elution of the column with 10% EA in PE gave a white
crystalline solid of unreacted 5a (18 mg, 18%) mp 95–96  C (mmp
96  C).6
4.5.2. 5-(3-Methylbut-1-en-2-yl)bicyclo[2.2.2]oct-5-en-2-one (6b) and
5-(2-methylpropanoyl)-2-methylenebicyclo[2.2.2]oct-5-ene
(7b). Prepared from 5b (382 mg, 2 mmol), methyltriphenylphosp-
honium iodide (888 mg, 2.2 mmol) and n-butyllithium (1.2 mL
1.7 M solution in hexane, 2 mmol). Elution of the column with 5%
EA in PE gave a colorless thick liquid of 7b (282 mg, 74%). Anal.
Calcd for C13H18O: C, 82.06; H, 9.53. Found: C, 82.17; H, 9.61. UV
(CH3CN): 235 nm (log 3 4.00), 319 (2.10). IR: 1666 cm1. 1H NMR:
d 1.08 (d, J 6.9 Hz, 3H), 1.10 (d, J 6.9 Hz, 3H), 1.22–1.33 (m, 1H),
1.38–1.48 (m, 1H), 1.58–1.66 (m, 1H), 1.70–1.79 (m, 1H), 1.96 (dp, J
16.7 and 2.6 Hz, 1H), 2.29 (ddd, J 16.7, 4.4 and 2 Hz, 1H), 3.25 (h, J
6.9 Hz) superimposed with 3.21–3.25 (m, total 2H), 3.42 (br m, 1H),
4.65 (dd, J 3.5 and 2.0 Hz, 1H), 4.85 (dd, J 3.5 and 2.0 Hz, 1H), 7.25
(dd, J 6.3 and 1.8 Hz, 1H). 13C NMR: d 19.7 (CH3), 19.8 (CH3), 24.9
(CH2), 26.6 (CH2), 29.5 (CH), 34.1 (CH), 34.4 (CH2), 42.6 (CH), 106.3
(CH2), 142.9 (CH), 145.2 (C), 148.7 (C), 202.4 (CO). HRMS (ES1) calcd
for C13H18ONa: 213.1255; found [MþNa]þ 213.1239. Further elution
of the column with the same solvent mixture gave a colorless thick
liquid of 6b (56 mg, 15%). Anal. Calcd for C13H18O: C, 82.06; H, 9.53.
Found: C, 82.26; H, 9.42. UV (CH3CN): 241 nm (log 3 3.80), 300
(2.70), 351 (1.60). IR: 1730 cm1. 1H NMR: d 1.07 (d, J 6.8 Hz, 3H),
1.08 (d, J 6.8 Hz, 3H), 1.60–1.95 (m, 4H), 2.05–2.08 (m, 2H), 2.63 (h, J
6.8 Hz, 1H), 3.18–3.21 (m, 1H), 3.27–3.30 (m, 1H), 4.97 (s, 1H), 5.15
(s, 1H), 6.14 (dd, J 6.6 and 1.8 Hz, 1H). 13C NMR: d 22.45 (CH3), 22.52
(CH3), 23.3 (CH2), 24.3 (CH2), 29.2 (CH), 34.0 (CH), 40.3 (CH2), 48.9
(CH), 107.7 (CH2), 120.9 (CH), 148.1 (C), 151.3 (C), 212.9 (CO). HRMS
(ES1) calcd for C13H18ONa: 213.1255; found [MþNa]þ 213.1274.
Further elution of the column with 10% EA in PE gave a colorless
thick liquid of unreacted 5b (20 mg, 5%).
4.5.3. 5-Benzoyl-2-methylene-4-phenylbicyclo[2.2.2]oct-5-ene
(7c). Prepared from 5c (455 mg, 1.5 mmol), methyltriphenylphosp-
honium iodide (679 mg, 1.66 mmol) and n-butyllithium (1.0 ml
1.5 M solution in hexane, 1.5 mmol). Elution of the column with 5%
EA in PE gave a solid of 7c (330 mg, 73%), mp 114–116  C, as col-
orless crystals after recrystallization from ether–PE (1:8) mixture.
Anal. Calcd for C22H20O: C, 87.96; H, 6.71. Found: C, 87.83; H, 6.78.
UV (CH3CN): 248 nm (log 3 3.60), 283 (2.70). IR: 1651 cm1. 1H
NMR: d 1.66–1.75 (m, 1H), 1.92–2.09 (m, 3H), 2.60 (dt, J 16.4 and
1.5 Hz, 1H), 2.75 (dd, J 16.4.and 2.3 Hz, 1H), 3.32–3.35 (m, 1H), 4.75
(d, J 1.3 Hz, 1H), 4.93 (d, J 1.3 Hz, 1H), 6.77 (d, J 6.7 Hz, 1H), 7.10–7.17
(m, 1H), 7.21–7.22 (m, 4H), 7.35–7.4 (m, 2H), 7.47–7.52 (m, 1H),
7.73–7.76 (m, 2H). 13C NMR: d 27.5 (CH2), 31.9 (CH2), 41.9 (CH2), 42.1
(CH), 46.1 (C), 105.5 (CH2), 125.9 (CH), 126.4 (CH), 127.9 (CH), 128
(CH), 129.7 (CH), 132.4 (CH), 137.5 (C), 141.5 (CH), 144.8 (C), 147.8 (C),
148.2 (C), 194.5 (CO). HRMS (ES1) calcd for C22H21O: 301.1587;
found [MþH]þ 301.1592.
Further elution of the column with 10% EA in PE gave a white
crystalline solid of unreacted 5c (96 mg, 21%) mp 97–98  C (mmp
98  C).
4.5.4. 5-Benzoyl-2-methylene-4-methylbicyclo[2.2.2]oct-5-ene
(7d). Prepared from 5d (240 mg, 1 mmol), methyltriphenylphosp-
honium iodide (445 mg, 1.1 mmol) and n-butyllithium (0.6 mL
1.8 M solution in hexane, 1 mmol). Elution of the column with 5%
EA in PE gave a colorless thick liquid of 7d (188 mg, 79%). Anal.
Calcd for C17H18O: C, 85.67; H, 7.61. Found: C, 85.74; H, 7.56. UV
(CH3CN): 247 nm (log 3 4.20), 279 (3.36), 343 (2.26), 364 (2.09). IR:
1651 cm1. 1H NMR: d 1.36 (s, 3H), 1.49–1.62 (m, 3H), 1.80–1.87 (m,
1H), 2.21 (br s, 2H), 3.18–3.21 (m, 1H), 4.67 (dd, J 3.6 and 2 Hz, 1H),
4.85 (dd, J 3.6 and 2 Hz, 1H), 6.62 (d, J 6.7 Hz, 1H), 7.40–7.45 (m, 2H),
7.51–7.54 (m, 1H), 7.76–7.79 (m, 2H). 13C NMR: d 22.6 (CH3), 27.4
(CH2), 33.6 (CH2), 38.2 (C), 41.9 (CH), 42.5 (CH2), 105.1 (CH2), 128.1
(CH), 129.8 (CH), 132.4 (CH), 138.1 (C), 141.1 (CH), 146.9 (C), 148.7 (C),
195.5 (CO). HRMS (ES1) calcd for C17H18ONa: 261.1255; found
[MþNa]þ 261.1222.
Further elution of the column with 10% EA in PE gave a white
crystalline solid of unreacted 5d (36 mg, 15%) mp 45–47  C (mmp
46  C).6
 Author's personal copy
A. Ghosh et al. / Tetrahedron 66 (2010) 164–171
4.5.5. 5-Benzoyl-2-methylene-4-methoxybicyclo[2.2.2]oct-5-ene
(7e) and 5-(1-phenylvinyl)-4-methoxybicyclo-[2.2.2]oct-5-en-2-
one (6e). Prepared from 5e (512 mg, 2 mmol), methyl-
triphenylphosphonium iodide (890 mg, 2.2 mmol) and n-butyl-
lithium (1.4 mL 1.5 M solution in hexane, 2 mmol). Elution of the
column with 5% EA in PE gave a colorless thick liquid of 7e
(315 mg, 62%). Anal. Calcd for C17H18O2: C, 80.28; H, 7.13. Found:
C, 80.12; H, 7.18. UV (CH3CN): 247 nm (log 3 4.00), 281 (3.10), 339
(1.80). IR: 1658 cm1. 1H NMR: d 1.59–1.71 (m, 1H), 1.78–1.89 (m,
3H), 2.49 (dt, J 15.8 and 1.8 Hz, 1H), 2.62 (dd, J 15.8 and 2 Hz, 1H),
3.14–3.17 (m, 1H), 3.23 (s, 3H), 4.73 (d, J 1 Hz, 1H); 4.91 (d, J 1 Hz,
1H), 6.50 (d, J 6.5 Hz, 1H), 7.41–7.46 (m, 2H), 7.52–7.57 (m, 1H),
7.83–7.86 (m, 2H). 13C NMR: d 26.8 (CH2), 30.2 (CH2), 38.9 (CH2),
41.5 (CH), 52.7 (OCH3), 80.8 (C), 106.8 (CH2), 128.6 (CH), 130.3
(CH), 133.2 (CH), 137.9 (C), 138.7 (CH), 146.31 (C), 146.33 (C), 194.3
(CO). HRMS (ES1) calcd for C17H19O2: 255.1380; found [MþH]þ
255.1386.
Further elution of the column with same solvent mixture gave
a colorless thick liquid of 6e (46 mg, 9%). Anal. Calcd for C17H18O2: C,
80.28; H, 7.13. Found: C, 80.39; H, 7.25. UV (CH3CN): 248 nm (log 3
3.90), 283 (3.20), 348 (2.00). IR: 1728 cm1. 1H NMR: d 1.72–1.96 (m,
4H), 2.28 (d, J 17.7 Hz, 1H), 2.46 (dd, J 17.7 and 2.6 Hz, 1H), 3.18 (s)
superimposed with 3.22–3.26 (m, total 4H), 5.33 (d, J 1.5 Hz, 1H),
5.34 (d, J 1.5 Hz, 1H), 6.05 (d, J 6.5 Hz, 1H), 7.27–7.37 (m, 5H). 13C
NMR: d 21.7 (CH2), 29.3 (CH2), 44.4 (CH2), 48.4 (CH), 51.6 (OCH3),
79.4 (C), 115.1 (CH2), 124.3 (CH), 126.8 (CH), 127.5 (CH), 128 (CH),
140.7 (C), 146.6 (C), 150.9 (C), 208.0 (CO). HRMS (ES1) calcd for
C17H19O2: 255.1380; found [MþH]þ 255.1421.
Further elution of the column with 10% EA in PE gave a white
crystalline solid of unreacted 5e (118 mg, 23%), mp 81–83  C (mmp
82  C).
4.5.6. 5-(1-Phenylvinyl)-1-methylbicyclo[2.2.2]oct-5-en-2-one
(6f). Prepared from 5f (101 mg, 0.42 mmol), methyltriphenylphosp-
honium iodide (188 mg, 0.46 mmol) and n-butyllithium (0.28 mL
1.5 M solution in hexane, 0.42 mmol). Elution of the column with 5% EA
in PE gave a pale yellow thick liquid of 6f (75 mg, 76%). Anal. Calcd for
C17H18O: C, 85.67; H, 7.61. Found: C, 85.58; H, 7.69. UV (CH3CN): 253 nm
(log 3 3.50), 314 (2.30), 328 (1.80). IR: 1720 cm1. 1H NMR: d 1.19 (s, 3H),
1.49–1.56 (m,1H),1.67–1.87 (m, 3H), 2.17–2.18 (br m, 2H), 3.26–3.29 (m,
1H), 5.14 (s, 1H), 5.38 (s, 1H), 5.61 (d, J 1.2 Hz, 1H), 7.23–7.25 (m, 2H),
7.29–7.34 (m, 3H). 13C NMR: d 17.7 (CH3), 25.9 (CH2), 31.1 (CH2), 33.9
(CH), 40.3 (CH2), 49.7 (C),112.9 (CH2),127.5 (CH),128.1 (CH),128.5 (CH),
131.1 (CH), 140.4 (C), 146.9 (C), 147.9 (C), 213.1 (CO). HRMS (ES1) calcd
for C17H19O: 239.1430; found [MþH]þ 239.1403.
Further elution of the column with 10% EA in PE gave a white
crystalline solid of unreacted 5f (18 mg, 18%) mp 95–97  C (mmp
96  C).6
4.5.7. 5-(2-Methylpropanoyl)-2-methylene-4-methyl-
bicyclo[2.2.2]oct-5-ene (7g). Prepared from 5g (260 mg, 1.27 mmol),
methyltriphenylphosphonium iodide (565 mg, 1.39 mmol) and n-
butyllithium (0.9 mL 1.4 M solution in hexane, 1.4 mmol). Elution of
the column with 5% EA in PE gave a colorless thick liquid of 7g
(168 mg, 58%). Anal. Calcd for C14H20O: C, 82.30; H, 9.87. Found: C,
82.43; H, 9.93. UV (CH3CN): 233 nm (log 3 3.50), 322 (2.20). IR:
1678 cm1. 1H NMR: d 1.05 (d, J 6.6 Hz, 3H), 1.07 (d, J 6.6 Hz, 3H),
1.33 (s, 3H), 1.37–1.50 (m, 3H), 1.72–1.80 (m, 1H), 2.06–2.08 (m, 2H),
3.09 (h, J 6.6 Hz) superimposed with 3.16–3.18 (m, total 2H), 4.60
(dd, J 3.6 and 2.1 Hz, 1H), 4.81 (dd, J 3.6 and 2.1 Hz, 1H), 6.93 (d, J
6.6 Hz, 1H). 13C NMR: d 18.5 (CH3), 18.7 (CH3), 23.2 (CH3), 27.1 (CH2),
33.6 (CH2), 36.8 (CH), 37.9 (C) 41.9 (CH), 42.6 (CH2), 104.9 (CH2),
139.3 (CH), 147.9 (C), 148.7 (C), 205.5 (CO). HRMS (ES1) calcd for
C14H21O: 205.1587; found [MþH]þ 205.1552.
Further elution of the column with 10% EA in PE gave a colorless
thick liquid of unreacted 5g (98 mg, 38%).
169
4.5.8. 5-Acetyl-2-methylene-4-methylbicyclo[2.2.2]oct-5-ene (7h) and
5-isopropenyl-4-methylbicyclo[2.2.2]oct-5-en-2-one (6h). Prepared
from 5h (430 mg, 2.42 mmol), methyltriphenylphosphonium
iodide (1.07 g, 2.65 mmol) and n-butyllithium (2.02 mL 1.1 M
solution in hexane, 2.42 mmol). Elution of the column with 5% EA in
PE gave a colorless thick liquid of 7h (221 mg, 52%). Anal. Calcd for
C12H16O: C, 81.77; H, 9.15. Found: C, 81.93; H, 9.27. UV (CH3CN):
233 nm (log 3 3.9), 318 (2.0). IR: 1674 cm1. 1H NMR: d 1.25–1.41 (m,
3H), 1.43 (s, 3H), 1.72–1.82 (m, 1H), 2.03–2.05 (m, 2H), 2.27 (s, 3H),
3.16–3.20 (m, 1H), 4.61 (dd, J 3.3 and 1.8 Hz, 1H), 4.82 (dd, J 3.3 and
1.8 Hz, 1H), 7.16 (d, J 6.8 Hz, 1H). 13C NMR: d 23.7 (CH3), 26.8 (CH2),
27.5 (CH3), 33.9 (CH2), 38.0 (C), 42.2 (CH), 42.9 (CH2), 105.2 (CH2),
143.9(CH), 147.7 (C), 148.4 (C), 197.9 (CO). HRMS (ES1) calcd for
C12H16ONa: 199.1099; found [MþNa]þ 199.1053.
Further elution of the column with 10% EA in PE gave a pale
yellow thick liquid of 6h (196 mg, 46%). Anal. Calcd for C12H16O: C,
81.77; H, 9.15. Found: C, 81.69; H, 9.21. UV (CH3CN): 224 nm (log 3
3.60), 295 (2.50). IR: 1732 cm1. 1H NMR: d 1.28(s, 3H), 1.42–1.52 (m,
2H), 1.61–1.71 (m, 2H); 1.85 (d, J 1 Hz, 3H); 1.91 (d, J 18.3 Hz)
superimposed with 1.86–1.92 (m, total 2H); 2.01 (dd, J 18.3 and
2.9 Hz, 1H), 4.70 (dd, J 2.2 and 1.0 Hz, 1H), 4.89 (dd, J 2.2 and 1.0 Hz,
1H), 5.92 (d, J 6.6 Hz, 1H). 13C NMR: d 22.6 (CH3), 23.78 (CH2), 23.81
(CH3), 33.2 (CH2), 39.9 (C), 47.9 (CH2), 48.9 (CH), 113.8 (CH2), 122.2
(CH), 143.8 (C), 154.7 (C), 212.7 (CO). HRMS (ES1) calcd for
C12H16ONa: 199.1099; found [MþNa]þ 199.1108.
4.5.9. 5-Benzoyl-2-methylene-1,4-dimethylbicyclo[2.2.2]oct-5-ene
(7i) and 5-(1-phenylvinyl)-1,4-dimethylbicyclo[2.2.2]oct-5-en-2-one
(6i). Prepared from 5i (200 mg, 0.79 mmol), methyltriphenylphosp-
honium iodide (350 mg, 0.87 mmol) and n-butyllithium (1.0 mL 0.8 M
solution in hexane, 0.8 mmol). Elution of the column with 5% EA in PE
gave a colorless thick liquid of 7i (22 mg, 11%). Anal. Calcd for C18H20O:
C, 85.67; H, 7.99. Found: C, 85.58; H, 8.03. UV (CH3CN): 248 nm (log 3
4.20), 270 (3.70), 338 (2.20). IR: 1651 cm1. 1H NMR: d 1.3 (s, 3H),1.35 (s,
3H), 1.42–1.47 (m, 1H), 1.50–1.68 (m, 3H), 2.28 (br s, 2H), 4.74 (d, J 2 Hz,
1H), 4.82 (d, J 2 Hz, 1H), 6.27 (s, 1H), 7.40–7.54 (m, 3H), 7.75–7.78 (m,
2H). 13C NMR: d 21.1 (CH3), 22.6 (CH3), 35.16 (CH2), 35.19 (CH2), 38.1 (C),
41.4 (C), 43.8 (CH2),103.3 (CH2),128.4 (CH),129.9 (CH),132.5 (CH),138.2
(C), 145.7 (CH), 146.8 (C), 151.9 (C), 195.6 (CO). HRMS (ES1) calcd for
C18H20ONa: 275.1412; found [MþNa]þ 275.1414.
Further elution of the column with the same solvent mixture gave
a colorless thick liquid of 6i (82 mg, 41%). Anal. Calcd for C18H20O: C,
85.67; H, 7.99. Found: C, 85.74; H, 7.87. UV (CH3CN): 245 nm (log 3 3.80),
304 (2.60), 363 (1.40). IR: 1718 cm1. 1H NMR: d 0.85 (s, 3H),1.29 (s, 3H),
1.55–1.65 (m, 3H), 1.72–1.78 (m, 1H), 1.93 (d, J 18.3 Hz, 1H), 2.07 (dd, J
18.3 and 1 Hz,1H), 5.03 (d, J 1.7 Hz,1H), 5.33 (d, J 1.7 Hz,1H), 5.87(s,1H),
7.28–7.32 (m, 5H). 13C NMR: d 17.6 (CH3), 22.2 (CH3), 31.9 (CH2), 34.9
(CH2), 40.2 (C), 47.9 (CH2), 49.9 (C), 114.7 (CH2), 126.6 (CH), 127.8 (CH),
128.4 (CH), 130.9 (CH), 140.3 (C), 148.4 (C), 152.2 (C), 213.2 (CO). HRMS
(ES1) calcd for C18H21O: 253.1587; found [MþH]þ 253.1562.
Further elution of the column with 10% EA in PE gave a pale
yellow thick liquid of unreacted 5i (92 mg, 46%).
4.5.10. 5-(1-Phenylvinyl)-4,7,7-trimethylbicyclo[2.2.2]oct-5-en-2-
one (6j). Prepared from 5j (402 mg, 1.5 mmol), methyltriphenyl-
phosphonium iodide (667 mg, 1.65 mmol) and n-butyllithium
(1.0 ml 1.5 M solution in hexane, 1.5 mmol). Elution of the column
with 5% EA in PE gave a solid of 6j (191 mg, 48%), a low melting
white solid. Anal. Calcd for C19H22O: C, 85.67; H, 8.32. Found: C,
85.48; H, 8.43. UV (CH3CN): 233 nm (log 3 4.30), 303 (2.70), 317
(2.20). IR: 1726 cm1. 1H NMR: d 0.79 (s, 3H), 1.08 (s, 6H), 1.39 (br s,
2H), 1.86 (d, J 18.2 Hz, 1H), 2.01 (br d, J 18.2 Hz, 1H), 2.83 (d, J 6.5 Hz,
1H), 5.04 (d, J 1.8 Hz, 1H), 5.35 (d, J 1.8 Hz, 1H), 6.16 (d, J 6.5 Hz, 1H),
7.28–7.33 (m, 5H). 13C NMR: d 22.2 (CH3), 29.8 (CH3), 30.9 (CH3),
35.9 (C), 40.8 (C), 46.1 (CH2), 49.5 (CH2), 62.1 (CH), 114.9 (CH2), 125.5
(CH), 126.6 (CH), 127.8 (CH), 128.4 (CH), 140.3 (C), 148.4 (C), 151.6
 Author's personal copy
170 A. Ghosh et al. / Tetrahedron 66 (2010) 164–171
(C), 212.3 (CO). HRMS (ES1) calcd for C19H22ONa: 289.1568; found
[MþNa]þ 289.1585.
Further elution of the column with 10% EA in PE gave a white
crystalline solid of unreacted 5j (157 mg, 39%), mp 95–97  C (mmp
96  C).6
4.5.11. 5-(2-Methylpropanoyl)-2-methylene-4,7,7-trimethylbicy-
clo[2.2.2]oct-5-ene (7k). Prepared from 5k (494 mg, 2.12 mmol),
methyltriphenylphosphonium iodide (942 mg, 2.33 mmol) and n-
butyllithium (1.42 mL 1.5 M solution in hexane, 2.12 mmol). Elution
of the column with 5% EA in PE gave a colorless thick liquid of 7k
(142 mg, 29%). Anal. Calcd for C16H24O: C, 82.70; H, 10.41. Found: C,
82.61; H, 10.04. UV (CH3CN): 236 nm (log 3 3.70), 323 (1.90). IR:
1678 cm1. 1H NMR: d 1.07 (s, 3H), 1.21 (s, 3H), 1.25 (d, J 6.9 Hz, 3H),
1.28 (d, J 6.9 Hz, 3H), 1.35 (d, J 13 Hz, 1H), 1.44 (d, J 13 Hz, 1H), 1.49 (s,
3H), 2.19–2.21 (br m, 2H), 2.87 (d, J 6.9 Hz, 1H), 3.32 (h, J 6.9 Hz, 1H),
4.89 (dd, J 3.7 and 2 Hz, 1H), 5.01 (dd, J 3.7 and 2 Hz, 1H), 7.14 (d, J
6.9 Hz,1H). 13C NMR: d 18.5 (CH3), 18.7 (CH3), 23.2 (CH3), 30.47 (CH3),
30.59 (CH3), 35.3 (C), 36.9 (CH), 39.1 (C), 40.9 (CH2), 50.2 (CH2), 54.7
(CH), 107.3 (CH2), 140.4 (CH), 146.2 (C), 146.8 (C), 205.4 (CO). HRMS
(ES1) calcd for C16H25O: 233.1900; found [MþH]þ 233.1923.
Further elution of the column with 10% EA in PE gave a colorless
thick liquid of unreacted 5k (331 mg, 67%).
4.5.12. 11-Benzoyl-9-methylene-tricyclo[6.2.2.01,6 ]dodec-11-ene
(7l). Prepared from 5l (280 mg, 1.0 mmol), methyltriphenylphos-
phonium iodide (445 mg, 1.1 mmol) and n-butyllithium (0.6 mL 1.8 M
solution in hexane, 1.0 mmol). Elution of the column with 5% EA in PE
gave a pale yellow thick liquid of 7l (203 mg, 73%).Anal. Calcd for
C20H22O: C, 86.29; H, 7.97. Found: C, 86.36; H, 7.69. UV (CH3CN): 247
(log 3 4.04), 348 (1.60). IR: 1651 cm1. 1H NMR: d 1.14–1.33 (m, 3H),
1.48–1.78 (m, 6H), 1.92 (bd, J 18 Hz) superimposed with 1.89–2.05 (m,
total 3H), 2.96 (d, J 18 Hz, 1H), 3.08 (m, 1H), 4.65 (d, J 1 Hz), 4.81 (d, J
1 Hz), 6.52 (d, J 6 Hz), 7.40–7.57(m, 3H), 7.79–7.81(m, 2H). 13C NMR:
d 22.0 (CH2), 26.6 (CH2), 30.8 (CH2), 31.9 (CH2), 32.9 (CH2), 35.2 (CH2),
38.8 (CH), 41.6 (C), 42.0 (CH), 104.9 (CH2), 128.5 (CH), 130.3 (CH), 132.9
(CH), 138.7 (C), 140.1 (CH), 149.6 (C), 149.8 (C), 196.1 (CO). HRMS (ES1)
calcd for C20H23O: 279.1671; found [MþH]þ 279.1702.
Further elution of the column with 10% EA in PE gave a white
crystalline solid of unreacted 5l (34 mg, 12%), mp 76–78  C (mmp
77  C).9
4.5.13. 11-(1-Phenylvinyl)-9-methylene-tricyclo-[6.2.2.01,6]dodec-11-
ene (10). Prepared from 5l (280 mg, 1.0 mmol), methyl-
triphenylphosphonium iodide (1 g, 2.5 mmol) and n-butyllithium
(1.3 mL 1.9 M solution in hexane, 2.5 mmol). Elution of the column
with 4% ethyl acetate (EA) in petroleum ether (PE) gave a pale
yellow thick liquid of 10 (226 mg, 82%). Anal. Calcd for C21H24: C,
91.25; H, 8.75. Found: C, 91.39; H, 8.69. UV (CH3CN): 248 nm (log 3
3.57), 340 (1.76). IR: no characteristic peak for keto functionality. 1H
NMR: d 0.88–1.44 (m, 8H), 1.72 (dd, J 18 and 2.1 Hz) superimposed
with 1.53–1.75 (m, total 3H), 1.89 (dt, J 12 and 3 Hz, 1H), 2.80 (d, J
18 Hz, 1H), 2.99–3.03 (m, 1H), 4.58 (d, J 1.8 Hz, 1H), 4.78 (d, J 1.8 Hz,
1H), 4.98 (d, J 2.1 Hz, 1H), 5.28 (d, J 2.1 Hz, 1H), 6.21 (d, J 6 Hz, 1H),
7.21–7.34 (m, 5H). 13C NMR: d 21.4 (CH2), 26.0 (CH2), 30.2 (CH2), 31.6
(CH2), 32.8 (CH2), 35.2 (CH2), 38.6 (CH), 41.1 (C), 41.5 (CH), 102.6
(CH2), 113.9 (CH2), 126.5 (CH), 127.2 (CH), 128.0 (CH), 129.7 (CH),
141.1 (C), 149.1 (C), 151.3 (C), 151.4 (C).
4.5.14. 9-Ketal of 11-(1-phenylvinyl)-tricyclo[6.2.2.01,6]dodec-11-en-
9-one (12). Prepared from 11 (324 mg, 1.0 mmol), methyl-
triphenylphosphonium iodide (445 mg, 1.1 mmol) and n-butyllithium
(0.6 mL 1.8 M solution in hexane, 1.0 mmol). The ketone was added to
the ylide solution in this experiment. Elution of the column with 5% EA
in PE gave a solid of 12 (274 mg, 85%), mp 114–116  C, as colorless
crystals after recrystallization from ether–PE (1:8) mixture. Anal. Calcd
for C22H26O2: C, 81.95; H, 8.13. Found: C, 82.13; H, 7.97. UV (CH3CN):
251 nm (log 3 3.94). IR: no characteristic peak for keto functionality. 1H
NMR: d 1.33 (d, J 15 Hz) superimposed with 1.08–1.40 (m, total 10H),
1.57–1.68 (m, 2H), 2.30 (d, J 15 Hz,1H), 2.54–2.57 (m,1H), 3.89–4.01 (m,
4H), 5.00 (d, J 2.1 Hz, 1H), 5.30 (d, J 2.1 Hz, 1H), 6.14 (d, J 6 Hz, 1H), 7.22–
7.39 (m, 5H). 13C NMR: d 21.5 (CH2), 26.0 (CH2), 29.5 (CH2), 29.6 (CH2),
31.8 (CH2), 37.8 (CH), 39.0 (CH), 39.1 (CH2), 41.1 (C), 63.9 (CH2), 64.0
(CH2), 113.8 (C), 113.9 (CH2), 126.7 (CH2), 127.3 (CH2), 128.2 (CH2), 128.6
(CH2), 141.0 (C), 149.0 (C), 152.0 (C). HRMS (ES1) calcd for C22H27O2:
323.2011; found [MþH]þ 323.2055.
4 . 5 .15 . 5 - e x o - ( 1 - p h e n y l v i n yl ) b i c y c l o [ 2 . 2 . 2 ] o c t a n - 2 - o n e
(6aH). Prepared from 5aH (114 mg, 0.5 mmol), methyltriphen-
ylphosphonium iodide (222 mg, 0.55 mmol) and n-butyllithium
(0.46 mL 1.1 M solution in hexane, 0.5 mmol). Elution of the column
with 5% EA in PE gave a colorless thick liquid of 6aH (98 mg, 87%). UV
(CH3CN): 245 nm (log 3 3.82), 277 (2.52), 325 (1.43). IR: 1726 cm1. 1H
NMR: d 1.66–1.69 (m,1H); 1.78–1.88 (m, 4H),1.99–2.12 (m, 3H), 2.33 (dt,
J 18 and 2.6 Hz, 1H), 2.45 (dt, J 18 and 2 Hz, 1H), 3.07 (br t, J 8.5 Hz, 1H),
5.03 (s, 1H); 5.31 (s, 1H), 7.27–7.34 (m, 5H). 13C NMR: d 23.1 (CH2), 26.2
(CH2), 28.6 (CH2), 31.2 (CH), 38.9 (CH), 39.9 (CH2), 43.3 (CH),112.5 (CH2),
126.8 (CH),127.6 (CH),128.4 (CH),141.5 (C),149.1 (C), 208.9 (CO). HRMS
(ES1) calcd for C16H18ONa: 249.1255; found [MþNa]þ 249.1275.
4.5.16. 5-Benzoyl-2-methylene-4-methylbicyclo[2.2.2]octane
(7dH). Prepared from 5dH (85 mg, 0.35 mmol), methyl-
triphenylphosphonium iodide (157 mg, 0.39 mmol) and n-butyl-
lithium (0.32 mL 1.1 M solution in hexane, 0.35 mmol). Elution of the
column with 5% EA in PE gave a colorless thick liquid of 7dH (75 mg,
89%). Anal. Calcd for C17H20O: C, 84.96; H, 8.39. Found: C, 85.05; H, 8.30.
UV (CH3CN): 242 nm (log 3 3.77), 277 (2.60), 327 (1.45). IR: 1676 cm1.
1
H NMR: d 0.76 (s, 3H), 1.09–1.20 (m, 1H), 1.57–1.69 (m, 1H), 1.78–1.97
(m, 3H), 2.08–2.17 (m,1H), 2.20 (t, J 2.4 Hz,1H), 2.24, (dd, J 2.2 and 5 Hz,
1H), 2.34 (p, J 2.7 Hz,1H), 3.51 (ddd, J 10.5, 7 and 1.5 Hz,1H), 4.67 (dd, J 4
and 2 Hz, 1H), 4.81 (dd, J 4 and 2 Hz, 1H), 7.42–7.56 (m, 3H), 7.92–7.95
(m, 2H). 13C NMR: d 25.9 (CH3), 26.5 (CH2), 27.8 (CH2), 31.9 (CH2), 34.2
(C), 35.8 (CH), 44.7 (CH2), 46.9 (CH), 105.4 (CH2), 128.2 (CH), 128.5 (CH),
132.7 (CH), 138.8 (C), 151.5 (C), 204.1 (CO). HRMS (ES1) calcd for
C17H20ONa: 263.1412; found [MþNa]þ 263.1453.
4.6. Wittig reaction of 5d in absence of Li-salt
An oven dried two neck 25 mL R.B. flask fitted with a septum was
charged with freshly prepared methyltriphenylphosphonium iodide
(445 mg, 1.1 mmol, 1.1 equiv) suspended in dry toluene (6 mL) under
argon atmosphere. To this suspension was added freshly prepared
potassium-t-butoxide (112 mg, 1.0 mmol, 1 equiv) maintaining the
bath temperature in between 25 and 20  C. After stirring for 10–
15 min the resulting bright yellow colored ylide solution was trans-
ferred in a syringe and added dropwise to the well stirred solution of 5d
(240 mg, 1 mmol, 1 equiv) dissolved in dry toluene (5 mL) at 25 to
20  C under argon atmosphere. The reaction mixture was then left
stirring to reach the room temperature gradually for next 0.5 h and
then was rapidly quenched by addition of 2–3 mL of water. The mixture
was extracted with ether (325 mL). The organic phases were com-
bined, dried over Na2SO4, and evaporated in vacuo. The residue was
chromatographed over a silica gel column. Elution of the column with
5% EA in PE gave a colorless thick liquid of 7d (180 mg, 76%).
Further elution of the column with 10% EA in PE gave a white
crystalline solid of unreacted 5d (38 mg, 15%), mp 45–46  C (mmp
46  C).6
Acknowledgements
Single crystal X-ray diffraction was performed at the DST-fun-
ded National Single Crystal Diffractometer Facility at the
 Author's personal copy
A. Ghosh et al. / Tetrahedron 66 (2010) 164–171
Department of Inorganic Chemistry. Financial support was received
from the Department of Science and Technology, Govt. of India.
Appendix. Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tet.2009.11.006.
References and notes
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