Palladium-catalyzed synthesis of indane and cyclobuta[a]indenes from homoallylic alcohols derived from Baylis-Hillman adducts: Base-dependent stereoselectivity for the benzylidene group in cyclobuta[a]indene

Article abstract of DOI:10.1016/j.tet.2011.03.070

Various indane and cyclobuta[a]indene derivatives were synthesized by palladium-catalyzed cyclization of homoallylic alcohol derivatives prepared from Baylis-Hillman adducts. Especially, cyclobuta[a]indene derivative was synthesized stereoselectively by p

Full text of DOI:10.1016/j.tet.2011.03.070

Tetrahedron 67 (2011) 3328e3336
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Palladium-catalyzed synthesis of indane and cyclobuta[a]indenes from
homoallylic alcohols derived from BayliseHillman adducts: base-dependent
stereoselectivity for the benzylidene group in cyclobuta[a]indene
,
Ko Hoon Kim a, Se Hee Kim a, Sunhong Park b, Jae Nyoung Kim a
*
a Department of Chemistry and Institute of Basic Science, Chonnam National University, Gwangju 500-757, Republic of Korea
b Department of Chemistry and Research Institute of Natural Science, Gyeongsang National University, Jinju 660-701, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 1 March 2011
Received in revised form 18 March 2011
Accepted 22 March 2011
Available online 26 March 2011
Various indane and cyclobuta[a]indene derivatives were synthesized by palladium-catalyzed cyclization
of homoallylic alcohol derivatives prepared from BayliseHillman adducts. Especially, cyclobuta[a]indene
derivative was synthesized stereoselectively by palladium-catalyzed 5-exo-trig/4-exo-trig cascade cycli-
zation, albeit in moderate yield. The Z isomer was formed exclusively in the presence of Et3N by usual
Heck-type carbopalladation process while E isomer with Cs2CO3 most likely by a concerted metalation/
deprotonation (CMD) process.
Keywords:
Palladium
Ó 2011 Elsevier Ltd. All rights reserved.
Heck reaction
Domino reactions
Concerted metalation/deprotonation (CMD)
BayliseHillman adducts
1. Introduction
1A.8 During the studies, we were interested in the Pd-catalyzed re-
action of 2-phenylstyryl derivative 1a. The formations of 2a and 3a
The palladium-catalyzed domino reactions coupled with suit-
ably designed starting materials allow for rapid establishment of
complex molecules.1e3 In particular, a palladium-catalyzed con-
secutive carbonecarbon bond-formation through a Heck-type
cascade cyclization has become one of the most popular methods
for the synthesis of multiple ring system.2 The formation of
were expected. Heck-type cyclization reaction to the 2-phenylstyryl
moiety (position-a) would produce an indane derivative 3a, while
a cyclization reaction to the acrylate moiety (position-b) would
produce 2a via a Heck-type cascade cyclization (5-exo-trig/4-exo-
trig),5 as shown in Scheme 1B.
Br
A
a s-alkylpalladium(II) intermediate lacking a suitable b-hydrogen
TBSO
TBSO
H
Pd0 (Ref. 8)
syn with respect to the palladium center is highly required for the
effective cascade bond formations.3 The formation of a cyclobutane
ring through a Heck-type cascade cyclization, however, has been
scarcely observed.4,5 In addition, most of the reported examples
suffer from low yield, and the structures of cyclobutane derivatives
were so limited.4,5
Recently, BayliseHillman adducts have been used extensively for
the synthesis of various important compounds.6,7 Among the nu-
merous chemical transformations of the BayliseHillman adducts
Pd-catalyzed reactions have received a special attention,7,8 including
inter- and intramolecular Heck-type reactions. Very recently, we
reported an intramolecular Heck/arylation cascade to make the
indeno[2,1-a]indene scaffold from a TBS-protected homoallylic
alcohol, prepared from BayliseHillman adduct, as shown in Scheme
5-exo-trig/arylation
COOMe
COOMe
COOMe
Br
B
TBSO
Pd0 (this work)
TBSO
Ph
TBSO
b
+
H
b
a
Ph
Ph
MeOOC
a
a
Ph
Ph
COOMe
Ph
2a
1a
3a
Scheme 1. Synthetic rationale of cyclobuta[a]indane and/or indane.
2. Results discussion
The starting material 1a was prepared in four steps from 3-phe-
nylcinnamaldehyde via the BayliseHillman reaction with methyl
acrylate, bromination, indium-mediated Barbier-type reaction with
* Corresponding author. Tel.: þ82 62 530 3381; fax: þ82 62 530 3389; e-mail
address: kimjn@chonnam.ac.kr (J.N. Kim).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.03.070

K.H. Kim et al. / Tetrahedron 67 (2011) 3328e3336
3329
2-bromobenzaldehyde, and protection of the hydroxyl group with
TBSCl in good overall yield, according to our previous paper (Scheme
2).8 When we carried out the reaction of 1a under the influence of Pd
(OAc)2/PPh3/Cs2CO3 in DMF (120 ꢀC, 30 min), cyclobuta[a]indene 2a9
was isolated in good yield (77%) along with a methyleneindane 4a
(14%),10 as shown in Scheme 2.11 Cyclobuta[a]indene derivative 2a
might be formed via an initial 5-exo-trig cyclization of an arylpalla-
dium bromide I to acrylate moiety, and subsequent 4-exo-trig cycli-
syn b-H elimination could explain the formation of 2b-Z. The quite
different stereochemical results and the formation of unusual 2b-E
were very interesting, although the regioselectivities for the first
5-exo-trig carbopalladation of arylpalladium complex (positions
b:a) were moderate (31e36:51e56).
Br
RO
TBSO
Ph
RO
RO
RO
E
Pd0
b
zation of the reactive
2-phenylstyryl moiety and
derivative 4a might be formed via a
s
-alkylpalladium complex II4a,12 to the
-H elimination. Methyleneindane
-carbon elimination/de-
E
b
a
E
E
H
H
b
H
H
b
a
PdBr
Ph
Ph
COOMe
d
Ph
Ph
III
1b
E = COOMe, R = TBS
carboxylation of intermediate II.7c,8,13 Interestingly, the formation of
indane 3a was not observed at all. Heck reaction of arylpalladium
complex to sterically hindered alkene is known to be difficult,14 thus
theformation ofan indane derivative 3aviaa 5-exo-trig cyclization to
the 2-phenylstyryl moiety (position-a) would be difficult, while
2b-E
2b-Z
3b
Cs2CO3/DMF, 110 oC, 10 min
(entry 1 in Table 1)
34
2
51
Et3N/DMF, 110 oC, 30 min
(entry 14 in Table 1)
0
31
56
4-exo-trig cyclization of a reactive s-alkylpalladium complex II could
be conducted even to the sterically congested 2-phenylstyryl moiety
Scheme 3. Stereoselective synthesis of 2b-E (under Cs2CO3) and 2b-Z (under Et3N).
to give 2a.
BrPd
(i) Barbier reaction
(In, 2-BrPhCHO)
TBSO
Pd0
b
TBSO
Ph
COOMe
PdBr
H
1a
b
(ii) TBSCl/ImH
a
Ph
a
Ph
COOMe
Ph
I
II
Ph
COOMe
Ph
TBSO
4-exo-trig (for 2a)
+
2a
Br
-carbon elimination
/decarboxylation (for 4a)
Ph
(i) B-H reaction
(ii) bromination
Ph
4a
Pd(OAc)2 (10 mol%), PPh3 (20 mol%)
Cs2CO3 (2.0 equiv), DMF, 120 oC, 30 min
77%
18%
14%
Ph
CHO
Pd(OAc)2 (10 mol%), PPh3 (20 mol%)
Et3N (2.0 equiv), DMF, 120 oC, 30 min
Ph
71%
Scheme 2. Regioselective formation of cyclobuta[a]indene 2a (under Cs2CO3) and methyleneindane 4a (under Et3N).
Interestingly, methyleneindane 4a was obtained as a major
We then performed the reactions of 1b under different condi-
tions in order to get more insights on the regio- and stereo-
selectivities, as summarized in Table 1. The regioselectivity for the
first carbopalladation (2b vs 3b) was not high in most entries, es-
pecially in DMF. Interestingly, a highly selective carbopalladation to
styryl moiety forming 3b was observed in toluene (entries 3, 17 and
18), and the yield reached to 92%. The highest yield of 2b-E reached
to 44% (entries 11 and 12) while that of 2b-Z to maximum 31%
(entry 14). As noted above, the most interesting point was the
stereochemistry of 2b. Generally, 2b-E was the major product under
the influence of Cs2CO3 (entries 1e7 and 11e13) while 2b-Z in the
presence of an organic base (entries 14e21). The best result for 2b-E
was obtained when Cs2CO3 and pivalic acid were used together
(entry 11).16a,c,e In addition, a similar result was obtained without
pivalic acid by reducing the amounts of Pd(OAc)2 and PPh3 (entries
12 and 13). The relatively high yield of 2b-E (39%) under the Jeffery
conditions (entry 7) is noteworthy.
product (71%) when the reaction was carried out in the presence of
Et3N, along with a low yield of 2a (18%). The results stated that
4-exo-trig cyclization of an alkylpalladium intermediate II was fa-
cilitated with Cs2CO3 while Et3N made the d-carbon elimination/
decarboxylation process more facile. Although complete regio-
control (2aþ4a:3a¼89e91:0) was achieved very nicely in the first
carbopalladation of arylpalladium intermediate I; however the
highly dependent nature of products distribution (2a:4a) on the
reaction conditions made us suspect the mechanism for the 4-exo-
trig carbopalladation step to 2a.
Thus we decided to examine the reaction of cinnamyl derivative
1b in order to obtain more insights on the mechanism of 4-exo-trig
cyclization. The reaction of 1b under the influence of Cs2CO3
afforded three compounds, 2b-E (34%),15 2b-Z (2%),15 and an indane
derivative 3b (51%), as shown in Scheme 3. The structures of 2b-E
and 2b-Z were confirmed unequivocally by their X-ray crystal
structures (Fig. 1). In this entry, a 5-exo-trig cyclization to the styryl
moiety (position-a) occurred to produce 3b as a major product, in
sharply contrast to the reaction of 1a, which did not produce 3a at
all. In contrast, the reaction of 1b under Et3N conditions gave 2b-Z
(31%) and 3b (56%). Compound 2b-Z is a generally expected com-
pound that could be formed via a 5-exo-trig/4-exo-trig cascade
cyclization. The usual syn-carbopalladation of an alkylpalladium
intermediate III, rotation around the CeC bond, and the following
As noted above, the formation of 2b-Z is usually expected while
the formation of 2b-E is quite unusual. Several mechanistic sce-
narios could account for the formation of 2b-E from the alkylpal-
ladium intermediate III (Scheme 4). The first mechanism is an
electrophilic metalation/deprotonation (EMD),12a,17
a
stepwise
metalation process similar to SEAr, which involves the ionization of
the PdeBr -bond to form an electrophilic cationic palladium
species,17a,b subsequent formation of a carbocationic intermediate,
s

3330
K.H. Kim et al. / Tetrahedron 67 (2011) 3328e3336
Table 1
Pd-catalyzed cyclizations of 1b
Entry
Conditionsa,b
2b-Ec
2b-Zc
3bc
1
2
3
4
Cs2CO3, DMF, 110 ꢀC, 10 min
Cs2CO3, CH3CN, reflux, 10 min
Cs2CO3, toluene, reflux, 10 min
Cs2CO3, DMF, 140 ꢀC, 10 min
Cs2CO3, DMF, 80 ꢀC, 20 min
Cs2CO3, DMF, 110 ꢀC, 3 h
Cs2CO3, DMF, 120 ꢀC, 20 min
Na2CO3, DMF, 120 ꢀC, 30 min
NaHCO3, DMF, 120 ꢀC, 30 min
KOAc, DMF, 110 ꢀC, 20 min
Cs2CO3, DMF, 120 ꢀC, 30 min
Cs2CO3, DMF, 120 ꢀC, 10 min
Cs2CO3, DMF, 120 ꢀC, 2 h
Et3N, DMF, 110 ꢀC, 30 min
Et3N, DMF, 80 ꢀC, 30 h
34
13
5
2
4
5
4
3
51
68
82
56
63
49
33
54
54
51
53
51
50
56
53
77
87
92
69
35
64
31
25
30
39
20
25
24
44
44
41
0
0
0
0
0
0
11
0
5
6d
7e
8
2
4
18
19
20
<1
<1
<1
31
26
17
7
9
10
11f
12g
13h
14
15
16
17
18
19
20
21
Et3N, CH3CN, reflux, 1 h
Et3N, toluene, reflux, 3 h
Et3N, toluene, 70 ꢀC, 12 h
DIEA, DMF, 110 ꢀC, 10 min
DBU, DMF, 120 ꢀC, 20 min
DABCO, DMF, 110 ꢀC, 2 h
3
23
19
13
a
Pd(OAc)2 (10 mol %), PPh3 (20 mol %) is common unless otherwise stated.
Base was used in 2.0 equiv unless otherwise stated.
Isolated yield (%).
(t-Bu)3P was used instead of PPh3.
TBAC (3.0 equiv) was used instead of PPh3.
PivOH (30 mol %) was added.
b
c
d
e
f
g
h
Pd(OAc)2 (10 mol %) and PPh3 (5 mol %) were used.
Pd(OAc)2 (3 mol %) and PPh3 (1 mol %) were used.
assumed that the most likely mechanism would be a CMD process,
which could produce 2b-E as the sole product. Although the base-
mediated CMD process has been suggested mostly in palladium-
catalyzed aryl CeH activation by arylpalladium intermediate16,18
the mechanism might be acting in the case of alkenyl CeH activa-
tion by alkylpalladium species.4a,21 However, there was no example
involving an alkenyl CeH activation, most likely by a CMD process,
by alkylpalladium species, to the best of our knowledge.
TBSO
H
TBSO
H
- HBr
- Pd0
electrophilic
2b-E
2b-Z
Br
H
H
COOMe
Br
COOMe
Ph
Pd
Ph
Pd
Fig. 1. ORTEP drawings of compounds 2b-E and 2b-Z in their OH forms.
TBSO
H
- CsHCO3
- CsBr, - Pd0
CMD
COOMe
2b-E
a base (or bromide)-assisted proton abstraction, and reductive
elimination of Pd0. The expected product might be a mixture of
2b-Z and 2b-E. The second possibility is a concerted metalation/
deprotonation (CMD) process that suggested by many research
groups including Fagnou,16 Sames,18a Charette,18b DeBoef,18c and
Chang,18d and the stereochemical outcome of our experiment could
be explained nicely with this mechanism. In addition, the reaction
conditions that produce 2b-E in high yield (entries 11e13 in Table 1)
are very similar to those of the reactions that proceed by a CMD
mechanism involving the intermediate IV.16a,c,e The third possibil-
ity could be a formation of 2b-Z as an initial product via the usual
Heck reaction and a subsequent double bond isomerization cata-
lyzed by HPdBr species.5b,14b,19 However, the first and third mech-
anisms are insufficient to explain the high E-selectivity (>44/1)
when we consider the small energy difference20 between 2b-E and
2b-Z although both mechanisms cannot be ruled out completely. In
addition, the possibility for HPdBr-catalyzed isomerization of 2b-Z
to 2b-E was found to be very low based on the following experi-
ment, shown in Scheme 4. Compound 2b-Z was recovered com-
pletely intact under the reaction conditions, and compounds 2b-E
and 3b must be produced from the reaction of 1b. Thus, we
III
H
Pd
O
Ph
O
Cs
IV
O
TBSO
isomerization
by HPdBr
rotation
- HPdBr
BrPd
Ph
H
Heck
2b-E
2b-Z
COOMe
Pd(OAc)2 (10 mol%)
PPh3 (20 mol%)
2b-E
(41%)
2b-Z
(20%)
3b
+
+
+
1b
2b-Z
Cs2CO3 (2.0 equiv)
DMF, 120 oC, 60 min
(53%)
(1.0 mmol) (0.2 mmol)
Scheme 4. Plausible mechanisms for the formation of 2b-E.
In order to check the contribution of EMD mechanism, we ex-
amined the reactions of p-fluoro derivative 1c and p-methoxy
derivative 1d. If an EMD mechanism contributes to some extent,
then even a subtle change could be observed in the reaction rate or
on the ratios of 2/3 and E/Z. However, the results were very similar
with that of 1b, as shown in Table 2 (entries 1 and 2). Corre-
sponding E-isomers were obtained in 37e39% under the influence

K.H. Kim et al. / Tetrahedron 67 (2011) 3328e3336
3331
a low yield of 4g under the influence of Cs2CO3.11 Under the con-
ditions of Et3N, the first cyclization also occurred to the acrylate
Table 2
Palladium-catalyzed domino reactions of 1ceh
moiety; however,
d-carbon elimination/decarboxylation process
Entry Substrate
Br
Product (%)a
proceeded predominantly to produce methyleneindane 4g as the
major product (57%). The structure of 5 was confirmed un-
equivocally by its X-ray crystal structure (Fig. 2).22 The reaction of
nitrile derivative 1h (entry 5) produced 3h as the major product
(73%) along with a naphthalene 6 (17%) via a 6-endo cyclization/
aromatization process, as observed in our previous paper.8
OTBS
OTBS
Ar
H
MeOOC
TBSO
1b
Ar
Ar
COOMe
2c
COOMe
1c
3c
Condition A: 2c-E (37), 2c-Z (0), 3c (55)
Condition B: 2c-E (0), 2c-Z (30), 3c (59)
Br
TBSO
OTBS
OTBS
Ar
MeOOC
H
2c
Ar
Ar
COOMe
2d
COOMe
3d
1d
Condition A: 2d-E (39), 2d-Z (0), 3d (52)
Condition B: 2d-E (0), 2d-Z (23),d 3d (62)d
Br
OR
OR
Ph
MeOOC
H
RO
3
Ph
Ph
COOMe
2e, 2f
COOMe
3e, 3f
1e, 1f
Condition A: 2e-E (23), 2e-Z (0), 3e (29)
Condition B: 2e-E (0), 2e-Z (15), 3e (57)
Condition A: 2f-E (40), 2f-Z (0), 3f (55)
1e: RO = AcO
1f: RO = TBDPSO
Br
OTBS
Ph
OTBS
H
TBSO
4
Ph
Ph
COOMe
5
COOMe
4g
Fig. 2. ORTEP drawing of compound 5.
1g
Condition A: 5 (85), 4g (12)
Condition B: 5 (22), 4g (57)
As a last entry, we examined the propenyl derivative 1i under
the influence of Cs2CO3, as shown in Scheme 5. Vinylindane 3i was
produced as a major product (75%) via 5-exo-trig cyclization to the
Br
TBSO
OTBS
NC
5
Ph
propenyl moiety and the following
b-H elimination, which oc-
Ph
Ph
CN
6
curred regioselectively at the methyl group to form the vinylindane
3i.11 The stereochemistry of 3i was deduced by NOE experiments,
and the results stated that the 5-exo-trig cyclization of arylpalla-
dium intermediate occurred selectively to a Si face of the propenyl
moiety. Although cyclobuta[a]indene 2i was formed in a trace
amount (4%) the stereochemistry was again E that produced most
likely by a CMD process.
CN
3h
1h
Condition A: 3h (73), 6 (17)
aCondition A: Pd(OAc)2 (10 mol %), PPh3 (5 mol %), Cs2CO3 (2.0 equiv), DMF, 120 ꢀC,
30 min. Condition B: Pd(OAc)2 (10 mol %), PPh3 (20 mol %), Et3N (2.0 equiv), DMF,
120 ꢀC, 30 min.
bAr is 4-fluorophenyl.
cAr is 4-methoxyphenyl.
dCompounds 2d-Z and 3d were isolated together in 85%, and the ratio was de-
termined based on 1H NMR.
Br
Pd(OAc)2 (10 mol%)
PPh3 (5 mol%)
TBSO
H
TBSO
TBSO
COOMe
+
H
of Cs2CO3 (condition A), while Z-isomers 23e30% in the presence of
Et3N (condition B) along with indane derivatives 3c and 3d in
52e62%. Thus, the EMD mechanism would not be the major process
for the formation of E-isomers, 2c-E and 2d-E. The reaction of the
acetate 1e showed a similar reactivity (entry 3) although the
combined yield of 2e and 3e was somewhat lower in both condi-
tions. However, the E/Z selectivity was strictly obeyed; 2e-E was
formed under the influence of Cs2CO3 while 2e-Z with Et3N. TBDPS
derivative 1f showed the same reactivity (entry 3). Based on the
experimental results, we tentatively concluded that the formation
of E-isomers of 2aef would involve an alkenyl CeH activation
process most likely via a CMD mechanism. When we block the
Cs2CO3 (2.0 equiv)
DMF, 120 oC, 10 min
H
MeOOC
H
H
Me
nOe
H
H
nOe
COOMe
1i
H
Me
3i (75%)
2i-E (4%)
Scheme 5. Regio- and stereoselective synthesis of vinylindane 3i.
In conclusion, various cyclobuta[a]indenes were synthesized
stereoselectively along with cyclopenta[a]indene, methylene- and
arylideneindane derivatives by palladium-catalyzed reactions from
modified BayliseHillman adducts of cinnamaldehydes. Reaction
conditions affected much on the regioselectivity as well as stereo-
chemistry of products. During the formation of a cyclobutane ring,
the first example of alkenyl CeH activation, most likely via a CMD
process, was observed in the presence of Cs2CO3. In contrast, usual
a
-position of the styryl moiety with a methyl group as in 1g (entry
4) in order to prevent 4-exo-trig cyclization, the reaction proceeded
in a 5-exo/5-endo cascade cyclization to produce cyclopenta[a]
indene derivative 522,23 as the major product (85%), along with
syn-carbopalladation, a kind of
p-bond activation of C]C double

3332
K.H. Kim et al. / Tetrahedron 67 (2011) 3328e3336
bond, worked in the presence of Et3N. As far as we are aware this is
the first example where alkene is activated stereoselectively by
adopting different Heck protocols. The result implies that, whereas
olefin coordination (Heck reaction) is favored in the presence of
Et3N, the alkenylCeH activation (mostlikelybyCMDprocess)occurs
preferentially in the presence of Cs2CO3. A few examples have been
washed with water, dried over MgSO4, and concentrated under
vacuum. The residue was purified by column chromatographic pu-
rification process (hexanes/ethyl acetate 30:1) to afford Bay-
liseHillman bromide (503 mg, 94%) as a pale yellow solid. Its
selected spectroscopic data are as follows: mp 136e139 ꢀC; IR (KBr)
3054,1709,1604,1278cmꢁ1;1HNMR (CDCl3, 300 MHz)
d
3.74 (s, 3H),
4.50 (s, 2H), 7.02 (d, J¼12.0 Hz,1H), 7.19e7.24 (m, 2H), 7.31e7.38 (m,
5H), 7.40e7.44 (m, 4H); 13C NMR (CDCl3, 75 MHz)
25.16, 52.12,
reported that could not be explained by a syn b-H elimination pro-
cess during the Heck reaction,21 and our observation strongly sug-
gests the involvement of a direct CeH activation process, most likely
via a CMD process. Further studies are underway in this regard.
d
121.56, 127.62, 128.27, 128.43, 128.51, 128.68, 129.13, 130.58, 138.29,
140.10, 141.45, 153.26, 166.47; ESIMS m/z 357 [MþH]þ, 359
[MþHþ2]þ. Anal. Calcd for C19H17BrO2: C, 63.88; H, 4.80. Found: C,
63.92; H, 4.97.
3. Experimental
To a stirred solution of the prepared BayliseHillman bromide
(536 mg, 1.5 mmol) and 2-bromobenzaldehyde (306 mg, 1.7 mmol)
in aqueous THF (1:1, 5 mL) was added indium powder (188 mg,
1.7 mmol) and stirred at room temperature for 1 h. The reaction
mixture was poured into water (10 mL), extracted with diethyl ether
(30 mLꢂ3). The combined organic layers were washed with brine
and dried over MgSO4, and concentrated under vacuum. The residue
was purified by column chromatography (hexanes/EtOAc, 10:1) to
afford homoallyl alcohol (syn) as colorless oil, 534 mg (77%). Its se-
lected spectroscopic data are as follows: IR (film) 3435, 3056, 1716,
3.1. General procedure
All reactions were carried out in oven-dried glassware under an
atmosphere of dry nitrogen unless otherwise noted. Thin layer
chromatography (TLC) was performed with pre-coated silica gel
plates (Kieselgel 60F254, Merck). Visualization on TLC was achieved
by the use of UV light (254 nm) or treatment with p-anisaldehyde
stain followed by heating. The separations were carried out by flash
column chromatography over silica gel 60 (230e400 mesh ASTM).
Organic extracts were dried over anhydrous MgSO4 and the sol-
vents were removed on a rotary evaporator under water aspirator
pressure. All reagents were purchased from commercial sources
and used without further treatment.
1441, 1266 cmꢁ1 1H NMR (CDCl3, 300 MHz)
; d 3.73e3.78 (m, 1H),
3.79 (s, 3H), 4.25 (d, J¼2.1 Hz, 1H), 5.19 (t, J¼2.1 Hz, 1H), 5.64 (t,
J¼1.2 Hz, 1H), 6.20 (d, J¼0.9 Hz, 1H), 6.47e6.52 (m, 3H), 7.07 (ddd,
J¼7.5, 7.5 and 1.8 Hz, 1H), 7.14e7.31 (m, 9H), 7.38 (dd, J¼8.1 and
1.2 Hz,1H), 7.62 (dd, J¼7.8 and 1.5 Hz,1H); 13C NMR (CDCl3, 75 MHz)
Melting points were measured with a ThomaseHoover melting
point apparatus and are uncorrected. 1H NMR (300 MHz) spectra
were measured on a Varian Unity Plus 300. The signal positions are
d
48.49, 52.35, 75.17, 122.04, 132.02, 126.93, 127.12, 127.28, 127.89,
128.04 (2C), 128.49, 128.76, 129.03, 132.41, 139.07, 141.21, 141.23,
141.72, 145.34, 168.75 (one carbon is overlapped); ESIMS m/z 463
[MþH]þ, 465 [MþHþ2]þ. Anal. Calcd for C26H23BrO3: C, 67.39; H,
5.00. Found: C, 67.52; H, 5.24.
reported in parts per million relative to TMS (d scale) used as an
internal standard. Splitting patterns are indicated as s, singlet; d,
doublet; t, triplet; q, quartet; m, multiplet. Chemical shifts of the 13C
NMR (75 MHz) spectra were measured relative to CDCl3
(77.23 ppm). IR spectra were recorded on a Jasco FT-IR 410 spec-
trometer and are reported in cmꢁ1. Mass spectra were obtained
from the Korea Basic Science Institute (Gwangju branch) using ESIþ
method. Elemental analyses (C, H, and N) were performed with
a Fisons EA-1108 Elemental Analyzer machine at Korea Research
Institute of Chemical Technology, Daejeon, Korea.
A solution of the prepared homoallyl alcohol (463 mg,1.0 mmol),
TBSCl (300 mg, 2.0 mmol), and imidazole (204 mg, 3.0 mmol) in DMF
(3 mL) was stirred at room temperature for 12 h under nitrogen
atmosphere. The reaction mixture was poured into water (10 mL),
extracted with diethyl ether (30 mLꢂ3). The combined organic
layers were washed with brine, dried over MgSO4, and concentrated
under vacuum. The residue was purified by column chromato-
graphic purification process (hexanes/ether, 50:1) to afford com-
pound 1a, 487 mg (83%) as colorless oil. Other compounds 1bei
were prepared similarly and the spectroscopic data are as follows.
Preparation of starting materials for the synthesis of 1aei is noted in
detail in Supplementary data with their spectroscopic data.
3.2. Typical procedure for the synthesis of starting material
1a
A solution of
b-phenylcinnamaldehyde (625 mg, 3.0 mmol),
DABCO (168 mg,1.5 mmol), and phenol (85 mg, 0.9 mmol) in methyl
acrylate (1291 mg,15.0 mmol) was stirred at room temperature for 4
days under nitrogen atmosphere, quenched with water (10 mL), and
extracted with diethyl ether (30 mLꢂ3). The combined organic
layers were washed with dilute HCl solution, brine, dried over
MgSO4, and concentrated under vacuum. The residue was purified
by column chromatographic purification process (hexanes/ethyl
acetate 20:1) to afford a BayliseHillman alcohol (582 mg, 66%) as
colorless oil. Its selected spectroscopic data are as follows: IR (film)
3.2.1. Compound 1a. Yield 83%; colorless oil; IR (film) 2949, 2855,
1722,1257,1081 cmꢁ1; 1H NMR (CDCl3, 300 MHz)
d 0.00 (s, 3H), 0.22
(s, 3H),1.13 (s, 9H), 3.96 (s, 3H), 4.04 (dd, J¼10.8 and 3.6 Hz,1H), 5.55
(d, J¼3.6 Hz, 1H), 5.94 (s, 1H), 6.58 (s, 1H), 6.66 (d, J¼10.8 Hz, 1H),
6.81e6.84 (m, 2H), 7.29 (ddd, J¼7.5, 7.5 and 1.5 Hz,1H), 7.38e7.52 (m,
9H), 7.63 (dd, J¼8.1 and 1.2 Hz, 1H), 7.77 (d, J¼6.3 Hz, 1H); 13C NMR
(CDCl3, 75 MHz)
d
ꢁ4.88, ꢁ4.59, 18.42, 26.16, 46.86, 51.98, 74.28,
121.94, 126.04, 126.69, 127.15, 127.27, 127.39, 128.13, 128.31, 128.55,
128.71, 129.39, 130.01, 132.56, 139.76, 140.76, 142.58, 142.75, 143.86,
167.34; ESIMS m/z 577 [MþH]þ, 579 [MþHþ2]þ. Anal. Calcd for
C32H37BrO3Si: C, 66.54; H, 6.46. Found: C, 66.39; H, 6.65.
3474, 3024, 1719, 1275 cmꢁ1 1H NMR (CDCl3, 300 MHz)
; d 3.09 (d,
J¼6.0 Hz,1H), 3.77 (s, 3H), 4.95 (dd, J¼9.3 and 6.0 Hz,1H), 5.75 (s,1H),
6.23 (s, 1H), 6.24 (d, J¼9.3 Hz, 1H), 7.19e7.23 (m, 2H), 7.25e7.27 (m,
5H), 7.30e7.40 (m, 3H); 13C NMR (CDCl3, 75 MHz)
d 51.96, 69.77,
126.14, 127.49, 127.58, 127.62, 127.76, 128.14, 128.23, 129.59, 138.92,
141.38, 141.50, 144.79, 166.94; ESIMS m/z 317 [MþNa]þ. Anal. Calcd
for C19H18O3: C, 77.53; H, 6.16. Found: C, 77.72; H, 6.20.
To a stirred solution of the prepared BayliseHillman alcohol
(441 mg, 1.5 mmol) in dry dichloromethane (5 mL) was added
dropwise a solution of PBr3 (405 mg,1.5 mmol, in 2.5 mL dry CH2Cl2)
at 0 ꢀC over 10 min. The reaction mixture was stirred for 1 h at the
same temperature. The reaction mixture was poured into ice water
and extracted with dichloromethane. The organic layers were
3.2.2. Compound 1b. Yield 95%; colorless oil; IR (film) 2951, 2857,
1723, 1464, 1255 cmꢁ1 1H NMR (CDCl3, 300 MHz)
; d 0.00 (s, 3H),
0.24 (s, 3H), 1.08 (s, 9H), 3.97 (s, 3H), 4.02 (dd, J¼9.3 and 5.1 Hz, 1H),
5.61 (d, J¼5.1 Hz, 1H), 5.92 (s, 1H), 6.44 (d, J¼15.9 Hz, 1H), 6.53 (s,
1H), 6.71 (dd, J¼15.9 and 9.3 Hz,1H), 7.26 (ddd, J¼7.5, 7.5 and 1.8 Hz,
1H), 7.41e7.52 (m, 6H), 7.68e7.73 (m, 2H); 13C NMR (CDCl3,
75 MHz)
d
ꢁ5.03, ꢁ4.85, 18.05, 25.79, 51.41, 51.82, 74.30, 121.87,
126.14, 126.71, 127.09, 127.71, 127.76, 128.39, 128.63, 129.88, 132.19,
132.66, 137.47, 140.04, 142.30, 167.09; ESIMS m/z 501 [MþH]þ, 503

K.H. Kim et al. / Tetrahedron 67 (2011) 3328e3336
3333
[MþHþ2]þ. Anal. Calcd for C26H33BrO3Si: C, 62.27; H, 6.63. Found:
and 1.2 Hz, 1H), 7.52 (d, J¼8.1 Hz, 1H); 13C NMR (CDCl3, 75 MHz)
C, 62.46; H, 6.59.
d
ꢁ5.16, ꢁ4.80, 18.14, 25.72, 56.36, 75.82, 118.20, 122.02, 122.50,
125.72, 126.41, 127.28, 127.75, 128.55, 129.16, 132.32, 132.74, 133.14,
136.57, 141.02 (one carbon is overlapped); ESIMS m/z 468 [MþH]þ,
470 [MþHþ2]þ. Anal. Calcd for C25H30BrNOSi: C, 64.09; H, 6.45; N,
2.99. Found: C, 64.28; H, 6.53; N, 2.77.
3.2.3. Compound 1c. Yield 85%; colorless oil; IR (film) 2952, 2856,
1722, 1509, 1233 cmꢁ1
;
1H NMR (CDCl3, 300 MHz)
d
ꢁ0.23 (s, 3H),
0.02 (s, 3H), 0.85 (s, 9H), 3.75 (s, 3H), 3.79 (dd, J¼9.3 and 5.4 Hz,1H),
5.38 (d, J¼5.4 Hz, 1H), 5.68 (s, 1H), 6.18 (d, J¼15.9 Hz, 1H), 6.30 (s,
1H), 6.40 (dd, J¼15.9 and 9.3 Hz, 1H), 6.94e7.08 (m, 3H), 7.20e7.28
3.2.9. Compound 1i. Yield 90%; colorless oil; IR (film) 2952, 2857,
(m, 3H), 7.46e7.49 (m, 2H); 13C NMR (CDCl3, 75 MHz)
d
ꢁ4.74,
1723, 1256, 1084 cmꢁ1
;
1H NMR (CDCl3, 300 MHz)
d
ꢁ0.25 (s, 3H),
ꢁ4.56, 18.34, 26.06, 51.83, 52.14, 115.58 (d, J¼21.2 Hz), 122.21,
127.01, 127.80, 127.90, 128.04, 128.97, 130.12, 131.75, 132.52, 133.90
(d, J¼3.4 Hz), 140.22, 142.57, 162.34 (d, J¼245.0 Hz), 167.36; ESIMS
m/z 519 [MþH]þ, 521 [MþHþ2]þ. Anal. Calcd for C26H32BrFO3Si: C,
60.11; H, 6.21. Found: C, 60.15; H, 6.44.
0.00 (s, 3H), 0.85 (s, 9H), 1.60 (dd, J¼6.6 and 1.5 Hz, 3H), 3.57 (dd,
J¼9.3 and 5.4 Hz, 1H), 3.72 (s, 3H), 5.20e5.32 (m, 2H), 5.62 (s, 1H),
5.65e5.74 (m, 1H), 6.24 (s, 1H), 7.06 (ddd, J¼7.8, 7.8 and 1.5 Hz, 1H),
7.23 (d, J¼7.5 Hz, 1H), 7.43e7.46 (m, 2H); 13C NMR (CDCl3, 75 MHz)
d
ꢁ5.09, ꢁ4.87, 17.91, 18.06, 25.76, 51.05, 51.73, 74.21, 121.89, 126.46,
127.35, 128.33 (2C), 128.43, 130.12, 132.06, 140.40, 142.56, 167.31;
ESIMS m/z 439 [MþH]þ, 441 [MþHþ2]þ. Anal. Calcd for
C21H31BrO3Si: C, 57.39; H, 7.11. Found: C, 57.58; H, 7.02.
3.2.4. Compound 1d. Yield 78%; colorless oil; IR (film) 2951, 2855,
1721, 1511, 1250 cmꢁ1
;
1H NMR (CDCl3, 300 MHz)
d
ꢁ0.32 (s, 3H),
ꢁ0.08 (s, 3H), 0.76 (s, 9H), 3.64 (s, 3H), 3.69 (s, 3H), 3.65e3.70 (m,
1H), 5.28 (d, J¼5.1 Hz, 1H), 5.91 (s, 1H), 6.06 (d, J¼15.9 Hz, 1H), 6.19
(s, 1H), 6.24 (dd, J¼15.9 and 9.0 Hz, 1H), 6.71e6.76 (m, 2H),
6.91e6.96 (m, 1H), 7.09e7.15 (m, 3H), 7.35e7.41 (m, 2H); 13C NMR
3.3. Typical procedure for the Pd-catalyzed reaction of 1a
A solution of 1a (173 mg, 0.3 mmol), Pd(OAc)2 (7 mg, 10 mol %),
PPh3 (16 mg, 20 mol %), and Cs2CO3 (195 mg, 0.6 mmol) in DMF
(2 mL) was stirred at 120 ꢀC for 30 min under nitrogen atmosphere.
The reaction mixture was allowed to cool to room temperature,
quenched with water (10 mL), and extracted with diethyl ether
(30 mLꢂ3). The combined organic layers were washed with dilute
HCl solution, brine, dried over MgSO4, and concentrated under
vacuum. The residue was purified by column chromatographic
purification process (hexanes/ether 50:1) to afford compounds 2a
(115 mg, 77%) as a white solid and 4a (18 mg, 14%) as colorless oil.
(CDCl3, 75 MHz)
d
ꢁ5.04, ꢁ4.87, 18.03, 25.77, 51.43, 51.76, 55.15,
74.34, 113.80, 121.86, 125.44, 126.65, 127.22, 127.61, 128.56, 129.91,
130.29, 132.03, 132.13, 140.18, 142.36, 158.83, 167.11; ESIMS m/z 531
[MþH]þ, 533 [MþHþ2]þ. Anal. Calcd for C27H35BrO4Si: C, 61.01; H,
6.64. Found: C, 61.23; H, 6.55.
3.2.5. Compound 1e. Yield 99%; colorless oil; IR (film) 3026, 1743,
1722, 1228 cmꢁ1; 1H NMR (CDCl3, 300 MHz)
d 2.04 (s, 3H), 3.72 (s,
3H), 4.10 (m, 1H), 5.75 (s, 1H), 6.28e6.38 (m, 3H), 6.49 (d, J¼6.3 Hz,
1H), 7.09 (ddd, J¼7.8, 7.8 and 1.5 Hz,1H), 7.19e7.31 (m, 6H), 7.37 (dd,
J¼8.1 and 1.8 Hz, 1H), 7.52 (dd, J¼8.1 and 1.2 Hz, 1H); 13C NMR
3.3.1. Compound 2a. Yield 77%; white solid, mp 127e129 ꢀC; IR
(CDCl3, 75 MHz)
d
20.91, 48.73, 52.00, 75.12, 122.85, 126.28, 126.69,
(KBr) 2951, 2856, 1729, 1252, 1077 cmꢁ1; 1H NMR (CDCl3, 300 MHz)
127.10, 127.45, 127.47, 128.46, 129.01, 129.37, 132.92, 133.43, 136.96,
137.94, 139.28, 166.58, 169.55; ESIMS m/z 429 [MþH]þ, 431
[MþHþ2]þ. Anal. Calcd for C22H21BrO4: C, 61.55; H, 4.93. Found: C,
61.83; H, 5.07.
d
ꢁ0.22 (s, 3H), ꢁ0.20 (s, 3H), 0.75 (s, 9H), 2.94 (dd, J¼16.2 and
3.3 Hz, 1H), 3.57 (d, J¼16.2 Hz, 1H), 3.72 (s, 3H), 4.18 (d, J¼3.3 Hz,
1H), 4.8 (s, 1H), 6.94e6.98 (m, 2H), 7.10e7.43 (m, 11H), 7.45e7.49
(m, 1H); 13C NMR (CDCl3, 75 MHz)
d
ꢁ4.87, ꢁ4.56, 17.85, 25.59,
42.65, 52.14, 54.28, 61.49, 77.28, 125.06, 125.82, 126.69, 127.10,
127.94, 128.04, 128.38, 128.65, 129.07, 129.15, 132.99, 138.99, 140.04,
140.32, 143.76, 146.22, 174.03; ESIMS m/z 519 [MþNa]þ. Anal. Calcd
for C32H36O3Si: C, 77.38; H, 7.31. Found: C, 77.64; H, 7.49.
3.2.6. Compound 1f. Yield 88%; colorless oil; IR (film) 3057, 2951,
2857, 1721, 1434, 1076 cmꢁ1 1H NMR (CDCl3, 300 MHz)
; d 0.97 (s,
9H), 3.54 (s, 3H), 3.83e3.88 (m, 1H), 5.46e5.48 (m, 2H), 6.11 (s, 1H),
6.23e6.35 (m, 2H), 6.97 (ddd, J¼7.5, 7.5 and 1.5 Hz, 1H), 7.11e7.42
(m, 15H), 7.61e7.65 (m, 3H); 13C NMR (CDCl3, 75 MHz)
d
19.31,
3.3.2. Compound 4a. Yield 71%; colorless oil; IR (film) 2958, 2855,
26.98, 51.67, 52.63, 75.26, 122.87, 126.27, 126.77, 127.12, 127.36,
128.01, 128.30, 128.63, 129.29, 129.42, 130.14, 132.01, 132.57, 133.15,
133.52, 136.02, 136.14, 137.31, 139.12, 141.76, 166.79 (two carbons
are overlapped); ESIMS m/z 625 [MþH]þ, 627 [MþHþ2]þ. Anal.
Calcd for C36H37BrO3Si: C, 69.11; H, 5.96. Found: C, 69.44; H, 6.14.
1259, 1083 cmꢁ1; 1H NMR (CDCl3, 300 MHz)
d 0.15 (s, 3H), 0.22 (s,
3H), 0.92 (s, 9H), 3.74e3.81 (m, 1H), 5.08 (d, J¼2.7 Hz, 1H), 5.13 (d,
J¼6.3 Hz, 1H), 5.52 (d, J¼3.0 Hz, 1H), 6.08 (d, J¼10.2 Hz, 1H),
7.24e7.32 (m, 13H), 7.44e7.47 (m, 1H); 13C NMR (CDCl3, 125 MHz)
d
ꢁ4.33, ꢁ4.01, 18.01, 25.81, 56.49, 79.97, 104.72, 120.60, 124.15,
127.21, 127.27, 127.55, 128.06, 128.09, 128.17, 128.81, 128.82, 129.73,
138.86, 139.39, 142.69, 145.37, 146.17, 149.30; ESIMS m/z 461
[MþNa]þ. Anal. Calcd for C30H34OSi: C, 82.14; H, 7.81. Found: C,
82.39; H, 7.67.
3.2.7. Compound 1g. Yield 90%; colorless oil; IR (film) 2951, 2893,
2857, 1723, 1440, 1251, 1086 cmꢁ1 1H NMR (CDCl3, 300 MHz)
;
d
ꢁ0.36 (s, 3H), ꢁ0.06 (s, 3H), 0.82 (s, 9H),1.84 (d, J¼1.2 Hz, 3H), 3.63
(s, 3H), 4.00 (d, J¼7.8 Hz,1H), 5.49 (d, J¼7.8 Hz,1H), 5.98 (s,1H), 6.23
(s, 1H), 6.56 (s, 1H), 7.05e7.10 (m, 1H), 7.16e7.33 (m, 6H), 7.45 (dd,
J¼8.1 and 1.5 Hz, 1H), 7.56 (d, J¼7.5 Hz, 1H); 13C NMR (CDCl3,
3.3.3. Compound 2b-E. Yield 44%; white solid, mp 116e118 ꢀC; IR
(KBr) 2951, 2889, 2855, 1731, 1233, 1075 cmꢁ1 1H NMR (CDCl3,
;
75 MHz)
d
ꢁ5.05, ꢁ4.61, 17.08, 17.93, 25.72, 51.85, 55.73, 73.53,
300 MHz)
d
0.21 (s, 3H), 0.23 (s, 3H), 0.94 (s, 9H), 2.98 (ddd, J¼16.5,
122.98, 126.04, 126.36, 127.25, 127.95, 128.88, 128.94, 129.28,
129.99, 132.23, 135.87, 138.37, 138.95, 142.23, 167.43; ESIMS m/z 515
[MþH]þ, 517 [MþHþ2]þ. Anal. Calcd for C27H35BrO3Si: C, 62.90; H,
6.84. Found: C, 63.11; H, 6.59.
2.7 and 2.7 Hz, 1H), 3.74 (s, 3H), 3.79 (dd, J¼16.5 and 2.7 Hz, 1H),
4.01 (t, J¼2.7 Hz, 1H), 5.20 (s, 1H), 6.39 (q, J¼2.7 Hz, 1H), 7.12e7.16
(m, 3H), 7.22e7.40 (m, 5H), 7.44e7.46 (m, 1H); 13C NMR (CDCl3,
75 MHz)
d
ꢁ4.34, ꢁ4.32, 18.27, 25.86, 42.62, 52.30, 55.92, 61.64,
80.02, 124.97, 125.45, 126.15, 126.67, 127.21, 128.35, 128.40, 129.35,
136.74, 137.78, 143.14, 146.00, 173.87; ESIMS m/z 443 [MþNa]þ.
Anal. Calcd for C26H32O3Si: C, 74.24; H, 7.67. Found: C, 74.46; H, 7.69.
3.2.8. Compound 1h. Yield 85%; white solid, mp 81e83 ꢀC; IR (KBr)
2932, 2856, 2222, 1256, 1088 cmꢁ1 1H NMR (CDCl3, 300 MHz)
;
d
ꢁ0.21 (s, 3H), 0.11 (s, 3H), 0.91 (s, 9H), 3.35 (t, J¼6.0 Hz, 1H), 5.32
(d, J¼6.0 Hz, 1H), 5.50 (s, 1H), 5.88 (s, 1H), 6.32e6.40 (m, 2H), 7.11
(ddd, J¼7.8, 7.8 and 1.8 Hz, 1H), 7.23e7.34 (m, 6H), 7.48 (dd, J¼7.8
3.3.4. Compound 2b-Z. Yield 31%; colorless oil; IR (film) 2951, 2855,
1730, 1235, 1082 cmꢁ1 1H NMR (CDCl3, 300 MHz)
; d 0.00 (s, 3H),

3334
K.H. Kim et al. / Tetrahedron 67 (2011) 3328e3336
0.13 (s, 3H), 0.91 (s, 9H), 2.75 (ddd, J¼15.9, 3.3 and 2.1 Hz, 1H), 3.65
(dd, J¼15.9 and 2.1 Hz, 1H), 3.81 (s, 3H), 4.35 (t, J¼3.3 Hz, 1H), 5.17
(s, 1H), 6.22 (q, J¼2.1 Hz, 1H), 7.26e7.33 (m, 3H), 7.34e7.44 (m, 5H),
129.73, 134.98, 143.32, 146.12, 158.35, 173.96; ESIMS m/z 473
[MþNa]þ. Anal. Calcd for C27H34O4Si: C, 71.96; H, 7.60. Found: C,
72.21; H, 7.39.
7.54 (d, J¼7.8 Hz, 1H); 13C NMR (CDCl3, 75 MHz)
d
ꢁ4.32, ꢁ3.91,
17.98, 25.61, 42.70, 52.20, 54.89, 61.72, 76.90, 125.03, 125.92, 126.59,
126.67, 127.71, 127.94, 128.54, 129.22, 136.16, 136.78, 143.40, 145.96,
174.00; ESIMS m/z 443 [MþNa]þ. Anal. Calcd for C26H32O3Si: C,
74.24; H, 7.67. Found: C, 74.31; H, 7.86.
3.3.10. Compound 2d-Z. Yield 23% (based on 1H NMR); colorless
oil; 1H NMR (CDCl3, 300 MHz)
d
ꢁ0.04 (s, 3H), 0.09 (s, 3H), 0.87 (s,
9H), 2.67 (ddd, J¼15.9, 3.0 and 2.1 Hz, 1H), 3.57 (dd, J¼15.9 and
2.1 Hz, 1H), 3.75 (s, 3H), 3.81 (s, 3H), 4.26 (t, J¼3.0 Hz, 1H), 5.14 (s,
1H), 6.11 (q, J¼2.1 Hz, 1H), 7.23e7.35 (m, 7H), 7.47e7.50 (m, 1H); 13C
3.3.5. Compound 3b. Yield 92%; colorless oil; IR (film) 2952, 2891,
NMR (CDCl3, 75 MHz)
d
ꢁ4.24, ꢁ3.86, 17.96, 25.61, 42.63, 52.13,
2857, 1719, 1251, 1131 cmꢁ1
;
1H NMR (CDCl3, 300 MHz)
d
0.14 (s,
53.38, 54.87, 61.53, 76.89, 113.93, 125.01, 125.91, 127.88, 128.88,
129.17, 129.63, 133.46, 143.49, 145.92, 158.31, 174.00 (one carbon is
overlapped).
3H), 0.22 (s, 3H), 0.93 (s, 9H), 3.79 (s, 3H), 4.90 (d, J¼7.2 Hz,1H), 5.33
(t, J¼1.2 Hz,1H), 5.42 (d, J¼7.2 Hz,1H), 6.12 (d, J¼0.9 Hz,1H), 7.01 (d,
J¼1.2 Hz, 1H), 7.21e7.24 (m, 1H), 7.29e7.38 (m, 7H), 7.59e7.62 (m,
1H); 13C NMR (CDCl3, 75 MHz)
d
ꢁ4.83, ꢁ4.72, 18.19, 25.78, 50.13,
3.3.11. Compound 3d. Yield 62%; colorless oil; IR (film) 2952, 2895,
51.84, 77.10, 119.52, 121.50, 124.86, 126.62, 127.01, 128.26, 128.46
(2C), 128.66, 136.71, 138.22, 141.20, 144.87, 167.70 (one carbon is
overlapped); ESIMS m/z 443 [MþNa]þ. Anal. Calcd for C26H32O3Si:
C, 74.24; H, 7.67. Found: C, 74.47; H, 7.69.
2856,1719,1512,1252 cmꢁ1; 1H NMR (CDCl3, 300 MHz)
d 0.38 (s, 3H),
0.47 (s, 3H),1.18 (s, 9H), 4.04 (s, 3H), 4.05 (s, 3H), 5.11 (d, J¼7.2 Hz,1H),
5.58 (t, J¼0.9 Hz, 1H), 5.66 (d, J¼7.2 Hz, 1H), 6.35 (d, J¼0.9 Hz, 1H),
7.08e7.13 (m, 2H), 7.20 (d, J¼1.2 Hz, 1H), 7.49e7.58 (m, 5H),
7.80e7.83 (m, 1H); 13C NMR (CDCl3, 75 MHz)
d
ꢁ4.81, ꢁ4.71, 18.21,
3.3.6. Compound 2c-E. Yield 37%; colorless oil; IR (film) 2952, 2891,
25.80, 50.06, 51.83, 55.26, 77.22, 113.95, 119.26, 121.02, 124.81,
126.53, 128.20, 128.26, 129.55, 129.81, 138.19, 138.97, 141.49, 144.55,
158.65, 167.85; ESIMS m/z 473 [MþNa]þ, 319 [Mþ1ꢁTBSOH]þ.
2857, 1731, 1509, 1234, 1075 cmꢁ1; 1H NMR (CDCl3, 300 MHz)
d 0.21
(s, 3H), 0.22 (s, 3H), 0.94 (s, 9H), 3.94 (ddd, J¼16.2, 3.0 and 3.0 Hz,
1H), 3.74 (s, 3H), 3.75 (dd, J¼16.2 and 3.0 Hz, 1H), 3.99 (t, J¼3.0 Hz,
1H), 5.19 (s,1H), 6.36 (q, J¼2.4 Hz,1H), 6.90e6.97 (m, 2H), 7.07e7.12
(m, 2H), 7.29e7.40 (m, 3H), 7.42e7.47 (m, 1H); 13C NMR (CDCl3,
3.3.12. Compound 2e-E. Yield 23%; colorless oil; IR (film) 3027,
2952, 1732, 1232 cmꢁ1 1H NMR (CDCl3, 300 MHz)
; d 2.10 (s, 3H),
75 MHz)
d
ꢁ4.32 (2C), 18.26, 25.85, 42.39, 52.29, 55.91, 61.63, 80.05,
3.03 (ddd, J¼16.5, 2.7 and 2.7 Hz, 1H), 3.87 (s, 3H), 3.84 (dd, J¼16.5
and 2.7 Hz, 1H), 4.11 (t, J¼2.7 Hz, 1H), 6.16 (s, 1H), 6.60 (q, J¼2.7 Hz,
1H), 7.12e7.17 (m, 3H), 7.21e7.30 (m, 2H), 7.31e7.43 (m, 2H),
115.32 (d, J¼21.2 Hz), 124.38, 124.97, 126.18, 128.40, 128.73 (d,
J¼8.0 Hz), 129.40, 132.95 (d, J¼2.9 Hz), 137.25, 143.15, 146.02, 161.15
(d, J¼246.0 Hz), 173.81; ESIMS m/z 461 [MþNa]þ, 307
[Mþ1ꢁTBSOH]þ. Anal. Calcd for C26H31FO3Si: C, 71.20; H, 7.12.
Found: C, 71.42; H, 7.30.
7.48e7.51 (m, 2H); 13C NMR (CDCl3, 75 MHz)
d 21.33, 42.71, 52.49,
55.93, 58.29, 80.32, 125.04, 126.79, 126.86, 127.04, 127.33, 128.43,
128.69, 130.37, 135.54, 136.60, 141.73, 144.51, 170.92, 173.39; ESIMS
m/z 371 [MþNa]þ. Anal. Calcd for C22H20O4: C, 75.84; H, 5.79.
Found: C, 76.03; H, 5.89.
3.3.7. Compound 2c-Z. Yield 30%; colorless oil; IR (film) 2951, 2856,
1732, 1509, 1233, 1084 cmꢁ1; 1H NMR (CDCl3, 300 MHz)
d
ꢁ0.56 (s,
3H), 0.06 (s, 3H), 0.86 (s, 9H), 2.69 (ddd, J¼15.9, 3.0 and 2.1 Hz, 1H),
3.58 (dd, J¼15.9 and 2.1 Hz, 1H), 3.76 (s, 3H), 4.25 (t, J¼3.0 Hz, 1H),
5.09 (s, 1H), 6.12 (q, J¼2.1 Hz, 1H), 7.00e7.07 (m, 2H), 7.24e7.39 (m,
3.3.13. Compound 2e-Z. Yield 15%; colorless oil; IR (film) 3027,
2953, 1734, 1231 cmꢁ1 1H NMR (CDCl3, 300 MHz)
; d 2.07 (s, 3H),
2.77 (ddd, 15.9, 3.3 and 2.4 Hz, 1H), 3.63 (dd, J¼15.9 and 2.4 Hz, 1H),
3.80 (s, 3H), 4.56 (t, J¼3.0 Hz, 1H), 6.14 (s, 1H), 6.22 (q, J¼2.4 Hz, 1H),
7.21e7.28 (m, 2H), 7.30e7.34 (m, 4H), 7.39e7.44 (m, 2H), 7.51e7.54
5H), 7.49 (d, J¼7.5 Hz,1H); 13C NMR (CDCl3, 75 MHz)
ꢁ4.30, ꢁ3.86,
d
17.97, 25.59, 42.67, 52.22, 54.87, 61.49, 76.95, 115.45 (d, J¼21.1 Hz),
125.05 (d, J¼1.1 Hz), 125.40, 125.93, 128.00, 129.22 (d, J¼7.4 Hz),
129.30, 132.95 (d, J¼2.8 Hz), 135.80, 143.34, 145.81, 161.53 (d,
J¼245.0 Hz), 173.91; ESIMS m/z 461 [MþNa]þ, 307 [Mþ1ꢁTBSOH]þ.
Anal. Calcd for C26H31FO3Si: C, 71.20; H, 7.12. Found: C, 71.02; H,
7.31.
(m,1H); 13C NMR (CDCl3, 75 MHz)
d 21.26, 42.74, 52.50, 55.00, 57.71,
77.42, 124.95, 127.10 (2C), 127.71, 127.83, 128.49, 128.59, 130.28,
133.70, 135.87, 142.11, 144.34, 170.31, 173.46; ESIMS m/z 371
[MþNa]þ. Anal. Calcd for C22H20O4: C, 75.84; H, 5.79. Found: C,
75.86; H, 6.07.
3.3.8. Compound 3c. Yield 59%; colorless oil; IR (film) 2952, 2857,
3.3.14. Compound 3e. Yield 57%; colorless oil; IR (film) 3026, 2951,
1718, 1509, 1245, 1130 cmꢁ1
;
1H NMR (CDCl3, 300 MHz)
d
0.12 (s,
1733, 1237 cmꢁ1; 1H NMR (CDCl3, 300 MHz)
d 2.05 (s, 3H), 3.81 (s,
3H), 0.22 (s, 3H), 0.93 (s, 9H), 3.79 (s, 3H), 4.84 (d, J¼7.2 Hz,1H), 5.31
(d, J¼0.9 Hz, 1H), 5.42 (d, J¼7.2 Hz, 1H), 6.11 (d, J¼0.9 Hz, 1H), 6.96
(d, J¼0.9 Hz, 1H), 6.98e7.05 (m, 2H), 7.25e7.36 (m, 5H), 7.57e7.59
3H), 4.95 (d, J¼7.8 Hz, 1H), 5.50 (t, J¼1.2 Hz, 1H), 6.18 (s, 1H), 6.61 (d,
J¼7.8 Hz, 1H), 7.12 (d, J¼1.8 Hz, 1H), 7.19e7.41 (m, 8H), 7.67 (d,
J¼7.8 Hz, 1H); 13C NMR (CDCl3, 75 MHz)
d 21.07, 47.84, 52.33, 76.41,
(m, 1H); 13C NMR (CDCl3, 75 MHz)
d
ꢁ4.82, ꢁ4.71, 18.17, 25.77,
120.11, 122.92, 125.69, 127.48, 127.53, 128.75, 128.97, 129.31, 129.53,
136.52, 136.79, 140.07, 140.92, 142.02, 167.88, 170.61; ESIMS m/z 371
[MþNa]þ. Anal. Calcd for C22H20O4: C, 75.84; H, 5.79. Found: C,
75.97; H, 5.51.
49.93, 51.87, 77.00, 115.39 (d, J¼21.1 Hz), 119.44, 120.24, 124.91,
126.63, 128.29, 128.71, 130.04 (d, J¼8.0 Hz), 132.94 (d, J¼3.4 Hz),
138.09, 140.92, 141.05, 144.85, 161.68 (d, J¼246.0 Hz), 167.69; ESIMS
m/z 461 [MþNa]þ. Anal. Calcd for C26H31FO3Si: C, 71.20; H, 7.12.
Found: C, 71.43; H, 7.19.
3.3.15. Compound 2f-E. Yield 40%; white solid, mp 173e175 ꢀC; IR
(KBr) 3067, 2951, 2895, 2858, 1731, 1232 cmꢁ1 1H NMR (CDCl3,
;
3.3.9. Compound 2d-E. Yield 39%; colorless oil; IR (film) 2951,
300 MHz)
d
1.10 (s, 9H), 2.84 (ddd, J¼16.2, 2.7 and 2.7 Hz, 1H), 3.68
2856, 1730, 1512, 1251, 1074 cmꢁ1; 1H NMR (CDCl3, 300 MHz)
d
0.21
(dd, J¼16.2 and 2.7 Hz, 1H), 3.80 (s, 3H), 3.93 (t, J¼2.7 Hz, 1H), 5.11
(s, 1H), 5.28 (q, J¼2.7 Hz, 1H), 6.89e6.92 (m, 2H), 7.04e7.09 (m, 1H),
7.14e7.19 (m, 2H), 7.24e7.37 (m, 3H), 7.40e7.51 (m, 7H), 7.78e7.83
(s, 3H), 0.22 (s, 3H), 0.94 (s, 9H), 2.4 (ddd, J¼16.2, 2.7 and 2.7 Hz,
1H), 3.74 (s, 3H), 3.76 (s, 3H), 3.72e3.80 (m, 1H), 3.98 (t, J¼2.7 Hz,
1H), 5.18 (s,1H), 6.33 (q, J¼2.7 Hz,1H), 6.77e6.80 (m, 2H), 7.06e7.09
(m, 2H), 7.30e7.39 (m, 3H), 7.43e7.46 (m, 1H); 13C NMR (CDCl3,
(m, 4H); 13C NMR (CDCl3, 75 MHz)
d 19.29, 26.96, 42.19, 52.25,
55.92, 61.49, 80.89, 124.76, 125.49, 126.48, 126.55, 127.01, 127.75,
127.84, 128.26, 129.44, 129.81, 129.86, 133.85, 134.03, 136.14, 136.22,
136.82, 143.74, 145.72, 173.93 (two carbons are overlapped); ESIMS
75 MHz)
d
ꢁ4.30, ꢁ4.32, 18.27, 25.87, 42.46, 52.24, 55.23, 55.97,
61.62, 80.11, 113.87, 124.85, 124.96, 126.18, 128.30, 128.42, 129.30,

K.H. Kim et al. / Tetrahedron 67 (2011) 3328e3336
3335
m/z 567 [MþNa]þ. Anal. Calcd for C36H36O3Si: C, 79.37; H, 6.66.
5.85 (s, 1H), 6.53 (s, 1H), 7.20e7.36 (m, 4H); 13C NMR (CDCl3,
75 MHz)
117.74, 124.39, 124.90, 126.90, 127.65, 128.21, 136.76, 138.50, 143.70,
145.27, 167.72; ESIMS m/z 381 [MþNa]þ. Anal. Calcd for C21H30O3Si:
C, 70.35; H, 8.43. Found: C, 70.59; H, 8.57.
Found: C, 79.71; H, 6.81.
d
ꢁ4.75, ꢁ4.17, 18.07, 25.74, 49.93, 51.77, 54.00, 75.32,
3.3.16. Compound 3f. Yield 55%; colorless oil; IR (film) 3058, 2951,
2859, 1716, 1243, 1121 cmꢁ1 1H NMR (CDCl3, 300 MHz)
; d 1.06 (s,
9H), 3.71 (s, 3H), 5.02 (dd, J¼7.2 and 1.2 Hz, 1H), 5.37 (s, 1H), 5.70 (d,
J¼7.2 Hz, 1H), 6.20 (d, J¼0.9 Hz, 1H), 6.49 (dd, J¼7.8 and 0.9 Hz, 1H),
6.88 (ddd, J¼7.5, 7.5 and 0.9 Hz,1H), 6.96 (d, J¼1.5 Hz,1H), 7.14e7.24
(m, 2H), 7.30e7.45 (m, 10H), 7.51 (d, J¼7.5 Hz, 1H), 7.65e7.69 (m,
Acknowledgements
This research was supported by Basic Science Research Program
through the National Research Foundation of Korea (NRF) funded
by the Ministry of Education, Science and Technology (2010-
0015675). Spectroscopic data were obtained from the Korea Basic
Science Institute, Gwangju branch.
2H), 7.76e7.80 (m, 2H); 13C NMR (CDCl3, 75 MHz)
d 19.40, 26.95,
49.83, 51.85, 78.12, 119.26, 121.04, 125.58, 126.93, 127.17, 127.61,
127.73, 128.01, 128.09, 128.37, 128.58, 129.64, 129.77, 133.41, 134.48,
135.96, 136.03, 136.78, 138.35, 141.37, 141.44, 144.19, 167.85; ESIMS
m/z 567 [MþNa]þ. Anal. Calcd for C36H36O3Si: C, 79.37; H, 6.66.
Found: C, 79.44; H, 6.49.
Supplementary data
3.3.17. Compound 5. Yield 85%; white solid, mp 104e106 ꢀC; IR
(KBr) 3028, 2933, 2856, 1731, 1442, 1248, 1077 cmꢁ1 1H NMR
;
These data include experimental details, DFT calculations, X-ray
structures, and copies of 1H and 13C NMR spectra. Supplementary
data related to this article can be found online at doi:10.1016/
j.tet.2011.03.070.
(CDCl3, 300 MHz)
d 0.18 (s, 3H), 0.22 (s, 3H), 0.90 (s, 9H), 1.92e1.93
(m, 3H), 3.00 (ddd, J¼16.2, 2.7 and 2.7 Hz,1H), 3.66 (ddd, J¼16.2, 2.7
and 2.7 Hz, 1H), 3.70 (s, 3H), 3.87 (t, J¼0.9 Hz, 1H), 5.21 (s, 1H),
7.15e7.21 (m, 3H), 7.24e7.35 (m, 5H), 7.45e7.48 (m, 1H); 13C NMR
(CDCl3, 75 MHz)
d
ꢁ4.25, ꢁ4.02, 14.41, 18.04, 25.76, 48.35, 52.32,
References and notes
60.75, 70.54, 77.79, 125.33, 125.36, 126.70, 127.83, 128.01, 128.20,
128.79,132.58, 133.32, 137.09, 143.97, 145.36, 175.58; ESIMS m/z 457
[MþNa]þ, 303 [Mþ1ꢁTBSOH]. Anal. Calcd for C27H34O3Si: C, 74.61;
H, 7.88. Found: C, 74.93; H, 7.96.
1. Synthesis of complex molecules by palladium-catalyzed domino reactions, see:
(a) de Meijere, A.; Brase, S. J. Organomet. Chem. 1999, 576, 88e110; (b) de
Meijere, A.; Meyer, F. E. Angew. Chem., Int. Ed. Engl. 1994, 33, 2379e2411; (c)
Zeni, G.; Larock, R. C. Chem. Rev. 2006, 106, 4644e4680; (d) Hu, Y.; Yu, C.; Ren,
D.; Hu, Q.; Zhang, L.; Cheng, D. Angew. Chem., Int. Ed. 2009, 48, 5448e5451; (e)
Trost, B. M.; O’Boyle, B. M.; Hund, D. Chem.dEur. J. 2010, 16, 9772e9776; (f) Kim,
E. S.; Kim, K. H.; Park, S.; Kim, J. N. Tetrahedron Lett. 2010, 51, 4648e4652.
2. Heck-type cascade for the synthesis of complex molecules, see: (a) de Meijere,
A.; von Zezschwitz, P.; Brase, S. Acc. Chem. Res. 2005, 38, 413e422; (b) Negishi,
E.-I.; Coperet, C.; Ma, S.; Liou, S.-Y.; Liu, F. Chem. Rev. 1996, 96, 365e393; (c)
Miyazaki, F.; Uotsu, K.; Shibasaki, M. Tetrahedron 1998, 54, 13073e13078; (d)
Overman, L. E.; Ricca, D. J.; Tran, V. D. J. Am. Chem. Soc. 1993, 115, 2042e2044;
(e) Schweizer, S.; Song, Z.-Z.; Meyer, F. E.; Parsons, P. J.; de Meijere, A. Angew.
Chem., Int. Ed. 1999, 38, 1452e1454; (f) Schweizer, S.; Tokan, W. M.; Parsons, P.
J.; de Meijere, A. Eur. J. Org. Chem. 2010, 4687e4699; (g) Hu, Y.; Ouyang, Y.; Qu,
Y.; Hu, Q.; Yao, H. Chem. Commun. 2009, 4575e4577; (h) Taniguchi, T.; Zaimoku,
H.; Ishibashi, H. J. Org. Chem. 2009, 74, 2624e2626; (i) Grigg, R.; Sakee, U.;
Sridharan, V.; Sukirthalingam, S.; Thangavelauthum, R. Tetrahedron 2006, 62,
9523e9532; (j) Gowrisankar, S.; Lee, H. S.; Lee, K. Y.; Lee, J.-E.; Kim, J. N. Tet-
rahedron Lett. 2007, 48, 8619e8622.
3. (a) Huang, Q.; Fazio, A.; Dai, G.; Campo, M. A.; Larock, R. C. J. Am. Chem. Soc.
2004, 126, 7460e7461; (b) Ruck, R. T.; Huffman, M. A.; Kim, M. M.; Shevlin, M.;
Kandur, W. V.; Davies, I. W. Angew. Chem., Int. Ed. 2008, 47, 4711e4714; (c)
Brown, D.; Grigg, R.; Sridharan, V.; Tambyrajah, V. Tetrahedron Lett. 1995, 36,
8137e8140; (d) Jana, R.; Samanta, S.; Ray, J. K. Tetrahedron Lett. 2008, 49,
851e854; (e) Liron, F.; Knochel, P. Tetrahedron Lett. 2007, 48, 4943e4946; (f)
Kim, S. H.; Lee, H. S.; Kim, K. H.; Kim, J. N. Tetrahedron Lett. 2010, 51, 4267e4271.
4. (a) Terao, Y.; Satoh, T.; Miura, M.; Nomura, M. Bull. Chem. Soc. Jpn. 1999, 72,
2345e2350; (b) Brase, S. Synlett 1999, 1654e1656; (c) Innitzer, A.; Brecker, L.;
Mulzer, J. Org. Lett. 2007, 9, 4431e4434; (d) Larock, R. C.; Han, X. J. Org. Chem.
1999, 64, 1875e1887; (e) Khan, F. A.; Czerwonka, R.; Reissig, H.-U. Eur. J. Org.
Chem. 2000, 3607e3617.
3.3.18. Compound 4g. Yield 57%; white solid, mp 58e60 ꢀC; IR
(KBr) 2928, 2857, 1465, 1076 cmꢁ1; 1H NMR (CDCl3, 300 MHz)
d 0.14
(s, 3H), 0.21 (s, 3H), 0.96 (s, 9H),1.79 (d, J¼1.2 Hz, 3H), 3.57e3.60 (m,
1H), 4.94 (d, J¼2.7 Hz, 1H), 5.26 (d, J¼5.7 Hz, 1H), 5.57 (d, J¼3.0 Hz,
1H), 6.56 (s, 1H), 7.22e7.41 (m, 8H), 7.51e7.53 (m, 1H); 13C NMR
(CDCl3, 75 MHz)
d
ꢁ4.29, ꢁ3.99, 14.70, 18.12, 25.87, 66.32, 77.26,
104.11, 120.63, 124.88, 126.27, 128.11, 128.25, 128.93, 130.39, 136.57,
138.09, 139.25, 146.20, 148.26 (one carbon is overlapped); ESIMS m/
z 399 [MþNa]þ. Anal. Calcd for C25H32OSi: C, 79.73; H, 8.56. Found:
C, 79.98; H, 8.41.
3.3.19. Compound 3h. Yield 73%; colorless oil; IR (film) 3027, 2952,
2892, 2857, 2222,1466,1255,1077 cmꢁ1; 1H NMR (CDCl3, 300 MHz)
d
0.09 (s, 3H), 0.12 (s, 3H), 0.82 (s, 9H), 3.90 (s, 1H), 5.15 (d, J¼2.1 Hz,
1H), 5.56 (s, 1H), 5.65 (s, 1H), 7.14e7.31 (m, 9H), 7.52e7.55 (m, 1H);
13C NMR (CDCl3, 75 MHz)
d
ꢁ4.19, ꢁ4.01, 17.94, 25.77, 57.53, 79.81,
118.02, 120.35, 121.82, 124.27, 125.59, 127.45, 128.36, 128.85, 129.17,
129.20, 131.88, 135.96, 138.49, 140.75, 143.47; ESIMS m/z 410
[MþNa]þ. Anal. Calcd for C25H29NOSi: C, 77.47; H, 7.54; N, 3.61.
Found: C, 77.29; H, 7.61; N, 3.39.
5. Examples involving 5-exo-trig/4-exo-trig cascade cyclizations are rather limited,
see: (a) Grigg, R.; Sridharan, V.; Sukirthalingam, S. Tetrahedron Lett. 1991, 32,
3855e3858; (b) Yip, K.-T.; Zhu, N.-Y.; Yang, D. Org. Lett. 2009, 11, 1911e1914.
6. For the general review on BayliseHillman reaction, see: (a) Basavaiah, D.; Rao, A.
J.; Satyanarayana, T. Chem. Rev. 2003, 103, 811e891; (b) Singh, V.; Batra, S. Tet-
rahedron 2008, 64, 4511e4574; (c) Ciganek, E. In Organic Reactions; Paquette, L. A.,
Ed.; John Wiley & Sons: New York, NY, 1997; Vol. 51, pp 201e350; (d) Basavaiah,
D.; Rao, P. D.; Hyma, R. S. Tetrahedron1996, 52, 8001e8062; (e) Drewes, S. E.; Roos,
G. H. P. Tetrahedron 1988, 44, 4653e4670; (f) Kim, J. N.; Lee, K. Y. Curr. Org. Chem.
2002, 6, 627e645; (g) Lee, K. Y.; Gowrisankar, S.; Kim, J. N. Bull. Korean Chem. Soc.
2005, 26,1481e1490; (h) Langer, P. Angew. Chem., Int. Ed. 2000, 39, 3049e3052; (i)
Radha Krishna, P.; Sachwani, R.; Reddy, P. S. Synlett 2008, 2897e2912; (j) De-
clerck, V.; Martinez, J.; Lamaty, F. Chem. Rev. 2009, 109, 1e48.
7. For our Pd-catalyzed chemical transformations of BayliseHillman adducts, see:
(a) Gowrisankar, S.; Lee, H. S.; Kim, S. H.; Lee, K. Y.; Kim, J. N. Tetrahedron 2009,
65, 8769e8780 and further references cited therein;; (b) Kim, K. H.; Kim, E. S.;
Kim, J. N. Tetrahedron Lett. 2009, 50, 5322e5325; (c) Kim, H. S.; Lee, H. S.; Kim,
S. H.; Kim, J. N. Tetrahedron Lett. 2009, 50, 3154e3157; (d) Kim, J. M.; Kim, S. H.;
Lee, H. S.; Kim, J. N. Tetrahedron Lett. 2009, 50, 1734e1737; (e) Park, J. B.; Ko, S.
H.; Hong, W. P.; Lee, K.-J. Bull. Korean Chem. Soc. 2004, 25, 927e930; (f) Vasu-
devan, A.; Tseng, P.-S.; Djuric, S. W. Tetrahedron Lett. 2006, 47, 8591e8593; (g)
Kim, J. M.; Kim, K. H.; Kim, T. H.; Kim, J. N. Tetrahedron Lett. 2008, 49,
3248e3251.
3.3.20. Compound 6. Yield 17%; pale yellow oil; IR (film) 3053,
2927, 2856, 2221,1494 cmꢁ1; 1H NMR (CDCl3, 300 MHz)
d 7.33e7.44
(m, 4H), 7.51e7.65 (m, 5H), 7.83e7.90 (m, 2H), 8.19 (s, 1H), 8.24 (s,
1H); ESIMS m/z 278 [MþNa]þ.
3.3.21. Compound 2i-E. Yield 4%; colorless oil; IR (film) 2952, 2857,
1734, 1228, 1075 cmꢁ1 1H NMR (CDCl3, 300 MHz)
; d 0.19 (s, 6H),
0.94 (s, 9H), 1.43e1.47 (m, 3H), 2.62 (d, J¼15.3 Hz, 1H), 3.34 (ddd,
J¼15.3, 2.1 and 2.1 Hz, 1H), 3.73 (s, 3H), 3.78e3.80 (m, 1H), 5.08 (s,
1H), 5.47e5.55 (m, 1H), 7.31e7.45 (m, 3H), 7.46e7.49 (m, 1H);
ESIMS m/z 381 [MþNa]þ. Anal. Calcd for C21H30O3Si: C, 70.35; H,
8.43. Found: C, 70.51; H, 8.54.
3.3.22. Compound 3i. Yield 75%; colorless oil; IR (film) 2952, 2893,
2857, 1721, 1466, 1073 cmꢁ1 1H NMR (CDCl3, 300 MHz)
; d 0.00 (s,
3H), 0.03 (s, 3H), 0.80 (s, 9H), 3.30 (dd, J¼9.6 and 4.8 Hz,1H), 3.81 (s,
3H), 4.10 (t, J¼9.6 Hz, 1H), 5.24e5.32 (m, 3H), 5.66e5.78 (m, 1H),

3336
K.H. Kim et al. / Tetrahedron 67 (2011) 3328e3336
8. Kim, K. H.; Lee, H. S.; Kim, S. H.; Kim, S. H.; Kim, J. N. Chem.dEur. J. 2010, 16,
2375e2380.
Rousseaux, S.; Davi, M.; Sofack-Kreutzer, J.; Pierre, C.; Kefalidis, C. E.; Clot, E.;
Fagnou, K.; Baudoin, O. J. Am. Chem. Soc. 2010, 132, 10706e10716; (e) Rousseaux,
S.; Gorelsky, S. I.; Chung, B. K. W.; Fagnou, K. J. Am. Chem. Soc. 2010, 132,
10692e10705; (f) Stuart, D. R.; Fagnou, K. Science 2007, 316, 1172e1175; (g)
Lapointe, D.; Fagnou, K. Chem. Lett. 2010, 39, 1118e1126.
9. Various biologically important natural substances having a cyclobuta[a]indene
moiety have been known including artochamins HeJ, and the synthetic ap-
proaches for this backbone have received much attention, see: (a) Nicolaou, K.
C.; Lister, T.; Denton, R. M.; Gelin, C. F. Tetrahedron 2008, 64, 4736e4757; (b)
Nicolaou, K. C.; Lister, T.; Denton, R. M.; Gelin, C. F. Angew. Chem., Int. Ed. 2007,
46, 7501e7505; (c) Wang, Y.-H.; Hou, A.-J.; Chen, D.-F.; Weiller, M.; Wendel, A.;
Staples, R. J. Eur. J. Org. Chem. 2006, 3457e3463; (d) Christl, M.; Fischer, H.;
Arnone, M.; Engels, B. Chem.dEur. J. 2009, 15, 11266e11272; (e) Binot, G.; Zard,
S. Z. Tetrahedron Lett. 2003, 44, 7703e7706; (f) Devineau, A.; Grosbois, M.;
Carletti, I.; Vacher, B. J. Org. Chem. 2009, 74, 757e763; (g) Bonnaud, B.; Mariet,
N.; Vacher, B. Eur. J. Org. Chem. 2006, 246e256.
10. Synthesis of methylene- or alkylideneindanes and their synthetic applications,
see: (a) Brase, S.; Rumper, J.; Voigt, K.; Albecq, S.; Thurau, G.; Villard, R.;
Waegell, B.; de Meijere, A. Eur. J. Org. Chem. 1998, 671e678; (b) Jang, H.-Y.;
Krische, M. J. J. Am. Chem. Soc. 2004, 126, 7875e7880; (c) Clive, D. L. J.; Kong, X.;
Paul, C. C. Tetrahedron 1996, 52, 6085e6116; (d) Snyder, S. A.; Breazzano, S. P.;
Ross, A. G.; Lin, Y.; Zografos, A. L. J. Am. Chem. Soc. 2009, 131, 1753e1765; (e)
Jeffrey, J. L.; Sarpong, R. Tetrahedron Lett. 2009, 50, 1969e1972.
17. (a) Glover, B.; Harvey, K. A.; Liu, B.; Sharp, M. J.; Tymoschenko, M. F. Org. Lett.
2003, 5, 301e304; (b) Pivsa-Art, S.; Satoh, T.; Kawamura, Y.; Miura, M.; Nomura,
M. Bull. Chem. Soc. Jpn. 1998, 71, 467e473; (c) Lane, B. S.; Brown, M. A.; Sames, D.
J. Am. Chem. Soc. 2005, 127, 8050e8057; (d) Park, C.-H.; Ryabova, V.; Seregin, I.
V.; Sromek, A. W.; Gevorgyan, V. Org. Lett. 2004, 6, 1159e1162.
18. For the discussion of CeH (aryl) activation with CMD process by other groups,
see: (a) Joo, J. M.; Toure, B. B.; Sames, D. J. Org. Chem. 2010, 75, 4911e4920; (b)
Mousseau, J. J.; Fortier, A.; Charette, A. B. Org. Lett. 2010, 12, 516e519; (c) Po-
tavathri, S.; Pereira, K. C.; Gorelsky, S. I.; Pike, A.; LeBris, A. P.; DeBoef, B. J. Am.
Chem. Soc. 2010, 132, 14676e14681; (d) Hwang, S. J.; Cho, S. H.; Chang, S. J. Am.
Chem. Soc. 2008, 130, 16158e16159; (e) Geary, L. M.; Hultin, P. G. Eur. J. Org.
Chem. 2010, 5563e5573; (f) Pinto, A.; Neuville, L.; Retailleau, P.; Zhu, J. Org. Lett.
2006, 8, 4927e4930; (g) Hennessy, E. J.; Buchwald, S. L. J. Am. Chem. Soc. 2003,
125, 12084e12085.
19. For the isomerization of double bond catalyzed by XPdH species, see: (a)
Huang, Q.; Larock, R. C. J. Org. Chem. 2003, 68, 7342e7349; (b) Nasveschuk, C.
G.; Frein, J. D.; Jui, N. T.; Rovis, T. Org. Lett. 2007, 9, 5099e5102; (c) Soderberg, B.
C. G.; Hubbard, J. W.; Rector, S. R.; O’Neil, S. N. Tetrahedron 2005, 61,
3637e3649; (d) Shi, L.; Narula, C. K.; Mak, K. T.; Kao, L.; Xu, Y.; Heck, R. F. J. Org.
Chem. 1983, 48, 3894e3900; (e) Calo, V.; Nacci, A.; Monopoli, A.; Laera, S.; Cioffi,
N. J. Org. Chem. 2003, 68, 2929e2933; (f) Jeffery, T.; David, M. Tetrahedron Lett.
1998, 39, 5751e5754.
11. Reaction mechanisms for the formation of 2a and 4a are discussed in detail in
Supplementary data. The mechanisms for the formation of 5, 4g, and 3i are also
proposed in Supplementary data.
12. For the isolation and reactivity of
s-alkylpalladium intermediates, see: (a)
Martin-Matute, B.; Mateo, C.; Cardenas, D. J.; Echavarren, A. M. Chem.dEur. J.
2001, 7, 2341e2348; (b) Beccalli, E. M.; Borsini, E.; Brenna, S.; Galli, S.; Riga-
monti, M.; Broggini, G. Chem.dEur. J. 2010, 16, 1670e1678; (c) Yao, T.; Hirano,
K.; Satoh, T.; Miura, M. Chem.dEur. J. 2010, 16, 12307e12311.
20. We have carried out density functional theory (DFT) calculations with 6-31G
*
13. Examples on concomitant
d
-carbon elimination/decarboxylation, see: (a) Kim,
basis sets using a suite of Gaussian 03 programs. The relative energy of 2b-E
and 2b-Z was compared. The energy of 2b-E was found to be slightly more
stable than 2b-Z by ca. 2.18 kcal/mol (see Supplementary data).
H. S.; Gowrisankar, S.; Kim, S. H.; Kim, J. N. Tetrahedron Lett. 2008, 49,
3858e3861; (b) Kim, H. S.; Gowrisankar, S.; Kim, E. S.; Kim, J. N. Tetrahedron
Lett. 2008, 49, 6569e6572.
21. For related Pd-catalyzed functionalization of vinylic CeH bond, see: (a) Giri,
R.; Yu, J.-Q. J. Am. Chem. Soc. 2008, 130, 14082e14083; (b) Lu, J.; Tan, X.;
Chen, C. J. Am. Chem. Soc. 2007, 129, 7768e7769 and this paper disclosed
a CeH activation of 2-imidazolone;; (c) Rigby, J. H.; Hughes, R. C.; Heeg, M. J.
J. Am. Chem. Soc. 1995, 117, 7834e7835; (d) Lautens, M.; Fang, Y.-Q. Org. Lett.
2003, 5, 3679e3682; (e) Chida, N.; Ohtsuka, M.; Ogawa, S. J. Org. Chem. 1993,
58, 4441e4447; (f) Ikeda, M.; El Bialy, S. A. A.; Yakura, T. Heterocycles 1999,
51, 1957e1970 and further references cited therein. Most of the intra-
molecular Heck reactions involving a formal anti-elimination process could
14. For the Heck reaction with highly substituted alkenes, see: (a) Heck, R. F. Org.
React. 1982, 27, 345e390; (b) Dankwardt, J. W.; Flippin, L. A. J. Org. Chem. 1995,
60, 2312e2313; (c) Abelman, M. M.; Oh, T.; Overmann, L. E. J. Org. Chem. 1987,
52, 4130e4133; (d) Nadri, S.; Joshaghani, M.; Rafiee, E. Organometallics 2009,
28, 6281e6287.
15. The X-ray crystal data of 2b-E and 2b-Z were obtained as their OH forms after
removal of TBS with TBAF, and the data were deposited as CCDC 777031 and
CCDC 777032, respectively. Crystal data of cyclobuta[a]indene 2b-E in its OH
form: solvent of crystal growth (hexane); empirical formula C20H18O3, Fw¼306.
34, crystal dimensions 0.14ꢂ0.14ꢂ0.08 mm3, monoclinic, space group P2(1)/n,
be understood actually by syn
a carbopalladation intermediate via a palladium enolate or the epimerization
of -H.
b-H elimination after the epimerization of
ꢀ
ꢀ
ꢀ
a¼16.441(3) A, b¼10.8317(18) A, c¼17.319(3) A,
a
¼90ꢀ,
b
¼94.114(11)ꢀ,
g
¼90ꢀ,
b
3
V¼3076.4(9) A , Z¼8, Dcalcd¼1.323 mg/m3, F000¼1296, Mo K
a
(l
¼0.71073 A),
22. Crystal data of cyclopenta[a]indene 5: solvent of crystal growth (hexane);
empirical formula C27H34O3Si, Fw¼434.63, crystal dimensions 0.57ꢂ0.35ꢂ0.
ꢀ
ꢀ
R1¼0.0702, wR2¼0.1969 (I>2
s(I)). The X-ray data has been deposited in CCDC
3
ꢀ
ꢀ
with number 777031. Crystal data of cyclobuta[a]indene 2b-Z in its OH form:
solvent of crystal growth (hexane); empirical formula C20H18O3, Fw¼306.34,
crystal dimensions 0.34ꢂ0.26ꢂ0.13 mm3, triclinic, space group Pꢁ1, a¼7.7931
30 mm , monoclinic, space group P2(1)/n, a¼12.3305(7) A, b¼8.0062(4) A,
3
ꢀ
ꢀ ꢀ
c¼24.8844(13) A,
a
¼90ꢀ,
b
¼98.541(3)ꢀ,
g
¼90 , V¼2429.4(2) A , Z¼4, Dcalcd¼1.
188 mg/m3, F000¼936, Mo K
a
(l
¼0.71073 A), R1¼0.0471, wR2¼0.1286 (I>2
s(I)).
ꢀ
ꢀ
ꢀ
3
ꢀ
ꢀ
(15) A, b¼10.072(2) A, c¼10.395(2) A,
a
¼97.022(11)ꢀ,
b
¼91.049(10)ꢀ,
g
K
¼107.799
The X-ray data has been deposited in CCDC with number 783972.
(10)ꢀ, V¼769.7(3) A , Z¼2, Dcalcd¼1.322 mg/m3, F000¼324, Mo
a
(
l
¼0.
23. For the synthesis and biological activity of cyclopenta[a]indene-containing
substances including cyanosporasides and sporolides, see: (a) Oh, D.-C.; Wil-
liams, P. G.; Kauffman, C. A.; Jensen, P. R.; Fenical, W. Org. Lett. 2006, 8,
1021e1024; (b) Aburano, D.; Inagaki, F.; Tomonaga, S.; Mukai, C. J. Org. Chem.
2009, 74, 5590e5594; (c) Bonazzi, S.; Binaghi, M.; Fellay, C.; Wach, J.-Y.; Ga-
demann, K. Synthesis 2010, 631e642; (d) Ethirajan, M.; Oh, H.-S.; Cha, J. K. Org.
Lett. 2007, 9, 2693e2696; (e) Lin, Y.; Jones, G. B.; Hwang, G.-S.; Kappen, L.;
Goldberg, I. H. Org. Lett. 2005, 7, 71e74.
ꢀ
71073 A), R1¼0.0837, wR2¼0.2725 (I>2
s(I)). The X-ray data has been deposited
in CCDC with number 777032.
16. For the discussion of CeH (aryl or alkyl) activation with CMD (concerted
metalation/deprotonation) mechanism by Fagnou, see: (a) Gorelsky, S. I.; La-
pointe, D.; Fagnou, K. J. Am. Chem. Soc. 2008, 130, 10848e10849; (b) Lafrance,
M.; Rowley, C. N.; Woo, T. K.; Fagnou, K. J. Am. Chem. Soc. 2006, 128, 8754e8756;
(c) Rene, O.; Lapointe, D.; Fagnou, K. Org. Lett. 2009, 11, 4560e4563; (d)