Synthesis of 3-methyleneindan-1-ol scaffold from modified Baylis-Hillman adduct: Tandem Pd-catalyzed 5-exo-trig cyclization and iodide ion-assisted formal δ-carbon elimination/decarboxylation

Article abstract of DOI:10.1016/j.tetlet.2011.08.082

An efficient synthetic method of 3-methyleneindan-1-ol scaffold was developed from Baylis-Hillman adducts. The reaction involved palladium-catalyzed 5-exo-trig cyclization and iodide ion-assisted formal δ-carbon elimination/decarboxylation process.

Full text of DOI:10.1016/j.tetlet.2011.08.082

Tetrahedron Letters 52 (2011) 5605–5609
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Synthesis of 3-methyleneindan-1-ol scaffold from modified Baylis–Hillman
adduct: tandem Pd-catalyzed 5-exo-trig cyclization and iodide ion-assisted
formal d-carbon elimination/decarboxylation
⇑
Ko Hoon Kim, Hyun Seung Lee, Se Hee Kim, Jae Nyoung Kim
Department of Chemistry and Institute of Basic Science, Chonnam National University, Gwangju 500-757, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient synthetic method of 3-methyleneindan-1-ol scaffold was developed from Baylis–Hillman
adducts. The reaction involved palladium-catalyzed 5-exo-trig cyclization and iodide ion-assisted formal
d-carbon elimination/decarboxylation process.
Received 12 August 2011
Accepted 12 August 2011
Available online 26 August 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Baylis–Hillman adducts
Palladium
3-Methyleneindan-1-ol
Iodide ion
Palladium-catalyzed domino reactions coupled with suitably de-
signed substrates allow for the rapid establishment of complex mol-
ecules.1 Chemical transformations of Baylis–Hillman adducts have
received much attention during the last two decades.2–4 Various
cyclic and acyclic compounds have been synthesized by a variety
of chemical transformations,2–4 including a palladium-catalyzed
reaction of suitably modified Baylis–Hillman adducts.2i,3,4
Recently, we reported a Pd-catalyzed domino reaction of acrylate
derivative 1a, prepared from Baylis–Hillman adduct via an indium-
mediated Barbier type reaction, to form an indeno[2,1-a]indane 2a
(Scheme 1).4 This compound was formed by selective 5-exo-trig-car-
bopalladation and aryl C–H activation cascade. In the reaction, a
trace amount of methyleneindane 3a (3%) was formed together via
a formal d-carbon elimination and concomitant decarboxylation.4,5,7
Synthesis of 3-alkylideneindan-1-ol derivatives has received
much attention due to their usefulness as synthetic intermediates.6
We assumed that methyleneindane 3a could be formed as a major
product by suppressing the aryl C–H activation process using a weak
base such as Et3N instead of Cs2CO3.5,7 At the same time, the yield of
3a could be increased by promoting the formal d-carbon elimination
TBSO
H
Cs2CO3
(Ref. 4)
3a (3%)
2a (0%)
+
+
aryl C-H
activation
TBSO
COOMe
2a (89%)
Pd0
TBSO
5-exo
Br
Ph
COOMe
PdBr
I
Et3N/NaI
(this work)
formal δ-carbon
elimination/
decarboxylation
TBSO
COOMe
1a
Ph
3a (88%)
Scheme 1.
⇑
Corresponding author. Tel.: +82 62 530 3381; fax: +82 62 530 3389.
E-mail address: kimjn@chonnam.ac.kr (J.N. Kim).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.08.082

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K. H. Kim et al. / Tetrahedron Letters 52 (2011) 5605–5609
Table 1
Optimization of reaction conditions for the synthesis of 3a from 1a
Entry
Conditionsa
2ab (%)
3ab (%)
1c
2
Cs2CO3 (2.0 equiv), DMF, 110 °C, 1 h
Et3N (2.0 equiv), DMF, 120 °C, 2 h
89
28
45
64
0
3
65
50
12
88
59
0
3
i-Pr2NEt (2.0 equiv), TBAI (1.0 equiv), DMF, 120 °C, 2 h
Et3N (2.0 equiv), TBAI (1.0 equiv), DMF, 120 °C, 12 h
Et3N (2.0 equiv), NaI (1.0 equiv), DMF, 120 °C, 6 h
Et3N (2.0 equiv), NaCl (1.0 equiv), DMF, 120 °C, 2 h
no Et3N, NaI (10 equiv), DMF, 120 °C, 4 h
4d
5
6
7
37
0
a
b
c
Pd(OAc)2 (5 mol %) and PPh3 (10 mol %) are common.
Isolated yield.
Ref. 4: Pd(OAc)2 (10 mol %) and PPh3 (20 mol %) were used.
Without PPh3.
d
aq HBr
OH
or PBr3
COOMe
Br
TBSO
R
(i) In/2-bromoarylaldehyde
(ii) TBSCl/ImH/DMF
R
COOMe
R
Br
COOMe
1a-j (syn)
Scheme 2. R = Ph, 4-MePh, 4-ClPh, n-pentyl, Me, H, Ph2C@CH–, PhCH@C(Me)– (See Tables 2–4 for R and 2-bromoarylaldehyde of 1a–j).
Table 2
Synthesis of methyleneindanes 3a–d
Entry Substrate
Productsa (%)
TBSO
H
TBSO
TBSO
Ph
Br
Ph
COOMe
1
3a
3
65
88
2a
COOMe
A:b
B:c
C:d
89
28
0
1a
TBSO
H
TBSO
TBSO
Br
COOMe
Me
2
3b
2b
Me
COOMe
1b
Me
A:b
5
62
84
88
30
0
B:c
C:d
Me
Br
TBSO
H
TBSO
Me
TBSO
Ph
Ph
Me
COOMe
3
3c
2c
COOMe
1c
A:b
6
60
81
86
35
0
B:c
C:d
TBSO
H
TBSO
TBSO
Br
COOMe
Cl
4
3d
2d
Cl
COOMe
1d
Cl
A:b
4
60
86
87
35
0
B:c
C:d
a
b
c
Isolated yields.
Results in Ref. 4 for comparision in the presence of Cs2CO3.
Conditions: Pd(OAc)2 (5 mol %), PPh3 (10 mol %), Et3N (2.0 equiv), DMF, 120 °C, 2 h.
Conditions: Pd(OAc)2 (5 mol %), PPh3 (10 mol %), Et3N (2.0 equiv), NaI (1.0 equiv), DMF, 120 °C, 6 h.
d

K. H. Kim et al. / Tetrahedron Letters 52 (2011) 5605–5609
5607
and concomitant decarboxylation process.4,5,7 The presence of a
highly nucleophilic species such as an iodide ion in the reaction mix-
ture would be helpful for the formation of a palladacycle intermedi-
ate (III, vide infra) and eventually could increase the yield of 3a.8,9
Actually, the yield of 3a increased to 88% when we carried out the
reaction in the presence of Et3N/NaI, as shown in Scheme 1. Under
the reaction conditions, indenoindane 2a was not formed in any
trace amount.
At the outset of our experiments, we carried out the reaction of 1a
under various conditions, as summarized in Table 1. As expected, the
use of Et3N changed the ratio of 2a/3a dramatically (entry 2) as com-
pared to the previous result employing Cs2CO3 (entry 1).4 N,N-Diiso-
propylethylamine produced almost equal amounts of 2a and 3a
(entry 3). The use of tetrabutylammonium iodide was not effective
(entry 4). The best result was observed in the presence of Et3N and
NaI (entry 5). Sodium chloride was not effective (entry 6), and no
reaction was observed without Et3N (entry 7).
Encouraged by the results, various starting materials 1a–j (syn)
were prepared from the corresponding bromides of Baylis–Hillman
adducts via an indium-mediated Barbier type reaction and a fol-
lowing protection of the alcohol moiety with tert-butyldimethylsi-
lyl chloride according to the previous reports,4,7,10 as shown in
Scheme 2.
The syntheses of methyleneindanes 3b–d were carried out via a
Pd-catalyzed reaction with aryl-substituted substrates 1b–d, as
summarized in Table 2.10 We conducted the reactions under the
influence of Et3N with and without NaI, in order to compare the ef-
fect of an iodide ion. As observed in all the cases, a combined use
of Et3N/NaI was superior to the system employing Et3N alone. 2-
Aryl-3-methyleneindan-1-ol derivatives 3b–d were isolated in high
yields (81–86%) as the sole products under the optimized
conditions.
Table 3
Synthesis of methyleneindanes 3e–h
Entry
Substrate
Productsa (%)
TBSO
TBSO
C5H11
Br
C5H11
1
3e
68
84
COOMe
B:b,c
C:d
1e
TBSO
TBSO
C5H11
Br
C5H11
2
3
4
3f
COOMe
B:b,c
62
82
1f
C:d
TBSO
TBSO
Me
Br
Me
3g
COOMe
B:b
C:d
not tried
86
1g
TBSO
TBSO
Br
3h
COOMe
1h
B:b
C:d
not tried
81
As a next experiment, we carried out the synthesis of 2-alkyl-3-
methyleneindanes 3e–h, and the results are summarized in Table
3. For the alkyl-substituted substrates 1e–g and un-substituted 1h,
the conditions of Et3N/NaI also showed better results than the con-
ditions of Et3N alone. The yields of 3e–h were also excellent (81–
86%) under the optimized conditions.
a
Isolated yields.
b
Conditions: Pd(OAc)2 (5 mol %), PPh3 (10 mol %), Et3N (2.0 equiv), DMF, 120 °C,
6 h.
c
Some intractable side products were formed including dihydronaphthalene 4.
Conditions: Pd(OAc)2 (5 mol %), PPh3 (10 mol %), Et3N (2.0 equiv), NaI
d
(1.0 equiv), DMF, 120 °C, 6 h.
Table 4
Synthesis of methyleneindanes 3i and 3j
Entry
Substrate
Productsa (%)
TBSO
H
TBSO
TBSO
Ph
Ph
Ph
Ph
Ph
Ph
Br
COOMe
3i
1
4
COOMe
1i
A:b
B:c
C:d
14
71
86
77
18
0
TBSO
H
TBSO
TBSO
Ph
Me
Ph
Br
Ph
COOMe
Me
3j
2
5
Me COOMe
1j
A:b
B:c
C:d
12
57
82
85
22
0
a
b
c
Isolated yields.
Results in Ref. 7 for comparison in the presence of Cs2CO3.
Results in Ref. 4 for comparison in the presence of Et3N.
d
Conditions: Pd(OAc)2 (5 mol %), PPh3 (10 mol %), Et3N (2.0 equiv), NaI (1.0 equiv), DMF, 120 °C, 6 h.

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K. H. Kim et al. / Tetrahedron Letters 52 (2011) 5605–5609
TBSO
Ph
Pd
TBSO
Ph
TBSO
Ph
Pd
TBSO
Ph
- Pd0
Pd0
NaI
- NaBr, - MeI
1a
3a
PdBr
COOMe
- CO2
COOMe
PdBr
I
O
O
O
O
Me
I
Br
II
III
TBSO
Ph
α
β γ
δ
Br Pd
O
O
Me
I
Scheme 3.
2. For the general reviews on Baylis–Hillman reaction, see: (a) Basavaiah, D.; Rao,
A. J.; Satyanarayana, T. Chem. Rev. 2003, 103, 811–891; (b) Basavaiah, D.; Reddy,
B. S.; Badsara, S. S. Chem. Rev. 2010, 110, 5447–5674; (c) Singh, V.; Batra, S.
Tetrahedron 2008, 64, 4511–4574; (d) Declerck, V.; Martinez, J.; Lamaty, F.
Chem. Rev. 2009, 109, 1–48; (e) Ciganek, E. In Organic Reactions; Paquette, L. A.,
Ed.; John Wiley & Sons: New York, 1997; pp 201–350. Vol. 51; (f) Radha
Krishna, P.; Sachwani, R.; Reddy, P. S. Synlett 2008, 2897–2912; (g) Kim, J. N.;
Lee, K. Y. Curr. Org. Chem. 2002, 6, 627–645; (h) Lee, K. Y.; Gowrisankar, S.; Kim,
J. N. Bull. Korean Chem. Soc. 2005, 26, 1481–1490; (i) Gowrisankar, S.; Lee, H. S.;
Kim, S. H.; Lee, K. Y.; Kim, J. N. Tetrahedron 2009, 65, 8769–8780.
3. For our selected examples on palladium-catalyzed chemical transformations of
Baylis–Hillman adducts, see: (a) Kim, S. H.; Lee, S.; Lee, H. S.; Kim, J. N.
Tetrahedron Lett. 2010, 51, 6305–6309; (b) Kim, K. H.; Kim, S. H.; Park, B. R.;
Kim, J. N. Tetrahedron Lett. 2010, 51, 3368–3371; (c) Kim, K. H.; Kim, E. S.; Kim, J.
N. Tetrahedron Lett. 2009, 50, 5322–5325; (d) Kim, J. M.; Kim, S. H.; Lee, H. S.;
Kim, J. N. Tetrahedron Lett. 2009, 50, 1734–1737; (e) Kim, J. M.; Kim, K. H.; Kim,
T. H.; Kim, J. N. Tetrahedron Lett. 2008, 49, 3248–3251; (f) Gowrisankar, S.; Lee,
H. S.; Lee, K. Y.; Lee, J.-E.; Kim, J. N. Tetrahedron Lett. 2007, 48, 8619–8622; For
the selected examples of other research groups, see: (g) Biswas, S.; Singh, V.;
Batra, S. Tetrahedron 2010, 66, 7781–7786; (h) Amarante, G. W.; Coelho, F.
Tetrahedron 2010, 66, 6749–6753; (i) Cao, H.; Vieira, T. O.; Alper, H. Org. Lett.
2011, 13, 11–13; (j) Alcaide, B.; Almendros, P.; del Campo, T. M.; Quiros, M. T.
Chem. Eur. J. 2009, 15, 3344–3346.
As a last trial, we examined the selective synthesis of 2-alkenyl-
3-methyleneindane derivatives 3i and 3j from 1i and 1j, as summa
rized in Table 4. Recently, we reported a novel synthesis of cyclobu
ta[a]indene 4 (77%) and cyclopenta[a]indene 5 (85%) by a Pd-cata-
lyzed cyclization reaction under the influence of Cs2CO3 from 1i
and 1j, respectively.7 We also examined the reactions in the pres-
ence of Et3N; however, the yields of 3i and 3j were moderate (57–
71%).7 The yields of 3i and 3j increased under the present optimized
conditions employing NaI to 86% and 82%, respectively.
The mechanism for the formation of methyleneindane 3a from
1a could be proposed, as shown in Scheme 3. Oxidative addition of
Pd0 to the C–Br bond of 1a and the following 5-exo-trig-carbopalla-
dation generated an alkylpalladium intermediate I. The intermedi-
ate I could form an oxonium ion intermediate II via the interaction
with nearby ester moiety.8 A highly nucleophilic iodide ion may
facilitate the formations of both II and III. Five-membered pallada-
cycle intermediate III furnished 3a by disruption with the elimina-
tion of CO2 and regeneration of Pd0. The formation of III could
occur via a concerted mechanism from an alkylpalladium interme-
diate I involving a bond cleavage between an oxygen atom (d-posi-
tion) and a methyl group, as also shown in Scheme 3.9 However,
this point is not clear at this stage whether the conversion of I to
III is concerted or stepwise.
We used TBS derivatives 1a–j as starting materials in every en-
try.11 The TBS group could be easily removed by treatment with
TBAF.4 As an example, compound 3g was converted to 2-methyl-
3-methyleneindan-1-ol (6) almost quantitatively (97%, TBAF, THF,
rt, 1 h).
In summary, an efficient synthetic method of 3-methylenein-
dan-1-ol scaffold was developed from Baylis–Hillman adducts.
The reaction involved a palladium-catalyzed 5-exo-trig cyclization
and an iodide ion-assisted formal d-carbon elimination/decarbox-
ylation process. The latter process was mostly effective under the
influence of Et3N and NaI.
4. Kim, K. H.; Lee, H. S.; Kim, S. H.; Kim, S. H.; Kim, J. N. Chem. Eur. J. 2010, 16,
2375–2380.
5. For the concomitant d -carbon elimination/decarboxylation, see: (a) Kim, H. S.;
Lee, H. S.; Kim, S. H.; Kim, J. N. Tetrahedron Lett. 2009, 50, 3154–3157; (b) Kim,
H. S.; Gowrisankar, S.; Kim, E. S.; Kim, J. N. Tetrahedron Lett. 2008, 49, 6569–
6572; (c) Kim, S. H.; Lee, H. S.; Kim, K. H.; Kim, J. N. Tetrahedron Lett. 2010, 51,
4267–4271; (d) Kim, H. S.; Gowrisankar, S.; Kim, S. H.; Kim, J. N. Tetrahedron
Lett. 2008, 49, 3858–3861.
6. For the synthesis and synthetic applications of 3-methyleneindan-1-ol
derivatives, see: (a) Yu, X.; Lu, X. Org. Lett. 2009, 11, 4366–4369; (b) Kesavan,
S.; Panek, J. S.; Porco, J. A., Jr. Org. Lett. 2007, 9, 5203–5206; (c) Cvengros, J.;
Schutte, J.; Schlorer, N.; Neudorfl, J.; Schmalz, H.-G. Angew. Chem., Int. Ed. 2009,
48, 6148–6151; (d) Gai, X.; Grigg, R.; Collard, S.; Muir, J. E. Chem. Commun.
2000, 1765–1766; (e) Coogan, M. P.; Pottenger, M. J. J. Organomet. Chem. 2005,
690, 1409–1411; (f) Boger, D. L.; Turnbull, P. J. Org. Chem. 1998, 63, 8004–8011;
(g) Zhao, J.; Yang, X.; Jia, X.; Luo, S.; Zhai, H. Tetrahedron 2003, 59, 9379–9382;
(h) Kundig, E. P.; Ratni, H.; Crousse, B.; Bernardinelli, G. J. Org. Chem. 2001, 66,
1852–1860; (i) Cassidy, J. H.; Farthing, C. N.; Marsden, S. P.; Pedersen, A.; Slater,
M.; Stemp, G. Org. Biomol. Chem. 2006, 4, 4118–4126; (j) Nishimura, T.;
Yasuhara, Y.; Hayashi, T. J. Am. Chem. Soc. 2007, 129, 7506–7507; (k) Brase, S.;
Rumper, J.; Voigt, K.; Albecq, S.; Thurau, G.; Villard, R.; Waegell, B.; de Meijere,
A. Eur. J. Org. Chem. 1998, 671–678.
7. Kim, K. H.; Kim, S. H.; Park, S.; Kim, J. N. Tetrahedron 2011, 67, 3328–3336.
8. For the formation and reactivity of similar palladacycle intermediate, see: (a)
Fernandez-Rivas, C.; Cardenas, D. J.; Martin-Matute, B.; Monge, A.; Gutierrez-
Puebla, E.; Echavarren, A. M. Organometallics 2001, 20, 2998–3006; (b) Larock,
R. C.; Han, X.; Doty, M. J. Tetrahedron Lett. 1998, 39, 5713–5716; (c) Lee, S. H.;
Lee, K. H.; Lee, J. S.; Jung, J. D.; Shim, J. S. J. Mol. Catal. A 1997, 115, 241–246; (d)
Maehara, A.; Tsurugi, H.; Satoh, T.; Miura, M. Org. Lett. 2008, 10, 1159–1162; (e)
Mei, T.-S.; Giri, R.; Maugel, N.; Yu, J.-Q. Angew. Chem., Int. Ed. 2008, 47, 5215–
5219.
Acknowledgments
This work was supported by the National Research Foundation
of Korea Grant funded by the Korean Government (2011-0002570).
Spectroscopic data were obtained from the Korea Basic Science
Institute, Gwangju branch.
9. For the example of iodide ion-assisted dealkoxycarbonylation, see: Lee, H. S.;
Kim, S. H.; Kim, Y. M.; Kim, J. N. Tetrahedron Lett. 2010, 51, 5071–5075.
10. Typical procedure for the synthesis of compound 1e: To a stirred solution of
methyl (2Z)-2-(bromomethyl)oct-2-enoate12 (125 mg, 0.5 mmol) and 2-
bromobenzaldehyde (102 mg, 0.55 mmol) in aqueous THF (1:1, 1.5 mL) was
added indium powder (63 mg, 0.55 mmol), and the reaction mixture was
stirred at room temperature for 1 h. After the usual aqueous workup and
column chromatographic purification process (hexanes/EtOAc, 10:1) the
corresponding homoallyl alcohol was obtained, 134 mg (syn, 75%) and 14 mg
References and notes
1. For the selected examples of palladium-catalyzed domino reactions, see: (a) de
Meijere, A.; Brase, S. J. Organomet. Chem. 1999, 576, 88–110; (b) de Meijere, A.;
Meyer, F. E. Angew. Chem., Int. Ed. 1994, 33, 2379–2411; (c) Zeni, G.; Larock, R. C.
Chem. Rev. 2006, 106, 4644–4680; (d) Hu, Y.; Yu, C.; Ren, D.; Hu, Q.; Zhang, L.;
Cheng, D. Angew. Chem., Int. Ed. 2009, 48, 5448–5451; (e) Trost, B. M.; O’Boyle,
B. M.; Hund, D. Chem. Eur. J. 2010, 16, 9772–9776; (f) Satyanarayana, G.;
Maichle-Mossmer, C.; Maier, M. E. Chem. Commun. 2009, 1571–1573; (g) Kim,
E. S.; Kim, K. H.; Park, S.; Kim, J. N. Tetrahedron Lett. 2010, 51, 4648–4652.
(anti, 8%) as colorless oils.
A solution of syn-homoallyl alcohol (107 mg,
0.3 mmol), TBSCl (90 mg, 0.6 mmol), and imidazole (61 mg, 0.9 mmol) in DMF

K. H. Kim et al. / Tetrahedron Letters 52 (2011) 5605–5609
5609
(1.0 mL) was stirred at room temperature for 12 h under nitrogen atmosphere.
After the usual aqueous workup and column chromatographic purification
process (hexanes/Et2O, 50:1) compound 1e was obtained as colorless oil,
127 mg (90%). Other starting materials 1a–j were prepared similarly,4,7 and the
selected spectroscopic data of unknown compounds 1e–h are as follows.
compounds 3e–h and 6 are as follows.
Compound 3e: 84%; colorless oil; IR (film) 2955, 2929, 2858, 1465, 1254,
1074 cmÀ1 1H NMR (CDCl3, 300 MHz) d 0.01 (s, 3H), 0.03 (s, 3H), 0.70–0.85 (m,
;
12H), 1.09–1.36 (m, 6H), 1.45–1.55 (m, 2H), 2.61–2.68 (m, 1H), 4.81 (d,
J = 3.6 Hz, 1H), 4.85 (d, J = 2.4 Hz, 1H), 5.40 (d, J = 2.4 Hz, 1H), 7.10–7.16 (m,
2H), 7.17–7.23 (m, 1H), 7.31–7.36 (m, 1H); 13C NMR (CDCl3, 75 MHz) d À4.03,
À3.86, 14.10, 18.14, 22.59, 25.92, 26.06, 31.73, 32.30, 53.77, 79.08, 103.58,
120.60, 125.22, 128.22, 128.62, 140.08, 146.12, 150.48; ESIMS m/z 331 [M+H]+.
Anal. Calcd for C21H34OSi: C, 76.30; H, 10.37. Found: C, 76.53; H, 10.16.
Compound 3f: 82%; colorless oil; IR (film) 2955, 2929, 2857, 1463, 1254,
Compound 1e: 90%; colorless oil; IR (film) 2953, 2857, 1723, 1463, 1256 cmÀ1
;
1H NMR (CDCl3, 300 MHz) d À0.29 (s, 3H), 0.02 (s, 3H), 0.77–0.97 (m, 12H),
1.06–1.32 (m, 6H), 1.51–1.62 (m, 1H), 1.71–1.85 (m, 1H), 2.97–3.09 (m, 1H),
3.63 (s, 3H), 5.04 (d, J = 6.6 Hz, 1H), 5.52 (d, J = 0.6 Hz, 1H), 6.23 (s, 1H), 7.02–
7.07 (m, 1H), 7.25 (t, J = 7.5 Hz, 1H), 7.42 (dd, J = 7.8 and 1.2 Hz, 1H), 7.51 (d,
J = 7.5 Hz, 1H); 13C NMR (CDCl3, 75 MHz) d À5.04, À4.89, 14.05, 18.03, 22.49,
25.79, 26.72, 28.83, 31.87, 47.63, 51.64, 75.05, 122.43, 126.78, 127.16, 128.49,
130.02, 132.17, 139.35, 142.65, 167.80; ESIMS m/z 491 [M+Na]+, 493
[M+Na+2]+. Anal. Calcd for C23H37BrO3Si: C, 58.83; H, 7.94. Found: C, 58.98;
H, 8.02.
1108 cmÀ1 1H NMR (CDCl3, 300 MHz) d 0.16 (s, 3H), 0.21 (s, 3H), 0.81–1.00 (m,
;
12H), 1.19–1.50 (m, 6H), 1.65–1.72 (m, 2H), 2.83–2.89 (m, 1H), 4.98 (d,
J = 3.6 Hz, 1H), 5.30 (d, J = 1.8 Hz, 1H), 5.92 (d, J = 2.1 Hz, 1H), 7.44–7.57 (m,
3H), 7.76 (d, J = 8.4 Hz, 1H), 7.87 (d, J = 7.2 Hz, 1H), 8.47 (d, J = 8.4 Hz, 1H); 13C
NMR (CDCl3, 75 MHz) d À3.98, À3.90, 14.11, 18.19, 22.61, 25.93, 26.38, 31.64,
32.28, 55.94, 78.89, 107.89, 122.95, 124.46, 125.54, 126.86, 129.03, 129.35,
129.64, 134.19, 134.80, 145.24, 150.81; ESIMS m/z 381 [M+H]+. Anal. Calcd for
Compound 1f: 90%; colorless oil; IR (film) 2954, 2930, 2857, 1723, 1257,
1076 cmÀ1
;
1H NMR (CDCl3, 300 MHz) d À0.31 (s, 3H), 0.06 (s, 3H), 0.81–0.86
(m, 12H), 1.04–1.26 (m, 6H), 1.59–1.71 (m, 1H), 1.79–1.87 (m, 1H), 3.08–3.15
(m, 1H), 3.55 (s, 3H), 5.38 (d, J = 6.9 Hz, 1H), 5.53 (s, 1H), 6.18 (d, J = 0.9 Hz, 1H),
7.47–7.59 (m, 2H), 7.64 (d, J = 8.4 Hz, 1H), 7.74–7.80 (m, 2H), 8.32 (d, J = 7.5 Hz,
1H); 13C NMR (CDCl3, 75 MHz) d À4.97, À4.85, 14.03, 18.06, 22.51, 25.81,
26.81, 29.14, 31.90, 48.08, 51.57, 76.00, 122.14, 126.33, 126.91, 126.98, 127.06,
127.26, 127.82, 127.97, 131.84, 133.96, 139.23, 140.85, 167.70; ESIMS m/z 541
[M+Na]+, 543 [M+Na+2]+. Anal. Calcd for C27H39BrO3Si: C, 62.41; H, 7.57.
Found: C, 62.65; H, 7.42.
C
25H36OSi: C, 78.89; H, 9.53. Found: C, 78.74; H, 9.49.
Compound 3g: 86%; white solid, mp 48–49 °C; IR (KBr) 2958, 2930, 2857, 1464,
1256, 1106 cmÀ1 1H NMR (CDCl3, 300 MHz) d 0.17 (s, 3H), 0.21 (s, 3H), 0.96 (s,
;
9H), 1.32 (d, J = 6.9 Hz, 3H), 2.75–2.85 (m, 1H), 4.77 (d, J = 5.4 Hz, 1H), 4.96 (d,
J = 2.4 Hz, 1H), 5.47 (d, J = 2.7 Hz, 1H), 7.23–7.29 (m, 2H), 7.30–7.35 (m, 1H),
7.45–7.48 (m, 1H); 13C NMR (CDCl3, 75 MHz) d À4.06, À4.03, 16.26, 18.10,
25.90, 49.12, 81.33, 102.51, 120.50, 124.53, 128.05, 128.71, 139.44, 146.07,
151.39; ESIMS m/z 275 [M+H]+. Anal. Calcd for C17H26OSi: C, 74.39; H, 9.55.
Found: C, 74.71; H, 9.34.
Compound 1g: 88%; colorless oil; IR (film) 2953, 2931, 2857, 1723, 1466,
1259 cmÀ1
;
1H NMR (CDCl3, 300 MHz) d 0.00 (s, 3H), 0.26 (s, 3H), 1.14 (s, 9H),
Compound 3h: 81%; colorless oil; IR (film) 2954, 2930, 2857, 1646, 1468, 1358,
1.33 (d, J = 7.2 Hz, 3H), 3.43–3.51 (m, 1H), 3.99 (s, 3H), 5.41 (d, J = 4.8 Hz, 1H),
5.90 (t, J = 1.2 Hz, 1H), 6.55 (s, 1H), 7.36 (ddd, J = 7.5, 7.5 and 1.8 Hz, 1H), 7.53–
7.58 (m, 1H), 7.75 (dd, J = 8.1 and 1.5 Hz, 1H), 7.80 (d, J = 7.2 Hz, 1H); 13C NMR
1255 cmÀ1 1H NMR (CDCl3, 300 MHz) d 0.16 (s, 3H), 0.18 (s, 3H), 0.95 (s, 9H),
;
2.62–2.71 (m, 1H), 3.12 (dddd, J = 16.2, 7.2, 1.8 and 1.8 Hz, 1H), 5.03 (dd, J = 1.8
and 1.8 Hz, 1H), 5.30 (dd, J = 7.2 and 5.4 Hz, 1H), 5.46 (dd, J = 2.7 and 1.8 Hz,
1H), 7.24–7.29 (m, 2H), 7.30–7.39 (m, 1H), 7.46–7.51 (m, 1H); 13C NMR (CDCl3,
75 MHz) d À4.60, À4.38, 18.25, 25.90, 43.29, 73.67, 103.32, 120.41, 124.85,
128.13, 128.67, 139.73, 146.50, 147.61; ESIMS m/z 261 [M+H]+. Anal. Calcd for
(CDCl3, 75 MHz)
d
À5.20, À4.94, 13.76, 18.07, 25.81, 40.20, 51.65, 74.27,
121.84, 126.55, 126.61, 128.48, 129.91, 132.38, 141.90, 142.57, 167.66; ESIMS
m/z 435 [M+Na]+, 437 [M+Na+2]+. Anal. Calcd for C19H29BrO3Si: C, 55.20; H,
7.07. Found: C, 55.51; H, 7.23.
C
16H24OSi: C, 73.79; H, 9.29. Found: C, 73.83; H, 9.01.
Compound 6: 97%; white solid, mp 106–107 °C; IR (KBr) 3345, 2960, 2859,
1642, 1466, 1327, 1046 cmÀ1 1H NMR (CDCl3, 300 MHz) d 1.35 (d, J = 6.9 Hz,
Compound 1h: 85%; colorless oil; IR (film) 2953, 2931, 2857, 1726, 1631,
1468 cmÀ1
;
1H NMR (CDCl3, 300 MHz) d À0.26 (s, 3H), À0.09 (s, 3H), 0.77 (s,
;
9H), 2.49 (ddd, J = 13.2, 8.1 and 0.9 Hz, 1H), 2.63 (ddd, J = 13.2, 4.5 and 1.2 Hz,
1H), 3.65 (s, 3H), 5.18 (dd, J = 8.1 and 4.5 Hz, 1H), 5.42–5.43 (m, 1H), 6.13 (d,
J = 1.5 Hz, 1H), 6.98–7.03 (m, 1H), 7.18–7.25 (m, 1H), 7.39 (dd, J = 8.1 and
1.2 Hz, 1H), 7.47 (dd, J = 7.8 and 1.8 Hz, 1H); 13C NMR (CDCl3, 75 MHz) d À4.88,
À4.71, 18.37, 26.03, 42.09, 52.03, 72.46, 121.74, 127.63, 128.60, 128.81, 132.47,
136.84, 144.18, 167.79 (one carbon is overlapped); ESIMS m/z 421 [M+Na]+,
423 [M+Na+2]+. Anal. Calcd for C18H27BrO3Si: C, 54.13; H, 6.81. Found: C,
54.19; H, 6.64.
3H), 1.96 (br s, 1H), 2.70–2.81 (m, 1H), 4.75 (s, 1H), 5.01 (d, J = 2.1 Hz, 1H), 5.51
(d, J = 2.7 Hz, 1H), 7.28–7.34 (m, 2H), 7.41–7.52 (m, 2H); 13C NMR (CDCl3,
75 MHz) d 16.56, 49.50, 81.05, 103.25, 120.69, 124.56, 128.65, 128.96, 139.63,
145.24, 151.13; ESIMS m/z 161 [M+H]+. Anal. Calcd for C11H12O: C, 82.46; H,
7.55. Found: C, 82.18; H, 7.43.
11. The use of TBS-protected starting materials was crucial for the effective
reaction. When we use the corresponding acetate derivative instead of 1a, both
5-exo-trig and 6-endo-trig carbopalladation compete, as previously observed.4
In addition, the use alcohol derivatives directly without protection with TBS
Typical procedure for the synthesis of compound 3a: A solution of 1a4 (143 mg,
0.3 mmol), Pd(OAc)2 (3 mg, 5 mol%), PPh3 (8 mg, 10 mol%), triethylamine
(61 mg, 0.6 mmol) and NaI (45 mg, 0.3 mmol) in DMF (1.0 mL) was stirred at
120 °C for 6 h under nitrogen atmosphere. After the usual aqueous workup and
column chromatographic purification process (hexanes/Et2O 50:1) compound
3a was obtained as colorless oil, 89 mg (88%).4 Other compounds 3b–j4,7 were
synthesized similarly, and the selected spectroscopic data of unknown
moiety showed the formation of intractable complex mixtures including
c-
hydroxybutenolide.4,7
12. (a) Basavaiah, D.; Reddy, K. R.; Kumaragurubaran, N. Nat. Protoc. 2007, 2, 2665–
2676; (b) Das, B.; Damodar, K.; Bhunia, N.; Shashikanth, B. Tetrahedron Lett.
2009, 50, 2072–2074.