An expedient synthesis of poly-substituted 1-arylisoquinolines from δ-ketonitriles via indium-mediated Barbier reaction protocol

Article abstract of DOI:10.1016/j.tetlet.2009.09.013

We developed an efficient synthetic strategy of poly-substituted 1-arylisoquinolines via an indium-mediated Barbier type allylation from δ-ketonitriles. Initial attack of allylindium species occurred at the nitrile group selectively to form the enamine intermediate, which reacted with the ketone group intramolecularly to furnish the isoquinolines.

Full text of DOI:10.1016/j.tetlet.2009.09.013

Tetrahedron Letters 50 (2009) 6476–6479
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An expedient synthesis of poly-substituted 1-arylisoquinolines
from d-ketonitriles via indium-mediated Barbier reaction protocol
*
Sung Hwan Kim, Hyun Seung Lee, Ko Hoon 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:
We developed an efficient synthetic strategy of poly-substituted 1-arylisoquinolines via an indium-med-
iated Barbier type allylation from d-ketonitriles. Initial attack of allylindium species occurred at the nitrile
group selectively to form the enamine intermediate, which reacted with the ketone group intramolecu-
larly to furnish the isoquinolines.
Received 17 August 2009
Revised 1 September 2009
Accepted 1 September 2009
Available online 6 September 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Isoquinolines
Indium
Barbier reaction
d-Ketonitriles
Allylindium reagents have been used extensively for the intro-
duction of allyl group in a Barbier type manner.1–3 Although allylin-
dium reagents can be added to many reactive functional groups
including aldehyde, ketone, and activated imine with acyl or tosyl
group,1,2 the reaction with nitrile has not been reported muchexcept
recent Yamamoto’s Letter3 and ours.4 According to the results intro-
duction of allylindium can be carried out with only nitrile com-
prepared in moderate yields (51–63%) from 2-fluorobenzophenone
derivatives 1a–c and active methylene compounds 2a–c under the
influence of Cs2CO3 in DMSO (130–140 °C, 5 h).7 Compound 3d
(R1 = R3 = H, Ar = Ph) was prepared from 2-methylbenzophenone.8
The reaction of 3b–f and allyl bromide in the presence of in-
dium powder showed the formation of desired 3-allylisoquinoline
derivatives 4b–f in good to moderate yields (65–76%) in a one-pot
in short time (30–60 min),7 as summarized in Table 1. The reaction
was also effective when we used methallyl bromide (entry 7) or
crotyl bromide (entry 8) instead of allyl bromide. In these cases,
however, excess amounts of indium (2.0 equiv) and the corre-
sponding bromides (4.0 equiv) were required for the reasonable
yields of compounds 4g and 4h.
pounds having both an a-hydrogen atom and an a
-EWG group.3,4
Isoquinoline and related compounds play an important role in
organic chemistry as key structural units in many biologically
interesting substances including illudinine, berberine, coptisine,
noscapine and PK11195,5 and there have been reported numerous
approaches for the synthesis of this framework.6 Recently we re-
ported an efficient synthesis of diallylated d-valerolactam4a and
poly-substituted pyrroles4b via an indium-mediated Barbier type
allylation, as summarized in Scheme 1. During the synthesis of pyr-
roles4b we found that benzoyl group was less reactive than nitrile
to allylindium. Thus, we imagined that d-ketonitrile such as 3a
could be converted to 1-phenylisoquinoline 4a via the chemoselec-
tive allylation at the nitrile and the following cyclization of the en-
amine intermediate, as shown in Scheme 2. As expected the
reaction of 3a and allyl bromide (2.0 equiv) in the presence of in-
dium powder (1.0 equiv) in THF afforded 4a in 74% in short reac-
tion time (reflux, 30 min).7
As a next trial, we examined the reaction of 3g9 and 3h9 which
have ester group instead of benzoyl moiety, as shown in Scheme 3.
As expected, the reaction of 3g and allylindium provided isoquin-
oline derivative 5a7 in moderate yield (51%). Diallyl dihydroiso-
quinolinone 6a (19%) was formed as a minor product via the
double allylation reaction.4a In the case of compound 3h, the yields
of mono-allyl and di-allyl compounds were relatively low. Instead
enamine 8 was isolated in appreciable amounts (45%). This enam-
ine was easily converted into mono-allyl compound 5b7 under the
influence of acid catalyst (AcOH, toluene, reflux, 10 h, 83%). The
nucleophilicity of the amino group in 8 might be low due to the
presence of conjugated ester moiety. Thus the next cyclization of
8 to 5b was not effective under the Barbier reaction conditions.
In order to check the relative reactivity between aromatic and
aliphatic nitriles, we prepared compound 3i9 and carried out the
reaction as shown in Scheme 4. Compound 9a was isolated in
52% and we could not isolate the other compounds in appreciable
Encouragedbytheresults,wepreparedvarious d-ketonitriles3b–f
and examined the reactionwithallyl bromide, methallylbromideand
crotyl bromide as shown in Table 1. Compounds 3a–c, 3e and 3f were
* 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 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.09.013

S. H. Kim et al. / Tetrahedron Letters 50 (2009) 6476–6479
6477
O
allyl bromide
In, THF, reflux
COOEt
Ph
Ph
NH
CN
Ref. 4a
COOMe
COOMe
N
C
H
N
O
O
allyl bromide
In, THF, reflux
O
Ph
Ph
Ph
and/or
Ph
COOMe
NH2
Ref. 4b
Ph
COOMe
Ph
Scheme 1.
Ph
Ph
O
Ph
Ph
F
allyl bromide
In, THF, reflux
- H2O
NCCH2COOMe (2a)
O
N
C
N
O
NH2
Cs2CO3/DMSO
COOMe
COOMe
COOMe
1a
4a
3a
Scheme 2.
Table 1
Synthesis of starting materials 3a–f and 1-arylisoquinolines 4a–h
OMe
Ar
Ar
N
Ph
F
Ph
F
R3
R3
F
NCCH2COOMe (2a)
NCCH2COOEt (2b)
NCCH2SO2Ph (2c)
O
C
O
O
N
R2
O
R1
R1
1a
1b
1c
3a-f
4a-h
F
Entry
1 + 2
3a (%)
Conditions
Isoquinoline 4 (%)
1
2
3
4
5
6
7
8
1a + 2a
1a + 2b
3a (63)
3b (61)
3c (51)
3db
3e (62)
3f (59)
3a
Allyl bromide (2.0 equiv), ln (1.0 equiv) THF, reflux, 30 min
Allyl bromide (2.0 equiv), ln (1.0 equiv) THF, reflux, 30 min
Allyl bromide (2.0 equiv), ln (1.0 equiv) THF, reflux, 50 min
Allyl bromide (2.0 equiv), ln (1.0 equiv) THF, reflux, 30 min
Allyl bromide (2.0 equiv), ln (1.0 equiv) THF, reflux, 60 min
Allyl bromide (2.0 equiv), ln (1.0 equiv) THF, reflux, 60 min
Methallyl bromide (4.0 equiv), ln (2.0 equiv) THF, reflux, 7 h
Crotyl bromide (4.0 equiv), ln (2.0 equiv) THF, reflux, 7 h
4a (R1 = COOMe, R2 = allyl, R3 = H, Ar = Ph) (74)
4b (R1 = COOEt, R2 = allyl, R3 = H, Ar = Ph) (71)
4c (R1 = SO2Ph, R2 = allyl, R3 = H, Ar = Ph) (72)
4d (R1 = H, R2 = allyl, R3 = H, Ar = Ph) (65)
1a + 2c
b
1b + 2a
1c + 2b
—
4e (R1 = COOMe, R2 = allyl, R3 = F, Ar = Ph) (76)
4f (R1 = COOMe, R2 = allyl, R3 = H, Ar = 4-OMePh) (71)
4g (R1 = COOMe, R2 = CH2C(CH3)@CH2, R3 = H, Ar = Ph) (66)
4h (R1 = COOMe, R2 = CH(CH3)CH@CH2, R3 = H, Ar = Ph) (56)
—
3a
a
Conditions: compound 1 (1.0 mmol), compound 2 (2.0 equiv), Cs2CO3 (2.0 equiv), DMSO, 130–140 °C, 5 h.
b
See text.8
O
OH
OH
allyl bromide (4.0 equiv)
H
COOEt
In (2.0 equiv)
N
N
N
+
+
CN
THF, reflux, 30 min
5a (51%)
7 (5%)
6a (19%)
3g
O
N
OH
N
allyl bromide (4.0 equiv)
In (2.0 equiv)
COOMe
CN
COOMe
H
+
NH2
+
THF, reflux, 30 min
COOMe
COOMe
6b (16%)
COOMe
COOMe
8 (45%)
5b (28%)
3h
AcOH (cat), toluene, reflux, 10 h (83%)
Scheme 3.

6478
S. H. Kim et al. / Tetrahedron Letters 50 (2009) 6476–6479
NOE
H
H
NH2
N
H H
allyl bromide (2.0 equiv)
In (1.0 equiv)
CN
CN
H
NOE
N
O
NH
CN
+
THF, reflux, 30 min
NH2
COOMe
COOMe
COOMe
MeO
3i
10a (not formed)
9a (52%)
NH2
allyl bromide (2.0 equiv)
In (1.0 equiv)
CN
CN
CN
N
N
NH2
NH
CN
+
+
THF, reflux, 40 min
NH2
3j
H
H
9b (25%)
10b (18%)
Scheme 4.
allyl bromide (4.0 equiv)
In (2.0 equiv)
CN
COOMe
NH
O
N
NH
+
THF, reflux, 2 h
O
O
COOMe
COOMe
COOMe
O
O
3k
11 (28%)
12 (19%)
Scheme 5.
amounts. The structure of 9a7 was confirmed by NOE experiments.
The results clearly stated that first attack of allylindium occurred at
the aromatic nitrile instead of the nitrile of methyl cyanoacetate
moiety. In the case of compound 3j,9 two compounds 9b and 10b
were obtained although the combined yields were moderate
(43%). Similarly, we isolated compounds 11 and 1210 from the
reaction of compound 3k9 under the similar conditions (Scheme
5), albeit in low yields. From the results we could conclude that
the intrinsic reactivity of nitrile toward allylindium species is suf-
ficient to form the imine or enamine intermediates to cause subse-
quent reaction to form a cyclic compound when a suitable
electrophile (benzoyl, ester and nitrile) is present at the d-position
of the same molecule.
In summary, we developed an efficient synthetic strategy of
poly-substituted 1-arylisoquinolines via an indium-mediated ally-
lation of d-ketonitriles. In addition, we found that various allylated
cyclic compounds can be synthesized via the initial indium-medi-
ated allylation of nitrile and the following cyclization of the imine
or enamine intermediate with a suitable electrophile in the same
molecule such as benzoyl, ester and nitrile.
H. M. S.; Anjaneyulu, S.; Reddy, E. J.; Yadav, J. S. Tetrahedron Lett. 2000, 41,
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Das, A. Tetrahedron Lett. 2004, 45, 6875–6877.
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Fujiwara, N.; Yamamoto, Y. J. Org. Chem. 1999, 64, 4095–4101.
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1698; (b) Kim, S. H.; Kim, S. H.; Lee, K. Y.; Kim, J. N. Tetrahedron Lett. 2009, 50,
5744–5747.
5. For the synthesis and biological activities of isoquinoline-containing
compounds, see: (a) Bentley, K. W.. In The Isoquinoline Alkaloids; Hardwood
Academic: Amsterdam, 1998; Vol. 1; (b) Mach, U. R.; Hackling, A. E.; Perachon,
S.; Ferry, S.; Wermuth, C. G.; Schwartz, J.-C.; Sokoloff, P.; Stark, H. ChemBioChem
2004, 5, 508–518; (c) Muscarella, D. E.; O’Brien, K. A.; Lemley, A. T.; Bloom, S. E.
Toxicol. Sci. 2003, 74, 66–73; (d) Teske, J. A.; Deiters, A. J. Org. Chem 2008, 73,
342–345; Especially, 1-arylisoquinline derivative PK11195 is an important
antagonistic ligand of the mBzR (mitochondrial benzodiazepine receptor),5c
see: (e) Scarf, A. M.; Ittner, L. M.; Kassiou, M. J. Med. Chem. 2009, 52, 581–592;
(f) Yu, W.; Wang, E.; Voll, R. J.; Miller, A. H.; Goodman, M. M. Bioorg. Med. Chem.
2008, 16, 6145–6155.
6. For the synthesis and biological activities of isoquinoline derivatives, see: (a)
Huo, Z.; Yamamoto, Y. Tetrahedron Lett. 2009, 50, 3651–3653; (b) Fischer, D.;
Tomeba, H.; Pahadi, N. K.; Patil, N. T.; Yamamoto, Y. Angew. Chem., Int. Ed. 2007,
46, 4764–4766; (c) Hui, B. W.-Q.; Chiba, S. Org. Lett. 2009, 11, 729–732; (d) Niu,
Y.-N.; Yan, Z.-Y.; Gao, G.-L.; Wang, H.-L.; Shu, X.-Z.; Ji, K.-G.; Liang, Y.-M. J. Org.
Chem. 2009, 74, 2893–2896; (e) Gerfaud, T.; Neuville, L.; Zhu, J. Angew. Chem.,
Int. Ed. 2009, 48, 572–577; (f) Hwang, S.; Lee, Y.; Lee, P. H.; Shin, S. Tetrahedron
Lett. 2009, 50, 2305–2308; (g) Movassaghi, M.; Hill, M. D. Org. Lett. 2008, 10,
3485–3488; (h) Blackburn, T.; Ramtohul, Y. K. Synlett 2008, 1159–1164; (i)
Alonso, R.; Campos, P. J.; Garcia, B.; Rodriguez, M. A. Org. Lett. 2006, 8, 3521–
3523; (j) Xiang, Z.; Luo, T.; Lu, K.; Cui, J.; Shi, X.; Fathi, R.; Chen, J.; Yang, Z. Org.
Lett. 2004, 6, 3155–3158; (k) Ichikawa, J.; Wada, Y.; Miyazaki, H.; Mori, T.;
Kuroki, H. Org. Lett. 2003, 5, 1455–1458; (l) Ishii, H.; Imai, Y.; Hirano, T.; Maki,
S.; Niwa, H.; Ohashi, M. Tetrahedron Lett. 2000, 41, 6467–6471; (m) Roesch, K.
R.; Larock, R. C. Org. Lett. 1999, 1, 553–556; (n) Roesch, K. R.; Larock, R. C. J. Org.
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Acknowledgments
This work was supported by the Korea Research Foundation
Grant funded by the Korean Government (MOEHRD, KRF-2008-
313-C00487). Spectroscopic data were obtained from the Korea Ba-
sic Science Institute, Gwangju branch.
References and notes
7. Typical procedure for the synthesis of compounds 3a and 4a: A stirred mixture of
2-fluorobenzophenone (1a, 200 mg, 1.0 mmol), methyl cyanoacetate (2a,
198 mg, 2.0 mmol), Cs2CO3 (751 mg, 2.0 mmol) in DMSO (2 mL) was heated
to 130–140 °C for 5 h. After the usual aqueous workup and column
chromatographic purification process (hexanes/EtOAc/CH2Cl2, 16:2:1)
compound 3a was isolated as a pale yellow solid, 176 mg (63%). A stirred
mixture of compound 3a (140 mg, 0.50 mmol), allyl bromide (121 mg,
1.0 mmol) and indium powder (57 mg, 0.5 mmol) in THF (1 mL) was heated
to reflux for 30 min. After the usual aqueous workup and column
chromatographic purification process (hexanes/CH2Cl2/EtOAc, 16:1:1)
1. For the general review on indium-mediated reactions, see: (a) Auge, J.; Lubin-
Germain, N.; Uziel, J. Synthesis 2007, 1739–1764; (b) Li, C.-J.; Chan, T.-H.
Tetrahedron 1999, 55, 11149–11176; (c) Pae, A. N.; Cho, Y. S. Curr. Org. Chem.
2002, 6, 715–737.
2. For the indium-mediated Barbier type allylation of imine, acylimine,
sulfonimine and related compounds, see: (a) Vilaivan, T.; Winotapan, C.;
Banphavichit, V.; Shinada, T.; Ohfune, Y. J. Org. Chem. 2005, 70, 3464–3471; (b)
Schneider, U.; Chen, I.-H.; Kobayashi, S. Org. Lett. 2008, 10, 737–740; (c) Kumar,

S. H. Kim et al. / Tetrahedron Letters 50 (2009) 6476–6479
6479
compound 4a was isolated as pale yellow oil, 113 mg (74%). Other compounds
were synthesized similarly and the selected spectroscopic data of 3a, 4a, 4e, 4g,
5a, 5b, 9a and 11 are as follows.Compound 3a: 63%; pale yellow solid, mp 91–
1H), 5.37–5.44 (m, 1H), 5.94–6.07 (m, 1H), 7.47–7.53 (m, 1H), 7.70 (ddd, J = 8.7,
7.2 and 1.5 Hz, 1H), 7.87–7.90 (m, 1H), 8.43 (ddd, J = 8.1, 1.5 and 0.6 Hz, 1H),
11.46 (br s, 1H); 13C NMR (CDCl3, 75 MHz) d 36.79, 52.12, 109.24, 119.11,
124.21, 124.59, 126.66, 127.33, 132.94, 133.17, 135.52, 142.20, 163.91, 167.23;
ESIMS m/z 244 (M++1). Anal. Calcd for C14H13NO3: C, 69.12; H, 5.39; N, 5.76.
Found: C, 69.18; H, 5.63; N, 5.45.Compound 9a: 52%; pale yellow oil; IR (film)
92 °C; IR (KBr) 2252, 1752, 1658, 1448, 1272 cmÀ1 1H NMR (CDCl3, 300 MHz) d
;
3.72 (s, 3H), 5.71 (s, 1H), 7.44–7.52 (m, 4H), 7.59–7.66 (m, 2H), 7.77–7.81 (m,
3H); 13C NMR (CDCl3, 75 MHz) d 39.92, 53.78, 115.64, 128.42 (2C), 129.96,
129.99, 130.35, 131.27, 131.96, 133.33, 136.66, 137.18, 165.26, 197.31; ESIMS
m/z 280 (M++1).Compound 4a: 74%; pale yellow oil; IR (film) 2950, 1726, 1553,
3436, 3317, 1669, 1612, 1526, 1249 cmÀ1 1H NMR (CDCl3, 300 MHz) d 2.67–
;
2.85 (m, 2H), 3.60 (s, 3H), 5.09–5.22 (m, 3H, two vinyls and one NH), 5.66–5.80
(m, 1H), 7.27–7.30 (m, 1H), 7.35 (td, J = 7.5 and 1.5 Hz, 1H), 7.53 (td, J = 7.5 and
1.5 Hz, 1H), 7.64–7.67 (m, 1H), 8.85 (br s, 1H, one NH); 13C NMR (CDCl3,
75 MHz) d 37.99, 50.88, 94.62, 115.97, 118.42, 120.00, 127.04, 132.19 (2C),
132.46, 133.15, 141.80, 159.83, 168.94; ESIMS m/z 243 (M++1). Anal. Calcd for
C14H14N2O2: C, 69.41; H, 5.82; N, 11.56. Found: C, 69.69; H, 5.98; N,
11.28.Compound 11: 28%; pale yellow oil; IR (film) 3206, 1752, 1674, 1435,
1254, 1214 cmÀ1 1H NM (CDCl3, 300 MHz) d 3.85 (dt, J = 6.6 and 1.5 Hz, 2H),
;
4.05 (s, 3H), 5.08–5.21 (m, 2H), 6.08–6.22 (m, 1H), 7.46–7.55 (m, 4H), 7.65–7.72
(m, 3H), 7.89–7.92 (m, 1H), 8.05–8.08 (m, 1H); 13C NMR (CDCl3, 75 MHz) d
41.19, 52.39, 116.29, 122.33, 124.08, 124.71, 126.81, 127.77, 128.32, 128.84,
129.95, 130.84, 134.32, 135.70, 139.07, 150.02, 161.93, 168.94; ESIMS m/z 304
(M++1). Anal. Calcd for C20H17NO2: C, 79.19; H, 5.65; N, 4.62. Found: C, 79.44;
H, 5.89; N, 4.37.Compound 4e: 76%; white solid, mp 87–88 °C; IR (KBr) 2951,
1247 cmÀ1 1H NMR (CDCl3, 300 MHz) d 2.57–2.82 (m, 4H), 3.71 (s, 3H), 4.59 (s,
;
1726, 1556, 1250, 1214 cmÀ1
;
1H NMR (CDCl3, 300 MHz) d 3.84 (dt, J = 6.6 and
1H), 5.01–5.19 (m, 4H), 5.35–5.49 (m, 1H), 5.70–5.84 (m, 1H), 6.81 (br s, 1H),
7.26–7.30 (m, 1H), 7.33–7.45 (m, 2H), 7.52–7.55 (m, 1H); 13C NMR (CDCl3,
75 MHz) d 42.16, 47.50, 53.44, 61.82, 73.55, 120.31, 120.40, 124.98, 127.17,
128.17, 129.05, 131.31, 131.85, 132.22, 135.68, 168.34, 171.31; ESIMS m/z 286
(M++1). Anal. Calcd for C17H19NO3: C, 71.56; H, 6.71; N, 4.91. Found: C, 71.77;
H, 6.88; N, 4.67.
1.5 Hz, 2H), 4.06 (s, 3H), 5.08–5.20 (m, 2H), 6.07–6.20 (m, 1H), 7.45–7.57 (m,
4H), 7.63–7.72 (m, 3H), 7.95 (dd, J = 9.3 and 5.1 Hz, 1H); 13C NMR (CDCl3,
75 MHz) d 41.07, 52.50, 111.16 (JC–F = 22.1 Hz), 116.40, 121.29 (JC–F = 25.2 Hz),
122.12, 125.65 (JC–F = 8.0 Hz), 127.01 (JC–F = 8.3 Hz), 128.52, 129.10, 129.75,
131.43, 135.59, 138.64, 149.80 (JC–F = 2.6 Hz), 160.54 (JC–F = 247.3 Hz), 161.31
(JC–F = 5.5 Hz), 168.65; ESIMS m/z 322 (M++1). Anal. Calcd for C20H16FNO2: C,
74.75; H, 5.02; N, 4.36. Found: C, 74.91; H, 4.96; N, 4.22.Compound 4g: 66%;
8. Starting material 3d (R1 = R3 = H, Ar = Ph) was prepared from 2-
methylbenzophenone by successive bromination (NBS, AIBN, CCl4, reflux, 2 h,
80%) and displacement reaction with cyanide (KCN, DMF, rt, 1 h, 61%).
9. Compound 3g was prepared from o-toluic acid via three steps: (i) H2SO4 (cat)/
EtOH (reflux, 7 h, 96%), (ii) NBS/AIBN (cat)/CCl4 (reflux, 4 h, 81%), and (iii) KCN/
H2O/EtOH (reflux, 4 h, 74%). Compound 3h was prepared from homophthalic
acid via three steps: (i) H2SO4 (cat)/MeOH (reflux, 7 h, 94%), (ii) NBS/AIBN (cat)/
CCl4 (reflux, 4 h, 79%), and (iii) KCN/DMF (rt, 1 h, 69%). Compounds 3i and 3k
were prepared from 2-fluorobenzonitrile via a SNAr reaction with methyl
cyanoacetate and dimethyl malonate under the influence of Cs2CO3/DMSO
(100–110 °C, 5 h) in 61% and 63%, respectively. Compound 3j was purchased
from commercial source.
pale yellow oil; IR (film) 2949, 1727, 1552, 1252, 1214 cmÀ1 1H NMR (CDCl3,
;
300 MHz) d 1.79 (s, 3H), 3.84 (s, 2H), 4.03 (s, 3H), 4.70–4.71 (m, 1H), 4.85–4.86
(m, 1H), 7.45–7.55 (m, 4H), 7.65–7.72 (m, 3H), 7.89–7.92 (m, 1H), 8.06–8.10
(m, 1H); 13C NMR (CDCl3, 75 MHz) d 22.62, 44.69, 52.37, 112.37, 122.86,
124.14, 124.70, 126.81, 127.72, 128.32, 128.81, 129.97, 130.77, 134.30, 139.10,
143.36, 149.86, 161.59, 169.00; ESIMS m/z 318 (M++1). Anal. Calcd for
C21H19NO2: C, 79.47; H, 6.03; N, 4.41. Found: C, 79.64; H, 6.24; N,
4.35.Compound 5a: 51%; white solid, mp 132–133 °C; IR (KBr) 3170, 1681,
1647 cmÀ1 1H NMR (CDCl3, 300 MHz) d 3.43 (dd, J = 6.9 and 0.9 Hz, 2H), 5.20–
;
5.38 (m, 2H), 5.95–6.08 (m, 1H), 6.33 (s, 1H), 7.39–7.48 (m, 2H), 7.58–7.63 (m,
1H), 8.39 (dt, J = 8.1 and 0.6 Hz, 1H), 11.68 (br s, 1H); 13C NMR (CDCl3, 75 MHz)
d 37.45, 104.15, 118.71, 124.42, 125.68, 125.81, 127.16, 132.45, 133.14, 138.52,
139.85, 164.76; ESIMS m/z 186 (M++1). Anal. Calcd for C12H11NO: C, 77.81; H,
5.99; N, 7.56. Found: C, 78.03; H, 6.12; N, 7.52.Compound 5b: 28%; pale yellow
10. The compound 11 must be formed via a double Barbier type allylation as in our
previous Letter,4a however, the reactivity of 3k was sluggish than other
examples in this Letter. Interestingly, we observed the formation of allyl ester
12 in low yield (19%) together. For the similar In-catalyzed transesterification,
see: Ranu, B. C.; Dutta, P.; Sarkar, A. J. Org. Chem. 1998, 63, 6027–6028.
solid, mp 182–183 °C; IR (KBr) 3179, 1719, 1675, 1620, 1206 cmÀ1 1H NMR
;
(CDCl3, 300 MHz) d 3.61 (dt, J = 6.9 and 1.5 Hz, 2H), 3.97 (s, 3H), 5.19–5.24 (m,