Radical cyclization of 4-aryl-1-iodobutene derivatives to form dihydronaphthalene scaffold

Article abstract of DOI:10.1016/j.tetlet.2007.02.132

Synthesis of dihydronaphthalene derivatives was carried out by allyltributylstannane-mediated vinyl radical cyclization as the key step from 4-aryl-1-iodobutene derivatives, which were derived from Baylis-Hillman adducts via vinyl radical cyclization.

Full text of DOI:10.1016/j.tetlet.2007.02.132

Tetrahedron Letters 48 (2007) 3105–3108
Radical cyclization of 4-aryl-1-iodobutene derivatives to form
dihydronaphthalene scaffold
Saravanan Gowrisankar, Hyun Seung Lee and Jae Nyoung Kim*
Department of Chemistry and Institute of Basic Science, Chonnam National University, Gwangju 500-757, Republic of Korea
Received 9 January 2007; revised 29 January 2007; accepted 6 February 2007
Available online 2 March 2007
Abstract—Synthesis of dihydronaphthalene derivatives was carried out by allyltributylstannane-mediated vinyl radical cyclization as
the key step from 4-aryl-1-iodobutene derivatives, which were derived from Baylis–Hillman adducts via vinyl radical cyclization.
Ó 2007 Elsevier Ltd. All rights reserved.
Recently we reported the synthesis of exo-methylene
tetrahydrofurans,1 5-methylene tetrahydropyrancarb-
oxylates,2 and exo-methylene cyclopentanes3 via the
radical cyclization protocol as the key step starting from
the modified Baylis–Hillman adducts. Meantime we
were interested in the C–C bond formation between
the aryl group and the vinyl moiety in order for the syn-
thesis of dihydronaphthalene skeleton.4 We supposed
that the desired dihydronaphthalene 3 could be formed
by the consecutive generation of a vinyl radical from 2
and cyclization onto the benzene ring as shown in
Scheme 1. There were reported many examples on the
intramolecular C–C bond-forming reactions between
aryl halides and another arene moiety via radical
cyclization process.5 However, examples of radical cycli-
zations involving the addition of vinyl radical intermedi-
ates to proximal arenes are more limited5d,6 although
vinyl radical cyclizations to various alkene moiety have
been extensively studied.7
We presumed that treatment of vinyl iodide 2 with
n-Bu3SnH and AIBN would generate a vinyl radical
intermediate, and that this would rapidly abstract a
hydrogen atom from n-Bu3SnH to give vinyl compound
4 (vide infra). However, if we used allyltributylstannane
the vinyl radical would not be quenched by stannane as
in our previous report,2 leading to cyclization to give the
cyclized compound 3. The required vinyl iodide 2a was
prepared from the corresponding vinylstannane inter-
mediate with iodine as reported.7b Thus, we examined
the reaction of 2a and allyltributylstannane in the pres-
ence of AIBN in benzene. To our delight we obtained
the expected dihydronaphthalene compound 3a in 65%
in a short time. The compound might be formed via rad-
ical cyclization of the corresponding vinyl radical as
shown in Scheme 1. In addition, it is interesting to note
that the reaction of 2a in the presence of n-Bu3SnH
instead of allyltributylstannane under similar conditions
afforded simple reduction compound 4 in 92% as we
E
E
E
I
E
E
E
E
E
E
E
E
E
3
2
Scheme 1.
Keywords: Radical cyclization; Dihydronaphthalene; n-Bu3SnH; Allyltributylstannane; Baylis–Hillman adducts.
*
Corresponding author. Tel.: +82 62 530 3381; fax: +82 62 530 3389; e-mail: kimjn@chonnam.ac.kr
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.02.132

3106
S. Gowrisankar et al. / Tetrahedron Letters 48 (2007) 3105–3108
OAc
COOMe
Ph
1. diethyl malonate/K2CO3/CH3CN
2. propargyl bromide/NaH/DMF
3. n-Bu3SnH/AIBN/benzene
Ref. 3
4. I2/CH2Cl2
n
-Bu3SnCH2CH=CH2
n-Bu3SnH
MeOOC
I
MeOOC
MeOOC
EtOOC COOEt
EtOOC COOEt
EtOOC COOEt
4 (92%)
2a
3a (65%)
Scheme 2.
expected (Scheme 2). We examined the possibility for
the thermal synthesis of 3a from 2a.8 The reaction was
conducted either in refluxing benzene or p-xylene, but
we observed no reaction. When we used quinoline as
the solvent, severe decomposition of starting material
was observed.
yields irrespective of the substituents both on the cyclo-
pentane ring and aryl moiety. From the reaction of 2c
(entry 3) we could isolate 3c as the single diastereoiso-
mer, but we did not determine the stereochemistry. As
in entry 5, the use of bromovinyl compound gave the
same product 3b in 75%. However, the reaction of 2f7b
under the same reaction conditions did not produce
the desired compound 3e. When we used hexabutylditin
instead of allyltributylstannane, the result was same
(Scheme 3) to show the formation of many intractable
compounds.10
By applying the typical procedure we examined some
examples and the results are summarized in Table 1.9
As shown, the reaction proceeded similarly and we
obtained dihydronaphthalene derivatives 3b–d in good
Table 1. Radical cyclization to dihydronaphthalene derivatives
R1
R1
COOMe
MeOOC
MeOOC
X
R1
EWG2 EWG1
EWG2 EWG1
3a -d
1a-d
EWG2 EWG1
2a-e
Entry
1
Substratea
1a: R1 = H
EWG1 = COOEt
EWG2 = COOEt
1b: R1 = H
Vinyl halideb (%)
Time (h)
12
Productc (%)
2a: X = I (82)
3a (65)
2
3
4
5
2b: X = I (92)
2c: X = I (79)
2d: X = I (83)
2e: X = Br (88)d
8
8
3b (83)
3c (56)
3d (72)
3b (75)
EWG1 = COOMe
EWG2 = COOMe
1c: R1 = H
EWG1 = COOMe
EWG2 = CN
1d: R1 = CH3
14
3
EWG1 = COOMe
EWG2 = COOMe
1b
a Starting materials 1a–d were synthesized as in our previous paper.3
b Conditions: (i) 1 (1.0 equiv), n-Bu3SnH (1.2 equiv), AIBN (0.1 equiv), benzene, reflux, 1 h, (ii) I2, CH2Cl2, rt, 2 h.
c Conditions: 2 (1.0 equiv), allyltributylstannane (3.0 equiv), AIBN (0.1 equiv), benzene, reflux, 3–14 h.
d Conditions: (i) 1b (1.0 equiv), n-Bu3SnH (1.2 equiv), AIBN (0.1 equiv), benzene, reflux, 1 h, (ii) NBS, CH2Cl2, 0 °C, 1 h.

S. Gowrisankar et al. / Tetrahedron Letters 48 (2007) 3105–3108
3107
COOMe
Ref. 1, 7b
Ph
MeOOC
MeOOC
I
O
O
1e
O
2f (80%)7b
3e
Scheme 3.
Tae, J. S.; Chong, T. H.; Park, Y. C. Tetrahedron Lett.
1994, 35, 129.
8. For the thermal cyclization between aryl group and
halovinyl moiety, see Gopal, D.; Rajagopalan, K. Tetra-
hedron Lett. 1986, 27, 5883.
In summary, we disclosed an efficient synthesis of novel
tricyclic compounds by using the vinyl radical cycliza-
tion protocol starting from the corresponding vinyl iod-
ides, which were derived from Baylis–Hillman adducts.
Desired vinyl radical cyclization process was successfully
carried out by using allyltributylstannane-assisted vinyl
radical generation.
9. Typical procedure for the synthesis of 2a: To a stirred
solution of 1a3 (250 mg, 0.67 mmol), n-Bu3SnH (233 mg,
0.8 mmol) in benzene (10 mL) was added AIBN (11 mg,
0.07 mmol) and heated to reflux for 1 h under nitrogen
atmosphere. The reaction mixture was diluted with
CH2Cl2 and a solution of iodine in CH2Cl2 was added at
0 °C until the purple color persists and stirred for 2 h at
room temperature. The reaction mixture was diluted with
CH2Cl2 and washed with NaHSO3 solution and brine.
After the usual purification process using flash column
chromatography (hexanes/EtOAc, 7:3), we obtained 2a as
colorless oil, 275 mg (82%). Spectroscopic data of 2a–e are
as follows:
References and notes
1. Gowrisankar, S.; Lee, K. Y.; Kim, J. N. Tetrahedron Lett.
2005, 46, 4859.
2. Gowrisankar, S.; Lee, K. Y.; Kim, T. H.; Kim, J. N.
Tetrahedron Lett. 2006, 47, 5785.
3. Gowrisankar, S.; Lee, H. S.; Kim, J. N. Bull. Korean
Chem. Soc. 2006, 27, 2097.
Compound 2a: colorless oil; 82%; IR (neat) 3084, 1734,
1
1448, 1298 cmÀ1; H NMR (CDCl3, 500 MHz) d 1.23 (t,
4. For the synthesis and utility of similar dihydronaphtha-
lene derivatives, see: (a) Brown, S.; Clarkson, S.; Grigg,
R.; Sridharan, V. Tetrahedron Lett. 1993, 34, 157; (b)
Kretzschmann, H.; Eidenschink, R. Ger. Offen. DE
10110307 2002; Chem. Abstr. 2002, 137, 201158; (c)
Bedekar, A. V.; Watanabe, T.; Tanaka, K.; Fuji, K.
Tetrahedron: Asymmetry 2002, 13, 721; (d) Dyker, G.;
Hildebrandt, D.; Liu, J.; Merz, K. Angew. Chem., Int. Ed.
2003, 42, 4399; (e) Asao, N.; Kasahara, T.; Yamamoto, Y.
Angew. Chem., Int. Ed. 2003, 42, 3504, and further
references cited therein.
J = 7.0 Hz, 3H), 1.26 (t, J = 7.0 Hz, 3H), 2.73 (d,
J = 14.5 Hz, 1H), 2.77 (dd, J = 17.5 and 2.5 Hz, 1H),
2.83 (d, J = 13.0 Hz, 1H), 3.00 (d, J = 14.0 Hz, 1H), 3.20
(dq, J = 17.5 and 0.5 Hz, 1H), 3.35 (d, J = 13.5 Hz, 1H),
3.65 (s, 3H), 4.09–4.24 (m, 4H), 6.55 (t, J = 2.5 Hz, 1H),
7.11–7.13 (m, 2H), 7.22–7.28 (m, 3H); 13C NMR (CDCl3,
75 MHz) d 13.89, 13.95, 41.31, 44.89, 45.01, 52.47, 57.02,
58.84, 61.72, 61.84, 76.52, 126.94, 128.32, 129.68, 136.55,
152.43, 170.72, 171.16, 172.62.
Compound 2b: colorless oil; 92%; IR (neat) 2953, 1736,
1
1435, 1263 cmÀ1; H NMR (CDCl3, 300 MHz) d 2.72 (d,
5. For the aryl radical cyclizations onto aryl ring, see: (a)
Harrowven, D. C.; Woodcock, T.; Howes, P. D. Angew.
Chem., Int. Ed. 2005, 44, 3899; (b) Rosa, A. M.; Lobo, A.
M.; Branco, P. S.; Prabhakar, S. Tetrahedron 1997, 53,
285; (c) Bowman, W. R.; Mann, E.; Parr, J. J. Chem. Soc.,
Perkin Trans. 1 2000, 2991; (d) Harrowven, D. C.;
L’Helias, N.; Moseley, J. D.; Blumire, N. J.; Flanagan,
S. R. Chem. Commun. 2003, 2658.
J = 14.1 Hz, 1H), 2.73 (dd, J = 18.0 and 2.6 Hz, 1H), 2.81
(d, J = 13.5 Hz, 1H), 3.00 (dd, J = 14.4 and 1.5 Hz, 1H),
3.25 (d, J = 17.7 Hz, 1H), 3.37 (d, J = 13.8 Hz, 1H), 3.65
(s, 3H), 3.70 (s, 3H), 3.75 (s, 3H), 6.58 (t, J = 2.6 Hz, 1H),
7.09–7.12 (m, 2H), 7.22–7.28 (m, 3H); 13C NMR (CDCl3,
75 MHz) d 41.64, 44.94, 45.04, 52.56, 52.92, 53.01, 56.88,
58.86, 76.76, 127.00, 128.37, 129.61, 136.45, 152.24,
171.16, 171.55, 172.53; ESIMS m/z 473 (M++H).
6. For the vinyl radical cyclization onto aryl ring, see: (a)
Montevecchi, P. C.; Navacchia, M. L. J. Org. Chem. 1997,
62, 5600; (b) Boger, D. L.; Boyce, C. W. J. Org. Chem.
2000, 65, 4088; (c) Patel, V. F.; Andis, S. L.; Enkema, J.
K.; Johnson, D. A.; Kennedy, J. H.; Mohamadi, F.;
Schultz, R. M.; Soose, D. J.; Spees, M. M. J. Org. Chem.
1997, 62, 8868; (d) Montevecchi, P. C.; Navacchia, M. L.
J. Org. Chem. 1998, 63, 537; (e) Benati, L.; Montevecchi,
P. C.; Spagnolo, P. J. Chem. Soc., Perkin Trans. 1 1992,
1659.
Compound 2c: colorless oil; 79%; IR (neat) 2954, 2245,
1
1741, 1367 cmÀ1; H NMR (CDCl3, 300 MHz) d 1.32 (t,
J = 7.2 Hz, 3H), 2.53 (d, J = 14.4 Hz, 1H), 2.90 (d,
J = 13.5 Hz, 1H), 2.97 (dd, J = 17.4 and 3.0 Hz, 1H),
3.07–3.15 (m, 2H), 3.38 (d, J = 13.5 Hz, 1H), 3.75 (s, 3H),
4.28 (q, J = 7.2 Hz, 2H), 6.76 (t, J = 2.7 Hz, 1H), 7.05–
7.09 (m, 2H), 7.25–7.28 (m, 3H); 13C NMR (CDCl3,
75 MHz) d 13.88, 43.51, 45.00, 45.45, 47.70, 52.81, 58.99,
63.45, 78.58, 118.94, 127.30, 128.53, 129.60, 135.80,
150.01, 168.06, 171.90.
7. For the radical cyclizations of vinyl halides toward C@C
and other double bonds, see: (a) Hiramatsu, N.; Taka-
hashi, N.; Noyori, R.; Mori, Y. Tetrahedron 2005, 61,
8589; (b) Shanmugam, P.; Rajasingh, P. Tetrahedron 2004,
60, 9283; (c) Shanmugam, P.; Rajasingh, P. Tetrahedron
Lett. 2005, 46, 3369; (d) Shanmugam, P.; Rajasingh, P.
Synlett 2005, 939; (e) Ryu, I.; Ogura, S.-i.; Minakata, S.;
Komatsu, M. Tetrahedron Lett. 1999, 40, 1515; (f) Lee, E.;
Compound 2d: colorless oil; 83%; IR (neat) 2953, 1736,
1263 cmÀ1 1H NMR (CDCl3, 300 MHz) d 2.29 (s, 3H),
;
2.71 (d, J = 14.4 Hz, 1H), 2.73 (dd, J = 18.0 and 2.6 Hz,
1H), 2.76 (d, J = 13.5 Hz, 1H), 3.00 (dd, J = 14.1 and
1.4 Hz, 1H), 3.24 (d, J = 17.7 Hz, 1H), 3.32 (d,
J = 13.5 Hz, 1H), 3.64 (s, 3H), 3.69 (s, 3H), 3.74 (s, 3H),
6.56 (t, J = 2.6 Hz, 1H), 6.98 (d, J = 8.1 Hz, 2H), 7.06 (d,
J = 8.1 Hz, 2H); 13C NMR (CDCl3, 75 MHz) d 20.93,

3108
S. Gowrisankar et al. / Tetrahedron Letters 48 (2007) 3105–3108
41.61, 44.65, 44.92, 52.44, 52.83, 52.91, 56.81, 58.92, 76.63,
J = 14.4 Hz, 1H), 3.04 (d, J = 15.0 Hz, 1H), 3.12 (d,
J = 15.3 Hz, 1H), 3.42 (d, J = 15.0 Hz, 2H), 3.55 (s, 3H),
4.31 (q, J = 7.2 Hz, 2H), 6.53 (d, J = 1.8 Hz, 1H), 7.04–
7.06 (m, 1H), 7.12–7.19 (m, 3H); 13C NMR (CDCl3,
75 MHz) d 13.95, 38.61, 42.88, 46.44, 47.46, 51.17, 52.56,
63.36, 120.22, 123.76, 126.30, 127.15, 127.64, 127.68,
132.73, 132.82, 139.62, 167.67, 174.04.
129.00, 129.42, 133.27, 136.47, 152.21, 171.11, 171.47,
172.51.
Compound 2e: colorless oil; 88%; IR (neat) 2953, 1738,
1
1435, 1267 cmÀ1; H NMR (CDCl3, 300 MHz) d 2.68 (d,
J = 14.4 Hz, 1H), 2.80 (dd, J = 15.3 and 2.7 Hz, 1H), 2.84
(d, J = 13.5 Hz, 1H), 2.94 (dd, J = 14.4 and 1.5 Hz, 1H),
3.29 (dq, J = 15.6 and 1.2 Hz, 1H), 3.33 (d, J = 13.5 Hz,
1H), 3.65 (s, 3H), 3.69 (s, 3H), 3.74 (s, 3H), 6.47 (t,
J = 2.7 Hz, 1H), 7.09–7.12 (m, 2H), 7.21–7.26 (m, 3H);
13C NMR (CDCl3, 75 MHz) d 40.68, 41.35, 45.03, 52.45,
52.81, 52.90, 57.16, 58.40, 104.47, 126.97, 128.30, 129.56,
136.36, 146.49, 171.08, 171.48, 172.59.
Typical procedure for the synthesis of 3a: To a stirred
solution of 2a (84 mg, 0.17 mmol), allyltributylstannane
(167 mg, 0.5 mmol) in benzene (2 mL) was added AIBN
(3 mg, 0.018 mmol) and heated to reflux for 12 h under
nitrogen atmosphere. After the usual aqueous extractive
workup with CH2Cl2 and the following column chro-
matographic purification process (hexanes/EtOAc, 6:4),
we obtained 3a as colorless oil, 41 mg (65%). Spectro-
scopic data of 3a–d are as follows:
Compound 3d: colorless oil; 72%; IR (neat) 2954, 1736,
1
1433, 1254 cmÀ1; H NMR (CDCl3, 300 MHz) d 2.26 (s,
3H), 2.53 (d, J = 14.4 Hz, 1H), 2.84 (d, J = 16.2 Hz, 1H),
2.89 (d, J = 14.1 Hz, 1H), 3.16 (d, J = 17.1 Hz, 1H), 3.36
(d, J = 15.3 Hz, 1H), 3.48 (d, J = 17.4 Hz, 1H), 3.52 (s,
3H), 3.73 (s, 3H), 3.74 (s, 3H), 6.36 (s, 1H), 6.83 (s, 1H),
6.88 (d, J = 7.5 Hz, 1H), 7.00 (d, J = 7.5 Hz, 1H); 13C
NMR (CDCl3, 75 MHz) d 21.01, 38.09, 39.79, 44.73,
51.99, 52.23, 52.94, 53.06, 59.53, 121.92, 126.73, 127.37,
127.60, 129.87, 133.45, 136.31, 141.92, 171.44, 171.95,
174.82.
Synthesis of compound 4: To a stirred solution of 2a
(50 mg, 0.1 mmol), n-Bu3SnH (35 mg, 0.12 mmol) in
benzene (2 mL) was added AIBN (2 mg, 0.01 mmol) and
heated to reflux for 1 h. After the usual aqueous extractive
workup with EtOAc and the following column chromato-
graphic purification process (hexanes/EtOAc, 7:3), we
obtained 4 as colorless oil, 34 mg (92%).
Compound 3a: colorless oil; 65%; IR (neat) 2926, 1734,
1254 cmÀ1
;
1H NMR (CDCl3, 300 MHz) d 1.26 (t,
J = 7.2 Hz, 6H), 2.54 (d, J = 14.1 Hz, 1H), 2.88 (d,
J = 13.8 Hz, 1H), 2.92 (d, J = 15.3 Hz, 1H), 3.15 (d,
J = 16.8 Hz, 1H), 3.39 (d, J = 15.3 Hz, 1H), 3.47 (d,
J = 16.8 Hz, 1H), 3.52 (s, 3H), 4.16–4.24 (m, 4H), 6.39 (s,
1H), 6.99–7.01 (m, 1H), 7.07–7.12 (m, 3H); 13C NMR
(CDCl3, 75 MHz) d 14.00 (2C), 38.46, 39.74, 44.62, 51.81,
52.24, 59.63, 61.77, 61.87, 121.73, 125.84, 126.83, 126.97,
127.55, 132.97, 133.61, 142.26, 170.97, 171.50, 174.84.
Compound 3b: colorless oil; 83%; IR (neat) 2954, 1739,
Compound 4: colorless oil; 92%; IR (neat) 2956, 1732,
;
1259 cmÀ1 1H NMR (CDCl3, 300 MHz) d 1.22 (t,
J = 7.2 Hz, 3H), 1.24 (t, J = 7.2 Hz, 3H), 2.64 (d,
J = 14.4 Hz, 1H), 2.76 (d, J = 16.2 Hz, 1H), 2.78 (d,
J = 13.5 Hz, 1H), 2.86 (d, J = 14.7 Hz, 1H), 3.18 (d,
J = 16.2 Hz, 1H), 3.44 (d, J = 13.8 Hz, 1H), 3.65 (s, 3H),
4.06–4.24 (m, 4H), 5.20 (t, J = 2.1 Hz, 1H), 5.30 (t,
J = 2.1 Hz, 1H), 7.17–7.29 (m, 5H); 13C NMR (CDCl3,
75 MHz) d 13.96, 13.99, 39.95, 41.03, 44.34, 52.29, 57.09,
57.93, 61.53, 61.66, 110.25, 126.67, 128.24, 129.84, 137.62,
150.76, 171.09, 171.69, 174.04.
1255 cmÀ1 1H NMR (CDCl3, 300 MHz) d 2.49 (d,
;
J = 14.4 Hz, 1H), 2.83 (d, J = 14.4 Hz, 2H), 3.09 (d,
J = 17.1 Hz, 1H), 3.32 (d, J = 15.3 Hz, 1H), 3.42 (d,
J = 17.1 Hz, 1H), 3.45 (s, 3H), 3.67 (s, 3H), 3.68 (s, 3H),
6.33 (s, 1H), 6.93–6.95 (m, 1H), 7.01–7.07 (m, 3H); 13C
NMR (CDCl3, 75 MHz) d 38.43, 39.81, 44.73, 51.80,
52.28, 52.98, 53.10, 59.55, 121.87, 125.89, 126.87, 127.04,
127.57, 132.93, 133.56, 142.0, 171.43, 171.97, 174.76;
ESIMS m/z 345 (M++H).
10. From the reaction of 2f (hexabutylditin, AIBN, toluene,
reflux, 10 h) we could obtain 3e in trace amount (5–6%).
However, the product was contaminated with appreciable
amounts of tin derivatives. 1H NMR spectrum of crude 3e
1
is as follows: oil; H NMR (CDCl3, 300 MHz) d 2.85 (d,
J = 15.3 Hz, 1H), 3.41 (d, J = 15.3 Hz, 1H), 3.60 (s, 3H),
3.76 (d, J = 8.7 Hz, 1H), 4.45 (d, J = 8.7 Hz, 1H), 4.54
(dd, J = 13.8 and 1.8 Hz, 1H), 4.76 (dd, J = 13.8 and
1.8 Hz, 1H), 6.45 (t, J = 1.8 Hz, 1H), 7.06–7.17 (m, 4H).
Compound 3c: colorless oil; 56%; IR (neat) 2954, 2254,
1
1747, 1232 cmÀ1; H NMR (CDCl3, 300 MHz) d 1.35 (t,
J = 7.2 Hz, 3H), 2.48 (d, J = 14.4 Hz, 1H), 3.00 (d,