Table 3. Cascade Iodocyclization to1,3-Diiodinated Naphtha-
lene Derivativesa
Scheme 1
products/
entry
substrate
yieldb (%)
1
2
3
4
5
6
7
8
9
R1 = H, R2 = Ph, R3 = H, R4 = H
2a/90
2b/72
2c/74
R1 = H, R2 = p-Me-C6H4, R3 = H, R4 = H
R1 = H, R2 = o-Me-C6H4, R3 = H, R4 = H
R1 = H, R2 = 3,4-dimethylphenyl, R3 = H, R4 = H 2d/58
R1 = H, R2 = o-Cl-C6H4, R3 = H, R4 = H
R1 = H, R2 = m-Cl-C6H4, R3 = H,R4 = H
R1 = H, R2 = p-Cl-C6H4, R3 = H, R4 = H
R1 = H, R2 = o-Br-C6H4, R3 = H, R4 = H
R1 = H, R2 = m-Br-C6H, R3 = H, R4 = H
2e/88
2f/87
2g/95
2h/80
2i/88
2j/99
decd
10 R1 = H, R2 = p-Br-C6H4, R3 = H, R4 = H
11 R1 = H, R2 = p-OMe-C6H4, R3 = H, R4 = H
12 R1 = H, R2 = 1-naphthyl, R3 = H, R4 = H
13 R1 = H, R2 = n-propyl, R3 = H, R4 = H
14 R1 = H, R2 = TMS, R3 = H, R4 = H
15 R1 = H, R2 = Ph, R3 = F, R4 = H
16 R1 = H, R2 = Ph, R3 = OMe, R4 = H
17 R1 = H, R2 = Ph, R3 = H, R4 = Me
18 R1 = H, R2 = Ph, R3 = H, R4 = Cl
2l/83
2m/72
nrc
well with the compounds 1l and 1m having a naphthyl or
an aliphatic group at R2, which proceeded to give the
desired 1,3-diiodinated products 2l and 2m in good yields
(entries 12 and 13), while compound 1n with a TMS R2
group gave no desired product 2n and was recovered in
40% yield (entry 14). We have also investigated the effect
of substituent at R3 and R4. To our delight, 1o and 1p gave
the corresponding products in good yield (entry 15À16),
but 1q and 1r only gave the desired product in yields of 7%
and 4%, respectively (entries 17 and 18). We considered
that the failure to get a good yield of 1q and 1r may be the
result of the steric effect of the substituent at R4 to prevent
the second cyclization step (Scheme 1). We further tested
the effect of substituent at R1. Similarly, the substrates
1sÀv underwent the cyclization smoothly to give the corre-
sponding 1,3-diiodinated naphthalenes (entries 19À22).
However, compounds with more steric effects gave a lower
yield. Furthermore, to expand the scope of this reaction,
we also investigated 1w with a vinyl group. It was found
that compound 1w was smoothly converted into the cor-
responding 1,3-diiodinated naphthalene 2w, which, however,
only was obtained in a low yield of 30% (entry 23).
2o/85
2p/74
2q/7
2r/4
19 R1 = ethyl, R2 = Ph, R3 = H, R4 = H
20 R1 = isopropyl, R2 = Ph, R3 = H, R4 = H
21 R1 = Ph, R2 = Ph, R3 = H, R4 = H
2s/70
2t/68
2u/42
2v/43
2w/30
22 R1 = m-Me-C6H4, R2 = Ph, R3 = H, R4 = H
23 R1 = H, R2 = cyclohexenyl, R3 = H, R4 = H
a All reactions were run under the following conditions, unless
otherwise indicated: 0.2 mmol of 1 with 2.5 equiv of ICl in 4 mL of
n-propanol at room temperature. b Isolated yield. c nr = starting 1 was
recovered in 40%. d dec = decomposed.
electron-withdrawing aryl groups got better results than
those with an electron-donating group in this reaction
(entries 2À4 vs 5À10). We envisioned that an electron-
withdrawing aromatic R2 group led to the decline of the
density of the electron of the alkynyl moiety, which was
unfavorable for coordination with the iodide cation, while
the other alkynyl moiety with an electron-rich group was
more easy to react. This was conducive to the first cycliza-
tion step (Scheme 1). Subsequently, we designed com-
pound 1k and discovered that it even failed to obtain the
corresponding product, which was in accord with the
above presumption (entry 11). The reactions also worked
On the basis of the above observations, we propose
the following plausible mechanisms for this sequential cas-
cade iodocyclization (Scheme 1). We envisioned the fol-
lowing. (i) Coordination of the alkynyl moiety of A to an
iodide cation gave the complex B. (ii) The hydroxyl group
(11) (a) Yang, F.; Jin, T.; Yamamoto, Y. Chem. Commun. 2011, 47,
4013. (b) Lian, J.-J .; Liu, R.-S. Chem. Commun. 2007, 1337. (b) Dawei,
Y.; Della.-Ca, N.; Larock, R.-C. J. Org. Chem. 2006, 71, 3381. (c)
Barluenga, J.; Vazquez-Villa, H.; Ballesteros, A.; Gonzalez, J.-M. Org.
(9) (a) Rossi, R.; Carpita, A.; Bellina, F.; Stabile, P.; Mannina, L.
Tetrahedron. 2003, 59, 2067. (b) Yao, T.; Larock, R.-C. J. Org. Chem.
2003, 68, 5936. (c) Oliver, M.-A.; Gandour, R.-D. J. Org. Chem. 1984,
49, 558. (d) Biagetti, M.; Bellina, F.; Carpita, A.; Stabile, P.; Rossi, R.
Tetrahedron 2002, 58, 5023. (e) Yao, T.; Larock, R.-C. Tetrahedron Lett.
2002, 43, 7401.
(10) (a) Zhang, X.; Sarkar, S.; Larock, R.-C. J. Org. Chem. 2006, 71,
236. (b) Barluenga, J.; Vazque-Villa, H.; Merino, I.; Ballesteros, A.;
Gonzalez, J.-M. Chem.;Eur. J. 2006, 12, 5790.
ꢀ
Lett. 2003, 5, 4121.
(12) (a) Khan, Z.-A.; Wirth, T. Org. Lett. 2009, 11, 229. (b) Bi, H.-P.;
Guo, L.-N.; Duan, X.-H.; Gou, F.-R.; Huang, S.-H.; Liu, X.-Y.; Liang,
Y.-M. Org. Lett. 2007, 9, 397.
(13) Chen, C.-C.; Yang, S.-C.; Wu, M.-J. J. Org. Chem. 2011, 76,
10269.
1992
Org. Lett., Vol. 14, No. 8, 2012