HI-mediated cyclization of o-Alkynylstyrenes

Article abstract of DOI:10.1246/cl.2000.722

o-Alkynylstyrenes cyclized in the presence of hydroiodic acid to yield polysubstituted iodoindenes. This reaction provides an efficient synthetic method for the preparation of polysubstituted iodoindenes.

Full text of DOI:10.1246/cl.2000.722

722
Chemistry Letters 2000
HI-Mediated Cyclization of o-Alkynylstyrenes
Shinichi Saito, Miyako Homma,† Valdimir Gevorgyan,† and Yoshinori Yamamoto*†
Institute for Chemical Reaction Science, Tohoku University, Sendai 980-8578
†Department of Chemistry, Graduate School of Science, Tohoku University, Sendai 980-8578
(Received April 7, 2000; CL-000323)
o-Alkynylstyrenes cyclized in the presence of hydroiodic
yields (entries 3, 4). The reaction proceeded even in the pres-
ence of hydroxyl group in the diyne moiety, though the yield of
the product 3e was low (38%) and a larger amount of the cata-
lyst was employed for this reaction (entry 5). It may be possible
to explain the lower yield of the product in terms of the com-
plexation of the hydroxyl group to the palladium catalyst.
acid to yield polysubstituted iodoindenes. This reaction pro-
vides an efficient synthetic method for the preparation of poly-
substituted iodoindenes.
o-Ethynylstyrenes are useful precursors for the synthesis of
bicyclic rings. Recent studies revealed that these compounds
cyclized in the presence of transition metals to give naphthalene
derivatives and related compounds in good yields (eq 1).1 On the
other hand, the cyclization of o-alkynylstyrenes has been studied
to much less extent.2 While we were studying the cyclization
reaction of the o-alkynylstyrenes, we found that the cyclization
reaction occurred in the presence of hydroiodic acid to yield an
iodoindene. In this paper we report the preparation and HI-medi-
ated cyclization of o-alkynylstyrenes (eq 2).
The preparation of o-alkynylstyrenes was carried out by the
palladium catalyzed cross-benzannulation3,4 of dienynes with
diynes and the results are summarized in Table 1. 2,5-Dimethyl-
1,5-hexadien-3-yne (1), which was prepared in one step by the
Sonogashira coupling of 2-methyl-1-buten-3-yne with vinyl bro-
mide, reacted in the presence of Pd(PPh3)4 and (o-tolyl)3P3,4
with diyne 2a to give polysubstituted o-alkynylstyrene 3a in 61%
yield (Table 1, entry 1). It was necessary to carry out the reac-
tion at elevated temperature (120 °C), and the reactivity of 1
seems to be comparable to those of other 2,4-disubstituted
enynes.3,4 As is the case for the reaction of other conjugated
enynes with diynes, the reaction proceeded in a highly regiose-
lective manner, and 3a was isolated as a single isomer. It is note-
worthy that the homo-benzannulation product was not isolated,
and the mode of the reaction of 1 with the diynes 2 was not
affected by the presence of an additional olefinic moiety. The
reactions of 1 with other diynes proceeded smoothly to give the
corresponding products in good yields. Thus, the reaction of 1
with 2,4-hexadiyne 2b gave 3b (entry 2), and sterically hindered
diynes such as 2c and 2d also reacted with 1 to give the polysub-
stituted o-ethynylstyrenes 3c and 3d, respectively, in moderate
We treated the alkynylstyrenes under various conditions and
found that the cyclization reaction occurred in the presence of a
protic acid. Though o-alkynylstyrene 3a did not cyclize in the
presence of protic acids such as HCl, HBr, or CF3SO3H, the
cyclization reaction proceeded smoothly in the presence of
hydroiodic acid and the results are summarized in Table 2. Thus,
compound 3a cyclized in the presence of 1 equiv of HI (condi-
tion A) to yield iodoindene 4a in 53% yield. The reaction also
proceeded smoothly in the presence of chlorotrimethylsilane/
sodium iodide (condition B),5 and 4a was isolated in 73% yield.
The reaction of other alkynylstyrenes (3f–h) also proceeded effi-
ciently, and the yields of the products were generally higher when
the reaction was carried out under condition B (entries 3–8).
While we were monitoring the reaction by gas chromatog-
raphy, we observed the formation of an intermediate during the
reaction. In order to investigate the mechanism of this reaction,
we isolated the intermediate by carrying out the reaction in
toluene6 and isolated iodovinylbenzene 5.7 Compound 5 react-
Copyright © 2000 The Chemical Society of Japan

Chemistry Letters 2000
723
In summary, we found that the cyclization of o-alkynyl-
styrenes proceeds smoothly in the presence of hydroiodic acid
under mild conditions. This reaction complements the previ-
ously known synthetic methods for the preparation of polysub-
stituted iodoindenes.
References and Notes
1
a) C. A. Merlic and M. E. Pauly, J. Am. Chem. Soc., 118, 11319
(1996). b) K. Maeyama and N. Iwasawa, J. Am. Chem. Soc., 120,
1928 (1998). c) K. Maeyama and N. Iwasawa, J. Org. Chem., 64,
1344 (1999).
2
3
A palladium-mediated cyclization of o-alkynylstyrenes has been
reported. See, W. Münzenmaier and H. Straub, Synthesis 1976,
49.
a) V. Gevorgyan, A. Takeda, M. Homma, N. Sadayori, U.
Radhakrishnan, and Y. Yamamoto, J. Am. Chem. Soc., 121, 6391
(1999). b) V. Gevorgyan, A. Takeda, Y. Yamamoto, J. Am.
Chem. Soc., 119, 11313 (1997).
ed in the presence of a catalytic amount of hydroiodic acid to
yield 4a in good yield (eq 3).
4
5
Reviews: a) S. Saito and Y. Yamamoto, Chem. Rev., in press. b)
V. Gevorgyan and Y. Yamamoto, J. Organomet. Chem., 576, 232
(1999).
S. Irifune, T. Kibayashi, Y. Ishii, and M. Ogawa, Synthesis 1988,
366.
6
7
The rate of the reaction was much slower in this solvent.
Spectroscopic data of 5: colorless oil, 1H NMR (300 MHz,
CDCl3) δ 6.94 (d, 1H, J = 1.8 Hz), 6.80 (d, 1H, J = 1.5 Hz), 6.44
(t, 1H, J = 7.2 Hz), 5.13–5.11 (m, 1H), 4.92–4.91 (m, 1H),
2.66–2.57 (m, 2H), 2.30 (s, 3H), 2.12 (s, 3H), 1.79–1.16 (m, 8H),
0.96 (t, 3H, J = 7.2 Hz), 0.83 (t, 3H, J = 7.1 Hz). 13C NMR (75
MHz, CDCl3) δ 145.5, 144.8, 143.0, 140.3, 137.7, 134.5, 128.5,
126.9, 115.2, 93.7, 32.7, 32.5, 32.4, 30.5, 24.1, 23.0, 22.4, 21.3,
14.0, 13.9; IR (neat) 3080, 3015, 2957, 2928, 2858, 1715, 1632,
1601, 1456, 1377, 1340, 1313, 1265, 1244, 1209, 1180, 1136,
1038, 968, 932, 895, 860, 818, 762, 719, 631 cm–1; HRMS Found
396.1313. Calcd for C20H29I: 396.1313. Anal. Found: C, 60.52;
H, 7.62%. Calcd for C20H29I: C, 60.61; H, 7.37%. The geome-
try of the double bond was determined by the observation of the
coupling constant between the olefinic proton of 8, which was
prepared by the reduction (Bu3SnH−Pd(PPh3)4) of 5.
Based on these results, we currently assume the mecha-
nism of the cyclization as shown in Scheme 1. Thus, the
regioselective addition of hydrogen iodide to 3a would occur to
give the intermediate 5, which would be protonated to give the
benzyl cation 6. Subsequent cyclization would yield the
iodobenzyl cation 7. Proton would be eliminated from 7 and
the iodoindene 4a would be formed as the final product.