Cyclization of 1-bromo-2,7- and 1-bromo-2,8-enynes mediated by indium

Article abstract of DOI:10.1021/ol048175r

(Chemical Equation Presented) The cyclization of 1-bromo-2,7- and 1-bromo-2,8-enynes mediated by indium in DMF produced five- and six-membered cyclic compounds. Although KI was a necessary additive in the cyclization of terminal 1-bromo-2,7-enynes to give the desired products at 25°C, reactions of terminal 1-bromo-2,8-enynes and internal 1-bromo-2,7-enynes with indium proceeded at 100°C in DMF without KI. After cyclizations, subsequent cross-coupling reaction and iodolysis increase the usefulness of this reaction.

Full text of DOI:10.1021/ol048175r

ORGANIC
LETTERS
2004
Vol. 6, No. 26
4825-4828
Cyclization of 1-Bromo-2,7- and
1-Bromo-2,8-Enynes Mediated by Indium
Phil Ho Lee,*,† Sundae Kim,† Kooyeon Lee,† Dong Seomoon,† Hyunseok Kim,†
Seokju Lee,† Misook Kim,† Mijeong Han,† Kwanghyun Noh,† and
Tom Livinghouse‡
Department of Chemistry, Kangwon National UniVersity,
Chunchon 200-701, Republic of Korea, Department of Chemistry,
Montana State UniVersity, Bozeman, Montana 59717
phlee@kangwon.ac.kr
Received September 9, 2004
ABSTRACT
The cyclization of 1-bromo-2,7- and 1-bromo-2,8-enynes mediated by indium in DMF produced five- and six-membered cyclic compounds.
Although KI was a necessary additive in the cyclization of terminal 1-bromo-2,7-enynes to give the desired products at 25 C, reactions of
C in DMF without KI. After cyclizations, subsequent
°
terminal 1-bromo-2,8-enynes and internal 1-bromo-2,7-enynes with indium proceeded at 100
cross-coupling reaction and iodolysis increase the usefulness of this reaction.
°
Organoindium reagents such as allylindiums, propargyl-
indiums, and allenylindiums are of considerable value for
regioselective and stereoselective allylation, propargylation,
and allenylation of a variety of carbonyl and imine com-
pounds to give the corresponding alcohols and amines.1 Also,
a range of indium-mediated organic reactions are useful for
Reformatsky reactions,2 Michael addition reactions,3 cross-
coupling reactions,4 and allylic substitution reactions.5 The
intermolecular addition of organoindium reagents to C-C
multiple bonds and nitriles are especially important synthetic
tools for constructing 1,4-diene derivatives.6 The reaction
of allylindium with terminal alkynols and allenols in DMF
at 100-140 °C produced the corresponding allylation
products in good yields.7 Although metal-catalyzed cycliza-
tions have long been established as efficient methods for
providing various types of cyclic compounds,8 cyclization
reactions involving organoindium reagents remain less-well
explored. Despite the synthetic usefulness of intermolecular
indium-mediated C-C bond formation,1 the corresponding
indium-mediated intramolecular cyclizations are mainly
limited to Pd-In-mediated arylative cyclizations of allenyl
carbonyl compounds,9 intramolecular allylindation of ter-
† Kangwon National University.
‡ Montana State University.
(3) (a) Araki, S.; Shimizu, T.; Jin, S.-J.; Butsugan, Y. Chem. Commun.
1991, 824. (b) Perez, I.; Sestelo, J. P.; Maestro, M. A.; Mourino, A.;
Sarandeses, L. A. J. Org. Chem. 1998, 63, 10074. (c) Wang, L.; Sun, X.;
Zhang, Y. Synth. Commun. 1998, 28, 3263. (d) Araki, S.; Horie, T.; Kato,
M.; Hirashita, T.; Yamamura, H.; Kawai, M. Tetrahedron Lett. 1999, 40,
2331. (e) Lee, P. H.; Lee, K.; Kim, S. Org. Lett. 2001, 3, 3205. (f) Lee, P.
H.; Ahn, H.; Lee, K.; Sung, S.-Y.; Kim, S. Tetrahedron Lett. 2001, 42, 37.
(g) Iwasawa, N.; Miura, T.; Kiyota, K.; Kusama, H.; Lee, K.; Lee, P. H.
Org. Lett. 2002, 4, 4463. (h) Miura, T.; Kiyota, K.; Kusama, H.; Lee, K.;
Kim, H.; Kim, S.; Lee, P. H.; Iwasawa, N. Org. Lett. 2003, 5, 1725. (i)
Lee, P. H.; Seomoon, D.; Lee, K.; Heo, Y. J. Org. Chem. 2003, 68, 2510.
(j) Lee, K.; Kim, H.; Miura, T.; Kiyota, K.; Kusama, H.; Kim, S.; Iwasawa,
N.; Lee, P. H. J. Am. Chem. Soc. 2003, 125, 9682.
(1) (a) Li, C.-J. Chem. ReV. 1993, 93, 2023. (b) Cintas, P. Synlett 1995,
1087. (c) Li, C.-J. Tetrahedron 1996, 52, 5643. (d) Li, C.-J.; Chan, T.-H.
Organic Reactions in Aqueous Media; Wiley: New York, 1997. (e) Li,
C.-J.; Chan, T.-H. Tetrahedron 1999, 55, 11149. (f) Babu, G.; Perumal, P.
T. Aldrichimica Acta 2000, 33, 16. (g) Chauhan, K. K.; Frost, C. G. J.
Chem. Soc., Perkin Trans. 1 2000, 3015. (h) Pae, A. N.; Cho, Y. S. Curr.
Org. Chem. 2002, 6, 715. (i) Podlech, J.; Maier, T. C. Synthesis 2003, 633.
(2) (a) Araki, S.; Ito, H.; Butsugan, Y. Synth. Commun. 1988, 18, 453.
(b) Araki, S.; Katsumura, N.; Kawasaki, K.-I.; Butsugan, Y. J. Chem. Soc.,
Perkin Trans. 1 1991, 499. (c) Lee, P. H.; Bang, K.; Lee, K.; Sung, S.-Y.;
Chang, S. Synth. Commun. 2001, 31, 3781. (d) Bang, K.; Lee, K.; Park, Y.
K.; Lee, P. H. Bull. Korean Chem. Soc. 2002, 23, 1272.
10.1021/ol048175r CCC: $27.50
© 2004 American Chemical Society
Published on Web 10/22/2004

Scheme 1
Table 2. Cyclization of Terminal 1-Bromo-2,7- and
1-Bromo-2,8-Enynes Mediated by Indium
minal alkynes in aqueous media,10 cyclizations of tethered
propargyl bromides to carbonyl compounds,11 atom-transfer
cyclizations,12 and cyclizations via trans-hydrometalation of
alkynes by InCl3 and DIBAL-H.13 As part of the continuing
effort to expand the synthetic utility of organoindium
reagents,14 we now report efficient intramolecular cycliza-
tions of 1-bromo-2,7- and 1-bromo-2,8-enynes with indium
(Scheme 1).
Our initial study focused on the use of N-(E)-4-bromo-2-
butenyl-N-propargyl-p-toluenesulfonamide (1a) as a cycliza-
tion substrate (Table 1). Although treatment of 1a with 1
Table 1. Reaction Optimization
time temp isolated yield
entry
X
additive solvent
(h)
(°C)
(%)a
1
2
3
4
5
6
7
8
9
Br
Br
Br
Br
Br
I
Br
Br
Br
THF
PhH
PhCH3
DMF
DMF
DMF
PhH
PhCH3
DMF
40
5
12
1
1
1
5
12
1
70
50
80
25
80
25
50
80
25
28
0
0
0
82
80
0
0
83
a Reactions were performed with 1 equiv of indium and 3 equiv of KI
unless otherwise noted. b Diastereomeric ratio. c KI was not used.
Klb
Klb
Klb
yield (entry 5). Reaction of 1b with indium gave the desired
product 10 in 80% yield (25 °C, 1 h, entry 6). Addition of
potassium iodide (3 equiv) as an additive to 1a gave the best
result and afforded the carbocycle 10 in 83% yield (25 °C,
1 h, entry 9). We believe that KI is involved in the generation
of allyl iodide derivatives during the cyclization reaction
because indium-mediated cyclization of 1a did not occur
without KI at 25 °C for 1 h. DMF was the best solvent among
several reaction media (DMF, THF, PhH, and PhCH3) that
were screened.
a Reaction performed with 1 equiv of indium and 1 equiv of substrate.
b Performed with 3 equiv of KI.
equiv of indium did not produce the desired product 10 (25
°C, DMF, entry 4), heating 1a at 80 °C gave 10 in 82%
(4) (a) Perez, I.; Sestelo, J. P.; Sarandeses, L. A. Org. Lett. 1999, 1,
1267. (b) Gelman, D.; Schumann, H.; Blum, J. Tetrahedron Lett. 2000, 41,
7555. (c) Lee, P. H.; Sung, S.-Y.; Lee, K. Org. Lett. 2001, 3, 3201. (d)
Perez, I.; Sestelo, J. P.; Sarandeses, L. A. J. Am. Chem. Soc. 2001, 123,
4155. (e) Hirashita, T.; Yamamura, H.; Kawai, M.; Araki, S. Chem.
Commun. 2001, 387. (f) Takami, K.; Yorimitsu, H.; Shnokubo, H.;
Matsubara, S.; Oshima, K. Org. Lett. 2001, 3, 1997. (g) Pena, M. A.; Perez,
I.; Sestelo, J. P.; Sarandeses, L. A. Chem. Commun. 2002, 2246. (h) Lee,
K.; Lee, J.; Lee, P. H. J. Org. Chem. 2002, 67, 8265. (i) Lee, K.; Seomoon,
D.; Lee, P. H. Angew. Chem., Int. Ed. 2002, 41, 3901. (j) Hirashita, T.;
Hayashi, Y.; Mitsui, K.; Araki, S. J. Org. Chem. 2003, 68, 1309. (k)
Lehmann, U.; Awasthi, S.; Minehan, T. Org. Lett. 2003, 5, 2405. (l) Lee,
P. H.; Lee, S. W.; Lee, K. Org. Lett. 2003, 5, 1103. (m) Pena, M. A.; Sestelo,
J. P.; Sarandeses, L. A. Synthesis 2003, 780. (n) Lee, P. H.; Lee, S. W.;
Seomoon, D. Org. Lett. 2003, 5, 4963. (o) Lee, S. W.; Lee, K.; Seomoon,
D.; Kim, S.; Kim, H.; Kim, H.; Shim, E.; Lee, M.; Lee, S.; Kim, M. Lee,
P. H. J. Org. Chem. 2004, 69, 4852.
The cyclizations of terminal 1-bromo-2,7- and 1-bromo-
2,8-enynes mediated by indium are summarized in Table 2.
(5) (a) Lee, P. H.; Sung, S.-Y.; Lee, K.; Chang, S. Synlett 2001, 146.
(b) Rodriguez, D.; Sestelo, J. P.; Sarandeses, L. A. J. Org. Chem. 2003,
68, 2518.
(6) (a) Ranu, B. C.; Majee, A. Chem. Commun. 1997, 1225. (b) Fujiwara,
N.; Yamamoto, Y. J. Org. Chem. 1997, 62, 2318. (c) Fujiwara, N.;
Yamamoto, Y. J. Org. Chem. 1999, 64, 4095.
(7) (a) Araki, S.; Imai, A.; Shimizu, K.; Yamada, M.; Mori, A.; Butsugan,
Y. J. Org. Chem. 1995, 60, 1841. (b) Araki, S.; Usui, H.; Kato, M.;
Butsugan, Y. J. Am. Chem. Soc. 1996, 118, 4699. (c) Klaps, E.; Schmid,
W. J. Org. Chem. 1999, 64, 7537.
4826
Org. Lett., Vol. 6, No. 26, 2004

Scheme 2
Table 3. Cyclization of Internal 1-Bromo-2,7-enynes Mediated
by Indiuma
Encouraged by these results, we next examined the
cyclization of internal 1-bromo-2,7-enynes (Table 3). Ex-
posure of 19 to indium in DMF at 100 °C produced the
desired product 23 in 60% yield (dr ) 1:3) (entry 1).
Although KI was used as an additive at 25 °C in this reaction,
23 was not produced.15 Phenyl, bromo, and trimethylsilyl
groups as substituents did not affect the cyclization, and
cyclopentane derivatives were obtained in good yields
(entries 2-4).
On the basis of the results above, the cyclization of diethyl
4-bromo-2-butyn-1-yl propargyl malonate (27) under a
variety of reaction conditions was attempted. Unfortunately,
the cyclized compound was not produced, but diethyl 2,3-
butadien-1-yl propargyl malonate (28) was obtained in 87%
yield (Scheme 2).
a Reactions were performed with 1 equiv of indium unless otherwise
noted. b Diastereomeric ratio. c Isolated yield of dehalogenated compound
14.
After N-(E)-4-bromo-2-butenyl-N-propargyl-p-toluene-
sulfonamide (1a) was treated with indium in the presence
of KI in DMF at 25 °C for 1 h, addition of 4 mol % Pd-
(PPh3)4, LiI (3 equiv), and 1-iodo-4-nitrobenzene (3 equiv)
to the reaction mixture gave coupling product 29 in 78%
yield. Subsequent iodolysis (3 equiv of I2, 25 °C, 18 h) under
the same reaction conditions produced vinyl iodide 30 in
58% yield (Scheme 3).
The terminal 1,6-enyne 2 reacted with indium in the presence
of 3 equiv of KI in DMF at 25 °C for 30 min to afford
3-methylene-4-vinyl tetrahydrofuran 11 in 90% yield (entry
2). Under the same conditions, propargyl ether 3 was cyclized
to give the desired product 12 in 95% yield (dr ) 1:3.1)
(entry 3). When the malonate-branched terminal 1,6-enyne
5 was treated with indium in the presence of KI, 14 was
obtained in 77% yield (entry 5). Similarly, intramolecular
cyclization of the bis(sulfone)- and phenylsulfonyl acetate-
branched terminal 1,6-enynes (6 and 7) proceeded smoothly
to produce cyclopentane derivatives (15 and 16) in good
yields (entries 6 and 7). This indium-mediated cyclization
was then extended to synthesize cyclohexane derivatives.
Although terminal 1-bromo-2,8-enyne 8 was not cyclized at
25 °C even in the presence of KI,15 heating enyne 8 at 100
°C for 30 min with indium produced 17 in 70% yield in the
absence of KI in DMF (entry 8). Cyclization of N-(E)-4-
bromo-2-butenyl-N-4-pentynyl-p-toluenesulfonamide to pre-
pare a cycloheptane derivative met with failure under the
present conditions.
Scheme 3
(8) (a) Collman, J. P.; Hegedus, L. S.; Norton, J. R.; Finke, R. G.
Principles and Applications of Organotransition Metal Chemistry; Univer-
sity Science Books: Mill Valley, CA, 1987. (b) Trost, B. M.; Krische, M.
J. Synlett 1988, 1. (c) Negishi, E.; Coperet, C.; Ma. S.; Liou, S.-Y.; Liu, F.
Chem. ReV. 1996, 96, 365. (d) Ojima, I.; Tzamarioudak, M.; Li, Z.; Donovan,
R. J. Chem. ReV. 1996, 96, 635. (e) Negishi, E. Organopalladium Chemistry;
Wiley-Interscience: New York, 2002; Vols. I and II. (f) Zhu, G.; Zhang,
Z. Org. Lett. 2003, 5, 3645.
(9) Kang, S.-K.; Lee, S.-W.; Jung, J.; Lim, Y. J. Org. Chem. 2002, 67,
4376.
(10) (a) Salter, M. M.; Sardo-Inffiri, S. Synlett 2002, 2068. (b) Nair, V.;
Ros, S.; Jayan, C. N.; Pillai, B. S. Tetrahedron 2004, 60, 1959.
(11) Kang, H.-Y; Kim, Y.-T.; Yu, Y.-K.; Cha, J. W.; Cho, Y. S.; Koh,
H. Y. Synlett 2004, 45.
In summary, we have demonstrated that cyclization of
1-bromo-2,7- and 1-bromo-2,8-enynes mediated by indium
produced five- and six-membered cyclic compounds in good
yield. KI was a necessary additive in the cyclization of
(14) (a) Lee, P. H.; Bang, K.; Lee, K.; Lee, C.-H.; Chang, S. Tetrahedron
Lett. 2000, 41, 7521. (b) Lee, P. H.; Seomoon, D.; Lee, K. Bull. Korean
Chem. Soc. 2001, 22, 1380. (c) Lee, P. H.; Bang, K.; Ahn, H.; Lee, K.
Bull. Korean Chem. Soc. 2001, 22, 1385. (d) Lee, P. H.; Lee, K.; Chang,
S. Synth. Commun. 2001, 31, 3189. (e) Lee, P. H.; Lee, K.; Sung, S.-Y.;
Chang, S. J. Org. Chem. 2001, 66, 8646. (f) Lee, P. H.; Seomoon, D.;
Kim, S.; Nagaiah, K.; Damle, S. V.; Lee, K. Synthesis 2003, 2189.
(15) Although starting material disappeared on TLC in the presence of
KI (3 equiv) at 25 °C, the desired product was not obtained and a
complicated TLC was observed.
(12) Yanada, R.; Nishimori, N.; Matsumura, A.; Fujii, N.; Takemoto,
Y. Tetrahedron Lett. 2002, 43, 4585.
(13) Takami, K.; Yorimitsu, H.; Oshima, K. Org. Lett. 2002, 4, 2993.
Org. Lett., Vol. 6, No. 26, 2004
4827

terminal 1-bromo-2,7-enynes to give the desired products at
25 °C. Treatment of terminal 1-bromo-2,8- and internal
1-bromo-2,7-enynes with indium afforded cyclic compounds
in good yields without KI at 100 °C in DMF. After
cyclizations, subsequent cross-coupling reaction and iodolysis
increase the usefulness of the present reaction. Further studies
to explain the utility and mechanism of this reaction are in
progress in our laboratory.
mass data were obtained from the central instrumental facility
in Kangwon National University.
Supporting Information Available: Experimental pro-
cedures and characterization data for all compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
Acknowledgment. This work was supported by the Korea
Research Foundation (KRF-2001-005-D00048). NMR and
OL048175R
4828
Org. Lett., Vol. 6, No. 26, 2004