heteroatom bond formation strategies.6-14 For instance, we
recently reported Yb(OTf)3 to be an efficient catalyst for the
regioselective formation of conjugated enynes based on
nucleophilic ring opening of unactivated 1-cyclopropyl-2-
propyn-1-ols with aryl sulfonamides.7 On the basis of these
earlier studies we reasoned that a strategy that made use of
propargylic alcohols8 and phenols in the presence of a rare
earth metal Lewis acid catalyst9 would hold promise as a
new method for indenol synthesis. To our knowledge,
approaches to indenes that explore combining ecologically
benign Lewis acid catalysts10 with propargylic alcohols have
thus far been limited to three recent reports describing the
synthesis of 3-phenyl-1H-indenes,11 spiroindenes,12 and
indenyl sulfonamides.13 In addition, those that involve the
use of phenols have been previously reported to typically
give the propargylation, benzofuran, and benzopyran
products.6i,14 As part of an ongoing program examining the
utility of alcohols in organic synthesis,7,15 we report herein
the use of Yb(OTf)3 for tandem Friedel-Crafts alkylation/
hydroarylation of propargylic alcohols with phenols (Scheme
1). The reactions were found to proceed to give 6-indenols
Scheme 1
.
Yb(OTf)3-Catalyzed Formation of 6-Indenols from
Propargylic Alcohols and Phenols
(5) (a) Ahn, J. H.; Shin, M. S.; Jung, S. H.; Kwang, R. K.; Rhee, S. D.;
Jung, H. W.; Yang, S. D.; Kim, S. J.; Woo, J. R.; Lee, J. H.; Cheon, H. G.;
Kim, S. S. J. Med. Chem. 2006, 49, 4781. (b) Clegg, N. J.; Paruthiyil, S.;
Leitman, D. C.; Scanlan, T. S. J. Med. Chem. 2005, 48, 5989. (c) Anstead,
G. M.; Ensign, J. L.; Peterson, C. S.; Katzenellenbogen, J. A. J. Org. Chem.
1989, 54, 1485. (d) Friedman, S.; Kaufman, M. L.; Blaustein, B. D.; Dean,
R. E.; Wender, I. Tetrahedron 1965, 21, 485. (e) Sliverman, M.; Bogert,
M. T. J. Org. Chem. 1946, 11, 34. (f) Solmssen, U. V. J. Am. Chem. Soc.
1943, 65, 2370. (g) Plentl, A. A.; Bogert, M. T. J. Am. Chem. Soc. 1941,
63, 989.
in good to excellent yields up to 99% and with complete
regioselectivity for a wide variety of substrates under mild
conditions.
Initially, we chose to focus our attention on the reaction
of 1,1,3-triphenylprop-2-yn-1-ol 1a and 2,6-dimethylphenol
2a by a variety of Lewis acid catalysts to establish the
reaction conditions (Table 1). This revealed treating a
(6) For selected recent examples, see 4e, i, o, p and (a) Yoshimatsu,
M.; Yamamoto, T.; Sawa, A.; Kato, T.; Tanabe, G.; Muraoka, O. Org. Lett.
2009, 11, 2952. (b) Li, G. T.; Zhang, G. Z.; Zhang, L. M. J. Am. Chem.
Soc. 2008, 130, 3740. (c) Ito, H.; Yusuke, Y.; Sawamura, M. J. Am. Chem.
Soc. 2008, 120, 15774. (d) Yoshimatsu, M.; Otani, T.; Matsuda, S.;
Yamamoto, T.; Sawa, A. Org. Lett. 2008, 10, 4251. (e) Huang, W.; Shen,
Q. S.; Wang, J. L.; Zhou, X. G. J. Org. Chem. 2008, 73, 1586. (f) Sanz,
´
R.; Miguel, D.; Mart´ınez, A.; Alvarez-Gutie´rrez, J. M.; Rodr´ıguez, F. Org.
Lett. 2007, 9, 727. (g) Zhan, Z.-P.; Cai, X.-B.; Wang, S.-P.; Yu, J.-L.; Liu,
H.-J.; Cui, Y.-Y. J. Org. Chem. 2007, 72, 9838. (h) Qin, H.; Yamagiwa,
N.; Matsunaga, S.; Shibasaki, M. Angew. Chem., Int. Ed. 2007, 46, 409. (i)
Zhan, Z.-P.; Yu, J.-L.; Liu, H.-J.; Cui, Y.-Y.; Yang, R.-F.; Yang, W.-Z.;
Li, J.-P. J. Org. Chem. 2006, 71, 8298. (j) Georgy, M.; Boucard, V.;
Campagne, J. M. J. Am. Chem. Soc. 2005, 127, 14180.
Table 1. Optimization of Reaction Conditionsa
(7) Rao, W.; Zhang, X.; Sze, E. M. L.; Chan, P. W. H. J. Org. Chem.
2009, 74, 1740.
(8) For reviews on the use of propargylic alcohols as pro-electrophiles,
see: (a) Bandini, M.; Tragni, M. Org. Biomol. Chem. 2009, 7, 1501. (b)
Muzart, J. Tetrahedron 2008, 64, 5815. (c) Muzart, J. Eur. J. Org. Chem.
2007, 3077. (d) Muzart, J. Tetrahedron 2005, 61, 4179. (e) Tamaru, Y.
Eur. J. Org. Chem. 2005, 2647.
entry
catalyst
solvent
yield (%)b
1
2
3
4
5
6
7
8
Yb(OTf)3
Yb(OTf)3
Yb(OTf)3
Cu(OTf)2
InCl3
FeCl3·6H2O
AlCl3
AuBr3
MeNO2
MeCN
90
77
86
46
47
c
26
85
82
64
72d
(9) For other lanthanide-catalyzed reactions of alcohol pro-electrophiles,
see refs 6a and 6e and (a) Noji, M.; Konno, Y.; Ishii, K. J. Org. Chem.
2007, 72, 5161. (b) Huang, W.; Wang, J.; Shen, Q.; Zhou, X. Tetrahedron
Lett. 2007, 48, 3969. (c) Tsuchimoto, T.; Tobita, K.; Hiyama, T.; Fukuzawa,
S. J. Org. Chem. 1997, 62, 6997. (d) Tsuchimoto, T.; Tobita, K.; Hiyama,
T.; Fukuzawa, S. Synlett 1996, 557.
(CH2Cl)2
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
(10) For recent reviews, see: (a) Lewis Acids in Organic Synthesis;
Yamamoto, H., Ed.; Wiley-VCH Verlag GmbH: Weinheim; Vols. 1 and 2,
2000. (b) Carbocation Chemistry; Olah, G. A., Prakash, G. K. S., Eds.;
John Wiley & Sons: New York, 2004. (c) Nakamura, I.; Yamamoto, Y.
Chem. ReV. 2004, 104, 2127. (d) Kagan, H. B. Chem. ReV. 2002, 102, 1805.
(11) Shchukin, A. O.; Vasil’ev, A. V. Russ. J. Org. Chem. 2007, 43,
784.
9
10
11
PtCl2
TfOH
TfOH
a All reactions were performed at 80 °C for 24 h with catalyst/1a/2a
ratio ) 1:10:20. b Isolated yield. c Mixture of unknown side products
afforded based on 1H NMR analysis of the crude mixture. d Reaction
conducted with TfOH catalyst loading of 20 mol %.
(12) Huang, W.; Zheng, P. Z.; Zhang, Z. X.; Liu, R.; Chen, Z. X.; Zhou,
X. G. J. Org. Chem. 2008, 73, 6845.
(13) Wang, S. Y.; Zhu, Y. X.; Wang, Y. G.; Lu, P. Org. Lett. 2009, 11,
2615.
(14) Selected recent examples: (a) Gabriele, B.; Mancuso, R.; Salerno,
G. J. Org. Chem. 2008, 73, 7336. (b) Srihari, P.; Reddy, J. S. S.; Mandal,
S. S.; Satyanarayana, K.; Yadav, J. S. Synthesis 2008, 1853. (c) Srihari, P.;
Bhunia, D. C.; Sreedhar, P.; Mandal, S. S.; Reddy, J. S. S.; Yadav, J. S.
Tetrahedron Lett. 2007, 48, 8120. (d) Kumar, M. P.; Liu, R.-S. J. Org.
Chem. 2006, 71, 4951. (e) Zhan, Z.-P.; Yang, W.-Z.; Yang, R.-F.; Yu, J.-
L.; Li, J.-P.; Liu, H.-J. Chem. Commun. 2006, 3352. (f) Sanz, R.; Mart´ınez,
solution of reaction containing 1a (1 equiv) and 2a (2 equiv)
with 10 mol % Yb(OTf)3 at 80 °C for 24 h gave the best
result (entry 1). Under these conditions, 5,7-dimethyl-1,1,3-
triphenyl-1H-inden-6-ol 3a was afforded in 90% yield. The
indenol product was confirmed by 1H NMR analysis and an
X-ray crystal structure determination of a closely related
product (see below). On the other hand, a slightly lower
product yield was observed when the reaction was performed
´
A.; Alvarez-Gutie´rrez, J. M.; Rodr´ıguez, F. Eur. J. Org. Chem. 2006, 1383.
(g) Kennedy-Smith, J. J.; Young, L. A.; Toste, F. D. Org. Lett. 2004, 6,
1325. (h) Zhao, W.; Carreira, E. M. Org. Lett. 2003, 5, 4153. (i)
Nishibayashi, Y.; Inada, Y.; Yoshikawa, M.; Hidai, M.; Uemura, S. Angew.
Chem., Int. Ed. 2003, 42, 1495. (j) Nishibayashi, Y.; Inada, Y.; Hidai, M.;
Uemura, S. J. Am. Chem. Soc. 2002, 124, 7900.
Org. Lett., Vol. 11, No. 21, 2009
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