4.6 A 1,2-hydrogen shiftwould thenoccur to formalkene 5,
which would subsequently isomerize4cꢀg to the thermo-
dynamically stable furan (6).7 On the basis of this mechan-
istic hypothesis, we anticipated the appropriate conditions
could facilitate carbene formation, and perhaps also dic-
tate the reactivity of this carbene.
reasoned that the variance was in part due to inconsistent
solubilization of the catalyst.10 Ultimately, we found that
readily soluble Zeise’s dimer ([(C2H4)PtCl2]2) was the opti-
mal catalyst for this transformation, affording furan 8in 90%
isolated yield at 1.5 mol % catalyst loading at room tem-
perature in 5 min.
Table 1. Optimization for Pt-Catalyzed Furan Formation
Scheme 1
As a test case for this study, we synthesized homopro-
pargylic alcohol 78 and subjected it to a variety of alkyne
activation conditions. We found that PtCl2, in combination
with an olefinic ligand, produced furan 8 in a range of yields
(Table 1).9 The alkene ligand was necessary for optimal
reactivity, as ligands such as Et3N, pyridine, PPh3, and CO
were less effective. Based on our observations of the differ-
ential reactivity of 0.05 and 1.0 equiv alkene ligand, we
(4) For select examples of metal-catalyzed cyclization approaches to
furans, see: (a) Dudnik, A. S.; Xia, Y.; Li, Y.; Gevorgyan, V. J. Am.
Chem. Soc. 2010, 132, 7645–7655. (b) Dudnik, A. S.; Sromek, A. W.;
Rubina, M.; Kim, J. T.; Kel’in, A. V.; Gevorgyan, V. J. Am. Chem. Soc.
2008, 130, 1440–1452. (c) Marshall, J. A.; Sehon, C. A. J. Org. Chem.
1995, 60, 5966–5968. (d) Seiller, B.; Bruneau, C.; Dixneuf, P. H. Tetra-
hedron 1995, 51, 13089–13102. (e) Gabriele, B.; Salerno, G.; Lauria, E. J.
Org. Chem. 1999, 64, 7687–7692. (f) Hashmi, A. S. K.; Schwarz, L.;
Choi, J. ꢀH.; Frost, T. M. Angew. Chem., Int. Ed. 2000, 39, 2285–2288.
(g) Liu, Y.; Song, F.; Song, Z.; Liu, M.; Yan, B. Org. Lett. 2005, 7, 5409–
5412. (h) Yoshida, M.; Al-Amin, M.; Shishido, K. Synthesis 2009, 2454–
2466. (i)Barluenga, J.; Riesgo, L.; Vicente, R.; Lopez, L. A.; Tomas, M. J.
Am. Chem. Soc. 2008, 130, 13528–13529. (j) Suhre, M. H.; Reif, M.;
Kirsch, S. F. Org. Lett. 2005, 7, 3925–3927. (k) Patil, N. T.; Wu, H.;
Yamamoto, Y. J. Org. Chem. 2005, 70, 4531–4534. (l) Yao, T.; Zhang, X.;
Larock, R. C. J. Am. Chem. Soc. 2004, 126, 11164–11165. (m) Marshall,
J. A.; Robinson, E. D. J. Org. Chem. 1990, 55, 3450–3451. (n) Waka-
bayashi, Y.; Fukuda, Y.; Shiragami, H.; Utimoto, K.; Nozaki, H.
Tetrahedron 1985, 41, 3655–3661. (o) Aponick, A.; Li, C. ꢀY.; Malinge,
J.; Marques, E. F. Org. Lett. 2009, 11, 4624–4627. (p) Egi, M.; Azechi, K.;
Akai, S. Org. Lett. 2009, 11, 5002–5005 and the references therein.
(5) For select reviews on regioselective syntheses of polysubstituted
heterocycles, see: (a) Schmuck, C.; Rupprecht, D. Synthesis 2007, 3095–
3110. (b) Kirsch, S. F. Org. Biomol. Chem. 2006, 4, 2076–2080.
(c) Brown, R. C. D. Angew. Chem., Int. Ed. 2005, 44, 850–852. (d)
Balme, G. Angew. Chem., Int. Ed. 2004, 43, 6238–6241. (e) Hou, X. L.;
Cheung, H. Y.; Hon, T. Y.; Kwan, P. L.; Lo, T. H.; Tong, S. Y.; Wong,
H. N. C. Tetrahedron 1998, 54, 1955–2020.
a Yield determined by GC with 4,40-tert-butylbiphenyl as the internal
standard. b Used instead of PtCl2. c Isolated yield.
ꢀ
ꢀ
The nature of the propargylic leaving group is impor-
tant. As depicted in Table 2, strongly dissociative leaving
groups caused a noticeable erosion in yield. Esters were
also ineffective (entry 4), as competing known processes of
propargylic carboxylates were likely occurring.1,11,12 In all
of these cases, the strong leaving group would be prone to
immediate ionization once the alkyne coordinates to the
(10) The variable times required for the ligandless conditions (entry
1) also suggest complications due to solubilization.
(11) Marion, N.; Nolan, S. P. Angew. Chem., Int. Ed. 2007, 46, 2750–
2752.
(12) Lactone i, which is geometrically constrained from undergoing
an analogous [3,3]-rearrangement, did produce the furan product.
Yields were still modest, however, underscoring the importance of a
weaker leaving group being necessary for generating these carbene
species effectively.
(6) A recent report described a similar mode of carbene generation
toward the formation of polycyclic compounds via [3 þ 2] cycloaddi-
tions. See: Saito, K.; Sogou, H.; Suga, T.; Kusama, H.; Iwasawa, N.
J. Am. Chem. Soc. 2011, 133, 689–691.
(7) For related cycloisomerizations of alkynyl azides, see: (a) Gorin,
D. J.; Davis, N. R.; Toste, F. D. J. Am. Chem. Soc. 2005, 127, 11260–
11261. (b) Hiroya, K.; Matsumoto, S.; Ashikawa, M.; Ogiwara, K.;
Sakamoto, T. Org. Lett. 2006, 8, 5349–5352. (c) Xia, Y.; Huang, G.
J. Org. Chem. 2010, 75, 7842–7854. (d) Wetzel, A.; Gagosz, F. Angew.
Chem., Int. Ed. 2011, 50, 7354–7358.
(8) See Supporting Information for experimental details.
(9) For select examples of the use of alkene ligands in platinum
catalysis, see: (a) Nakamura, I.; Bajracharya, G. B.; Wu, H.; Oishi, K.;
Mizushima, Y.; Gridnev, I. D.; Yamamoto, Y. J. Am. Chem. Soc. 2004,
126, 15423–15430. (b) Nakamura, I.; Mizushima, Y.; Yamamoto, Y.
J. Am. Chem. Soc. 2005, 127, 15022–15023.
(13) The efficacy of alkoxy leaving groups could arise from a facile
proton transfer process that generates an oxonium leaving group.
Additionally, the benign byproduct alcohol could be inconsequential
relative to the strongly acidic byproducts that would arise from the
substrates with more electron-withdrawing leaving groups.
Org. Lett., Vol. 13, No. 21, 2011
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