In this Letter, we demonstrate that the zinc-mediated
decomposition of dienyl azides provides a general method
for the synthesis of pyrroles.
We recently reported that rhodium(II) catalyzed the
construction of indoles from azidoacrylates.16 We wanted
to extend this chemistry to the formation of pyrroles from
dienyl azides (Table 1) and found that rhodium(II) perfluo-
only efficient catalyst for indole formation,16 a range of metal
salts smoothly catalyzed pyrrole 4 from dienyl azide 3
(entries 4-7).17 Both copper(II) triflate and zinc iodide
transformed 3 into pyrrole 4 at room temperature (entries 5
and 7). Diminished yields were observed with other Lewis
acids, including mercury(II) triflate (entry 8),18 gold(I) triflate
(entry 9),19 rhodium(II,III) caprolactamate (entry 10),20 or
triflic acid (entry 11).21 Optimization of the solvent revealed
that methylene chloride was superior to ethereal or aromatic
solvents.
Table 1. Optimization of Pyrrole Formation
The most reactive catalysts were compared by examining
the reaction progress after 3 h (Table 2). Both copper(II)
temp
(°C)
yielda
(%)
Table 2. Examination of Catalyst Reactivity
entry
catalyst
none
Rh2(O2CC3F7)4
Rh2(OAc)4
(CuOTf)2‚PhH
Cu(OTf)2
ZnCl2
mol %
solvent
1
2
3
4
5
6
7
8
9
n.a.
2
10
5
5
5
5
5
10
10
2
40
40
40
25
25
25
25
25
25
25
25
PhMe
PhMe
PhMe
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
PhMe
14
>95
11
90
>95
86
>95
39b
n.r.
n.r.
dec.b
entry
catalyst
conversiona (%)
1
2
3
4
5
Rh2(O2CC3F7)4
ZnI2
Cu(OTf)2
(CuOTf)2‚PhH
ZnCl2
40
53
64
30
34
ZnI2
Hg(OTf)2
AuOTf
Rh2(cap)4Brc
HOTf
10
11
CH2Cl2
1
a As determined using H NMR spectroscopy.
a As determined using 1H NMR spectroscopy. b Complete consumption
of 1 was observed. c cap ) caprolactamate.
triflate and zinc iodide were found to be more reactive than
Rh2(O2CC3F7)4 (entries 2 and 3). Changing the oxidation state
of copper or the counterion of the zinc salt inhibited the
reaction progress (entries 4 and 5). While copper(II) triflate
and zinc iodide exhibited similar activities, we chose to focus
method development on the less expensive zinc salt ($0.40/g
versus $10/g).22,23
The scope and limitations of the method were subsequently
investigated (Table 3).24 The reaction tolerated both electron-
rich and electron-poor aryl substituents (entries 1-12). As
robutyrate efficiently promoted this process (entry 2). As
before,16 increasing the electron-donating nature of the
carboxylate ligand significantly reduced the reactivity of the
catalyst (entry 3). While rhodium(II) perfluorobutyrate is the
(11) (a) Hemetsberger, H.; Spira, I.; Schoenfelder, W. J. Chem. Res. (S)
1977, 247. (b) Boukou-Poba, J. P.; Farnier, M.; Guilard, R. Tetrahedron
Lett. 1979, 20, 1717. (c) Moody, C. J.; Rees, C. W.; Rodrigues, J. A. R.;
Tsoi, S. C. J. Chem. Res. (S) 1985, 238. (d) Hinz, W.; Jones, R. A.; Patel,
S. U.; Karatza, M.-H. Tetrahedron 1986, 42, 3753. (e) Geist, B.; Knittel,
D. Monatsh. Chem. 1988, 119, 571. (f) Pinna, G. A.; Loriga, G.; Murineddu,
G.; Grella, G.; Mura, M.; Vargiu, L.; Murgioni, C.; La Colla, P. Chem.
Pharm. Bull. 2001, 49, 1406.
(12) For reviews of azide reactivity, see: (a) L’abbe´, G. Angew. Chem.,
Int. Ed. Engl. 1975, 14, 775. (b) Scriven, E. F. V.; Turnbull, K. Chem.
ReV. 1988, 88, 297. (c) Bra¨se, S.; Gil, C.; Knepper, K.; Zimmermann, V.
Angew. Chem., Int. Ed. 2005, 44, 5188.
(13) For recent discussions of Lewis acidity, see: (a) Kobayashi, S.;
Busujuma, T.; Nagayama, S. Chem.sEur. J. 2000, 6, 3491. (b) Lewis Acids
in Organic Synthesis; Yamamoto, H., Ed.; Wiley-VCH: Weinheim,
Germany, 2000; Vols. 1, 2. (c) Kobayashi, S.; Manabe, K. Acc. Chem. Res.
2002, 35, 209. (d) Yamamoto, Y. J. Org. Chem. 2007, 72, 7817.
(14) For recent examples, see: (a) Bernardi, L.; Zhuang, W.; Jørgensen,
K. A. J. Am. Chem. Soc. 2005, 127, 5772. (b) Nicewicz, D. A.; Johnson,
J. S. J. Am. Chem. Soc. 2005, 127, 6170. (c) Berliner, M. A.; Belecki, K.
J. Org. Chem. 2005, 70, 9618. (d) Hatano, M.; Suzuki, S.; Ishihara, K. J.
Am. Chem. Soc. 2006, 128, 9998. (e) Trost, B. M.; Lupton, D. W. Org.
Lett. 2007, 9, 2023.
(15) (a) Evans, D. A.; Truesdale, L. K. Tetrahedron Lett. 1973, 14, 4929.
(b) Miller, J. A. Tetrahedron Lett. 1975, 16, 2959. (c) Prakash, G. K. S.;
Iyer, P. S.; Arvanaghi, M.; Olah, G. A. J. Org. Chem. 1983, 48, 3358. (d)
Farooq, O.; Wang, Q.; Wu, A.-H.; Olah, G. A. J. Org. Chem. 1990, 55,
4282. (e) Himo, F.; Demko, Z. P.; Noodleman, L.; Sharpless, K. B. J. Am.
Chem. Soc. 2003, 125, 9983. (f) Lebel, H.; Leogane, O. Org. Lett. 2005, 7,
4107. (g) Hajra, S.; Sinha, D.; Bhowmick, M. Tetrahedron Lett. 2006, 47,
7017.
(17) For reviews of Lewis acid mediated Schmidt reactions involving
azide additions to olefins, see: (a) Judd, W. R.; Katz, C. E. Aube´, J. Sci.
Synth. 2005, 21, 133. (b) Lang, S.; Murphy, J. A. Chem. Soc. ReV. 2006,
35, 146.
(18) For examples of mercury-promoted azide additions to olefins, see:
(a) Heathcock, C. H. Angew. Chem., Int. Ed. Engl. 1969, 8, 134. (b) Galle,
J. E.; Hassner, A. J. Am. Chem. Soc. 1972, 94, 3930. (c) Marchand, A. P.;
Sorokin, V. D.; Rajagopal, D.; Bott, S. G. Synth. Commun. 1994, 24, 3141.
(d) Pearson, W. H.; Hutta, D. A.; Fang, W.-k. J. Org. Chem. 2000, 65,
8326.
(19) For gold-mediated additions of azides to acetylenes, see: Gorin,
D. J.; Davis, N. R.; Toste, F. D. J. Am. Chem. Soc. 2005, 127, 11260.
(20) For the use of the mixed-valent rhodium(II,III) complexes as Lewis
acids, see: Catino, A. J.; Nichols, J. M.; Forslund, R. E.; Doyle, M. P.
Org. Lett. 2005, 7, 2787.
(21) For examples of Brønsted acid mediated additions of azides to
olefins, see: (a) Pearson, W. H.; Schkeryantz, J. M. Tetrahedron Lett. 1992,
33, 5291. (b) Pearson, W. H.; Walavalkar, R.; Schkeryantz, J. M.; Fang,
W.-k.; Blickensdorf, J. D. J. Am. Chem. Soc. 1993, 115, 10183. (c) Pearson,
W. H.; Fang, W.-k. J. Org. Chem. 2000, 65, 7158. (d) Mahoney, J. M.;
Smith, C. R.; Johnston, J. N. J. Am. Chem. Soc. 2005, 127, 1354.
(22) From Sigma-Aldrich: 98% Cu(OTf)2, 5 g, $51.40 (283673); g98%
ZnI2, 50 g, $19.90 (223883).
(23) Refer to the Supporting Information for a tabular comparison of
the reactivities of the dienyl azides with Cu(OTf)2 and Rh2(O2CC3F7)4
catalysts.
(16) Stokes, B. J.; Dong, H.; Leslie, B. E.; Pumphrey, A. L.; Driver, T.
G. J. Am. Chem. Soc. 2007, 129, 7500.
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Org. Lett., Vol. 9, No. 25, 2007