SmI2-mediated synthesis of 2,4-diarylpyrroles from phenacyl azides

Article abstract of DOI:10.1016/S0040-4039(02)00108-9

A novel reduction of phenacyl azides induced by SmI₂ was investigated and 2,4-diarylpyrroles were prepared in moderate to good yields under mild conditions.

Full text of DOI:10.1016/S0040-4039(02)00108-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 1863–1865
SmI -mediated synthesis of 2,4-diarylpyrroles from
2
phenacyl azides
a,c
a,b,
Xuesen Fan and Yongmin Zhang
*
a
Department of Chemistry, Zhejiang University (Campus Xixi ), Hangzhou 310028, PR China
b
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
Shanghai 200032, PR China
c
Department of Chemistry, Henan Normal University, Xinxiang 453002, PR China
Received 25 October 2001; revised 2 January 2002; accepted 14 January 2002
Abstract—A novel reduction of phenacyl azides induced by SmI2 was investigated and 2,4-diarylpyrroles were prepared in
moderate to good yields under mild conditions. © 2002 Elsevier Science Ltd. All rights reserved.
The synthesis of pyrroles is an important area of hete-
rocyclic chemistry due primarily to the fact that many
pyrroles are subunits of natural products, pharmaceuti-
We found that SmI can efficiently promote the reduc-
2
tion of phenacyl azides at room temperature. This
reductive process is completed within a few minutes and
affords 2,4-diarylpyrroles in fair yields. In addition,
both phenacyl azides bearing electron-donating groups
1
cal agents and polymers. A wide variety of chemistry
2
has been used for the preparation of pyrroles, but most
of the available methods lead to pyrroles which are
substituted at various positions with functional groups
and thus require further synthetic operations to afford
simple alkyl or aryl substituted pyrroles. In particular,
synthetic routes to simple 2,4-diaryl substituted pyrroles
(
4-Me and 4-OMe, entries 2 and 3, Table 1) and
phenacyl azides bearing electron-withdrawing groups
4-Br and 4-Cl, entries 4 and 5, Table 1) underwent
(
smooth reduction under the same conditions. The
absence of observable substituent effect suggests that
this method may afford a general method for the
preparation of 2,4-diarylpyrroles bearing various sub-
stituents on the aryl rings.
3
are limited and convenient procedures for preparing
2
,4-diarylpyrroles with substituents on the aryl rings are
3e
even more rare.
4
Kagan’s reagent, samarium(II) iodide is an exceptional
reagent for promoting reductive reactions, and the
Although the detailed mechanism of the above reaction
has not been clarified, a plausible mechanism (shown in
chemistry of this reagent has been well documented in
5
several reviews. The reactivity of SmI towards various
2
6
nitrogen-containing organic compounds including
Table 1. Reduction of phenacyl azides mediated by SmI2
nitro compounds, imines, oximes, hydrazones and azo
compounds has already been examined and it has been
reported that SmI can efficiently promote the reduc-
2
tion of alkyl, aryl and aroyl azides to give the corre-
7
sponding primary amines and amides. However, to our
knowledge, there are no literature precedents for the
reduction of phenacyl azides by this reagent. In this
Entry
Ar
Reaction time (min)
Yield (%)a
8
report, we describe, for the first time, the efficient
reduction of phenacyl azides upon treatment with SmI2
to afford 2,4-diarylpyrroles in moderate to good yields.
The results are summarized in Table 1.
1
2
3
4
5
6
C H
4-CH C H
4-CH OC H
4
4-BrC
4-ClC H
5
5
5
5
5
72
70
65
76
75
56
6
5
3
6
4
3
6
H
4
6
6
4
2-Naphthyl
10
Keywords: samarium(II) iodide; pyrroles; phenacyl azides; reduction.
a
*
Corresponding author. E-mail: yminzhang@mail.hz.zj.cn
Isolated yields based on phenacyl azides.
0
040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00108-9

1
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X. Fan, Y. Zhang / Tetrahedron Letters 43 (2002) 1863–1865
Scheme 1.
Scheme 1) for the formation of 2,4-diarylpyrroles is
proposed based on the literature. In a first step, the
treatment with SmI , 2-azidopropiophenone (4) was
transformed into propiophenone (5) rather than the
expected 2,4-diphenyl-3,5-dimethylpyrrole (6).
2
cleavage of the CꢀN bond takes place through two
3
SET (single electron transfer) processes with SmI2
donating two electrons sequentially and leads to the
In conclusion, with high yields, mild and neutral condi-
9
10
corresponding enolate (a). By abstracting a proton
tions as well as easily accessible starting materials, the
from another substrate molecule, (a) is transformed8
present work may provide a useful method for the
11
into a new enolate (b) and the aryl methyl ketone (3).
preparation of 2,4-diarylpyrroles. Further studies to
Then enolate (b) loses a N molecule to be transformed
clarify the mechanism of this process and to develop
2
into anion (c). As a strong base, anion (c) can abstract
a proton from acetophenone (3) to afford the phenyl
glyoxal imino intermediate (d) and enolate (a). Reac-
tion of the phenyl glyoxal imino intermediate (d) and
other new uses of SmI are now in progress in our
2
laboratory.
enolate (a) followed by the loss of two HOSmI frag-
Acknowledgements
2
ments from the resulting intermediate (e) gives the
2,4-diarylpyrrole (2) as the final product.
We are grateful to the National Natural Science Foun-
dation of China (Project No. 20072033) and the NSF of
Zhejiang province for financial support.
Another possible mechanism for the formation of 2,4-
diarylpyrroles may involve the concurrent formation
and reaction of enolate (a) and intermediate (d). While
enolate (a) may be formed through the cleavage of the
CꢀN bond mediated by SmI , the formation of inter-
3
2
References
mediate (d) probably involves a one-electron transfer
process from SmI to the azido group to give an aminyl
2
7
c
1
2
. Comprehensive Heterocyclic Chemistry; Katritzky, A.;
Rees, C. W.; Scriven, E. F. V., Eds.; Pergamon: Oxford,
radical, which could then be transformed into inter-
mediate (d) upon receipt of another electron from SmI2.
1996; Vol. 2, pp. 1–257.
. (a) Sundberg, R. J. In Comprehensive Heterocyclic Chem-
istry; Katritzky, A.; Rees, C. W.; Scriven, E. F. V., Eds.;
Pergamon: Oxford, 1996; Vol. 2, pp. 119–206; (b)
Gilchrist, T. L. J. Chem. Soc., Perkin Trans. 1 1999, 2849;
In addition, the reduction of 2-azidopropiophenone (4)
was also investigated (as shown in Scheme 2). On
(
6
c) Gilchrist, T. L. J. Chem. Soc., Perkin Trans. 1 1998,
15.
3
. (a) Campi, E. M.; Fallon, G. D.; Jackson, W. R.;
Nilsson, Y. Aust. J. Chem. 1992, 45, 1167; (b) Buchwald,
S. L.; Wannamaker, M. W.; Watson, B. T. J. Am. Chem.
Soc. 1989, 111, 776; (c) Nitta, M.; Kobayashi, T. Chem.
Lett. 1983, 1715; (d) Padwa, A.; Gruber, R.; Pashayan,
D. J. Org. Chem. 1968, 33, 454; (e) Deady, L. W.
Tetrahedron 1967, 23, 3505; (f) Sato, S.; Kato, H.; Ohta,
Scheme 2.

X. Fan, Y. Zhang / Tetrahedron Letters 43 (2002) 1863–1865
1865
M. Bull. Chem. Soc. Jpn. 1967, 40, 2936; (g) Allen, C. F.;
Wilson, C. V. Organic Synthesis; Wiley: New York, 1947;
Vol. 27, p. 22.
a-haloester to give an enolate, see: (a) Zhang, Y. M.; Liu,
T. C.; Lin, R. H. Synth. Commun. 1988, 18, 2003; (b)
Molander, G. A.; Hahn, G. J. Org. Chem. 1986, 51, 1135.
10. Phenacyl azides were conveniently prepared from
phenacyl bromides and sodium azide according to the
following literature: Boyer, H. J.; Straw, D. J. J. Am.
Chem. Soc. 1953, 75, 1642.
4
. Girard, P.; Namy, J. L.; Kagan, H. B. J. Am. Chem. Soc.
1
980, 102, 2693.
5
. For reviews, see: (a) Krief, A.; Laval, A. M. Chem. Rev.
1999, 99, 745; (b) Molander, G. A. Acc. Chem. Res. 1998,
31, 603; (c) Molander, G. A.; Harris, C. R. Tetrahedron
1998, 54, 3321; (d) Molander, G. A.; Harris, C. R. Chem.
11. Representative procedure: A solution of phenacyl azide (1
mmol) in dry THF (3 mL) was added dropwise to a
Rev. 1996, 96, 307; (e) Imamota, T. In Lanthanides in
Organic Synthesis; Academic Press: London, 1994; Chap-
ter 4; (f) Molander, G. A. Chem. Rev. 1992, 92, 29; (g)
Curran, D. P.; Fevig, T. L.; Jasperse, C. P.; Totleben, M.
J. Synlett 1992, 943.
. (a) Souppe, J.; Danon, L.; Namy, J. L.; Kagan, H. B. J.
Organomet. Chem. 1983, 250, 227; (b) Zhang, Y. M.; Lin,
R. H. Synth. Commun. 1987, 17, 329; (c) Mukaiyama, T.;
Yoyozu, K.; Kato, K.; Yamada, T. Chem. Lett. 1982,
solution of SmI (2.5 mmol) in THF (20 mL) at room
2
temperature under a nitrogen atmosphere. The deep blue
color of the solution changed to yellow immediately.
After stirring for ca. 5 min, the reaction mixture was
quenched with dilute HCl (0.1 mol/L, 3 mL) and
extracted with ether (3×20 mL). The organic phase was
6
successively washed with a saturated solution of Na
(10 mL), saturated brine (10 mL), and dried over anhy-
drous Na SO . The solvent was removed under reduced
S O
2 2 3
2
4
1
81; (d) Kende, A. S.; Mendoza, J. S. Tetrahedron Lett.
pressure to give the crude product, which was purified by
preparative TLC using ethyl acetate and cyclohexane
(1:6) as eluant to yield 2,4-diphenylpyrrole (72%), mp
1
991, 32, 1699.
7
. (a) Natale, N. R. Tetrahedron Lett. 1982, 23, 5009; (b)
Benati, L.; Monievecohi, P. C.; Nanni, D.; Spagnolo, P.;
Volta, M. Tetrahedron Lett. 1995, 36, 7313; (c) Gou-
laouic-Dubois, C.; Hesse, M. Tetrahedron Lett. 1995, 36,
3a
166–169°C (lit. 166–170°C); IR (KBr): w 3350 (NH)
−
1 1
cm ; H NMR (400 MHz, DMSO): l 6.95 (t, 1H, J=2
Hz), 7.10–7.19 (m, 2H), 7.30–7.39 (m, 5H), 7.61 (d, 2H,
J=7.2 Hz), 7.68 (d, 2H, J=7.6 Hz), 11.3 (bs, 1H, NH);
7
427.
13
8
. For electrochemical reduction of phenacyl azides leading
to the formation of 2-aroyl-4-arylimidazoles rather than
2
C NMR (100 MHz, DMSO): l 103.7, 117.1, 123.9,
124.9, 125.2, 125.5, 126.2, 129.0, 129.2, 132.7, 133.1,
+
,4-diarylpyrroles, see: Batanero, B.; Escudero, J.; Barba,
136.2; MS m/z (%): 219 (M , 100), 191 (13), 116 (17), 115
F. Org. Lett. 1999, 1, 1521.
(21), 89 (6), 77 (5). Anal. calcd for C16
5.98; N, 6.39. Found: C, 87.57; H, 6.08; N, 6.34.
H13N: C, 87.67; H,
9
. For SmI -mediated dehalogenation of a-haloketone or
2