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Table 2 Scope of Pd(OCOCF3)2-catalyzed synthesis of pyrroles 4a
New York, 1992; (c) Pyrroles, Part II, ed. R. A. Jones, Wiley,
New York, 1992; (d) C. T. Walsh, S. Garneau-Tsodikova and
A. R. Howard-Jones, Nat. Prod. Rep., 2006, 23, 517; (e) F. Bellina
and R. Rossi, Tetrahedron, 2006, 62, 7213.
2 P. Cozzi and N. Mongelli, Curr. Pharm. Des., 1998, 4, 181.
3 G. Daidone, B. Maggio and D. Schillari, Pharmazie, 1990, 45, 441.
4 A. M. Almerico, P. Diana, P. Barraja, G. Dattolo, F. Mingoia,
A. G. Loi, F. Scintu, C. Milia, I. Puddu and P. La Colla, Farmaco,
1998, 53, 33.
5 (a) R. A. Jones, Pyrroles, Part II, The Synthesis, Reactivity and Physical
Properties of Substituted Pyrroles, Wiley, New York, 1992;
(b) E. T. Pelkey, Prog. Heterocycl. Chem., 2005, 17, 109.
6 D. H. R. Barton and S. Z. Zard, J. Chem. Soc., Chem. Commun., 1985,
1098.
7 (a) L. Knorr, Ber. Dtsch. Chem. Ges., 1884, 17, 1635; (b) C. Paal,
Ber. Dtsch. Chem. Ges., 1885, 18, 367.
Entrya
R1, R2, R3, R4, 4
Yieldb (%)
1
2
3
4
5
6
7
8
Me, Me, H, 4-MeOPh, 4a
Me, Me, H, 3-MeOPh, 4b
Me, Me, H, 2-MeOPh, 4c
Me, Me, H, Ph, 4d
Me, Me, H, 4-MePh, 4e
Me, Me, H, 4-CF3OPh, 4f
Me, Me, H, 4-PhOPh, 4g
Me, Me, H, 2-naphthyl, 4h
Me, Me, H, 3,4-MePh, 4i
Me, Me, H, 2-Me-4-MeOPh, 4j
Me, Me, H, 3-FPh, 4k
Me, Me, H, 4-NO2Ph, 4l
Me, Me, H, 4-MeO-benzyl, 4m
Me, Me, H, isopentyl, 4n
Et, Et, H, 4-MeOPh, 4o
Me, Ph, H, 4-MeOPh, 4p
Me, Ph, H, Ph, 4q
88
86
70
77
82
81
84
84
85
74
50
40
91
90
83
78
75
85
60
8 A. Hantzsch, Ber. Dtsch. Chem. Ges., 1890, 23, 1474.
9 D. C. Black, in Science of Synthesis, ed. G. Maas, Georg Thieme
Verlag, Stuttgart, New York, 2001, vol. 9, p. 441.
9
10 For recent reviews, see: (a) I. Dion and A. M. Beauchemin, Angew.
Chem., Int. Ed., 2011, 50, 8233; (b) D. Crozet, M. Urrutigoity and
P. Kalck, ChemCatChem, 2011, 3, 1102; (c) G. Zi, J. Organomet. Chem.,
2010, 696, 68; (d) N. T. Patil and V. Singh, J. Organomet. Chem., 2010,
696, 419; (e) J. Jenter, A. Luehl, P. W. Roesky and S. Blechert,
J. Organomet. Chem., 2010, 696, 406; ( f ) K. D. Hesp and
M. Stradiotto, ChemCatChem, 2010, 2, 1192; (g) A. S. K. Hashmi
and C. Hubbert, Angew. Chem., Int. Ed., 2010, 49, 1010; (h) S. R.
Chemler, Org. Biomol. Chem., 2009, 7, 3009; (i) P. W. Roesky, Angew.
Chem., Int. Ed., 2009, 48, 4892; ( j) T. E. Mueller, K. C. Hultzsch,
M. Yus, F. Foubelo and M. Tada, Chem. Rev., 2008, 108, 3795;
(k) J.-J. Brunet, N.-C. Chu and M. Rodriguez-Zubiri, Eur. J. Org.
Chem., 2007, 4711; (l) R. Severin and S. Doye, Chem. Soc. Rev., 2007,
36, 1407; (m) R. A. WidenHoefer and X. Han, Eur. J. Org. Chem., 2006,
4555; (n) K. K. Hii, Pure Appl. Chem., 2006, 78, 341; (o) K. C. Hultzsch,
Adv. Synth. Catal., 2005, 347, 367; (p) S. Hong and T. J. Marks, Acc.
Chem. Res., 2004, 37, 673; (q) P. W. Roesky and T. E. Mueller, Angew.
Chem., Int. Ed., 2003, 42, 2708.
10
11c
12c
13
14
15
16
17
18
19
Me, OEt, H, 4-MeOPh, 4r
Me, Me, Ph, 4-MeOPh, 4s
a
A solution of 1 (1.2 mmol) and 2 (0.6 mmol) with catalyst (0.12 mmol)
b
c
in xylenes (2 mL) was stirred at 60 1C for 16 h. Isolated yield. 20 mol%
catalyst used.
Pd–alkyl intermediate IV,19 which can undergo second
b-hydride elimination to aromatize the system to give pyrrole 4.
Catalyst Pd(II) is regenerated through Pd(0) oxidized by O2.
Finally, pyrrole 4 is formed via acid-catalyzed isomerization of
40 (Scheme 3).
In summary, we have developed an unprecedented
palladium-catalyzed cascade Wacker-type process for the
‘one-pot’ synthesis of synthetically and biologically meaningful
pyrroles. Unlike reported methods relying on preformed
enamines and active halogenated terminal alkenes, the process
uses simple 2-alkenal-dicarbonyl compounds and primary
amines to synthesise highly substituted pyrroles in a cascade
fashion in moderate to excellent yields for a diverse range of
substrates. Moreover, non-terminal alkenes can be applied in a
highly regioselective manner.
11 (a) A. Arcadi, S. Giuseppe, F. Marinelli and E. Rossi, Adv. Synth.
¨
Catal., 2001, 343, 443; (b) S. Aggarwal and H.-J. Knolker, Org. Biomol.
Chem., 2004, 2, 3060; (c) R. Martin, M. R. Rivero and S. L. Buchwald,
Angew. Chem., Int. Ed., 2006, 45, 7079; (d) X. Liu, L. Huang, F. Zheng
and Z. Zhan, Adv. Synth. Catal., 2008, 350, 2778; (e) Y. Wang, X. Bi,
D. Li, P. Liao, Y. Wang, J. Yang, Q. Zhang and Q. Liu, Chem.
Commun., 2011, 47, 809.
12 (a) R. Dhawan and B. A. Arndtsen, J. Am. Chem. Soc., 2004, 126, 468;
(b) A. Mizuno, H. Kusama and N. Iwasawa, Angew. Chem., Int. Ed.,
2009, 48, 8318; (c) A. Saito, T. Konishi and Y. Hanzawa, Org. Lett.,
2010, 12, 372.
13 (a) S. R. Fix, J. L. Brice and S. S. Stahl, Angew. Chem., Int. Ed., 2002,
41, 164; (b) R. M. Trend, Y. K. Ramtohul, E. M. Ferreira and
B. M. Stoltz, Angew. Chem., Int. Ed., 2003, 42, 2892;
(c) M. S. Sigman and M. J. Schultz, Org. Biomol. Chem., 2004,
2, 2551; (d) B. M. Stoltz, Chem. Lett., 2004, 33, 362; (e) G. Liu and
S. S. Stahl, J. Am. Chem. Soc., 2007, 129, 6328; ( f ) K. H. Jensen and
M. S. Sigman, Org. Biomol. Chem., 2008, 6, 4083; (g) K. M. Gligorich
and M. S. Sigman, Chem. Commun., 2009, 3854; (h) J. A. Keith and
P. M. Henry, Angew. Chem., Int. Ed., 2009, 48, 9038.
14 G. Zeni and R. C. Larock, Chem. Rev., 2004, 104, 2285.
15 (a) H. Tsutsui, M. Kitamura and K. Narasaka, Bull. Chem. Soc. Jpn.,
2002, 75, 1451; (b) An intramolecular version: Z. Zhang, J. Zhang,
J. Tan and Z.-Y. Wang, J. Org. Chem., 2008, 73, 5180.
16 A. Demir, I. Akhmedov and O. Sesenoglu, Tetrahedron, 2002,
58, 9793.
The financial support from the Shanghai Pujiang Program
(11PJ1411900), East China University of Science & Technology,
The Shanghai Committee of Science and Technology (grant
11DZ2260600) and the China 111 Project (Grant B07023) is
appreciated.
Notes and references
17 H. M. C. Ferraz, F. L. C. Pereira, F. S. Leite, M. R. S. Nunes and
M. E. P. Arrua, Tetrahedron, 1999, 55, 10915.
18 There is also evidence for this step occurring in a syn manner:
R. I. McDonald, G. Liu and S. S. Stahl, Chem. Rev., 2011, 111, 2981.
19 See ESI† for the deuterated mechanism study (Scheme S1).
1 (a) F. S. Yates, in Comprehensive Heterocyclic Chemistry, ed.
A. J. Boulton and A. McKillop, Pergamon, Oxford, 1984, vol. 2,
p. 511, Part 2A; (b) R. A. Jones, Pyrroles, Part II, The Synthesis,
Reactivity and Physical Properties of Substituted Pyrroles, Wiley,
c
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Chem. Commun., 2013, 49, 4667--4669 4669