LETTER
Monoheterocyclic Compounds; Sainsbury, M., Ed.;
Suzuki Coupling Reactions in Heterocyclic Chemistry
831
solution was treated with 1 mL of 1 M HCl. After eva-
poration of the solvents, the mixture was washed with
diethyl ether. The organic layer was discarded before
Elsevier: Oxford, 1997, 457–556. (c) Ketcha, D. M. In
Progress in Heterocyclic Chemistry, Vol. 11; Gribble G. W.,
Gilchrist T. L., Pergamon-Elsevier: Oxford, 1999, 124–143.
(d) Black, D. S. In Hetarenes and Related Ring Systems:
Fully Unsaturated Small-Ring Heterocycles and Monocyclic
Five-Membered Hetarenes with One Heteroatom, Vol. 9;
Maas, G.; Regitz, M.; Ley, S. V., Eds.; Georg Thieme
Verlag: Stuttgart, New York, 2001, 441–552.
treatment with 1 M NaOH (1 mL). The free pyrroline was
extracted with CH2Cl2. Distillation of the solvent afforded
oil, which was distilled with Kugelrohr. Selected data: 3e:
1H NMR (300 MHz, CDCl3) 2.32 (s, 3 H), 3.67–3.74 (m,
2 H), 3.85–3.93 (m, 4 H), 6.05 (dd, J = 1.7 and 2.0 Hz, 1 H),
6.25 (dd, J = 1.7 and 3.2 Hz, 1 H), 6.34 (dd, J = 2.0 and 3.2
Hz, 1 H), 7.10 (d, J = 7.9 Hz, 2 H), 7.25 (d, J = 7.9 Hz, 2 H),
7.35–7.40 (m, 1 H). 13C NMR (75.5 MHz, CDCl3) 21.2,
51.9, 59.6, 60.2, 107.6, 110.0, 120.7, 125.3, 129.1, 131.5,
137.3, 139.4, 142.0, 153.0. HRMS m/z calcd for C16H17NO
(M+) 239.13101, found 239.1312.
(3) Anderson, H. J.; Loader, C. E. Synthesis 1985, 353.
(4) Campi, E. M.; Fallon, G. D.; Jackson, W. R.; Nilsson, Y.
Aust. J. Chem. 1992, 45, 1167.
(5) (a) Bean, G. P. In Pyrroles Part 1., The Synthese and the
Physical and Chemical Aspects of the Pyrroles Ring; Jones,
R. A., Ed.; John Wiley and Sons: New York, 1990, 182–
183. (b) Lamberth, C. J. Prakt. Chem./Chem.-Ztg. 1998,
340, 483.
(6) Bujard, M.; Briot, A.; Gouverneur, V.; Mioskowski, C.
Tetrahedron Lett. 1999, 40, 8785.
(7) Li, J. J.; Gribble, G. W. In Palladium in Heterocyclic
Chemistry; Baldwin, J. E.; Williams, R. M., Eds.; Pergamon-
Elsevier: Oxford, 2000.
(16) Pawda, A.; Norman, B. H. Tetrahedron Lett. 1988, 29, 3041.
(17) A representative procedure is as follows: A chloroform
solution (5 mL) of alkenylboronate 1 (1 mmol) and three
equivalents of the amine was stirred overnight at r.t. The
solvent was then evaporated in vacuo. After dilution of the
residue in toluene (6 mL), 1 mmol of DDQ (227 mg) was
added to the solution. The slurry was stirred at r.t. over night.
The solvent was removed and the residue was washed with
(8) Chung, Y. J.; Lee, C. W. Tetrahedron Lett. 2000, 41, 3423.
(9) For some examples of synthesis and reactivity of pyrrole-2-
boronic ester, see: (a) Johnson, C. N.; Stemp, G.; Anand, N.;
Stephen, S. C.; Gallagher, T. Synlett 1998, 1025.
(b) Alvarez, A.; Guzman, A.; Ruiz, A.; Velarde, E.;
Muchowski, J. M. J. Org. Chem. 1992, 57, 1653.
(c) D’Alessio, R.; Rossi, A. Synlett 1996, 513. (d) Martina,
S.; Enkelmann, V.; Wegner, G.; Schluter, A. D. Synthesis
1991, 613.
2
20 mL of pentane, filtered through a pad of celite and
concentrated in vacuo. The pyrrole 4 was purified by column
chromatography on silica gel (EtOAc–heptane, 10:90).
Selected data 4a: 1H NMR (300 MHz, CDCl3) 1.34 (s,
12 H), 5.05 (s, 2 H), 6.56 (t, J = 1.8 Hz, 1 H), 6.72 (t, J = 1.8
Hz, 1 H), 7.16–7.33 (m, 6 H). 13C NMR (75.5 MHz, CDCl3)
24.9, 53.4, 82.8, 114.6, 122.3, 127.4, 127.8, 128.8, 130.3,
137.6. HRMS m/z calcd for C17H22BNO2 (M+) 283.1743,
found 283.11754.
(10) For a recent preparation of a N-(Boc)pyrrole-3-boronic ester,
see: Renaud, J.; Ouellet, S. G. J. Am. Chem. Soc. 1998, 34,
7995.
(11) Kamabuchi, A.; Miyaura, N.; Suzuki, A. Tetrahedron Lett.
1993, 34, 4827.
(12) For similar reactions without the boronic moiety, see:
(a) Margaret, M.; Bowers, N.; Lee, J.; Jouille, M. M. Synth.
Commun 1983, 13, 1117. (b) Taylor, E. C.; Ahmed, Z. J.
Org. Chem. 1991, 56, 5443.
(18) Yagi, T.; Aoyama, T.; Shiori, T. Synlett 1997, 1063.
(19) A representative procedure is as follows: A mixture of pyr-
roline 2b (1 mmol) and activated manganese oxide (870 mg,
10 mmol) in THF (12 mL) was heated under reflux for 48 h.
The reaction mixture was filtered through a pad of celite and
the filtrate was concentrated in vacuo The residue was
purified by column chromatography on silica gel (EtOAc–
Heptane, 10:90). Representative data for the selected
compound 3e: 1H NMR (300 MHz, CDCl3) 1.30 (s, 12 H),
1.43 (d, J = 6.7 Hz, 6 H), 4.24 (sept., J = 6.7 Hz, 1 H), 6.47
(dd, J = 2.5 and 1.7 Hz, 1 H), 6.74 (t, J = 2.5 Hz, 1 H); 7.19
(t, J = 1.7 Hz, 1 H). 13C NMR (75.5 MHz, CDCl3) 23.9,
24.8, 50.9, 82.7, 113.7, 119.7, 127.3. HRMS m/z calcd for
C13H22BNO2 (M+) 235.1746, found 235.11743.
(20) A representative procedure is as follows: To a solution of
pyrrole-3-boronate 4 (1 mmol) in THF (10 mL), under an
argon atmosphere, were added CsCO3 (978 mg, 3 mmol),
PdCl2(dppf)CH2Cl2 (72 mg, 0.090 mmol), aryl or heteroaryl
iodide (290 mg, 1.5 mmol) and water (1 mL). The reaction
mixture was stirred at reflux temperature for 18 h, then
cooled to r.t. and partitioned between water (20 mL) and
diethyl ether (50 mL 3). The combined extracts were
washed with 1 N HCl (20 mL) and dried over magnesium
sulfate. The solvent was removed in vacuo and the crude
product was purified by silica gel column chromatography
(eluting with EtOAc–Heptane 10:90). Selected data: 5b: 1H
NMR (300 MHz, CDCl3) 5.06 (s, 2 H), 6.55 (dd, J = 1.8
and 2.8 Hz, 1 H), 6.73 (dd, J = 2.3 and 2.8 Hz, 1 H), 7.11 (dd,
J = 2.3 and 1.8 Hz, 1 H), 7.20–7.35 (m, 5 H), 8.46–8.54 (m,
2 H). 13C NMR (75.5 MHz, CDCl3) 53.8, 106.8, 119.4,
119.7, 122.3, 123.1, 127.2, 128.0, 128.9, 137.2, 143.2,
149.9. HRMS m/z calcd for C16H14N2 (M+) 234.1157, found
234.1165.
(13) A representative procedure is as follows: A solution of
alkenylboronate 1 (1 mmol) and three equivalents of the
amine in chloroform (5 mL) was stirred overnight at r.t. The
residue obtained upon evaporation of the solvent was
dissolved in 7 mL of acetonitrile and stirred for 2 h at r.t.
with 6 mmol (828 mg) of K2CO3. Solids were removed by
filtration and solvents were evaporated to dryness to afford a
crude product, which was subjected to distillation under
reduced pressure. Selected data: 2b: 1H NMR (300 MHz,
CDCl3) 1.10 (d, J = 6.3 Hz, 6 H), 1.28 (s,12 H), 2.60 (sept,
J = 6.3 Hz, 1 H), 3.52–3.63 (m, 4 H); 6.52 (s broad, 1 H). 13
NMR (75.5 MHz, CDCl3) 21.7, 24.7, 54.1, 59.0, 59.4,
83.3, 143.2. HRMS m/z calcd for C13H24BNO2 (M+)
237.1899, found 237.1902.
C
(14) Bläckvall, J. E.; Nyström, J. E. J. Chem. Soc., Chem.
Commun. 1981, 59.
(15) A representative procedure is as follows: A mixture of
pyrroline boronic ester 2 (1 mmol), aryl halide (1.5 mmol),
Pd(PPh3)4 (0.05 mmol) and CsF (4 mmol) in freshly distilled
THF (10 mL) was heated at reflux under argon for 2 h.
Saturated NH4Cl solution (10 mL) and diethyl ether (30 mL)
were added to the cooled solution. Aqueous layer was
extracted with diethyl ether and the combined extracts were
dried (Na2SO4) and evaporated to dryness in vacuo. The
residue was dissolved in CH2Cl2 (10 mL) and the resulting
Synlett 2002, No. 5, 829–831 ISSN 0936-5214 © Thieme Stuttgart · New York