References and Notes
For recent examples of the synthesis
and isolation of pyrrole-containing natural products, see:
1a
Fürstner A.
Szillat H.
Gabor B.
Mynott R.
J. Am. Chem.
Soc.
1998,
120:
8305
1b
Umeyama A.
Ito S.
Yuasa E.
Arihara S.
Yamada T.
J. Nat. Prod.
1998,
61:
1433
1c
Jones TH.
Flournoy RC.
Torres JA.
Snelling RR.
Spande TF.
Garraffo HM.
J. Nat. Prod.
1999,
62:
1343
1d
Assmann M.
Zea S.
Köck M.
J.
Nat. Prod.
2001,
64:
1593
1e
Grube A.
Köck M.
J. Nat. Prod.
2006,
69:
1212
1f
Grube A.
Lichte E.
Köck M.
J.
Nat. Prod.
2006,
69:
125
2
Sundberg RJ. In
Comprehensive Heterocyclic Chemistry II
Vol.
4:
Katritzky AR.
Rees CW.
Scriven EFV.
Elsevier;
Amsterdam:
1996. 380-382,
431
3 Roth BD. inventors; US
Patent 4681893.
; Chem. Abstr. 1987, 107, 198087
4 Anzalone S. inventors; Eur.
Patent Appl. 0755679.
; Chem. Abstr. 1997, 126, 139884
For selected recent examples of
pyrrole synthesis, see:
5a
Binder JT.
Kirsch SF.
Org.
Lett.
2006,
8:
2151
5b
Harrison TJ.
Kozak JA.
Corbella-Pané M.
Dake GR.
J.
Org. Chem.
2006,
71:
4525
5c
Hiroya K.
Matsumoto S.
Ashikawa M.
Ogiwara K.
Sakamoto T.
Org.
Lett.
2006,
8:
5349
5d
Winkler JD.
Ragains JR.
Org.
Lett.
2006,
8:
4031
5e
Dong H.
Shen M.
Redford
JE.
Stokes BJ.
Pumphrey AL.
Driver TG.
Org.
Lett.
2007,
9:
5191
5f
Zanatta N.
Schneider JMFM.
Schneider PH.
Wouters AD.
Bonacorso HG.
Martins MAP.
Wessjohann LA.
J.
Org. Chem.
2006,
71:
6996
5g
Alonso-Cruz CR.
Freire R.
Rodríguez MS.
Suárez E.
Synlett
2007,
2723
5h
Huang X.
Shen R.
Zhang T.
J.
Org. Chem.
2007,
72:
1534
5i
Istrate FM.
Gagosz F.
Org. Lett.
2007,
9:
3181
5j
Martín R.
Larsen CH.
Cuenca A.
Buchwald SL.
Org.
Lett.
2007,
9:
3379
5k
Milgram BC.
Eskildsen K.
Richter SM.
Scheidt WR.
Scheidt KA.
J. Org. Chem.
2007,
72:
3941
5l
Rivero MR.
Buchwald SL.
Org.
Lett.
2007,
9:
973
5m
Shindo M.
Yoshimura Y.
Hayashi M.
Soejima H.
Yoshikawa T.
Matsumoto K.
Shishido K.
Org.
Lett.
2007,
9:
1963
5n
St. Cyr DJ.
Martin N.
Arndtsen BA.
Org. Lett.
2007,
9:
449
5o
Chiba S.
Wang Y.-F.
Lapointe G.
Narasaka K.
Org. Lett.
2008,
10:
313
6
Schmuck C.
Rupprecht D.
Synthesis
2007,
3095
7 The instability of pyrroles to oxidative
conditions is well precedented. See: Chierici L.
Gardini GP.
Tetrahedron
1966,
22:
53
For the reaction of magnesium nitride
with water/deuterated water, see:
8a
Moser L.
Herzner R.
Monatsh. Chem.
1923,
44:
115 ; Chem. Abstr. 1924, 18, 3625
8b
Ley SV.
Paquette LA.
J. Am. Chem. Soc.
1974,
96:
6670
For the reaction of magnesium nitride with alcoholic solvents,
see:
8c
Veitch GE.
Bridgwood KL.
Ley SV.
Org. Lett.
2008,
10: 3623
8d
Bridgwood KL.
Veitch GE.
Ley
SV.
Org. Lett.
2008,
10: 3627
9a
Paal C.
Ber.
1884,
17:
2756
9b
Knorr L.
Ber.
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17:
2863
For recent improvements, see:
9c
Banik BK.
Banik I.
Renteria M.
Dasgupta SK.
Tetrahedron
Lett.
2005,
46:
2643
9d
Werner S.
Iyer PS.
Synlett
2005,
1405
10
Representative
Procedure for the Microwave-Assisted Synthesis of 1
H
-Pyrroles:
To a stirred solution of 1-phenyl-pentane-1,4-dione (100 mg, 0.57
mmol) in MeOH (5.5 mL) at 0 ˚C was added magnesium nitride
(143 mg, 1.43 mmol). The reaction vessel was sealed and allowed
to warm to r.t. over 1 h during which time the brown solution became white,
indicating the formation of magnesium alkoxide species and the release
of NH3. The reaction was then heated to 120 ˚C
for 1 h in the microwave. After cooling to r.t., the reaction was
partitioned between CH2Cl2 (20 mL) and H2O (20
mL). The aqueous layer was acidified to pH 7 using 1 N HCl then
the organic layer was separated, dried (MgSO4) and concentrated
in vacuo. Flash column chromatography on silica (10% EtOAc
in hexanes) afforded 2 as an off-white solid
(96 mg, 99%). ¹H NMR (400 MHz, CDCl3): δ = 8.09 (br
s, 1 H), 7.42 (d, J = 7.6 Hz,
2 H), 7.33 (t, J = 7.4 Hz, 2 H),
7.16 (t, J = 7.4 Hz, 1 H), 6.39
(br s, 1 H), 5.95 (br s, 1 H), 2.32 (s, 3 H). ¹³C
NMR (100 MHz, CDCl3): δ = 133.0, 130.8, 129.1,
128.9, 125.7, 123.4, 108.0, 106.3, 13.2. IR (film): 3397, 2921,
1603, 1511, 1216, 899, 772, 750, 687 cm-¹. HRMS
(ESI): m/z [M + H]+ calcd
for C11H12N: 158.0971; found: 158.0964. Data
consistent with literature values.¹8
11
Representative
Procedure for the Thermally Assisted Synthesis of 1
H
-Pyrroles (Table
2): To a stirred solution of 1-phenylpentane-1,4-dione (100
mg, 0.57 mmol) in MeOH (5.5 mL) at 0 ˚C was added magnesium
nitride (143 mg, 1.43 mmol). The reaction vessel was sealed and
heated to 80 ˚C for 24 h. After cooling to r.t., the reaction
was subjected to workup and column chromatography as before.
12
Physical Data
for 2-(4-Bromophenyl)-5-methyl-1
H
-pyrrole (4): ¹H NMR
(400 MHz, CDCl3): δ = 8.06 (br s, 1 H),
7.44 (d, J = 8.5 Hz, 2 H), 7.28
(d, J = 8.5 Hz, 2 H), 6.39 (t, J = 2.4 Hz, 1 H), 5.95 (br s,
1 H), 2.33 (s, 3 H). ¹³C NMR (100 MHz,
CDCl3): δ = 131.9, 131.8, 129.6, 129.6,
124.7, 118.9, 108.2, 106.8, 13.2. IR (film): 3437, 2921, 2851, 1506, 819,
768 cm-¹. HRMS (ESI): m/z [M + H]+ calcd
for C11H11BrN: 236.0077; found: 236.0080.
13
Physical Data
for 2-Methyl-5-[4-(trifluoromethyl)phe-nyl]-1
H
-pyrrole (5): ¹H
NMR (400 MHz, CDCl3): δ = 8.17 (br
s, 1 H), 7.57 (d, J = 8.6 Hz,
2 H), 7.49 (d, J = 8.4 Hz, 2 H),
6.51 (t, J = 2.9 Hz, 1 H), 5.99
(br s, 1 H), 2.35 (s, 3 H). ¹³C NMR
(100 MHz, CDCl3): δ = 136.0, 130.5,
129.2, 127.1 (q, J = 31.5 Hz),
125.8 (q, J = 3 Hz), 124.3 (q, J = 270 Hz), 122.9, 108.6, 108.1,
13.2. IR (film): 3397, 2918, 2852, 1617, 1333, 1112, 844, 778 cm-¹.
HRMS (ESI): m/z [M + H]+ calcd for
C12H11F3N: 226.0839; found: 226.0849.
14
General Procedure
for the Thermally Assisted Synthesis of 1
H
-Pyrroles (Table 3): To a stirred solution
of the 1,4-dicarbonyl compound (0.13 mmol) in MeOH (1.3 mL) at
0 ˚C
was added magnesium nitride (1.3 mmol). The reaction vessel was
sealed and allowed to stir for 10 min before heating to 80 ˚C
for 24 h. After cooling to r.t., the reaction was subjected to workup
and column chromatography as before. For pyrroles 10 and 11, neutral alumina was employed for chromatography
to prevent decomposition.
15
Physical Data
for 3-(Thiophen-2-yl)-2-
p
-tolyl-5-[4-(trifluoromethyl)phenyl]-1
H
-pyrrole (11): ¹H
NMR (600 MHz, CDCl3): δ = 8.41 (br
s, 1 H), 7.59 (AB q, J = 8.6
Hz, 4 H), 7.44 (d, J = 8.1 Hz,
2 H), 7.23 (d, J = 7.9 Hz, 2
H), 7.21 (dd, J = 5.0, 1.0 Hz,
1 H), 6.99 (dd, J = 5.0, 3.5
Hz, 1 H), 6.96 (dd, J = 3.5,
1.0 Hz, 1 H), 6.66 (d, J = 2.8
Hz, 1 H), 2.38 (s, 3 H). ¹³C NMR (150
MHz, CDCl3): δ = 138.0, 137.0, 136.1, 133.4,
129.7, 128.8, 128.8 (q, J = 33
Hz), 127.6, 127.4, 127.3, 125.6 (q, J = 3
Hz), 124.2 (q, J = 273 Hz),
124.7, 124.1, 124.0, 118.0, 109.0, 21.2. IR (film): 3427, 2919, 2849,
1616, 1324, 1164, 1121, 1068 cm-¹.
HRMS (ESI):
m/z [M]+ calcd
for C22H16NF3S: 383.0956; found:
383.0960.
16
Physical Data
for 2-Phenyl-4,5-dihydro-1
H
-benzo[
g
]indole (14): ¹H
NMR (600 MHz, CDCl3): δ = 8.46 (br
s, 1 H), 7.53 (d, J = 7.6 Hz,
2 H), 7.39 (t, J = 7.6 Hz, 2 H),
7.21-7.26 (m, 4 H), 7.08 (t, J = 7.2
Hz, 1 H), 6.43 (d,
J = 1.8
Hz, 1 H), 2.96 (t, J = 7.2 Hz,
2 H), 2.78 (t, J = 7.2 Hz, 2
H). ¹³C NMR (150 MHz, CDCl3): δ = 135.0,
132.6, 132.5, 129.0, 128.9, 128.4, 126.6, 126.2, 125.2, 123.7, 122.2, 118.2,
106.1, 29.9, 29.7. IR (film): 3442, 2923, 2850, 1609, 1507, 1291,
1263 cm-¹. HRMS (ESI): m/z [M]+ calcd
for C18H15N: 245.1205; found: 245.1192.
17
Physical Data
for 2-(4-Fluorophenyl)-3-(4-methoxy-phenyl)-5-(naphthalen-2-yl)-1
H
-pyrrole (15): ¹H
NMR (500 MHz, CDCl3): δ = 8.47 (br
s, 1 H), 7.90 (br s, 1 H), 7.81-7.87 (m, 3 H), 7.71 (dd, J = 8.5, 1.4 Hz, 1 H), 7.48
(td, J = 8.0, 1.0 Hz, 1 H),
7.38-7.45 (m, 3 H), 7.31 (d, J = 8.8
Hz, 2 H), 7.04 (d, J = 8.7 Hz,
2 H), 6.86 (dt, J = 9.6, 2.9
Hz, 2 H), 6.77 (d, J = 2.6 Hz,
1 H), 3.82 (s, 3 H). ¹³C NMR (125 MHz, CDCl3): δ = 161.9
(d, J = 245 Hz), 158.1, 133.8,
132.2, 132.1, 129.5, 129.5, 129.2, 129.2, 128.7, 128.6, 128.3, 127.8,
127.7, 126.6, 125.5, 123.7, 123.0, 121.0, 115.7 (d, J = 21.5 Hz), 113.9, 109.1,
55.2. IR (film): 3425, 2922, 1629, 1604, 1519, 1506, 1483 cm-¹.
HRMS (ESI): m/z [M + H]+ calcd
for C27H21NOF: 394.1607; found: 394.1617.
18
Trofimov BA.
Tarasova OA.
Mikhaleva AI.
Kalinina NA.
Sinegovskaya LM.
Henkelmann J.
Synthesis
2000,
1585
