An expedient synthesis of pyrrole-2-phosphonates via direct oxidative phosphorylation and γ-hydroxy-γ-butyrolactams from pyrroles

Article abstract of DOI:10.1016/j.tetlet.2013.11.082

An expedient oxidative phosphorylation of pyrroles has been disclosed. The reaction of dialkyl phosphite and pyrrole in the presence of AgNO ₃/K₂S₂O₈ in DMF/H₂O (8:1) produced pyrrole-2-phosphonates in good yields. In the absence of dialkyl phosphite, γ-hydroxy-γ-butyrolactam derivative was formed as a major product.

Full text of DOI:10.1016/j.tetlet.2013.11.082

Tetrahedron Letters 55 (2014) 531–534
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Tetrahedron Letters
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An expedient synthesis of pyrrole-2-phosphonates via direct
oxidative phosphorylation and
from pyrroles
c-hydroxy-c-butyrolactams
⇑
Se Hee Kim, Ko Hoon Kim, Jin Woo Lim, Jae Nyoung Kim
Department of Chemistry and Institute of Basic Science, Chonnam National University, Gwangju 500-757, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
An expedient oxidative phosphorylation of pyrroles has been disclosed. The reaction of dialkyl phosphite
and pyrrole in the presence of AgNO3/K2S2O8 in DMF/H2O (8:1) produced pyrrole-2-phosphonates in
Received 11 October 2013
Revised 12 November 2013
Accepted 19 November 2013
Available online 28 November 2013
good yields. In the absence of dialkyl phosphite,
major product.
c
-hydroxy-
c-butyrolactam derivative was formed as a
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Pyrrole-2-phosphonates
Oxidative phosphorylation
c
-Hydroxy-c-butyrolactams
Dialkyl phosphites
Aryl and heteroaryl phosphonates are an important class of com-
pounds, and many of them possess interesting biological activities.1
Among various methods for the synthesis of heteroaryl phospho-
nates, the dehydrogenative cross-coupling reaction of heteroarenes
with phosphites has become an efficient and promising strategy.1b
The synthesis of pyrrole phosphonates has been reported by the
reaction of pyrrylmagnesium or pyrryllithium reagents with diethyl
chlorophosphate; however, the yield was very low due to formation
of many side products.1b,2 Although a direct oxidative coupling
method has been applied for the synthesis of pyrrole phosphonates,
very simple and limited number of pyrroles have been included as
entries.3 Thus, a construction of pyrrole nucleus from the precursor
bearing a phosphonate moiety is a prevalent method for the synthe-
sis of pyrrole phosphonates until now.4
Thus, we examined the reaction of 1a under various condi-
tions,3,5–7 as summarized in Table 1. The reaction with Mn(OAc)3
at room temperature (entry 2) showed a sluggish reactivity, and
the amount of 3a increased. The reaction of 1a in the presence of
AgNO3/K2S2O8 was also sluggish both in CH2Cl2/H2O and THF/
H2O (entries 3 and 4).3b,5 Formation of many intractable side prod-
ucts was observed when aqueous acetone was used as a reaction
medium (entry 5). The yield of 2a was not improved in CH3CN/
H2O (entry 6) and in variable ratios (1:1 to 4:1) of DMF/H2O (en-
tries 7–9). When we used DMF/H2O (8:1) as solvent (entry 10),
2a could be obtained in good yield (75%); however, lactam 3a
was also formed albeit in low yield (14%). We found that the phos-
phorylation was somewhat sensitive to solvent composition. Such
a solvent effect has been reported in many phosphorylation reac-
tions.3b,5,6b Reducing the amount of AgNO3 (entry 11) and the use
of Na2S2O8 (entry 12) were not effective. The use of 0.4 equiv of
AgNO3 (entry 13) showed a similar result to that of entry 10. The
use of Ag2SO4 (entry 14)6a and AgOAc (entry 15) showed a similar
result. Based on the experimental results, we selected the condi-
tions of entry 10 as an optimum one.
Recently, we reported an efficient synthesis of 5-phosphory-
lated uracil derivatives via
a dehydrogenative cross-coupling
reaction between uracil derivatives and dialkyl phosphites in the
presence of Mn(OAc)3 in AcOH.5 As a continuous study, we
examined the phosphorylation of pyrrole derivatives using the
same cross-coupling method. Initially, we examined the reaction
of 1,2,4-triphenylpyrrole (1a), as a model substrate, under the
influence of Mn(OAc)3 in AcOH. However, a desired product
2a was obtained in moderate yield (43%) along with unexpected
Encouraged by the successful results various pyrrole derivatives
1a and 1d–i were prepared according to the reported methods,8a,b,f
as shown in Table 2. The other starting materials 1j–l were pre-
pared as reported,8c–e and the phosphorylation of these com-
pounds was examined under the optimized conditions (entry 10
in Table 1).9 The results are summarized in Table 2. The reaction
of 1a with dimethyl phosphite and diisopropyl phosphite afforded
2b and 2c in 87% and 54% yields, respectively. The lower yield of 2c
c-hydroxy-c-butyrolactam derivative 3a (19%), as shown in Table 1
(entry 1).
⇑
Corresponding author. Tel.: +82 62 530 3381; fax: +82 62 530 3389.
E-mail address: kimjn@chonnam.ac.kr (J.N. Kim).
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.11.082

532
S. H. Kim et al. / Tetrahedron Letters 55 (2014) 531–534
Table 1
Optimization of phosphorylation of 1aa
Ph
N
Ph
N
Ph
N
O
HP(O)(OEt)2 (3.0 equiv)
Oxidants / Conditions
HO
Ph
O
Ph
Ph
P(OEt)2
+
Ph
Ph
Ph
3a
1a
2a
Entry
Oxidantb
Conditions
1a/2a/3a (%)c
1
2
Mn(OAc)3 (3.0)
Mn(OAc)3 (3.0)
AcOH, 80 °C, 2 h
AcOH, 25 °C, 8 h
0/43/19e
50/5/40
3
4
5
6
7
8
9
AgNO3 (0.2)/K2S2O8 (3.0)
AgNO3 (0.2)/K2S2O8 (3.0)
AgNO3 (0.2)/K2S2O8 (3.0)
AgNO3 (0.2)/K2S2O8 (3.0)
AgNO3 (0.2)/K2S2O8 (3.0)
AgNO3 (0.2)/K2S2O8 (3.0)
AgNO3 (0.2)/K2S2O8 (3.0)
AgNO3 (0.2)/K2S2O8 (3.0)
AgNO3 (0.1)/K2S2O8 (3.0)
AgNO3 (0.2)/Na2S2O8 (3.0)
AgNO3 (0.4)/K2S2O8 (3.0)
Ag2SO4 (0.2)/K2S2O8 (3.0)
AgOAc (0.2)/K2S2O8 (3.0)
CH2Cl2/H2O (1:1), reflux, 4 h
THF/H2O (1:1), reflux, 8 h
acetone/H2O (1:1), reflux, 2 h
CH3CN/H2O (1:1), reflux, 2 h
DMF/H2O (1:1), 80 °C, 2 h
DMF/H2O (2:1), 50 °C, 2 h
DMF/H2O (4:1), 50 °C, 2 h
DMF/H2O (8:1), 50 °C, 2 h
DMF/H2O (8:1), 50 °C, 2 h
DMF/H2O (8:1), 50 °C, 2 h
DMF/H2O (8:1), 50 °C, 2 h
DMF/H2O (8:1), 50 °C, 2 h
DMF/H2O (8:1), 50 °C, 2 h
85/5/trace
90/5/trace
0/20/tracee
0/48/40
0/40/5e
0/55/tracee
0/53/tracee
0/75/14
0/36/45
18/38/24
0/69/9
10d
11
12
13
14
15
0/68/20
0/68/18
a
Pyrrole 1a (0.2 mmol) and HP(O)(OEt)2 (3.0 equiv) were used.
Equivalent in parenthesis.
Isolated yield (%).
Pyrrole 1a (0.5 mmol) was used.
Formation of many intractable side products was observed.
b
c
d
e
Table 2
Preparation of various pyrrole-2-phosphonates 2a-la,b
HP(O)(OR4)2 (3.0 equiv)
AgNO3 (0.2 equiv)
R3
N
R3
N
R3
N
O
R3-NH2
Ref. 8a
MeOOC
R2
O
O
Ref. 8f
R1
R1
P(OR4)2
O
R1
COOMe
R2
R2
R1
K2S2O8 (3.0 equiv)
DMF/H2O (8:1)
50°C, 2 h
R1
R2
R2
2a-i
1a, 1d-i
Ph
Ph
N
Ph
Ph
N
Ph
N
Ph
N
O
O
O
O
O
O
N
N
Ph
P(OEt)2
Ph
P(OMe)2
Ph
P(OiPr)2
Ph
P(OEt)2
Ph
P(OEt)2
Ph
P(OMe)2
Ph
2a (75%)c
Ph
2b (87%)
Ph
2c (54%)
Ph
2d (77%)d
Ph
Ph
2e (74%)e
2f (76%)f
OMe
Ph
Ph
Ph
O
H
N
H
N
O
O
O
O
N
O
O
N
N
N
P(OEt)2
H3C
P(OEt)2
P(OEt)2
Ph
P(OEt)2 Ph
P(OEt)2
P(OEt)2
Ph
Ph
Ph
Ph
2g (43%)
Ph
COOMe
2j (58%)
Ph
2h (77%)g
Ph
2i (68%)
Ph
COOMe
2k (63%)h
2l (66%)
a
Synthesis of 1a and 1d–i was carried out by using the reported methods.8a,b,f
b
The starting materials 1j–l for the preparation of 2j–l were prepared according to the reported methods.8c–e
c Lactam 3a (14%) was isolated.
d Lactam 3d (13%) was isolated.
e Lactam 3e (10%) was isolated.
f Lactam 3f (14%) was isolated.
g Lactam 3h (12%) was isolated.
h Reaction time was 3 h.
relative to 2a or 2b might be due to the larger size of isopropyl than
the methyl or ethyl groups.5,7a The reactions of 1d–l with di-
methyl- or diethyl phosphite afforded 2d–l in good to moderate
yields (43–77%).
in the absence of diethyl phosphite. To our delight, lactam 3a
was isolated in high yield (83%). The syntheses of lactams 3d–f
and 3h were carried out similarly, and the results are summarized
in Table 3.13 However, the mechanism for the formation of lactam
is not clear at this stage.14
As noted above, the corresponding
c-hydroxy-c-butyrolac-
tam10–12 was formed in variable amounts in most cases. Thus, we
As the next examination, the optimized phosphorylation condi-
tion was applied to 2,5-disubstituted pyrroles 1m, 1n, and some
examined the reaction of 1a under the same reaction conditions

S. H. Kim et al. / Tetrahedron Letters 55 (2014) 531–534
533
Ag+
Ag2+
SO4
2-
2-
Table 3
Preparation of
-
+
+
+
S2O8
SO4
c
-hydroxy-
c
-butyrolactams.
AgNO3 (0.2 equiv)
R3
N
R3
N
O
P
OEt
O
HO
Ph
Ag2+
Ag+
O
2a
- e
Ph
H
OEt
H
P OEt
OEt
K2S2O8 (3.0 equiv)
DMF/H2O (8:1)
50°C, 2 h
Ph
Ph
- 2H
3
1
Ph
N
OMe
Ag+
Ag2+
OH
P
OH
OH
H
Ph
1a
Ph
Ph
Ph
OEt
OEt
P
OEt
P
OEt
Ph
N
HO
Ph
OEt
OEt
I
HO
N
O
O
HO
Ph
Ph
HO
Ph
N
Ph
O
II
N
O
HO
N
O
Ph
Ph
Ph
3d (74%)
Scheme 1.
Ph
3e (67%)
Ph
3f (57%)
Ph
3h (94%)
3a (83%)
dialkyl phosphite,
c
-hydroxy-c-butyrolactam derivatives were
produced in good yields.
selected heterocyclic compounds, as summarized in Table 4. The
phosphorylation of methyl 1,3,5-triphenyl-2-pyrrolecarboxylate
(1m)8a and 1,2,5-triphenylpyrrole (1n) failed. We could not obtain
the products 2m and 2n in appreciable amounts due to the forma-
tion of many intractable side products and sluggish reactivity. 3-
Methylindole (1o) and N-methylindole (1p) produced 2o and 2p
in low to moderate yields (29–50%), as is often the case with re-
ported oxidative phosphorylation of indole derivatives.7a The reac-
tion with indoles also produced many intractable side products
presumably including their oxidative dimerization products such
as 2,20-biindolyl and 2,30-biindolyl.15 As compared to 1o and 1p,
the reaction of 2-phenylindole (1q) afforded 2q in better yield
(62%). The phosphorylation of 2,4-diphenylthiophene (1r) afforded
2r in good yield (64%), while the reactivity of 2,4-diphenylfuran
(1s) was sluggish under the same reaction conditions. The phos-
phorylation was somewhat sensitive to the reaction medium.3b,5,6b
As an example, the reaction of furfural (1t) in DMF/H2O (8:1)
showed very sluggish reactivity, while the reaction in CH2Cl2/H2O
(1:1)3b gave the product 2t in moderate yield (54%).
The reaction mechanism of phosphorylation of 1a with diethyl
phosphite could be proposed, as shown in Scheme 1, according to
the mechanism proposed by Effenberger and Kottmann.6b Ag(I) is
oxidized to Ag(II) by peroxodisulfate. Diethyl phosphite is con-
verted into radical cation I by the action of Ag(II). An electrophilic
addition of this radical cation to 1a forms an intermediate II, which
loses an electron and two protons affording the product 2a.
In summary, we disclosed an efficient synthesis of pyrrole-2-
phosphonates via a direct oxidative phosphorylation with dialkyl
phosphite and pyrroles in the presence of AgNO3 (0.2 equiv) and
K2S2O8 (3.0 equiv) in DMF/H2O (8:1) at 50 °C. In the absence of
Acknowledgments
This research was supported by the Basic Science Research Pro-
gram through the National Research Foundation of Korea (NRF)
funded by the Ministry of Education, Science and Technology
(2012R1A1B3000541). Spectroscopic data were obtained from
the Korea Basic Science Institute, Gwangju branch.
References and notes
1. For the reviews on the synthesis and biological activity of azaheterocyclic
phosphonates including pyrrole-2-phosphonates, see: (a) Moonen, K.; Laureyn,
I.; Stevens, C. V. Chem. Rev. 2004, 104, 6177–6215; (b) Van der Jeught, S.;
Stevens, C. V. Chem. Rev. 2009, 109, 2672–2702.
2. Griffin, C. E.; Peller, R. P.; Peters, J. A. J. Org. Chem. 1965, 30, 91–96.
3. For the synthesis of pyrrole-2-phosphonates by direct oxidative coupling, see:
(a) Mu, X.-J.; Zou, J.-P.; Qian, Q.-F.; Zhang, W. Org. Lett. 2006, 8, 5291–5293; (b)
Xiang, C.-B.; Bian, Y.-J.; Mao, X.-R.; Huang, Z.-Z. J. Org. Chem. 2012, 77, 7706–
7710.
4. For the synthesis of pyrrole-2-phosphonates from their precursors bearing a
phosphonate moiety, see: (a) Palacios, F.; Ochoa de Retana, A. M.; Velez del
Burgo, A. J. Org. Chem. 2011, 76, 9472–9477; (b) Moonen, K.; Dieltiens, N.;
Stevens, C. V. J. Org. Chem. 2006, 71, 4006–4009; (c) Dieltiens, N.; Moonen, K.;
Stevens, C. V. Chem. Eur. J. 2007, 13, 203–214; (d) Dieltiens, N.; Stevens, C. V.
Org. Lett. 2007, 9, 465–468; (e) Cal, D.; Zagorski, P. Phosphorous, Sulfur Silicon
2011, 186, 2295–2302; (f) Davis, F. A.; Bowen, K. A.; Xu, H.; Velvadapu, V.
Tetrahedron 2008, 64, 4174–4182; For the indirect synthesis of pyrrole-3-
phosphonates, see: (g) Demir, A. S.; Tural, S. Tetrahedron 2007, 63, 4156–4161;
(h) Attanasi, O. A.; Favi, G.; Mantellini, F.; Moscatelli, G.; Santeusanio, S. J. Org.
Chem. 2011, 76, 2860–2866; (i) de los Santos, J. M.; Ignacio, R.; Aparicio, D.;
Palacios, F.; Ezpeleta, J. M. J. Org. Chem. 2009, 74, 3444–3448.
5. Kim, S. H.; Kim, S. H.; Kim, C. H.; Kim, J. N. Tetrahedron Lett. 2013, 54, 1697–
1699.
6. For the oxidative coupling between arenes and dialkyl phosphites using AgNO3
(or Ag2SO4)/K2S2O8 system, see: (a) Mao, X.; Ma, X.; Zhang, S.; Hu, H.; Zhu, C.;
Cheng, Y. Eur. J. Org. Chem. 2013, 4245–4248; (b) Effenberger, F.; Kottmann, H.
Table 4
Attempted phosphorylation of similar substratesa
Ph
N
Ph
N
Me
O
Ph
Ph
O
Ph
COOMe
Ph
P(OEt)2
P(OEt)2
N
Me
N
H
P(OEt)2
O
(EtO)2P
O
2p (29%)
2o (50%)
2m (failed)
2n (failed)
O
O
O
O
O
P(OEt)2
O
Ph
P(OEt)2
S
OHC
P(OMe)2
Ph
P(OEt)2
N
H
2q (62%)
Ph
Ph
2r (64%)
2s (30%)
2t (<5%)b
a
Substrate 1m–t (0.5 mmol) was used, and the reaction was carried out in DMF/H2O (8:1).
b Compound 2t was obtained in 54% in CH2Cl2/H2O (1:1).

534
S. H. Kim et al. / Tetrahedron Letters 55 (2014) 531–534
Tetrahedron 1985, 41, 4171–4182; For the oxidation of Ag(I) to Ag(II) by
peroxydisulfate, see: (c) Minisci, F.; Citterio, A. Acc. Chem. Res. 1983, 16, 27–32.
CDCl3) d 7.97; ESIMS m/z 498 [M+H]+. Anal. Calcd for C28H36NO5P: C, 67.59; H,
7.29; N, 2.82. Found: C, 67.81; H, 7.46; N, 2.86.
7. For the other oxidative couplings between dialkyl phosphites and arenes/
heteroarenes including indoles and pyridinones, see: (a) Wang, H.; Li, X.; Wu,
F.; Wan, B. Synthesis 2012, 44, 941–945; (b) Sun, W.-B.; Ji, Y.-F.; Pan, X.-Q.;
Zhou, S.-F.; Zou, J.-P.; Zhang, W.; Asekun, O. Synthesis 2013, 45, 1529–1533; (c)
Xu, W.; Zou, J.-P.; Zhang, W. Tetrahedron Lett. 2010, 51, 2639–2643.
8. For the preparation of starting materials, see: (a) Kim, S. H.; Lim, J. W.; Lim, C.
H.; Kim, J. N. Bull. Korean Chem. Soc. 2012, 33, 620–624; (b) Kim, S. H.; Lim, J.
W.; Yu, J.; Kim, J. N. Bull. Korean Chem. Soc. 2013, 34, 2604–2608; (c) Kim, J. M.;
Lee, S.; Kim, S. H.; Lee, H. S.; Kim, J. N. Bull. Korean Chem. Soc. 2008, 29, 2215–
2220; (d) Lee, H. S.; Kim, J. M.; Kim, J. N. Tetrahedron Lett. 2007, 48, 4119–4122;
(e) Li, Q.; Fan, A.; Lu, Z.; Cui, Y.; Lin, W.; Jia, Y. Org. Lett. 2010, 12, 4066–4069;
For the preparation of required 2,5-diketo esters, see: (f) Kim, S. H.; Kim, K. H.;
Kim, J. N. Adv. Synth. Catal. 2011, 353, 3335–3339.
Compound 2k: White solid, mp 139–141 °C; IR (KBr) 3412, 1727, 1639, 1241,
1019 cmꢀ1 1H NMR (300 MHz, CDCl3) d 1.39 (t, J = 7.2 Hz, 6H), 3.70 (s, 3H),
;
4.19–4.36 (m, 4H), 7.01–7.10 (m, 7H), 7.24 (t, J = 8.7 Hz, 1H), 7.38 (d, J = 7.8 Hz,
2H), 10.30 (br s, 1H); 13C NMR (75 MHz, CDCl3) d 16.29 (d, JPC = 6.9 Hz), 51.44,
63.36 (d, JPC = 5.7 Hz), 121.54, 123.22, (d, JPC = 224.9 Hz), 127.22, 127.31,
127.54, 128.97, 130.66, 131.20 (d, JPC = 10.7 Hz), 131.91, 132.44, 133.12 (d,
JPC = 10.9 Hz), 136.42, 163.64, 187.24; ESIMS m/z 442 [M+H]+. Anal. Calcd for
C
23H24NO6P: C, 62.58; H, 5.48; N, 3.17. Found: C, 62.59; H, 5.71; N, 3.08.
Compound 2r: White solid, mp 66–68 °C; IR (KBr) 1487, 1250, 1022 cmꢀ1
;
1H
NMR (300 MHz, CDCl3) d 1.17 (t, J = 7.2 Hz, 6H), 3.92–4.14 (m, 4H), 7.26–7.50
(m, 7H), 7.56–7.69 (m, 4H); 13C NMR (75 MHz, CDCl3) d 15.97 (d, JPC = 7.4 Hz),
62.57 (d, JPC = 5.2 Hz), 121.64 (d, JPC = 207.2 Hz), 126.11, 127.27 (d,
JPC = 16.7 Hz), 128.05, 128.08, 128.66, 128.91 (d, JPC = 1.2 Hz), 129.06, 133.05
(d, JPC = 1.7 Hz), 135.75 (d, JPC = 2.9 Hz), 150.41 (d, JPC = 7.4 Hz), 150.60 (d,
JPC = 10.4 Hz); ESIMS m/z 373 [M+H]+. Anal. Calcd for C20H21O3PS: C, 64.50; H,
5.68. Found: C, 64.76; H, 5.80.
9. Typical procedure for the synthesis of 2a. A solution of 1a (148 mg, 0.5 mmol),
diethyl phosphite (208 mg, 1.5 mmol), AgNO3 (17 mg, 0.1 mmol), and K2S2O8
(406 mg, 1.5 mmol) in DMF/H2O (8:1, 6.0 mL) was heated to 50 °C for 2 h. After
the usual aqueous extractive workup and column chromatographic purification
process (hexanes/EtOAc, 1:1) compound 2a was obtained as a white solid,
162 mg (75%) along with lactam 3a, 23 mg (14%). Other compounds were
synthesized similarly, and the selected spectroscopic data of 2a, 2c, 2d, 2g, 2j,
2k, and 2r are as follows.
10. For the synthesis of
c-hydroxy-c-butyrolactams from pyrroles using an
oxidant, see: (a) Howard, J. K.; Hyland, C. J. T.; Just, J.; Smith, J. A. Org. Lett.
2013, 15, 1714–1717; (b) Alp, C.; Ekinci, D.; Gultekin, M. S.; Senturk, M.; Sahin,
E.; Kufrevioglu, O. I. Bioorg. Med. Chem. 2010, 18, 4468–4474; (c) Troegel, B.;
Lindel, T. Org. Lett. 2012, 14, 468–471; (d) Procopiou, P. A.; Highcock, R. M. J.
Chem. Soc., Perkin Trans 1 1994, 245–247; (e) Sakata, R.; Iwamoto, R.; Fujinami,
S.; Ukaji, Y.; Inomata, K. Heterocycles 2011, 82, 1157–1162.
Compound 2a: White solid, mp 116–118 °C; IR (KBr) 1496, 1257, 1025 cmꢀ1 1H
;
NMR (300 MHz, CDCl3) d 0.79 (t, J = 7.2 Hz, 6H), 3.36–3.39 (m, 2H), 3.59–3.72
(m, 2H), 6.38 (d, JPH = 4.8 Hz, 1H), 7.00–7.34 (m, 13H), 7.51–7.55 (m, 2H); 13C
NMR (75 MHz, CDCl3) d 15.63 (d, JPC = 7.4 Hz), 61.72 (d, JPC = 5.7 Hz), 112.19 (d,
JPC = 13.7 Hz), 118.29 (d, JPC = 226.7 Hz), 126.91, 127.21, 127.65, 127.97, 128.02,
128.42, 128.87(2C), 129.74, 131.97 (d, JPC = 1.7 Hz), 135.93, 136.88 (d,
JPC = 16.69 Hz), 139.45, 140.13 (d, JPC = 10.9 Hz); 31P NMR (121 MHz, CDCl3) d
9.14; ESIMS m/z 432 [M+H]+. Anal. Calcd for C26H26NO3P: C, 72.38; H, 6.07; N,
3.25. Found: C, 72.51; H, 6.18; N, 3.09.
11. For the oxidation of pyrroles using singlet oxygen and the synthesis of
isochrysohermidin, see: (a) Boger, D. L.; Baldino, C. M. J. Org. Chem. 1991, 56,
6942–6944; (b) Boger, D. L.; Baldino, C. M. J. Am. Chem. Soc. 1993, 115, 11418–
11425; (c) Alberti, M. N.; Vougioukalakis, G. C.; Orfanopoulos, M. J. Org. Chem.
2009, 74, 7274–7282.
12. For the other synthetic routes of c-hydroxy-c-butyrolactams, see: (a) Lim, C.
H.; Kim, S. H.; Kim, J. N. Bull. Korean Chem. Soc. 2012, 33, 1622–1626; (b) Kim, S.
H.; Kim, S. H.; Lee, H. J.; Kim, J. N. Bull. Korean Chem. Soc. 2012, 33, 2079–2082;
(c) Yang, L.; Lei, C.-H.; Wang, D.-X.; Huang, Z.-T.; Wang, M.-X. Org. Lett. 2010,
12, 3918–3921.
Compound 2c: Colorless oil; IR (film) 1497, 1258, 1029 cmꢀ1
;
1H NMR
(300 MHz, CDCl3) d 0.93 (d, J = 6.0 Hz, 6H), 1.12 (d, J = 6.0 Hz, 6H), 4.31–4.52
(m, 2H), 6.47 (d, JPH = 4.5 Hz, 1H), 7.08–7.41 (m, 13H), 7.59–7.63 (m, 2H); 13C
NMR (75 MHz, CDCl3) d 23.24 (d, JPC = 5.2 Hz), 23.82 (d, JPC = 4.1 Hz), 70.53 (d,
JPC = 5.7 Hz), 112.22 (d, JPC = 13.8 Hz), 119.52 (d, JPC = 228.9 Hz), 126.73, 127.08,
127.47, 127.90, 127.98, 128.13, 128.89, 129.25, 129.95, 132.13 (d, JPC = 1.7 Hz),
136.27, 136.39 (d, JPC = 16.6 Hz), 139.53, 139.95 (d, JPC = 10.9 Hz); ESIMS m/z
460 [M+H]+. Anal. Calcd for C28H30NO3P: C, 73.19; H, 6.58; N, 3.05. Found: C,
73.02; H, 6.77; N, 2.90.
13. The lactams 3a and 3d are known,12c and the selected spectroscopic data of 3e
and 3h are as follows.
Compound 3e: White solid, mp 194–196 °C; IR (KBr) 3355, 1681, 1492,
1450 cmꢀ1 1H NMR (300 MHz, CDCl3 + DMSO-d6) d 2.59–2.69 (m, 1H), 2.78–
;
2.93 (m, 1H), 3.09–3.20 (m, 1H), 3.53–3.63 (m, 1H), 5.22 (s, 1H), 6.98 (s, 1H),
7.04–7.43 (m, 13H), 7.84–7.88 (m, 2H); 13C NMR (75 MHz, CDCl3 + DMSO-d6) d
34.59, 41.26, 89.65, 125.94, 125.98, 127.27, 128.17, 128.23, 128.30, 128.43,
128.61, 128.75, 130.76, 133.77, 137.68, 139.28, 143.21, 169.13; ESIMS m/z 356
[M+H]+. Anal. Calcd for C24H21NO2: C, 81.10; H, 5.96; N, 3.94. Found: C, 81.21;
H, 6.03; N, 3.75.
Compound 2d: Colorless oil; IR (film) 1484, 1242, 1024 cmꢀ1
;
1H NMR
(300 MHz, CDCl3) d 0.81 (t, J = 7.2 Hz, 6H), 3.41–3.53 (m, 2H), 3.66–3.79 (m,
2H), 5.62 (s, 2H), 6.30 (d, JPH = 4.5 Hz, 1H), 6.84–6.88 (m, 2H), 7.07–7.31 (m,
11H), 7.42–7.47 (m, 2H); 13C NMR (75 MHz, CDCl3) d 15.64 (d, JPC = 7.5 Hz),
49.69, 61.64 (d, JPC = 5.2 Hz), 112.00 (d, JPC = 13.1 Hz), 115.51 (d, JPC = 224.9 Hz),
126.17, 126.75, 126.81, 127.54, 128.14, 128.20, 128.43, 129.46, 129.63, 132.13,
136.06, 136.79 (d, JPC = 16.0 Hz), 139.53, 141.43 (d, JPC = 12.5 Hz); ESIMS m/z
446 [M+H]+. Anal. Calcd for C27H28NO3P: C, 72.79; H, 6.34; N, 3.14. Found: C,
72.71; H, 6.58; N, 3.02.
Compound 3h: White solid, mp 70–72 °C; IR (KBr) 3355, 1682, 1513,
1449 cmꢀ1 1H NMR (300 MHz, CDCl3) d 3.61 (s, 3H), 3.88 (br s, 1H), 6.59 (d,
;
J = 9.0 Hz, 2H), 6.90 (s, 1H), 7.12–7.33 (m, 10H), 7.75–7.78 (m, 2H); 13C NMR
(75 MHz, CDCl3) d 55.16, 91.09, 113.80, 126.08, 126.85, 127.53, 128.37, 128.43,
128.46, 128.49, 129.17, 130.34, 133.90, 137.08, 142.94, 157.51, 168.82; ESIMS
m/z 358 [M+H]+. Anal. Calcd for C23H19NO3: C, 77.29; H, 5.36; N, 3.92. Found: C,
77.42; H, 5.29; N, 3.68.
Compound 2g: Colorless oil; IR (film) 1509, 1242, 1024 cmꢀ1
;
1H NMR
(300 MHz, CDCl3) d 0.91 (t, J = 7.2 Hz, 6H), 2.17 (s, 3H), 3.56–3.67 (m, 2H),
3.76–3.87 (m, 2H), 5.62 (s, 2H), 6.10 (d, JPH = 4.2 Hz, 1H), 6.98–7.01 (m, 2H),
7.19–7.49 (m, 8H); 13C NMR (75 MHz, CDCl3) d 12.40 (d, JPC = 1.7 Hz), 15.66 (d,
JPC = 7.4 Hz), 49.08, 61.52 (d, JPC = 5.2 Hz), 110.85 (d, JPC = 13.8 Hz), 114.04 (d,
JPC = 224.9 Hz), 125.93, 126.60, 126.86, 127.43, 128.43, 129.62, 136.22 (d,
JPC = 12.0 Hz), 136.27 (d, JPC = 17.2 Hz), 136.33, 138.61; 31P NMR (121 MHz,
CDCl3) d 10.59; ESIMS m/z 384 [M+H]+. Anal. Calcd for C22H26NO3P: C, 68.92; H,
6.83; N, 3.65. Found: C, 69.06; H, 6.68; N, 3.49.
14. The lactam 3a was formed in 42% yield in the presence of K2S2O8 (3.0 equiv) in
DMF/H2O (8:1) at 50 °C for 10 h without the aid of AgNO3. The result stated
that the use of AgNO3 accelerates the reaction rate when we compared the
yield of 3a (83%) and reaction time (2 h) in the presence of AgNO3. In addition,
the synthesis of alkyl-substituted lactams 3g and 3j failed. The formations of
3g and 3j were observed on TLC in low yields at the right position; however,
the separation failed due to the presence of some side products. Further studies
on the reaction mechanism including the involvement of air and/or water for
the production of lactam are under progress.
Compound 2j: Colorless oil; IR (film) 1731, 1260, 1023 cmꢀ1
;
1H NMR
(300 MHz, CDCl3) 0.75 (t, J = 6.6 Hz, 3H), 1.11–1.13 (m, 4H), 1.16 (t,
d
J = 7.2 Hz, 6H), 1.28–1.41 (m, 2H), 2.43–2.49 (m, 2H), 3.67 (s, 3H), 3.83–4.08
(m, 4H), 5.61 (s, 2H), 6.95–6.98 (m, 2H), 7.20–7.38 (m, 8H); 13C NMR (75 MHz,
CDCl3) d 13.75, 15.97 (d, JPC = 6.8 Hz), 21.97, 24.58, 29.60, 31.42, 49.22, 51.87,
62.38 (d, JPC = 5.2 Hz), 117.20 (d, JPC = 223.8 Hz), 123.21 (d, JPC = 12.1 Hz),
125.78, 126.68, 126.73 (d, JPC = 15.5 Hz), 127.14, 128.05, 128.52, 129.52, 134.34
(d, JPC = 1.1 Hz), 138.04 (d, JPC = 10.9 Hz), 138.12, 166.64; 31P NMR (121 MHz,
15. For the oxidative dimerization of indoles, see: (a) Niu, T.; Zhang, Y. Tetrahedron
Lett. 2010, 51, 6847–6851; (b) Li, Y.; Wang, W.-H.; Yang, S.-D.; Li, B.-J.; Feng, C.;
Shi, Z.-J. Chem. Commun. 2010, 4553–4555; (c) Liang, Z.; Zhao, J.; Zhang, Y. J.
Org. Chem. 2010, 75, 170–177; (d) Dohi, T.; Morimoto, K.; Maruyama, A.; Kita,
Y. Org. Lett. 2006, 8, 2007–2010.