Vinyl azides derived from allenes: Thermolysis leading to multisubstituted 1,4-pyrazines and Mn(III)-catalyzed photochemical reaction leading to pyrroles

Article abstract of DOI:10.1021/jo301694n

Thermolysis of phosphorus-based vinyl azides under solvent- and catalyst-free conditions furnished a new route for 1,4-pyrazines. A simple one-pot, Mn(III)-catalyzed photochemical route has been developed for multisubstituted pyrroles starting from allenes and 1,3-dicarbonyls via in situ-generated vinyl azides. The utility of new phosphorus-based pyrroles is also demonstrated in the Horner reaction. The structures of key products are unequivocally confirmed by X-ray crystallography.

Full text of DOI:10.1021/jo301694n

Article
pubs.acs.org/joc
Vinyl Azides Derived from Allenes: Thermolysis Leading to
Multisubstituted 1,4-Pyrazines and Mn(III)-Catalyzed Photochemical
Reaction Leading to Pyrroles
K. V. Sajna and K. C. Kumara Swamy*
School of Chemistry, University of Hyderabad, Hyderabad 500 046, A. P., India
S
* Supporting Information
ABSTRACT: Thermolysis of phosphorus-based vinyl azides under
solvent- and catalyst-free conditions furnished a new route for 1,4-
pyrazines. A simple one-pot, Mn(III)-catalyzed photochemical route
has been developed for multisubstituted pyrroles starting from allenes
and 1,3-dicarbonyls via in situ-generated vinyl azides. The utility of new
phosphorus-based pyrroles is also demonstrated in the Horner
reaction. The structures of key products are unequivocally confirmed
by X-ray crystallography.
click reaction to generate a diverse class of triazoles.5Recently,
INTRODUCTION
■
there have been two reports on the preparation of pyrroles that
Allenes are interesting substrates among the unsaturated
involve a vinyl azide and 1,3-dicarbonyl compounds as starting
systems because of their high reactivity,1 and hence they
materials.8 In this direction, we surmised that in situ-generated
serve as potential precursors for highly complex and strained
phosphono-vinyl azides by starting with the corresponding
target molecules of biological and industrial importance.2
allenes could lead to multisubstituted phosphono-pyrroles.
Allenylphosphonates/allenylphosphine oxides are also excellent
Although there have been many methods for the synthesis of
precursors for the preparation of synthetically important
pyrroles,9 it is still challenging to prepare polysubstituted
molecules.3,4 One class of compounds that can be prepared
pyrroles directly from the building blocks such as allenes.
via allenes are vinyl azides. The latter substrates are versatile
Because phosphonylated nitrogen heterocycles constitute an
intermediates for the synthesis of nitrogen heterocycles such as
important class of compounds with significant biological
triazoles,5 azirines,6 (Scheme 1) or other heterocycles.7 The
potential,10 new routes toward these molecules are still
intermediate vinyl azides can also be used in the alkyne−azide
warranted; only limited reports are available for the synthesis
of phosphorus-based pyrroles.11,12 In the course of our
investigations on such a system, we stumbled upon a new
reaction of vinyl azides leading to 1,4-pyrazines. This reaction
Scheme 1. Formation of Triazoles or Azirines via Vinyl
Azides Generated from Allenes
as well as the one-pot generation of phosphorus-based pyrroles
from the corresponding phosphono-vinyl azides photochemically
under Mn(III)-catalyzed conditions is described herein. Further
synthetic potential of thus derived phosphono-pyrroles in the
Horner−Wittig reaction is also highlighted herein. The
precursor allenes 1−6 (Chart 1) have been prepared for this
work by the synthetic routes available in the literature.13,14
RESULTS AND DISCUSSION
■
We shall first discuss the thermolysis of vinyl azides leading to
1,4-pyrazines. This will be followed by the reaction of vinyl
azides with 1,3-diketones leading to multisubstituted pyrroles.
Received: August 9, 2012
Published: September 10, 2012
© 2012 American Chemical Society
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Chart 1. Allene Precursors Used in the Present Study
Scheme 4. Formation of 1,4-Pyrazines 13−17 upon Thermal
Treatment of Vinyl Azides 7−11
When the latter contained a Ph2P(O)CH2 moiety, synthetic
utility in Horner reaction is demonstrated.
1. Vinyl Azides. Facile Pyrolysis Leading to 1,4-
Pyrazines. Vinyl azides 7−11 required for the present study
are obtained by treatment of allenylphosphonates/allenylphos-
phine oxides with Me3SiN3 in DMF at room temperature
(Scheme 2);5c the vinyl azide 12 is prepared from allenoate 6
Scheme 5. Possible Pathway for the Formation of 1,4-
Pyrazines
Scheme 2. Synthesis of Vinyl Azides 7−11 via Allenes 1−6
by using a reported method.15 Among these, 7 and 9−11 are
new. Vinyl azides under pyrolysis conditions are known to
afford azirines (Scheme 3; also see Scheme 1 shown above).6
in the transition state, but at the moment this is only a
speculation. An approximate weight loss of 10% from
compound 10 observed in the TGA analysis (Figure 1) also
supported the nitrogen gas elimination.
Scheme 3. Generation of Azirines from Vinyl Azides via
Nitrenes
Initially, while checking the melting point of azide 7, gas
evolution at the melting region (of temperature) was observed.
Upon further heating, gas evolution stopped resulting in a solid
material. To analyze the chemistry behind this, we heated ca.
0.2 g of compound 7 above its melting point (15 min) to get
the new solid material 13. The structure of this compound is
ascertained conclusively by single crystal X-ray crystallography
of a similar product 14 obtained from the azide 8 (Figure S1 in
Supporting Information). Thus, the resulting product upon
heating phosphorus-based vinyl azides under neat condition
was 1,4-pyrazines (Scheme 4) and not the expected azirines. To
our knowledge, this reaction is new. In an analogous manner,
azides 9−11 also led to 1,4-pyrazines 15−17 (Scheme 4).
Although vinyl azide 12 appears to eliminate gaseous nitrogen,
there were many products (TLC) and hence isolation was not
attempted.
The above pyrazines are likely to have formed via a radical
mechanism via a nitrene intermediate (I) as shown in Scheme
5. Involvement of a radical is indicated by the reduction in the
yield of the product (to <50% as revealed by 31P NMR) when
the reaction was performed in the presence of a radical
quencher (20 mol % of p-hydroquinone). The dimerization of
this intermediate followed by aromatization by the loss of
hydrogen leads to the pyrazines 13−17. It is possible that the
there is some interaction between phosphorus and the nitrogen
Figure 1. TGA behavior of azide 10.
2. One Pot Synthesis of Multisubstituted Pyrroles
from Allenes and 1,3-Diketones via Vinyl Azides. Mn(III)
Catalysis and Photochemical Activation. Our intended
target was to synthesize multisubstituted pyrroles by in situ-
generated vinyl azides from allenes. To check the feasibility of
product formation though, we first treated the azide 7 with
ethyl acetoacetate (EAA) in the presence of catalytic amount of
Mn(OAc)3·2H2O (Scheme 6)8 and were successful in
obtaining the phosphono-pyrrole 18 in good yield (60%). We
could reduce the reaction time from 12 to 4 h and also increase
the yield to 80% by using photochemical conditions (λ = 254
nm). As a means of confirmation, the X-ray structure of 18 was
determined (Figure S2 in Supporting Information). The
presence of the NH group was also revealed by its hydrogen-
bonding interaction with the phosphoryl oxygen.
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10 was straightforward but needed a solvent such as DMF;
methanol did not work for this step. For the next step, we
added methanol. There was no reaction in the absence of the
catalyst [Mn(OAc)3·2H2O] or additive (acetic acid) (cf., Table
1, entries 1 and 2). However, in the presence of the catalyst and
additive, the reaction occurred smoothly to give product 27
(entry 3) in excellent yield. The use of EtOH or i-PrOH
lowered the yield, and in fact there was no reaction in t-BuOH
(entries 4−6). DMF as a solvent was not effective for the
second step (entry 7). Trifluoroacetic acid or trifluoromethane
sulfonic acid as an additive worked, but the yield was lower
(entries 8 and 9). PTSA was ineffective as an additive (entry
10). Ceric ammonium nitrate (CAN) in place of Mn-
(OAc)3·2H2O also did not work (entry 11). Thus, efforts
toward the preparation of the pyrrole by employing the same
solvent system (methanol or DMF) in two consecutive steps
failed. While DMF facilitates the azide formation, methanol is
required for the formation of pyrrole from azide. Hence, we
carried out the first step in DMF, and then a solution of ethyl
acetoacetate, Mn(OAc)3·2H2O, and acetic acid in methanol
was added to the crude azide under photochemical conditions
to obtain the product. This procedure was then adapted to
other allenes and 1,3-diketones as shown in Table 2. The yields
were good to excellent. An interesting point here is that in the
reaction of the allenes 1−5 with ethyl 4-chloroacetoacetate the
Cl atom was exchanged for the OMe group in the products 19,
22, 25, 28, and 31 (cf., Table 2, entries 2, 5, 8, 11, and 14). This
exchange substantiates the radical mechanism proposed in the
literature for similar reactions.8 To confirm the authenticity of
our result, compound 20 was also characterized by single crystal
X-ray crystallography (Figure S3 in Supporting Information).
To compare the reactivity of phosphorus-based allenes with
allenoate, we carried out the reaction of the in situ-formed vinyl
azide 12 with 1,3-dicarbonyls under the above reaction
conditions. The result was fully substituted pyrroles 33−35
(Scheme 8). It is clear that in the case of phosphorylated
allenes, the β,γ-carbon atoms of allenes are involved in the
pyrrole ring formation (Table 2) whereas in allenoate 6, α,β-
carbons are participating (Scheme 8). Single crystal X-ray data
was also collected for compound 35 (Figure S4 in Supporting
Information). This product exists in a dimeric form due to
hydrogen-bonding interaction between NH and the carbonyl
oxygen of the ester group.
Scheme 6. Mn(III)-Catalyzed Photochemical Conversion of
Vinyl Azide 7 to Phosphono-pyrrole 18
To perform the above reaction in one pot using allenes 1−5
and also to maximize the yield of the products 18−32 under
photochemical conditions, we have screened various cosolvents
and additives. For this optimization, we chose allene 4 and ethyl
acetoacetate (EAA) as model reactants; this led to pyrrole 27
via azide 10 (cf. Scheme 7 and Tables 1-2). Formation of azide
Scheme 7. One-Pot Transformation of Allenes 1−5 to
Multisubstituted Pyrroles 18−32 via Mn(III)-Catalyzed
Reaction
Table 1. Details on the Conditions Shown in Scheme 7b
Using Vinyl Azide 10 and Ethyl Acetoacetate [Ⓟ ≡ Ph2P(O);
a
R1 = R2 = H; R3 = OEt, R4 = Me] leading to 27
product
cosolvent (i.e., in
addition to DMF)
yield 27
The above reactions can be assumed to take place via the
vinyl azides. Possible intermediates based on the literature8 for
the formation of 18−32 include II−IV. Similar intermediates
are likely to be present in the formation of 33−35. As can be
expected, the ring closure from III can occur at the carbon
close to R3 also; the choice between the two possibilities should
depend on the electronic factors.
b
entry
catalyst
additive
(%)
1
none
acetic acid
−
MeOH
MeOH
MeOH
EtOH
iPrOH
tBuOH
−
MeOH
MeOH
MeOH
MeOH
n.r.
n.r.
88
2
Mn(OAc)3·2H2O
Mn(OAc)3·2H2O
Mn(OAc)3·2H2O
Mn(OAc)3·2H2O
Mn(OAc)3·2H2O
Mn(OAc)3·2H2O
Mn(OAc)3·2H2O
Mn(OAc)3·2H2O
Mn(OAc)3·2H2O
CAN
3
acetic acid
acetic acid
acetic acid
acetic acid
acetic acid
CF3CO2H
CF3SO3H
PTSA
4
65
5
30
6
n.r.
n.r.
46
7
8
9
10
10
11
n.r.
n.r.
acetic acid
a
Conditions: To a solution of Me3SiN3 (0.5 mmol) in DMF (3 mL)
was added allene (0.42 mmol), and the reaction mixture was stirred at
rt for 4 h. To this was added a solution of ethyl acetoacetate (0.62
mmol), catalyst (10 mol %), and additive (2 equiv) in cosolvent (1.5
mL), and the mixture was irradiated in a photoreactor (λ = 254 nm)
3. Utility of Phosphorus-Based Pyrroles in the Horner
Reaction. We were interested to see if at least some of the
phosphorus-based pyrroles synthesized as above could be
utilized further, and in this direction, we felt that the Horner
reaction of these products possessing a PCH2 group should be
b
for an additional 4 h. Based on 31P NMR analysis.
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a
Table 2. Details on Pyrrole Derivatives 18−32 Synthesized from Allenes 1−5, Me3SiN3, and 1,3-Dicarbonyls
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Table 2. continued
a
Conditions: Me3SiN3 (1.2 equiv), DMF, allene (1.0 equiv), 2−4 h, then add ethyl acetoacetate (1.5 equiv), Mn(OAc)3·2H2O (10 mol %) and
b
acetic acid (2 equiv) in MeOH and irradiate (λ = 254 nm) for an additional 4 h. After isolation.
straightforward.5c Because the NH moiety interfered in the
reaction of 27 with 4-nitrobenzaldehyde by using NaH as base
(TLC evidence), we protected the pyrrole-NH with CH2Ph by
using a known procedure16 to obtain the N-benzylated
compound 36. We then performed the olefination using p-
nitrobenzaldehyde, ferrocene carboxaldehyde, compound 37,17
and 9-anthraldehyde, respectively, which led to phosphorus-free
extended conjugated pyrroles 38−41 in good yields (Scheme
9). The 1H NMR spectra of these compounds suggest that the
olefins have an (E)-configuration. The structure of one of these
compounds 41 is confirmed by X-ray crystallography (Figure
S5 in Supporting Information). Thus, this reaction clearly
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using Mn(OAc)3·2H2O as the catalyst under photochemical
conditions. In the case of phosphorus-based allenes 1−5 the
β,γ-carbon atoms of allenes participated in the pyrrole ring
formation whereas in allenoate 6, the α,β-carbon atoms are
involved. Finally, utility of the phosphorus-based pyrroles was
shown in the Horner reaction that led to multisubstituted
phosphorus-free extended conjugated pyrroles 38−41.
Scheme 8. Synthesis of Multisubstituted Pyrroles by Using
Allenoate 6 and 1,3-Dicarbonyls
EXPERIMENTAL SECTION
■
1. General Comments. Solvents were dried according to known
methods as appropriate.18 1H, 13C, and 31P NMR spectra (1H, 400
MHz or 500 MHz; 13C, 100 or 125 MHz; 31P, 162 MHz) were
recorded using a 400 or 500 MHz spectrometer in CDCl3 (unless
stated otherwise) with shifts referenced to SiMe4 (δ = 0) or 85%
H3PO4 (δ = 0). IR spectra were recorded on an FTIR
spectrophotometer. Melting points were determined by using a local
hot-stage melting point apparatus and are uncorrected. Elemental
analyses were carried out on a CHN analyzer. Mass spectra were
recorded using LCMS or HRMS (ESI-TOF analyzer) instruments.
2. Synthesis of Allenes 1−6. The phosphorus-based allenes 1−
52b,13 and allenoate 614 were synthesized according to literature
procedures.
Scheme 9. Horner Reaction of the Protected Pyrrole 36
Leading to Phosphorus-Free Extended Conjugated Pyrroles
38−41
3. Synthesis of Vinyl Azides 7−12. Compounds 7−11 were
prepared by a procedure developed in our laboratory.5c To a solution
of Me3SiN3 (0.15 g, 1.3 mmol) in DMF (5 mL) was added the allene 1
(0.21 g, 1.1 mmol), and mixture was stirred at room temperature for
2−4 h. The solvent was removed under reduced pressure to give the
crude product 7, which was purified by column chromatography on
silica gel using EtOAc−hexane (3:2) as the eluent. Compounds 8−11
were also prepared similarly. Among these, 7 and 9−11 are new. The
vinyl azide 12 was synthesized from allenoate 6 by using a reported
method.15
Compound 7. Yield 0.22 g (88%); mp 64−66 °C (white solid); IR
(KBr, cm−1) 2976, 2101, 1630, 1478, 1265, 1059, 1009, 982; 1H NMR
(400 MHz, CDCl3) δ 1.05 and 1.15 (2 s, 6H), 2.74 (d, J = 21.2 Hz,
2H), 3.87−3.93 and 4.23−4.28 (2 m, 4H), 4.91−4.93 and 5.01−5.02
(2 dd, J ∼ 2.0, 5.0 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 21.4,
21.5, 30.5 (d, J = 136.7 Hz), 32.6 (d, J = 6.1 Hz), 75.5, 75.6, 102.7 (d, J
= 10.6 Hz), 137.1 (d, J = 11.6 Hz); 31P NMR (162 MHz, CDCl3) δ
19.8; LC/MS m/z 232 [M + 1]+; Anal. Calcd for C8H14N3O3P: C,
41.56; H, 6.10; N, 18.18. Found: C, 41.63; H, 6.14; N, 18.25.
Compound 9. This azide was synthesized from the allene 3 (0.20 g,
1.0 mmol) and was isolated by using ethyl acetate−hexane (3:2)
mixture as the eluent. Yield 0.21 g (87%); mp 76−78 °C (white solid);
1
IR (KBr, cm−1) 2967, 2128, 1744, 1476, 1229, 1057, 1013, 853; H
NMR (400 MHz, CDCl3) δ 0.99 and 1.12 (2 s, 6H), 1.43 (dd, J ∼ 18.2
Hz, J ∼ 7.0 Hz, 3H), 2.66−2.77 (m, 1H), 3.78−3.89 and 4.21−4.26 (2
m, 4H), 4.89 and 5.04 (2 br, 2H); 13C NMR (100 MHz, CDCl3) δ
13.5 (d, J = 5.5 Hz), 21.4, 21.7, 32.8 (d, J = 5.8 Hz), 35.8 (d, J = 135.7
Hz), 75.1 (d, J = 2.2 Hz), 75.2 (d, J = 2.5 Hz), 101.0 (d, J = 10.0 Hz),
143.3 (d, J = 9.3 Hz); 31P NMR (162 MHz, CDCl3) δ 23.9; LC/MS
m/z 246 [M + 1]+; Anal. Calcd for C9H16N3O3P: C, 44.08; H, 6.58; N,
17.14. Found: C, 44.16; H, 6.51; N, 17.12.
Compound 10. This azide was synthesized from the allene 4 (0.50
g, 2.1 mmol) and was isolated by using ethyl acetate−hexane (3:2)
mixture as the eluent. Yield 0.52 g (89%); mp 102−104 °C (white
1
solid); IR (KBr, cm−1) 3056, 2124, 1616, 1437, 1186, 1121, 853; H
NMR (400 MHz, CDCl3) δ 3.08 (d, J = 13.2 Hz, 2H), 4.79 and 4.90
(2 br, 2H), 7.48−7.54 and 7.74−7.79 (2 m, 10H); 13C NMR (100
MHz, CDCl3) δ 36.1 (d, J = 66.4 Hz), 102.9 (d, J = 7.8 Hz), 128.6,
128.7, 131.0, 131.1, 131.9 (d, J = 100.2 Hz), 132.1, 137.5 (d, J = 9.4
Hz); 31P NMR (162 MHz, CDCl3) δ 28.1; LC/MS m/z 284 [M + 1]+;
Anal. Calcd for C15H14N3OP: C, 63.60; H, 4.98; N, 14.83. Found: C,
63.51; H, 4.91; N, 14.75.
shows one possible avenue for utililizing these phosphorus-
based pyrroles.
CONCLUSION
■
Thermolysis of phosphorus-based vinyl azides under solvent-
free and catalyst-free conditions provided an entirely new route
for 1,4-pyrazines 13−17. A simple one-pot method for
multisubstituted pyrroles have been obtained starting from
allenes via in situ-generated vinyl azides and 1,3-dicarbonyls
Compound 11. This azide was synthesized from the allene 5 (0.41
g, 1.6 mmol) and was isolated by using ethyl acetate−hexane (3:2)
mixture as the eluent. Yield 0.39 g (83%); mp 98−100 °C (white
1
solid); IR (KBr, cm−1) 3057, 2116, 1437, 1271, 1177, 1119, 843; H
NMR (400 MHz, CDCl3) δ 1.55−1.57 (m, 3H), 3.13 (d, J = 14.0 Hz,
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2H), 5.30−5.35 (m, 1H), 7.46−7.56 and 7.76−7.81 (2 m, 10H); 13C
NMR (100 MHz, CDCl3) δ 13.2, 32.3 (d, J = 66.7 Hz), 114.0 (d, J =
8.8 Hz), 128.5, 128.6, 129.2 (d, J = 10.9 Hz), 131.1, 131.2, 132.0, 132.3
(d, J = 99.1 Hz); 31P NMR (162 MHz, CDCl3) δ 28.3; LC/MS m/z
298 [M + 1]+; Anal. Calcd for C16H16N3OP: C, 64.64; H, 5.42; N,
14.13. Found: C, 64.51; H, 5.38; N, 14.25.
4. Synthesis of Phosphorus-Based 1,4-Pyrazines 13−17.
Azide 7 (0.20 g, 0.80 mmol) was taken in a round-bottomed flask,
which was then stoppered and heated at 120 °C for 15 min. The
reaction mixture was cooled to rt, and the product 13 was precipitated
by adding ethyl acetate (5 mL). Compounds 14−17 were also
synthesized by following the same method.
(0.67 g, 11.2 mmol) in MeOH (5 mL), and the mixture was irradiated
in a photoreactor (λ = 254 nm) for further 4 h. Solvent was removed
under reduced pressure and the crude product treated with ethyl
acetate (20 mL). The resulting slurry was filtered through a plug of
silica pad. Ethyl acetate was removed from the filtrate, and the product
18 was purified by column chromatography (EtOAc−hexane: 7:3).
Compounds 19−35 were also prepared similarly.
Compound 18. Yield 1.42 g (80%); mp 110−112 °C (white solid);
1
IR (KBr, cm−1) 3248, 2969, 1699, 1599, 1263, 1063, 1007; H NMR
(400 MHz, CDCl3) δ 0.96 and 1.06 (2 s, 6H), 1.30 (t, J ∼ 7.0 Hz,
3H), 2.37 (s, 3H), 3.23 (d, J = 19.6 Hz, 2H), 3.80−3.86 and 4.07−4.12
(m, 4H), 4.21−4.22 (m, 2H), 6.35 (s, 1H), 9.67 (br, 1H); 13C NMR
(100 MHz, CDCl3) δ 13.1, 14.5, 21.3, 21.4, 23.8 (d, J = 136.8 Hz),
32.6 (d, J = 6.4 Hz), 59.3, 75.9, 76.0, 110.1 (d, J = 10.0 Hz), 111.9,
117.7 (d, J = 11.1 Hz), 136.0, 165.5; 31P NMR (162 MHz, CDCl3) δ
20.0; LC/MS m/z 316 [M + 1]+; Anal. Calcd for C14H22NO5P: C,
53.33; H, 7.03; N, 4.44. Found: C, 53.41; H, 6.92; N, 4.62; HRMS
(ESI) Calcd for C14H22NO5PNa [M + Na]+ 338.1134, found
338.1134. This compound was crystallized from dichloromethane−
hexane (9:1) at 25 °C. The X-ray structure was determined for this
sample.
Compound 19. This pyrrole was prepared from allene 1 (0.24 g,
1.3 mmol) and ethyl 4-chloroacetoacetate (0.31 g, 1.9 mmol). It was
isolated by using ethyl acetate−hexane (7:3) mixture as the eluent.
Yield 0.34 g (78%); mp 126−128 °C; IR (KBr, cm−1) 3246, 1699,
1597, 1269, 1055, 1001; 1H NMR (400 MHz, CDCl3) δ 0.99 and 1.01
(2 s, 6H), 1.32 (t, J ∼ 7.0 Hz, 3H), 3.24 (d, J = 20.0 Hz, 2H), 3.43 (s,
3H), 3.77−3.84 and 4.16−4.27 (2 m, 6H), 4.75 (s, 2H), 6.41 (s, 1H),
9.20 (br, 1H); 13C NMR (100 MHz, CDCl3) δ 14.5, 21.37, 21.40, 24.2
(d, J = 138.1 Hz), 32.6 (d, J = 6.3 Hz), 58.6, 59.5, 66.8, 75.6, 75.7,
110.2 (d, J = 9.1 Hz), 112.0, 119.4 (d, J = 10.9 Hz), 135.9, 164.9; 31P
NMR (162 MHz, CDCl3) δ 20.5; LC/MS m/z 346 [M + 1]+; Anal.
Calcd for C15H24NO6P: C, 52.17; H, 7.01; N, 4.06. Found: C, 52.05;
H, 7.11; N, 4.12; HRMS (ESI) Calcd for C15H24NO6P [M]+ 345.1341,
found 345.1341.
Compound 20. This pyrrole was prepared from allene 1 (0.17 g,
0.9 mmol) and acetylacetone (0.14 g, 1.4 mmol). It was isolated by
using ethyl acetate−hexane (7:3) mixture as the eluent. Yield 0.19 g
(72%); mp 86−88 °C (white solid); IR (KBr, cm−1) 3221, 2975, 1655,
1258, 1061, 1007; 1H NMR (400 MHz, CDCl3) δ 0.99 and 1.05 (2 s,
6H), 2.34 (s, 3H), 2.41 (s, 3H), 3.24 (d, J = 20.0 Hz, 2H), 3.81−3.87
and 4.11−4.16 (2 m, 4H), 6.31 (s, 1H), 9.79 (br, 1H); 13C NMR (100
MHz, CDCl3) δ 13.8, 21.3, 21.4, 24.0 (d, J = 137.3 Hz), 28.5, 32.6 (d, J
= 6.1 Hz), 75.9, 76.0, 110.2 (d, J = 9.4 Hz), 117.7 (d, J = 10.9 Hz),
121.2, 135.7, 194.7; 31P NMR (162 MHz, CDCl3) δ 20.4; LC/MS m/z
284 [M − 1]+; Anal. Calcd for C13H20NO4P: C, 54.73; H, 7.07; N,
4.91. Found: C, 54.65; H, 7.15; N, 4.85; HRMS (ESI) Calcd for
C13H21NO4P [M + H]+ 286.1208, found 286.1208. This compound
was crystallized from dichloromethane−hexane (9:1) at 25 °C. X-ray
structure was determined for this sample.
Compound 21. This pyrrole was prepared from allene 2 (0.38 g,
1.9 mmol) and ethyl acetoacetate (0.38 g, 2.9 mmol). It was isolated
by using ethyl acetate−hexane (7:3) mixture as the eluent. Yield 0.51 g
(81%); mp 162−164 °C (white solid); IR (KBr, cm−1) 3250, 1686,
1262, 1165, 1049, 1001; 1H NMR (400 MHz, CDCl3) δ 0.98 and 1.04
(2 s, 6H), 1.33 (t, J = 7.2 Hz, 3H), 2.18 (d, J = 2.8 Hz, 3H), 2.42 (d, J
= 1.2 Hz, 3H), 3.17 (d, J = 19.6 Hz, 2H), 3.76−3.82 (m, 2H), 4.12−
4.27 (m, 4H), 9.01 (br, 1H); 13C NMR (100 MHz, CDCl3) δ 11.1,
13.8, 14.5, 21.2, 21.4, 22.1 (d, J = 135.5 Hz), 32.6 (d, J = 6.1 Hz), 59.0,
75.8, 75.9, 110.7, 114.6 (d, J = 11.5 Hz), 118.7 (d, J = 9.7 Hz), 135.7,
166.2; 31P NMR (162 MHz, CDCl3) δ 21.3; LC/MS m/z 330 [M +
1]+; Anal. Calcd for C15H24NO5P: C, 54.71; H, 7.35; N, 4.25. Found:
C, 54.91; H, 7.36; N, 4.32; HRMS (ESI) Calcd for C15H24NO5PNa
[M + Na]+ 352.1290, found 352.1290.
Compound 13. Yield 0.27 g (78%); mp 224−226 °C (white solid);
1
IR (KBr, cm−1) 2982, 1487, 1408, 1265, 1065, 1003; H NMR (400
MHz, CDCl3) δ 0.89 and 1.01 (2 s, 12H), 3.51 (d, J = 20.8 Hz, 4H),
3.85−3.91 and 4.14−4.19 (2 m, 8H), 8.60 (s, 2H); 13C NMR (100
MHz, CDCl3) δ 21.3, 21.4, 32.2 (d, J = 131.8 Hz), 32.5 (d, J = 5.9 Hz),
75.6, 75.7, 144.8, 146.5 (d, J = 2.5 Hz); 31P NMR (162 MHz, CDCl3)
δ 19.1; LC/MS m/z 405 [M + 1]+; Anal. Calcd for C16H26N2O6P2: C,
47.53; H, 6.48; N, 6.93. Found: C, 47.62; H, 6.52; N, 6.85; HRMS
(ESI) Calcd for C16H27N2O6P2 [M + H]+ 405.1344, found 405.1344.
Compound 14. This product was synthesized from the azide 8
(0.15 g, 0.6 mmol). Yield 0.20 g (75%); mp 222−224 °C (white
solid); IR (KBr, cm−1) 2965, 1474, 1377, 1244, 1055, 1015; 1H NMR
(400 MHz, CDCl3) δ 0.90 and 1.06 (2 s, 12H), 2.64 (s, 6H), 3.53 (d, J
= 20.4 Hz, 4H), 3.89−3.95 and 4.11−4.16 (2 m, 8H); 13C NMR (100
MHz, CDCl3) δ 21.1, 21.5, 21.6, 32.1 (d, J = 131.1 Hz), 32.5 (d, J =
6.5 Hz), 75.7, 75.8, 144.2, 149.9; 31P NMR (162 MHz, CDCl3) δ 19.3;
LC/MS m/z 431 [M − 1]+; Anal. Calcd for C18H30N2O6P2: C, 50.00;
H, 6.99; N, 6.48. Found: C, 50.12; H, 6.92; N, 6.41; HRMS (ESI)
Calcd for C18H31N2O6P2 [M + H]+ 433.1657, found 433.1657. This
compound was crystallized from methanol (2 mL) at 25 °C. The X-ray
structure was determined for this sample.
Compound 15. This product was synthesized from the azide 9
(0.15 g, 0.6 mmol). Yield 0.20 g (74%); mp 222−224 °C (white
1
solid); IR (KBr, cm−1) 2922, 2114, 1647, 1534, 1269, 1047, 1017; H
NMR (400 MHz, CDCl3) δ 0.91 and 0.96 (2 s, 12H), 1.73 (dd, J =
18.0 Hz, J ∼ 7.2 Hz, 6H), 3.59−3.87 (m, 6H), 4.16−4.25 (m, 4H),
8.64 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 13.6, 21.39, 21.45, 32.6
(br), 37.3 (d, J = 133.1 Hz), 75.1, 75.2, 144.1, 151.3; 31P NMR (162
MHz, CDCl3) δ 23.5; LC/MS m/z 431 [M − 1]+; Anal. Calcd for
C18H30N2O6P2: C, 50.00; H, 6.99; N, 6.48. Found: C, 49.95; H, 7.06;
N, 6.55; HRMS (ESI) Calcd for C18H31N2O6P2 [M + H]+ 433.1657,
found 433.1657.
Compound 16. This product was synthesized from the azide 10
(0.20 g, 0.7 mmol). Yield 0.26 g (72%); mp 258−260 °C (white
1
solid); IR (KBr, cm−1) 3052, 1483, 1437, 1402, 1177, 1121, 1032; H
NMR (400 MHz, CDCl3) δ 3.87 (d, J = 13.6 Hz, 4H), 7.43−7.55 and
7.69−7.74 (2 m, 20H), 8.42 (s, 2H); 13C NMR (100 MHz, CDCl3) δ
38.3 (d, J = 63.7 Hz), 128.6, 128.66, 128.72, 131.02, 131.07, 131.12,
131.8 (d, J = 100.7 Hz), 132.1, 144.9, 146.5; 31P NMR (162 MHz,
CDCl3) δ 29.3; LC/MS m/z 507 [M − 1]+; Anal. Calcd for
C30H26N2O2P2: C, 70.86; H, 5.15; N, 5.51. Found: C, 70.73; H, 5.08;
N, 5.60; HRMS (ESI) Calcd for C30H26N2O2P2Na [M + Na]+
531.1367, found 531.1368.
Compound 17. This product was synthesized from the azide 11
(0.20 g, 0.7 mmol). Yield 0.26 g (73%); mp 232−234 °C (white
solid); IR (KBr, cm−1) 2951, 1435, 1227, 1186, 1121, 1074; 1H NMR
(400 MHz, CDCl3) δ 2.29 (s, 6H), 3.83 (d, J = 14.0 Hz, 4H), 7.42−
7.51 and 7.71−7.75 (2 m, 20H); 13C NMR (100 MHz, CDCl3) δ 21.2,
37.8 (d, J = 64.0 Hz), 128.31, 128.37, 128.43, 131.25, 131.31, 131.9,
132.9, 144.1, 150.1; 31P NMR (162 MHz, CDCl3) δ 30.6; LC/MS m/z
537 [M + 1]+; Anal. Calcd for C32H30N2O2P2: C, 71.63; H, 5.64; N,
5.22. Found: C, 71.52; H, 5.68; N, 5.16; HRMS (ESI) Calcd for
C32H31N2O2P2 [M + H]+ 537.1861, found 537.1861.
Compound 22. This pyrrole was prepared from allene 2 (0.36 g,
1.8 mmol) and ethyl 4-chloroacetoacetate (0.44 g, 2.7 mmol). It was
isolated by using ethyl acetate−hexane (7:3) mixture as the eluent.
Yield 0.44 g (69%); mp 170−172 °C (white solid); IR (KBr, cm−1)
3353, 1688, 1472, 1372, 1269, 1169, 1059, 1009; 1H NMR (400 MHz,
CDCl3) δ 0.94 and 0.99 (2 s, 6H), 1.34 (t, J ∼ 7.2 Hz, 3H), 2.19 (s,
5. Synthesis of Multisubstituted Pyrrole Derivatives 18−35.
To a solution of Me3SiN3 (0.77 g, 6.7 mmol) in DMF (10 mL) was
added the allene 1 (1.05 g, 5.6 mmol), and the reaction mixture stirred
for 2−4 h. To this was added a solution of ethyl acetoacetate (1.10 g,
8.4 mmol), Mn(OAc)3·2H2O (0.15 g, 0.56 mmol), and acetic acid
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3H), 3.20 (d, J = 19.6 Hz, 2H), 3.43 (s, 3H), 3.72−3.81 (m, 2H),
4.16−4.28 (m, 4H), 4.72 (s, 2H), 9.12 (br, 1H); 13C NMR (100 MHz,
CDCl3) δ 14.5, 20.8, 21.4, 21.5, 24.3 (d, J = 138.8 Hz), 32.7 (d, J = 6.3
Hz), 58.6, 59.6, 66.9, 75.67, 75.72, 110.3 (d, J = 8.8 Hz), 112.0, 119.5
(d, J = 11.3 Hz), 135.9, 165.0; 31P NMR (162 MHz, CDCl3) δ 21.3;
LC/MS m/z 360 [M + 1]+; Anal. Calcd for C16H26NO6P: C, 53.48; H,
7.29; N, 3.90. Found: C, 53.36; H, 7.36; N, 3.82; HRMS (ESI) Calcd
for C16H27NO6P [M + H]+ 360.1576, found 360.1576.
Compound 23. This pyrrole was prepared from allene 2 (0.42 g,
2.1 mmol) and acetylacetone (0.32 g, 3.2 mmol). It was isolated by
using ethyl acetate−hexane (7:3) mixture as the eluent. Yield 0.45 g
(72%); mp 178−180 °C (white solid); IR (KBr, cm−1) 3223, 1644,
1478, 1250, 1053, 999; 1H NMR (400 MHz, CDCl3) δ 1.03 and 1.07
(2 s, 6H), 2.23 (d, J = 2.8 Hz, 3H), 2.41 (s, 3H), 2.45 (s, 3H), 3.20 (d,
J = 19.6 Hz, 2H), 3.80−3.86 and 4.15−4.21 (2 m, 4H), 9.22 (br, 1H);
13C NMR (100 MHz, CDCl3) δ 11.8, 15.1, 21.4, 21.6 (d, J = 138.0
Hz), 30.9 (d, J = 3.2 Hz), 32.6 (d, J = 6.1 Hz), 75.6, 75.7, 115.0 (d, J =
11.1 Hz), 118.2 (d, J = 9.8 Hz), 121.4, 134.9 (d, J = 7.3 Hz), 195.1 (d,
J = 4.8 Hz); 31P NMR (162 MHz, CDCl3) δ 21.3; LC/MS m/z 300
[M + 1]+; Anal. Calcd for C14H22NO4P: C, 56.18; H, 7.41; N, 4.68.
Found: C, 56.35; H, 7.32; N, 4.81; HRMS (ESI) Calcd for
C14H23NO4P [M + H]+ 300.1364, found 300.1364.
Compound 24. This pyrrole was prepared from allene 3 (0.10 g,
0.5 mmol) and ethyl acetoacetate (0.09 g, 0.7 mmol). It was isolated
by using ethyl acetate−hexane (7:3) mixture as the eluent. Yield 0.13 g
(79%); mp 124−126 °C (white solid); IR (KBr, cm−1) 3233, 2922,
1694, 1260, 1061; 1H NMR (400 MHz, CDCl3) δ 0.97 and 1.04 (2 s,
6H), 1.30 (t, J ∼ 7.0 Hz, 3H), 1.56 (dd, J ∼ 18.2 Hz, J = 7.2 Hz, 3H),
2.39 (s, 3H), 3.28−3.39 (m, 1H), 3.69−3.84 and 4.14−4.24 (2 m,
6H), 6.37 (s, 1H), 9.60 (br, 1H); 13C NMR (100 MHz, CDCl3) δ
13.1, 14.0, 14.6, 21.4, 21.6, 30.0 (d, J = 137.2 Hz), 32.7 (d, J = 5.9 Hz),
59.2, 75.2 (d, J = 6.6 Hz), 75.4 (d, J = 6.5 Hz), 108.6 (d, J = 9.2 Hz),
111.6 (d, J = 1.4 Hz), 124.3 (d, J = 9.5 Hz), 136.1, 165.6; 31P NMR
(162 MHz, CDCl3) δ 24.7; LC/MS m/z 330 [M + 1]+; Anal. Calcd
for C15H24NO5P: C, 54.71; H, 7.35; N, 4.25. Found: C, 54.81; H, 7.28;
N, 4.33; HRMS (ESI) Calcd for C15H25NO5P [M + H]+ 330.1470,
found 330.1470.
Compound 25. This pyrrole was prepared from allene 3 (0.24 g,
1.2 mmol) and ethyl 4-chloroacetoacetate (0.30 g, 1.8 mmol). It was
isolated by using ethyl acetate−hexane (7:3) mixture as the eluent.
Yield 0.33 g (77%); mp 134−136 °C (white solid); IR (KBr, cm−1)
3351, 1692, 1468, 1375, 1227, 1059, 1009; 1H NMR (400 MHz,
CDCl3) δ 0.94 and 1.02 (2 s, 6H), 1.32 (t, J = 7.2 Hz, 3H), 1.59 (dd, J
= 18.2 Hz, J ∼ 7.4 Hz, 3H), 3.30−3.39 (m, 1H), 3.42 (s, 3H), 3.69−
3.80 and 4.20−4.27 (2 m, 6H), 4.75 (s, 2H), 6.42 (s, 1H), 9.43 (br,
1H); 13C NMR (100 MHz, CDCl3) δ 13.8, 14.5, 21.3, 21.6, 30.1 (d, J
= 137.7 Hz), 32.7 (d, J = 5.6 Hz), 58.6, 59.6, 66.8, 75.1, 75.2, 108.7 (d,
J = 8.8 Hz), 111.7, 125.9 (d, J = 9.2 Hz), 135.8, 165.0; 31P NMR (162
MHz, CDCl3) δ 24.8; LC/MS m/z 360 [M + 1]+; Anal. Calcd for
C16H26NO6P: C, 53.48; H, 7.29; N, 3.90. Found: C, 53.62; H, 7.23; N,
3.81; HRMS (ESI) Calcd for C16H26NO6P [M]+ 359.1498, found
359.1498.
1688, 1437, 1331, 1177, 1073; 1H NMR (400 MHz, CDCl3) δ 1.28 (t,
J ∼ 7.0 Hz, 3H), 2.25 (s, 3H), 3.66 (d, J = 11.6 Hz, 2H), 4.17−4.21
(m, 2H), 6.10 (s, 1H), 7.45−7.71 (m, 10H), 10.43 (br, 1H); 13C NMR
(100 MHz, CDCl3) δ 13.1, 14.5, 29.6 (d, J = 68.0 Hz, PCH), 59.2,
109.9, 111.5, 119.0, 128.7, 128.9, 130.9, 131.3, 132.2, 136.1, 165.7; 31P
NMR (162 MHz, CDCl3) δ 30.9; LC/MS m/z 368 [M + 1]+; Anal.
Calcd for C21H22NO3P: C, 68.66; H, 6.04; N, 3.81. Found: C, 68.56;
H, 6.12; N, 3.76; HRMS (ESI) Calcd for C21H22NO3PNa [M + Na]+
390.1235, found 390.1235.
Compound 28. This pyrrole was prepared from allene 4 (0.29 g,
1.2 mmol) and ethyl 4-chloroacetoacetate (0.31 g, 1.9 mmol). It was
isolated by using ethyl acetate−hexane (7:3) mixture as the eluent.
Yield 0.38 g (80%); mp 182−184 °C (white solid); IR (KBr, cm−1)
3351, 2122, 1703, 1618, 1437, 1285, 1186, 1024; 1H NMR (400 MHz,
CDCl3) δ 1.30 (t, J ∼ 7.0 Hz, 3H), 3.37 (s, 3H), 3.62 (d, J = 12.8 Hz,
2H), 4.21 (qrt, J ∼ 7.0 Hz, 2H), 4.69 (s, 2H), 6.24 (s, 1H), 7.44−7.55
and 7.66−7.70 (2 m, 10H), 9.92 (br, 1H); 13C NMR (100 MHz,
CDCl3) δ 14.5, 29.5 (d, J = 68.2 Hz), 58.5, 59.5, 66.8, 110.2 (d, J = 7.4
Hz), 111.6, 120.9 (d, J = 9.2 Hz), 128.7, 128.8, 130.8, 130.9, 131.8 (d, J
= 99.3 Hz), 132.2, 135.9, 165.0; 31P NMR (162 MHz, CDCl3) δ 30.5;
LC/MS m/z 398 [M + 1]+; Anal. Calcd for C22H24NO4P: C, 66.49; H,
6.09; N, 3.52. Found: C, 66.59; H, 6.14; N, 3.45; HRMS (ESI) Calcd
for C22H24NO4PNa [M + Na]+ 420.1341, found 420.1341.
Compound 29. This pyrrole was prepared from allene 4 (0.29 g,
1.2 mmol) and acetylacetone (0.19 g, 1.9 mmol). It was isolated by
using ethyl acetate−hexane (7:3) mixture as the eluent. Yield 0.28 g
(70%); mp 92−94 °C (white solid); IR (KBr, cm−1) 3289, 1645, 1437,
1175, 1115, 945; 1H NMR (400 MHz, CDCl3) δ 2.21 (s, 3H), 2.41 (s,
3H), 4.16 (d, J = 12.4 Hz, 2H), 6.61 (s, 1H), 7.37−7.49 and 7.71−7.76
(2 m, 10H), 10.90 (br, 1H); 13C NMR (100 MHz, CDCl3) δ 13.9,
28.4, 29.5 (d, J = 68.4 Hz), 110.2 (d, J = 7.8 Hz), 119.2 (d, J = 9.6 Hz),
121.0, 128.7, 128.8, 130.8, 130.9, 131.3, 131.7 (d, J = 99.5 Hz), 131.8
(d, J = 10.9 Hz), 132.3, 135.6, 194.5; 31P NMR (162 MHz, CDCl3) δ
33.0; LC/MS m/z 338 [M + 1]+; Anal. Calcd for C20H20NO2P: C,
71.21; H, 5.98; N, 4.15. Found: C, 71.36; H, 5.88; N, 4.21.
Compound 30. This pyrrole was prepared from allene 5 (0.53 g,
2.1 mmol) and ethyl acetoacetate (0.40 g, 3.1 mmol). It was isolated
by using ethyl acetate−hexane (7:3) mixture as the eluent. Yield 0.64 g
(81%); mp 116−118 °C (white solid); IR (KBr, cm−1) 3229, 1699,
1439, 1267, 1175, 953; 1H NMR (400 MHz, CDCl3) δ 1.30 (t, J ∼ 7.0
Hz, 3H), 1.85 (d, J = 2.0 Hz, 3H), 2.31 (s, 3H), 3.57 (d, J = 12.0 Hz,
2H), 4.20 (qrt, J ∼ 7.0 Hz, 2H), 7.41−7.54 and 7.64−7.69 (2 m, 10H),
10.19 (br, 1H); 13C NMR (100 MHz, CDCl3) δ 10.8, 14.0, 14.5, 27.6
(d, J = 69.1 Hz), 58.9, 110.4, 115.9 (d, J = 9.6 Hz), 118.6 (d, J = 7.3
Hz), 128.7, 128.8, 130.8, 131.0, 132.0 (d, J = 98.3 Hz), 132.2, 136.0,
166.4; 31P NMR (162 MHz, CDCl3) δ 30.8; LC/MS m/z 382 [M +
1]+; Anal. Calcd for C22H24NO3P: C, 69.28; H, 6.34; N, 3.67. Found:
C, 69.12; H, 6.29; N, 3.75.
Compound 31. This pyrrole was prepared from allene 5 (0.43 g,
1.7 mmol) and ethyl 4-chloroacetoacetate (0.41 g, 2.5 mmol). It was
isolated by using ethyl acetate−hexane (7:3) mixture as the eluent.
Yield 0.54 g (77%); mp 120−122 °C (white solid); IR (KBr, cm−1)
1
Compound 26. This pyrrole was prepared from allene 3 (0.20 g,
1.0 mmol) and acetylacetone (0.15 g, 1.5 mmol). It was isolated by
using ethyl acetate−hexane (7:3) mixture as the eluent. Yield 0.21 g
(71%); mp 104−106 °C; IR (KBr, cm−1) 3212, 2978, 1649, 1474,
1256, 1065, 1011; 1H NMR (400 MHz, CDCl3) δ 0.97 and 1.10 (2 s,
6H), 1.59 (dd, J = 18.0 Hz, J = 7.2 Hz, 3H), 2.37 (s, 3H), 2.48 (s, 3H),
3.31−3.36 (m, 1H), 3.74−3.85 and 4.22−4.25 (m, 4H), 6.34 (s, 1H),
9.30 (br, 1H); 13C NMR (100 MHz, CDCl3) δ 14.0, 14.1 (d, J = 5.1
Hz), 21.3, 21.7, 28.5, 29.9 (d, J = 137.4 Hz), 32.7 (d, J = 5.8 Hz), 75.1,
75.2, 108.9 (d, J = 9.5 Hz), 120.9, 124.2 (d, J = 9.2 Hz), 135.6, 194.7;
31P NMR (162 MHz, CDCl3) δ 25.1; LC/MS m/z 300 [M + 1]+;
Anal. Calcd for C14H22NO4P: C, 56.18; H, 7.41; N, 4.68. Found: C,
56.32; H, 7.48; N, 4.61; HRMS (ESI) Calcd for C14H23NO4P [M +
H]+ 300.1364, found 300.1364.
3250, 2926, 1698, 1437, 1181, 1100; H NMR (400 MHz, CDCl3) δ
1.32 (t, J ∼ 7.0 Hz, 3H), 2.01 (s, 3H), 3.40 (s, 3H), 3.53 (d, J = 12.4
Hz, 2H), 4.22 (qrt, J ∼ 7.0 Hz, 2H), 4.70 (s, 2H), 7.46−7.56 and
7.65−7.69 (2 m, 10H), 9.65 (br, 1H); 13C NMR (100 MHz, CDCl3) δ
10.5, 14.5, 27.3 (d, J = 68.9 Hz), 58.6, 59.2, 67.6, 110.1, 117.7 (d, J =
9.0 Hz), 118.9 (d, J = 7.4 Hz), 128.7, 128.8, 130.76, 130.83, 132.06 (d, J
= 98.6 Hz), 132.11, 132.13, 135.9, 165.7; 31P NMR (162 MHz, CDCl3)
δ 30.8; LC/MS m/z 412 [M + 1]+; Anal. Calcd for C23H26NO4P: C,
67.14; H, 6.37; N, 3.40. Found: C, 67.25; H, 6.41; N, 3.34; HRMS
(ESI) Calcd for C23H26NO4PNa [M + Na]+ 434.1497, found
434.1497.
Compound 32. This pyrrole was prepared from allene 5 (0.33 g,
1.3 mmol) and acetylacetone (0.19 g, 1.9 mmol). It was isolated by
using ethyl acetate−hexane (7:3) mixture as the eluent. Yield 0.33 g
(73%); mp 180−182 °C (white solid); IR (KBr, cm−1) 3148, 1630,
Compound 27. This pyrrole was prepared from allene 4 (0.41 g,
1.7 mmol) and ethyl acetoacetate (0.34 g, 2.6 mmol). It was isolated
by using ethyl acetate−hexane (7:3) mixture as the eluent. Yield 0.55 g
(88%); mp 178−180 °C (white solid); IR (KBr, cm−1) 3208, 2924,
1
1437, 1169, 1116, 965; H NMR (400 MHz, CDCl3) δ 2.01 (s, 3H),
2.05 (s, 3H), 2.34 (s, 3H), 4.10 (d, J = 12.8 Hz, 2H), 7.41−7.47 and
7.75−7.79 (2 m, 10H), 9.51 (br, 1H); 13C NMR (100 MHz, CDCl3) δ
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11.0, 15.3, 27.7 (d, J = 69.1 Hz, PCH2), 30.4, 109.2 (d, J = 9.5 Hz),
120.6, 126.7 (d, J = 6.7 Hz), 128.0, 128.1, 131.4, 131.5, 132.8, 133.0
(d, J = 96.2 Hz), 195.0; 31P NMR (162 MHz, CDCl3) δ 32.0; LC/MS
m/z 352 [M + 1]+; Anal. Calcd for C21H22NO2P: C, 71.78; H, 6.31; N,
3.99. Found: C, 71.65; H, 6.39; N, 3.89.
Compound 33. This pyrrole was prepared from allene 6 (0.11 g,
1.0 mmol) and ethyl acetoacetate (0.20 g, 1.6 mmol). It was isolated
by using ethyl acetate−hexane (1:4) mixture as the eluent. Yield 0.18 g
(75%); mp 90−92 °C (white solid); IR (KBr, cm−1) 3289, 1669, 1445,
1215, 1157, 1028; 1H NMR (400 MHz, CDCl3) δ 1.36−1.41 (m, 6H),
2.54 and 2.58 (2 s, 6H), 4.29−4.38 (m, 4H), 9.00 (br, 1H); 13C NMR
(100 MHz, CDCl3) δ 11.9, 14.3, 14.4, 14.5, 59.5, 60.3, 113.7, 117.9,
130.9, 138.7, 161.6, 165.4; LC/MS m/z 240 [M + 1]+; Anal. Calcd for
C12H17NO4: C, 60.24; H, 7.16; N, 5.85. Found: C, 60.32; H, 7.08; N,
5.81; HRMS (ESI) Calcd for C12H18NO4 [M + H]+ 240.1236, found
240.1236.
the mixture stirred for 12 h at room temperature. Water (10 mL) was
added and the aqueous layer thoroughly extracted with diethyl ether (3
× 20 mL). The organic layer was collected, dried (Na2SO4), and
filtered, and the solvent removed from the filtrate to give a residue that
was purified by column chromatography [silica gel, ethyl acetate−
hexane (1:4)] to furnish 38. Compounds 39−41 were also synthesized
in a manner similar to that for compound 38.
Compound 38. Yield 0.09 g (73%); mp 124−126 °C (yellow
solid); IR (KBr, cm−1) 2963, 1703, 1588, 1343, 1262, 1020; 1H NMR
(400 MHz, CDCl3) δ 1.39 (t, J = 7.2 Hz, 3H), 2.54 (s, 3H), 4.32 (qrt,
J = 7.2 Hz, 2H), 5.24 (s, 2H), 6.95−7.01 (m, 3H), 7.08 (s, 1H), 7.30−
7.46 (m, 6H), 8.12−8.15 (m, 2H); 13C NMR (100 MHz, CDCl3) δ
11.5, 14.5, 47.0, 59.7, 109.6, 113.6, 120.6, 124.2, 124.6, 125.6, 126.2,
127.9, 128.1, 128.6, 129.2, 130.4, 136.5, 138.4, 144.0, 165.1; LC/MS
m/z 391 [M + 1]+; Anal. Calcd for C23H22N2O4: C, 70.75; H, 5.68; N,
7.17. Found: C, 70.68; H, 5.75; N, 7.22; HRMS (ESI) Calcd for
C23H22N2O4Na [M + Na]+ 413.1477, found 413.1478.
Compound 39. This compound was prepared from 36 (0.34 g, 0.75
mmol) and ferrocene carboxaldehyde (0.16 g, 0.75 mmol). It was
isolated by using hexane as the eluent. Yield 0.24 g (74%); mp 118−
120 °C (violet solid); IR (KBr, cm−1) 3372, 2926, 1696, 1427, 1240,
1211, 1161, 1028; 1H NMR (400 MHz, CDCl3) δ 1.39 (t, J = 7.2 Hz,
3H), 2.52 (s, 3H), 4.02 (s, 5H), 4.21−4.30 (m, 6H), 5.16 (s, 2H), 6.39
(d, J ∼ 15.8 Hz, 1H), 6.66 (d, J ∼ 15.8 Hz), 6.84 (s, 1H), 6.99−7.01
(m, 2H), 7.29−7.36 (m, 3H); 13C NMR (100 MHz, CDCl3) δ 11.3,
14.6, 46.9, 59.4, 66.5, 68.9, 69.2, 83.4, 106.3, 112.6, 114.0, 125.8, 126.6,
127.6, 128.9, 131.9, 136.4, 137.1, 165.5; LC/MS m/z 452 [M − 1]+;
Anal. Calcd for C27H27NO2Fe: C, 71.53; H, 6.00; N, 3.09. Found: C,
71.42; H, 6.08; N, 3.15; HRMS (ESI) Calcd for C27H28NO2Fe [M +
H]+ 454.1469, found 454.1469.
Compound 34. This pyrrole was prepared from allene 6 (0.35 g,
3.1 mmol) and ethyl 4-chloroacetoacetate (0.76 g, 4.6 mmol). It was
isolated by using ethyl acetate−hexane (1:4) mixture as the eluent.
Yield 0.60 g (72%); mp 110−112 °C (white solid); IR (KBr, cm−1)
1
3366, 1651, 1429, 1155, 1030; H NMR (400 MHz, CDCl3) δ 1.32−
1.36 (m, 6H), 2.42 (s, 3H), 3.43 (s, 3H), 4.26−4.33 (m, 4H), 4.65 (s,
2H), 8.73 (br, 1H); 13C NMR: (100 MHz, CDCl3) δ 12.5, 14.3, 58.5,
60.16, 60.21, 66.4, 112.4, 112.7, 132.8, 133.1, 164.7, 165.3; LC/MS m/z
270 [M + 1]+; Anal. Calcd for C13H19NO5: C, 57.98; H, 7.11; N, 5.20.
Found: C, 57.85; H, 7.16; N, 5.31.
Compound 35. This pyrrole was prepared from allene 6 (0.45 g,
4.0 mmol) and acetylacetone (0.58 g, 5.8 mmol). It was isolated by
using ethyl acetate−hexane (1:4) mixture as the eluent. Yield 0.59 g
(71%); mp 122−124 °C (white solid); IR (KBr, cm−1) 3281, 1649,
1
1556, 1281, 1202, 1022; H NMR (400 MHz, CDCl3) δ 1.38 (t, J =
Compound 40. This compound was prepared from 36 (0.14 g, 0.3
mmol) and compound 3715 (0.08 g, 0.3 mmol). It was isolated by
using ethyl acetate−hexane (1:4) mixture as the eluent. Yield 0.11 g
(76%); mp 120−122 °C (white solid); IR (KBr, cm−1) 2976, 2930,
7.2 Hz, 3H), 2.45 (s, 3H), 2.53 (s, 3H), 2.59 (s, 3H), 4.31−4.37 (m,
2H), 9.21 (br, 1H); 13C NMR (100 MHz, CDCl3) δ 12.7, 14.5, 15.2,
31.4, 60.4, 118.0, 123.6, 129.4, 138.2, 161.7, 195.6; LC/MS m/z 210
[M + 1]+; Anal. Calcd for C11H15NO3: C, 63.14; H, 7.23; N, 6.69.
Found: C, 63.06; H, 7.31; N, 6.75; HRMS (ESI) Calcd for
C11H15NO3Na [M + Na]+ 232.0950, found 232.0951. This compound
was crystallized from ethyl acetate−hexane (9:1) at 25 °C. The X-ray
structure was determined for this sample.
1
1694, 1597, 1453, 1215, 1100, 1055; H NMR (400 MHz, CDCl3) δ
1.39 (t, J ∼ 7.0 Hz, 3H), 2.45 (s, 3H), 2.53 (s, 3H), 4.03 (s, 3H), 4.32
(qrt, J ∼ 7.0 Hz, 2H), 5.23 (s, 2H), 6.76−6.79 (m, 2H), 6.96 (s, 1H),
7.02−7.09 (m, 4H), 7.27−7.38 (m, 4H), 7.45−7.49 (m, 2H), 7.80−
7.82 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 9.7, 11.4, 14.6, 47.1,
56.3, 59.5, 105.1, 107.2, 109.9, 111.6, 112.8, 115.4, 125.9, 126.8, 127.6,
128.0, 128.6, 128.8, 129.0, 131.1, 131.6, 133.1, 136.96, 137.03, 142.8,
145.1, 151.5, 165.5. LC/MS m/z 506 [M + 1]+; Anal. Calcd for
C33H31NO4: C, 78.39; H, 6.18; N, 2.77. Found: C, 78.26; H, 6.21; N,
2.71.
Compound 41. This compound was prepared from 36 (0.30 g, 0.7
mmol) and 9-anthraldehyde (0.14 g, 0.7 mmol). It was isolated by
using ethyl acetate−hexane (1:4) mixture as the eluent. Yield 0.23 g
(78%); mp 128−130 °C (yellow solid); IR (KBr, cm−1) 2986, 2928,
1698, 1443, 1242, 1211, 1169, 1069 cm−1; 1H NMR (400 MHz,
CDCl3) δ 1.43 (t, J ∼ 7.0 Hz, 3H), 2.61 (s, 3H), 4.37 (qrt, J ∼ 7.0 Hz,
2H), 5.21 (s, 2H), 6.68 (d, J ∼ 16.2 Hz, 1H), 6.98−6.99 (m, 2H), 7.21
(s, 1H), 7.28−7.45 (m, 7H), 7.72 (d, J ∼ 16.2 Hz, 1H), 7.95−7.97 (m,
2H), 8.08−8.10 (m, 2H), 8.34 (s, 1H); 13C NMR (100 MHz, CDCl3)
δ 11.4, 14.6, 47.0, 59.6, 107.8, 112.9, 123.6, 125.1, 125.4, 125.7, 125.8,
126.0, 126.3, 127.6, 128.6, 129.0, 129.6, 131.2, 131.4, 132.6, 136.8,
137.3, 165.5; LC/MS m/z 446 [M + 1]+; Anal. Calcd for C31H27NO2:
C, 83.57; H, 6.11; N, 3.14. Found: C, 83.45; H, 6.17; N, 3.19; HRMS
(ESI) Calcd for C31H28NO2 [M + H]+ 446.2120, found 446.2120.
This compound was crystallized from ethyl acetate−hexane (9:1) at 25
°C. X-ray structure was determined for this sample.
6. Utility of Phosphorus-Based Pyrrole in the Horner
Reaction: Synthesis of Phosphorus-Free Extended Conjugated
Pyrroles 38−41. a. Synthesis of N-Benzylated Pyrrole 36. Pyrrole
27 (0.20 g, 0.54 mmol) was added to toluene (5 mL) and aq NaOH (2
mL 50% solution). To this suspension were added tetrabutylammo-
nium iodide (2.00 mg, 0.01 mmol) and benzyl bromide (0.09 g, 0.54
mmol). The mixture was heated under reflux for 24 h. The solvent was
removed under reduced pressure, and water (10 mL) was added. The
mixture was extracted with ethyl acetate (3 × 10 mL), dried (Na2SO4),
and filtered, and the solvent was removed from the filtrate to give the
crude product. Pure compound 36 was obtained by column
chromatography (silica gel, ethyl acetate−hexane, 1:1) as a white
solid. Yield 0.17 g (68%); mp 162−164 °C (white solid); IR (KBr,
1
cm−1) 2926, 1696, 1437, 1184, 1069; H NMR (400 MHz, CDCl3) δ
1.31 (t, J = 7.2 Hz, 3H), 2.45 (s, 3H), 3.50 (d, J = 12.0 Hz, 2H), 4.22
(qrt, J = 7.2 Hz, 2H), 5.29 (s, 2H), 6.17 (s, 1H), 6.85 (d, J = 6.8 Hz,
2H), 7.25−7.32 (m, 3H), 7.45−7.57 (m, 6H), 7.65−7.70 (m, 4H); 13C
NMR (100 MHz, CDCl3) δ 11.5, 14.5, 29.6 (d, J = 68.6 Hz), 47.0,
59.3, 111.4 (d, J = 4.5 Hz), 111.9, 121.2 (d, J = 6.7 Hz), 125.6, 127.3,
128.5, 128.7, 128.9, 131.0, 131.1, 131.4, 131.5, 131.9 (d, J = 98.4 Hz),
132.00 (d, J = 98.6 Hz), 132.01, 132.03, 136.8, 137.1, 165.4; 31P NMR
(162 MHz, CDCl3) δ 28.8; LC/MS m/z 457 [M − 1]+; Anal. Calcd
for C28H28NO3P: C, 73.51; H, 6.17; N, 3.06. Found: C, 73.45; H, 6.22;
N, 3.12; HRMS (ESI) Calcd for C28H29NO3P [M + H]+ 458.1885,
found 458.1885.
b. Synthesis of Phosphorus-Free Extended Conjugated Pyrroles
38−41. The phosphonate 36 (0.14 g, 0.30 mmol) was dissolved in dry
THF (5 mL) and added dropwise (10 min) to a suspension of NaH
(0.014 g, 0.60 mmol) in THF (5 mL) at 0 °C with stirring. The
mixture was stirred further at this temperature for 0.5 h. Then 4-
nitrobenzaldehyde (0.05 g, 0.30 mmol) in THF (2 mL) was added and
7. X-ray Data. X-ray data for compounds 14, 18, 20·H2O, 35, and
41 were collected on an X-ray diffractometer using Mo Kα (λ =
0.71073 Å) radiation. The structures were solved and refined by
standard methods.19 CCDC numbers are CCDC 892102−892106.
8. Crystal Data. 14: C18H30N2O6P2, M = 432.38, monoclinic, space
group P2(1)/c, a = 15.587(2), b = 6.0979(8), c = 11.5256(15) Å, β =
103.146(2)°, V = 1066.8(2) Å3, Z = 2, μ = 0.240 mm−1, data/
restraints/parameters: 1886/0/130, R indices (I > 2σ(I)): R1 =
0.0385, wR2 (all data) = 0.1021. CCDC no. 882102.
8720
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Article
18: C14H22NO5P, M = 315.30, orthorhombic, space group Pna2(1),
a = 22.0358(19), b = 6.0237(5), c = 24.783(2) Å, V = 3289.6(5) Å3, Z
= 8, μ = 0.186 mm−1, data/restraints/parameters: 5788/4/384, R
indices (I > 2σ(I)): R1 = 0.0802, wR2 (all data) = 0.2050. CCDC no.
882103.
20·H2O: C13H22NO5P, M = 303.29, triclinic, space group P-1, a =
5.5991(8), b = 10.8370(15), c = 13.4812(18) Å, α = 104.942(12)°, β =
99.962(11)°, γ = 96.168(11)°, V = 768.43(18) Å3, Z = 2, μ = 0.197
mm−1, data/restraints/parameters: 2604/0/189, R indices (I > 2σ(I)):
R1 = 0.0483, wR2 (all data) = 0.1337. CCDC no. 882104.
35: C11H15NO3, M = 209.24, monoclinic, space group P2(1)/c, a =
8.0841(11), b = 6.8413(9), c = 20.348(3) Å, β = 103.655(5)°, V =
1093.6(3) Å3, Z = 4, μ = 0.093 mm−1, data/restraints/parameters:
1921/0/140, R indices (I > 2σ(I)): R1 = 0.0548, wR2 (all data) =
0.1447. CCDC no. 882105.
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11.605(3), b = 20.308(5), c = 10.711(3) Å, β = 106.598(5)°, V =
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ASSOCIATED CONTENT
■
S
* Supporting Information
Materials including ORTEP drawings; copies of H/13C NMR
1
spectra of all new products; CIF files. This material is available
free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: kckssc@yahoo.com; kckssc@uohyd.ernet.in. Fax:
(+91)-40-23012460.
■
Tetrahedron Lett. 1999, 40, 789. (f) Banert, K.; Kohler, F. Angew.
̈
Notes
Chem., Int. Ed. 2001, 40, 174. (g) Brel, V. K. Synthesis 2002, 1829.
The authors declare no competing financial interest.
́
(h) Timen, A. S.; Risberg, E.; Somfai, P. Tetrahedron Lett. 2003, 44,
5339. (i) Brase, S.; Gil, C.; Knepper, K.; Zimmermann, V. Angew.
Chem., Int. Ed. 2005, 44, 5188. (j) Banert, K.; Meier, B. Angew. Chem.,
Int. Ed. 2006, 45, 4015.
ACKNOWLEDGMENTS
■
We acknowledge the Department of Science and Technology
(DST), New Delhi, and the University Grants Commission,
New Delhi, for funding and equipment. K.V.S. thanks the
Council of Scientific and Industrial Research (CSIR), New
Delhi, for a fellowship. K.C.K.S. also thanks the DST for the J.
C. Bose Fellowship.
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