A Photoinduced Cobalt-Catalyzed Synthesis of Pyrroles through in Situ-Generated Acylazirines

Article abstract of DOI:10.1021/acs.joc.6b00511

Tetrasubstituted pyrroles can be synthesized in a one-pot procedure from isoxazoles. The process includes the photoinduced in situ formation of acylazirines combined with a subsequent cobalt(II)-catalyzed ring expansion with 1,3-diketones.

Full text of DOI:10.1021/acs.joc.6b00511

Subscriber access provided by UNIV OF CALIFORNIA SAN DIEGO LIBRARIES
Article
A Photoinduced Cobalt-Catalyzed Synthesis of
Pyrroles through In-Situ Generated Acylazirines
Stefan Pusch, Danuta Kowalczyk, and Till Opatz
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b00511 • Publication Date (Web): 15 Apr 2016
Downloaded from http://pubs.acs.org on April 21, 2016
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
The Journal of Organic Chemistry is published by the American Chemical Society.
1155 Sixteenth Street N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 32
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
A Photoinduced Cobalt-Catalyzed Synthesis of
Pyrroles through In-Situ Generated Acylazirines
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Stefan Pusch, Danuta Kowalczyk, and Till Opatz*
Institute of Organic Chemistry, Johannes Gutenberg University,
Duesbergweg 10–14, 55128 Mainz, Germany
Abstract Graphic
Abstract
Tetrasubstituted pyrroles can be synthesized in a oneꢀpot procedure from isoxazoles. The process
includes the photoinduced inꢀsitu formation of acylazirines combined with a subsequent
cobalt(II)ꢀcatalyzed ring expansion with 1,3ꢀdiketones.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 32
1
2
3
4
Introduction
5
6
7
8
An attractive strategy for the construction of heterocycles is the utilization of ring strain present
in smallꢀring systems.1 Ideally, these highꢀenergy compounds are generated as intermediates inꢀ
situ from stable precursors and are directly transformed into the desired heterocyclic products
under the conditions of their formation. This methodology would obviate the use of kinetically
stable intermediates if the subsequent step is faster than a competing uncatalyzed transformation
of the intermediate and could even be utilized to synthesize compounds of a higher energy
content compared to the original starting material. Thus, the formation of lowꢀenergy coꢀproducts
such as borates, trialkyltin halides or ureas resulting from classical C–Cꢀ and C–heteroatom bond
formations could be circumvented. Recently, we developed a oneꢀpot synthesis of tetrasubstituted
imidazoles 5 from acylazirines 2 generated inꢀsitu by a photochemical ring transformation of
isoxazoles 1 (Scheme 1).2
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 1. Isomerization of isoxazoles to azirines/oxazoles, previous baseꢀmediated imidazole
synthesis and envisioned metalꢀcatalyzed pyrrole synthesis.
The photochemical isomerization of isoxazoles 1 to the corresponding acylazirines 2 is well
known3 but the maximally achievable yield of the azirine 2 itself is limited due to the competing
irreversible formation of oxazoles 3 as byproducts unless an efficient secondary reaction on
intermediates 2 is established. While the synthesis of imidazoles 5 from acylazirines 2 was
ACS Paragon Plus Environment

Page 3 of 32
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
achieved in high yield by reaction with αꢀ(alkylideneamino)nitriles 4 formed from aldehydes and
αꢀaminonitriles in a oneꢀpot procedure, we also intended to combine the photochemical activation
step with transition metal catalysis. Such a dual activation appears very attractive in terms of the
accessible products as well as in terms of resource efficiency by minimizing the amount of
undesired coꢀproducts. A prerequisite for dual photoꢀ and metal catalysis is the compatibility of
the employed catalyst with the photoactivation of the substrate. The stability of common
transition metal catalysts against UV light is not an issue in standard catalysis but it must be taken
into account in the described setting, as most catalytically active transition metal complexes do
not provide sufficient transparency in the spectral range required for substrate photoactivation. As
a case study for the feasibility of the dual activation approach, we sought for a route to synthesize
2,4ꢀdiacyl substituted pyrroles 7 from intermediates 2 by condensation with 1,3ꢀdiketones 6.
Pyrroles are an important class of heterocyclic compounds and are not only present in synthetic
compounds and materials but also in a wide variety of natural products. Preparations of pyrroles
bearing electronꢀwithdrawing acyl groups such as the Knorr or the Hantzsch syntheses are known
for over a century.4 The pyrroleꢀforming condensation reaction between azirines and carbonyl
compounds was first reported in 1967 by Ohta and coꢀworkers,5 and the same principle was later
adopted by other groups.6 A recent study from Khlebnikov and coꢀworkers7 incorporates the ironꢀ
catalyzed isomerization of 5ꢀalkoxyisoxazoles found by Auricchio8 with a nickelꢀcatalyzed
condensation reaction. Additionally, vinyl azides were employed as azirine equivalents by Chiba
and Narasaka.9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Results and Discussion
The initial task was to identify a suitable metal catalyst that does not interfere with the
photoisomerization and is stable under irradiation with the UV light required for the formation of
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 32
1
2
3
4
5
6
7
8
9
intermediates 2. A screening was performed with cheap and widely available firstꢀrow transition
metal salts and complexes using LC/MS. They were selected for their ability to produce pyrrole
7a from isoxazole 1a and acetylacetone (6a) under irradiation with 300 nm UV light (Table 1).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 1. Catalyst screening using a model reaction.
Yield[a,b]
0%
Entry Catalyst
1
none
2
Mn(acac)3
57%
3
Mn(OAc)3ꢁ2H2O n.d.
4
5
6
7
Fe(acac)3
Co(acac)2
Co(acac)3
CoCl2
n.d.
83%[c]
n.d.
37%
n.d.
n.d.
n.d.
n.d.
73%
n.d.
63%
8
9
CoCl2(dppf)
CoCl2(PPh3)2
Co(hfacac)2
Co(OAc)2
Co(OiPr)2
Co(salen)
Co(SCN)2
Ni(acac)2ꢁxH2O 74%
NiCl2
Ni(NH3)6Cl2
Cu(MeCN)4PF6 n.d.
10
11
12
13
14
15
16
17
18
19
20
21
n.d.
n.d.
Cu(NTf2)2
Cu(OAc)2
(CuOTf)2ꢁC6H6 n.d.
n.d.
n.d.
[a] Isolated yields after chromatography. [b] n.d. = not determined, low yield as judged by LC/MS. [c] When
performed in a pyrex instead of quartz tube, the yield was 79%
In the absence of a metal catalyst, no pyrrole formation was observed. Therefore, a deꢀMayoꢀtype
photoreaction between the enol of acetylacetone and the azirine can be excluded. Furthermore, no
reaction was detetcted when the isoxazoleꢀdiketone mixture was stirred in the presence of
Co(acac)2 in the dark. Thus, a cobaltꢀcatalyzed condensation reaction between the isoxazole itself
ACS Paragon Plus Environment

Page 5 of 32
The Journal of Organic Chemistry
1
2
3
4
and acetylacetone can be ruled out. Significant catalytic activity was found for the
5
6
acetylacetonato complexes of MnIII, CoII or NiII with Co(acac)2 giving the highest yield of all
,
7
8
9
screened compounds. Slightly lower yields can be obtained using Co(SCN)2 and Co(OiPr)2, while
it can be assumed that Co(acac)2 is formed inꢀsitu from both precursors. Cobalt compounds with
phosphine ligands or chelating ligands proved to be ineffective, the same applied to CoIII(acac)3.
A condensation reaction only catalyzed by base can also be excluded as no pyrrole formation
could be detected if the corresponding azirine 2a was stirred with acetylacetone and DBU
(20 molꢀ%) at room temperature in dichloromethane, whereas an almost quantitative yield was
obtained using Co(acac)2 (10 molꢀ%). Thus, it is evident that the oneꢀpot photoreaction is
advantageous as the isolated yield of azirine 2a was limited to about 50% in our hands in an
earlier study (vide supra).2 The structure of the product could be unambiguously determined by
NMR spectroscopy and Xꢀray crystallography (see supporting information for details). With
Co(acac)2 as the optimal catalyst, we screened the solvent as well as the catalyst loading (Table
2).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 2. Screening of the solvent and catalyst loading.
Yield[a]
Entry Catalyst loading
Solvent
MeOH
MeCN
DCM
DCM
DCM
1
2
3
4
5
10 molꢀ%
10 molꢀ%
10 molꢀ%
5 molꢀ%
61%
64%
83%
31%
87%
20 molꢀ%
[a] Isolated yields after chromatography.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 32
1
2
3
4
5
6
7
8
9
Methanol and acetonitrile turned out to be inferior compared to dichloromethane as solvents.
Dichloromethane is furthermore advantageous due to the often limited solubility of
diarylisoxazoles in acetonitrile which is a common solvent for photoreactions due to the broad
spectral window. Lowering of the initial catalyst loading to 5 molꢀ% resulted in a drastically
reduced yield, while the use of 20 molꢀ% instead of 10 molꢀ% of the catalyst did not lead to a
significant increase of the isolated yield. Using the optimized conditions, different isoxazoles 1
were reacted to give the corresponding tetrasubstituted pyrroles 7 (Table 3).10
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 3. Photochemical cobaltꢀcatalyzed oneꢀpot synthesis of pyrroles from isoxazoles.
Yield[a]
Entry
Isoxazole
1a
R1
R2
Product
1
Ph
Ph
83%
2
3
Ph
Ph
Me
56%
41%
1b
1c
2ꢀnaphthyl
4
5
Ph
Ph
pꢀC6H4ꢀF
94%
30%
1d
1e
pꢀC6H4ꢀOMe
ACS Paragon Plus Environment

Page 7 of 32
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
6
7
Ph
Ph
pꢀC6H4ꢀCO2Me
92%
1f
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
–
1g,h
8
9
Ph
Ph
Ph
mꢀC6H4ꢀNO2
2ꢀfuryl
63%
70%
63%
1i
1j
10
2ꢀthienyl
1k
11
12
pꢀC6H4ꢀNMe2
pꢀC6H4ꢀOMe
pꢀC6H4ꢀiPr
84%
92%
1l
pꢀC6H4ꢀCF3
1m
13
14
tBu
Ph
Ph
H
29%[b]
85%
1n
1o
[a] Isolated yields after chromatography. [b] Incomplete isoxazole consumption, yield (brsm): 84%.
The replacement of a phenyl group in the 3ꢀposition on the isoxazole with a methyl substituent
leads to lower yields, the same observation was made for a naphthyl group (entries 2 and 3). In
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 32
1
2
3
4
5
6
7
8
9
the latter case, the photochemical ring enlargement appears to be too fast and the corresponding
oxazole byproduct is being formed in spite of the reaction being performed in a oneꢀpot fashion.
A pꢀfluorophenyl group is well tolerated (entry 4). The introduction of a pꢀmethoxy group (at the
3ꢀphenyl substituent) results in a poor yield whereas an excellent yield was obtained for the pꢀ
methoxycarbonyl derivative (entries 5 and 6). This is in accordance with a putative mechanism
consisting of the nucleophilic addition to the C=N double bond of the azirine which is discussed
below. The reaction failed with oꢀnitro groups (entry 7) while an mꢀnitro substituent was tolerated
(entry 8). The phenyl group can also be replaced with a furyl or thienyl group (entries 9 and 10).
The incorporation of additional electronꢀdonating groups in the R1 substituent gave high yields
(entries 11 and 12) in contrast to the observations made for the R2 group. A low yield was
observed for an isoxazole with an R1 alkyl group (entry 13) whereas the monosubstituted
commercially available isoxazole 1o was reacted in high yield (entry 14). In general, at least one
aryl group – preferably as R1 – is required in this synthetic protocol to enable the initial
photoisomerization in this particular setting.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
The exclusion of oxygen during the reaction turned out to be essential as the stable cobalt(III)
complexes 8a–c could be isolated and characterized if the photoreaction was conducted in the
presence of air (Figure 1). The integrity of the complex in solution was checked by DOSY NMR
spectroscopy. As in the case of Co(acac)3, complex 8a turned out to be catalytically inactive and
very stable even towards concentrated hydrochloric acid at room temperature.
Figure 1. Structures of the cobalt(III) complexes isolated as byproducts.
ACS Paragon Plus Environment

Page 9 of 32
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
Next, we found that Co(acac)2 as a catalyst can be replaced by mixtures of cobalt(II) chloride and
potassium tertꢀbutoxide. The molar ratio of CoCl2 and KOtBu turned out to be crucial in this case
and significant product formation could only be observed for a ratio of 1:2 while complex
mixtures were obtained for a 1:1 and a 1:4 stoichiometry (Table 4, see the Supporting
Information for LC/MS traces).
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 4. Replacement of Co(acac)2 with an alternative catalyst system.
Yield[a,b]
n.d.
80%
n.d.
Entry CoCl2
KOtBu
10 molꢀ%
20 molꢀ%
40 molꢀ%
Molar Ratio
1
2
3
10 molꢀ%
10 molꢀ%
10 molꢀ%
1:1
1:2
1:4
[a] Isolated yields after chromatography. [b] n.d. = not determined, low yield as judged by LC/MS.
Thus, Co(acac)2 can be replaced with CoCl2/KOtBu (1:2) without a significant loss of yield.
However, the CoCl2/KOtBu mixture does not catalyze the reaction of azirines 2 with other 1,3ꢀ
diketones such as 3,5ꢀheptanedione (6b) or dibenzoylmethane (6c). Co(acac)2 is not suitable as a
catalyst as the acetylacetonato ligands would also be incorporated in the final pyrrole instead of
the added 1,3ꢀdiketone, leading to the formation of product mixtures. The extension of the
substrate spectrum could finally be accomplished using Co(OiPr)2 as a catalyst (Scheme 2).
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 32
1
2
3
4
Scheme 2. Pyrrole synthesis using nonꢀacetylacetone diketones.
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Using this catalyst, alkyl or aryl groups can be used for R3. The structure of pyrrole 7q could be
confirmed by Xꢀray crystallography (see supporting information). When the unsymmetrical
diketone benzoylacetone (6d) was employed, a 84:16 regioisomeric mixture of pyrroles 7r and 7s
was isolated. As expected, the preferred pathway is the cyclization via the more reactive acetyl
group (compared to the benzoyl group).
A plausible mechanism for this reaction would include the coordination of the metal catalyst to
the nitrogen atom of the azirine (Scheme 3) and possibly the additional formation of a chelate
ring involving the neighboring carbonyl oxygen atom.
Scheme 3. Plausible mechanism for the pyrrole formation.
ACS Paragon Plus Environment

Page 11 of 32
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
A nucleophilic attack of anion 9 (which may also be bound to a metal center) at the C=N double
bond of the azirine 1 would form intermediate 10. Anion 10 could then in turn form the bicyclic
system 11 as already suggested by Khlebnikov and coꢀworkers.6b,7 Alternatively, anion 10 could
tautomerize to enolate 12, which is prone a ringꢀopening yielding anion 13. Either intermediates
11 or 13 could finally form the pyrrole 7.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
If a solution of Co(acac)2 in MeCN was directly infused into an ESIꢀMS source, a dominant
+
species with m/z = 415 could be observed (base peak), corresponding to CoII (acac)3 . The dimer
2
2+
CoII (acac)6 could be ruled out based on the structure of the isotopic pattern (cobalt(II)
4
acetylacetonate is known to have a tetrameric structure at least in the solid state).11 Upon addition
of azirine 2a as well as acetylacetone (6a) to the mixture, a number of new peaks emerged, the
strongest one being found at m/z = 479 corresponding to cations 14 or 15 (Figure 2).
Figure 2. Putative cations observed during an ESIꢀMS experiment (for simplicity, separate
constituents are shown).
Isolation and fragmentation of m/z = 479 yields mainly m/z = 379, corresponding to cations 16 or
17 formed by extrusion of acetylacetone. Finally, MS/MS of m/z = 379 produces m/z = 280,
corresponding to cation 18, formed by abstraction of acetylacetonyl radical with accompanying
reduction of CoII to CoI (see supporting information for mass spectra). Evidently, the conditions
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 32
1
2
3
4
5
6
7
8
9
inside an ESI source strongly deviate from the conditions applied in synthesis but the observed
ions and the fragmentation pathway at least suggest an coordination of cobalt to the azirine, thus
enhancing the electrophilicity of the C=N moiety.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Conclusion
2,4ꢀDiacylpyrroles could be synthesized from isoxazoles and acetylacetone in a photochemical
oneꢀpot procedure via azirines generated inꢀsitu and a subsequent Co(acac)2ꢀ or CoCl2/KOtBuꢀ
catalyzed ring expansion reaction. The synthetic protocol can be extended to different 1,3ꢀ
diketones when Co(OiPr)2 was used as a catalyst. The formation of catalytically inactive
pyrrolatoꢀcobalt(III)ꢀcomplexes could be observed in the presence of air.
ACS Paragon Plus Environment

Page 13 of 32
The Journal of Organic Chemistry
1
2
3
4
5
Experimental Section
6
7
8
General Information
9
Anhydrous acetonitrile and dichloromethane were distilled from CaH2 under nitrogen. Solvents
were degassed using freezeꢀpumpꢀthaw cycles or by nitrogen bubbling and an ultrasonic bath.
CDCl3 was stored over alumina (Brockmann activity grade I). All reagents were purchased from
commercial suppliers and used without further purification. Photochemical reactions were
performed in quartz tubes using a Rayonet Photochemical Reactor equipped with a circular array
of 16 UV lamps (λmax ca. 300 nm, 8 W each), a magnetic stirrer and a cooling fan. TLC was
carried out on silica gel 60 F254 plates (UV visualization). Preparative normalꢀphase
chromatography was performed on silica gel (35–70 ꢂm). Preparative reversedꢀphase
chromatography was carried out using an ACE5ꢀC18PFP column (pore size: 5 ꢂm, length: 15 cm,
diameter: 30 mm) using a total flow rate of 37.5 mL min–1. Melting points were determined in
open capillary tubes. NMR spectra were recorded with 300 MHz, 400 MHz and 600 MHz
instruments using standard pulse sequences. The chemical shifts are given in ppm (downfield
relative to TMS) and were referenced to the residual solvent signal (δH = 7.26 ppm, δC =
77.16 ppm) or an external standard (α,α,αꢀtrifluorotoluene in CDCl3: δF = –63.9 ppm). IR spectra
were recorded using a diamond ATR unit; wavenumbers are given in cm–1. ESIꢀMS and ESIꢀ
HRMS spectra (given: m/z values) were recorded using an ion trap and an QꢀToF instrument with
dual source and suitable external calibrant, respectively.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Isoxazole Synthesis
Compounds 1a,3b 1b,12 1n,13 and 2a2ꢀ3 were prepared as previously reported. Compound 1o was
purchased from a commercial supplier. Compounds 1c–m were prepared according to the general
procedure by Fokin and coꢀworkers14 from the corresponding aldehyde and alkyne precursors:
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 32
1
2
3
4
5
6
3-(Naphthalen-2-yl)-5-phenyl-1,2-oxazole (1c).
7
8
9
Purification by flash chromatography (silica gel, cyclohexane/ethyl acetate 10:1). Colorless solid
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(768 mg, 34%). Rf = 0.25 (cyclohexane/ethyl acetate 20:1); mp 145.6–146.7 °C; IR (ATR) 3118,
1
3053, 1572, 1496, 1449, 1408, 949, 907, 866, 828, 813, 763, 748, 691; H NMR (400 MHz,
CDCl3) 8.34–8.31 (m, 1H), 8.03 (dd, J = 8.5, 1.7 Hz, 1H), 7.97–7.86 (m, 5H), 7.58–7.45 (m, 5H),
6.98 (m, 1H); 13C NMR (101 MHz, CDCl3) 170.7, 163.2, 134.2, 133.4, 130.4, 129.2, 128.9,
128.6, 128.0, 127.6, 127.2, 126.8, 126.71, 126.67, 126.0, 124.1, 97.7; MS (ESI) 272.0 [M+H]+.
Analytical data in accordance with literature.15
3-(4-Fluorophenyl)-5-phenyl-1,2-oxazole (1d).
Purification by flash chromatography (silica gel, cyclohexane/ethyl acetate 10:1). Colorless solid
(109 mg, 48%). Rf = 0.53 (cyclohexane/ethyl acetate 5:1); mp 167.4–168.3 °C; IR (ATR) 1606,
1
1527, 1493, 1448, 1430, 1231, 951, 845, 816, 765, 694; H NMR (400 MHz, CDCl3) 7.90–7.81
(m, 4H), 7.53–7.43 (m, 3H), 7.21–7.14 (m, 2H), 6.79 (s, 1H); 13C NMR (101 MHz, CDCl3)
170.7, 164.0 (d, J = 250.0 Hz), 162.2, 130.5, 129.2, 128.9 (d, J = 8.2 Hz), 127.5, 126.0, 125.5 (d,
J = 3.1 Hz), 116.2 (d, J = 21.7 Hz), 97.5; 19F NMR (376 MHz, CDCl3) –111.7 (tt, J = 8.5,
5.2 Hz); MS (ESI) 240.0 [M+H]+. Analytical data in accordance with literature.16
3-(4-Methoxyphenyl)-5-phenyl-1,2-oxazole (1e).
Purification by flash chromatography (silica gel, cyclohexane/ethyl acetate 10:1). Colorless solid
(1.45 g, 58%). Rf = 0.28 (cyclohexane/ethyl acetate 10:1); mp 120.0–121.3 °C; IR (ATR) 1612,
1
1529, 1493, 1448, 1429, 1252, 1178, 1031, 837, 808, 763, 686; H NMR (400 MHz, CDCl3)
13
7.86–7.78 (m, 4H), 7.52–7.42 (m, 3H), 7.04–6.97 (m, 2H), 6.78 (s, 1H), 3.87 (s, 3H); C NMR
ACS Paragon Plus Environment

Page 15 of 32
The Journal of Organic Chemistry
1
2
3
4
5
6
(101 MHz, CDCl3) 170.3, 162.7, 161.2, 130.3, 129.1, 128.4, 127.7, 126.0, 121.8, 114.5, 97.4,
55.5; MS (ESI) 252.0 [M+H]+. Analytical data in accordance with literature.15,16b
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
3-[4-(Methoxycarbonyl)phenyl]-5-phenyl-1,2-oxazole (1f).
Purification by flash chromatography (silica gel, cyclohexane/ethyl acetate 10:1). Colorless solid
(768 mg, 28%). Rf = 0.48 (cyclohexane/ethyl acetate 5:1); mp 195.0–195.9 °C; IR (ATR) 1716,
1
1449, 1279, 1114, 864, 767, 693; H NMR, COSY (400 MHz, CDCl3) 8.18–8.14 (m, 2H, H3’/5’),
7.98–7.93 (m, 2H, H2’/6’), 7.87–7.83 (m, 2H, H2’’/6’’), 7.54–7.45 (m, 3H, H3’’/5’’, H4’’), 6.88 (s, 1H,
H4), 3.96 (s, 3H, CH3); 13C NMR, HSQC, HMBC (101 MHz, CDCl3) 171.1 (C5), 166.7
(CO2CH3), 162.3 (C3), 133.5 (C1’), 131.6 (C4’), 130.6 (C4’’), 130.4 (C3’/5’), 129.2 (C3’’/5’’), 127.4
(C1’’), 126.9 (C2’/6’), 126.0 (C2’’/6’’), 97.7 (C4), 52.5 (CH3); MS (ESI) 280.1 [M+H]+; HRMS (ESI)
+
calcd for C17H14NO3 280.0974, found 280.0974.
3-(2-Nitrophenyl)-5-phenyl-1,2-oxazole (1g).
Purification by flash chromatography (silica gel, cyclohexane/ethyl acetate 10:1). Yellow solid
(544 mg, 32%). Rf = 0.50 (cyclohexane/ethyl acetate 10:3); mp 89.7–90.5 °C; IR (ATR) 1572,
1
1529, 1451, 1403, 1351, 766, 690; H NMR (400 MHz, CDCl3) 8.00–7.96 (m, 1H), 7.83–7.77
(m, 2H), 7.77–7.66 (m, 2H), 7.66–7.59 (m, 1H), 7.51–7.42 (m, 3H), 6.63 (s, 1H); 13C NMR
(101 MHz, CDCl3) 170.5, 160.4, 148.7, 133.1, 131.7, 130.8, 130.6, 129.1, 127.1, 126.0, 124.6,
124.3, 99.7; MS (ESI) 267.0 [M+H]+. Analytical data in accordance with literature.17
3-[(E)-2-(2-Nitrophenyl)ethenyl]-5-phenyl-1,2-oxazole (1h).
Purification by flash chromatography (silica gel, cyclohexane/ethyl acetate 5:1). Yellow solid
(421 mg, 14%). Rf = 0.51 (cyclohexane/ethyl acetate 5:3); mp 134.2–135.5 °C; IR (ATR) 1573,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 32
1
2
3
4
5
6
7
8
9
1534, 1495, 1437, 1357, 962, 928, 777, 763, 743, 684; 1H NMR, COSY (400 MHz, CDCl3) 8.04–
7.99 (m, 1H, H3’’), 7.84–7.75 (m, 3H, H6’’, H2’’’/6’’’), 7.72 (d, J = 16.4 Hz, 1H, H2’), 7.68–7.61 (m,
1H, H5’’), 7.52–7.41 (m, 4H, H4’, H3’’’/5’’’, H4’’’), 7.16 (d, J = 16.4 Hz, 1H, H1’), 6.80 (s, 1H, H4);
13C NMR, HSQC, HMBC (101 MHz, CDCl3) 170.3 (C5), 162.0 (C3), 148.1 (C2’’), 133.6 (C5’’),
131.7 (C1’’), 130.9 (C2’), 130.5 (C4’’’), 129.3 (C4’’), 129.1 (C3’’’/5’’’), 128.6 (C6’’), 127.2 (C1’’’),
125.9 (C2’’’/6’’’), 125.0 (C3’’), 121.3 (C1’), 96.7 (C4); MS (ESI) 293.1 [M+H]+; HRMS (ESI) calcd
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
+
for C17H13N2O3 293.0926, found 293.0922.
3-(3-Nitrophenyl)-5-phenyl-1,2-oxazole (1i).
Purification by flash chromatography (silica gel, cyclohexane/ethyl acetate 10:1). Yellow solid
(382 mg, 22%). Rf = 0.53 (cyclohexane/ethyl acetate 10:3); mp 179.3–180.0 °C; IR (ATR) 1571,
1
1532, 1505, 1348, 807, 766, 740, 688; H NMR (400 MHz, CDCl3) 8.69–8.67 (m, 1H), 8.32 (dd,
J = 8.2, 2.3, 1.1 Hz, 1H), 8.25 (ddd, J = 7.8, 1.6, 1.1 Hz, 1H), 7.89–7.82 (m, 2H), 7.68 (pseudoꢀt,
J = 8.0 Hz, 1H), 7.55–7.45 (m, 3H), 6.92 (s, 1H); 13C NMR (75 MHz, CDCl3) 171.6, 161.3,
148.8, 132.6, 131.1, 130.8, 130.2, 129.3, 127.1, 126.1, 124.8, 122.0, 97.4; MS (ESI) 267.0
[M+H]+. Analytical data in accordance with literature.18
3-(Furan-2-yl)-5-phenyl-1,2-oxazole (1j).
Purification by flash chromatography (silica gel, cyclohexane/ethyl acetate 20:1). Colorless solid
(388 mg, 19%). Rf = 0.24 (cyclohexane/ethyl acetate 20:1); mp 96.0–97.5 °C; IR (ATR) 1616,
1570, 1508, 1453, 1436, 1016, 970, 885, 810, 765, 687, 670; 1H NMR (300 MHz, CDCl3) 7.87–
7.80 (m, 2H), 7.59–7.56 (m, 1H), 7.53–7.42 (m, 3H), 6.99–6.94 (m, 1H), 6.79 (s, 1H), 6.58–6.53
(m, 1H); 13C NMR (75 MHz, CDCl3) 170.3, 155.5, 144.5, 144.0, 130.5, 129.2, 127.3, 126.0,
111.9, 110.3, 97.1; MS (ESI) 212.0 [M+H]+. Analytical data in accordance with literature.19
ACS Paragon Plus Environment

Page 17 of 32
The Journal of Organic Chemistry
1
2
3
4
5
6
5-Phenyl-3-(thiophen-2-yl)-1,2-oxazole (1k).
7
8
9
Purification by flash chromatography (silica gel, cyclohexane/ethyl acetate 30:1). Colorless solid
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(668 mg, 29%). Rf = 0.22 (cyclohexane/ethyl acetate 30:1); mp 107.5–108.4 °C; IR (ATR) 1614,
1
1592, 1576, 1491, 1447, 1432, 1394, 910, 848, 804, 763, 712, 685; H NMR (300 MHz, CDCl3)
7.87–7.79 (m, 2H), 7.55–7.42 (m, 5H), 7.17–7.12 (m, 1H), 6.76 (s, 1H); 13C NMR (75 MHz,
CDCl3) 170.5, 158.3, 131.0, 130.5, 129.2, 127.8, 127.7, 127.4, 126.0, 97.6; MS (ESI) 227.9
[M+H]+. Analytical data in accordance with literature.20
5-(N,N-Dimethylphenyl)-3-[4-(propan-2-yl)phenyl]-1,2-oxazole (1l).
Purification by flash chromatography (silica gel, cyclohexane/ethyl acetate 10:1). Colorless solid
(198 mg, 32%). Rf = 0.41 (cyclohexane/ethyl acetate 5:1); mp 141.0–141.8 °C; IR (ATR) 2959,
1
1615, 1517, 1438, 1373, 1194, 951, 839, 818, 795; H NMR, COSY (400 MHz, CDCl3) 7.81–
7.77 (m, 2H, H2’/6’), 7.73–7.68 (m, 2H, H2’’/6’’), 7.35–7.31 (m, 2H, H3’/5’), 6.78–6.73 (m, 2H,
H3’’/5’’), 6.60 (s, 1H, H4), 3.04 (s, 6H, N(CH3)2), 2.97 (septet, J = 6.9 Hz, CH(CH3)2), 1.29 (d, J =
13
6.9 Hz, CH(CH3)2); C NMR, HSQC, HMBC (101 MHz, CDCl3) 171.2 (C5), 162.9 (C3), 151.5
(C4’’), 150.9 (C4’), 127.3 (C1’), 127.2 (C2’’/6’’), 127.1 (C3’/5’), 126.9 (C2’/6’), 115.7 (C1’’), 112.0
(C3’’/5’’), 94.8 (C4), 40.4 (N(CH3)2), 34.2 (CH(CH3)2), 24.0 (CH(CH3)2); MS (ESI) 307.1 [M+H]+;
HRMS (ESI) calcd for C20H23N2O+ 307.1810, found 307.1797.
5-(4-Methoxyphenyl)-3-[4-(trifluoromethyl)phenyl]-1,2-oxazole (1m).
Purification by flash chromatography (silica gel, cyclohexane/ethyl acetate 40:1). Colorless solid
(156 mg, 68%). Rf = 0.33 (cyclohexane/ethyl acetate 10:1); mp 192.1–193.2 °C; IR (ATR) 1616,
1
1508, 1439, 1323, 1256, 1167, 1113, 1065, 1030, 951, 841, 808; H NMR, COSY (600 MHz,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 18 of 32
1
2
3
4
5
6
7
8
9
CDCl3) 8.01–7.97 (m, 2H, H2’/6’), 7.81–7.77 (m, 2H, H2’’/6’’), 7.77–7.72 (m, 2H, H3’/5’), 7.04–6.99
(m, 2H, H3’’/5’’), 6.75 (s, 1H, H4), 3.88 (s, 3H, CH3); 13C NMR, HSQC, HMBC (151 MHz,
CDCl3) 171.2 (C5), 161.9 (C3), 161.5 (C4’’), 132.9 (C1’), 131.9 (q, J = 32.8 Hz, C4’), 127.7
(C2’’/6’’), 127.3 (C2’/6’), 126.1 (q, J = 3.6 Hz, C3’/5’), 124.0 (q, J = 271.9 Hz, CF3), 120.1 (C1’’),
114.6 (C3’’/5’’), 96.2 (C4), 55.6 (CH3); 19F NMR (376 MHz, CDCl3) –64.0 (s, CF3); MS (ESI)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
+
320.1 [M+H]+; HRMS (ESI) calcd for C17H13F3NO2 320.0898, found 320.0898.
Pyrrole Synthesis
General procedure A: To an ovenꢀdried quartz tube under a nitrogen atmosphere were added the
corresponding isoxazole 1, acetylacetone (6a, 1.10 equiv), Co(acac)2 (0.10 equiv) and dry
dichloromethane (20 mL). The solution was degassed and irradiated (300 nm, 16 × 8 W). After
TLC or LC/MS analysis indicated consumption of the starting material, the solvent was removed
in vacuo and the residue was purified by flash chromatography (silica gel, cyclohexane/ethyl
acetate, 98:2 ꢀ 60:40).
General procedure B: To an ovenꢀdried quartz tube under a nitrogen atmosphere were added the
corresponding isoxazole 1 as well as 1,3ꢀdiketone 6 (2.00 equiv), Co(OiPr)2 (0.10 equiv) and dry
dichloromethane (20 mL). Otherwise identical to general procedure B.
1-(5-Benzoyl-2-methyl-4-phenyl-1H-pyrrol-3-yl)ethanone (7a).
Following general procedure A, isoxazole 1a (60.0 mg, 0.271 mmol) afforded the title compound
(68.0 mg, 0.224 mmol, 83%) as a colorless solid. Rf = 0.31 (cyclohexane/ethyl acetate 3:1); mp
195.6–196.7 °C; IR (ATR) 3261, 1656, 1602, 1575, 1544, 1481, 1413, 1285, 918, 738, 697, 669;
1H NMR, COSY, NOESY (400 MHz, CDCl3) 11.04 (br s, 1H, NH), 7.31–7.26 (m, 2H, H2’’’/6’’’),
7.18–7.13 (m, 1H, H4’’’), 7.09–6.95 (m, 7H, H2’’/6’’, H3’’/5’’, H4’’, H3’’’/5’’’), 2.63 (s, 3H, C2’CH3),
ACS Paragon Plus Environment

Page 19 of 32
The Journal of Organic Chemistry
1
2
3
4
13
1.81 (s, 3H, H2); C NMR, HSQC, HMBC (101 MHz, CDCl3) 197.3 (C1), 188.0 (C5CO), 140.9
5
6
(C2’), 137.7 (C1’’’), 134.7 (C1’’), 134.1 (C4’), 131.0 (C4’’’), 130.9 + 127.8 + 127.4 (C2’’/6’’, C3’’/5’’
,
7
8
9
C3’’’/5’’’), 128.7 (C2’’’/6’’’), 127.5 (C4’’), 127.0 (C5’), 124.4 (C3’), 30.8 (C2), 14.4 (C2’CH3); MS
+
(ESI) 304.1 [M+H]+; HRMS (ESI) calcd for C20H18NO2 304.1338, found 304.1347. Crystals
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
suitable for Xꢀray crystallography could be obtained by recrystallization of 7a from
cyclohexane/ethyl acetate (1:1).
If the irradiation was performed with 1.00 equiv Co(acac)2 in the presence of air,
bis(acetylacetonatoꢀκ2O,O’)ꢀ(1ꢀ{2ꢀmethylꢀ5ꢀ[(oxoꢀκO)(phenyl)methyl]ꢀ4ꢀphenylꢀ1Hꢀpyrrolꢀ3ꢀylꢀ
κN}ethanonato)cobalt(III) (8a, 34.9 mg, 62.3 µmol, 23%) could be isolated as a green
lyophilisate after purification by preparative HPLC (MeCN/H2O 60:40, Rt = 6.5–8.0 min). Rf =
0.24 (cyclohexane/ethyl acetate 3:1); IR (ATR) 1650, 1571, 1516, 1480, 1371, 1250, 1022, 931,
739, 701, 664, 636; H NMR, COSY, NOESY (600 MHz, CDCl3) 7.17–7.08 (m, 4H, H4’’,
1
H
2’’’/6’’’, H4’’’), 7.08–6.99 (m, 4H, H2’’/6’’, H3’’/5’’), 6.94–6.87 (m, 2H, H3’’’/5’’’), 5.55 (s, 1H,
CHacac), 5.54 (s, 1H, CHacac), 2.53 (s, 3H, C2’CH3), 2.26 (s, 3H, CH3acac), 2.16 (s, 3H, CH3acac),
2.11 (s, 3H, CH3acac), 2.10 (s, 3H, CH3acac), 1.83 (s, 3H, H2); 13C NMR, HSQC, HMBC
(151 MHz, CDCl3) 197.1 (C1), 194.6 (C5’CO), 190.6 (COacac), 189.9 (COacac), 189.6 (COacac),
189.5 (COacac), 157.4 (C2’), 142.7 + 139.5 (C4’, C5’), 135.5 (C1’’), 134.6 (C1’’’), 130.6 (C3’’/5’’),
130.4 (C4’’’), 129.7 (C3’), 128.8 (C2’’’/6’’’), 127.8 (C2’’/6’’), 127.4 (C4’’), 127.0 (C3’’’/5’’’), 97.8
(CHacac), 97.1 (CHacac), 31.0 (C2), 26.48 (CH3acac), 26.42 (CH3acac), 26.35 (CH3acac), 25.8 (CH3acac),
13.6 (C2’CH3); MS (ESI) 560.1 [M+H]+; HRMS (ESI) calcd for C30H30CoNNaO6 582.1303,
+
found 582.1324.
1-(5-Benzoyl-2,4-dimethyl-1H-pyrrol-3-yl)ethanone (7b).
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 20 of 32
1
2
3
4
5
6
Following general procedure A, isoxazole 1b (43.1 mg, 0.271 mmol) afforded the title compound
(36.4 mg, 0.151 mmol, 56%) as a colorless solid. Rf = 0.19 (cyclohexane/ethyl acetate 3:1); mp
7
8
9
1
140.6–141.5 °C; IR (ATR) 3264, 1600, 1548, 1506, 1415, 1285, 701; H NMR, COSY, NOESY
(400 MHz, CDCl3) 10.18 (br s, 1H, NH), 7.69–7.65 (m, 2H, H2’’/6’’), 7.58–7.52 (m, 1H, H4’’),
7.49–7.44 (m, 2H, H3’’/5’’), 2.58 (s, 3H, C2’CH3), 2.44 (s, 3H, H2), 2.16 (s, 3H, C4’CH3); 13C
NMR, HSQC, HMBC (101 MHz, CDCl3) 195.6 (C1), 187.6 (C5’CO), 140.8 (C2’), 139.5 (C1’’),
132.0 (C4’’), 130.4 (C4’), 128.8 (C2’’/6’’), 128.6 (C3’’/5’’), 127.7 (C5’), 124.4 (C3’), 31.5 (C1), 15.4
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
+
(C2’CH3), 14.6 (C4’CH3); MS (ESI) 242.0 [M+H]+; HRMS (ESI) calcd for C15H16NO2 242.1181,
found 242.1171. Analytical data in accordance with literature.21
If the irradiation was performed with 1.00 equiv Co(acac)2 in the presence of air,
bis(acetylacetonatoꢀκ2O,O’)ꢀ(1ꢀ{2,4ꢀdimethylꢀ5ꢀ[(oxoꢀκO)(phenyl)methyl]ꢀ1Hꢀpyrrolꢀ3ꢀylꢀ
κN}ethanonato)cobalt(III) (8b, 20.2 mg, 40.7 µmol, 15%) could be isolated as a green
lyophilisate after purification by preparative HPLC (MeCN/H2O 45:55, Rt = 11.5–14.5 min). Rf =
0.14 (cyclohexane/ethyl acetate 3:1); IR (ATR) 1645, 1572, 1516, 1373, 1254, 1070, 1013, 938,
1
778, 716, 635; H NMR, COSY, NOESY (600 MHz, CDCl3) 7.62–7.59 (m, 2H, H2’’/6’’), 7.52–
7.48 (m, 1H, H4’’), 7.44–7.39 (m, 2H, H3’’/5’’), 5.524 (s, 1H, CHacac), 5.517 (s, 1H, CHacac), 2.50
(s, 3H, C2’CH3), 2.46 (s, 3H, H2), 2.27 (s, 3H, C4’CH3), 2.25 (s, 3H, CH3acac), 2.13 (s, 3H,
CH3acac), 2.09 (s, 3H, CH3acac), 2.07 (s, 3H, CH3acac); 13C NMR, HSQC, HMBC (151 MHz,
CDCl3) 195.4 (C1), 193.3 (C5’CO), 190.7 (COacac), 189.9 (COacac), 189.6 (COacac), 189.4 (COacac),
158.6 (C2’), 140.5 + 140.0 (C4’, C5’), 135.8 (C1’’), 131.3 (C4’’), 130.2 (C3’), 129.0 (C2’’/6’’), 128.1
(C3’’/5’’), 97.9 (CHacac), 97.2 (CHacac), 31.7 (C2), 26.54 (CH3acac), 26.44 (CH3acac), 26.41 (CH3acac),
25.9 (CH3acac), 15.0 (C4’CH3), 14.3 (C2’CH3); MS (ESI) 498.0 [M+H]+; HRMS (ESI) calcd for
+
C25H28CoNNaO6 520.1146, found 520.1143.
ACS Paragon Plus Environment

Page 21 of 32
The Journal of Organic Chemistry
1
2
3
4
1-[5-Benzoyl-2-methyl-4-(naphthalen-2-yl)-1H-pyrrol-3-yl]ethanone (7c).
5
6
7
8
Following general procedure A, isoxazole 1c (73.5 mg, 0.271 mmol) afforded the title compound
(39.1 mg, 0.111 mmol, 41%) as a colorless solid. Rf = 0.30 (cyclohexane/ethyl acetate 3:1); mp
9
1
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
180.5–181.6 °C; IR (ATR) 3262, 1601, 1544, 1414, 1284, 742, 697; H NMR, COSY, NOESY
(400 MHz, CDCl3) 10.31 (br s, 1H, NH), 7.74–7.69 (m, 1H, H5’’), 7.58–7.53 (m, 2H, H4’’), 7.46–
7.36 (m, 3H, H1’’, H6’’, H7’’), 7.27–7.22 (m, 2H, H2’’’/6’’’), 7.20–7.15 (m, 1H, H3’’), 6.87–6.82 (m,
1H, H4’’’), 6.78–6.72 (m, 2H, H3’’’/5’’’), 2.66 (s, 3H, C2’CH3), 1.83 (s, 3H, H2); C NMR, HSQC,
13
HMBC (101 MHz, CDCl3) 197.3 (C1), 187.9 (C5’CO), 140.5 (C2’), 137.7 (C1’’’), 133.8 (C4’),
132.7 (C8a’’), 132.4 (C4a’’), 132.0 (C2’’), 130.7 (C4’’’), 130.3 (C1’’), 128.5 (C3’’), 128.4 (C2’’’/6’’’),
127.8 +127.5 (C6’’, C7’’), 127.6 (C5’’), 127.3 (C3’’’/5’’’), 126.3 + 126.2 (C4’’, C8’’), 124.5 (C3’), 31.1
(C2), 14.6 (C2’CH3); MS (ESI) 354.1 [M+H]+; HRMS (ESI) calcd for C24H20NO2 354.1494,
+
found 354.1483.
1-[5-Benzoyl-4-(4-fluorophenyl)-2-methyl-1H-pyrrol-3-yl]ethanone (7d).
Following general procedure A, isoxazole 1d (53.6 mg, 0.224 mmol) afforded the title compound
(67.7 mg, 0.211 mmol, 94%) as a colorless solid. Rf = 0.27 (cyclohexane/ethyl acetate 3:1); mp
181.6–182.4 °C; IR (ATR) 1655, 1599, 1522, 1479, 1415, 1275, 1222, 917, 843, 815, 745, 697,
1
667; H NMR, COSY, NOESY (400 MHz, CDCl3) 10.68 (br s, 1H, NH), 7.28–7.20 (m, 3H,
H2’’’/6’’’, H4’’’), 7.07–7.01 (m, 2H, H3’’’/5’’’), 7.01–6.94 (m, 2H, H2’’/6’’), 6.78–6.71 (m, 2H, H3’’/5’’),
2.62 (s, 3H, C2’CH3), 1.84 (s, 3H, H2); 13C NMR, HSQC, HMBC (101 MHz, CDCl3) 197.0 (C1),
187.9 (C5’CO), 162.3 (d, J = 247.4 Hz, C4’’), 140.8 (C2’), 137.7 (C1’’’), 132.7 (C4’), 132.5 (d, J =
8.1 Hz, C2’’/6’’), 131.2 (C4’’’), 130.7 (d, J = 3.7 Hz, C1’’), 128.7 (C2’’’/6’’’), 127.6 (C3’’’/5’’’), 127.2
(C5’), 124.5 (C3’), 114.9 (d, J = 21.5 Hz, C3’’/5’’), 31.0 (C2), 14.5 (C2’CH3); F NMR (376 MHz,
19
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 22 of 32
1
2
3
4
CDCl3) –115.6 (tt, J = 8.6, 5.2 Hz, F4’’); MS (ESI) 322.1 [M+H]+; HRMS (ESI) calcd for
5
6
+
C20H16FNNaO2 344.1063, found 344.1072.
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1-[5-Benzoyl-4-(4-methoxyphenyl)-2-methyl-1H-pyrrol-3-yl]ethanone (7e).
Following general procedure A, isoxazole 1e (68.1 mg, 0.271 mmol) afforded the title compound
(26.0 mg, 80.0 µmol, 30%) as a colorless lyophilisate after purification by preparative HPLC
(MeCN/H2O 50:50, Rt = 5.2–6.7 min). Rf = 0.25 (cyclohexane/ethyl acetate 3:1); IR (ATR) 3262,
1
1604, 1574, 1525, 1482, 1418, 1286, 1246, 1178, 697; H NMR, COSY, NOESY (400 MHz,
CDCl3) 10.01 (br s, 1H, NH), 7.29–7.23 (m, 2H, H2’’’/6’’’), 7.23–7.19 (m, 1H, H4’’’), 7.05–6.99 (m,
2H, H3’’’/5’’’), 6.93–6.88 (m, 2H, H2’’/6’’), 6.61–6.56 (m, 2H, H3’’/5’’), 3.72 (s, 3H, OCH3), 2.61 (s,
13
3H, C2’CH3), 1.85 (s, 3H, H2); C NMR, HSQC, HMBC (101 MHz, CDCl3) 197.4 (C1), 187.7
(C5’CO), 159.2 (C4’’), 140.2 (C2’), 137.8 (C1’’’), 133.6 (C4’), 132.0 (C2’’/6’’), 130.9 (C4’’’), 128.7
(C2’’’/6’’’), 127.5 (C3’’’/5’’’), 127.0 (C5’), 126.8 (C1’’), 124.5 (C3’), 113.5 (C3’’/5’’), 55.4 (OCH3), 30.9
(C2), 14.6 (C2’CH3); MS (ESI) 334.2 [M+H]+; HRMS (ESI) calcd for C21H19NNaO3 356.1263,
+
found 356.1272.
1-{5-Benzoyl-4-[4-(methoxycarbonyl)phenyl]-2-methyl-1H-pyrrol-3-yl}ethanone (7f).
Following general procedure A, isoxazole 1f (75.7 mg, 0.271 mmol) afforded the title compound
(90.0 mg, 0.250 mmol, 92%) as a colorless solid. Rf = 0.21 (cyclohexane/ethyl acetate 3:1); mp
1
168.0–168.9 °C; IR (ATR) 3262, 1720, 1609, 1480, 1415, 1275, 1177, 1110, 918, 742, 700; H
NMR, COSY, NOESY (400 MHz, CDCl3) 10.93 (br s, 1H, NH), 7.75–7.66 (m, 2H, H3’’/5’’),
7.31–7.21 (m, 2H, H2’’’/6’’’), 7.21–7.12 (m, 1H, H4’’’), 7.12–7.04 (m, 2H, H2’’/6’’), 7.04–6.93 (m,
2H, H3’’’/5’’’), 3.88 (s, 3H, CO2CH3), 2.62 (s, 3H, C2’CH3), 1.81 (s, 3H, H2); C NMR, HSQC,
13
HMBC (101 MHz, CDCl3) 196.7 (C1), 187.8 (C5’CO), 166.8 (CO2CH3), 140.9 (C2’), 139.9 (C1’’),
ACS Paragon Plus Environment

Page 23 of 32
The Journal of Organic Chemistry
1
2
3
4
137.5 (C1’’’), 132.6 (C4’), 131.4 (C4’’’), 130.9 (C2’’/6’’), 129.0 (C4’’), 128.9 (C3’’/5’’), 128.7 (C2’’’/6’’’),
5
6
127.6 (C3’’’/5’’’), 127.0 (C5’), 124.3 (C3’), 52.3 (CO2CH3), 30.9 (C2), 14.4 (C2’CH3); MS (ESI)
7
8
9
+
362.2 [M+H]+; HRMS (ESI) calcd for C22H19NNaO4 384.1212, found 384.1230.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1-[5-Benzoyl-2-methyl-4-(3-nitrophenyl)-1H-pyrrol-3-yl]ethanone (7i).
Following general procedure A, isoxazole 1i (72.2 mg, 0.271 mmol) afforded the title compound
(60.0 mg, 0.170 mmol, 63%) as a yellow solid. Rf = 0.15 (cyclohexane/ethyl acetate 3:1); mp
187.8–188.9 °C; IR (ATR) 3271, 1605, 1529, 1409, 1347, 1278, 1074, 939, 865, 732, 696, 664;
1H NMR, COSY, NOESY (400 MHz, CDCl3) 10.65 (br s, 1H, NH), 7.92 (ddd, J = 8.2, 2.3,
1.1 Hz, 1H, H3’’), 7.82–7.80 (m, 1H, H2’’), 7.45–7.40 (m, 1H, H6’’), 7.31–7.21 (m, 3H, H5’’,
H2’’/6’’), 7.19–7.14 (m, 1H, H4’’’), 7.03–6.97 (m, 2H, H3’’’/5’’’), 2.66 (s, 3H, C2’CH3), 1.95 (s, 3H,
H2); 13C NMR, HSQC, HMBC (101 MHz, CDCl3) 195.6 (C1), 187.6 (C5’CO), 147.4 (C3’’), 140.8
(C2’), 137.6 (C1’’’), 136.7 (C6’’), 136.5 (C1’’), 131.3 (C4’’’), 131.0 (C4’), 128.7 (C5’’), 128.4
(C2’’’/6’’’), 127.8 (C3’’’/5’’’), 127.5 (C5’), 125.9 (C1’’), 124.0 (C3’), 122.3 (C4’’), 31.2 (C2), 14.7
(C2’CH3); MS (ESI) 349.2 [M+H]+; HRMS (ESI) calcd for C20H16N2NaO4 371.1008, found
+
371.0999.
If the irradiation was performed with 1.00 equiv Co(acac)2 in the presence of air,
bis(acetylacetonatoꢀκ2O,O’)ꢀ(1ꢀ{2ꢀmethylꢀ4ꢀ(3ꢀnitrophenyl)ꢀ5ꢀ[(oxoꢀκO)(phenyl)methyl]ꢀ1Hꢀ
pyrrolꢀ3ꢀylꢀκN}ethanonato)cobalt(III) (8c, 26.2 mg, 43.4 µmol, 16%) could be isolated as a green
lyophilisate after purification by preparative HPLC (MeCN/H2O 45:55, Rt = 3.0–4.5 min). Rf =
0.13 (cyclohexane/ethyl acetate 3:1); IR (ATR) 1654, 1573, 1519, 1473, 1411, 1373, 1347, 1252,
1
939, 701; H NMR, COSY, NOESY (400 MHz, CDCl3) 7.98–7.93 (m, 1H, H4’’), 7.80–7.75 (m,
1H, H2’’), 7.49–7.42 (m, 1H, H6’’), 7.34–7.26 (m, 1H, H5’’), 7.15–7.10 (m, 1H, H4’’’), 7.10–7.06
(m, 2H, H2’’’/6’’’), 6.95–6.89 (m, 2H, H3’’’/5’’’), 5.57 (s, 1H, CHacac), 5.56 (s, 1H, CHacac), 2.52 (s,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 24 of 32
1
2
3
4
5
6
7
8
9
3H, C2’CH3), 2.27 (s, 3H, CH3acac), 2.16 (s, 3H, CH3acac), 2.14 (br s, 6H, 2 × CH3acac), 1.91 (s, 3H,
H2); 13C NMR, HSQC, HMBC (101 MHz, CDCl3) 195.8 (C1), 195.4 (C5’CO), 190.9 (COacac),
190.0 (COacac), 189.8 (COacac), 189.6 (COacac), 157.3 (C2’), 147.5 (C3’’), 139.8 (C5’), 138.9 (C4’),
137.3 (C1’’), 136.6 (C6’’), 134.5 (C1’’’), 130.7 (C4’’’), 129.7 (C3’), 128.6 (C5’’), 128.5 (C2’’’/6’’’),
127.4 (C3’’’/5’’’), 125.6 (C2’’), 122.2 (C4’’), 97.9 (CHacac), 97.1 (CHacac), 31.4 (C2), 26.5 (CH3acac),
26.4 (2 × CH3acac), 25.8 (CH3acac), 13.7 (C2’CH3); MS (ESI) 605.1 [M+H]+; HRMS (ESI) calcd
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
+
for C30H30CoN2O8 605.1334, found 605.1333.
1-[5-Benzoyl-4-(furan-3-yl)-2-methyl-1H-pyrrol-3-yl]ethanone (7j).
Following general procedure A, isoxazole 1j (57.2 mg, 0.271 mmol) afforded the title compound
(56.2 mg, 0.190 mmol, 70%) as a colorless solid. Rf = 0.33 (cyclohexane/ethyl acetate 3:1); mp
1
150.9–151.7 °C; IR (ATR) 3263, 1618, 1544, 1479, 1407, 1283, 1181, 941, 740, 697, 665; H
NMR, COSY, NOESY (400 MHz, CDCl3) 11.05 (br s, 1H, NH), 7.47–7.43 (m, 2H, H2’’’/6’’’),
7.35–7.29 (m, 2H, H4’’, H4’’’), 7.23–7.17 (m, 2H, H3’’’/5’’’), 6.04 (dd, J = 3.3, 1.8 Hz, 1H, H3’’),
13
5.86 (dd, J = 3.3, 0.8 Hz, 1H, H2’’), 2.65 (s, 3H, C2’CH3), 1.96 (s, 3H, H2); C NMR, HSQC,
HMBC (101 MHz, CDCl3) 196.3 (C1), 187.7 (C5’CO), 145.3 (C1’’), 142.1 (C4’’), 141.4 (C2’),
138.1 (C1’’’), 131.5 (C4’’’), 128.4 (C2’’’/6’’’), 128.2 (C5’), 127.8 (C3’’’/5’’’), 123.9 (C3’), 121.9 (C4’),
112.6 (C2’’), 111.4 (C3’’), 29.1 (C2), 14.6 (C2’CH3); MS (ESI) 294.1 [M+H]+; HRMS (ESI) calcd
+
for C18H15NNaO3 316.0950, found 316.0963.
1-[5-Benzoyl-2-methyl-4-(thiophen-3-yl)-1H-pyrrol-3-yl]ethanone (7k).
Following general procedure A, isoxazole 1k (61.6 mg, 0.271 mmol) afforded the title compound
(52.3 mg, 0.170 mmol, 63%) as a colorless solid. Rf = 0.36 (cyclohexane/ethyl acetate 3:1); mp
1
163.8–164.8 °C; IR (ATR) 3248, 1656, 1600, 1573, 1534, 1480, 1428, 1282, 736, 694, 665; H
ACS Paragon Plus Environment

Page 25 of 32
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
NMR, COSY, NOESY (400 MHz, CDCl3) 10.88 (br s, 1H, NH), 7.46–7.41 (m, 2H, H2’’’/6’’’),
7.30–7.24 (m, 1H, H4’’’), 7.14–7.08 (m, 3H, H4’’, H3’’’/5’’’), 6.72 (dd, J = 4.9, 3.5 Hz, 1H, H3’’),
6.70 (d, J = 3.5, 1.4 Hz, 1H, H2’’), 2.61 (s, 3H, C2’CH3), 1.96 (s, 3H, H2); 13C NMR, HSQC,
HMBC (101 MHz, CDCl3) 197.1 (C1), 187.9 (C5’CO), 140.7 (C2’), 137.9 (C1’’’), 135.0 (C4’),
131.3 (C4’’’), 129.9 (C2’’), 128.4 (C2’’’/6’’’), 128.1 (C5’), 127.6 (C3’’’/5’’’), 127.4 (C4’’), 126.9 (C3’’),
125.2 (C3’), 124.8 (C1’’), 30.2 (C2), 14.4 (C2’CH3); MS (ESI) 310.1 [M+H]+; HRMS (ESI) calcd
for C18H15NNaO2S+ 332.0721, found 332.0723.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1-{5-[4-(Dimethylamino)benzoyl]-2-methyl-4-[4-(propan-2-yl)phenyl]-1H-pyrrol-3-
yl}ethanone (7l).
Following general procedure A, isoxazole 1l (83.0 mg, 0.271 mmol) afforded the title compound
(88.8 mg, 0.229 mmol, 84%) as a colorless solid. Rf = 0.19 (cyclohexane/ethyl acetate 3:1); mp
196.5–197.4 °C; IR (ATR) 1652, 1576, 1521, 1480, 1416, 1361, 1287, 1163, 921, 824, 774, 735;
1H NMR, COSY, NOESY (400 MHz, CDCl3) 10.75 (br s, 1H, NH), 7.33–7.26 (m, 2H, H2’’’/6’’’),
7.04–6.98 (m, 2H, H2’’/6’’), 6.98–6.93 (m, 2H, H3’’/5’’), 6.25–6.19 (m, 2H, H3’’’/5’’’), 2.89 (s, 6H,
N(CH3)2), 2.78 (septet, J = 6.9 Hz, 1H, CH(CH3)2), 2.60 (s, 3H, C2’CH3), 1.88 (s, 3H, H2), 1.15
13
(d, J = 6.9 Hz, 6H, CH(CH3)2); C NMR, HSQC, HMBC (101 MHz, CDCl3) 197.9 (C1), 186.6
(C5’CO), 152.5 (C4’’’), 147.9 (C4’’), 139.2 (C2’), 132.8 (C1’’), 132.0 (C4’), 131.7 (C2’’’/6’’’), 131.1
(C2’’/6’’), 127.6 (C5’), 125.9 (C3’’/5’’), 124.9 (C1’’’), 123.8 (C3’), 110.0 (C3’’’/5’’’), 40.0 (N(CH3)2),
33.9 (CH(CH3)2), 31.0 (C2), 24.0 (CH(CH3)2), 14.3 (C2’CH3); MS (ESI) 389.2 [M+H]+; HRMS
+
(ESI) calcd for C25H28N2NaO2 411.2048, found 411.2048.
1-{5-(4-Methoxybenzoyl)-2-methyl-4-[4-(trifluoromethyl)phenyl]-1H-pyrrol-3-yl}ethanone
(7m).
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 26 of 32
1
2
3
4
5
6
7
8
9
Following general procedure A, isoxazole 1m (60.0 mg, 0.188 mmol) afforded the title
compound (69.6 mg, 0.173 mmol, 92%) as a colorless solid. Rf = 0.17 (cyclohexane/ethyl acetate
3:1); mp 154.6–155.7 °C; IR (ATR) 1602, 1483, 1422, 1324, 1256, 1166, 1124, 1067, 842, 775,
1
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
614; H NMR, COSY, NOESY (400 MHz, CDCl3) 10.73 (br s, 1H, NH), 7.37–7.32 (m, 2H,
H3’’/5’’), 7.26–7.21 (m, 2H, H2’’’/6’’’), 7.19–7.15 (m, 2H, H2’’/6’’), 6.51–6.45 (m, 2H, H3’’’/5’’’), 3.69
(s, 3H, OCH3), 2.63 (s, 3H, C2’CH3), 1.91 (s, 3H, H2); 13C NMR, HSQC, HMBC (101 MHz,
CDCl3) 196.6 (C1), 186.8 (C5’CO), 162.5 (C4’’’), 140.3 (C2’), 139.1 (C1’’), 131.4 (C2’’/6’’), 131.3
(C4’), 131.1 (C2’’’/6’’’), 129.8 (C1’’’), 129.5 (q, J = 32.6 Hz, C4’’), 127.5 (C5’), 124.7 (q, J = 3.8 Hz,
C3’’/5’’), 124.1 (q, J = 272.2 Hz, CF3), 124.0 (C3’), 113.0 (C3’’’/5’’’), 55.3 (OCH3), 31.2 (C2), 14.5
(C2’CH3); 19F NMR (376 MHz, CDCl3) –63.9 (s, CF3); MS (ESI) 402.1 [M+H]+; HRMS (ESI)
+
calcd for C22H18F3NNaO3 424.1136, found 424.1127.
1-[5-(2,2-Dimethylpropanoyl)-2-methyl-4-phenyl-1H-pyrrol-3-yl]ethanone (7n).
Following general procedure A, isoxazole 1n (96.9 mg, 0.481 mmol) afforded the title compound
(40.1 mg, 0.142 mmol, 29%) as a colorless solid. A part of the starting isoxazole (62.7 mg,
0.312 mmol, 65%) was recovered unchanged. Rf = 0.36 (cyclohexane/ethyl acetate 3:1); mp
1
191.1–192.6 °C; IR (ATR) 3310, 2969, 1635, 1476, 1432, 1409, 1182, 935, 733, 700; H NMR,
COSY, NOESY (600 MHz, CDCl3) 9.43 (br s, 1H, NH), 7.42–7.36 (m, 3H, H3’’/5’’, H4’’), 7.33–
7.29 (m, 2H, H2’’/6’’), 2.55 (s, 3H, C2’CH3), 1.68 (s, 3H, H2), 1.07 (s, 9H, C(CH3)3); C NMR,
13
HSQC, HMBC (151 MHz, CDCl3) 198.4 (C5’CO), 197.2 (C1), 137.9 (C2’), 136.7 (C1’’), 130.9
(C2’’/6’’), 130.5 (C4’), 128.2 (C3’’/5’’), 128.1 (C4’’), 126.0 (C5’), 124.2 (C3’), 42.9 (C(CH3)3), 30.8
(C2), 27.6 (C(CH3)3), 14.8 (C2’CH3); MS (ESI) 284.2 [M+H]+; HRMS (ESI) calcd for
+
C18H22NO2 284.1651, found 284.1656.
ACS Paragon Plus Environment

Page 27 of 32
The Journal of Organic Chemistry
1
2
3
4
1-(5-Benzoyl-2-methyl-1H-pyrrol-3-yl)ethanone (7o).
5
6
7
8
Following general procedure A, isoxazole 1o (80.0 µL, 91.1 mg, 0.627 mmol) afforded the title
compound (121.6 mg, 0.535 mmol, 85%) as a colorless solid. Rf = 0.27 (cyclohexane/ethyl
acetate 3:1); mp 210.9–211.6 °C; IR (ATR) 3247, 1669, 1608, 1548, 1506, 1290, 1142, 950, 728;
1H NMR, COSY, NOESY (400 MHz, CDCl3) 10.79 (br s, 1H, NH), 7.94–7.88 (m, 2H, H2’’/6’’),
7.65–7.58 (m, 1H, H4’’), 7.57–7.50 (m, 2H, H3’’/5’’), 7.18 (d, J = 2.3 Hz, 1H, H4’), 2.69 (s, 3H,
C2’CH3), 2.44 (s, 3H, H2); 13C NMR, HSQC, HMBC (101 MHz, CDCl3) 194.7 (C1), 185.0
(C5’CO), 142.4 (C2’), 137.9 (C1’’), 132.4 (C4’’), 129.1 (C2’’/6’’), 128.7 (C3’’/5’’), 128.6 (C5’), 123.5
(C3’), 121.7 (C4’), 28.4 (C2), 14.4 (C2’CH3); MS (ESI) 228.1 [M+H]+; HRMS (ESI) calcd for
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
+
C14H14NO2 228.1025, found 228.1033.
1-(5-Benzoyl-2-ethyl-4-phenyl-1H-pyrrol-3-yl)propan-1-one (7p).
Following general procedure B, isoxazole 1a (90.0 mg, 0.407 mmol) and 3,5ꢀheptanedione (6b,
110 µL, 104 mg, 0.814 mmol) afforded the title compound (126.3 mg, 0.381 mmol, 93%) as a
colorless solid. Rf = 0.49 (cyclohexane/ethyl acetate 3:1); mp 144.6–145.5 °C; IR (ATR) 1597,
1
1574, 1463, 1416, 1257, 913, 735, 694; H NMR, COSY, NOESY (400 MHz, CDCl3) 10.74 (br
s, 1H, NH), 7.34–7.26 (m, 2H, H2’’’/6’’’), 7.22–7.14 (m, 1H, H4’’’), 7.11–6.95 (m, 7H, H2’’/6’’
3’’/5’’, H4’’, H3’’’/5’’’), 3.02 (q, J = 7.4 Hz, 2H, C2’CH2CH3), 2.06 (q, J = 7.2 Hz, 2H, H2), 1.34 (t, J
,
H
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
13
= 7.4 Hz, 3H, C2’CH2CH3), 0.85 (t, J = 7.2 Hz, 3H, H3); C NMR, HSQC, HMBC (101 MHz,
CDCl3) 201.2 (C1), 188.2 (C5’CO), 145.5 (C2’), 137.8 (C1’’’), 134.8 (C1’’), 133.3 (C4’), 131.0
(C4’’’), 130.8 + 127.8 + 127.38 (C2’’/6’’, C3’’/5’’, C3’’’/5’’’), 128.8 (C2’’’/6’’’), 127.41 (C4’’), 127.0 (C5’),
123.7 (C3’), 35.8 (C2), 21.2 (C2’CH2CH3), 13.5 (C2’CH2CH3), 8.6 (C3); MS (ESI) 332.2 [M+H]+;
+
HRMS (ESI) calcd for C22H21NaNO2 354.1470, found 354.1483.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 28 of 32
1
2
3
4
(3,5-Diphenyl-1H-pyrrole-2,4-diyl)bis(phenylmethanone) (7q).
5
6
7
8
Following general procedure B, isoxazole 1a (80.0 mg, 0.362 mmol) and dibenzoylmethane (6c,
162.2 mg, 0.7233 mmol) afforded the title compound (113.5 mg, 0.2655 mmol, 73%) as a
colorless solid. Rf = 0.47 (cyclohexane/ethyl acetate 3:1); mp 223.3–224.4 °C; IR (ATR) 3269,
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
1661, 1602, 1575, 1542, 1475, 1412, 1288, 738, 697; H NMR, COSY, NOESY (400 MHz,
CDCl3) 9.87 (br s, 1H, NH), 7.67–7.62 (m, 2H, H2’’’/6’’’), 7.55–7.51 (m, 2H, H2’’’’/6’’’’), 7.44–7.39
(m, 2H, H2’/6’), 7.36–7.27 (m, 4H, H4’’’, H3’’’’/5’’’’, H4’’’’), 7.23–7.17 (m, 1H, H4’), 7.16–7.11 (m,
2H, H3’’’/5’’’), 7.04–6.98 (m, 2H, H3’/5’), 6.96–6.92 (m, 2H, H2’’/6’’), 6.90–6.81 (m, 3H, H3’’/5’’
,
H4’’); C NMR, HSQC, HMBC (101 MHz, CDCl3) 194.3 (C4CO), 187.7 (C2CO), 138.1 (C1’’’),
137.9 (C5), 137.4 (C1’), 133.8 + 133.3 + 130.4 (C3, C1’’, C1’’’’), 132.9 (C4’’’), 131.5 (C4’), 130.8
(C2’’/6’’), 129.9 (C2’’’/6’’’), 129.3 (C2’/6’), 129.1 (C4’’’’), 129.0 (C3’’’’/5’’’’), 128.1 (C3’’’/5’’’), 128.0
(C2’’’’/6’’’’ overlapping with C2), 127.6 (C3’/5’), 127.5 (C3’’/5’’), 127.1 (C4’’), 123.4 (C4); MS (ESI)
13
428.2 [M+H]+; HRMS (ESI) calcd for C30H21NaNO2 450.1470, found 450.1482. Analytical data
+
in accordance with literature.22 Crystals suitable for Xꢀray crystallography could be obtained by
recrystallization of 7q from acetonitrile.
(5-Methyl-3-phenyl-1H-pyrrole-2,4-diyl)bis(phenylmethanone) (7r)
diphenyl-1H-pyrrol-3-yl)ethanone (7s).
/
1-(5-benzoyl-2,4-
Following general procedure B, isoxazole 1a (60.0 mg, 0.271 mmol) and benzoylacetone (6d,
87.9 mg, 0.542 mmol) afforded a nonseparable mixture (70.2 mg, 0.192 mmol, 71%) of the two
isomers 7r and 7s (ratio approx. 84:16 based on 1H NMR integration) as a colorless oil. Rf = 0.39
1
(cyclohexane/ethyl acetate 3:1); IR (ATR) 3261, 1598, 1574, 1414, 1279, 907, 730, 695, 652; H
NMR, COSY, NOESY (600 MHz, CDCl3) compound 7r: 11.05 (br s, 1H, NH), 7.54–7.51 (m,
2H, H2’’’/6’’’), 7.37–7.33 (m, 2H, H2’/6’), 7.25–7.22 (m, 1H, H4’’’), 7.18–7.14 (m, 1H, H4’), 7.12–
ACS Paragon Plus Environment

Page 29 of 32
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
7.07 (m, 2H, H3’’’/5’’’), 6.99–6.94 (m, H3’/5’), 6.81–6.75 (m, 3H, H2’’/6’’, H4’’), 6.74–6.70 (m, 2H,
H3’’/5’’), 2.53 (s, 3H, CH3), compound 7s (signals partially superimposed): 10.71 (br s, 1H, NH),
7.67–7.65 (m, 2H, H2’’/6’’), 7.45–7.42 (m, 3H, H3’’/5’’, H4’’), 7.39–7.37 (m, 2H, H2’’’’/6’’’’), 7.22–
7.18 (m, 1H, H4’’’’), 7.12–7.04 (m, 5H, H2’’’/6’’’, H3’’’/5’’’, H4’’’), 7.04–7.00 (m, 2H, H3’’’’/5’’’’), 1.96
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
13
(s, 3H, H2); C NMR, HSQC, HMBC (151 MHz, CDCl3) compound 7r: 194.1 (C4CO), 188.0
(C2CO), 139.6 (C5), 138.8 (C1’’’), 137.5 (C1’), 134.2 (C3), 133.7 (C1’’), 132.0 (C4’’’), 131.3 (C4’),
131.0 (C2’’/6’’), 129.6 (C2’’’/6’’’), 129.27 (C2’/6’), 127.74 (C3’’’/5’’’), 127.42 (C3’/5’), 127.2 (C3’’/5’’),
126.6 (C2, C4’’), 123.2 (C4), 13.2 (CH3), compound 7s: 198.6 (C1), 188.1 (C5’CO), 139.1 (C2’),
137.4 (C1’’’’), 133.8 (C1’’’), 133.3 (C4’), 131.4 (C4’’’’), 130.89 (C1’’), 130.86 (C2’’’/6’’’), 129.31
(C4’’), 129.10 + 129.09 (C2’’/6’’, C2’’’’/6’’’’), 128.7 (C3’’/5’’), 128.2 (C5’), 127.76 (C3’’’/5’’’), 127.51
(C3’’’’/5’’’’), 127.45 (C4’’’), 125.4 (C3’), 31.7 (C2); MS (ESI) 366.2 [M+H]+; HRMS (ESI) calcd for
+
C25H19NaNO2 388.1313, found 388.1302.
Associated Content
Reaction monitoring, NMR spectra, crystallographic data for compounds 7a and 7q, and ESIꢀMS
experiments.
Author Information
Corresponding Author
*Eꢀmail: opatz@uniꢀmainz.de
Notes
The authors declare no competing financial interest.
ACS Paragon Plus Environment