Symmetric and unsymmetric 3,3′-linked bispyrroles via ring-enlargement reactions of furan-derived donor-acceptor cyclopropanes

Article abstract of DOI:10.1039/c3ob40228b

A short and concise sequence for the synthesis of symmetrically and unsymmetrically substituted 3,3′-linked bispyrroles is described. Furan as a starting material is subjected to a twofold cyclopropanation by a diazo ester. Conversion of the ester functionalities to the respective ketones is achieved via Weinreb amide formation and the attack of a Grignard reagent. In the presence of amines the ketone moieties form imines that rearrange by ring-enlargement of the three-membered to the five-membered rings. In situ generated dihydropyrrole moieties eliminate water and afford aromatic pyrrole units. Unsymmetric bispyrroles are obtained by using different cyclopropanating agents or varying Grignard reagents for ketone formation before the addition of amines initiates the cascade to the respective bispyrroles. The Royal Society of Chemistry.

Full text of DOI:10.1039/c3ob40228b

Organic &
Biomolecular Chemistry
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Symmetric and unsymmetric 3,3’-linked bispyrroles
via ring-enlargement reactions of furan-derived
donor–acceptor cyclopropanes†
Cite this: Org. Biomol. Chem., 2013, 11,
3494
Johannes Kaschel,a Tobias F. Schneider,a Daniel Kratzert,b Dietmar Stalkeb and
Daniel B. Werz*a,c
A short and concise sequence for the synthesis of symmetrically and unsymmetrically substituted 3,3’-
linked bispyrroles is described. Furan as a starting material is subjected to a twofold cyclopropanation by
a diazo ester. Conversion of the ester functionalities to the respective ketones is achieved via Weinreb
amide formation and the attack of a Grignard reagent. In the presence of amines the ketone moieties
form imines that rearrange by ring-enlargement of the three-membered to the five-membered rings.
In situ generated dihydropyrrole moieties eliminate water and afford aromatic pyrrole units. Unsymmetric
bispyrroles are obtained by using different cyclopropanating agents or varying Grignard reagents for
ketone formation before the addition of amines initiates the cascade to the respective bispyrroles.
Received 1st February 2013,
Accepted 26th March 2013
DOI: 10.1039/c3ob40228b
www.rsc.org/obc
sometimes not an easy task. Due to their highly polarized π
system some positions are prone to react immediately in halo-
Introduction
The union of aromatic subunits by single bonds has occupied genation reactions whereas others are almost inert. If one tries
chemists’ minds since Ullmann’s discovery in 1901.1 He to substitute the 3-position of pyrroles with halides one will
employed aryl halides and copper powder to access symmetric realize that only bulky substituents such as TIPS at the pyrrolic
biaryls. With the advent of Pd-catalyzed cross-coupling reac- nitrogen allow a successful transformation.4 Indeed, there are
tions in the 1970s new powerful tools have emerged to link no reports on the assembly of 3,3′-linked dimers of pyrroles
two arenes.2 In the classical Stille or Suzuki–Miyaura reactions, via a metal-mediated cross-coupling strategy since the starting
one uses an aromatic halide and a respective stannane or materials are rather difficult to obtain.
boronic acid as the coupling partners.2 With the new discov-
However, a few other methods have been developed to
eries in the emerging field of C–H activation directing groups access 3,3′-linked bispyrroles. A transformation found by
determine the positions of the arene to be coupled whereas Gleiter et al. employs strained diazacyclodiynes such as 1 that
the reacting moiety itself is a C–H bond.3 However, with all rearrange under the influence of palladium on charcoal at
these novel methods there are still difficulties to be overcome, 140 °C to 3,3′-bispyrroles 2 (Scheme 1a).5 The mechanistic
since almost all methods rely on the regioselective introduc- picture involves several bond isomerizations, 1,3-hydrogen
tion of either reactive groups at the arene or the respective shifts and reductive eliminations. Although mechanistically
directing groups that often have to be cleaved later during the very interesting the preparative value is rather limited because
synthetic route.
the synthesis of the starting materials is challenging and no
Especially in the chemistry of heterocycles the regioselective further substituents are attached to the pyrrole units. Another
introduction of functional groups at distinct positions is route uses a double Michael addition involving diaroyl acety-
lene 3, appropriate 1,3-dicarbonyls such as 4 and ammonium
acetate 5 as the nitrogen source under the influence of a Lewis
aInstitut für Organische und Biomolekulare Chemie, Georg-August-Universität
acid. As a result highly substituted bispyrroles (e.g. 6) are
Göttingen, Tammannstr. 2, D-37077 Göttingen, Germany. E-mail: dwerz@gwdg.de;
obtained (Scheme 1b).6 Also procedures using Barton–Zard
Fax: +49 (551)399476; Tel: +49 (551)3933251
syntheses7 or oxidative copper-mediated methods starting
from pyrroles are known.8 Higher 3,3′-linked oligomers have
been achieved by using isonitrile chemistry in a repetitive
manner.9
bInstitut für Anorganische Chemie, Georg-August-Universität Göttingen,
Tammannstr. 4, D-37077 Göttingen, Germany
cInstitut für Organische Chemie, TU Braunschweig, Hagenring 30, D-38106
Braunschweig, Germany
†Electronic supplementary information (ESI) available: 1H and 13C NMR spectra
for all new compounds. CCDC 849623 and 849627. For ESI and crystallographic
data in CIF or other electronic format see DOI: 10.1039/c3ob40228b
We came across this field when studying the reactive behav-
iour of donor–acceptor (D–A) cyclopropanes.10–12 In 1988,
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Scheme 3 Synthesis of bisacetal 12 by D–A cyclopropanes.14
Scheme 1 Selected previous syntheses to access 3,3’-linked bispyrroles.5,6
Scheme 2 Reißig’s pyrrole synthesis based on D–A cyclopropanes.13
Reißig and co-workers developed a pyrrole synthesis relying on
the facile ring-enlargement of D–A cyclopropanes.13 Therefore,
enolates of cyclopropyl esters 7 were reacted with phenyl iso-
thiocyanates. The anionic intermediate underwent ring-enlar-
gement followed by trapping of the respective thiolate with
methyl iodide. The action of trifluoroacetic acid led to aromati-
zation affording 8 (Scheme 2).13
Recently, we developed a repetitive strategy for the prepa-
ration of oligocyclic oligoacetals such as 12 based on the tetra-
hydrofuran motif by using D–A cyclopropanes.14 The starting
material was furan (9) that was converted via a 3-step sequence
into the corresponding tricyclic bisacetal. After a twofold cyclo-
propanation the ester moieties in 10 were converted to alde-
Scheme 4 Our retrosynthetic analysis for 3,3’-linked bispyrroles.
respective bispyrrole 13 should be performed in a domino-like
fashion.17 Thus, a facile and flexible synthetic route to the
respective diketones allowing the modular installation of
different residues R1/R1′ and R2/R2′ starting from furan is
highly desirable. In this paper, we discuss the synthesis of the
starting materials for the domino sequence, the scope for the
bispyrrole formation, side-products, the mechanistic picture,
crystal structures of the products and the possibility to obtain
also bispyrroles with a different substitution pattern at the two
subunits.
hyde functionalities by
a reduction–oxidation sequence
leading instantaneously to the rearranged product 12
(Scheme 3).14
Theoretical studies we performed for the ring-enlargement
of a variety of D–A cyclopropanes revealed that a similar trans-
formation should also work with imine acceptors.15 However,
Results and discussion
the resulting dihydropyrrole units were expected to eliminate Our synthetic strategy to afford highly substituted bispyrroles
water creating a 3,3′-linkage between two pyrrole moieties. in a modular way commenced with the cyclopropanation of
Indeed, recently we were able to demonstrate that this concept furan (9).18 Due to the difficulties associated with the use of
works.16 A retrosynthetic analysis of this approach is depicted diazo ketones as cyclopropanating agents we employed the
in Scheme 4. Ideally, the conversion of the diketone 16 to the respective diazo esters. The latter are either commercially
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Scheme 5 Synthesis of symmetric and unsymmetric precursors; for R1, R2 and R3 see Table 1.
available or easily accessible by the conversion of respective equivalents of each organometallic reagent, one added after
esters using a weak base and a tosyl azide derivative in order the other. The major product is the mixed diketone 21 bearing
to install the diazo functionality.19,20 Another possibility is residues R2 and R2′ in combination with the corresponding
their generation from the respective amino acid esters. Three symmetric diketones as side products. The synthesis of unsym-
different diazo esters were used for our study, one derived metrically substituted diesters was accomplished by reacting
from glycine (R1 = H), the other formally derived from alanine furan initially with one equivalent of diazo compound bearing
(R1 = Me) and the third from phenylalanine (R1 = Ph). The residue R1 leading to 2221 and in a second step with another
twofold cyclopropanation to 18 was effected in dichloro- diazo compound bearing R1′ (Scheme 5b).
methane by using copper triflate or dirhodium tetraacetate in
The unsymmetric diesters 17 (R1 ≠ R1′) thus obtained were
catalytic amount.18 Depending on the kind of substitution converted to Weinreb amides 23. The addition of Grignard
pattern several different routes are feasible (Scheme 5). For reagent or the lithiated species led to unsymmetric diketones
symmetric 3,3′-linked bispyrroles the symmetric diesters 18 of type 24. The use of different organometallic reagents –
were transformed to the respective Weinreb amides 19 in very similar as in Scheme 5a – afforded a random mixture of four
good yield (Scheme 5a). The addition of Grignard reagents or possible products; therefore we refrained from investigating
respective lithiated species at 0 °C in THF led to diketones. If this possibility further.
3.5 equivalents of the same Grignard or 3.0 equivalents of the
Diketone 20a (R1 = H; R2 = Me) was selected as the model
organolithium reagent are employed symmetric diketones 20 substrate to explore optimized reaction conditions for the antici-
are obtained. As the residues (R2) of the ketone aliphatic moi- pated domino process consisting of imine formation, ring-
eties such as methyl, n-propyl, i-propyl and aromatic rings enlargement and elimination of water. As the reaction partner,
such as phenyl, 2-furyl, 2-thienyl and 2-(N-methyl)pyrryl were aniline was chosen. The best results were achieved using
chosen (see Table 1). At this stage, also two different substitu- p-toluenesulfonic acid in benzene at 80 °C after a reaction time
ents R2 and R2′ could be introduced by employing 1.2 of 2 h. Employing Lewis acids such as InCl3 or BF3·OEt2 also
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source16 or with a cyano substituent attached to the phenyl
ring of the amine (entry 4 in Table 1), this monopyrrole 26 was
even the only product.
Table 1 Transformation of symmetric diketones 20 into bispyrroles 25 and
monopyrroles 26
Mechanistically, we suppose that the sequence to the bis-
pyrroles is initiated by the formation of imine units
(Scheme 6, path A). According to our computations,15 imine
moieties as in 27 act as a slightly better acceptor in the ring-
enlargement reaction than ketones. Thus, in the second step,
the five-membered rings are formed. Since 2,3-dihydropyrrole
(as in 28) has a high tendency towards aromatization, water is
eliminated, leading to the desired product 25. The formation
of the side-product 26 – only observed in the case of R1 = H –
is explained by a nucleophilic attack of the amine at the acti-
vated cyclopropane in a Michael-type fashion leading to a clea-
vage of the cyclopropane moiety in 29 (Scheme 6, path B).
Under the influence of acids the central ring in 30 revealing a
bis(N,O-acetal) unit opens to 31. Of course, also another scen-
ario can be envisioned for the formation of the monopyrrole
26. The reaction of the ketone unit with electron-poor amines
to imines might be too slow. Ring-opening might lead to a
zwitterion (not depicted). The tendency of the electrophilic
oxonium part of this zwitterion to react even with electron-
poor amines is high. Intermediate 29 is formed as well.
Whether a Michael-like attack to the ketone activated by
protons or the formation of a zwitterion takes place is specu-
lation; thus, we would like to refrain from a deeper discussion.
Finally, the acetal-aminal-like structure in 33 is prone to eli-
minate one molecule of water and one molecule of amine to
reach aromaticity in the five-membered ring.
Yield
[%]
Entry 20
R1
R2
R3
25 26
116
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
20a
H
H
H
H
H
H
H
H
H
H
H
H
Me
Me
Me
Me
nPr
nPr
nPr
nPr
iPr
iPr
Ph
Ph
aa
81
ab 45
—
—
20a
20a
20a
20b
20b
20b
20b
20c
20c
20d
20d
4-F3C–C6H4
4-Me–C6H4–SO2 ac
4-NC–C6H4
Ph
4-HO–C6H4
4-F3C–C6H4
26 35
ad
ba 70 23
bb 79
bc 33 60
—
36
—
4-Me–C6H4–SO2 bd 23 59
Ph ca 41 48
4-Me–C6H4–SO2 cb 69
8
Ph
da 33 53
db 21 69
Ph
4-F3C–C6H4
4-MeO–C6H4
Ph
20e Me 2-Furyl
20e Me 2-Furyl
ea
eb 76
fa 61
76
—
—
—
—
—
—
In addition to symmetrically substituted bispyrroles, also
several unsymmetrically substituted congeners were generated
by our methodology. The starting points were unsymmetric
diketones of type 21 and 24. The former results in different
substituents at position 5 of the pyrrole moieties whereas the
latter leads to a different pattern at position 4. The same reac-
20f
Me 2-Thienyl
4-MeO–C6H4
20g Me 2-(N-Me)pyrryl 4-MeO–C6H4
ga 41
ha 28
20h Ph
20h Ph
Me
Me
4-MeO–C6H4
4-Me–C6H4–SO2 hb 35
provided the desired product but in lower yield. The use of tion conditions as mentioned before were applied. Ten
TiCl4 and TMSBr as Lewis acids did not lead to any significant examples 34a–34e and 35a–35e with their corresponding yields
formation of the bispyrrole. Although water is generated during are compiled in Scheme 7. For the products on the left side
the transformation the use of molecular sieves (MS 4 Å) effected precursors differing in R2 and R2′ were utilized whereas the
neither an improvement nor an acceleration of the reaction.
right side shows examples with R1 ≠ R1′. Moderate to good
After our initial experiments published recently16 we yields are obtained in all cases. Corresponding monopyrrole
extended the scope of this sequence by testing a large variety derivatives could not be detected. Attempts to achieve unsym-
of different precursors under the optimized reaction con- metric compounds by the simultaneous reaction of two
ditions to afford the bispyrroles 25 (Table 1). As the substituent different amines (R3, R3′) with the diketone were not success-
R1 at the cyclopropane ring in geminal position to the acceptor ful. Electron-rich aniline derivatives proved to be much more
unit H, Me and Ph were chosen. The residues at the ketone reactive than electron-poor aniline derivatives; thus, only sym-
were Me, nPr, iPr and Ph, but also heteroaromatic systems metric bispyrroles were obtained. In the case of very similar
such as furyl, thienyl and pyrryl substitutents were under amines (aniline vs. toluidine) a statistical mixture of the sym-
investigation (Table 1, entries 13–16). As we already had metric and the unsymmetric reaction products was formed
demonstrated,16 electron-rich amines such as 4-hydroxyaniline which could not be separated by common column
and 4-methoxyaniline revealed the best results (e.g. entry 6 in chromatography.
Table 1). Commonly, the yields dramatically decrease by utiliz-
For one representative example of a bispyrrole (25aa) as well
ing amines with electron-withdrawing substituents such as as for one monopyrrole derivative (26da) we were able to grow
CF3 or cyano moieties. In most of these cases, but only when single crystals suitable for X-ray crystallography. The respective
R1 = H, another product, a monopyrrole derivative 26, was also molecular structures are depicted in Fig. 1. The mean planes
found. In very few cases, e.g. with sulfonamides as the nitrogen of the central bispyrrole units in 25aa are twisted by 23.2°
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Scheme 6 Proposed mechanism for the formation of bispyrroles 25 and monopyrroles 26.
whereas the phenyl rings are rotated against the adjacent procedures and distilled prior to use. Commercially available
pyrrole unit by about 50°. In 26da the conjugated π units are compounds were used without further purification unless
almost in one plane (dihedral angle of 2.3°).
otherwise stated. Proton (1H) and carbon (13C) NMR spectra
were recorded on a 300, 500 or 600 MHz instrument using the
residual signals from CHCl3, δ = 7.26 ppm and δ = 77.0 ppm,
DMSO, δ = 2.54 ppm and δ = 40.45 ppm, acetone, δ = 2.09 ppm
and δ = 30.92 ppm, δ = 207.07 ppm, and methanol, δ =
Conclusion
1
We have developed a synthetic route to access symmetrically and
unsymmetrically substituted 3,3′-linked bispyrroles by making
use of the special features of donor–acceptor cyclopropanes. The
starting point of our synthesis was furan. Twofold cyclopropana-
tion led to the respective esters that were converted via the
Weinreb amides into ketones. In a domino sequence consisting
of imine formation, ring-enlargement of the donor–acceptor
cyclopropane and elimination of water the latter were trans-
formed into bispyrroles. Side products were monopyrroles that
are the result of an attack of the amine at the three-membered
ring rather than at the ketone. A stepwise preparation of the di-
esters or the diketones, respectively, enabled access to unsymme-
trically substituted congeners. Our methodology allows the
creation of 3,3′-linked bispyrroles without the use of cross-coup-
ling reactions. This might be a great advantage since a selective
functionalization at the 3-position of pyrroles is often a very
challenging transformation. The compounds obtained might
find useful applications in terms of organic electronic materials.
4.87 ppm and δ = 49.2 ppm, as internal references for H and
13C chemical shifts, respectively. Assignments of the respective
signals were made by the combination of H,H-COSY, HSQC
and HMBC experiments. Unclear assignments were marked
with *. ESI–HRMS spectrometry was carried out on an FTICR
instrument. IR spectra were measured with an ATR spectro-
meter. UV spectra were measured with a common photometer.
Symmetric precursors as well as the model compound 25aa
were already published.16
General procedures†
(A) Preparation of bispyrroles with non-polar amines. To a
solution of diketone (1.0 equiv.) in benzene (5 mL) was added
the amine (3.5 equiv.) and p-toluenesulfonic acid monohydrate
(5 mol%). The reaction mixture was stirred for 2 h at 80 °C.
The crude product was purified by flash column chromato-
graphy on basic aluminium oxide.
(B) Preparation of bispyrroles with polar amines. To a
solution of diketone (1.0 equiv.) in benzene (4 mL) was added
the amine (3.5 equiv.) and acetic acid (1 mL). The reaction
mixture was stirred for 1 h at 80 °C. The mixture was diluted
with water (5 mL) and extracted with ethyl acetate (3×). The
Experimental section
General remarks
All reactions were performed in flame-dried glassware under combined organic phases were washed subsequently with an
an argon atmosphere. The solvents were dried by standard aqueous solution of sodium hydrogencarbonate, water (2×)
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[a]
Scheme 7 Synthesis of unsymmetrically substituted bispyrroles – a compilation with the respective yields.
Instead of p-TsOH, acetic acid was used; the reaction
time was 20 h.
and dried over sodium sulfate. The crude product was purified 1H-NMR (300 MHz, CDCl3): δ [ppm] = 1.09–1.31 (m, 6H, CH3),
by flash column chromatography on silica gel. 1.39 (s, 3H, Me), 1.85–1.89 (m, 1H, 2′-H), 2.13–2.23 (m, 1H, 3′-
Diester 17a. To a well-stirred mixture of ethyl exo-2-oxabi- H), 2.40 (d, J = 5.8 Hz, 1H, 2-H), 3.77 (d, J = 5.8 Hz, 1H, 1-H),
cyclo[3.1.0]hex-3-ene-6-carboxylate21 (22) (361 mg, 2.34 mmol, 3.84–3.92 (m, 1H, 1′-H), 4.01–4.14 (m, 4H, OCH2CH3).
1.0 equiv.) and Rh2(OAc)4 (26 mg, 59 μmol, 2.5 mol%) in 13C-NMR (150 MHz, CDCl3): δ [ppm] = 7.6 (Me), 14.2 (CH3),
dichloromethane (20 mL), a solution of ethyl 2-diazopropano- 14.2 (CH3), 26.8 (C-3′), 26.9 (C-2′*), 27.8 (C-3), 33.6 (C-2*), 60.7
ate19 (900 mg, 7.03 mmol, 3.0 equiv.) in dichloromethane (OCH2CH3), 60.9 (OCH2CH3), 65.5 (C-1*), 66.1 (C-1′*), 170.5
(8 mL) was slowly added via a syringe pump (1 mL h−1) at rt. (CO), 172.1 (CO). IR (ATR): ˜ν (cm−1) = 2981, 1711, 1291,
The resulting mixture was stirred for 6 h at rt. After purifi- 1237, 1174, 1104, 1022. UV (CH3CN): λmax [nm] (lg ε) = 194
cation by flash column chromatography (SiO2, pentane–EtOAc, (4.11). MS (ESI): m/z (%) = 277.1 (45) [M + Na]+. HRMS (ESI):
9 : 1 → 8 : 1) the product was obtained as a colourless oil m/z calculated for C13H18O5Na [M + Na]+ 277.1046; observed:
(314 mg, 1.23 mmol, 53%). Rf: 0.46 (hexane–EtOAc 6 : 1). 277.1046.
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and then for 30 min at room temperature. The mixture was
cooled to 0 °C and a solution of bis-Weinreb amide 19b16
(102 mg, 342 μmol, 1.0 equiv.) in THF (10 mL) was added. The
reaction mixture was stirred for 90 min at room temperature,
quenched with sat. ammonium chloride solution, extracted
with ethyl acetate (3×) and dried over sodium sulfate. After
flash column chromatography (SiO2, pentane–EtOAc 5 : 1 →
4 : 1) the product was obtained as a white solid (106 mg,
308 μmol, 90%). Rf: 0.60 (hexane–EtOAc = 2 : 1). 1H-NMR
(300 MHz, CDCl3): δ [ppm] = 1.77 (s, 6H, Me), 2.49 (d, J = 5.6
Hz, 2H, 2,2′-H), 3.95 (d, J = 5.6 Hz, 2H, 1,1′-H), 7.14 (dd, J = 3.9,
5.0 Hz, 2H, 7,7′-H), 7.62 (dd, J = 1.1, 5.0 Hz, 6,6′-H), 7.81 (dd, J
= 1.1, 3.9 Hz, 8,8′-H). 13C-NMR (125 MHz, CDCl3): δ [ppm] =
11.0 (Me), 29.6 (C-2,2′), 34.5 (C-3,3′), 68.5 (C-1,1′), 127.8
(C-7,7′), 132.5, 133.1 (C-6,6′,8,8′), 142.8 (C-5,5′), 191.8 (C-4,4′).
IR (ATR): ˜ν (cm−1) = 1601, 1411, 1293, 1250, 1065. UV (CH3CN):
λmax [nm] (lg ε) = 262 (4.26), 286 (4.28). MS (ESI): m/z (%) =
345.1 (82) [M + H]+, 367.1 (57) [M + Na]+, 711.1 (100) [2M +
Na]+. HRMS (ESI): m/z calculated for C18H16O3S2Na [M + Na]+
367.0433; observed: 367.0433.
Diketone 20g. To a solution of N-methylpyrrole (74 mg,
915 μmol, 3.0 equiv.) in THF (5 mL) at −78 °C was added tert-
butyllithium solution (570 μL, 1.6 m in pentane, 915 μmol, 3.0
equiv.), and the mixture was stirred for 10 min at −78 °C and
then for 30 min at room temperature. The mixture was cooled
to 0 °C and a solution of bis-Weinreb amide 19b16 (91 mg,
305 μmol, 1.0 equiv.) in THF (10 mL) was added. The reaction
mixture was stirred for 90 min at room temperature, quenched
Fig. 1 The structures of 25aa (top) and 26da (bottom), depicted with anisotro-
pic displacement parameters at the 50% probability level.
Diketone 20e. To a solution of furan (68 mg, 996 μmol, 3.0 with sat. ammonium chloride solution, extracted with ethyl
equiv.) in THF (5 mL) at −78 °C was added tert-butyllithium acetate (3×) and dried over sodium sulfate. After flash column
solution (620 μL, 1.6 m in pentane, 996 μmol, 3.0 equiv.), and chromatography (SiO2, pentane–EtOAc 5 : 1
→ 4 : 1) the
the mixture was stirred for 10 min at −78 °C and then for product was obtained as a colourless oil (85 mg, 251 μmol,
30 min at room temperature. The mixture was cooled to 0 °C 82%). Rf: 0.45 (hexane–EtOAc = 2 : 1). 1H-NMR (300 MHz,
and a solution of bis-Weinreb amide 19b16 (99 mg, 332 μmol, CDCl3): δ [ppm] = 1.65 (s, 6H, Me), 2.32 (d, J = 5.7 Hz, 2H, 2,2′-
1.0 equiv.) in THF (10 mL) was added. The reaction mixture H), 3.74–3.95 (m, 8H, 1,1′,Me), 6.14 (dd, J = 2.5, 4.1 Hz, 2H,
was stirred for 90 min at room temperature, quenched with 7,7′-H), 6.69–6.80 (m, 2H, 6,6′-H), 7.04 (dd, J = 1.6, 4.1 Hz, 2H,
sat. ammonium chloride solution, extracted with ethyl acetate 8,8′-H). 13C-NMR (125 MHz, CDCl3): δ [ppm] = 12.0 (Me), 27.5
(3×) and dried over sodium sulfate. After flash column chrom- (C-2,2′), 34.5 (C-3,3′), 37.3 (Me), 67.3 (C-1,1′), 107.9 (C-7,7′),
atography (SiO2, pentane–EtOAc 3 : 1) the product was 119.8 (C-6,6′), 129.2 (C-5,5′), 130.4 (C-8,8′), 189.9 (C-4,4′). IR
obtained as a pale yellow solid (96 mg, 307 μmol, 93%). Rf: (ATR): ˜ν (cm−1) = 2937, 1629, 1401, 1323, 1238, 1057. UV
0.48 (hexane–EtOAc = 3 : 1). 1H-NMR (300 MHz, CDCl3): δ (CH3CN): λmax [nm] (lg ε) = 293 (4.51). MS (ESI): m/z (%) = 339
[ppm] = 1.75 (s, 6H, Me), 2.49 (d, J = 5.5 Hz, 2H, 2,2′-H), 3.96 (100) [M + H]+, 361 (28) [M + Na]+, 699.3 (8) [2M + Na]+. HRMS
(d, J = 5.5 Hz, 2H, 1,1′-H), 6.52 (dd, J = 1.7, 3.6 Hz, 2H, 7,7′-H), (ESI): m/z calculated for C20H23N2O3 [M + H]+ 339.1703;
7.22 (dd, J = 0.7, 3.6 Hz, 2H, 6,6′-H), 7.58 (dd, J = 0.7, 1.7 Hz, observed: 339.1703.
2H, 8,8′-H). 13C-NMR (125 MHz, CDCl3): δ [ppm] = 9.6 (Me),
Diketone 21a. To a solution of bis-Weinreb amide 19a16
30.8 (C-2,2′), 34.0 (C-3,3′), 69.6 (C-1,1′), 111.9 (C-7,7′), 118.4 (338 mg, 1.25 mmol, 1.0 equiv.) in anhydrous THF (22 mL) at
(C-6,6′), 145.9 (C-8,8′), 151.9 (C-5,5′), 187.3 (C-4,4′). IR (ATR): ˜ν −10 °C, phenylmagnesium chloride solution (0.69 mL,
(cm−1) = 1620, 1460, 1385, 1297, 1256, 1174. UV (CH3CN): λmax 1.38 mmol, 2 m in THF, 1.1 equiv.) was added and the mixture
[nm] (lg ε) = 222 (3.93), 277 (4.53). MS (ESI): m/z (%) = 313.1 was stirred for 1 h at 0 °C. Methylmagnesium chloride solution
(67) [M + H]+, 335.1 (66) [M + Na]+, 647.2 (100) [2M + Na]+. (0.46 mL, 1.38 mmol, 3 m in THF, 1.1 equiv.) was added and
HRMS (ESI): m/z calculated for C18H16O5Na [M
335.0890; observed: 335.0892.
+
Na]+ the mixture was stirred for 2 h at 0 °C. After the addition of
sat. ammonium chloride solution the mixture was extracted
Diketone 20f. To
a solution of thiophene (86 mg, with ethyl acetate (3 × 25 mL) and the combined organic
1.03 mmol, 3.0 equiv.) in THF (5 mL) at −78 °C was added tert- phases were dried over sodium sulfate. The crude product was
butyllithium solution (640 μL, 1.6 m in pentane, 1.03 mmol, purified by flash column chromatography (SiO2, pentane–
3.0 equiv.), and the mixture was stirred for 10 min at −78 °C EtOAc, 5 : 1 → 4 : 1 → 3 : 1) to yield 127 mg (0.52 mmol, 42%)
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of the desired product 21a as a white solid and 46 mg symmetric products 20e (16 mg, 51 μmol, 14%) and 20f
(0.15 mmol, 12%) and 44 mg (0.24 mmol, 20%) of the bisphe- (48 mg, 139 μmol, 38%) could also be isolated. Rf: 0.20
1
nylketone 20d16 and the bismethylketone 20a16 both as white (hexane–EtOAc = 5 : 1). H-NMR (300 MHz, CDCl3): δ [ppm] =
solids. Analytical data of 21a: Rf: 0.53 (hexane–EtOAc 2 : 1). 1.75 (s, 3H, Me), 1.77 (s, 3H, Me), 2.40–2.59 (m, 2H, 2,2′-H),
1H-NMR (300 MHz, CDCl3): δ [ppm] = 2.23–2.28 (m, 1H, 2′-H), 3.90–4.02 (m, 2H, 1,1′-H), 6.50–6.57 (m, 1H, 7-H), 7.06–7.17
2.30 (s, 3H, Me), 2.55–2.61 (m, 1H, 3′-H), 2.69–2.76 (m, 1H, (m, 1H, 7′-H), 7.20–7.30 (m, 1H, 6-H), 7.57–7.66 (m, 2H, 6′,8-
3-H), 2.84–2.89 (m, 1H, 2-H), 3.90 (d, J = 5.3 Hz, 1H, 1′-H), 3.98 H), 7.78–7.85 (m, 1H, 8′-H). 13C-NMR (125 MHz, CDCl3): δ
(d, J = 5.2 Hz, 1H, 1-H), 7.41–7.64 (m, 3H, Ph), 7.90–8.04 (m, [ppm] = 9.6 (Me), 11.1 (Me), 29.5, 30.9 (C-2,2′), 34.3, 34.3
2H, Ph). 13C-NMR (125 MHz, CDCl3): δ [ppm] = 31.1 (Me), 32.4 (C-3,3′), 68.7, 69.5 (C-1,1′), 111.9 (C-7), 118.4 (C-6), 127.8 (C-7′),
(C-2), 32.7, 32.8 (C-3,3′), 36.2 (C-2′), 66.7 (C-1′), 67.5 (C-1), 128.0 132.5, 133.1 (C-6′,8′), 142.8 (C-5′), 146.0 (C-8), 152.0 (C-5), 187.3
(Phtert), 128.6 (Phtert), 133.2 (Phtert), 137.0 (Phquart), 196.0 (C-4), (C-4), 191.8 (C-4′). IR (ATR): ˜ν (cm−1) = 1602, 1461, 1412, 1295,
204.2 (C-4′). IR (ATR): ˜ν (cm−1) = 3063, 1681, 1654, 1382, 1219, 1253. UV (CH3CN): λmax [nm] (lg ε) = 278 (4.41). MS (ESI): m/z
1098, 1036. UV (CH3CN): λmax [nm] (lg ε) = 244 (4.22), 200 (%) = 329.1 (100) [M + H]+, 351.1 (60) [M + Na]+, 679.2 (95)
(4.51). MS (ESI): m/z (%) = 265.1 (9) [M + Na]+. HRMS (ESI): m/z [2M + Na]+. HRMS (ESI): m/z calculated for C18H17O4S [M + H]+
calculated for C15H14O3Na [M + Na]+ 265.0835; observed: 329.0842; observed: 329.0841.
265.0831.
Diketone 21b. To a solution of bis-Weinreb amide 19a16 (258 mg, 1.05 mmol, 1.0 equiv.) in anhydrous THF (20 mL)
(433 mg, 1.52 mmol, 1.0 equiv.) in anhydrous THF (25 mL) at was added N,O-dimethylhydroxylamine hydrochloride
Bis-Weinreb amide 23a. To a solution of diester 17a
−10 °C, methylmagnesium chloride solution (0.56 mL, (495 mg, 5.08 mmol, 5.0 equiv.) and the mixture was cooled to
1.68 mmol, 3 m in THF, 1.1 equiv.) was added and the mixture −20 °C. Isopropylmagnesium chloride solution (4.06 mL,
was stirred for 1 h at 0 °C. n-Propylmagnesium chloride solu- 8.12 mmol, 2 m in THF, 8.0 equiv.) was added slowly. The reac-
tion (0.84 mL, 1.68 mmol, 2 m in Et2O, 1.1 equiv.) was added tion mixture was stirred for 4 h at −10 °C and then for 2 h at rt
and the mixture was stirred for 2 h at 0 °C. After the addition until the reaction was stopped by the addition of sat.
of sat. ammonium chloride solution the mixture was extracted ammonium chloride solution. The solution was extracted with
with ethyl acetate (3 × 25 mL) and the combined organic ethyl acetate (3 × 20 mL) and the combined organic phases
phases were dried over sodium sulfate. The crude product was were dried over sodium sulfate. The crude product was puri-
purified by flash column chromatography (SiO2, pentane– fied by flash column chromatography (SiO2, pentane–EtOAc,
EtOAc, 5 : 1 → 4 : 1 → 1 : 1) to yield 124 mg (595 μmol, 39%) of 2 : 1 → 1 : 2) to yield 232 mg (816 μmol, 80%) of a colourless
the desired product 21b as a white solid and 36 mg oil. Rf: 0.30 (EtOAc). 1H-NMR (300 MHz, CDCl3): δ [ppm] = 1.41
(0.15 mmol, 10%) and 97 mg (0.54 mmol, 35%) of the bispro- (s, 3H, Me), 2.20–2.40 (m, 3H, 2,2′,3′-H), 3.19 (s, 6H, NMe),
pylketone 20b16 and the bismethylketone 20a,16 both as white 3.72 (s, 3H, OMe), 3.78–3.80 (m, 4H, OMe, 1′-H), 3.83 (d, J = 5.3
solids. Analytical data of 21b: Rf: 0.57 (hexane–EtOAc, 2 : 1). Hz, 1H, 1-H). 13C-NMR (150 MHz, CDCl3): δ [ppm] = 9.3 (Me),
1H-NMR (300 MHz, CDCl3): δ [ppm] = 0.81 (t, J = 7.4 Hz, 3H, 24.5 (C-2′*), 26.6 (C 2*), 29.1 (C-3), 30.1 (C-3′), 32.2 (NMe), 33.6
CH2CH2CH3), 1.37–1.63 (m, 2H, CH2CH2CH3), 2.01–2.11 (m, (NMe), 60.6 (OMe), 61.6 (OMe), 62.8 (C-1*), 66.5 (C-1′*), 170.5
2H, 3,3′-H), 2.16 (s, 3H, Me), 2.23–2.56 (m, 4H, 2,2′-H, (CO), 171.7 (CO). IR (ATR): ˜ν (cm−1) = 2939, 1711, 1645, 1300,
CH2CH2CH3), 3.63–3.74 (m, 2H, 1,1′-H). 13C-NMR (125 MHz, 1234, 1095, 1005. UV (CH3CN): λmax [nm] (lg ε) = 199 (4.05). MS
CDCl3): δ [ppm] = 13.7 (CH2CH2CH3), 17.3 (CH2CH2CH3), 31.1 (ESI): m/z (%) = 307.1 (100) [M + Na]+, 591.3 (48) [2M + Na]+,
(Me), 31.8, 32.3 (C-3,3′), 35.5, 36.2 (C 2,2′), 45.9 (CH2CH2CH3), 875.4 (9) [3M
66.3, 66.6 (C-1,1′), 204.3, 206.6 (C-4,4′). IR (ATR): ˜ν (cm−1) = C13H20N2O5Na [M + Na]+ 307.1264; observed: 307.1265.
2961, 1713, 1681, 1390, 1281, 1156, 1034, 1005. UV (CH3CN): Diketone 24a. Methylmagnesium chloride solution
λmax [nm] (lg ε) = 273 (2.14), 215 (4.00). MS (ESI): m/z (%) = (0.52 mL, 1.57 mmol, 3 m in THF, 3.0 equiv.) was added slowly
231.1 (6) [M
Na]+. HRMS (ESI): m/z calculated for to a solution of bis-Weinreb amide 23a (149 mg, 524 μmol, 1.0
C12H16O3Na [M + Na]+ 231.0992; observed: 231.0991.
equiv.) in anhydrous THF (20 mL) at −10 °C. The mixture was
+
Na]+. HRMS (ESI): m/z calculated for
+
Diketone 21c. To a solution of furan (30 mg, 438 μmol, 1.2 stirred for 3 h at 0 °C and stopped by the addition of sat.
equiv.) and thiophene (37 mg, 438 μmol, 1.2 equiv.) in THF ammonium chloride solution. The solution was extracted with
(5 mL) at −78 °C was added tert-butyllithium solution (550 μL, ethyl acetate (3 × 20 mL) and the combined organic phases
1.6 m in pentane, 876 μmol, 2.4 equiv.), the mixture was were dried over sodium sulfate. After flash column chromato-
stirred for 10 min at −78 °C and then for 30 min at room graphy (SiO2, pentane–EtOAc, 1 : 1 → 1 : 2 → 1 : 3) the product
temperature. The mixture was cooled to 0 °C and a solution of was obtained as a pale yellow solid (86 mg, 443 μmol, 85%). Rf:
bis-Weinreb amide 19b16 (109 mg, 365 μmol, 1.0 equiv.) in 0.71 (EtOAc). 1H NMR (300 MHz, CDCl3): δ [ppm] = 1.46 (s,
THF (10 mL) was added. The reaction mixture was stirred for 3H, Me), 2.16–2.31 (m, 8H, Me,Me,2′-H,3′-H), 2.45 (d, J = 5.7
90 min at room temperature, quenched with sat. ammonium Hz, 1H, 2-H), 3.63 (d, J = 5.7 Hz, 1H, 1-H), 3.82 (d, J = 5.1 Hz,
chloride solution, extracted with ethyl acetate (3×) and dried 1H, 1′-H). 13C NMR (125 MHz, CDCl3): δ [ppm] = 8.8 (Me), 28.4
over sodium sulfate. After flash column chromatography (SiO2, (Me), 29.2 (C-3′), 31.1 (Me), 35.1 (C-2*), 35.4 (C-3), 35.7 (C-2′*),
pentane–EtOAc 7 : 1 → 6 : 1 → 4 : 1) the desired product 21c 68.2 (C-1′*), 69.1 (C-1*), 204.5 (CO), 206.9 (CO). IR (ATR):
was obtained as a white solid (41 mg, 125 μmol, 34%). The ˜ν (cm−1) = 2924, 1682, 1671, 1358, 1232, 1172, 1098. UV
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(CH3CN): λmax [nm] (lg ε) = 217 (4.02). MS (ESI): m/z (%) = 1.0 equiv.) in THF (10 mL) was added. The reaction mixture
217.1 (100) [M + Na]+, 411.2 (45) [2M + Na]+. HRMS (ESI): m/z was stirred for 90 min at room temperature, quenched with
calculated for C11H14O3Na [M + Na]+ 217.0835; observed: sat. ammonium chloride solution, extracted with ethyl acetate
217.0834.
(3×) and dried over sodium sulfate. After flash column chrom-
Diketone 24b. To a well-stirred mixture of ethyl exo-2-oxabi- atography (SiO2, pentane–EtOAc 2 : 1) the product was
cyclo[3.1.0]hex-3-ene-6-carboxylate21 (22) (300 mg, 1.95 mmol, obtained as a yellow solid (115 mg, 385 μmol, 98%). Rf: 0.39
1
1.0 equiv.) and Rh2(OAc)4 (22 mg, 49 μmol, 2.5 mol%) in (hexane–EtOAc = 2 : 1). H-NMR (300 MHz, CDCl3): δ [ppm] =
dichloromethane (20 mL), a solution 1-phenyl ethyl diazoace- 1.71 (s, 3H, Me), 2.41–2.58 (m, 1H, 3′-H), 2.72 (d, J = 5.7 Hz,
tate20 (1.48 g, 7.78 mmol, 4.0 equiv.) in dichloromethane 1H, 2-H), 2.88 (d, J = 3.5 Hz, 1H, 2′-H), 3.96 (d, J = 5.7 Hz, 1H,
(8 mL) was added slowly via a syringe pump (1 mL h−1) at rt. 1-H), 4.07 (d, J = 5.1 Hz, 1H, 1′-H), 6.44–6.63 (m, 2H, 7,7′-H),
The resulting mixture was stirred for 6 h at rt. After purifi- 7.10–7.33 (m, 2H, 6,6′-H), 7.55–7.73 (m, 2H, 8,8′-H). 13C-NMR
cation by flash column chromatography (SiO2, pentane–EtOAc, (125 MHz, CDCl3): δ [ppm] = 9.2 (Me), 29.2, 31.8, 34.5
10 : 1 → 8 : 1 → 6 : 1) the still impure diester 17b was obtained (C-2,2′,3′), 34.5 (C-3), 67.0, 69.5 (C-1,1′), 111.9, 112.4 (C-7,7′),
as a yellow solid (928 mg, HRMS (ESI): m/z calculated for 116.9, 118.5 (C-6,6′), 146.0, 146.6 (C-8,8′), 151.9, 152.6 (C-5,5′),
C18H20O5Na [M + Na]+ 339.1203; observed: 339.1199) which 184.9, 187.0 (C-4,4′). IR (ATR): ˜ν (cm−1) = 1645, 1625, 1462,
was dissolved in anhydrous THF (40 mL) and cooled to 1306, 1168, 1012. UV (CH3CN): λmax [nm] (lg ε) = 219 (3.95),
−20 °C. After the addition of N,O-dimethylhydroxylamine 278 (4.51). MS (ESI): m/z (%) = 299.1 (85) [M + H]+, 321.1 (57)
hydrochloride (1.14 g, 11.7 mmol, 6.0 equiv.) a 2 M solution of [M + Na]+, 619.2 (100) [2M + Na]+. HRMS (ESI): m/z calculated
isopropylmagnesium chloride in THF (8.78 mL, 17.6 mmol, for C17H15O5 [M + H]+ 299.0914; observed: 299.0914.
9.0 equiv.) was added. The reaction mixture was stirred for 4 h
5,5′-Dimethyl-1,1′-bis(4-(trifluoromethyl)phenyl)-3,3′-bipyr-
at −10 °C and then 2 h at rt until the reaction was stopped by role (25ab). General procedure A: Diketone 20a16 (25 mg,
the addition of sat. ammonium chloride solution. The solution 139 μmol, 1.0 equiv.), 4-(trifluoromethyl)aniline (78 mg,
was extracted with ethyl acetate (3 × 30 mL) and the combined 487 μmol, 3.5 equiv.), p-toluenesulfonic acid (1.3 mg, 6.9 μmol,
organic phases were dried over sodium sulfate. The crude 5 mol%). Purification: Flash column chromatography (basic
product was purified by flash column chromatography (SiO2, Al2O3, pentane–EtOAc, 10 : 1). Yield: Yellow solid (28 mg,
pentane–EtOAc, 2 : 1 → 1 : 1 → 0 : 1) to yield 384 mg of the still 62 μmol, 45%). Rf: 0.76 (hexane–EtOAc, 1 : 1). 1H-NMR
impure bis-Weinreb amide 23b as a yellow solid (HRMS (ESI): (300 MHz, CDCl3): δ [ppm] = 2.26 (s, 6H, 6,6′-H), 6.21 (s, 2H,
m/z calculated for C18H22N2O5Na [M + Na]+ 369.1421; observed: 4,4′-H), 6.89 (s, 2H, 2,2′-H), 7.45 (d, J = 8.3 Hz, 4H, 8,8′,8a,8a′-
369.1425). The product was dissolved in anhydrous THF H), 7.69 (d, J = 8.3 Hz, 4H, 9,9′,9a,9a′-H). 13C-NMR (125 MHz,
(20 mL), cooled to −10 °C and reacted with methylmagnesium CDCl3): δ [ppm] = 13.2 (C-6,6′), 108.6 (C-4,4′), 116.5 (C-2,2′),
1
chloride (1.30 mL, 3.90 mmol, 3 m in THF, 2.0 equiv.). The 119.7 (C-3,3′), 123.9 (q, JC–F
= 272 Hz, CF3), 125.3
2
mixture was stirred for 3 h at 0 °C until the reaction was (C-8,8′,8a,8a′), 126.3 (C-9,9′,9a,9a′), 128.5 (q, JC–F = 32.8 Hz,
stopped by the addition of sat. ammonium chloride solution. C-10,10′), 129.4 (C-5,5′), 143.3 (C-7,7′). IR (ATR): ˜ν (cm−1) =
The solution was extracted with ethyl acetate (3 × 20 mL) and 2923, 2358, 1614, 1522, 1390, 1378, 1321, 1161, 1106, 1066. UV
the combined organic phases were dried over sodium sulfate. (CH3CN): λmax [nm] (lg ε) = 265 (4.23). MS (ESI): m/z (%) =
After flash column chromatography (SiO2, pentane–EtOAc 449.2 (84) [M + H]+, 471.1 (22) [M + Na]+, 919.3 (24) [2M + Na]+.
3 : 1) the pure diketone was obtained as a pale yellow oil HRMS (ESI): m/z calculated for C24H18N2F6Na [M + Na]+
(164 mg, 640 μmol, 33% over 3 steps). Analytical data of the 471.1266; observed: 471.1258.
diketone: Rf: 0.42 (hexane–EtOAc, 1 : 1). 1H-NMR (300 MHz,
CDCl3): δ [ppm] = 1.90 (s, 3H, Me), 2.07–2.37 (m, 5H, Me,2′,3′- tosyl-1H-pyrrole-3,4-diyl)bis(propan-2-one)
5,5′-Dimethyl-1,1′-ditosyl-3,3′-bipyrrole (25ac) and 1,1′-(1-
(26ac). General
H), 2.90 (d, J = 5.3 Hz, 1H, 2-H), 3.06 (d, J = 5.1 Hz, 1H, 1-H), procedure A: Diketone 20a16 (25 mg, 139 μmol, 1.0 equiv.),
3.99 (d, J = 5.3 Hz, 1H, 1′-H), 7.08–7.66 (m, 5H, Ph). 13C-NMR p-tosylamide (83 mg, 485 μmol, 3.5 equiv.), p-toluenesulfonic
(150 MHz, CDCl3): δ [ppm] = 30.0 (Me), 30.9 (C-3′), 31.0 (Me), acid (1.3 mg, 6.9 μmol, 5 mol%). Purification: Flash column
35.6 (C-2′), 37.5 (C-2), 46.0 (C-3), 67.7 (C-1′), 69.7 (C-1), 127.9 chromatography (basic Al2O3, pentane–EtOAc, 10 : 1 → 5 : 1 →
(Phtert), 128.9 (Phtert), 131.9 (Phtert), 132.7 (Phquart), 204.1 (C-4′), 2 : 1). Yield: 25ac as a yellow solid (17 mg, 36.3 μ, 26%), 26ac as
205.8 (C-4). IR (ATR): ˜ν (cm−1) = 1678, 1384, 1355, 1225, 1138, a yellow oil (16 mg, 48 μmol, 35%). Analytical data of com-
1
1088, 1013. UV (CH3CN): λmax [nm] (lg ε) = 292 (3.05), 259 pound 25ac: Rf: 0.68 (hexane–EtOAc, 1 : 1). H-NMR (300 MHz,
(3.02). MS (ESI): m/z (%) = 257.1 (30) [M + H]+, 279.1 (36) [M + CDCl3): δ [ppm] = 2.30 (s, 6H, 6,6′-H), 2.40 (s, 6H, 11,11′-H),
Na]+. HRMS (ESI): m/z calculated for C16H16O3Na [M + Na]+ 6.09 (s, 2H, 4,4′-H), 7.28 (d, J = 8.2 Hz, 4H, 8,8′,8a,8a′-H), 7.33
279.0992; observed: 279.0991.
(s, 2H, 2,2′-H), 7.68 (d, J = 8.2 Hz, 4H, 9,9′,9a,9a′-H). 13C-NMR
Diketone 24c. To a solution of furan (81 mg, 1.18 mmol, 3.0 (125 MHz, CDCl3): δ [ppm] = 13.6 (C-6,6′), 21.6 (C-11,11′),
equiv.) in THF (5 mL) at −78 °C was added tert-butyllithium 111.8 (C-4,4′), 117.2 (C-2,2′), 119.9 (C-3,3′), 126.8 (C-9,9′,9a,9a′),
solution (740 μL, 1.6 m in pentane, 1.18 mmol, 3.0 equiv.), 130.0 (C-8,8′,8a,8a′), 131.7 (C-5,5′), 136.2 (C-7,7′), 144.8
and the mixture was stirred for 10 min at −78 °C and then for (C-10,10′). IR (ATR): ˜ν (cm−1) = 2367, 1595, 1493, 1447, 1354,
30 min at room temperature. The mixture was cooled to 0 °C 1170, 1155, 1096, 1045. UV (CH3CN): λmax [nm] (lg ε) = 196
and a solution of bis-Weinreb amide 23a (112 mg, 394 μmol, (4.76), 209 (4.48), 227 (4.41), 249 (4.26). MS (ESI): m/z (%) =
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491.1 (12) [M
Paper
+
Na]+. HRMS (ESI): m/z calculated for 17.3 (C-7,7′), 40.1 (C-4,4′), 43.7 (C-6,6′), 117.6 (C-3,3′), 118.6
C24H24N2O4S2Na [M + Na]+ 491.1070; observed: 491.1063.
(C-2,2′), 119.8 (C-10,10′) 125.4 (C-12), 129.5 (C-11,11′), 140.3
Analytical data of compound 26ab: Rf: 0.30 (hexane–EtOAc, (C-9), 209.0 (C-5,5′). IR (ATR): ˜ν (cm−1) = 2959, 2360, 1705,
1
1 : 1). H-NMR (300 MHz, CDCl3): δ [ppm] = 2.10 (s, 6H, 6,6′- 1599, 1528, 1498, 1388, 1055. UV (CH3CN): λmax [nm] (lg ε) =
H), 2.38 (s, 3H, 11-H), 3.40 (s, 4H, 4,4′-H), 7.03 (s, 2H, 2,2′-H), 264 (4.14). MS (ESI): m/z (%) = 334.2 (36) [M + Na]+, 645.4 (100)
7.27 (d, J = 8.4 Hz, 2H, 8,8′-H), 7.70 (d, J = 8.4 Hz, 2H, 9,9′-H). [2M + Na]+. HRMS (ESI): m/z calculated for C20H25NO2Na
13C-NMR (125 MHz, CDCl3): δ [ppm] = 21.6 (C-11), 29.2 [M + Na]+ 334.1778; observed: 334.1776.
(C-6,6′), 40.5 (C-4,4′), 119.8 (C-2,2′), 121.1 (C-3,3′), 126.8
1,1′-Bis(4-hydroxyphenyl)-5,5′-dipropyl-3,3′-bipyrrole (25bb).
(C-9,9′), 130.0 (C-8,8′), 136.0 (C-7), 145.0 (C-10), 205.5 (C-5,5′). General procedure B: Diketone 20b16 (33 mg, 140 μmol, 1.0
IR (ATR): ˜ν (cm−1) = 2923, 1710, 1596, 1357, 1168, 1092, 1064. equiv.), 4-aminophenol (54 mg, 490 μmol, 3.5 equiv.). Purifi-
UV (CH3CN): λmax [nm] (lg ε) = 194 (4.57), 224 (4.09), 243 cation: Flash column chromatography (SiO2, pentane–EtOAc,
(4.04). MS (ESI): m/z (%) = 356.1 (44) [M + Na]+, 689.2 (100) [2M 3 : 1). Yield: Yellow solid (44 mg, 110 μmol, 79%). Rf: 0.48
+
Na]+. HRMS (ESI): m/z calculated for C17H19NO4SNa (hexane–EtOAc, 1 : 1). 1H-NMR (300 MHz, CD3OD): δ [ppm] =
[M + Na]+ 356.0927; observed: 356.0919.
0.85 (t, J = 7.3 Hz, 6H, 8,8′-H), 1.40–1.54 (m, 4H, 7,7′-H), 2.43
1,1′-(1-Benzonitrile-1H-pyrrole-3,4-diyl)bis(propan-2-one) (t, J = 7.8 Hz, 4H, 6,6′-H), 4.87 (s, 2H, OH), 6.07 (s, 2H, 4,4′-H),
(26ad). General procedure A: Diketone 20a16 (25 mg, 6.72 (s, 2H, 2,2′-H), 6.83 (d, J = 8.7 Hz, 4H, 11,11′,11a,11a′-H),
139 μmol, 1.0 equiv.), p-cyanoaniline (57 mg, 485 μmol, 3.5 7.10 (d, J = 8.7 Hz, 4H, 10,10′,10a,10a′-H). 13C-NMR (125 MHz,
equiv.), p-toluenesulfonic acid (1.3 mg, 6.9 μmol, 5 mol%). DMSO-d6: δ [ppm] = 13.7 (C-8,8′), 21.8 (C-7,7′), 28.2 (C-6,6′),
Purification: Flash column chromatography (basic Al2O3, 104.7 (C-4,4′), 115.5 (C-11,11′,11a,11a′), 116.5 (C-2,2′), 118.4
pentane–EtOAc, 5 : 1 → 3 : 1 → 1 : 1). Yield: Orange solid (C-3,3′), 126.9 (C-10,10′,10a,10a′), 131.5 (C-5,5′) 133.1 (C-9,9′),
1
(14 mg, 50 μmol, 36%). Rf: 0.38 (hexane–EtOAc, 1 : 1). H-NMR 156.2 (C-12,12′). IR (ATR): ˜ν (cm−1) = 3431, 2955, 1705, 1514,
(300 MHz, CDCl3): δ [ppm] = 2.21 (s, 6H, 6,6′-H), 3.56 (s, 4H, 1438, 1261, 1179, 1162. UV (MeOH): λmax [nm] (lg ε) = 229
4,4′-H), 7.05 (s, 2H, 2,2′-H), 7.42 (d, J = 8.9 Hz, 2H, 9,9′-H), 7.69 (4.38). MS (ESI): m/z (%) = 401.2 (74) [M + H]+, 423.2 (76) [M +
(d, J = 8.9 Hz, 2H, 8,8′-H). 13C-NMR (125 MHz, CDCl3): δ [ppm] Na]+, 823.5 (70) [2M + Na]+. HRMS (ESI): m/z calculated for
= 29.3 (C-6,6′), 40.7 (C-4,4′), 108.5 (C-10), 118.3 (C-2,2′), 118.4 C26H28N2O2Na [M + Na]+ 423.2043; observed: 423.2034.
(CN), 119.3 (C-3,3′) 119.4 (C-8,8′), 133.8 (C-9,9′), 143.1 (C-7),
5,5′-Dipropyl-1,1′-bis(4-(trifluoromethyl)phenyl)-3,3′-bipyr-
206.3 (C-5,5′). IR (ATR): ˜ν (cm−1) = 2921, 2852, 2221, 1706, role (25bc) and 1,1′-(1-(trifluoromethyl)phenyl-1H-pyrrole-
1605, 1515, 1383, 1324, 1160, 1042. UV (CH3CN): λmax [nm] 3,4-diyl)bis(pentan-2-one) (26bc). General procedure B: Dike-
(lg ε) = 219 (4.11), 296 (4.36). MS (ESI): m/z (%) = 303.1 (48) tone 20b16 (33 mg, 140 μmol, 1.0 equiv.), 4-(trifluoromethyl)-
[M + Na]+, 583.3 (100) [2M + Na]+. HRMS (ESI): m/z calculated aniline (79 mg, 490 μmol, 3.5 equiv.), p-toluenesulfonic acid
for C17H16N2O2Na [M + Na]+ 303.1104; observed: 303.1106.
(1.3 mg, 6.9 μmol, 5 mol%). Purification: Flash column chrom-
1,1′-Diphenyl-5,5′-dipropyl-3,3′-bipyrrole (25ba) and 1,1′-(1- atography (basic Al2O3, pentane–EtOAc, 15 : 1 → 12 : 1 → 8 : 1).
phenyl-1H-pyrrole-3,4-diyl)bis(pentan-2-one) (26ba). General Yield: 25bc yellow solid (23 mg, 46 μmol, 33%), 26bc yellow oil
procedure A: Diketone 20b16 (33 mg, 140 μmol, 1.0 equiv.), (32 mg, 84 μmol, 60%). Analytical data of compound 25bc: Rf:
aniline (46 mg, 490 μmol, 3.5 equiv.), p-toluenesulfonic acid 0.79 (hexane–EtOAc, 1 : 1). 1H-NMR (300 MHz, CDCl3): δ [ppm]
(1.3 mg, 6.9 μmol, 5 mol%). Purification: Flash column chrom- = 0.91 (t, J = 7.4 Hz, 6H, 8,8′-H), 1.48–1.67 (m, 4H, 7,7′-H), 2.55
atography (basic Al2O3, pentane–EtOAc, 20 : 1 → 10 : 1 → 5 : 1). (t, J = 7.6 Hz, 4H, 6,6′-H), 6.26 (s, 2H, 4,4′-H), 6.89 (s, 2H, 2,2′-
Yield: 25ba yellow oil (36 mg, 98 μmol, 70%), 26ba yellow oil H), 7.45 (d, J = 8.3 Hz, 4H, 10,10′,10a,10a′-H), 7.71 (d, J = 8.3
(10 mg, 32 μmol, 23%). Analytical data of compound 25ba: Rf: Hz, 4H, 11,11′,11a,11a′-H). 13C-NMR (125 MHz, CDCl3): δ
0.82 (hexane–EtOAc, 1 : 1). 1H-NMR (300 MHz, CDCl3): δ [ppm] [ppm] = 13.9 (C-8,8′), 22.4 (C-7,7′), 29.0 (C-6,6′), 106.7 (C-4,4′),
1
= 0.89 (t, J = 7.3 Hz, 6H, 8,8′-H), 1.38–1.74 (m, 4H, 7,7′-H), 2.52 116.6 (C-2,2′), 119.6 (C-3,3′), 124.0 (q, JC–F = 272 Hz, CF3),
(t, J = 7.9 Hz, 4H, 6,6′-H), 6.22 (s, 2H, 4,4′-H), 6.88 (s, 2H, 2,2′- 125.8 (C-10,10′,10a,10a′), 126.3 (C-11,11′,11a,11a′), 128.7 (q,
H), 7.13–7.67 (m, 10H, Ph). 13C-NMR (125 MHz, CDCl3): δ 2JC–F = 32.7 Hz, C-12,12′), 134.5 (C-5,5′), 143.5 (C-9,9′). IR (ATR):
[ppm] = 13.9 (C-8,8′), 22.4 (C-7,7′), 28.9 (C-6,6′), 105.6 (C-4,4′), ˜ν (cm−1) = 2928, 1703, 1614, 1521, 1321, 1121, 1106, 1066. UV
116.8 (C-2,2′), 119.0 (C-3,3′), 126.0 (C-10,10′,10a,10a′), 126.7 (MeOH): λmax [nm] (lg ε) = 204 (4.26), 261 (4.03). MS (ESI): m/z
(C-12,12′), 129.0 (C-11,11′,11a,11a′), 134.4 (C-5,5′), 140.6 (%) = 505.2 (100) [M + H]+. HRMS (ESI): m/z calculated for
(C-9,9′). IR (ATR): ˜ν (cm−1) = 2958, 2360, 1706, 1597, 1498, C28H27N2F6 [M + H]+ 505.2073; observed: 505.2058.
1361, 1220, 1145. UV (CH3CN): λmax [nm] (lg ε) = 242 (4.19),
Analytical data of compound 25bc: Rf: 0.69 (hexane–EtOAc,
1
199 (4.54). MS (ESI): m/z (%) = 391.2 (26) [M + Na]+. HRMS 1 : 1). H-NMR (300 MHz, CDCl3): δ [ppm] = 0.91 (t, J = 7.9 Hz,
(ESI): m/z calculated for C26H28N2Na [M + Na]+ 391.2145; 6H, 8,8′-H), 2.41–1.83 (m, 4H, 7,7′-H), 2.47 (t, J = 7.3 Hz, 4H,
observed: 391.2132.
6,6′-H), 3.53 (s, 4H, 4,4′-H), 7.03 (s, 2H, 2,2′-H), 7.43 (d, J = 8.3
Analytical data of compound 26ba: Rf: 0.74 (hexane–EtOAc, Hz, 2H, 10,10′-H), 7.65 (d, J = 8.3 Hz, 2H, 11,11′-H). 13C-NMR
1
1 : 1). H-NMR (300 MHz, CDCl3): δ [ppm] = 0.90 (t, J = 7.4 Hz, (125 MHz, CDCl3): δ [ppm] = 13.7 (C-8,8′), 17.3 (C-7,7′), 39.9
6H, 8,8′-H), 1.40–1.80 (m, 4H, 7,7′-H), 2.47 (t, J = 7.3 Hz, 4H, (C-4,4′), 43.9 (C-6,6′), 118.4 (C-2,2′), 118.8 (C-3,3′), 119.3
1
6,6′-H), 3.53 (s, 4H, 4,4′-H), 6.98 (s, 2H, 2,2′-H), 7.10–7.58 (m, (C-10,10′), 124.0 (q, JC–F = 271.7 Hz, CF3), 126.8 (C-11,11′),
2
5H, Ph). 13C-NMR (125 MHz, CDCl3): δ [ppm] = 13.7 (C-8,8′), 127.1 (q, JC–F = 32.9 Hz, C-12), 142.7 (C-9), 208.7 (C-5,5′).
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IR (ATR): ˜ν (cm−1) = 2962, 1709, 1615, 1532, 1385, 1322, 1163, 1185. UV (CH3CN): λmax (lg ε) = no absorbance maximum
1112, 1049. UV (MeOH): λmax [nm] (lg ε) = 203 (4.05), 276 between 190 and 350 nm. MS (ESI): m/z (%) = 369.3 (100) [M +
(4.17). MS (ESI): m/z (%) = 402.2 (47) [M + Na]+, 781.4 (100) H]+. HRMS (ESI): m/z calculated for C26H29N2 [M + H]+
[2M + Na]+. HRMS (ESI): m/z calculated for C21H24NO2F3Na 369.2325; observed: 369.2317.
[M + Na]+ 402.1651; observed: 402.1651.
5,5′-Dipropyl-1,1′-ditosyl-3,3′-bipyrrole (25bd) and 1,1′-(1- 4 : 1). 1H-NMR (300 MHz, CDCl3): δ [ppm] = 1.12 (d, J = 6.9 Hz,
tosyl-1H-pyrrole-3,4-diyl)bis(pentan-2-one) (26bd). General 12H, Me), 2.72–2.82 (m, 2H, 6,6′-H), 3.60 (s, 4H, 4,4′-H), 6.98
Analytical data of compound 26ca: Rf: 0.69 (hexane–EtOAc,
procedure B: Diketone 20b16 (33 mg, 140 μmol, 1.0 equiv.), (s, 2H, 2,2′-H), 7.09–7.54 (m, 5H, Ph). 13C-NMR (125 MHz,
p-tosylamide (84 mg, 490 μmol, 3.5 equiv.), p-toluenesulfonic CDCl3): δ [ppm] = 18.5 (C-7,7a,7′,7a′), 37.9 (C-4,4′), 39.8
acid (1.3 mg, 6.9 μmol, 5 mol%). Purification: Flash column (C-6,6′), 117.6 (C-3,3′), 118.5 (C-2,2′), 119.7 (C-9,9′), 125.2
chromatography (basic Al2O3, pentane–EtOAc, 10 : 1 → 5 : 1 → (C-11), 129.3 (C-10,10′), 140.2 (C-8), 212.3 (C-5,5′). IR (ATR): ˜ν
2 : 1). Yield: 25bd yellow solid (17 mg, 32 μmol, 23%), 26bd (cm−1) = 2967, 1704, 1599, 1529, 1498, 1383, 1055, 1039. UV
yellow solid (32 mg, 82 μmol, 59%). Analytical data of com- (CH3CN): λmax [nm] (lg ε) = 264 (4.14). MS (ESI): m/z (%) =
pound 25bd: Rf: 0.73 (hexane–EtOAc, 1 : 1). 1H-NMR (300 MHz, 312.2 (36) [M + H]+, 334.2 (27) [M + Na]+, 645.4 [2M + Na]+.
CDCl3): δ [ppm] = 0.94 (t, J = 7.3 Hz, 6H, 8,8′-H), 1.37–1.79 (m, HRMS (ESI): m/z calculated for C20H26NO2 [M + H]+ 312.1958;
4H, 7,7′-H), 2.40 (s, 6H, 13,13′-H), 2.63 (t, J = 7.7 Hz, 4H, 6,6′- observed: 312.1962.
H), 6.13 (s, 2H, 4,4′-H), 7.28 (d, J = 8.4 Hz, 4H, 10,10′,10a,10a′-
5,5′-Diisopropyl-1,1′-ditosyl-3,3′-bipyrrole (25cb) and 1,1′-(1-
H), 7.35 (s, 2H, 2,2′-H), 7.66 (d, J = 8.4 Hz, 4H, 11,11′,11a,11a′- tosyl-1H-pyrrole-3,4-diyl)bis(3-methylbutan-2-one) (26cb). Gen-
H). 13C-NMR (125 MHz, CDCl3): δ [ppm] = 13.8 (C-8,8′), 21.6 eral procedure A: Diketone 20c16 (30 mg, 127 μmol, 1.0 equiv.),
(C-13,13′), 21.8 (C-7,7′), 29.2 (C-6,6′), 110.5 (C-4,4′), 117.3 p-tosylamide (76 mg, 444 μmol, 3.5 equiv.), p-toluenesulfonic
(C-2,2′), 120.0 (C-3,3′), 126.7 (C-11,11′,11a,11a′), 130.0 acid (1.0 mg, 6.0 μmol, 5 mol%). Purification: Flash column
(C-10,10′,10a,10a′), 136.4 (C-9,9′), 136.7 (C-5,5′), 144.7 chromatography (basic Al2O3, pentane–EtOAc, 6 : 1). Yield:
(C-12,12′). IR (ATR): ˜ν (cm−1) = 2958, 1723, 1495, 1354, 1169, 25cb white solid (5.0 mg, 10 μmol, 8%), 26cb yellow oil (34 mg,
1137, 1099, 1048. UV (CH3CN): λmax [nm] (lg ε) = 195 (4.70), 87 μmol, 69%). Analytical data of compound 25cb: Rf: 0.38
227 (4.27). MS (ESI): m/z (%) = 547.2 (100) [M + Na]+, 1071.4 (hexane–EtOAc, 4 : 1). 1H-NMR (300 MHz, CDCl3): δ [ppm] =
(67) [2M
+
Na]+. HRMS (ESI): m/z calculated for 1.12 (d, J = 6.8 Hz, 12H, Me), 2.38 (s, 6H, 12,12′-H), 3.20–3.30
(m, 2H, 6,6′-H), 6.18 (d, J = 1.4 Hz, 2H, 4,4′-H), 7.17–7.29 (m,
C28H32N2O4S2Na [M + Na]+ 547.1696; observed: 547.1684.
Analytical data of compound 26bd: Rf: 0.65 (hexane–EtOAc, 4H, 10,10a,10′,10a′-H), 7.32 (d, J = 1.9 Hz, 2H, 2,2′-H),
1
1 : 1). H-NMR (300 MHz, CDCl3): δ [ppm] = 0.85 (t, J = 7.7 Hz, 7.48–7.70 (m, 4H, 9,9a,9′,9a′). 13C-NMR (125 MHz, CDCl3): δ
6H, 8,8′-H), 1.30–1.96 (m, 4H, 7,7′-H), 2.11–2.82 (m, 7H, [ppm] = 21.7 (C-12,12′), 23.9 (C-7,7a,7′,7a′), 26.4 (C-6,6′), 108.5
6,6′,13-H), 3.40 (s, 4H, 4,4′-H), 7.04 (s, 2H, 2,2′-H), 7.25 (d, J = (C-4,4′), 117.3 (C-2,2′), 120.1 (C-3,3′), 126.4 (C-9,9a,9′,9a′), 129.9
8.4 Hz, 2H, 10,10′-H), 7.72 (d, J = 8.4 Hz, 2H, 11,11′-H). (C-10,10a,10′,10a′), 136.5 (C-8,8′), 143.9 (C-11,11′), 144.6
13C-NMR (125 MHz, CDCl3): δ [ppm] = 13.6 (C-8,8′), 17.1 (C-5,5′). IR (ATR): ˜ν (cm−1) = 2923, 1714, 1373, 1355, 1166,
(C-7,7′), 21.6 (C-13), 39.6 (C-4,4′), 43.8 (C-6,6′), 119.8 (C-2,2′), 1117, 1034. UV (CH3CN): λmax [nm] (lg ε) = 195 (4.83), 226
121.2 (C-3,3′), 126.8 (C-11,11′), 129.9 (C-10,10′), 136.0 (C-9), (4.41). MS (ESI): m/z (%) = 525.2 (75) [M + H]+, 547.2 (56) [M +
144.9 (C-12), 207.6 (C-5,5′). IR (ATR): ˜ν (cm−1) = 2961, 2359, Na]+. HRMS (ESI): m/z calculated for C28H33N2O4S2 [M + H]+
1714, 1367, 1172, 1093, 1067. UV (CH3CN): λmax [nm] (lg ε) = 525.1876; observed: 525.1861.
242 (3.92), 223 (4.03), 194 (4.57). MS (ESI): m/z (%) = 412.2 (32)
[M + Na]+, 801.4 (100) [2M + Na]+. HRMS (ESI): m/z calculated 4 : 1). 1H-NMR (300 MHz, CDCl3): δ [ppm] = 1.02 (d, J = 6.9 Hz,
for C21H27NO4SNa [M + Na]+ 412.1553; observed: 412.1550.
12H, Me), 2.35 (s, 3H, 12-H), 2.58–2.65 (m, 2H, 6,6′-H), 3.44 (s,
Analytical data of compound 26cb: Rf: 0.30 (hexane–EtOAc,
5,5′-Diisopropyl-1,1′-diphenyl-3,3′-bipyrrole (25ca) and 1,1′- 4H, 4,4′-H), 7.00 (s, 2H, 2,2′-H), 7.15–7.37 (m, 2H, 10,10′-H),
(1-phenyl-1H-pyrrole-3,4-diyl)bis(3-methylbutan-2-one) (26ca). 7.58–7.84 (m, 2H, 9,9′-H). 13C-NMR (125 MHz, CDCl3): δ [ppm]
General procedure A: Diketone 20c16 (28 mg, 120 μmol, 1.0 = 18.3 (C-7,7a,7′,7a′), 21.6 (C-12), 37.5 (C-4,4′), 40.1 (C-6,6′),
equiv.), aniline (39 mg, 420 μmol, 3.5 equiv.), p-toluenesulfonic 119.6 (C-2,2′), 121.3 (C-3,3′), 126.6 (C-9,9′), 129.8 (C-10,10′),
acid (1.0 mg, 6.0 μmol, 5 mol%). Purification: Flash column 135.9 (C-8), 144.7 (C-11), 211.1 (C-5,5′). IR (ATR): ˜ν (cm−1) =
chromatography (basic Al2O3, pentane–EtOAc, 15 : 1 → 10 : 1 → 2970, 1710, 1466, 1364, 1169, 1039. UV (CH3CN): λmax [nm]
5 : 1). Yield: 25ca pale yellow solid (18 mg, 49 μmol, 41%), 26ca (lg ε) = 194 (4.60), 225 (4.13). MS (ESI): m/z (%) = 390.2 (29)
pale yellow oil (18 mg, 58 mmol, 48%). Analytical data of com- [M + H]+, 412.2 (43) [M + Na]+, 801.4 (100) [2M + Na]+. HRMS
1
pound 25ca: Rf: 0.76 (hexane–EtOAc, 4 : 1). H-NMR (300 MHz, (ESI): m/z calculated for C21H27NO4SNa [M + Na]+ 412.1553;
CDCl3): δ [ppm] = 1.13 (d, J = 6.8 Hz, 12H, Me), 2.90–2.98 (m, observed: 412.1555.
2H, 6,6′-H), 6.23 (d, J = 2.0 Hz, 2H, 4,4′-H), 6.84 (d, J = 2.0 Hz,
1,1′,5,5′-Tetraphenyl-3,3′-bipyrrole (25da) and 2,2′-(1-phenyl-
2H, 2,2′-H), 7.29–7.54 (m, 10H, Ph). 13C-NMR (125 MHz, 1H-pyrrole-3,4-diyl)bis(1-phenylethanone) (26da). General pro-
CDCl3): δ [ppm] = 23.3 (C-7,7a,7′,7a′), 25.5 (C-6,6′), 102.8 cedure A: Diketone 20d16 (43 mg, 140 μmol, 1.0 equiv.), aniline
(C-4,4′), 116.9 (C-2,2′), 118.8 (C-3,3′), 126.4 (C-9,9a,9′,9a′), 128.9 (46 mg, 490 μmol, 3.5 equiv.), p-toluenesulfonic acid (1.3 mg,
(C-11,11′), 140.7 (C-10,10a,10′,10a′), 140.7 (C-5,5′), 141.0 6.9 μmol, 5 mol%). Purification: Flash column chromato-
(C-8,8′). IR (ATR): ˜ν (cm−1) = 2957, 1594, 1498, 1387, 1295, graphy (basic Al2O3, pentane–EtOAc, 15 : 1 → 8 : 1 → 3 : 1).
3504 | Org. Biomol. Chem., 2013, 11, 3494–3509
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Yield: 25da white solid (20 mg, 46 μmol, 33%), 26da yellow (4.36), 276 (4.25). MS (ESI): m/z (%) = 470.2 (21) [M + Na]+,
solid (28 mg, 74 μmol, 53%). Analytical data of compound 917.3 (100) [2M + Na]+. HRMS (ESI): m/z calculated for
25da: Rf: 0.68 (hexane–EtOAc, 1 : 1). 1H-NMR (300 MHz, C27H20F3NO2Na [M + Na]+ 470.1338; observed: 470.1337.
CDCl3): δ [ppm] = 6.64 (s, 2H, 4,4′-H), 7.14 (s, 2H, 2,2′-H),
5,5′-Di(2-furyl)-1,1′-bis(4-methoxyphenyl)-4,4′-dimethyl-3,3′-
7.16–7.39 (m, 20H, Ph). 13C-NMR (125 MHz, CDCl3): δ [ppm] = bipyrrole (25ea). General procedure B: reaction time was 20 h:
109.1 (C-4,4′), 119.8 (C-3,3′), 120.0 (C-2,2′), 125.6 Diketone 20e (37 mg, 118 μmol, 1.0 equiv.), 4-methoxyaniline
(C-11,11′,11a,11a′), 126.3, 126.4 (C-9,9′, C-13,13′), 128.0, 128.3, (51 mg, 415 μmol, 3.5 equiv.). Purification: Flash column
129.0 (C-7,7′,7a,7a′, C-8,8′,8a,8a′, C-12,12′, 12a,12a′), 133.0, chromatography (SiO2, pentane–EtOAc, 5 : 1). Yield: Yellow
134.2 (C-5,5′, C-6,6′), 140.6 (C-10,10′). IR (ATR): ˜ν (cm−1) = solid (45 mg, 89 μmol, 76%). Rf: 0.38 (hexane–EtOAc = 5 : 1).
2922, 1737, 1593, 1500, 1466, 1379, 1184, 1044. UV (CH3CN): 1H-NMR (300 MHz, CDCl3): δ [ppm] = 2.29 (s, 6H, Me), 3.83 (s,
λmax [nm] (lg ε) = 197 (4.65), 267 (4.37), 291 (4.24). MS (ESI): 6H, OMe), 6.04 (dd, J = 0.7, 3.3 Hz, 2H, 8,8′-H), 6.36 (dd, J =
m/z (%) = 459.2 (35) [M + Na]+, 895.4 (71) [2M + Na]+. HRMS 1.8, 3.3 Hz, 2H, 7,7′-H), 6.79–7.01 (m, 6H, 2,2′,Ph), 7.09–7.30
(ESI): m/z calculated for C32H24N2Na [M + Na]+ 459.1832; (m, 4H, Ph), 7.35 (dd, J = 0.7, 1.8 Hz, 2H, 9,9′-H). 13C-NMR
observed: 459.1830.
(125 MHz, CDCl3): δ [ppm] = 11.4 (Me), 55.4 (OMe), 108.6
Analytical data of compound 26da: Rf: 0.60 (hexane–EtOAc, (C-7,7′), 110.5 (C-8,8′), 113.9 (Phtert), 118.3, 119.8, 121.7
1
1 : 1). H-NMR (300 MHz, CDCl3): δ [ppm] = 4.21 (s, 4H, 4,4′- (C-3,3′,4,4′,5,5′), 121.9 (C-2,2′), 126.4 (Phtert), 134.0 (Phquart),
H), 7.00 (s, 2H, 2,2′-H), 7.08–8.33 (m, 15H, Ph). 13C-NMR 141.4 (C-9,9′), 147.0 (C-6,6′), 158.1 (Phquart). IR (ATR): ˜ν (cm−1
)
(125 MHz, CDCl3): δ [ppm] = 36.1 (C-4,4′), 117.9 (C-3,3′), 118.7 = 2931, 2086, 1510, 1245, 1031. UV (CH3CN): λmax [nm] (lg ε) =
(C-2,2′), 119.9 (C-11,11′), 125.3 (C-13), 128.5, 128.6 263 (4.37). MS (ESI): m/z (%) = 505.2 (100) [M + H]+, 527.2 (25)
(C-7,7′,7a,7a′, C-8,8′,8a,8a′), 129.4 (C-12,12′), 133.0 (9,9′), 136.7 [M + Na]+, 1031.4 (33) [2M + Na]+. HRMS (ESI): m/z calculated
(C-6,6′), 140.3 (C-10), 198.1 (C-5,5′). IR (ATR): ˜ν (cm−1) = 2923, for C32H28N2O4Na [M + Na]+ 527.1941; observed: 527.1938.
1680, 1596, 1507, 1445, 1386, 1244, 1207, 1049. UV (CH3CN):
5,5′-Di(2-furyl)-4,4′-dimethyl-1,1′-diphenyl-3,3′-bipyrrole
λmax [nm] (lg ε) = 197 (4.55), 249 (4.13), 293 (3.46). MS (ESI): (25eb). General procedure B: reaction time was 20 h: Diketone
m/z (%) = 402.1 (17) [M + Na]+, 781.3 (100) [2M + Na]+. HRMS 20e (35 mg, 112 μmol, 1.0 equiv.), aniline (37 mg, 392 μmol,
(ESI): m/z calculated for C26H21NO2Na [M + Na]+ 402.1465; 3.5 equiv.). Purification: Flash column chromatography (SiO2,
observed: 402.1452.
pentane–EtOAc, 10 : 1). Yield: Yellow solid (38 mg, 86 μmol,
5,5′-Diphenyl-1,1′-bis(4-(trifluoromethyl)phenyl)-3,3′-bipyr- 76%). Rf: 0.60 (hexane–EtOAc = 5 : 1). 1H-NMR (300 MHz,
role (25db) and 2,2′-(1-(4-(trifluoromethyl)phenyl)-1H- CDCl3): δ [ppm] = 2.27 (s, 6H, Me), 6.12 (d, J = 3.2 Hz, 2H, 8,8′-
pyrrole-3,4-diyl)bis(1-phenylethanone) (26db). General pro- H), 6.38 (dd, J = 1.8, 3.2 Hz, 2H, 7,7′-H), 6.98 (s, 2H, 2,2′-H),
cedure A: Diketone 20d (43 mg, 140 μmol, 1.0 equiv.), 4-(tri- 7.11–7.64 (m, 12H, 9,9′-H,Ph). 13C-NMR (125 MHz, CDCl3): δ
fluoromethyl)aniline (79 mg, 490 μmol, 3.5 equiv.), p- [ppm] = 11.4 (Me), 109.1 (C-7,7′), 110.6 (C-8,8′), 118.7, 120.6,
toluenesulfonic acid (1.3 mg, 6.9 μmol, 5 mol%). Purification: 121.4 (C-3,3′,4,4′,5,5′), 121.7 (C-2,2′), 124.8 (Phtert), 126.3
Flash column chromatography (basic Al2O3, pentane–EtOAc, (Phtert), 128.8 (Phtert), 140.7 (Phquart), 141.6 (C-9,9′), 146.8
15 : 1 → 10 : 1 → 5 : 1). Yield: 25db brown solid (17 mg, (C-6,6′). IR (ATR): ˜ν (cm−1) = 2922, 1596, 1498, 1347, 1003. UV
30 μmol, 21%), 26db orange solid (43 mg, 96 μmol, 69%). (CH3CN): λmax [nm] (lg ε) = 263 (4.60). MS (ESI): m/z (%) =
Analytical data of compound 25db: Rf: 0.81 (hexane–EtOAc, 445.2 (80) [M + H]+, 467.2 (5) [M + Na]+. HRMS (ESI): m/z calcu-
1
1 : 1). H-NMR (300 MHz, CDCl3): δ [ppm] = 6.66 (s, 2H, 4,4′- lated for C30H24N2O2Na [M
H), 7.05–7.76 (m, 20H, 2,2′-H, Ph). 13C-NMR (125 MHz, CDCl3): 467.1730.
+
Na]+ 467.1730; observed:
δ [ppm] = 110.2 (C-4,4′), 119.6 (C-2,2′), 120.3 (C-3,3′), 123.9 (q,
1,1′-Bis(4-methoxyphenyl)-4,4′-dimethyl-5,5′-di(2-thienyl)-
1JC–F
=
272 Hz, CF3), 125.4 (C-11,11′,11a,11a′), 126.2 3,3′-bipyrrole (25fa). General procedure B: reaction time was
2
(C-12,12′,12a,12a′), 126.9 (C-9,9′), 128.3 (q, JC–F = 32.8 Hz, 20 h: Diketone 20f (38 mg, 110 μmol, 1.0 equiv.), 4-methoxy-
C-13,13′), 128.3, 128.4 (C-7,7′,7a,7a′, C-8,8′,8a,8a′), 132.4, 134.5 aniline (48 mg, 386 μmol, 3.5 equiv.). Purification: Flash
(C-5,5′, C-6,6′), 143.3 (C-10,10′). IR (ATR): ˜ν (cm−1) = 2922, column chromatography (SiO2, pentane–EtOAc, 5 : 1). Yield:
1613, 1470, 1380, 1321, 1163, 1104, 1065. UV (CH3CN): λmax Yellow solid (36 mg, 67 μmol, 61%). Rf: 0.30 (hexane–EtOAc =
[nm] (lg ε) = 272 (4.42). MS (ESI): m/z (%) = 573.2 (47) [M + H]+. 5 : 1). H-NMR (300 MHz, CDCl3): δ [ppm] = 2.28 (s, 6H, Me),
1
HRMS (ESI): m/z calculated for C34H23F6N2 [M + H]+ 573.1715; 3.81 (s, 6H, OMe), 6.60–7.39 (m, 16H, 2,2′,7,7′,8,8′,9,9′-H,Ph).
observed: 573.1706.
13C-NMR (125 MHz, CDCl3): δ [ppm] = 11.8 (Me), 55.4 (OMe),
Analytical data of compound 26db: Rf: 0.69 (hexane–EtOAc, 113.9 (Phtert), 118.3, 119.0 (C-3,3′,4,4′), 121.6 (C-2,2′), 124.1
1
1 : 1). H-NMR (300 MHz, CDCl3): δ [ppm] = 4.21 (s, 4H, 4,4′- (C-5,5′), 125.3, 126.5 (C-7,7′,8,8′), 127.1 (Phtert), 127.4 (C-9,9′),
H), 7.05 (s, 2H, 2,2′-H), 7.27–8.09 (m, 14H, Ph). 13C-NMR 133.6, 134.3 (C-6,6′,Phquart), 158.2 (Phquart). IR (ATR): ˜ν (cm−1) =
(125 MHz, CDCl3): δ [ppm] = 35.9 (C-4,4′), 118.6 (C-2,2′), 119.1 1509, 1440, 1244, 1179, 1031. UV (CH3CN): λmax [nm] (lg ε) =
1
(C-3,3′), 119.3 (C-11,11′), 124.0 (q, JC–F = 271.6 Hz, CF3), 126.7 277 (4.47). MS (ESI): m/z (%) = 536.2 (100) [M]+. HRMS (ESI):
2
(C-12,12′), 127.0 (q, JC–F = 33.1 Hz, C-13), 128.5, 128.6 m/z calculated for C32H28N2O2S2 [M]+ 536.1587; observed:
(C-7,7a,7′,7a′, C-8,8a,8′,8a′), 133.2 (C-9,9′), 136.6 (C-6,6′), 142.7 536.1589.
(C-10), 197.9 (C-5,5′). IR (ATR): ˜ν (cm−1) = 2923, 1679, 1613,
1,1′-Bis(4-methoxyphenyl)-4,4′-dimethyl-5,5′-di(N-methyl-2-
1530, 1324, 1114, 1053. UV (CH3CN): λmax [nm] (lg ε) = 244 pyrryl)-3,3′-bipyrrole (25ga). General procedure B: reaction
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time was 20 h: Diketone 20g (45 mg, 133 μmol, 1.0 equiv.), EtOAc, 7 : 1). Yield: Yellow oil (27 mg, 62 μmol, 60%). Rf: 0.77
4-methoxyaniline (57 mg, 465 μmol, 3.5 equiv.). Purification: (hexane–EtOAc, 2 : 1). 1H-NMR (300 MHz, CDCl3): δ [ppm] =
Flash column chromatography (SiO2, pentane–EtOAc, 6 : 1). 2.19 (s, 3H, Me), 3.81 (s, 3H, OMe), 3.86 (s, 3H, OMe), 6.20 (s,
Yield: Pale yellow solid (29 mg, 55 μmol, 41%). Rf: 0.33 1H, 4′-H), 6.51–6.59 (m, 1H, 4-H), 6.78–7.42 (m, 15H, C-2,2′,
1
(hexane–EtOAc = 5 : 1). H-NMR (300 MHz, CDCl3): δ [ppm] = Ph). 13C-NMR (125 MHz, CDCl3): δ [ppm] = 12.8 (Me), 55.4
2.20 (s, 3H, Me), 3.16 (s, 3H, NMe), 3.79 (s, 3H, OMe), (OMe), 55.5 (OMe), 106.3 (C-4′), 108.5 (C-4), 114.0 (Phtert),
6.01–6.30 (m, 4H, 7,7′,8,8′-H), 6.52–6.69 (m, 2H, 9,9′-H), 114.1 (Phtert), 117.0 (C-2′), 118.3, 120.0 (C-3,3′), 120.0 (C-2),
6.75–6.93 (m, 4H, Ph), 6.95–7.25 (m, 6H, 2,2′-H,Ph). 13C-NMR 126.0 (Phtert), 126.8 (Phtert), 126.9 (Phtert), 127.9 (Phtert), 128.1
(125 MHz, CDCl3): δ [ppm] = 11.9 (Me), 33.9 (NMe), 55.3 (Phtert), 129.7 (Phquart), 133.1, 133.5, 133.9, 134.0 (C-5,5′,Phquart
,
(OMe), 107.4 (C-8,8′), 111.8 (C-7,7′), 114.0 (Phtert), 118.2 (C-6,6′*), Phquart), 158.0 (Phquart), 158.3 (Phquart). IR (ATR): ˜ν (cm−1) =
119.5 (C-2,2′*), 120.0 (C-4,4′*), 122.0 (C-9,9′*), 122.4 (C-3,3′*), 3360, 1695, 1508, 1243, 1161, 1031. UV (CH3CN): λmax [nm]
124.6 (C-5,5′*), 124.9 (Phtert), 134.1 (Phquart), 157.3 (Phquart). IR (lg ε) = 229 (4.42). MS (ESI): m/z (%) = 457.2 (7) [M + Na]+. HRMS
(ATR): ˜ν (cm−1) = 1509, 1245, 1183, 1095, 1032. UV (CH3CN): (ESI): m/z calculated for C29H26N2O2Na [M + Na]+ 457.1886;
λmax [nm] (lg ε) = 194 (5.10), 252 (4.61). MS (ESI): m/z (%) = observed: 457.1874.
531.3 (100) [M
+
H]+. HRMS (ESI): m/z calculated for
5′-Methyl-1,1′,5-triphenyl-3,3′-bipyrrole (34b). General pro-
cedure A: Diketone 21a (25 mg, 103 μmol, 1.0 equiv.), aniline
C34H35N4O2 [M + H]+ 531.2755; observed: 531.2745.
1,1′-Bis(4-methoxyphenyl)-5,5′-dimethyl-4,4′-diphenyl-3,3′- (34 mg, 361 μmol, 3.5 equiv.), p-toluenesulfonic acid (1.0 mg,
bipyrrole (25ha). General procedure B: the reaction mixture 5.0 μmol, 5 mol%). Purification: Flash column chromato-
was stirred for 14 h at 80 °C: Diketone 20h16 (35 mg, 105 μmol, graphy (basic Al2O3, pentane–EtOAc, 12 : 1). Yield: Yellow solid
1
1.0 equiv.), 4-methoxyaniline (45 mg, 369 μmol, 3.5 equiv.). (17 mg, 45 μmol, 44%). Rf: 0.83 (hexane–EtOAc, 2 : 1). H-NMR
Purification: Flash column chromatography (SiO2, pentane– (300 MHz, CDCl3): δ [ppm] = 2.25 (s, 3H, Me), 6.22–6.26 (m,
EtOAc, 8 : 1 → 5 : 1). Yield: White solid (15 mg, 29 μmol, 28%). 1H, 4′-H), 6.56–6.60 (m, 1H, 4-H), 6.93–6.97 (m, 1H, 2′-H),
Rf: 0.42 (hexane–EtOAc, 4 : 1). 1H-NMR (300 MHz, CDCl3): δ 7.05–7.08 (m, 1H, 2-H), 7.10–7.70 (m, 15H, Ph). 13C-NMR
[ppm] = 2.13 (s, 6H, Me), 3.83 (s, 6H, OMe), 6.33 (s, 2H, 2,2′- (125 MHz, CDCl3): δ [ppm] = 13.0 (Me), 107.0, 109.2 (C-4,4′),
H), 6.85–7.35 (m, 18H, Ph). 13C-NMR (125 MHz, CDCl3): δ 116.9 (C-2′), 118.6 (C-3′), 119.8 (C-2), 120.2 (C-3), 125.6 (Phtert),
[ppm] = 11.9 (Me), 55.5 (OMe), 114.0 (Phtert), 116.4 (C-4,4′), 125.6 (Phtert), 126.2 (Phtert), 126.3 (Phtert), 126.6 (Phtert), 128.0
119.9 (C-2,2′), 122.1 (C-3,3′), 125.1 (Phtert), 125.7 (C-5,5′), 126.7 (Phtert), 128.2 (Phtert), 128.9 (Phtert), 129.0 (Phtert), 129.5, 133.1,
(Phtert), 127.5 (Phtert), 130.4 (Phtert), 133.4 (Phquart), 136.8 134.0 (C-5,5′,Phquart), 140.4 (Phquart), 140.6 (Phquart). IR (ATR): ˜ν
(Phquart), 158.0 (Phquart). IR (ATR): ˜ν (cm−1) = 2922, 1510, 1442, (cm−1) = 3365, 1691, 1595, 1496, 1383, 1315, 1156. UV
1247, 1166, 1035. UV (CH3CN): λmax [nm] (lg ε) = 258 (4.48). MS (CH3CN): λmax [nm] (lg ε) = 260 (4.37). MS (ESI): m/z (%) =
(ESI): m/z (%) = 525.3 (100) [M + H]+, 547.2 (38) [M + Na]+. 375.2 (100) [M + H]+, 397.2 (69) [M + Na]+, 771.4 (19) [2M +
HRMS (ESI): m/z calculated for C36H32N2O2Na [M + Na]+ Na]+. HRMS (ESI): m/z calculated for C27H22N2Na [M + Na]+
547.2356; observed: 547.2351.
397.1675; observed: 397.1663.
5,5′-Dimethyl-4,4′-diphenyl-1,1′-ditosyl-3,3′-bipyrrole (25hb).
1,1′-Bis(4-hydroxyphenyl)-5′-methyl-5-propyl-3,3′-bipyrrole
General procedure A: the reaction mixture was stirred for 14 h (34c). General procedure B: Diketone 21b (21 mg, 101 μmol,
at 80 °C: Diketone 20h16 (32 mg, 96 μmol, 1.0 equiv.), p-tosyl- 1.0 equiv.), p-hydroxyaniline (39 mg, 353 μmol, 3.5 equiv.).
amide (58 mg, 337 μmol, 3.5 equiv.), p-toluenesulfonic acid Purification: Flash column chromatography (basic SiO2,
(1.0 mg, 5.0 μmol, 5 mol%). Purification: Flash column chrom- pentane–EtOAc, 4 : 1 → 3 : 1 → 2 : 1). Yield: Greenish solid
1
atography (basic Al2O3, pentane–EtOAc, 10 : 1 → 8 : 1 → 5 : 1). (31 mg, 83 μmol, 82%). Rf: 0.67 (hexane–EtOAc, 1 : 1). H-NMR
Yield: White solid (21 mg, 34 μmol, 35%). Rf: 0.29 (hexane– (300 MHz, CDCl3): δ [ppm] = 0.88 (t, J = 7.3 Hz, 3H,
EtOAc, 4 : 1). 1H-NMR (300 MHz, CDCl3): δ [ppm] = 2.18 (s, 6H, CH2CH2CH3), 1.54 (dq, J = 7.4, 14.7 Hz, 2H, CH2CH2CH3), 2.16
Me), 2.45 (s, 6H, Ph-Me), 6.75–6.81 (m, 4H, Ph), 6.94 (s, 2H, (s, 3H, Me), 2.35–2.57 (m, 2H, CH2CH2CH3), 5.31 (sbr, 2H, OH),
2,2′-H), 7.09–7.21 (m, 6H, Ph), 7.31 (d, J = 8.1 Hz, 4H, Ph), 7.59 6.13–6.22 (m, 2H, 4,4′-H), 6.78–6.80 (m, 2H, 2,2′-H), 6.81–6.88
(d, J = 8.3 Hz, 4H, Ph). 13C-NMR (125 MHz, CDCl3): δ [ppm] = (m, 4H, Ph), 7.12–7.23 (m, 4H, Ph). 13C-NMR (125 MHz,
11.9 (Me), 21.7 (Ph-Me), 119.0 (C-4,4′), 119.5 (C-2,2′), 126.2 CDCl3):
δ [ppm] = 12.8 (CH2CH2CH3), 13.9 (Me), 22.4
(Phtert), 126.9 (Phtert), 127.0 (C-3,3′*), 127.2 (C-5,5′*), 127.7 (CH2CH2CH3), 28.8 (CH2CH2CH3), 104.9, 106.2 (C-4,4′), 115.6
(Phtert), 129.8 (Phtert), 129.9 (Phtert), 133.7 (Phquart), 136.1 (Phtert), 115.6 (Phtert), 116.8, 117.0 (C-2,2′), 118.6, 118.8 (C-3,3′),
(Phquart), 144.6 (Phquart). IR (ATR): ˜ν (cm−1) = 1596, 1496, 1360, 127.1 (Phtert), 127.5 (Phtert) 129.6 (C-5′), 133.7 (Phquart), 133.7
1174, 1158, 1090. UV (CH3CN): λmax [nm] (lg ε) = 193 (4.63), (Phquart), 134.7 (C-5), 154.3 (Phquart), 154.4 (Phquart). IR (ATR): ˜ν
223 (4.16). MS (ESI): m/z (%) = 643.2 (98) [M + Na]+. HRMS (cm−1) = 3294, 1644, 1512, 1445, 1221, 1160. UV (CH3CN): λmax
(ESI): m/z calculated for C36H32N2O4S2Na [M + Na]+ 643.1696; [nm] (lg ε) = 228 (4.37). MS (ESI): m/z (%) = 373.2 (56) [M + H]+,
observed: 643.1672.
1,1′-Bis(4-methoxyphenyl)-5′-methyl-5-phenyl-3,3′-bipyrrole culated for C24H25N2O2 [M + H]+ 373.1911; observed: 373.1903.
(34a). General procedure B: Diketone 21a (25 mg, 103 μmol, 1,1′-Bis(4-bromophenyl)-5′-methyl-5-propyl-3,3′-bipyrrole
395.2 (33) [M + Na]+, 767.4 (9) [2M + Na]+. HRMS (ESI): m/z cal-
1.0 equiv.), p-methoxyaniline (45 mg, 361 μmol, 3.5 equiv.). (34d). General procedure A: Diketone 21b (23 mg, 110 μmol,
Purification: Flash column chromatography (SiO2, pentane– 1.0 equiv.), p-bromoaniline (66 mg, 386 μmol, 3.5 equiv.),
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p-toluenesulfonic acid (1.0 mg, 5.0 μmol, 5 mol%). Purification:
4,5,5′-Trimethyl-1,1′-diphenyl-3,3′-bipyrrole (35b). General
Flash column chromatography (basic Al2O3, pentane–EtOAc, procedure A: Diketone 16a (20 mg, 0.10 mmol, 1.0 equiv.),
12 : 1). Yield: Yellow solid (31 mg, 62 μmol, 57%). Rf: 0.70 aniline (34 mg, 360 μmol, 3.5 equiv.), p-toluenesulfonic acid
(hexane–EtOAc, 6 : 1). 1H-NMR (300 MHz, CDCl3): δ [ppm] = (1.0 mg, 5.0 μmol, 5 mol%). Purification: Flash column chrom-
0.89 (t, J = 7.3 Hz, 3H, CH2CH2CH3), 1.46–1.62 (m, 2H, atography (basic Al2O3, pentane–EtOAc, 15 : 1). Yield: Pale
CH2CH2CH3), 2.21 (s, 3H, Me), 2.40–2.66 (m, 2H, yellow solid (31 mg, 95 μmol, 92%). Rf: 0.73 (hexane–EtOAc,
1
CH2CH2CH3), 6.15–6.23 (m, 2H, 4,4′-H), 6.78–6.89 (m, 2H, 2,2′- 15 : 1). H-NMR (300 MHz, CDCl3): δ [ppm] = 2.18 (s, 3H, Me),
H), 7.12–7.27 (m, 4H, Ph), 7.51–7.64 (m, 4H, Ph). 13C-NMR 2.22 (s, 3H, Me), 2.25 (s, 3H, Me), 6.20 (s, 1H, 4′-H), 6.72–6.97
(125 MHz, CDCl3): δ [ppm] = 13.0 (CH2CH2CH3), 13.9 (Me), (m, 2H, 2,2′-H), 7.28–7.58 (m, 10H, Ph). 13C-NMR (125 MHz,
22.4 (CH2CH2CH3), 28.8 (CH2CH2CH3), 106.0, 107.4 (C-4,4′), CDCl3): δ [ppm] = 10.9 (Me), 11.0 (Me), 13.0 (Me), 108.2 (C-4′),
116.5, 116.7 (C-2,2′), 119.1, 119.4 (C-3,3′), 120.1 (Phquart), 120.4 114.4 (C-4), 116.8, 117.7 (C-2,2′), 118.7, 119.0 (C-3,3′), 125.6
(Phquart), 127.0 (Phtert), 127.5 (Phtert), 129.3 (C-5′), 132.2 (Phtert), (Phtert), 125.6 (Phtert), 126.3 (Phtert), 126.5 (Phtert), 128.8 (Phtert),
132.2 (Phtert), 134.4 (C-5), 139.5 (Phquart), 139.6 (Phquart). IR 128.9 (C-5*), 129.0 (Phtert), 129.1 (C-5*), 140.6, 140.7 (Phquart).
(ATR): ˜ν (cm−1) = 3339, 2960, 1686, 1489, 1376, 1069. UV IR (ATR): ˜ν (cm−1) = 2918, 1678, 1595, 1498, 1378, 1179, 1074.
(CH3CN): λmax [nm] (lg ε) = 247 (4.28), 194 (4.77). MS (ESI): UV (CH3CN): λmax [nm] (lg ε) = 251 (4.20). MS (ESI): m/z (%) =
m/z (%) = 499.0 (19) [M + H]+. HRMS (ESI): m/z calculated for 349.2 (26) [M
+
Na]+. HRMS (ESI): m/z calculated for
C24H23Br2N2 [M + H]+ 499.0203; observed: 499.0207.
C23H22N2Na [M + Na]+ 349.1675; observed: 349.1672.
5-(2-Furyl)-4,4′-dimethyl-1,1′-diphenyl-5′-(2-thienyl)-3,3′-
5,5′-Dimethyl-4-phenyl-1,1′-di-p-tolyl-3,3′-bipyrrole
(35c).
bipyrrole (34e). General procedure B: reaction time was 20 h: General procedure A: Diketone 16b (28 mg, 109 μmol, 1.0
Diketone 21c (30 mg, 91 μmol, 1.0 equiv.), aniline (30 mg, equiv.), p-toluidine (41 mg, 382 μmol, 3.5 equiv.), p-toluenesul-
320 μmol, 3.5 equiv.). Purification: Flash column chromato- fonic acid (1.0 mg, 5.0 μmol, 5 mol%). Purification: Flash
graphy (SiO2, pentane–EtOAc, 12 : 1). Yield: Yellow solid column chromatography (basic Al2O3, pentane–EtOAc, 15 : 1).
(26 mg, 56 μmol, 62%). Rf: 0.55 (hexane–EtOAc = 10 : 1). Yield: Pale yellow solid (35 mg, 84 μmol, 77%). Rf: 0.72
1H-NMR (300 MHz, CDCl3): δ [ppm] = 2.27 (s, 3H, Me), 2.29 (hexane–EtOAc, 1 : 1). 1H-NMR (300 MHz, CDCl3): δ [ppm] =
(s, 3H, Me), 6.12 (d, J = 2.8 Hz, 1H, 8-H*), 6.31–6.47 (m, 1H, 7- 2.11–2.17 (m, 6H, Me), 2.36 (s, 3H, Me), 2.42 (s, 3H, Me),
H*), 6.79 (d, J = 3.5 Hz, 1H, 8′-H*), 6.93–7.06 (m, 3H, 2,2′,7′- 5.89–6.03 (m, 1H, 4′-H), 6.33–6.38 (m, 1H, 2′-H), 6.88–6.92 (m,
H*), 7.15–7.47 (m, 12H, 9,9′-H,Ph). 13C-NMR (125 MHz, 1H, 2-H), 7.03–7.49 (m, 13H, Ph). 13C-NMR (125 MHz, CDCl3):
CDCl3): δ [ppm] = 11.4 (Me), 11.7 (Me), 109.1 (C-8), 110.6 (C-7), δ [ppm] = 11.6 (Me), 12.9 (Me), 20.9 (Me), 21.0 (Me), 107.8
118.6, 118.8, 119.7, 120.5, 121.4 (C-2,2′,3,3′,4,4′,5*), 121.5, (C-4′), 117.6 (C-2′), 117.6 (C-3′*), 118.1 (C-2), 118.1 (C-3*), 121.5
121.6 (C-2,2′), 123.7 (C-5′*), 124.8 (Phtert), 125.6 (C-8′*), 125.7 (C-4*), 125.2 (Phtert), 125.5 (Phtert), 125.7 (Phtert), 126.6 (C-5′*),
(Phtert), 126.3, 126.4, 126.6, 127.7 (C-7′,9′,Phtert,Phtert), 128.8 127.7 (Phtert), 128.4 (C-5*), 129.4 (Phtert), 129.6 (Phtert),
(Phtert), 128.8 (Phtert), 134.2 (C-6′), 140.3 (Phquart), 140.7 130.8 (Phtert), 136.0 (Phquart), 136.4 (Phquart), 137.0 (Phquart),
(Phquart), 141.6 (C-9), 146.8 (C-6). IR (ATR): ˜ν (cm−1) = 2921, 137.9 (Phquart), 138.0 (Phquart). IR (ATR): ˜ν (cm−1) = 1696, 1514,
1596, 1497, 1346, 1189. UV (CH3CN): λmax [nm] (lg ε) = 269 1386, 1335, 1171, 1109. UV (CH3CN): λmax [nm] (lg ε) = 255
(4.52). MS (ESI): m/z (%) = 461.2 (89) [M + H]+. HRMS (ESI): m/z (4.40). MS (ESI): m/z (%) = 417.2 (100) [M + H]+. HRMS (ESI):
calculated for C30H25N2OS [M + H]+ 461.1682; observed: m/z calculated for C30H29N2 [M + H]+ 417.2325; observed:
461.1677.
417.2303.
4,5,5′-Trimethyl-1,1′-ditosyl-3,3′-bipyrrole (35a). General pro-
5,5′-Dimethyl-4-phenyl-1,1′-bis(4-(trifluoromethyl)phenyl)-
cedure A: Diketone 16a (20 mg, 103 μmol, 1.0 equiv.), p-tolue- 3,3′-bipyrrole (35d). General procedure A: Diketone 16b
nesulfonamide (62 mg, 360 μmol, 3.5 equiv.), p- (27 mg, 105 μmol, 1.0 equiv.), p-(trifluoromethyl)aniline
toluenesulfonic acid (1.0 mg, 5.0 μmol, 5 mol%). Purification: (59 mg, 369 μmol, 3.5 equiv.), p-toluenesulfonic acid (1.0 mg,
Flash column chromatography (basic Al2O3, pentane–EtOAc, 5.0 μmol, 5 mol%). Purification: Flash column chromato-
8 : 1). Yield: Yellow solid (23 mg, 48 μmol, 47%). Rf: 0.85 graphy (basic Al2O3, pentane–EtOAc, 15 : 1). Yield: Orange
(hexane–EtOAc, 1 : 1). 1H-NMR (300 MHz, CDCl3): δ [ppm] = solid (39 mg, 74 μmol, 71%). Rf: 0.66 (hexane–EtOAc, 1 : 1).
2.01 (s, 3H, Me), 2.23 (s, 3H, Me), 2.31 (s, 3H, Me), 2.40 (s, 6H, 1H-NMR (300 MHz, CDCl3): δ [ppm] = 2.19 (s, 3H, Me), 2.20 (s,
Me), 6.04–6.21 (m, 2H, 2,2′-H), 7.24–7.33 (m, 7H, 2,2′-H,Ph), 3H, Me), 5.92–6.10 (m, 1H, 4′-H), 6.33–6.40 (m, 1H, 2′-H),
7.63–7.72 (m, 4H, Ph). 13C-NMR (125 MHz, CDCl3): δ [ppm] = 6.93–6.98 (m, 1H, 2-H), 7.16–7.92 (m, 13H, Ph). 13C-NMR
10.9 (Me) 11.0 (Me), 13.6 (Me) 21.6 (Me), 21.6 (Me), 113.1 (125 MHz, CDCl3): δ [ppm] = 11.9 (Me), 13.2 (Me), 109.3 (C-4′),
(C-4′), 117.3, 117.8 (C-2,2′), 119.5, 119.8, 120.6 (C-3,3′,4), 126.8 117.3, 117.9 (C-2,2′), 118.4, 119.0, 123.0 (C-3,3′,4), 123.8 (q, 1JC–F
1
(Phtert), 126.8 (Phtert), 127.0 (C-5′*), 129.9 (Phtert), 130.0 (Phtert), = 271 Hz, CF3), 123.9 (q, JC–F = 271 Hz, CF3), 125.0 (Phtert),
131.2 (C-5*), 136.2 (Phquart), 136.3 (Phquart), 144.6 (Phquart), 125.4 (Phtert), 126.2 (Phtert), 126.3 (Phtert), 126.4 (Phtert), 126.7
2
144.8 (Phquart). IR (ATR): ˜ν (cm−1) = 2922, 1357, 1235, 1160, (C-5′*), 128.0 (Phtert), 128.2 (q, JC–F = 32.8 Hz, Phquart), 128.2
2
1093, 1013. UV (CH3CN): λmax [nm] (lg ε) = 225 (4.44), 195 (q, JC–F = 32.8 Hz, Phquart), 128.6 (C-5*), 130.7 (Phtert), 136.3
(4.89). MS (ESI): m/z (%) = 505.1 (100) [M + Na]+, 987.3 (25) (Phquart), 143.2 (Phquart), 143.3 (Phquart). IR (ATR): ˜ν (cm−1) =
[2M + Na]+. HRMS (ESI): m/z calculated for C25H26N2O4S2Na 1703, 1614, 1522, 1320, 1164, 1106, 1066. UV (CH3CN): λmax
[M + Na]+ 505.1226; observed: 505.1207.
[nm] (lg ε) = 265 (4.37). MS (ESI): m/z (%) = 525.2 (100)
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[M + H]+. HRMS (ESI): m/z calculated for C30H23N2F6 [M + H]+ 8.9581(15) Å, β = 93.106(8)°, V = 1970.9(6) Å3, Z = 4, ρcalcd
525.1760; observed: 525.1755.
=
=
=
1.279 Mg m−3, T = 100(2) K, μ(Mo Kα) = 0.636 mm−1, 2θmax
5,5′-Di(2-furyl)-4-methyl-1,1′-diphenyl-3,3′-bipyrrole
(35e). 68.4°, 16 522 reflections measured, 1777 independent (Rint
General procedure B: reaction time was 20 h: Diketone 24c 0.0289), R1 = 0.0297 (I > 2σ(I)), wR2 = 0.0790 (all data), res.
(30 mg, 100 μmol, 1.0 equiv.), aniline (33 mg, 350 μmol, 3.5 density peaks: 0.180 to −0.167 eÅ−3
equiv.). Purification: Flash column chromatography (SiO2,
.
pentane–EtOAc, 15 : 1). Yield: White solid (24 mg, 56 μmol,
56%). Rf: 0.44 (hexane–EtOAc = 10 : 1). 1H-NMR (300 MHz,
CDCl3): δ [ppm] = 2.35 (s, 3H, Me), 5.70 (d, J = 3.4 Hz, 1H, 4′-
Acknowledgements
H), 6.12 (d, J = 3.2 Hz, 1H, 8-H*), 6.21–6.31 (m, 1H, 8′-H*), We are grateful to the Deutsche Forschungsgemeinschaft
6.32–6.44 (m, 1H, 7′-H*), 6.72–6.82 (m, 1H, 7-H*), 6.94–7.03 (Emmy Noether Fellowship to D. B. W.), the Fonds der
(m, 1H, 2′-H*), 7.08 (s, 1H, 2-H*), 7.17–7.61 (m, 12H, 9,9′-H, Chemischen Industrie (Dozentenstipendium to D. B. W.) and
Ph). 13C-NMR (125 MHz, CDCl3): δ [ppm] = 11.5 (Me), 105.7 the German–Israeli Foundation (G.I.F. – Young Scientists’
(C-4′), 109.1, 109.4 (C-8,8′), 110.6, 110.8 (C-7,7′), 119.1, 119.3, Program). Furthermore, we thank Prof. Dr. Lutz F. Tietze for
119.5 (C-3,3′,5′*), 120.1, 121.1 (C-2,2′), 121.8 (C-5*), 124.7 generous support of our work.
(Phtert), 125.2 (C-4*), 126.3 (Phtert), 126.3 (Phtert), 127.5 (Phtert),
128.8 (Phtert), 129.0 (Phtert), 140.4 (Phquart), 140.7 (Phquart),
140.9, 141.7 (C-9,9′), 146.5, 147.3 (C-6,6′). IR (ATR): ˜ν (cm−1) =
Notes and references
2360, 1596, 1499, 1324, 1073. UV (CH3CN): λmax [nm] (lg ε) =
264 (4.62). MS (ESI): m/z (%) = 431.2 (100) [M + H]+. HRMS
(ESI): m/z calculated for C29H23N2O2 [M + H]+ 431.1754;
observed: 431.1749.
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X-ray crystallography
For the X-ray crystal structures of 25aa and 26da a single
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CCDC 849623 (25aa) and 849627 (26da) contain the sup-
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