Synthesis of Heterocycle-Containing 9,9-Diarylfluorenes Using Superelectrophiles

Article abstract of DOI:10.1021/acs.joc.7b00311

A superacid-promoted method for the synthesis of 9,9-diarylfluorenes is described. The chemistry involves cyclizations and arylations with biphenyl-substituted heterocyclic ketones and a mechanism is proposed involving superelectrophilic intermediates. The key reactive intermediates-dicationic and trication fluorenyl cations have been observed by low-temperature NMR and the mechanism has been further studied using DFT calculations.

Full text of DOI:10.1021/acs.joc.7b00311

Article
Synthesis of heterocycle-containing 9,9-
diarylfluorenes using superelectrophiles
Makafui Gasonoo, Akinari Sumita, Kenneth N. Boblak,
Kristen Giuffre, Tomohiko Ohwada, and Douglas A. Klumpp
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 30 May 2017
Downloaded from http://pubs.acs.org on May 31, 2017
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Synthesis of heterocycle-containing 9,9-diarylfluorenes using
superelectrophiles.
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Makafui Gasonoo,a Akinari Sumita,b Kenneth N. Boblak,a Kristen Giuffre,a Tomohiko
Ohwada,b,* and Douglas A Klumppa,*
aDepartment of Chemistry, Northern Illinois University, DeKalb, Illinois, United
States.
bGraduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
Abstract
A superacid-promoted method for the synthesis of 9,9-Diarylfluorenes is described.
The chemistry involves cyclizations and arylations with biphenyl-substituted
heterocyclic ketones and a mechanism is proposed involving superelectrophilic
intermediates. The key reactive intermediates – dicationic and trication fluorenyl
cations - have been observed by low-temperature NMR and the mechanism has
been further studied using DFT calculations.
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Introduction
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9,9-Diarylfluorenes are an important class of aromatic compounds. Examples of
these compounds have found use in electroluminescent devices and other
applications.1 Spirocyclic fluorenes have likewise been extensively studied, as their
unusual π-systems can been used in organic light emitting diodes, light harvesting
arrays, and organic-based electronics.2 Due to their value in electronic devices,
several useful synthetic methods have been developed for their synthesis. The most
common method involves a Friedel-Crafts-type reaction with a 9-aryl fluorenyl
cation, often generated from the corresponding fluoren-9-ol.3 Electrophilic
reactions at the fluorenyl cation provide the desired 9,9-diaryl fluorenes, including
some spirocyclic products.2 In the following manuscript, we describe a convenient
route to heterocycle-containing 9,9-diarylfluorenes by the superacid promoted
condensation of biaryl ketones. A mechanism is proposed involving
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superelectrophilic, di- and tricationic intermediates and the species have been
further studied by DFT calculations.
Results and Discussion
Dicationic carboxonium ions have been shown to be highly reactive electrophiles in
Friedel-Crafts type reactions.4 Both inter- and intramolecular transformations have
been demonstrated. Heterocycle-substituted carbonyl compounds are particularly
useful in Friedel-Crafts condensation reactions and they have been utilized in
several synthetic methodologies leading to condensed arenes.5 We reasoned that
the 9,9-diarylfluorenes may be prepared from heterocylic ketones having a biphenyl
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group. These substrates could be prepared by a number of approaches,6 but we
found that the reaction between heterocyclic nitriles and a Grignard reagent was
generally the most useful.7 Thus, 2-biphenylmagnesium bromide is reacted with 2-
pyridinecarbonitrile to provide the heterocyclic ketone (1a) in good yield upon
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aqueous work-up. A complimentary method was developed in which a metallated
heterocycle is reacted with 2-biphenylcarboxaldehyde, followed by oxidation with
PCC. This methodology provides ketone 1 with 2-benzothiazole (1h) and 1-methyl-
2-benzimidazole (1i) substituents.
When compounds 1a is reacted with arenes in the Brønsted superacid,
CF3SO3H (triflic acid), the condensation products (2a-g) are formed in generally
good yields (Table 1). For example, reaction with benzene in triflic acid gives the 9–
phenyl-9-(2-pyridyl)fluorene (2a) in 91% yield. Compound 2a itself has been used
in electroluminescent devices.8 Substituted arenes likewise provide the
condensation products (2b-g) in fair to good yields. Alkyl-substituted benzenes give
products 2b and 2c in good yields and regioselectivities. There is no evidence of
transalkylation products when alkyl-substituted benzenes are utilized as
nucleophiles. The condensation chemistry also produces a single regioisomer (2d)
from ethylsalicylate. For the bromo-, chloro-, and 1,2-dichlorobenzene, the
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Table 1. Products and yields for the reactions of arenes with ketone 1b.a
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condensations occur in good yields, however the chemistry gives mixtures of
regioisomers. Low yields of pure regioisomers are isolated by column
chromatograpy. 1,2-Dichlorobenzene is a moderately deactivated arene, and with
the good yield of product(s) 2g, this indicates a fairly reactive electrophile is
involved in the chemistry. The condensation chemistry has also been shown to be
efficient with a variety of N-heterocyclic substrates (Table 2). Thus, diazinyl groups
such as pyrazinyl, pyrimidyl, pyridazinyl-substrates provide good yields of products
(3a-d). Likewise, imidazole-substrates give condensation products 3e-f. Ring-fused
N-heterocycles may be incorporated into the substrates - providing compounds
such as 3g and 3h. In addition to these diarylfluorene condensation products,
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Table 2. Products and yields for the reactions of C6H6 with ketones 1b-i.a
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reaction of the diketone 4 provides the bis(fluorenyl)pyridine 5 in excellent yield
(Scheme 1). Thus, each carbonyl group undergoes condensation leading to the two
9-fluorenyl groups. As a substance with two reactive functional groups, diketone 4
has the potential to form macromolecular products in A2B2 polymerizations. To
explore this possibility, compounds 4 was also reacted with
4,4’diphenylbenzophenone in superacid. The resulting product (6) precipitated
from solution upon quenching of the reaction mixture with ice water. The high-
molecular weight product exhibited low solubility in organic solvents and a melting
point/glass transition temperature in excess of 200 °C. The material remains a solid
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Scheme 1. Condensation reactions with diketone 4.
even at 350 °C – though the sample begins to darken. The infrared spectrum of the
polymeric material shows a carbonyl group stretch at 1640 cm-1, which is in the
expected range of biaryl ketones, ca. 1660 cm-1, and 4,4’diphenylbenzophenone,
1638 cm-1.
In an effort to prepare spirocyclic structures, the benzyl-substituted
imidazoles 7 and 8 were prepared (eq 1). This synthetic approach is reminiscent of
the work done by Zhou and coworkers in their preparation of 9,9’spirobifluorene-
1,1’-diol.9 The desired precursors were synthesized in three steps from 1-
benzylimidazole. For example, 7 is prepared from 2-biphenyl carboxaldehyde by
reaction with the 2-lithiated 1-benzylimidazole, followed by PCC oxidation. When
substrate 7 is reacted with superacid, the spirocyclic fluorene derivative 9 is formed
in 88% yield. The chemistry is assumed to involve formation of the dicationic
species 11 by reaction at the carbonyl group. Cyclization of the benzyl group then
leads to product 9.
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In a similar respect, the condensation reactions of the other systems involve
superelectrophilic di- and tricationic species. Compound 1b leads to the dicationic
carboxonium ion (13), oxonium ion (14), and carbenium ion (15) intermediates
(Scheme 2). It is assumed that cyclization is rapid, so formation of 13-15 precludes
reaction with benzene. Low temperature (-40 °C) NMR studies were done using
Scheme 2. Proposed mechanism for the condensation of 1b and the intermediates
arising from 1c.
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compound 1b, and upon solvation in FSO3H-SO2ClF, the dication 15 is directly
observed. The spectrum of 15 matches the reported spectral data obtained from
ionization of 1b in magic acid solution, FSO3H-SbF5-SO2ClF.10,11 The intensely
colored (blue) ion 15 is formed almost instantaneously in the superacid – neither
the carboxonium 13 or oxonium ions were 14 detected in the NMR spectrum.
Fluorosulfonic acid has an acidity (Ho -15.1) similar to triflic acid (Ho -14.1),12 so it is
likely that ions 13 and 14 are transient species in the triflic acid-promoted
condensations. The dicationic carbenium ion 15 gives the final product 2a by
Friedel-Crafts reaction with benzene. In the cases where diazine substrates are
used, tricationic intermediates are likely involved. For example with the pyrimidine
derivative 1c, the tricationic species 16, 17, and 18, are involved in the conversion
to the condensation product 4a (Scheme 2). The tricationic carbenium ion 18 may
be directly observed by low temperature NMR with ionization of the pyrimidyl
ketone (1c) in FSO3H-SbF5-SO2ClF.10 In a similar respect, ionization of the diketone
4 under stable ion conditions leads to the tricationic structure 19 (Figure 1). The 14
signals from compounds 4 simplify to 9 13C signals observed from trication 19 (two
peaks overlap). With ionization of compound 4, the carbonyl signal at δ 197.5
disappears and the fluorenyl cation resonance arises at δ 187.2.
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Figure 1. 13C NMR of trication 19 from ionization of diketone 4 in FSO3H-SbF5-
SO2ClF at -40 °C (• denotes signals from d6-acetone external standard).
In order to compare the reactivities of the di- and tricationic electrophiles
with a monocationic homologue, 2-phenyl benzophenone (1j) was also reacted with
benzene and triflic acid. After 24 h of reaction time (25 °C), more than 90% of the
mixture was found to be unreacted ketone (1j) with some (<10%) 9-phenyl-fluoren-
9-ol (20) also present (Scheme 3). This suggests that the corresponding
monocationic carboxonium ion (vide infra) exhibits low electrophilic reactivity
compared to analogous superelectrophilic carboxonium ions (13 and 16).
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Scheme 3. Reactions of ketone 1j, alcohol 20, and the relative yields of products.
The superacid-promoted reaction was also attempted with 9-phenyl-9H-fluoren-9-
ol (20, Scheme 3). Thus, ionization of 20 in superacid with benzene provides the
Friedel-Crafts product 22 in low conversion (30%), along with recovered starting
material 20 (product ratio determined by GC-FID). With extended reaction time, the
ratio of 20 and 23 still favors the starting alcohol, indicating that an equilibrium
ratio is obtained (ca. 65:35, 20:23). With formation of the 9-fluorenyl cation 21, the
Friedel-Crafts reaction leads to the σ-complex 22 and then the product 23.
However, the superacid is capable of ipso-protonation of the phenyl group on 23,13
reversing the reaction path, and leading to the carbocation 21 and then 20 upon
aqueous workup. This equilibrium is likely a consequence of the stability - and
relatively low electrophilicity - of the monocation 21. These data are in accord with
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the observations of Huang and coworkers, where ion 21 is only found to react with
electron-rich or activated arenes and heteroarenes.3a In contrast, the di- and
tricationic fluorenyl cations (i.e., 15 and 18) provide complete conversions to the
respective phenylation products. It is suggested that the di- and tricationic fluorenyl
cations exhibit superelectrophilic character, leading to equilibria favoring the
Friedel-Crafts product.
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In order to further characterize the reactivities of the cationic intermediates,
DFT calculations were done.14 The calculations sought to compare the energetics of
cyclization and phenylation of the monocationic, dicationic, and tricationic
electrophiles. Starting from the proposed carboxonium ion intermediates, the
reaction pathways were divided into three steps: the cyclization step, the
dehydration step, and the SEAr step (Figures 2-4). The structures of the
intermediates and transition states were optimized at the CPCM-M062X/6-
311++G(d,p) level (solvent = CF3SO3H) and the energies of the optimized structures
were then calculated at the CPCM-B3LYP/6-31+G(d) (solvent = CF3SO3H) level.14
The first reaction step examined involves cyclization of the carboxonium ions at
the neighboring phenyl group. Thus, CꢀC bond formation occurs with monocation 24 to
give the cyclization intermediate 25 (Figure 2), with a calculated Gibbs activation energy
of 24.1 kcal/mol (TS1). The cyclization intermediate 25 is estimated to be less stable
(19.1 kcal/mol) than the carboxonium ion 24.
Increasing the charge on the carboxonium ion leads to significant changes in the
energetics of cyclization. In the case of the dication 13, the Gibbs activation energy is
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Figure 2. Calculated structures and energies, ꢀG kcal/mol (at 298.15K), for Friedelꢀ
Crafts reaction of monocationic species (ꢀH values in parentheses) a
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a) 26 cannot be defined as a local minimum, as it spontaneously collapses into
monocation 21 and water without an apparent transition state. The frequency and energy
of cation 26 was calculated using a structure modeled from the stable oxonium ion 14
(see Figure 3).
Figure 3. Calculated structures and energies, ꢀG kcal/mol (at 298.15K), for Friedelꢀ
Crafts reactions of dicationic species (ꢀH values in parentheses).
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Figure 4. Calculated structures and energies, ꢀG kcal/mol (at 298.15K), for Friedelꢀ
Crafts reactions of tricationic species (ꢀH values in parentheses).
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reduced (compared to the monocation) to 15.0 kcal/mol (Figure 3). This represents a 9.1
kcal/mol lowering of the activation energies for cyclization. This change may be
understood to be a consequence of the high electrophilic reactivity of 13 and the effective
separation of positive charge during the bondꢀforming step. Previous studies have shown
that charge separation is a strong driving force in the chemistry of multiplyꢀcharged
carbocations.15 In addition to the lower barrier to cyclization, the cyclization
intermediate 27 is only slightly less stable (+2.6 kcal/mol) than the carboxonium ion 13.
This is in contrast to the monocationic system, where the cyclization intermediate is
considerably less stable (+19.1 kcal/mol) than the carboxonium ion. The same trends are
observed with the tricationic cyclization (Figure 4), where the activation barrier is further
lowered to 12.2 kcal/mol and the cyclization intermediate (29) is found to be 9.2 kcal/mol
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more stable than the carboxonium ion (16). As the charge on the substituent
(heterocyclic) ring increases, the cyclization becomes increasingly favored – as seen with
lowered energy barriers and stabilized cyclization intermediates relative to the
carboxonium ions.
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The dehydration step involves formation of the appropriate oxonium ion which
undergoes loss of water to give a fluorenyl cation. In the case of the monocationic
system, the oxonium ion 26 could not be located as a minimum on the potential energy
surface (when the scanning procedure is conducted about the CꢀO bond length in 26, the
total energy is monotonously decreases without a transition state as the bond length
becomes longer. See footnote in Figure 2, and in detail, see the Supporting Information).
However, the transformation from the cyclization intermediate 25 to the fluorenyl cation
21 is calculated to be exergonic by more than 19 kcal/mol. Both the dicationic and
tricationic oxonium ions (14 and 17) were characterized as intermediates, protected only
by a small energy barrier leading to the respective fluorenyl cations (15 and 18).
Oxonium ion 14 provides the fluorenyl dication (15) through transition state TS4, which
is calculated to be just 4.3 kcal/mol less stable than 14 (Figure 3). The barrier to cleave
oxonium ion 17 to the fluorenyl trication 18 is only 2.5 kcal/mol (TS7, Figure 4). These
calculations are consistent with the experiment observations that no oxonium ions could
be observed by low temperature NMR. Evidently, the oxonium ions cleave almost
instantly to the fluorenyl cations.
As a measure of the electrophilic reactivities of the fluorenyl cations, the SEAr
step was also examined computationally, specifically comparing the energies of the
fluorenyl cations (with added benzene) and the resulting σꢀcomplexes. It was
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hypothesized that increasing electrophilic reactivities should be evident by decreasing
barriers to the transition states and increasing relative stabilities of the σꢀcomplexes. The
results from the calculations confirm this hypothesis. Thus, the monocationic system
involves formation of transition state TS2 from benzene the fluorenyl monocation (21),
wherein the Gibbs activation energy is calculated to be 16.5 kcal/mol for this
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transformation (Figure 2). Continuation of the reaction step leads to the σꢀcomplex 22
which is 8.9 kcal/mol less stable than the fluorenyl monocation 21 with benzene (Figure
2). In contrast, the Gibbs activation energy decreases to 8.9 kcal/mol for the dicationic
transition state (TS5, Figure 3) and further decreases to 6.7 kcal/mol for the tricationic
transition state (TS8, Figure 4). Both the dicationic and trication σꢀcomplexes (29 and
31) are found to be more stable than the respective fluorenyl cations and benzene. In the
case of the dication, σꢀcomplex 29 is found to be 1.4 kcal/mol more stable than the
fluorenyl dication 15 with benzene (Figure 3). The tricationic system is even more
exergonic ꢀ with the σꢀcomplex 31 found to be 14.0 kcal/mol more stable than the
fluorenyl trication 18 with benzene (Figure 4). These data are consistent with the
observations from the synthetic reactions, that is, the Nꢀheterocyclic systems provide
highly reactive electrophiles, or superelectrophiles, which give the 9,9ꢀdiarylfluorenes in
good to excellent yields. When the less reactive phenylꢀsubstituted fluorenyl monocation
is generated, only low yields of the 9,9ꢀdiphenylfluorene is obtained (Scheme 3).
Conclusions
With N-heterocyclic substituents, biphenyl ketones undergo efficient condensation
reactions with arene nucleophiles to give 9,9-diarylfluorenes in good yields. The
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chemistry may used to prepare spirocyclic products, as well as macromolecules by
condensation polymerization. A mechanism is proposed involving initial formation
of 9-fluorenyl cation electrophiles. With protonated N-heterocyclic substituents,
these 9-fluorenyl cations are part of di- and tricationic superelectrophilic systems.
Theoretical calculations show that the more highly charged 9-fluorenyl cations
exhibit greater reactivity towards cyclization and SEAr reactions.
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Experimental Section
General. All reactions were performed using oven–dried glassware under an Argon
atmosphere. Trifluoromethanesulfonic acid (triflic acid) was freshly distilled prior to use.
All purchased compounds and solvents were used as received. 1H and 13C NMR were
done using either a 300 or 500 MHz NMR spectrometer. Low–temperature NMR spectra
were done using acetoneꢀd6 as the external standard. Low–resolution mass spectra were
obtained from a gas chromatography instrument equipped with a mass–selective detector,
whereas high–resolution mass spectra were obtained from a commercial analytical
laboratory (electron impact ionization; sector instrument analyzer type). Compounds 1a,
1b, 1c, and 1j were prepared by published methods.10,16
Safety Considerations. In the procedures described below, flammable solvents and airꢀ
sensitive reagents are used, such as ethers and organolithium and Grignard reagents.
Triflic acid, fluorosulfonic acid, and antimony pentafluoride are considered superacids,
and as such, these materials are extremely corrosive. These substances pose significant
risk and should only be used by properly trained individuals having all necessary
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personal protective equipment. The toxicities of the substances reported are not fully
known, so it is imperative that all procedures are done in an efficient fume hood. No
direct skin contact should be made with any chemical reagents or products. The use of
thick rubber gloves is strongly advised.
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Preparation of heterocyclic ketones, 1. General Method A.
Magnesium turnings (72 mg, 3.0 mmol) are combined with 10 mL of THF and a crystal
of iodine. The solution is then heated to 60–65 °C and 2ꢀbromobiphenyl (0.52 mL, 3.0
mmol) is added. After stirring for 3ꢀ4 hr, the mixture is cooled to 0 °C after which a
solution of the nitrile (2.0 mmol in 5 mL of THF) is added slowly. The solution is then
allowed to warm to room temperature and stirred for an additional 14 hr. Following this
period, 15 mL of 6.0 M HCl is added directly to the product mixture and stirring is
continued for and additional 2 hr. The resulting solution is made basic (ca. pH 8) by
addition of 10 M NaOH, and the mixture partitioned between chloroform and water. The
aqueous layer is further extracted (2x), after which the organic extracts are combined,
washed with brine, dried over anhydrous sodium sulfate and filtered. The solvent is then
removed and the resulting product purified by column chromatography (1:1,
hexanes:ethyl acetate).
Preparation of heterocyclic ketones, 1. General Method B.
The heterocyclic derivative (2.24 mmol) is dissolved in 10 mL of THF and the solution is
cooled to ꢀ78 °·C. nꢀBuLi solution (0.89 mL, 2.24 mmol in hexanes) is added and the
mixture 1 h, after which 2ꢀbiphenyl carboxaldehyde (0.30 mL, 1.0 mmol dissolved in 5
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mL THF) is added. The solution is allowed to warm to 25 °C and stirred for 4 h.
Saturated ammonium chloride solution (5 mL) is added to the mixture and the products
are partitioned between ether and water. The aqueous layer is further extracted (2x) after
which the organic extracts are combined, washed with brine, dried over anhydrous
sodium sulfate and filtered. The solvent is then removed under reduced pressure. The
crude alcohol product is the dissolved in CH2Cl2 and then pyridinium chlorochromate
(1.20 g, 5.57 mmol) is added. The solution is stirred at 25 °C for at least 6 hr, after
which it is diluted with 15 mL of CH2Cl2 and filtered through a pad of Celite. Following
removal of the solvent, the product is purified by column chromatography (1:1,
hexanes:ethyl acetate).
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[1,1'-Biphenyl]-2-yl(pyrimidin-5-yl)methanone, 1d. Using General Method A,
compound 1d is isolated (0.39 g, 1.5 mmol, 75%) as solid, mp 79ꢀ81 °C. Rf = 0.35
(hexane: ethyl acetate, 3:1). 1 H NMR (300 MHz, CDCl3) δ, 7.12ꢀ7.21 (m, 5 H), 7.51 (t, J
= 9.8 Hz, 2 H), 7.63 (d, J = 5.0 Hz, 2 H), 8.71 (s, 2 H), 9.03 (s, 1 H). 13 C NMR (75 MHz,
CDCl3) δ, 127.9, 128.0, 128.7, 129.1, 129.3, 130.1, 130.6, 131.9, 137.0, 139.5, 141.4,
157.1, 160.3, 195.7 Low resolution MS (EI): 260 (M+), 231, 204, 181, 152, 127, 107, 76,
52. Highꢀresolution MS (EI), calcd for C17H12N2O, 260.0950, found 260.0948.
[1,1'-Biphenyl]-2-yl(pyridazin-3-yl)methanone, 1e. Using General Method A,
compound 1e is isolated (0.41 g, 1.58 mmol, 79%) as oil. Rf = 0.39 (hexane: ethyl
acetate, 1:1). 1 H NMR (300 MHz, CDCl3) δ, 7.08ꢀ7.16 (m, 3 H), 7.19ꢀ7.22 (m, 2 H),
7.36ꢀ7.40 (m, 1 H), 7.46ꢀ7.55 (m, 2 H), 7.60ꢀ7.66 (m, 1 H), 7.75ꢀ7.78 (m, 1 H), 7.81ꢀ7.85
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(m, 1 H), 9.01 (d, J = 6.39 Hz, 1 H). 13 C NMR (75 MHz, CDCl3) δ, 126.0, 126.4, 127.3,
127.4, 128.2, 129.2, 129.6, 129.9, 131.6, 137.6, 140.3, 142.2, 152.0, 157.9, 197.3. Low
resolution MS (EI): 260 (M+), 231, 204, 181, 152, 127, 101, 76, 51. Highꢀresolution MS
(EI), calcd for C17H12N2O, 260.0950, found 260.0946.
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(1-Butyl-1H-imidazol-4-yl)(4-methyl-[1,1'-biphenyl]-2-yl)methanone, 1f. 1ꢀButylꢀ1Hꢀ
imidazole (0.26 mL, 2.0 mmol) is dissolved in 5 mL THF and the solution is cooled to ꢀ
78 °C. To this is solution is slowly added nꢀBuLi solution (2.2 mmol). The mixture is
stirred for 2 hr and then 4'ꢀmethylꢀ2ꢀcyanobiphenyl 4'ꢀmethylꢀ2ꢀcyanobiphenyl (0.386 g,
2.0 mmol, dissolved in 10 mL THF) is added. The solution is stirred for 30 min at ꢀ78 °C
and then allowed to warm to 25 °C. After stirring an additional 4 hr, the reaction is
quenched with 15 mL of 6.0 M HCl. This solution is stirred for 2 hr and neutralized (to
pH ~8) by addition of 10 M NaOH. The mixture is partitioned between ether and water,
with the aqueous layer further extracted twice with ether. The organic fractions are
combined, washed with brine, dried over anhydrous sodium sulfate, and filtered. The
solvent is then removed and the resulting product purified by column chromatography
(hexane: ethyl acetate, 5:1). Compound 1f is isolated as a yellow resin (0.5897 g, 1.8
mmol, 93% yield). Rf = 0.15 (hexane: ethyl acetate, 5:1). 1 H NMR (500 MHz, CDCl3) δ
0.96 (t, J = 7.40 Hz, 3 H), 1.31 (septet, J = 7.70 Hz, 2 H), 1.70ꢀ1.76 (m, 2 H), 2.32 (s, 3
H), 4.36 (t, J = 7.30 Hz, 2 H), 7.00 (d, J = 0.80 Hz, 1 H), 7.08 (d, J = 0.80 Hz, 2 H), 7.10
(s, 1 H), 7.22 (d, J = 4.60 Hz, 2 H), 7.43ꢀ7.64 (m, 4 H). 13C NMR (125 MHz, CDCl3) δ
13.7, 19.7, 21.1, 33.0, 48.3, 125.4, 126.6, 128.3, 128.8, 128.9, 129.6, 130.2, 130.5, 136.6,
138.0, 139.0, 141.4, 143.2, 188.0. Low resolution MS (EI): 318 (M+), 289, 275, 261,
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165, 152. Highꢀresolution MS (ESIꢀTOF) m/z: [M+H]+ calcd for C21H23N2O, 319.1810,
found 319.1811.
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(1-Methyl-1H-imidazol-2-yl)(4-methyl-[1,1'-biphenyl]-2-yl)methanone, 1g. 1ꢀ
Methylimidazole (0.30 mL, 3.78 mmol) is dissolved in 5 mL THF and the solution is
cooled to ꢀ78 °C. To this is solution is slowly added nꢀBuLi solution (3.8 mmol). The
mixture is stirred for 2 hr and then 4'ꢀmethylꢀ2ꢀcyanobiphenyl 4'ꢀmethylꢀ2ꢀcyanobiphenyl
(487 mg, 2.52 mmol, dissolved in 10 mL THF) is added. The solution is stirred for 30
min at ꢀ78 °C and then allowed to warm to 25 °C. After stirring an additional 4 hr, the
reaction is quenched with 15 mL of 6.0 M HCl. This solution is stirred for 2 hr and
neutralized (to pH ~8) by addition of 10 M NaOH. The mixture is partitioned between
ether and water, with the aqueous layer further extracted twice with ether. The organic
fractions are combined, washed with brine, dried over anhydrous sodium sulfate, and
filtered. The solvent is then removed and the resulting product purified by column
chromatography (hexane: ethyl acetate, 3:1). Compound 1g is isolated (0.60 g, 2.2
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mmol, 86%) as a yellow solid MP 77–80 °C, Rf = 0.20 (hexane: ethyl acetate, 3:1). H
NMR (500 MHz, CDCl3) δ 2.33 (s, 3 H), 3.92 (s, 3 H), 6.91 (s, 1 H), 7.05 (s, 1 H), 7.11
(d, J = 7.90 Hz, 2 H), 7.24 (d, J = 8.05 Hz, 2 H), 7.43ꢀ7.47 (m, 2 H), 7.53ꢀ7.56 (m, 1H),
7.68ꢀ7.69 (m, 1 H). 13 C NMR (125 MHz, CDCl3) δ 21.2, 35.8, 126.5, 126.6, 128.7,
128.9, 129.2, 129.7, 130.3, 130.6, 136.7, 138.0, 138.7, 141.6, 143.9, 188.6 Low
resolution MS (EI): 276 (M+), 261, 247, 185, 165, 152. Highꢀresolution MS (EI), calcd
for C18H16N2O, 276.1263, found 276.1264.
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Benzo[d]thiazol-2-yl(4-methyl-[1,1'-biphenyl]-2-yl)methanone, 1h. Using General
Method B, compound 1h is isolated (0.47 g, 1.5 mmol, 67%) as oil, Rf = 0.28 (hexane:
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ethyl acetate, 7:1). H NMR (300 MHz, CDCl3) δ 7.12 (d, J = 1.2 Hz, 1 H), 7.22ꢀ7.27
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(m, 1H), 7.39 (d, J = 7.86 Hz, 2 H), 7.45ꢀ7.59 (m, 4 H), 7.67 (d, J = 8.34 Hz, 1 H), 7.90
(d, J = 7.05 Hz, 2 H), 8.08 (d, J = 7.29 Hz, 1 H).13 C NMR (75 MHz, CDCl3) δ 122.2,
125.6, 126.8, 127.2, 127.3, 127.6, 128.3, 129.0, 130.5, 131.7, 136.8, 137.1, 140.7, 142.6,
153.5, 166.8, 190.9. Low resolution MS (EI): 315 (M+), 286, 238, 181, 152, 127. Highꢀ
resolution MS (EI), calcd for C20H13NOS, 315.0718, found 315.0719.
(1-Benzyl-1H-imidazol-2-yl)(4-methyl-[1,1'-biphenyl]-2-yl)methanone, 1i. Using
General Method B, compound 1i is isolated (0.51 g, 1.5 mmol, 65%) as an oil, Rf = 0.21
(hexane: ethyl acetate, 3:1). 1 H NMR (500 MHz, CDCl3) δ 5.60 (s, 2 H), 6.97 (s, 1 H),
7.10 (s, 1 H), 7.19 (d, J = 7.6 Hz, 2 H), 7.26 (t, J = 2.45 Hz, 3 H), 7.35ꢀ7.39 (m, 5 H),
7.48ꢀ7.52 (m, 2 H), 7.57ꢀ7.60 (m, 1H), 7.71 (d, J = 7.30 Hz, 1 H).13 C NMR (125 MHz,
CDCl3) δ 51.5, 125.6, 126.9, 127.0, 127.9, 128.15, 128.23, 128.9, 129.0, 129.1, 130.3,
130.7, 136.5, 139.0, 141.0, 141.6, 143.3, 188.7. Low resolution MS (EI): 352 (M+), 362,
212, 196, 195, 167, 165, 152. Highꢀresolution MS (EI), calcd for C24H20N2O, 352.1576,
found 352.1575.
Preparation of 9,9-diarylfluorenes, 2 and 4. General Method C. The ketone substrate
1 (0.1 g, ca. 0.4 mmol) is dissolved in 1 mL of CH2Cl2 with the arene nucleophile (0.5
mL or 6 mmol). To this solution is slowly added triflic acid (0.5 mL, 5.5 mmol) and the
mixture is stirred for 4 hr at 25 °C. The solution is then poured over about 10 g of ice,
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neutralized with 10 M NaOH (pH > 7), and partitioned between chloroform and water.
The aqueous phase is extracted twice with chloroform and the combined organic extracts
are washed with water and then brine. Following drying with sodium sulfate, the solvent
is removed and the crude product subjected to column chromatography.
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2-(9-Phenyl-9H-fluoren-9-yl)pyridine, 2a. Compound 2a has been previously reported
in the patent literature.17 Using General Method C, [1,1'ꢀbiphenyl]ꢀ2ꢀyl(pyridinꢀ2ꢀ
yl)methanone, 1a (0.102 g, 0.39 mmol) and benzene (0.5 mL, 5.6 mmol), provides
compound 2a (0.11 g, 0.35 mmol, 91%) as a white solid, MP 166ꢀ170 °C, Rf = 0.41
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(hexane: ethyl acetate, 5:1). H NMR (500 MHz, CDCl3) δ 7.11ꢀ7.17 (m, 4 H), 7.24ꢀ
7.29 (m, 3 H), 7.34ꢀ7.37 (m, 2 H), 7.44 (td, J = 7.50 Hz, J = 1.0 Hz, 2 H), 7.47ꢀ7.51(m, 1
H), 7.68 (d, J =7.60 Hz, 2 H), 7.85 (d, J = 7.60 Hz, 2 H), 8.72ꢀ8.74 (m, 1 H). 13 C NMR
(125 MHz, CDCl3) δ 67.2, 120.2, 121.5, 121.8, 126.7, 127.8, 127.9, 128.4, 136.3, 140.5,
149.8, 149.9, 163.0. Low resolution MS (EI): 319 (M+), 241, 158. Highꢀresolution MS
(ESIꢀTOF) m/z: [M+H]+ calcd for C24H18N, 320.1439, found 320.1442.
2-(9-(p-Tolyl)-9H-fluoren-9-yl)pyridine, 2b. Using General Method C, [1,1'ꢀbiphenyl]ꢀ
2ꢀyl(pyridinꢀ2ꢀyl)methanone, 1b (0.05 g, 0.193 mmol) and toluene (0.5 mL, 4.70 mmol)
provides compound 2b (0.058 g, 0.17 mmol, 90%) as white solid, MP 169ꢀ169 °C. Rf =
1
0.18 (hexane: ethyl acetate, 19:1). H NMR (500 MHz, CDCl3) δ 2.36 (s, 3 H), 7.06 (d, J
= 8.25 Hz, 2 H), 7.11ꢀ7.17 (m, 4 H), 7.36ꢀ7.40 (m, 2 H), 7.44ꢀ7.51 (m, 3 H), 7.72 (d, J =
7.60 Hz, 2 H), 7.87 (d, J = 7.50 Hz, 2 H), 8.75ꢀ8.76 (m, 1 H).13 C NMR (125 MHz,
CDCl3) δ 21.1, 67.0, 120.2, 121.4, 121.5, 121.7, 126.8, 127.0, 127.76, 127.77, 127.82,
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129.1, 136.16, 136.23, 140.5, 143.1, 149.8, 150.1, 164.1. Low resolution MS (EI): 333
(M+), 317, 255, 239, 159. Highꢀresolution MS (ESIꢀTOF) m/z: [M+H]+ calcd for
C25H20N, 334.1596, found 334.1597.
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2-(9-(4-Isopropylphenyl)-9H-fluoren-9-yl)pyridine, 2c. Using General Method C,
[1,1'ꢀbiphenyl]ꢀ2ꢀyl(pyridinꢀ2ꢀyl)methanone 1a (0.05g, 0.19 mmol) and cumene (0.5 mL,
3.59 mmol) provides compound 2c (0.061 g, 0.17 mmol, 89%) as oil. Rf = 0.59 (hexane:
ethyl acetate, 5:1). 1 H NMR (500 MHz, CDCl3) δ 1.22 (d, J = 6.95 Hz, 6 H), 2.86 (q, J =
6.90 Hz, 1 H), 7.00 (d, J = 8.35 Hz, 2 H), 7.08ꢀ7.15 (m, 4 H), 7.30ꢀ7.34 (m, 2 H), 7.39ꢀ
7.43 (m, 2 H), 7.47ꢀ7.50 (m, 1 H), 7.64 (d, J = 7.60 Hz, 2 H), 7.81 (d, J = 7.55 Hz, 2 H),
8.70 (q, J = 3.75 Hz, 1 H).13 C NMR (125 MHz, CDCl3) δ 23.9, 33.6, 67.0, 120.1, 121.5,
121.6, 126.4, 126.8, 127.62, 127.65, 127.68, 136.2, 140.4, 143.1, 146.8, 149.7, 150.1,
164.0. Low resolution MS (EI): 361 (M+), 344, 318, 283, 267, 252, 241, 165. Highꢀ
resolution MS (ESIꢀTOF) m/z: [M+H]+ calcd for C27H24N, 362.1909, found 362.1907.
Ethyl 2-hydroxy-5-(9-(pyridin-2-yl)-9H-fluoren-9-yl)benzoate, 2d. Using General
Method C, [1,1'ꢀbiphenyl]ꢀ2ꢀyl(pyridinꢀ2ꢀyl)methanone 1 (0.05 g, 0.19 mmol) and ethyl
salicylate (0.5 mL, 3.40 mmol) provides compound 2d (0.064 g, 0.16 mmol, 83%) as oil.
Rf = 0.31 (hexane: ethyl acetate, 3:1). 1 H NMR (500 MHz, CDCl3) δ 1.29 (t, J = 7.10 Hz,
3 H), 4.31 (quartet, J = 7.10 Hz, 2 H), 6.88 (d, J = 8.80 Hz, 1 H), 7.04 (d, J = 7.95 Hz, 1
H), 7.15ꢀ7.21 (m, 2 H), 7.34 (quartet, J = 7.60 Hz, 2 H), 7.41ꢀ7.44 (m, 2 H), 7.47ꢀ7.51
(m, 1 H), 7.60 (d, J = 8.15 Hz, 3 H), 7.82 (d, J = 7.65 Hz, 2 H), 10.8 (s, 1 H).13 C NMR
(125 MHz, CDCl3) δ 14.1, 61.2, 66.3, 112.2, 117.7, 120.0, 120.3, 121.4, 121.8, 126.5,
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127.0, 127.86, 127.90, 128.5, 135.6, 136.4, 136.5, 140.4, 149.8, 160.5, 163.5, 170.1. Low
resolution MS (EI): 407 (M+), 361, 332, 304, 283, 255, 241, 226, 207, 180, 166, 152.
Highꢀresolution MS (EI), calcd for C27H21O3N, 407.1521, found 407.1526.
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2-(9-(4-Bromophenyl)-9H-fluoren-9-yl)pyridine, 2e-para. Using General Method C,
[1,1'ꢀbiphenyl]ꢀ2ꢀyl(pyridinꢀ2ꢀyl)methanone, 1b (0.100 g, 0.386 mmol), and
chlorobenzene (0.5 mL, 5.6 mmol) provide compound 2e as a mixture of regioisomers.
Product 2e-para is isolated (0.055 g, 0.139 mmol, 36%) by column chromatography
(hexane: ethyl acetate, 1:1) as an offꢀwhite powder, MP 143ꢀ145 °C. [Along with this,
isomeric products 2e are obtained (0.087 g, 0.220 mmol, 57%)] Rf = 0.74, 2e-para
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(hexane: ethyl acetate, 1:1). H NMR (500 MHz, CDCl3) δ 6.95 (d, J = 8.60 Hz, 2 H),
7.04 (d, J = 7.95 Hz, 1 H), 7.15ꢀ7.17 (m, 1 H), 7.31ꢀ7.36 (m, 4 H), 7.41ꢀ7.44 (m, 2 H),
7.47ꢀ7.50 (m, 1 H), 7.59 (d, J = 7.65 Hz, 2 H), 7.81 (d, J = 7.55 Hz, 2 H), 8.69 (t, J = 3.80
Hz, 1 H).13 C NMR (125 MHz, CDCl3) δ 66.7, 120.3, 120.7, 121.3, 121.9, 126.6, 127.9,
128.0, 129.6, 131.4, 136.4, 140.4, 145.1, 149.4, 149.9, 163.2. Low resolution MS (EI):
397 (M+), 319, 239, 213, 159, 145. Highꢀresolution MS (EI), calcd for C24H16NBr,
397.0466, found 397.0471.
2-(9-(4-Chlorophenyl)-9H-fluoren-9-yl)pyridine, 2f-para. Using General Method C,
[1,1'ꢀbiphenyl]ꢀ2ꢀyl(pyridinꢀ2ꢀyl)methanone, 1b (0.100 g, 0.386 mmol), and
chlorobenzene (0.5 mL, 4.53 mmol) provide compound 2f as a mixture of regioisomers.
Product 2f-para is isolated (0.053 g, 0.151 mmol, 39% yield) by column chromatography
(hexane: ethyl acetate, 3:1) as an offꢀwhite powder, MP 148ꢀ150 °C. [Along with this,
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isomeric products 2f are obtained (0.084 g, 0.212 mmol, 55 % yield) as an oil] Rf = 0.74,
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2f-para (hexane: ethyl acetate, 3:1). H NMR (500 MHz, CDCl3) δ 7.02ꢀ7.07 (m, 3 H),
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7.15ꢀ7.18 (m, 1 H), 7.21ꢀ7.23 (m, 2 H), 7.33ꢀ7.36 (m, 2 H), 7.42ꢀ7.50 (m, 3 H), 7.62 (d, J
= 7.60 Hz, 2 H), 7.83 (d, J = 7.55 Hz, 2 H), 8.72 (quartet, J = 3.75 Hz, 1 H). 13C NMR
(125 MHz, CDCl3) δ 66.6, 120.3, 121.3, 121.9, 126.6, 127.9, 128.0, 128.5, 129.3, 132.5,
136.4, 140.4, 144.6, 149.5, 149.9, 163.3 Low resolution MS (EI): 353 (M+), 317, 275,
239, 213, 159. Highꢀresolution MS (EI), calcd for C24H16NCl, 353.0971, found
353.0970.
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2-(9-(3,4-Dichlorophenyl)-9H-fluoren-9-yl)pyridine and 2-(9-(2,3-dichlorophenyl)-
9H-fluoren-9-yl)pyridine mixture, 2g. Using General Method C, [1,1'ꢀbiphenyl]ꢀ2ꢀ
yl(pyridinꢀ2ꢀyl)methanone, 1b (0.050 g, 0.19 mmol) and 1,2ꢀdichlorobenzene (0.5 mL,
4.42 mmol) provides compound 2g is isolated as (inseparable) isomeric mixture (0.061 g,
0.158 mmol, 83%) as an oil. Rf = 0.44 (hexane: ethyl acetate, 3:1). 1 H NMR (500 MHz,
CDCl3) δ 6.91ꢀ6.93 (m, 1 H), 6.96ꢀ7.04 (m, 3 H), 7.10ꢀ7.12 (m, 2 H), 7.15 (quartet, J =
1.85 Hz, 1 H), 7.24ꢀ7.33 (m, 6 H), 7.37ꢀ7.50 (m, 7 H), 7.55 (t, J = 7.55 Hz, 3 H), 7.60 (d,
J = 1.30 Hz, 1 H), 7.72 (d, J = 7.50 Hz, 1 H), 7.80 (t, J = 6.40 Hz, 2 H), 8.53 (d, J = 3.80
Hz, 1 H), 8.59 (d, J = 3.80 Hz, 1 H).13 C NMR (125 MHz, CDCl3) δ 66.2, 67.4, 119.8,
120.2, 120.3, 120.4, 121.2, 121.4, 121.7, 121.9, 126.3, 126.52, 126.54, 126.6, 127.61,
127.63, 127.7, 127.79, 127.80, 127.88, 127.93, 128.2, 129.6, 130.1, 130.7, 132.3, 136.5,
138.8, 140.4, 140.5, 146.2, 146.4, 148.4, 148.6, 149.5, 149.6, 149.7, 163.0, 164.0. Low
resolution MS (EI): 387 (M+), 352, 309, 273, 239, 207, 176, 158.
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2-(9-Phenyl-9H-fluoren-9-yl)pyrazine, 3a. Using General Method C, , [1,1'ꢀbiphenyl]ꢀ
2ꢀyl(pyrazinꢀ2ꢀyl)methanone, 1b (0.0984 g, 0.192 mmol), and benzene (0.5 mL, 5.6
mmol), compound 3a is isolated (0.056 g, 0.175 mmol, 91%) as a yellow solid, MP 168–
169 o C. Rf = 0.33 (hexane: ethyl acetate, 5:1). 1 H NMR (500 MHz, CDCl3) δ 7.07ꢀ7.29
(m, 5 H), 7.35 (dt, J = 1.0 Hz, J = 7.50 Hz, 2 H), 7.45 (dt, J = 0.90 Hz, J = 7.50 Hz, 2 H),
7.62 (d, J = 7.70 Hz, 2 H), 7.85 (d, J = 7.60 Hz, 2 H), 8.45 (d, J = 18.5 Hz, 2 H), 8.64 (s,
2 H).13 C NMR (125 MHz, CDCl3) δ 65.5, 120.4, 16.6, 127.0, 127.7, 128.0, 128.2, 128.5,
140.5, 143.0, 144.3, 145.0, 148.7, 159.8. Low resolution MS (EI): 320 (M+), 241, 160.
Highꢀresolution MS (ESIꢀTOF) m/z: [M+H]+ calcd for C23H17N2, 321.1392, found
321.1392.
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2-(9-Phenyl-9H-fluoren-9-yl)pyrimidine, 3b. Using General Method C, [1,1'ꢀbiphenyl]ꢀ
2ꢀyl(pyrimidinꢀ2ꢀyl)methanone, 1c (0.0453 mg, 0.174 mmol), and benzene (0.5 mL, 5.6
mmol) provides compound 3b in (0.046 g, 0.143 mmol, 82%) as an offꢀwhite solid, MP
218–220 °C, Rf = 0.17 (hexane: ethyl acetate, 7:1).1 H NMR (500 MHz, CDCl3) δ 7.04ꢀ
7.08 (m, 2 H), 7.14 (t, J=4.90 Hz, 1 H), 7.24ꢀ7.49 (m, 7 H), 7.79 (dd, J = 7.40 Hz, J =
19.1 Hz, 4 H), 8.72 (d, J = 4.90 Hz, 2 H).13 C NMR (125 MHz, CDCl3) δ 68.5, 119.0,
120.0, 126.8, 127.4, 127.5, 127.9, 128.4, 140.7, 145.8, 148.9, 157.1, 172.6. Low
resolution MS (EI): 320 (M+), 291, 241, 159. Highꢀresolution MS (ESIꢀTOF) m/z:
[M+H]+ calcd for C23H17N2, 321.1392, found 321.1396.
5-(9-Phenyl-9H-fluoren-9-yl)pyrimidine, 3c. Using General Method C, [1,1'ꢀ
biphenyl]ꢀ2ꢀyl(pyrimidinꢀ5ꢀyl)methanone 1d (0.050 g, 0.192 mmol) and benzene (0.5
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mL, 5.6 mmol), provides compound 3c (0.054 g, 0.169 mmol, 88%) as a white solid, MP
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182–185 °C, Rf = 0.12 (hexane: ethyl acetate, 7:1). H NMR (500 MHz, CDCl3) δ 7.17ꢀ
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7.19 (m, 2 H), 7.29ꢀ7.32 (m, 3 H), 7.33ꢀ7.39 (m, 2 H), 7.41 (d, J = 7.55 Hz, 2 H), 7.44 (q,
J = 6.75 Hz, 2 H), 7.84 (d, J = 7.60 Hz, 2 H), 8.62 (s, 2 H), 9.11 (s, 1 H). 13 C NMR (125
MHz, CDCl3) δ 61.9, 120.7, 125.8, 127.4, 127.7, 128.25, 128.31, 128.8, 139.8, 140.1,
143.5, 149.1, 156.3, 157.1 Low resolution MS (EI): 320 (M+), 292, 241, 189. Highꢀ
resolution MS (EI), calcd for C23H16N2, 320.1314, found 320.1318.
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2-(9-Phenyl-9H-fluoren-9-yl)pyridazine, 3d. Using General Method C, [1,1'ꢀbiphenyl]ꢀ
2ꢀyl(pyridazinꢀ3ꢀyl)methanone, 1e (0.0683 g, 0.26 mmol) and benzene (0.5 mL, 5.6
mmol) provides compound 3d (0.074 g, 0.23 mmol, 89%) as a brown solid, MP 212–215
o C. Rf = 0.10 (hexane: ethyl acetate, 3:1).1H NMR (300 MHz, CDCl3) δ 7.07ꢀ7.10 (m, 2
H), 7.22ꢀ7.24 (m, 5 H), 7.33 (t, J = 7.50 Hz, 2 H), 7.43 (t, J = 7.35 Hz, 2 H), 7.62 (d, J =
7.56 Hz, 2 H), 7.82 (d, J = 6.60 Hz, 2 H), 9.09 (s, 1 H).13 C NMR (75 MHz, CDCl3) δ
66.0, 120.3, 124.9, 126.8, 127.7, 128.1, 128.2, 128.4, 140.5, 144.8, 149.0. Low resolution
MS (EI): 320 (M+), 291, 239, 213, 189, 159, 77. Highꢀresolution MS (EI), calcd for
C23H16N2, 320.1314, found 320.1316.
1-Butyl-2-(2-methyl-9-phenyl-9H-fluoren-9-yl)-1H-imidazole, 3e. Using General
Method C, (1ꢀbutylꢀ1Hꢀimidazolꢀ4ꢀyl)(4ꢀmethylꢀ[1,1'ꢀbiphenyl]ꢀ2ꢀyl)methanone, 1f
(0.108 g, 0.34 mmol) and benzene (0.5 mL, 5.6 mmol) provides compound 3e is isolated
in 86% yield as solid, MP 136 ꢀ 142 °C, Rf = 0.08 (hexane: ethyl acetate, 5:1). 1 H NMR
(500 MHz, CDCl3) δ 0.52ꢀ1.08 (m, 7 H), 2.38 (s, 3 H), 3.00 (t, J = 7.90 Hz, 2 H), 6.82 (d,
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J = 1.20 Hz, 1 H), 7.08 (d, J = 1.20 Hz, 1 H), 7.20ꢀ7.41 (m, 1 H), 7.46 (d, J = 7.70 Hz, 1
H), 7.68 (d, J = 7.70 Hz, 1 H), 7.75 (d, J = 7.50 Hz, 1 H). 13 C NMR (125 MHz, CDCl3) δ
21.8, 32.5, 46.2, 61.4, 120.1, 120.2, 126.1, 126.7, 126.9, 127.2, 127.5, 127.9, 128.0,
128.4, 129.0, 137.5, 140.2, 143.7, 148.0, 148.7, 149.0. Low resolution MS (EI): 378
(M+), 377, 363, 349, 335, 321, 245. Highꢀresolution MS (EI), calcd for C27H26N2,
378.2098, found 378.2096.
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1-Methyl-2-(2-methyl-9-phenyl-9H-fluoren-9-yl)-1H-imidazole, 3f. Using General
Method C, (1ꢀmethylꢀ1Hꢀimidazolꢀ2ꢀyl)(4ꢀmethylꢀ[1,1'ꢀbiphenyl]ꢀ2ꢀyl)methanone, 1g
(0.0892 g, 0.323 mmol) and benzene (0.5 mL, 5.60 mmol) provides compound 3f (0.099
g, 0.294 mmol, 91%) as an oil. Rf = 0.16 (hexane: ethyl acetate, 3:1). 1 H NMR (500
MHz, CDCl3) δ 2.40 (s, 3 H), 2.74 (s, 3 H), 6.73 (d, J = 1 Hz, 1 H), 7.04 (d, J = 1.05 Hz,
1 H), 7.23ꢀ7.31 (m, 6 H), 7.39ꢀ7.42 (m, 3 H), 7.47 (d, J = 7.60 Hz, 1 H), 7.70 (d, J = 7.75
Hz, 1 H), 7.77 (d, J = 7.55 Hz, 1 H).13 C NMR (125 MHz, CDCl3) δ 21.8, 33.9, 61.3,
120.1, 120.2, 122.9, 126.0, 126.6, 126.8, 127.0, 127.6, 127.8, 128.08, 128.12, 129.1,
137.7, 138.1, 140.4, 143.3, 148.3, 148.6. Low resolution MS (EI): 336 (M+), 268, 245,
160. Highꢀresolution MS (EI), calcd for C24H20N2, 336.1627, found 336.1626.
2-(9-Phenyl-9H-fluoren-9-yl)benzo[d]thiazole, 3g. Using General Method C,
benzo[d]thiazolꢀ2ꢀyl(4ꢀmethylꢀ[1,1'ꢀbiphenyl]ꢀ2ꢀyl)methanone, 1h (0.180 g, 0.57 mmol)
and benzene (0.5 mL, 5.60 mmol), provides compound 3g (0.183 g, 0.49 mmol, 86%) as
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a light yellow solid, MP 197–199 C. Rf = 0.38 (hexane: ethyl acetate, 5:1). 1 H NMR
(500 MHz, CDCl3) δ 7.30 (t, J = 6.00 Hz, 5 H), 7.35ꢀ7.42 (m, 3 H), 7.50 (t, J = 5.85 Hz, 3
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