Ligand-Free Ru-Catalyzed Direct sp3 C-H Alkylation of Fluorene Using Alcohols

Article abstract of DOI:10.1021/acs.joc.9b02913

The sp³ C-H alkylation of 9H-fluorene using alcohol and a Ru catalyst via the borrowing hydrogen concept has been described. This reaction was catalyzed by the [Ru(p-cymene)Cl₂]₂ complex (3 mol %) and exhibited a broad reaction scope with different alcohols, allowing primary and secondary alcohols to be employed as nonhazardous and greener alkylating agents with the formation of environmentally benign water as a byproduct. A variety of 9H-fluorene underwent selective and exclusive mono-C9-alkylation with primary alcohols in good to excellent isolated yield (26 examples, 50-92% yield), whereas this reaction with secondary alcohols in the absence of any external oxidants furnished the tetrasubstituted alkene as the major product. Furthermore, a base-mediated C-H hydroxylation of the synthesized 9H-fluorene derivatives afforded 9H-hydroxy-functionalized quaternary fluorene derivatives in excellent yield.

Full text of DOI:10.1021/acs.joc.9b02913

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Article
Ligand-Free Ru-Catalyzed Direct sp3 C-
H Alkylation of Fluorene Using Alcohols
Moseen A Shaikh, Sandip G Agalave, Akash S Ubale, and Boopathy Gnanaprakasam
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b02913 • Publication Date (Web): 06 Jan 2020
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Ligand-Free Ru-Catalyzed Direct sp3 C-H
Alkylation of Fluorene Using Alcohols
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Moseen A. Shaikh, Sandip G. Agalave, Akash S. Ubale and Boopathy Gnanaprakasam*
Department of Chemistry, Indian Institute of Science Education and Research, Pune-411008,
India.
*Email- gnanaprakasam@iiserpune.ac.in
Table of Contents
ABSTRACT: The sp3 C-H alkylation of 9H-fluorene using alcohol and Ru-catalyst via
borrowing hydrogen concept has been described. This reaction was catalyzed by [Ru(p-
cymene)Cl2]2 complex (3 mol%) and exhibited a broad reaction scope with different alcohols,
allowing primary and secondary alcohols to be employed as non-hazardous and greener
alkylating agents with the formation of environmentally benign water as a by-product. A variety
of 9H-fluorene underwent selective and exclusive mono-C9-alkylation with primary alcohols in
good to excellent isolated yield (26 examples, 50–92% yield). Whereas this reaction with
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secondary alcohols in the absence of any external oxidants furnished the tetrasubstituted alkene
as major product. Further, a base mediated C-H hydroxylation of the synthesized 9H-fluorene
derivatives afforded 9H-hydroxy functionalized quaternary fluorene derivatives in excellent
yield.
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INTRODUCTION
Transition-metal catalyzed borrowing hydrogen (BH) or hydrogen auto-transfer
methodology is an attractive and greener approach for the formation of a C−C bond in modern
synthetic methods.1 In the BH process, multiple transformations occur sequentially in one step
via a domino manner. Typically, this methodology involves the abstraction of hydrogen from
alcohol by transition-metals to generate respective carbonyl compounds in situ, which then
subsequently undergoes Aldol or Knoevenegal type condensation reaction with nucleophilic
enolate to form C=C bond. In the end, metal-catalyzed saturation of the C=C by the addition of
“borrowed” hydrogen to form the desired α-branched carbonyl compounds. As a result, metal
promotes the concomitant redox process in the BH process to afford the product with the
formation of environmentally benign H2O as a sole by-product. Due to increasing demand for
environmentally benign chemical procedures, the direct substitution of alcohol through a BH
strategy has recently received noteworthy interest and it is considered one of the key green
chemistry research approaches by pharmaceutical manufacturers.2 An atom economy and
efficiency have been increased by using renewable, and inexpensive alcohol as an alkylating
agent, which avoids the use of mutagenic alkyl halides and sulfonate esters as alkylating agents,
resulting in water as the sole by-product.1 The α-alkylation of carbonyl compounds using various
primary and secondary alcohols catalyzed by transition metal-catalyst has been well studied. In
literature, homogeneous metal catalysts such as Ru3 and Ir4 complexes were known to be
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effective catalysts for this reaction. Other metal complexes such as Rh,5 Au,6 Cu,7 Ni,8 Fe,9 Mn,10
Pd,11 and Os12 were also reported as the alternative catalysts (Scheme 1).
Scheme 1. State of art for the borrowing hydrogen concept
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Furthermore, this transformation uses a limited group of compounds containing activated
methylene groups adjacent to electron-withdrawing substituents. For example, amides13 and
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nitriles14 were alkylated at the α-position using various alcohols in the presence of a metal
catalyst to afford the corresponding α-branched derivatives. Seminal reports on the catalytic
alkylation of methyl heteroarenes system with various alcohols by Ru, Ir, Ni, and Pt have been
reported (Scheme 1).15
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From the survey of the BH strategy, it is known that a selective group of compounds viz ketone,
ester, amide, nitrile, and heteroarene possessing methylene or methyl were frequently used as the
synthetic starting material for alkylation reaction using alcohols. The majority of the reported BH
method has been catalyzed by the specially made metal complexes or in situ generations of the
metal complexes by the reaction of the metal precursor with the ligands. In this regard, the
development of the ligand-free BH approach for the alkylation reaction using alcohol is highly
desirable. In this concept, Lang and co-workers reported the ligand-free Ru-catalyzed alkylation
of methylazarenes with alcohols.15c Besides, developing a BH strategy to other substrates
possessing methylene functionality is also challenging in this area. Thus, we envisioned from the
literature that the alkylation of the methylene group of the fluorene is not studied for the BH
concept. A specific interest of our research group relay on methylene alkylation of fluorene is
due to the widespread application in pharmaceutical and materials.16 In the last few decades, the
synthesis of 9-monoalkylated and 9,9-dialkylated fluorene monomers have attracted more
attention by chemist as they are key starting material for poly(alkylfluorene)s due to their
chemical, physical, and photoelectric properties.17 In literature, many methods are available for
the synthesis of 9,9-dialkylated fluorene by using excess alkyl halides in the presence of a strong
base such as n-BuLi18 or NaOH19. But there are only a few methods available for selective 9-
monoalkylation. A method for selective 9-monoalkylation of fluorene was carried out with
excess use of alkyl halides in the presence of n-BuLi,18 having very harsh reaction conditions
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with poor yield. In another method dehydrative alkylation of fluorene was carried out by using
only benzyl alcohol as an alkylating reagent under microwave condition at elevated
temperature20. However, this method is unsuccessful with aliphatic alcohols. Very recently, Qing
Xu reported CsOH mediated selective synthesis of 9-monoalkylated fluorene by dehydrative C-
alkylation with primary and secondary alcohols, which is catalyzed by aldehyde or ketone.21
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Although several other transformations are known for 9-monoalkylation/alkenylation of
fluorenes, Ruthenium-catalyzed alkylation of 9H-fluorene with primary and secondary alcohols
for the synthesis of 9-substituted products under ligand-free condition has not been developed.
Herein, we report the first example of the base-metal-catalyzed practical route to the synthesis of
9-monosubstituted fluorene by using aliphatic or aromatic alcohols under ligand-free conditions.
Moreover, C-H hydroxylation of fluorene derivatives promoted by the base is also described in
this work.
RESULT AND DISCUSSIONS
Initially, the reaction optimization for the 9-alkylation reaction of 9H-Fluorene 1a with
benzyl alcohol 2a using Ru-catalyst was performed by varying the concentrations of the catalyst,
base, and solvent (Table 1). A control experiment was performed for this reaction using 1.5
equivalent of t-BuOK in absence of a catalyst showed 45% of 9-benzyl-9H-fluorene 3a in
isolated yield (Table 1, entry 1). In another control experiment, a solution of 0.3 mmol of 9H-
Fluorene, 0.45 mmol of benzyl alcohol and 3 mol% of [Ru(p-cymene)Cl2]2] of catalyst were
heated at 120 C in the absence of base, and we found that there is no product formation (Table
1, entry 2). The absence of 9-benzyl-9H-fluorene 3a, emphasizes the importance of the t-BuOK
as a base for this reaction (Table 1, entry 2). An excess of the base (> 3 eq.) under the above
reaction condition results in a complicated reaction mixture. The best optimized condition was
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obtained by heating the reaction mixture of 9H-Fluorene 1a and benzyl alcohol 2a, in the
presence of 1.5 equivalent of t-BuOK and 3 mol% of [[Ru(p-cymene)Cl2]2] catalyst at 120 C for
18 hrs, which afford 9-
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Table 1. Optimization for the 9-alkylation reaction of 9H-Fluorenea
Entry
catalyst
base (1.5 eq.)
solvent
temp
yield of 3a (%)
(3 mol%)
(C)
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5
-
t-BuOKb
-
t-BuOK
KOH
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
1,4-Dioxane
DCE
120
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120
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[Ru(p-cymene)Cl2]2
[Ru(p-cymene)Cl2]2
[Ru(p-cymene)Cl2]2
[Ru(p-cymene)Cl2]2
[Ru(p-cymene)Cl2]2
[Ru(p-cymene)Cl2]2
[Ru(p-cymene)Cl2]2
RuCl3.XH2O
no reaction
99
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Traces
NaOH
6
7
8
K2CO3
Cs2CO3
Na2CO3
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
no reaction
no reaction
no reaction
90
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20c
21d
RuHClCO(PPh3)
RuH2CO(PPh3)3
RuH2(PPh3)4
83
92
93
23
Ru-MACHO
[Ru(p-cymene)Cl2]2
[Ru(p-cymene)Cl2]2
[Ru(p-cymene)Cl2]2
[Ru(p-cymene)Cl2]2
[Ru(p-cymene)Cl2]2
[Ru(p-cymene)Cl2]2
[Ru(p-cymene)Cl2]2
[Ru(p-cymene)Cl2]2
50
no reaction
no reaction
no reaction
Traces
49
DMF
DMSO
Toluene
Toluene
Toluene
Toluene
100
120
120
no reaction
58
Reaction Conditions: a 9H-fluorene 1a (0.3 mmol), benzyl alcohol 2a (0.45 mmol), catalyst (3
mol%), base (1.5 equiv.) were stirred at 120 ˚C for 18 hrs under nitrogen atmosphere. b excess of
base results complicated reaction mixture. c base (0.5 equiv.). d base (1 equiv.)
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Scheme 2. Ruthenium-catalyzed 9-alkylation reaction of 9H-fluorene with substituted
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aromatic alcohols and aliphatic alcohols
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a
Reaction conditions: 9H-fluorene (0.3 mmol), alcohol (0.45 mmol), catalyst (3 mol%), and t-
b
BuOK (1.5 equiv.) were heated at 120 °C under nitrogen atmosphere for 18 hrs. 9H-fluorene
(0.3 mmol), alcohol (0.45 mmol), catalyst (3 mol %), and t-BuOK (2 equiv.) were heated at 140
°C under nitrogen atmosphere for 48 hrs. Yields corresponds to isolated pure compounds.
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benzyl-9H- fluorene 3a in 99% yield (Table 1, entry 3). In contrast, KOH gave only moderate
yield of 3a under the present conditions (Table 1, entry 4). Other bases such as NaOH, K2CO3,
Cs2CO3, Na2CO3 are failed to deliver 9-benzyl-9H-fluorene 3a under similar reaction conditions
(Table 1, entries 5-8). Other Ru-catalysts such as RuCl3.XH2O, RuHClCO(PPh3)3,
RuH2CO(PPh3)3, RuH2(PPh3)4 also afforded 83-92% yield of 9-benzyl-9H-fluorene 3a under the
same reaction condition (Table 1, entries 9-12). Using the optimized reaction condition, a wide
range of primary alcohols were subjected to ruthenium-catalyzed 9-alkylation of 9H-fluorene
(Scheme 2).
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In general, benzyl alcohols bearing electron-donating and withdrawing substituents such as
methyl, methoxy, chloro, phenyl, fluoro, and trifluoromethyl afforded the corresponding 9-
alkylated 9H-fluorene in good to excellent yields. Electron-rich benzyl alcohols having methyl
group on ortho, meta and para position were converted into 3b, 3c and 3d in 89% 95% and 97%
yields, respectively. The 9-alkylation of 9H-fluorene with 2-methoxy, 3-methoxy, 4-methoxy
benzyl alcohols afforded the corresponding products 3e-3g in 86%, 87%, and 93% yield,
respectively. Notably, under standard experimental condition, 4-phenyl substituted benzyl
alcohols provided good to excellent yields of corresponding products 3h and 3i in 73% and 97%
respectively. The presence of an electron-withdrawing substituent such as 3-fluoro, 4-fluoro, 4-
trifluoromethyl, and 3-chloro on the aryl ring of benzyl alcohol provided 9-alkylated products 3j-
3m in excellent yield. Gratifyingly, heteroaryl methanols were tolerated under this catalytic 9-
alkylation reaction of 9H-fluorene. Furfuryl alcohol and 2-thiophenemethanol provided 9-
alkylated products 3o and 3p in good yields. Further, the scope of the reaction was evaluated
with aliphatic primary alcohols. When long-chain 1-octanol was subjected for alkylation reaction
under standard optimized condition, the 9-alkylated product was isolated in poor yield (35%). An
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increasing base loading to 2 equivalents afforded the product 3q in 47% in 48 hrs. Due to less
reactivity of aliphatic primary alcohols, the reaction required longer reaction time (48 hrs) to
provide 9-alkylated 9H-fluorene (3q-3t) in very good yield. Interestingly, 9H-fluoren-2-amine
was also successfully alkylated to afford 9-benzyl-9H-fluoren-2-amine 3u in 46% yield along
with the N-alkylated product 3u’ in 40% yield. A gram scale reaction was performed with
fluorene 1 and benzylalcohol under the standard condition to afford 1.34 g (87%) of the product
3a after column purification (Scheme 3).
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Scheme 3. Gram scale reaction
We further checked the generality of this reaction for the alkylation of 9H-fluorene by using
secondary alcohols (Scheme 4). A reaction of 9H-fluorene with diphenylmethanol under the
above optimized reaction condition by using 3 mol% of [Ru(p-cymene)Cl2]2 and t-BuOK (1.5
equivalent) for 18 hrs failed to deliver 9-sec-alkyl fluorene 5a. Hence, we have re-optimized the
reaction condition to obtain 9-sec-alkyl fluorene. Upon heating the reaction mixture containing
9H-fluorene (0.3 mmol) and diphenyl methanol (0.6 mmol) in the presence of 5 mol% of [Ru(p-
cymene)Cl2]2 and 2 equivalent of t-BuOK at 140 C, affording 9-benzhydryl-9H-fluorene 5a in
66% yield and 9-(diphenylmethylene)-9H-fluorene 6a in 21% yield. Furthermore, we set out the
substrate scope of this reaction by using substituted secondary alcohol. Thus the reaction of the
9H-fluorene 1 with various substituted benzhydrazol such as methyl-, methoxy-, trifluoromethyl-
, and chloro in the presence of 5 mol% [Ru(p-cymene)Cl2]2 and 2 equivalents of t-BuOK at 140
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C, afforded the respective alkene products 6b-e as the exclusive isomer in good yield.
Interestingly, in the case of secondary alcohols, higher selectivity for the formation of alkene was
observed which might be due to sterically hindered alkene difficult to coordinate with the Ru-
catalyst for further hydrogenation reaction.
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Scheme 4. Ruthenium-catalyzed 9-alkylation/alkenylation reaction of 9H-fluorene with
substituted aromatic secondary alcoholsa
Reaction conditions:a9H-fluorene (0.3 mmol), alcohol (0.6 mmol), catalyst (5 mol%), and t-
BuOK (2 equiv.) were heated at 140 °C under nitrogen atmosphere for 48 hrs. Yields
corresponds to isolated pure compounds.
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Next, selectivity on the alkylation of 9H-Fluorene with primary alcohols over secondary
alcohols was investigated under an optimized reaction condition using [Ru(p-cymene)Cl2]2 (3
mol%) and t-BuOK (1.5 equivalent) (Scheme 4). Hence, a reaction of 9H-fluorene (0.3 mmol)
with equimolar amount of benzyl alcohol and 1-butanol (each 0.45 mmol) under optimized
reaction condition afforded 9-benzyl-9H-fluorene (3a, 72% isolated yield, Scheme 5a), and 9-
butyl-9H-fluorene (3q, 26% isolated yield, Scheme 5a), which proves that aromatic alcohols are
more reactive and selective than aliphatic alcohols for this transformation. A similar experiment
using 2-methyl benzyl alcohol and 1-cyclohexanol was quantitatively converted to the 9-(2-
methylbenzyl)-9H-fluorene (3b, Scheme 5b) in 79% isolated yield, which confirms that benzyl
alcohol reacts faster than secondary alcohols. Remarkably, when 9H-fluorene (0.3 mmol) was
reacted with benzyl alcohol (0.45 mmol) and diphenylmethanol (0.45 mmol) in the presence of
[Ru(p-cymene)Cl2]2 (3 mol %) and t-BuOK (1.5 equivalent), quantitative conversion of 9-
benzyl-9H-fluorene (3a, 92% isolated yield, Scheme 5c) was observed. In another experiment
using 1- butanol and 1-cyclohexanol provided exclusively 9-alkylated 3q (58%, isolated yield,
Scheme 5d). These experimental results demonstrate that these reactions afforded high
chemoselectivity with aromatic primary alcohols. Moreover, secondary alcohols were either non-
reactive or less yield in these competitive experiments. High chemoselectivity was achieved with
the aliphatic primary alcohols over the aliphatic secondary alcohols, which might be due to the
steric effect present in the secondary alcohols. These reaction were also performed with various
diols such as 1,3-benzenedimethanol, 1-phenyl-1,2-ehanediol, 1,2-butandiol and 1,3-propandiol
under the standard condition as well as heated up to 160 °C. But this reaction was not successful
to afford the desired products (Scheme 5e).
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Scheme 5. Chemoselectivity of primary alcohols over secondary alcohols on the alkylation
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of 9H-Fluorene
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To study the hydroxylation reaction,22 9-alkylation of 9H-fluorene was exposed to air under
basic condition (Scheme 6). A solution of compound 3a and t-BuOK in DMSO was allowed to
stir at room temperature in an atmospheric air for 24 hrs. It was noted that the compound 3a
undergoes hydroxylation to afford the quaternary 9-hydroxy functionalized fluorene 7a in 84%
yield (Scheme 6). Similarly, other derivatives of compound 3 were incorporated for the C-H
hydroxylation reaction to afford the respective quaternary 9-hydroxy functionalized fluorene
derivative 7b-i in excellent yield (Scheme 6).
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Scheme 6. t-BuOK mediated C-H hydroxylation of 9-alkylated 9H-fluorenea
a
Reaction conditions: 9-alkyl-9H-fluorene (0.3 mmol), t-BuOK (1 equiv.) at room temperature
in an open-air atmosphere for 24 hrs. Yields corresponds to isolated pure compounds.
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A mercury-poisoning experiment23 was performed to examine the involvement of any
heterogeneous catalyst formed from the ruthenium catalyst under experimental reaction
conditions. The catalytic reaction of 9H-fluorene with benzyl alcohol was carried out in the
presence of mercury (10 equiv., relative to substrate 1a), which provided the corresponding
alkylated 9H-fluorene 3a in 76% isolated yield (against the 99% yield in the absence of mercury,
see Scheme 7), indicating that the reaction proceeds under homogeneous condition (Scheme 7a).
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To probe hydrogen source for reduction of unsaturated intermediate, a reaction of 9-(4-
fluorobenzylidene)- 9H-fluorene 8 with 4-fluorobenzyl alcohol in the standard condition was
performed, resulted in the formation of desired product 3k in 84% yield (Scheme 7b). Further, a
reaction of 9-(4-fluorobenzylidene)- 9H-fluorene 8 with 4-fluorobenzyl alcohol under standard
reaction condition led to product 3k in 87% yield with the formation of benzophenone 9 as a by-
product. This indicates that alcohol is necessary to generate hydride species which is required for
the reduction of the condensed product. To exclude the other possibility for the formation of 3k,
a reaction of 8 with 4-fluoro benzaldehyde 10 was performed and reveals no reaction. Deuterium
labeling experiment with deuterated benzyl alcohol 2a’ shows 57% (α) and 68% (β) D
incorporation (Scheme 7e). Moreover, a reaction of 9-(4-fluorobenzylidene)- 9H-fluorene 8 with
deuterated benzyl alcohol 2a’ afforded the product 3k’ with 56% (α) and 55% (β) D
incorporation (Scheme 7f). From the above experiments, deuteride transfer to Fluorene
derivative occurs from a Ru-deuteride intermediate. Besides, a similar reaction with deuterated
diphenyl methanol 4a’ shows the product 3k” with 56% (β) deuterium incorporation (Scheme
7g), which confirms deuteride transfer occurs at the β-position of Fluorene derivative from a Ru-
deuteride intermediate.
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Scheme 7. Mechanistic studies for the 9-alkylation of 9H-fluorene
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From the experimental observations and literature precedents, we have proposed a mechanistic
pathway for the alkylation reaction (Scheme 8).3,5 The ruthenium catalyst reacts with alcohol 2 to
generate aldehyde 2a’ and Ru-H2 species. Moreover, the formation of a hydride signal was
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confirmed by H-NMR analysis and the liberation of H2 gas was confirmed by GC analysis
(Figure 85, ESI). Subsequently, the condensation of an aldehyde with 9H-fluorene in the
presence of base afforded desired 9-benzylidene-9H-fluorene (2a’’). Further, condensed product
2a’’ undergoes catalytic hydrogenation to lead 9-benzyl-9H-fluorene 3 by the Ru-H2 complex.
Scheme 8. A plausible mechanism for the alkylation of 9H-fluorene
CONCLUSIONS
In conclusion, we have developed a novel, highly efficient and chemoselective catalytic method
for the alkylation/alkenylation of 9H-fluorene by using various primary and secondary alcohols
in absence of any external oxidants to afford the 9-monosubstituted-9H-fluorene in high yield.
This transformation was carried out by using inexpensive, highly air-stable [Ru(p-cymene)Cl2]2
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complex in the absence of ligand. This methodology developed an environmentally benign
conditions for the alkylation of fluorene by using greener and non-hazardous alkylating reagents
with the formation of water as a by-product. Moreover, an efficient C-H hydroxylation of 9H-
fluorene derivatives using inexpensive t-BuOK was demonstrated under simple reaction
conditions in the absence of any oxidants. A plausible mechanism for this transformation was
proposed with the experimental observation includes hydride detection and hydrogen liberation.
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EXPERIMENTAL SECTION
General information and data collection:
All the chemicals were purchased from Sigma Aldrich or Alfa-Aesar. All stoichiometric
reactions were performed under nitrogen atmosphere. Dry solvents were prepared according to
standard procedures. Column chromatographic separations performed over 100−200 Silica-gel.
Visualization was accomplished with UV light and phosphomolybdic acid (PMA), Ceric
ammonium molybdate (CAM) stain followed by heating. Deuterated solvents were used as
received. 1H, 13C{1H} NMR chemical shifts were reported in ppm downfield from
tetramethylsilane. Multiplicity is abbreviated as: s, singlet; d, doublet; dd, doublet of doublets; dt,
doublet of triplets; t, triplet; q, quartet; dq, doublet of quartets; td, triplet of doublets; m,
multiplet; br, broad. High-resolution mass spectra were recorded with Waters-synapt G2 using
electrospray ionization (ESI-TOF). The quantitative analysis of molecular hydrogen gas was
carried out by using gas chromatograph (GC) equipped with a TCD detector (Agilent 7890),
column type carbosieve and mesh range-100, max temp 225 oC with flow rate for other gases 14
mL/min and hydrogen 4 mL/min. The temperature gradient of the detector and oven were 200
oC, 60 oC respectively. The temperature of the injector was 150 oC during the experiment.
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A) General experimental procedure for the 9-alkylation of 9H-fluorene with primary
alcohol (Method A): [Ru(p-cymene)Cl2]2 (3 mol%), t-BuOK (1.5 equiv.), 9H-fluorene (0.3
mmol), alcohol (0.45 mmol), and toluene (2 mL) were added to an oven-dried 20 mL resealable
pressure tube (equipped with rubber septum) under a N2 atmosphere. The tube was purged with
N2 and sealed with a cap using a crimper. The reaction mixture was stirred at 120 °C for 18 h on
a preheated oil bath. The reaction mixture was cooled to room temperature and concentrated
under vacuum. DCM was added to the reaction mixture and passed through a plug of celite. The
filtrate was concentrated under reduced pressure and the residue was purified by 100-200 mesh
silica-gel column chromatography using ethyl acetate/petroleum ether (1:99) to afford the pure
product of 9-alkylated 9H-fluorene 3. (In the case of aliphatic alcohols, 5 mol% of [Ru(p-
cymene)Cl2]2 catalyst t-BuOK (2 equiv.) was used and kept for 48 h).
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B) General experimental procedure for the 9-alkylation of 9H-fluorene with secondary
alcohol (Method B): [Ru(p-cymene)Cl2]2 (5 mol%), t-BuOK (2 equiv.), 9H-fluorene (0.3
mmol), alcohol (0.60 mmol), and toluene (2 mL) were added to an oven-dried 20 mL resealable
pressure tube (equipped with rubber septum) under a N2 atmosphere. The tube was purged with
N2 and sealed with a cap using a crimper. The reaction mixture was stirred at 140 °C for 48 h on
a preheated oil bath. The reaction mixture was cooled to room temperature and concentrated
under reduced pressure. DCM was added to the reaction mixture and passed through a plug of
celite. The filtrate was concentrated under reduced pressure and the residue was purified by 100-
200 mesh silica-gel column chromatography using ethyl acetate/petroleum ether (1:99) to afford
the pure product of 9-alkylated 9H-fluorene.
C) Experimental procedure for control experiment in the absence of catalyst: t-BuOK (1.5
equiv.), 9H-fluorene (0.3 mmol), benzyl alcohol (0.45 mmol), and toluene (2 mL) were added to
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an oven-dried 20 mL resealable pressure tube (equipped with rubber septum) under N2
atmosphere. The tube was purged with N2 and sealed with a cap using a crimper. The reaction
mixture was stirred at 120 °C for 24 h on a preheated oil bath. The reaction mixture was cooled
to room temperature and concentrated under reduced pressure. DCM was added to the reaction
mixture and passed through a plug of celite. The filtrate was concentrated under reduced pressure
and the residue was purified by 100-200 mesh silica-gel column chromatography using ethyl
acetate/petroleum ether (1:99) to afford the 9-benzyl-9H-fluorene 3a in 45% yield.
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D) Experimental procedure for control experiment in the absence of base: [Ru(p-
cymene)Cl2]2 (3 mol%), 9H-fluorene (0.3 mmol), benzyl alcohol (0.45 mmol), and toluene (2
mL) were added to an oven-dried 20 mL resealable pressure tube (equipped with rubber septum)
under a N2 atmosphere. The tube was purged with N2 and sealed with a cap using a crimper. The
reaction mixture was stirred at 120 °C for 18 h on a preheated oil bath. This showed no reaction.
E) General experimental procedure for C-H hydroxylation of 9-alkyl-9H-fluorene: 9-Alkyl-
9H-fluorene (1 eq), t-BuOK (1 equiv.) and DMSO (2 mL) were added to a 20 mL tube with a
magnetic bar and then the mixture was stirred at room temperature in open air for 24 h. The
solution was then diluted with dichloromethane (10 mL), washed with water (5 x 3) and brine
(5x 5 mL), dried over anhydrous Na2SO4, filtered, and evaporated under vacuum. The crude
reaction mixture was purified by column chromatography on silica gel (ethyl acetate/petroleum
ether 05:95).
F) Experimental procedure for the detection of H2 gas using GC analysis: To an oven-dried
20 mL resealable pressure tube (equipped with a rubber septum), [Ru(p-cymene)Cl2]2 (3 mol%),
t-BuOK (1.5 equi.), 9H-fluorene (0.3 mmol), benzyl alcohol (0.45 mmol), and toluene (2 mL)
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were added under N2 atmosphere. The tube was purged with N2 and sealed with a cap using a
crimper. The reaction mixture was stirred at 120 °C for 6 h on a preheated oil bath. The gas
phase of the reaction mixture was taken out by a gas tight glass syringe and immediately injected
into the injector of the GC instrument. The liberation of H2 was detected by GC analysis.
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G) Experimental procedure for hydride detection in the reaction mixture: In a dry NMR
tube, charged with [Ru(p-cymene)Cl2]2 (20 mol%), t-BuOK (0.1 mmol), 9H-fluorene (0.1
mmol), and 4-methyl benzyl alcohol (0.1 mmol) in benzene-d6. The NMR tube was then kept in
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a preheated oil bath at 80 °C for 30 min. Subsequently, the sample was analyzed by H NMR
spectroscopy, hydride signals were detected at the δ -17.12 and -17.19 ppm (see ESI). The same
sample was then heated at 100 0C for 1 h and recorded 1H-NMR analysis. There was no chemical
shift change for the hydride signals. These experimental evidence support the formation of Ru-H
intermediate in the reaction mixture.
H) Experimental procedure for gram scale reaction: [Ru(p-cymene)Cl2]2 (74 mg, 2 mol%), t-
BuOK (1.011 g, 9.03 mmol), 9H-fluorene 1 (1.0 g, 6.02 mmol), benzyl alcohol 2a (975 mg, 9.03
mmol), and toluene (6 mL) were added to an oven-dried 30 mL resealable pressure tube
(equipped with rubber septum) under a N2 atmosphere. The tube was purged with N2 and sealed
with a cap using a crimper. The reaction mixture was stirred at 120 °C for 18 h on a preheated oil
bath. The reaction mixture was cooled to room temperature and concentrated under vacuum.
DCM was added to the reaction mixture and passed through a plug of celite. The filtrate was
concentrated under reduced pressure and the residue was purified by 100-200 mesh silica-gel
column chromatography using ethyl acetate/petroleum ether (1:99) to afford the pure 9-benzyl-
9H-fluorene 3a (1.34 g 87%).
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I) Analytical data for the product:
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9-Benzyl-9H-fluorene (3a)21: [Ru(p-cymene)Cl2]2 (5.4 mg, 0.009 mmol), t-BuOK (50.50 mg,
0.45 mmol), benzyl alcohol (65 mg, 0.45 mmol), 9H-fluorene (50 mg, 0.30 mmol) and toluene (2
mL) were allowed to react in 20 mL resealable pressure tube according to method A to afford 9-
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benzyl-9H-fluorene 3a (76 mg, 99 %) as a white solid. Melting point: 132−134 °C. H NMR
(400 MHz, CDCl3) δ 7.73 (d, J = 7.5 Hz, 2H), 7.38 – 7.13 (m, 11H), 4.23 (t, J = 7.6 Hz, 1H),
3.12 (d, J = 7.6 Hz, 2H). C{1H} NMR (100 MHz, CDCl3) δ 146.9, 140.9, 139.9, 129.6, 128.4,
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127.2, 126.7, 126.5, 124.9, 119.9, 48.8, 40.2. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C20H17
257.1330; Found 257.1335.
9-(2-Methylbenzyl)-9H-fluorene (3b): [Ru(p-cymene)Cl2]2 (5.4 mg, 0.009 mmol), t-BuOK
(50.50 mg, 0.45 mmol), 2-methylbenzyl alcohol (73 mg, 0.45 mmol), 9H-fluorene (50 mg, 0.30
mmol) and toluene (2 mL) were allowed to react in 20 mL resealable pressure tube according to
method A to afford 9-(2-methylbenzyl)-9H-fluorene 3b (73 mg, 89 %) as a white solid. Melting
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point: 70−72 °C. H NMR (400 MHz, CDCl3) δ 7.81 (d, J = 7.4 Hz, 2H), 7.40 (t, J = 7.4 Hz,
2H), 7.34 – 7.21 (m, 6H), 7.15 (d, J = 7.5 Hz, 2H), 4.24 (t, J = 8.0 Hz, 1H), 3.09 (d, J = 8.0 Hz,
2H), 2.32 (s, 3H). C{1H} NMR (100 MHz, CDCl3) δ 147.2, 140.8, 138.5, 136.8, 130.6, 130.5,
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127.2, 126.8, 126.7, 126.0, 124.9, 119.9, 47.7, 37.8, 19.8. HRMS (ESI-TOF) m/z: [M+Na]+
Calcd for C21H18Na 293.1306; Found 293.1305.
9-(3-Methylbenzyl)-9H-fluorene (3c): [Ru(p-cymene)Cl2]2 (5.4 mg, 0.009 mmol), t-BuOK
(50.50 mg, 0.45 mmol), 3-methylbenzyl alcohol (54 mg, 0.45 mmol), 9H-fluorene (50 mg, 0.30
mmol) and toluene (2 mL) were allowed to react in 20 mL resealable pressure tube according to
method A to afford 9-(3-methylbenzyl)-9H-fluorene 3c (77 mg, 95 %) as a white solid. Melting
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point: 114−116 °C. 1H NMR (400 MHz, CDCl3) δ 7.73 (d, J = 7.6 Hz, 2H), 7.34 (t, J = 7.4 Hz,
2H), 7.21 (td, J = 7.3, 0.9 Hz, 3H), 7.15 (d, J = 7.5 Hz, 2H), 7.06 (m, 3H), 4.22 (t, J = 7.7 Hz,
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1H), 3.06 (d, J = 7.7 Hz, 2H), 2.37 (s, 3H). C{1H} NMR (100 MHz, CDCl3) δ 147.0, 140.9,
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139.9, 138.0, 130.4, 128.3, 127.3, 127.2, 126.7, 126.6, 119.9, 48.8, 40.2, 21.6. HRMS (ESI-TOF)
m/z: [M+Na]+ Calcd for C21H18Na 293.1306; Found 293.1314.
9-(4-Methylbenzyl)-9H-fluorene (3d)21: [Ru(p-cymene)Cl2]2 (5.4 mg, 0.009 mmol), t-BuOK
(50.50 mg, 0.45 mmol), 4-methyl benzyl alcohol (54 mg, 0.45 mmol), 9H-fluorene (50 mg, 0.30
mmol) and toluene (2 mL) were allowed to react in 20 mL resealable pressure tube according to
method A to afford 9-(4-methylbenzyl)-9H-fluorene 3d (78 mg, 97 %) as a white solid. Melting
point: 134−136 °C. 1H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 7.5 Hz, 2H), 7.36 (t, J = 7.2 Hz,
2H), 7.27 – 7.18 (m, 4H), 7.14 (d, J = 1.4 Hz, 4H), 4.23 (t, J = 7.6 Hz, 1H), 3.09 (d, J = 7.6 Hz,
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2H), 2.38 (s, 3H). C{1H} NMR (100 MHz, CDCl3) δ 147.0, 140.9, 136.8, 135.9, 129.5, 129.1,
127.1, 126.7, 125.0, 119.9, 48.9, 39.7, 21.2. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for
C21H18Na 293.1306; Found 293.1309.
9-(2-Methoxybenzyl)-9H-fluorene (3e)21: [Ru(p-cymene)Cl2]2 (5.4 mg, 0.009 mmol), t-BuOK
(50.50 mg, 0.45 mmol 2-methoxybenzyl alcohol (62 mg, 0.45 mmol), 9H-fluorene (50 mg, 0.30
mmol) and toluene (2 mL) were allowed to react in 20 mL resealable pressure tube according to
method A to afford 9-(2-methoxybenzyl)-9H-fluorene 3e (74 mg, 86 %) as a sticky yellow solid.
1H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 7.6 Hz, 2H), 7.41 – 7.31 (m, 3H), 7.28 – 7.20 (m,
4H), 7.10 (dd, J = 7.3, 1.6 Hz, 1H), 6.96 (m, 2H), 4.41 (t, J = 7.6 Hz, 1H), 3.91 (s, 3H), 3.11 (d, J
= 7.6 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3) δ 158.1, 147.8, 140.8, 131.7, 128.7, 127.9,
126.9, 126.6, 125.1, 120.2, 119.8, 110.4, 55.4, 46.8, 35.7. HRMS (ESI-TOF) m/z: [M+H]+ Calcd
for C21H19O 287.1436; Found 287.1443.
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9-(3-Methoxybenzyl)-9H-fluorene (3f)21: [Ru(p-cymene)Cl2]2 (5.4 mg, 0.009 mmol), t-BuOK
(50.50 mg, 0.45 mmol), 3-methoxybenzyl alcohol (62 mg, 0.45 mmol), 9H-fluorene (50 mg, 0.30
mmol) and toluene (2 mL) were allowed to react in 20 mL resealable pressure tube according to
method A to afford 9-(3-methoxybenzyl)-9H-fluorene 3f (75 mg, 87 %) as a white solid. Melting
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point: 80−82 °C. H NMR (400 MHz, CDCl3) δ 7.74 (d, J = 7.6 Hz, 2H), 7.38 – 7.33 (m, 2H),
7.23 (dt, J = 6.8, 3.0 Hz, 5H), 6.86 – 6.75 (m, 3H), 4.24 (t, J = 7.5 Hz, 1H), 3.77 (s, 3H), 3.09 (d,
J =7.5, 2H). 13C{1H} NMR (100 MHz, CDCl3) δ 159.6, 146.9, 141.5, 140.9, 129.4, 127.6, 126.9,
125.1, 122.1, 119.9, 115.0, 112.1, 55.3, 48.6, 40.1. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for
C21H19O 287.1436; Found 287.1449.
9-(4-Methoxybenzyl)-9H-fluorene (3g)21: [Ru(p-cymene)Cl2]2 (5.4 mg, 0.009 mmol), t-BuOK
(50.50 mg, 0.45 mmol), 4-methoxybenzyl alcohol (62 mg, 0.45 mmol), 9H-fluorene (50 mg, 0.30
mmol) and toluene (2 mL) were allowed to react in 20 mL resealable pressure tube according to
method A to afford 9-(4-methoxybenzyl)-9H-fluorene 3g (80 mg, 93 %) as a white solid.
Melting point: 109−111 °C. 1H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 7.6 Hz, 2H), 7.36 (t, J =
7.3 Hz, 2H), 7.27 – 7.18 (m, 4H), 7.14 (d, J = 8.4 Hz, 2H), 6.86 (d, J = 8.4 Hz, 2H), 4.20 (t, J =
7.5 Hz, 1H), 3.83 (s, 3H), 3.07 (d, J = 7.5 Hz, 2H). C{1H} NMR (100 MHz, CDCl3) δ 158.2,
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147.0, 140.9, 131.9, 130.5, 127.1, 126.7, 124.9, 119.9, 113.7, 55.2, 48.9, 39.1. HRMS (ESI-TOF)
m/z: [M+H]+ Calcd for C21H19O 287.1436; Found 287.1450.
9-([1,1’-Biphenyl]-4-methyl)-9H-fluorene (3h): [Ru(p-cymene)Cl2]2 (5.4 mg, 0.009 mmol), t-
BuOK (50.50 mg, 0.45 mmol), ([1,1’-biphenyl]-4-methyl) alcohol (77 mg, 0.45 mmol), 9H-
fluorene (50 mg, 0.30 mmol) and toluene (2 mL) were allowed to react in 20 mL resealable
pressure tube according to method A to afford 9-([1,1’-biphenyl]-4-methyl)-9H-fluorene 3h (73
mg, 73 %) as a white solid. Melting point: 130−132 °C. 1H NMR (400 MHz, CDCl3) δ 7.75 (d, J
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= 7.8 Hz, 2H), 7.71 (m, 1H), 7.66 – 7.62 (m, 2H), 7.56 (d, J = 8.1 Hz, 2H), 7.46 (d, J = 7.4 Hz,
2H), 7.37 – 7.34 (m, 2H), 7.31 (d, J = 8.0 Hz, 2H), 7.26 – 7.22 (m, 4H), 4.27 (t, J = 7.5 Hz, 1H),
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3.16 (d, J = 7.5 Hz, 2H). C{1H} NMR (100 MHz, CDCl3) δ 146.9, 140.9, 139.2, 139.0, 130.0,
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128.9, 127.2, 127.1, 127.0, 126.8, 124.9, 119.9, 48.8, 39.8. HRMS (ESI-TOF) m/z: [M+H]+
Calcd for C26H21 333.1638; Found 333.1643.
9-(3-Phenoxybenzyl)-9H-fluorene (3i): [Ru(p-cymene)Cl2]2 (5.4 mg, 0.009 mmol), t-BuOK
(50.50 mg, 0.45 mmol), 3-phenoxybenzyl alcohol (90 mg, 0.45 mmol), 9H-fluorene (50 mg, 0.30
mmol) and toluene (2 mL) were allowed to react in 20 mL resealable pressure tube according to
method A to afford 9-(3-phenoxybenzyl)-9H-fluorene 3i (102 mg, 97 %) as a white solid.
Melting point: 96−98 °C. 1H NMR (400 MHz, CDCl3) δ 7.74 (d, J = 7.6 Hz, 2H), 7.40 – 7.31 (m,
4H), 7.29 – 7.22 (m, 5H), 7.13 – 7.08 (m, 1H), 6.99 – 6.86 (m, 5H), 4.23 (t, J = 7.4 Hz, 1H), 3.13
(d, J = 7.4 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3) δ 157.5, 157.0, 146.6, 141.7, 140.9,
129.8, 129.6, 127.2, 126.8, 124.9, 124.7, 123.1, 120.3, 119.9, 118.7, 117.3, 48.6, 39.9. HRMS
(ESI-TOF) m/z: [M+H]+ Calcd for C26H21O 349.1592; Found 349.1588.
9-(3-Fluorobenzyl)-9H-fluorene (3j): [Ru(p-cymene)Cl2]2 (5.4 mg, 0.009 mmol), t-BuOK (50.50
mg, 0.45 mmol), 3-fluorobenzyl alcohol (57 mg, 0.45 mmol), 9H-fluorene (50 mg, 0.30 mmol)
and toluene (2 mL) were allowed to react in 20 mL resealable pressure tube according to method
A to afford 9-(3-fluorobenzyl)-9H-fluorene 3j (76 mg, 92 %) as a white solid. Melting point:
90−92 °C. 1H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 7.6 Hz, 2H), 7.38 (t, J = 7.3 Hz, 2H), 7.30
13
– 7.20 (m, 5H), 6.98 (m, 3H), 4.25 (t, J = 7.4 Hz, 1H), 3.15 (d, J = 7.4 Hz, 2H). C{1H} NMR
(100 MHz, CDCl3) δ 162.88 (d, J = 243.8 Hz), 146.5, 142.4 (d, J = 7.1 Hz), 140.9, 129.8 (d, J =
8.2 Hz), 127.3, 126.8, 125.34 (d, J = 2.7 Hz), 124.8, 120.0, 116.4 (d, J = 20.8 Hz), 113.4 (d, J =
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20.8 Hz), 48.5, 39.8. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C20H16F 275.1236; Found
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275.1238.
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9-(4-Fluorobenzyl)-9H-fluorene (3k)21: [Ru(p-cymene)Cl2]2 (5.4 mg, 0.009 mmol), t-BuOK
(50.50 mg, 0.45 mmol), 4-fluorobenzyl alcohol (57 mg, 0.45 mmol), 9H-fluorene (50 mg, 0.30
mmol) and toluene (2 mL) were allowed to react in 20 mL resealable pressure tube according to
method A to afford 9-(4-fluorobenzyl)-9H-fluorene 3k (74 mg, 90 %) as a white solid. Melting
point: 136−138 °C. 1H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 7.6 Hz, 2H), 7.38 (t, J = 7.3 Hz,
2H), 7.27-7.20 (m, 4H), 7.15 (m, 2H), 6.98 (t, J = 8.6 Hz, 2H), 4.22 (t, J = 7.4 Hz, 1H), 3.14 (d, J
= 7.4 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3) δ 161.7 (d, J = 242.5 Hz), 146.6, 141.0, 135.3
(d, J = 3.2 Hz), 131.00 (d, J = 7.8 Hz), 127.3, 126.8, 124.8, 120.0, 115.1 (d, J = 20.9 Hz), 48.8,
39.2. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C20H16F 275.1236; Found 275.1223.
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9-(3-Trifluorobenzyl)-9H-fluorene (3l): [Ru(p-cymene)Cl2]2 (5.4 mg, 0.009 mmol), t-BuOK
(50.50 mg, 0.45 mmol), 3-trifluorobenzyl alcohol (79 mg, 0.45 mmol), 9H-fluorene (50 mg, 0.30
mmol) and toluene (2 mL) were allowed to react in 20 mL resealable pressure tube according to
method A to afford 9-(3-trifluorobenzyl)-9H-fluorene 3l (74 mg, 75 %) as a white solid. Melting
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point: 92−94 °C. H NMR (400 MHz, CDCl3) δ 7.72 (d, J = 7.5 Hz, 2H), 7.48 (d, J = 7.6 Hz,
1H), 7.41 (s, 1H), 7.39 – 7.29 (m, 4H), 7.25 – 7.18 (m, 4H), 4.25 (t, J = 7.2 Hz, 1H), 3.21 (d, J =
13
7.2 Hz, 2H). C{1H} NMR (100 MHz, CDCl3) δ 146.2, 141.0, 140.4, 133.0, 130.5 (q, J = 31.7
Hz), 128.6, 127.4, 126.8, 126.4 (q, J = 3.5 Hz), 124.8, 124.3 (q, J = 270 Hz), 123.3 (q, J = 3.7
Hz), 120.0, 48.4, 39.8. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C21H16F3 325.1204; Found
325.1195.
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9-(3-Chlorobenzyl)-9H-fluorene (3m)21: [Ru(p-cymene)Cl2]2 (5.4 mg, 0.009 mmol), t-BuOK
(50.50 mg, 0.45 mmol), 3-chlorobenzyl alcohol (64 mg, 0.45 mmol), 9H-fluorene (50 mg, 0.30
mmol) and toluene (2 mL) were allowed to react in 20 mL resealable pressure tube according to
method A to afford 9-(3-chlorobenzyl)-9H-fluorene 3m (78 mg, 88 %) as a white solid. Melting
point: 118−120 °C. 1H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 7.6 Hz, 2H), 7.41 (t, J = 7.4 Hz,
2H), 7.31 – 7.22 (m, 7H), 7.11 (d, J = 6.2 Hz, 1H), 4.26 (t, J = 7.5 Hz, 1H), 3.14 (d, J = 7.5 Hz,
2H). 13C{1H} NMR (100 MHz, CDCl3) δ 146.4, 141.8, 140.9, 134.1, 129.7, 129.6, 127.8, 127.4,
126.9, 126.7, 124.8, 120.0, 48.5, 39.8.
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9-(3-Phenylpropyl)-9H-fluorene (3n): [Ru(p-cymene)Cl2]2 (5.4 mg, 0.009 mmol), t-BuOK
(50.50 mg, 0.45 mmol), 3-phenylpropyl alcohol (62 mg, 0.45 mmol), 9H-fluorene (50 mg, 0.30
mmol) and toluene (2 mL) were allowed to react in 20 mL resealable pressure tube according to
method A to afford 9-(3-phenylpropyl)-9H-fluorene 3n (53 mg, 61 %) as a white solid. Melting
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point: 68−70 °C. H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 7.3 Hz, 2H), 7.50 (d, J = 7.3 Hz,
2H), 7.38 (t, J = 7.4 Hz, 2H), 7.32 (td, J = 7.3, 1.2 Hz, 2H), 7.26 (vt, J = 6.8 Hz, 2H), 7.18 (t, J =
7.3 Hz, 1H), 7.11 (d, J = 7.3 Hz, 2H), 4.02 (t, J = 5.8 Hz, 1H), 2.59 (t, J = 7.7 Hz, 2H), 2.09 (m,
2H), 1.58 – 1.48 (m, 2H). 13C{1H} NMR (100 MHz, CDCl3) δ 147.4, 142.3, 141.2, 128.5, 128.3,
127.0, 126.9, 125.8, 124.4, 119.9, 47.4, 36.2, 32.6, 27.3. HRMS (ESI-TOF) m/z: [M]+ Calcd for
C22H20 284.1565; Found 284.1562.
2-(9H-Fluoren-9-yl)methylfuran (3o)21: [Ru(p-cymene)Cl2]2 (5.4 mg, 0.009 mmol), t-BuOK
(50.50 mg, 0.45 mmol), furan-2-methanol (41 mg, 0.45 mmol), 9H-fluorene (50 mg, 0.30 mmol)
and toluene (2 mL) were allowed to react in 20 mL resealable pressure tube according to method
A to afford 2-(9H-Fluoren-9-yl)methylfuran 3o (45 mg, 61 %) as a white solid. Melting point:
62−64 °C. 1H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 7.5 Hz, 2H), 7.43 (d, J = 1.5 Hz, 1H), 7.37
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(t, J = 7.4 Hz, 2H), 7.28 – 7.23 (m, 2H), 7.19 (dd, J = 7.3, 0.6 Hz, 2H), 6.35 (dd, J = 3.1, 1.9 Hz,
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1H), 5.98 (dd, J = 3.2, 0.7 Hz, 1H), 4.33 (t, J = 7.6 Hz, 1H), 3.10 (d, J = 7.6 Hz, 2H). C{1H}
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NMR (100 MHz, CDCl3) δ 153.8, 146.6, 141.2, 140.9, 127.3, 127.0, 124.7, 119.9, 110.5, 107.2,
46.3, 32.4. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C18H15O 247.1123; Found 247.1122.
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2-(9H-Fluoren-9-yl)methylthiophene (3p)21: [Ru(p-cymene)Cl2]2 (5.4 mg, 0.009 mmol), t-BuOK
(50.50 mg, 0.45 mmol), thiophene-2-methanol (52 mg, 0.45 mmol), 9H-fluorene (50 mg, 0.30
mmol) and toluene (2 mL) were allowed to react in 20 mL resealable pressure tube according to
method A to afford 2-(9H-fluoren-9-yl)methylthiophene 3p (49 mg, 62 %) as a white solid.
Melting point: 95−97 °C. 1H NMR (400 MHz, CDCl3) δ 7.73 (d, J = 7.4 Hz, 2H), 7.36 (t, J = 7.2
Hz, 2H), 7.31 – 7.22 (m, 4H), 7.12 (dt, J = 5.0, 1.2 Hz, 1H), 6.88 (ddd, J = 5.2, 3.5, 1.8 Hz, 1H),
6.72 – 6.69 (m, 1H), 4.23 (t, J = 7.0 Hz, 1H), 3.39 (d, J = 6.9 Hz, 2H). 13C{1H} NMR (100 MHz,
CDCl3) δ 146.2, 142.1, 141.0, 127.4, 126.9, 126.6, 126.0, 124.7, 123.8, 119.9, 49.0, 34.0. HRMS
(ESI-TOF) m/z: [M+H]+ Calcd for C18H15S 263.0894; Found 263.0892.
9-Octyl-9H-fluorene (3q)21: [Ru(p-cymene)Cl2]2 (5.4 mg, 0.009 mmol), t-BuOK (50.50 mg, 0.45
mmol), octanol (78 mg, 0.60 mmol), 9H-fluorene (50 mg, 0.30 mmol) and toluene (2 mL) were
allowed to react in 20 mL resealable pressure tube according to method A to afford 9-octyl-9H-
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fluorene 3q (39 mg, 47 %) as sticky yellow oil. H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 7.1
Hz, 2H), 7.52 (d, J = 7.7 Hz, 2H), 7.39 – 7.28 (m, 4H), 3.98 (t, J = 5.9 Hz, 1H), 2.00 (m, 2H),
1.24 (m, 12H), 0.86 (t, J = 7.0 Hz, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 147.7, 141.2, 127.0,
126.9, 124.4, 119.8, 47.6, 33.2, 31.9, 30.1, 29.5, 29.4, 25.8, 22.7, 14.2.
9-Hexyl-9H-fluorene (3r)21: [Ru(p-cymene)Cl2]2 (5.4 mg, 0.009 mmol), t-BuOK (50.50 mg, 0.45
mmol), hexanol (62 mg, 0.60 mmol), 9H-fluorene (50 mg, 0.30 mmol) and toluene (2 mL) were
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allowed to react in 20 mL resealable pressure tube according to method A to afford 9-hexyl-9H-
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fluorene 3r (62 mg, 82 %) as sticky yellow oil. H NMR (400 MHz, CDCl3) δ 7.78 (d, J = 7.1
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Hz, 2H), 7.54 (dd, J = 7.5, 0.9 Hz, 2H), 7.38 (m, 2H), 7.33 (td, J = 7.4, 1.3 Hz, 2H), 4.00 (d, J =
5.9 Hz, 1H), 2.02 (m, 2H), 1.24 (m, 8H), 0.86 (t, J = 6.9 Hz, 3H). 13C{1H} NMR (100 MHz,
CDCl3) δ 147.7, 141.2, 126.94, 126.9, 124.4, 119.8, 47.5, 33.1, 31.6, 29.6, 25.7, 22.6, 14.1.
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9-Butyl-9H-fluorene (3s)20: [Ru(p-cymene)Cl2]2 (5.4 mg, 0.009 mmol), t-BuOK (50.50 mg, 0.45
mmol), butanol (45 mg, 0.60 mmol), 9H-fluorene (50 mg, 0.30 mmol) and toluene (2 mL) were
allowed to react in 20 mL resealable pressure tube according to method A to afford 9-butyl-9H-
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fluorene 3s (60 mg, 89 %) as sticky yellow oil. H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 7.3
Hz, 2H), 7.52 (d, J = 7.3 Hz, 2H), 7.36 (t, J = 7.1 Hz, 2H), 7.31 (td, J = 7.4, 1.1 Hz, 2H), 3.98 (t,
J = 5.9 Hz, 1H), 2.04 – 1.97 (m, 2H), 1.32 – 1.23 (m, 2H), 1.17 (m, 2H), 0.83 (t, J = 7.2 Hz, 3H).
13C{1H} NMR (100 MHz, CDCl3) δ 147.7, 141.2, 126.96, 126.90, 124.4, 119.9, 47.6, 32.9, 27.9,
23.1, 14.0.
9-Propyl-9H-fluorene (3t)16d: [Ru(p-cymene)Cl2]2 (5.4 mg, 0.009 mmol), t-BuOK (50.50 mg,
0.45 mmol), propanol (36 mg, 0.60 mmol), 9H-fluorene (50 mg, 0.30 mmol) and toluene (2 mL)
were allowed to react in 20 mL resealable pressure tube according to method A to afford 9-
propyl-9H-fluorene 3t (48 mg, 78 %) as sticky yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.77 (d,
J = 7.3 Hz, 2H), 7.54 (d, J = 7.3 Hz, 2H), 7.35 (m, 4H), 4.00 (d, J = 5.4 Hz, 1H), 2.00 (m, 2H),
1.34 – 1.20 (m, 2H), 0.94 – 0.86 (m, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 147.7, 141.2,
127.0, 126.9, 124.4, 119.9, 47.5, 35.5, 19.1, 14.5.
9-Benzyl-9H-fluoren-2-amine (3u)17c: [Ru(p-cymene)Cl2]2 (5.4 mg, 0.009 mmol), t-BuOK
(50.50 mg, 0.45 mmol), benzyl alcohol (48.73 mg, 0.45 mmol), 2-aminofluorene (54 mg, 0.30
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mmol) and toluene (2 mL) were allowed to react in 20 mL resealable pressure tube according to
method A to afford 9-benzyl-9H-fluoren-2-amine 3u (35 mg, 46 %) as a brownish solid. Melting
point: 119−121 °C. 1H NMR (400 MHz, CDCl3) δ 7.47 (d, J = 7.5 Hz, 1H), 7.40 (d, J = 8.4 Hz,
1H), 7.27 – 7.14 (m, 6H), 7.00 – 6.95 (m, 2H), 6.55 (dd, J = 8.0, 2.0 Hz, 1H), 6.35 (d, J = 1.7 Hz,
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1H), 4.02 (t, J = 7.6 Hz, 1H), 2.97 (d, J = 8.7 Hz, 2H). C{1H} NMR (101 MHz, CDCl3) δ
148.8, 146.0, 145.6, 141.3, 140.1, 132.1, 129.6, 128.4, 127.1, 126.4, 125.1, 124.6, 120.7, 118.6,
114.3, 111.8, 48.6, 40.3. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C20H18N 272.1439; Found
272.1440.
N,9-Dibenzyl-9H-fluoren-2-amine (3u΄): [Ru(p-cymene)Cl2]2 (5.4 mg, 0.009 mmol), t-BuOK
(50.50 mg, 0.45 mmol), benzyl alcohol (48.73 mg, 0.45 mmol), 2-aminofluorene (54 mg, 0.30
mmol) and toluene (2 mL) were allowed to react in 20 mL resealable pressure tube according to
method A to afford N,9-dibenzyl-9H-fluoren-2-amine 3u΄ (40 mg, 40 %) as a brownish solid.
Melting point: 75−77 °C. 1H NMR (400 MHz, CDCl3) δ 7.44 (m, 2H), 7.25 (d, J = 2.0 Hz, 4H),
7.19 – 7.09 (m, 7H), 6.99 (s, 2H), 6.51 (dd, J = 8.1 Hz 1H), 6.28 (s, 1H), 4.17 (s, 2H), 4.01 (t, J =
7.5 Hz, 1H), 3.03 (dd, J = 13.5, 7.5 Hz 1H), 2.91 (dd, J = 13.5, 8.0 Hz 1H). 13C{1H} NMR (101
MHz, CDCl3) δ 148.6, 147.3, 145.8, 141.4, 140.0, 139.3, 129.6, 128.6, 128.2, 127.5, 127.2,
127.0, 126.2, 124.7, 124.4, 120.5, 118.3, 112.3, 109.2, 48.6, 48.4, 40.4. HRMS (ESI-TOF) m/z:
[M+H]+ Calcd for C27H24N 362.1909; Found 362.1913.
9-Benzhydryl-9H-fluorene (5a)21: [Ru(p-cymene)Cl2]2 (9.1 mg, 0.015 mmol), t-BuOK (67mg,
0.60 mmol), benzhydrazol (110 mg, 0.60 mmol), 9H-fluorene (50 mg, 0.30 mmol) and toluene (2
mL) were allowed to react in 20 mL resealable pressure tube according to method B to afford 9-
benzhydryl-9H-fluorene 5a (66 mg, 66 %) as a white solid. Melting point: 218−220 °C 1H NMR
(400 MHz, CDCl3) δ 7.69 (d, J = 7.6 Hz, 2H), 7.32 – 7.19 (m, 12H), 6.99 (t, J = 7.5 Hz, 2H),
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