Aldehyde/ketone-catalyzed highly selective synthesis of 9-monoalkylated fluorenes by dehydrative C-alkylation with primary and secondary alcohols

Article abstract of DOI:10.1039/c6gc02518h

By using aldehydes or ketones as the catalyst and screening CsOH out as the more effective base than KOH in many instances, an efficient 9-C-alkylation of fluorenes with alcohols was achieved to provide a green and practical method for general synthesis of the useful 9-monoalkylated fluorenes in high selectivities. This new method tolerates a wide range of substrates including activated and unactivated primary and secondary alcohols, thus solving the issues remaining in the field and largely broadening the diversity of the 9-monoalkylated fluorenes. Consequently, fine-tuning of the alkylated fluorenes was made possible to provide specific fluorene monomers for function-oriented polyfluorenes. Preliminary mechanistic studies revealed that the external carbonyl compounds can be quantitatively regenerated and recovered in the reaction cycle.

Full text of DOI:10.1039/c6gc02518h

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DOI: 10.1039/C6GC02518H
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Aldehyde/Ketone‐Catalyzed Highly Selective Synthesis of 9‐
Monoalkylated Fluorenes by Dehydrative C‐Alkylation with
Primary and Secondary Alcohols†
Received 00th January 20xx,
Accepted 00th January 20xx
Jianhui Chen,‡a Yang Li,‡a Shuangyan Li,a Jianping Liu,a* Fei Zheng,a Zhengping Zhang,a and Qing
DOI: 10.1039/x0xx00000x
Xua,b*
By using aldehydes or ketones as the catalyst and screening CsOH method is, similar to the basic dialkylation reactions,2‐3 the
out as the more effective base than KOH in many instances, an direct monoalkylation of fluorenes with excess alkyl halides in
efficient 9‐C‐alkylation of fluorenes with alcohols was achieved to the presence of n‐BuLi under harsh conditions,5 but this
provide a green and practical method for general synthesis of the method gave only low to moderate yields of the target 9‐
useful 9‐monoalkyled fluorenes in high selectivities. This new monoalkylated fluorenes, most possibly due to the difficult‐to‐
method tolerates a wide range of substrates including acitvated control dialkylation as the side‐reaction.2 The other one is the
and unactivated primary and secondary alcohols, thus solving the dehydrative alkylation of fluorenes with alcohols,6 but large
issues remained in the field and largely broadened the diversity of excess amounts of KOH and alcohols as well as forcing reaction
the 9‐monoalkylated fluorenes. Consequently, fine‐tuning of the conditions were required, and these methods were mainly
alkylated fluorenes was made possible to provide specific fluorene limited to the more active (hetero)benzylic primary alcohols. In
monomers for function‐oriented polyfluorenes. Preliminary contrast, the direct alkylation of fluorenes with long chain
mechanistic studies revealed that the external carbonyl aliphatic alcohols could not be easily achieved, which was
compounds can be quantitatively regenerated and recovered in alternatively accomplished by initial basic condensation of
the reaction cycle.
fluorenes with aldehydes followed by Pd‐catalyzed
hydrogenation of the alkene intermediates.6b Moreover,
alkylation with secondary alcohols was not known yet. Due to
these limitations, there is still a great need to develop a
general but more efficient and practical method for selective
synthesis of the useful 9‐monoalkylated fluorenes, especially
by reactions using more effective catalysts under milder
Due to their unique optical, electrical, and semiconducting
properties, π‐conjugated polymers such as polyfluorenes are
promising photoelectrical materials widely applied in
optoelectronic devices such as polymer light emitting diodes
(PLEDs), polymer solar cells, field effect transistors,
electrochromic devices, and so on.1‐7 Therefore, synthesis of 9‐
monoalkylated and 9,9‐dialkylated fluorene monomers have
attracted much attention in the past decades as they are key
starting materials for poly(alkylfluorene)s.2‐7 With the 9‐carbon
position vacant for further transformations to unsymmetrical
9,9‐difunctionalized fluorenes with oriented functional groups
and hence oriented chemical, physical, and photoelectric
properties, 9‐monoalkylated fluorenes are a class of attractive
building blocks (Scheme 1).1,5‐7 However, in comparison with
the ready synthesis of symmetrical 9,9‐dialkylated fluorenes by
strong base‐mediated (n‐BuLi or NaOH) direct 9,9‐dialkylation
of fluorenes with excess alkyl halides,2‐3 methods for selective
9‐monoalkylation of fluorenes are still underdeveloped.5‐6 One
conditions.
R
direct
di-alkylation
1st
momo-alkylation
(R1 = R2)
2nd
R
R
R
momo-alkylation
(R1 ≠ R2)
R1 R2
R1
functionalization
R
*
n
*
R1 R2
R1 FG
(FG: functional groups)
optoelectronic
devices, etc.
a College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou,
Zhejiang 325035, P. R. China. E‐mail: 518liujianping@163.com; qing‐
xu@wzu.edu.cn; Fax: (+)‐86‐577‐86689302; Tel: (+)‐86‐138‐57745327
b School of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou,
Jiangsu 225002, China
† Electronic Supplementary Information (ESI) available: Experimental details,
product characterization, details of mechanistic studies, and copies of 1H and 13C
NMR spectra of the products. See DOI: 10.1039/x0xx00000x
Scheme 1. General transformation of fluorenes.
Alcohols are a class of comparatively greener chemicals
frequently used as alkylating reagents in synthesis.8‐10 In our
continuous work on alcohols‐based alkylation and aerobic
oxidative reactions,10‐12 we have also developed some efficient
‡ These two authors contributed equally to this work.
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and selective aldehyde/ketone‐catalyzed or autocatalyzed under the same conditions and gave a high yield of 3a (run 5).
View Article Online
dehydrative N‐ and C‐alkylation reactions (Scheme 2A).13 The In contrast, KOH, although reported tDoObI:e10.a103g9o/oCd6GbCa02s5e18iHn
groups of Wu and Shi also independently reported a ketone‐ previous alkylation of fluorenes with alcohols (but used in
initiated C‐alkylation of indoles and pyrroles with secondary large amounts and under harsh conditions),6 gave only a
alcohols (Scheme 2B)14 and a conjugate ketone‐catalyzed N‐ moderate yield of 3a under the present conditions (run 4).
alkylation of amines with primary alcohols (Scheme 2C).15 We Although KOH and CsOH are both strong alkali bases having
envisioned that aldehydes or ketones may also catalyze the 9‐ several similarities, the above results clearly showed their
monoalkylation of fluorenes with primary benzylic and great difference in this alcohol‐based dehydrative alkylation of
aliphatic alcohols even the secondary alcohols to afford a fluerenes, which may in part due to the interesting “cesium
general, efficient and practical method for selective synthesis effect” documented in the literature.16 CsOH was then chosen
of 9‐monoalkylated fluorenes (Scheme 2D), thus solving the as the best base for further optimization of the reaction
issues remained in the research and broadening the diversity conditions. Moreover, no obvious product formation was
of the useful 9‐monoalkylated fluorenes. Herein we report our observed without either PhCHO or CsOH (runs 6‐7), revealing
own findings in this research.
that they are both crucial and essential to the reaction. Under
an atmosphere of air, the yield of 3a decreased with formation
of byproduct 5a (run 8), suggesting that the reaction is better
performed under an inert atmosphere. Further evaluating the
influences of the reaction temperature and time, loadings of
the base and catalyst (runs 9‐12) showed that reduced catalyst
loading could improve the selectivity of 3a, and the
highest >99% selectivity and a high 95% isolated yield of 3a
could be obtained by using only 10 mol% PhCHO (run 12). To
check whether CsOH is the best base and whether KOH works
well or not under the optimized conditions, the same reaction
was also investigated using 20 mol% KOH instead of CsOH. The
results showed that KOH only led to a moderate 53% GC yield
of target 3a in a much lower selectivity of 58% as well as 38%
GC yield of the by‐product 4a in a selectivity of 42% (run 13).
This result clearly revealed that CsOH is a much more effective
base than KOH for the present reaction.
A. Aldehyde/Ketone-Catalyzed or -Autocatalyzed N- and C-Alkylation of Amines,
Amides, Seconday Alcohols, and Methyl Ketones with Alcohols13
OH
cat. R1CHO
or cat. R3COCH3
- H2O
OH
H
R1
N
R2-NH2
O
R1 OH
or
or
+
R2
R3
R1
R3 CH3
R2COCH3
-autocatalyzed
- H2O
OH
O
R1 OH
or
R1
R2
R2
R1
+
R2 CH3
B. Ketone-Initiated C-Alkylation of Indoles and Pyrroles with Secondary Alcohols14
R1
O
R2
OH
R3 R4
- H2O
cat.
+
R1 R2
N
R
N
R
C. Conjugated Ketone-Catalyzed N-Alkylation of Amines with Primary Alcohols15
O
R3
R4
cat.
H
R1
N
X
R1 OH
R2-NH2
R2
+
- H2O
D. Aldehyde/Ketone-Catalyzed Highly Selective 9-Monoalkylation of Fluorenes
with Primary and Secondary Alcohols (This work)
Table 1. Condition Optimization for Dehydrative 9‐C‐
R
R
Monobenzylation of Fluorene.a
OH
R
cat. R1CHO
+
R1 R2
or cat. R1COR2
- H2O
R3
R1
cat. PhCHO
+
OH
Ph
R1 R2
R1 = aryl, heteroaryl, alkyl
2 = H, aryl, alkyl
R1-R2 = cycloalkyl
R2
N2, base, toluene, T, 12 h
1a
R
R3 = alkyl, aryl
- H2O
up to 97% isolated yield
up to >99% selectivity
2a
Ph
3a
Scheme 2. Aldehydes/Ketones‐catalyzed Dehydrative N‐ and
C‐alkylation reactions with Alcohols.
4a
5a
O
Ph
run cat. (mol%)
base (mol%)
T (oC)
3a%b
4a%b
The model monoalkylation reaction of benzyl alcohol (1a
)
1
2
3
4
5
20
20
20
20
20
‐
20
20
20
20
20
10
10
K2CO3 (20)
Cs2CO3 (20)
NaOH (20)
130
130
130
130
130
130
130
130
110
110
110
130
130
trace
13
5
64
92
trace
trace
88
41
74
4
8
5
and fluorene (2a) was initially performed under air as in some
previous alkylation reactions.13 In addition to the normal
unsaturated 9‐benzylidenefluorene byproduct (4a), a small
amount of fluorenone byproduct (5a) was also found to be
generated in the reaction, most possibly due to oxidation by
air under the basic conditions. To obtain reliable and
repeatable results, the reaction was then carried out under
nitrogen atmosphere. On the other hand, realizing bases’
crucial roles in alcohol‐based dehydration alkylation reactions
as we have observed in many cases in previous studies,11‐13 we
firstly investigated the bases’ effect on the reaction to obtain
the best base for this specific reaction. As shown in Table 1,
while other bases gave only low to moderate yields of the
KOH (20)
trace
8
trace
trace
9
10
26
16
‐
CsOH∙H2O (20)
CsOH∙H2O (20)
‐
CsOH∙H2O (20)
CsOH∙H2O (20)
CsOH∙H2O (20)
CsOH∙H2O (40)
CsOH∙H2O (20)
KOH (20)
6
7
8c
9
10d
11
12
13
84
99 (95)
53
38
a
Unless otherwise noted, the mixture of 1a (4 mmol, 1.33 equiv.), 2a
o
target 9‐benzyl fluorene (3a) at 130 C in the presence of 20
mol% PhCHO (runs 1‐3), CsOH exhibited much higher activity
(3 mmol), PhCHO, and base in toluene (0.5 mL) was sealed under N2 in
a 20 mL Schlenk tube, heated for 12 h, and monitored by GC‐MS
2 | J. Name., 2012, 00, 1‐3
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b
c
Table 2. Aldehydes‐Catalyzed Selective 9‐C‐Monolkylation of
and/or TLC. GC yields (isolated yields in parenthesis) based on 2a
.
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Reaction performed in air. Formation of 3% 5a observed. d 24 h.
Fluorenes with (Hetero)Aryl Methanols and Primary Aliphatic
DOI: 10.1039/C6GC02518H
Alcohols.a
R1CHO (10 mol%)
R
The optimized conditions were then applied to other
benzylic alcohols to extend the scope of the selective 9‐C‐
monoalkylation method. As shown in Table 2, like benzyl
alcohol 1a (run 1), electron‐rich and –deficient benzylic
alcohols, including those with sterically more bulky ortho‐
substituents (runs 5, 9, 12) and those bearing reactive fluoro,
chloro, and bromo groups (runs 6‐11), all reacted efficiently
with 2a to give generally good to high yields of the target 9‐
monoalkylated fluorenes under the standard conditions (runs
2‐13). The halogen groups‐substituted products should be
promising chemicals in synthesis because they can be readily
converted into other useful compounds by further
transformations utilizing the reactive halogen groups. In
addition to benzylic alcohols, heteroaryl methanols such as the
pyridyl methanols (runs 14‐16), furyl methanol (run 17), and
thienyl methanol (run 18) also reacted efficiently with 2a to
give good to high yields of the target products. Like
unsubstituted fluorene and other halo‐substituted alcohols, 2‐
bromofluorene also reacted with benzyl alcohol to give a high
yield of the product with the reactive bromo group remained
intact under the basic conditions (run 19).
We then turned to the more demanding reactions of
aliphatic alcohols, which are known to be much less reactive as
alkylating reagents than the (hetero)benzylic alcohols and
usually require much harsher reaction conditions and
transition metal catalysts in the alkylation reactions. 8 Thus, n‐
octanol (n‐C8H17OH) was employed to react with 2a under the
above standard conditions. Only a moderate 52% GC yield of
the target product 6a was obtained after prolonged 24 h
(Table, 2, run 20). Further condition screening on the reaction
temperature, time, and base and catalyst loadings17 showed
that simply increasing the base loading to 75 mol% could
ensure a complete conversion of the reactants under the same
conditions, giving a high 97% isolated yield of 6a in a high
selectivity of >99% over the by‐product 7a (run 21). To check
whether CsOH is also the best base for the reactions of
aliphatic alcohols, 75 mol% KOH was then tested. However,
only 47% GC yield of 6a was detected in a much lower
selectivity of 87% (run 22). In this reaction, 6a was difficult to
be isolated pure due to the low selectivity. This result revealed
again that CsOH is also the best base for reactions using
aliphatic alcohols as the alkylating reagents.
R
CsOH H2O (20 mol%)
N2, toluene, 130 oC, 12 h
Ar/R1 OH
+
1
- H2O
Ar/R1
2
3, 6
(1) : Ar = Ph, 95%
3a
(7) 3g: Ar = 4-ClC6H4, 85%
(8) 3h: Ar = 3-ClC6H4, 82%
(9) 3i: Ar = 2-ClC6H4, 90%
(10) 3j: Ar = 4-BrC6H4, 82%
(11) 3k: Ar = 3-BrC6H4, 68%
(2) 3b: Ar = 4-MeC6H4, 87%
(3) 3c: Ar = 4-MeOC6H4, 93%
(4) 3d: Ar = 3-MeOC6H4, 93%
(5) 3e: Ar = 2-MeOC6H4, 90%
(6) 3f: Ar = 4-FC6H4, 80%
Ar
N
N
(12) 3l: 45%
(14) 3n: 81%
(15) 3o: 85%
(13) 3m: 89%
Br
N
S
O
Ph
(19) 3s: 85%
(16) 3p: 88%
(17) 3q: 85%
(18) 3r: 84%
(20) CsOH H2O (20 mol%), 130 oC, 24 h
6a: (52%)b
(21) CsOH H2O (75 mol%), 130 oC, 24 h
6a: 97% (99%),b 6a/7a >99/1
(22) KOH (75 mol%), 130 oC, 24 h
6a: (47%),b 6a/7a 87/13
n-C7H15
n-C7H15
6a
7a
(23)c 6b: R1 = n-C3H7, 75%
(24)c 6c: R1 = n-C4H9, 90%
(25)c 6d: R1 = n-C5H11, 95%
(26)c 6e: R1 = n-C6H13, 97%
(27)c 6f: R1 = n-C8H17, 94%
(28)c 6g: R1 = n-C9H19, 80%
(29)c 6h: R1 = n-C11H23, 80%
R1
(30)c 6i: R1 = n-C4H9, 77%
(31)c 6j: R1 = n-C6H13, 78%
(32)c 6k: R1 = n-C7H15, 83%
(33)c 6l: R1 = n-C8H17, 81%
(34)c 6m: R1 = n-C9H19, 87%
(35)c 6n: R1 = n-C11H23, 92%
Br
R1
a
Unless otherwise noted, see run 12 of Table 1 for detailed conditions.
Isolated yields based on 2. Unless otherwise noted, the ratios of target
product/by‐product 3/4 and 6/7 are >99/1. b The yields in parenthesis are GC
yields. c 75 mol% CsOH∙H2O, 130 oC, 24 h.
to its low availability in the past.1‐7 The reason that 9‐sec‐alkyl
fluorenes have not been achieved by previous dehydrative
alkylation of fluorenes with alcohols6 is possibly because even
harsher reaction conditions than the reported harsh conditions
for the more reactive benzylic alcohols may be required and
the lack of an efficient and milder catalytic method. The
reason that they have also not been obtained by coupling of
fluorenes with secondary alkyl halides may be that the
secondary alkyl halides are prone to undergo elimination
reactions to give alkene byproducts under the strong basic
A series short to long chain aliphatic alcohols were then
investigated in the reactions with 2a, all giving good to high
yields of the target 9‐alkylated fluorenes under the same
conditions (runs 23‐29). Even under the present more basic
conditions with 75 mol% of CsOH, 2‐bromofluorene also
reacted efficiently with these aliphatic alcohols to give good to
high yields of the target products with the reactive bromo
moiety remained intact (runs 30‐35).
We then investigated the possibility of using secondary
alcohols as the alkylating reagents to obtain 9‐sec‐alkyl
fluorenes, which, to our knowledge, have not been
investigated much in polyfluorene materials most possibly due
conditions.2,3 To test our assumption, 1‐phenyl ethanol (8a
)
was used to react with 2a at 130 oC, giving only a low yield of
the target product 9a even when 50 mol% of CsOH was used
(Table 3, run 1). Enhancing the base loading and the reaction
temperature both worked to improve the product’s yields
o
(runs 2‐3). Thus, the reaction was best carried out at 160 C
using 100 mol% of CsOH (run 4), which ensured an almost
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complete conversion of the reactant (94%) and gave a high 11). The reaction of a sterically more bulky benzylic
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DOI: 10.1039/C6GC02518H
88% isolated yield of 9a in a high selectivity of >99%. In tetrahydronaphthalenyl alcohol is also efficient under the
contrast, the same reaction using 100 mol% KOH gave only same conditions in the presence of CsOH, giving 75% isolated
70% isolated yield of 9a with a lower selectivity of 95%, as well yield of the target product 9e in high selectivity (run 12).
as the detection of ca. 4% yield of by‐product 10a by GC (run However, the same reaction with KOH was rather inefficient,
5). These results revealed again that CsOH still may be the best giving only 28% yield of the product (run 13). Moreover,
base even in the cases of secondary alcohols.
sterically bulky symmetrical secondary alcohols such as
benzohydrol and cyclopentanol also gave the target products
Table 3. Ketone‐Catalyzed 9‐C‐Monoalkylation of Fluorenes in high yields and selectivity in the presence of CsOH (runs 14
with Secondary Alcohols.a
and 16); while the corresponding reactions using KOH as the
base gave lower yields and selectivities of the products (runs
15 and 17). In the reaction of cyclopentanol with KOH (run 17),
the product could not be isolated pure due to low conversion
of the reactants and low selectivity (run 17). As to other
sterically bulky secondary aliphatic alcohols such as 2‐heptanol
and 2‐octanol that were usually unreactive in usual alkylation
reactions, they were also found to be effective alkylating
reagents in this reaction by using CsOH as the base (runs 18
and 20), giving high yields of the products in high selectivity. In
contrast, conversions of the same reactions using KOH as the
base were not complete, which led to difficult purification of
the products from the unreacted fluorene 2a (runs 19 and 21).
Finally, in the cases of sterically more hindered internal cyclic
cyclohexanol and linear 3‐pentanol, both the reactions using
CsOH and KOH as the base were less efficient and less selective
(runs 22‐25), which can be attributed to the stronger steric
repulsion generated during the reaction and the difficulty in
the transfer hydrogenation of intermediates 10 by the alcohol
substrates (vide infra). Thus, only low to moderate yields of
the products in lower selectivities were obtained using either
CsOH or KOH (runs 22‐25). Even there are unsatisfactory
results at present (runs 22 and 24), the above results still
revealed clearly that CsOH is generally a more advantageous
base than KOH in most cases of secondary alcohols.
As shown in most of the reactions using CsOH as the base,
the target 9‐monoalkylated fluorenes could generally be
obtained in high selectivities (>99%). These results clearly
revealed that: 1) CsOH is a more effective base than other
bases including KOH6 in many examples of 9‐C‐monoalkylation
reaction of fluorenes; 2) due to the generally high efficiencies
of the reactions and high selectivities and good to high yields
of the target products despite of the different steric and
electronic properties of the reactants, fine‐tuning of the
substituents and the steric and electronic properties of the 9‐
alkylated fluorenes are now possible. This is very important in
substituted fluorene synthesis since, in function‐oriented
polyfluorene materials, monomers of specific structures with
specific functional groups of specific steric or electronic
properties are usually required for special purposes.1‐7
a
Unless otherwise noted, the mixture of 2a (1 mmol), 7 (1.2 mmol, 1.2
equiv.), ketone (10 mol%), and CsOH∙H2O (100 mol%) in toluene (1 mL) was
sealed under N2 in a 20 mL Schlenk tube, heated at 160 C for 24 h, and
monitored by GC‐MS and/or TLC. Isolated yields based on 2. GC yields in
parenthesis based on 2. 100 mol% KOH. The products could not be
isolated pure from fluorene 2a due to incomplete conversion of 2a.
o
b
c
d
As shown in Table 3, various types of secondary alcohols
could be tolerated in this method. Thus, except the one with a
reactive chloro group at the meta‐position that gave a
moderate yield of the product (run 10), 1‐aryl ethanols usually
gave good yields of the products in high selectivities under the
optimized conditions (runs 6 and 8). In contrast, the same
reactions using 100 mol% KOH as the base gave products in
slightly lower yields and/or lower selectiviteis (runs, 7, 9, and
To certify that the selective 9‐momoalkylation of fluorenes
underwent
a carbonyl compounds‐catalyzed mechanism
(Scheme 3) similar to our previous aldehye‐ or ketone‐
catalyzed N‐ and C‐alkylation reactions,13 key steps of the
reaction was investigated. As shown in eq. 1, 9‐
benzylidenefluorene (4a) could be readily obtained in 80%
yield from the reaction of fluorene and benzaldehyde using 20
mol% CsOH at 100 oC, supporting the initial step of the
4 | J. Name., 2012, 00, 1‐3
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reaction mechanism (Scheme 3, step i). Then, transfer synthesis of the useful unsymmetrical 9,9‐difunctionalized
View Article Online
DOI: 10.1039/C6GC02518H
hydrogenation of 4a by
a secondary alcohol 8l was fluorenes.
investigated in the presence of 20 mol% CsOH (eq. 2). 1H NMR
spectroscopic analysis of the reaction mixture revealed that, in
addition to the generation of the target product 3a, 1 equiv. of
TBAI (20 mol%)
NaOH/H2O (50%)
N2, 80 oC, 24 h
(3)
n-C4H9Br
+
n-C4H9
12, 85% isolated yield
Ph
3a
Ph
ketone 11 (11/3a = 0.99/1.00) was also generated at the same
time.16 This result indicated that the added carbonyl catalyst
can be regenerated quantitatively in the transfer
hydrogenation step (Scheme 3, step ii) and will be recycled to
participate in next reaction cycle as the intermediate/catalyst.
In contrast, no reaction occurred with control reactions in the
absence of CsOH, showing again the crucial role of CsOH in the
reaction. Therefore, as shown in Scheme 3, a mechanism
involving the initial condensation of fluorenes with the
externally‐added carbonyl compounds (step i) followed by
transfer hydrogenation of the 9‐alkylidenefluorene
Cl
CsOH H2O (1.5 equiv.)
N2, MeCN, 80 oC, 24 h
(4)
+
Ph
O2N
NO2
13, 75% isolated yield
Ph
3a
Conclusions
In conclusion, by using aldehydes or ketones as the catalyst
and employing CsOH as the base, we developed a general,
green, efficient, practical, and highly selective 9‐
monoalkylation reaction of fluorenes with alcohols. This new
method can tolerate a wide range of substrates such as the
usual primary (hetero)benzylic alcohols, the less reactive short
to long chain primary alcohols, the sterically more bulky and
less reactive secondary benzylic, aliphatic, and cycloalkyl
alcohols, as well as alcohols and fluorenes bearing the reactive
fluoro, chloro and bromo substituents. Since CsOH was found
to be a more effective base than the analogous KOH in many
instances, this new method can solve the issues remained in
the field and largely broadened the diversity of the useful 9‐
monoalkylated fluorenes. The obtained 9‐monoalkylated
fluorenes could also be easily functionalized to give potentially
useful unsymmetrical 9,9‐disubstituted fluorenes. All these
results suggest that fine‐tuning of the alkylated fluorenes is
now made possible to provide potentially versatile specific
fluorene monomers for function‐oriented polyfluorenes.
Preliminary mechanistic studies also revealed that this reaction
most probably proceeded via similar transition‐metal free
relay race mechanism as proposed in previous N‐ and C‐
alkylation reactions,13 in which both catalyst aldehydes or
ketones and the additive base are crucial to the reaction and
the carbonyl catalysts can be quantitatively regenerated and
recovered in the reaction cycles. Further extension of the
method in alcohol‐based green and efficient dehydrative
alkylation reactions are still in progress in this group.
intermediates (4) by the substrate alcohols with production of
the target alkylated fluorenes and regeneration of the
carbonyl compounds was proposed.
Scheme 3. Proposed mechanism for aldehyde/ketone-catalyzed
selective 9-momo-alkylation of fluorenes with primary or secondary
alcohols.
Acknowledgements
We thank National Natural Science Foundation of China
(21672163), Natural Science Foundation of Zhejiang Province
for Distinguished Young Scholars (LR14B020002), and
Postgraduate Innovation Foundation of Wenzhou University
(3162015040) for financial support.
With 9‐momoalkylated fluorenes in hand, we next explored
their second mono‐functionalization to obtain unsymmetrical
9,9‐difunctionalized fluorenes. Firstly, in an aqueous NaOH
(50%) media and in the presence of 20 mol% TBAI, 9‐benzyl
fluorene (3a) could readily react with butyl bromide to afford a
good 85% yield of the target 9‐benzyl 9‐butyl fluorene (12
)
o
after heating at 80 C for 24 h (eq. 3). Similarly, the aromatic
nucleophilic substitution reaction of 3a and 4‐
chloronitrobenzene readily afforded 75% yield of the target 9‐
benzyl 9‐(4‐nitrophenyl) fluorene (13) in the presence of
excess CsOH (eq. 4). These results clearly revealed the high
potential of the obtained 9‐momoalkylated fluorenes in the
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DOI: 10.1039/C6GC02518H
Table of Contents
Aldehyde/Ketone-Catalyzed Highly Selective Synthesis of 9-Monoalkylated Fluorenes by Dehydrative
C-Alkylation with Primary and Secondary Alcohols
Jianhui Chen, Yang Li, Shuangyan Li, Jianping Liu,* Fei Zheng, Zhengping Zhang, and Qing Xu*
Carbonyl compounds efficiently catalyze the dehydrative 9-C-alkylation of fluorenes with various primary and
secondary alcohols to provide the useful 9-monoalkyled fluorenes in high selectivities.