Platinum- and palladium-catalyzed sequential reactions: Regioselective synthesis of 9-fluorenylidenes from 9-ethynylfluoren-9-yl carboxylates and furans

Article abstract of DOI:10.1055/s-0029-1217531

The transformation of 9-acyloxy-9-ethynylfluorene and furans with platinum and palladium co-catalysts gave 9-fluorenylidenes in excellent yields with high regioselectivity in a one-pot manner. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0029-1217531

LETTER
1937
Platinum- and Palladium-Catalyzed Sequential Reactions: Regioselective
Synthesis of 9-Fluorenylidenes from 9-Ethynylfluoren-9-yl Carboxylates
and Furans
R
egioselective Syn
o
thesis of 9-F
j
luoren
i
ylidene
s
Miki, Yoshinori Senda, Toshiyuki Kowada, Kouichi Ohe*
Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University, Nishikyo-ku, Kyoto 615-8510,
Japan
Fax +81(75)3832495; E-mail: ohe@scl.kyoto-u.ac.jp
Received 14 March 2009
R3
O
Abstract: The transformation of 9-acyloxy-9-ethynylfluorene and
R4
furans with platinum and palladium co-catalysts gave 9-fluor-
enylidenes in excellent yields with high regioselectivity in a one-pot
manner.
R3
R1
Y
O
Y
5 mol%
[M]
O
R1
+
R2
R4
O
R2
up to 90% yield
Key words: carbene, ring opening, fluorene, platinum, palladium
[M]
(a mixture of olefin regioisomers)
O
O
– [M]
Fluorene is the core structure of potent molecules such as
the blue-light emitting materials,1 interferon inducers,2
antitumor compounds,3 and inhibitor of microsomal tri-
glyceride-transfer protein.4 9-Fluorenylidene structure
has also been attracted and applied to a molecular motor
for reorganization of cholesteric molecules,5 organic
field-effect transistor devices,6 and pH sensors.7 Although
many reports to construct fluorenylidene skeleton have
been reported,8 simple and highly atom-economical cata-
lytic transformations from fluorene derivatives are still
limited.
R3
R1
Y
R3
R1
Y
R4
O
[M]
R4
O
R2
R2
M–
(R1, R2 = alkyl, aryl; R3 = Me, NMe2; Y = O, S)
Scheme 1 Transition-metal-catalyzed ring-opening reaction of
furans
5.0 mol%
OAc
[RuCl2(CO)3]2
8
7
Recently, we reported the ruthenium- and platinum-cata-
lyzed ring-opening reactions of furans with propargyl car-
boxylates, carbamates, and thiocarbamates to give
trienones (Scheme 1).9
6
5
toluene
50 °C, 7 h
4
3
2
1
(E,E)-2a (74%)
O
Although 5 mol% of ruthenium or platinum catalyst is
necessary, p-conjugated compounds are efficiently pro-
duced but as a mixture of olefin regioisomers. To con-
struct highly p-conjugated and planer fluorenylidene
skeleton, we preliminarily tried to apply our method to the
synthesis of fluorenylidenes from 9-ethynylfluoren-9-yl
carboxylates under transition-metal catalysis. In the
course of our continuous investigation, we found the plat-
inum-catalyzed ring-opening reactions of furans with 9-
ethynylfluoren-9-yl carboxylates and sequential palladi-
um-catalyzed isomerization of trienones to give com-
pletely trans-isomer in a one-pot manner.
OAc
+
OAc
O
2 equiv
1a
5.0 mol%
PtCl2
O
O
(Z,Z)-2a
toluene
50 °C, 2 h
+
OAc
(Z,E)-2a
2a [99%, (3Z,5Z)/(3Z,5E) = 63:37]
At first, we examined the reactivity of 9-ethynylfluoren-
9-yl acetate (1a)10 with 2-methylfuran in the presence of
ruthenium or platinum catalyst, which is an efficient cata-
lyst for in situ generated carbene transfer reactions
(Scheme 2).11,12
Scheme 2 Ru- and Pt-catalyzed ring-opening reaction of furans
In the case of the Ru-catalyzed ring-opening reaction,
(E,E)-2a (3E,5E-isomer) was obtained regioselectively
with unidentified byproducts.13 On the other hand, plati-
num(II) chloride gave the corresponding p-conjugated
products as a mixture of (Z,Z)-2a and (Z,E)-2a isomers in
excellent yields. These results indicate that the platinum
SYNLETT 2009, No. 12, pp 1937–1940
x
x
.x
x
.2
0
0
9
Advanced online publication: 01.07.2009
DOI: 10.1055/s-0029-1217531; Art ID: U03009ST
© Georg Thieme Verlag Stuttgart · New York

1938
K. Miki et al.
LETTER
Table 1 Transition Metal-Catalyzed Isomerization of Olefin
Moietiesa
catalyst is superior to the ruthenium one in the catalytic
activity for the ring-opening reaction, and the platinum
catalyst is inferior to the ruthenium one in the regioselec-
tivity for the isomerization of produced trienones. Among
the reaction conditions we tried, we could not improve the
chemoselectivity of the Ru-catalyzed reaction and the re-
gioselectivity of the Pt-catalyzed reaction, therefore we
next examined the isomerization reaction using other tran-
sition-metal compounds.
5.0 mol%
catalyst
OAc
OAc
50 °C, 7 h
O
(Z,Z)-2a and (Z,E)-2a
(E,E)-2a
O
(Z,Z/Z,E = 79:21)
Then, we examined the isomerization of olefin moieties in
2a to give one regioisomer with a catalytic amount of pal-
ladium compounds, which have been reported as good
catalysts for olefin isomerization.14 A mixture of regioiso-
mers 2a with a ratio of Z,Z/Z,E = 79:21 was employed in
the isomerization reaction, and selected results are sum-
marized in Table 1.15
Entry Catalyst
Solvent
toluene
Yield (%)b Z,Z/Z,E/E,Ec
1
2
3d
4
5
6
7
PtCl2
PdCl2
PdCl2
>99
>99
>99
>99
>99
>99
89
77:23:0
3:13:84
0:0:100
0:0:100
0:0:100
48:20:32
34:41:25
toluene
toluene
PdCl2(MeCN)2 toluene
After heating a mixture of (Z,Z)-2a and (Z,E)-2a at 50 °C
with 5 mol% of PtCl2, 2a was recovered quantitatively
with retaining an original ratio of regioisomers (Z,Z/
Z,E = 77:23; entry 1). This indicates that PtCl2 does not
cause olefin isomerization, hence the regioisomeric ratio
of (Z,Z)-2a and (Z,E)-2a obtained from the PtCl2-cata-
lyzed ring-opening reactions of 2-methylfuran with 1a
shown in Scheme 2 might be kinetically controlled. When
the isomerization reaction of 2a was carried out with a cat-
alytic amount of PdCl2 in toluene at 50 °C for 7 hours, a
mixture of (Z,Z)-2a and (Z,E)-2a was converted to all
trans-regioisomer (E,E)-2a in quantitative yield, although
the diluted conditions were necessary (entries 2 and 3).
The reaction with PdCl2(MeCN)2 also gave (E,E)-2a se-
lectively (entry 4). The isomerization of a mixture of
(Z,Z)-2a and (Z,E)-2a proceeded smoothly in THF solu-
tion, while CH2Cl2 gave 2a as a mixture of three regioiso-
mers (entries 5 and 6). Palladium(0) complex, such as
Pd(PPh3)4, underwent isomerization of 2a to some extent,
but 2a was converted into unidentified products with low
recovery of 2a (entry 7).
PdCl2
THF
PdCl2
CH2Cl2
toluene
Pd(PPh3)4
a Reaction conditions: 2a (0.20 mmol, Z,Z/Z,E = 79:21) and catalyst
(5 mol%) in solvent (2.0 mL) at 50 °C for 7 h.
b Isolated yield.
c Determined by 1H NMR.
d Toluene (4.0 mL) was used.
1.0 mol% PtCl2
OAc
1.0 mol% PdCl2
1a
+
toluene, 50 °C
7 h
O
1.1 equiv
O
(E,E)-2a (99% yield)
Scheme 3
1.0 mol%
Since we found that PdCl2 converts a mixture of regioiso-
mers 2a to (E,E)-2a with high selectivity, we next exam-
ined the ring-opening reaction of 2-methylfuran with 1a in
one-pot manner. When the reaction of 1a with 1.1 equiv-
alents of 2-methylfuran in the presence of 1 mol% of PtCl2
and PdCl2 was carried out in toluene at 50 °C for 7 hours,
we succeeded to obtain only one isomer (E,E)-2a in 99%
yield (Scheme 3).16–19 We next applied this one-pot trans-
formation reaction using PtCl2 and PdCl2 to various
furans. These results are summarized in Table 2.
PtCl2
1.0 mol%
PdCl2
OR
OR
+
toluene
50 °C
O
1.1 equiv
O
1b (R = Bz)
1c (R = Piv)
1d (R = COC7H15
(E,E)-2a-Bz (99% yield, 12 h)
(E,E)-2a-Piv (68% yield, 24 h)
(E,E)-2a-oct (76% yield, 24 h)
)
Scheme 4
The reaction of 2-methoxyfuran gave the corresponding
fluorenylidene (E,E)-2b in 85% yield, although furan
gave (E,E)-2c in lower yield (entries 2 and 3). 2-Acetoxy-
furan is not suitable for this transformation, giving a trace
amount of the corresponding product (entry 4). 2-Aryl-
furans afforded high yields of fluorenylidene 2d–g (en-
tries 5–8). 2-Benzylfuran afforded the corresponding
product (E,E)-2h in good yield (entry 9).
Finally, we examined the transformation of benzoate 1b,
pivalate 1c, and octanoate 1d with 2-methylfuran
(Scheme 4). As expected, the corresponding E,E-isomers
were obtained in each case, but giving pivalate (E,E)-2a-
Piv and octanoate (E,E)-2a-oct in a little lower yields, re-
spectively.
In conclusion, we have investigated one-pot transforma-
tion of 9-acyloxy-9-ethynylfluorenes to 9-fluorenylidenes
Synlett 2009, No. 12, 1937–1940 © Thieme Stuttgart · New York

LETTER
Regioselective Synthesis of 9-Fluorenylidenes
1939
(5) (a) Feringa, B. L. J. Org. Chem. 2007, 72, 6635.
Table 2 PtCl2/PdCl2-Catalyzed Ring-Opening Reaction of Furans
and Sequential Isomerizationa
(b) Eelkema, R.; Pollard, M. M.; Katsonis, N.; Vicario, J.;
Broer, D. J.; Feringa, B. L. J. Am. Chem. Soc. 2006, 128,
14397. (c) Pijper, D.; Feringa, B. L. Angew. Chem. Int. Ed.
2007, 46, 3693.
1.0 mol% PtCl2
1.0 mol% PdCl2
OAc
(6) Heeney, M.; Bailey, C.; Giles, M.; Shkunov, M.; Sparrowe,
D.; Tierney, S.; Zhang, W.; McCulloch, I. Macromolecules
2004, 37, 5250.
1a
+
R
O
toluene, 50 °C
1.1 equiv
(7) (a) Zheng, G.; Wang, Z.; Tang, L.; Lu, P.; Weber, W. P.
Sens. Actuators, B 2007, 122, 389. (b) Wang, Z.; Xing, Y.;
Shao, H.; Lu, P.; Weber, W. P. Org. Lett. 2005, 7, 87.
(c) Wang, Z.; Zheng, G.; Lu, P. Org. Lett. 2005, 7, 3669.
(d) Wang, Z.; Li, W.; Lu, P. Sens. Actuators, B 2007, 122,
389.
(8) For selected examples, see: (a) Dahl, B. J.; Mills, N. S.
J. Am. Chem. Soc. 2008, 130, 10179. (b) Johnson, A. W.;
LaCount, R. B. Tetrahedron 1960, 9, 130.
R
(E,E)-2
O
Entry
R
Time (h) Isolated yield (%)
1
2
3
4
5
6
7
8
9
Me
7
99 [(E,E)-2a]
85 [(E,E)-2b]
45 [(E,E)-2c]
trace
OMe
7
H
24
24
9
(9) (a) Ikeda, Y.; Murai, M.; Abo, T.; Miki, K.; Ohe, K.
Tetrahedron Lett. 2007, 48, 6651. (b) Miki, K.; Fujita, M.;
Uemura, S.; Ohe, K. Org. Lett. 2006, 8, 1741.
OCOMe
Ph
99 [(E,E)-2d]
99 [(E,E)-2e]
92 [(E,E)-2f]
95 [(E,E)-2g]
92 [(E,E)-2h]
(10) Hennion, G. F.; Fleck, B. R. J. Am. Chem. Soc. 1955, 77,
3253.
4-MeOC6H4
4-F3CC6H4
1-naphthyl
Bn
9
(11) General Procedure of Ring-Opening Reaction of
2-Methylfuran
15
15
15
In a flame-dried Schlenk tube, PtCl2 (6.5 mg, 0.025 mmol, 5
mol%) was dispersed in toluene (2.0 mL). To the solution
were added 1a (124 mg, 0.50 mmol) and 2-methylfuran (90
mL, 1.0 mmol) at r.t. The mixture was stirred at 50 °C for 7
h. The yellow suspension was cooled and the solvent was
removed under reduced pressure to give 2a. To remove the
platinum catalyst, the crude 2a was dissolved in THF (30
mL) and the solution was passed through a short Florisil
column. The THF solution was evaporated under reduced
pressure to give 2a (99%, Z,Z/Z,E = 63:37). In the case of
[RuCl2(CO)3]2, the THF solution obtained after a Florisil
column was evaporated in vacuo, and the residue was
purified by centrifuge with hexane and a small amount of
THF to give a first crop of (E,E)-2a (ca. 65% yield). The
hexane and THF solution containing a small amount of
(E,E)-2a was evaporated in vacuo, and the residue was
purified by column chromatography on SiO2 with hexane–
EtOAc (v/v = 4:1) to give a second crop of (E,E)-2a (ca.
10% yield). The yield in Scheme 2 was obtained by
combining first and second crops of (E,E)-2a.
a Reaction conditions: 1a (0.50 mmol), furan (0.55 mmol), and PtCl2
(1.0 mol%) and PdCl2 (1.0 mol%) in toluene (4 mL) at 50 °C.
under platinum/palladium co-catalyst system in excellent
yields with high regioselectivity. Trienone skeleton in 9-
fluorenylidenes is to be converted to more complex mole-
cules and high p-conjugated materials. These transforma-
tions are under investigation in our laboratory.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
Acknowledgment
(12) Analytical Data of (E,E)-2a, (Z,Z)-2a and (Z,E)-2a
Compound (E,E)-2a: yield 74%; a yellow solid; mp 203.7–
204.1 °C. IR (KBr): 3054, 1752 (C=O), 1654, 1198, 1176,
728 cm–1. 1H NMR (400 MHz, CDCl3): d = 2.34 (s, 3 H),
2.51 (s, 3 H), 6.32 (d, J = 15.2 Hz, 1 H), 6.63 (dd, J = 11.2,
14.6 Hz, 1 H), 7.25–7.34 (m, 5 H), 7.63 (d, J = 14.6 Hz, 1 H),
7.68 (d, J = 8.0 Hz, 1 H), 7.70 (d, J = 8.0 Hz, 1 H), 7.77 (d,
J = 8.0 Hz, 1 H), 7.79 (d, J = 8.0 Hz, 1 H). 13C NMR (100
MHz, CDCl3): d = 21.1, 27.6, 119.9, 120.2, 125.2, 125.3,
127.3, 127.7, 128.8, 129.2, 130.8, 131.1, 132.3, 132.7,
135.6, 136.7, 140.3, 140.9, 141.6, 144.8, 168.2, 198.0. Anal.
Calcd for C22H18O3: C, 79.98, H, 5.49. Found: C, 79.87; H,
5.66.
This work is supported by Research for Promoting Technological
Seeds from Japan Science and Technology Agency.
References and Notes
(1) (a) Grimsdale, A. C.; Müllen, K. Macromol. Rapid Commun.
2007, 28, 1676. (b) Chen, P.; Yang, G.; Liu, T.; Li, T.;
Wang, M.; Huang, W. Polym. Int. 2006, 55, 473.
(c) Scherf, U.; List, E. J. W. Adv. Mater. 2002, 14, 477.
(2) Lyakhov, S. A.; Lyakhova, E. A.; Karpenko, A. S.; Mal’tsev,
G. V.; Vel’cheva, I. V.; Litvinova, L. A.; Lebedyuk, M. N.;
Khorokhorina, G. A.; Fedchuk, V. P. Pharm. Chem. J. 2004,
38, 128.
(3) (a) Pan, H.-L.; Fletcher, T. L. J. Med. Chem. 1965, 8, 491.
(b) Morgan, L. R.; Thangaraj, K.; LeBlanc, B.; Rodgers, A.;
Wolford, L. T.; Hooper, C. L.; Fan, D.; Jursic, B. S. J. Med.
Chem. 2003, 46, 4552.
Compounds (Z,Z)-2a and (Z,E)-2a: yield 99%; a yellow
solid. 1H NMR (400 MHz, CDCl3): d [(Z,Z)-2a] = 2.27 (s, 3
H), 2.38 (s, 3 H), 6.14 (d, J = 11.7 Hz, 1 H), 7.04 (dd,
J = 11.2, 11.7 Hz, 1 H), 7.04 (d, J = 11.7 Hz, 1 H), 7.22–7.37
(m, 4 H), 7.64–7.70 (m, 4 H), 7.77-7.80 (m, 1 H); d [(Z,E)-
2a] = 2.27 (s, 3 H), 2.56 (s, 3 H), 6.17 (d, J = 11.2 Hz, 1 H),
6.68 (dd, J = 11.2, 11.2 Hz, 1 H), 7.22–7.37 (m, 4 H), 7.49
(d, J = 15.1 Hz, 1 H), 7.64–7.70 (m, 2 H), 7.81 (d, J = 8.0
Hz, 2 H), 7.97 (dd, J = 11.7, 15.1 Hz, 1 H). 13C NMR (100
MHz, CDCl3): d = 21.1, 21.2, 31.9, 31.9, 119.8, 119.8,
(4) Sulsky, R.; Robl, J. A.; Biller, S. A.; Harrity, T. W.;
Wetterau, J.; Conolly, F.; Jolibois, K.; Kunselman, L.
Bioorg. Med. Chem. Lett. 2004, 14, 5067.
Synlett 2009, No. 12, 1937–1940 © Thieme Stuttgart · New York

1940
K. Miki et al.
LETTER
(18) Since the reaction using [RuCl2 (CO)3]2 gave (E,E)-2a
120.0, 125.0, 125.1, 125.1, 125.4, 126.6, 127.1, 127.1,
127.4, 127.6, 127.7, 128.4, 128.5, 128.7, 128.9, 129.0,
130.2, 130.5, 130.8, 132.9, 135.7, 135.7, 136.4, 136.5,
136.8, 140.0, 140.1, 140.3, 140.7, 140.8, 144.0, 145.6,
167.7, 168.4, 198.5, 198.6 (two carbon peaks could not be
distinguished with other aromatic carbons).
regioselectively, as shown in Scheme 2, we also examined
co-catalytic system using [RuCl2 (CO)3]2 and PtCl2. When
the reaction of 1a with 2-methylfuran (2 equiv) in 5 mol% of
PtCl2 and 5 mol% of [RuCl2(CO)3]2 was carried out at 50 °C,
we obtained 2a with a mixture of three regioisomers (Z,Z/
Z,E/E,E = 27:28:45) in 93% yield. This indicates that the
ruthenium complex has comparatively lower catalytic
activity for isomerization reaction than palladium
compounds shown in Table 1.
(13) We reported that the Ru-catalyzed reaction of 3-methylbut-
1-yn-3-yl acetate with 2-methylfuran gave the
corresponding Z,E-isomer regioselectively.9b Although we
cannot explain the difference at present, we presume that the
reaction of 1a using the ruthenium catalyst would proceed
via a completely different pathway.
(19) General Procedure of Ring-Opening Reaction and
Sequential Isomerization Reaction
(14) (a) Yu, J.; Gaunt, M. J.; Spencer, J. B. J. Org. Chem. 2002,
67, 4627. (b) Kim, I. S.; Dong, G. R.; Jung, Y. H. J. Org.
Chem. 2007, 72, 5424; and references therein.
In a flame-dried Schlenk tube, PtCl2 (1.3 mg, 0.0050 mmol)
and PdCl2 (0.9 mg, 0.0050 mmol) were dispersed in toluene
(4.0 mL). To this solution were added 1a (124 mg, 0.50
mmol) and 2-methylfuran (50 mL, 0.55 mmol) at r.t. The
mixture was stirred at 50 °C for 7 h. The yellow suspension
was cooled, and the solvent was removed under reduced
pressure to give 2a. To remove the transition-metal catalysts,
the crude 2a was dissolved in THF (30 mL), and the solution
was passed through a short Florisil column. The THF
solution was evaporated under reduced pressure to give
(E,E)-2a in 99% yield. For reactions using other furans, the
THF solution obtained after a Florisil column was
evaporated in vacuo, and the residue was purified by
centrifuge with hexane and a small amount of THF to give a
first crop of (E,E)-2. The hexane and THF solution
containing a small amount of (E,E)-2 was evaporated in
vacuo, and the residue was purified by column
(15) General Procedure of Isomerization Reaction
In a flame-dried Schlenk tube, a mixture of (Z,Z)-2a and
(Z,E)-2a (66 mg, 0.20 mmol, Z,Z/Z,E = 79:21) and a
transition-metal compound (0.010 mmol) were dispersed in
toluene (2.0 mL). The mixture was stirred at 50 °C for 7 h.
The yellow suspension was cooled, and the solvent was
removed under reduced pressure. The purification step using
column chromatography on SiO2 was necessary for
Pd(PPh3)4-catalyzed reaction. PdCl2 was purchased from
Wako Pure Chemicals Inc. (Japan) and used without further
purification.
(16) Without PtCl2, no (E,E)-2a was detected, and 1a was
recovered in 70% yield.
(17) Although THF is one of the suitable solvents for the
isomerization reaction of 2a, the reaction of 1a and
2-methylfuran with PtCl2/PdCl2 in THF gave (E,E)-2a
selectively but in a lower yield than that in toluene because
of unidentified byproduct formation.
chromatography on SiO2 with hexane–EtOAc (v/v = 4:1) to
give a second crop of (E,E)-2. The yield in Table 2 was
obtained by combining first and second crops of (E,E)-2.
The analytical data of (E,E)-2 are summarized in the
Supporting Information.
Synlett 2009, No. 12, 1937–1940 © Thieme Stuttgart · New York

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