Highly regioselective synthesis of Lndene derivatives including an allene functional group via Pd/C-catalyzed cyclization reaction in air

Article abstract of DOI:10.1021/ol071385u

lndene derivatives including an aliene functional group are readily prepared in moderate to excellent yields with high regioselectivity under very mild reaction conditions by the Pd/C-catalyzed reaction of propargylic compounds. The resulting products can

Full text of DOI:10.1021/ol071385u

ORGANIC
LETTERS
2
007
Vol. 9, No. 18
527-3529
Highly Regioselective Synthesis of
Indene Derivatives Including an Allene
Functional Group via Pd/C-Catalyzed
Cyclization Reaction in Air
3
†
†
†
†
†
Hai-Peng Bi, Xue-Yuan Liu, Fa-Rong Gou, Li-Na Guo, Xin-Hua Duan, and
Yong-Min Liang*,
†,‡
State Key Laboratory of Applied Organic Chemistry, Lanzhou UniVersity, and State
Key Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physics, Chinese
Academy of Science, Lanzhou 730000, People’s Republic of China
liangym@lzu.edu.cn
Received June 12, 2007
ABSTRACT
Indene derivatives including an allene functional group are readily prepared in moderate to excellent yields with high regioselectivity under
very mild reaction conditions by the Pd/C-catalyzed reaction of propargylic compounds. The resulting products can be further elaborated
using Pd-catalyzed annulation reactions.
5
Allenes have received considerable attention in recent
years.1 The interesting reactivity of allenes originates
mainly from their unique strained structure, and thus
continuous efforts have been made to construct the 1,2-dienic
moieties. Allenes are usually prepared by one of the
following methods: (1) elimination of substituted alkenyl
of two vicinal halogen atoms from 2,3-dibromoalkenes; (3)
addition of organometallic reagents or metal hydrides to
-3
6
propargylic halides and analogues; (4) rearrangement of
acetylenic systems; (5) reaction of 1,1-dihalocyclopropanes
with MeLi; (6) addition of organolithiums to vinylacety-
lenes; and (7) coupling reaction of allenic metallic reagents
7
8
,9
10
4
11
triflates/halides or allylic halides; (2) reductive elimination
with organohalides.
To the best of our knowledge, there is no report about the
synthesis of allenyl indene derivatives.
†
Lanzhou University.
Lanzhou Institute of Chemical Physics.
‡
(
1) (a) The Chemistry of the Allenes; Landor, S. R., Ed.; Academic:
London, 1982; Vol. 1. (b) Modern Allene Chemistry; Krause, N., Hashmi,
A. S. K., Eds.; Wiley-VCH: Weinheim, 2004; Vols. 1 and 2. (c) Tsuji, J.
Topics in Organometallic Chemistry; Springer-Verlag: Berlin, Heidelberg,
(4) Naso, F.; Ronzini, L. J. Chem. Soc., Perkin Trans. 1 1974, 340.
(5) Bouis, M. Ann. Chim. Paris 1928, 9, 402.
(6) Brandsma, L.; Arens, J. F. Rec. TraV. Chim. 1967, 86, 734.
(7) Bowes, C. M.; Montecalvo, D. F.; Sondheimer, F. Tetrahedron Lett.
1973, 34, 3181.
(8) Schuster, H. F.; Coppola, G. M. Allenes in Organic Synthesis; John
Wiley & Sons: New York, 1988; p 20.
2
005.
2) (a) Zimmer, R.; Dinesh, C. U.; Nandanan, E.; Khan, F. A. Chem.
ReV. 2000, 100, 3067. (b) Bates, R. W.; Satcharoen, V. Chem. Soc. ReV.
002, 31, 12. (c) Ma, S. Acc. Chem. Res. 2003, 36, 701. (d) Hoffmann-
(
2
R o¨ der, A.; Krause, N. Angew. Chem., Int. Ed. 2004, 43, 1196. (e) Reissig,
H.-U.; Schade, W.; Amombo, M. O.; Pulz, R.; Hausherr, A. Pure Appl.
Chem. 2002, 74, 175. (f) Ma, S. Chem. ReV. 2005, 105, 2829.
(9) Jones, W. M.; Grasley, M. H.; Brey, W. S., Jr. J. Am. Chem Soc.
1963, 85, 2754.
(10) Petrov, A. A.; Kormer, V. A.; Savich, I. G. Zh. Obshch. Khim. 1960,
30, 3845.
(
3) For some of the most recent typical reactions of allenes, see: (a)
Ng, S.-S.; Jamison, T. F. J. Am. Chem. Soc. 2005, 127, 7320. (b) Sieber, J.
D.; Morken, J. P. J. Am. Chem. Soc. 2006, 128, 74. (c) Lee, P. H.; Lee, K.;
Kang, Y. J. Am. Chem. Soc. 2006, 128, 1139. (d) Lalonde, P. L.; Sherry,
B. D.; Kang, E. J.; Toste, F. D. J. Am. Chem. Soc. 2007, 129, 2452. (e)
Chang, H.-T.; Jayanth, T. T.; Cheng, C.-H. J. Am. Chem. Soc. 2007, 129,
(11) (a) Ruitenberg, K.; Kleijn, H.; Meijer, J.; Oostveen, E. A.; Vermeer,
P. J. Organomet. Chem. 1982, 224, 399. (b) de Graaf, W.; Boersma, J.;
van Koten, G.; Elsevier, C. J. J. Organomet. Chem. 1989, 378, 115. (c)
Aidhen, I. S.; Braslau, R. Synth. Commun. 1994, 24, 789. (d) Badone, D.;
Cardamone, R.; Guzzi, U. Tetrahedron Lett. 1994, 35, 5477. (e) Gillmann,
T.; Weeber, T. Synlett 1994, 649.
4
166. (f) Banaag, A. R.; Tius, M. A. J. Am. Chem. Soc. 2007, 129, 5328.
1
0.1021/ol071385u CCC: $37.00
© 2007 American Chemical Society
Published on Web 08/03/2007

Pd-catalyzed reactions of propargylic compounds have
been shown to be extremely effective for the construction
the catalytic activity of palladium catalysts was examined
(entries 6-9). Pd(PPh and Pd (dba) also showed good
results. Other palladium catalyst systems such as Pd (dba)
dppf and Pd(OAc) /PPh gave poor yields. Finally, the
amount of Pd/C was examined (entries 10-12). We found
that 0.5 mol % of Pd/C also afforded product in an excellent
yield. Although 0.2 mol % of Pd/C proved to be effective,
the use of 0.5 mol % of Pd/C realized high yield with good
reproducibility. The optimum reaction conditions thus far
3
)
4
2
3
1
2
of carbon-carbon and carbon-heteroatom bonds. In this
process, however, expensive and air-sensitive Pd catalysts,
environmentally harmful phosphine ligands, and high tem-
perature were usually used. In connection with our research
on carboannulation reactions,13 we herein report a novel
cyclization reaction of propargylic compounds for the
synthesis of indene derivatives with high regioselectivity in
the presence of a phosphine-free catalyst Pd/C under ambient
conditions of temperature and air. An allene functional group
was also formed in the product that could be engaged in
post-transformations (Scheme 1).
2
3
/
2
3
2 3
developed employ 1.0 equiv of 1a, 2.0 equiv of Cs CO ,
and 0.5 mol % of Pd/C in DMF at room temperature in air.
Under the optimized reaction conditions above, the breadth
and scope of the reaction of substituted secondary and tertiary
propargyl substrates were investigated next. Substituted
secondary carbonates, having methyl or phenyl substituents,
produced high yields of the indene derivatives (Table 2
Scheme 1
Table 2. Pd-Catalyzed Cyclization of Propargylic Compounds 1
Our initial study began with the reaction of 3-(2-(2,2-di-
(
ethoxycarbonyl)ethyl)phenyl)prop-2-ynyl ethyl carbonate
Ca time (h)
b
entry
1
1
2
yield (%)
(1a, 0.5 mmol) and 10% Pd/C (0.05 equiv) in the absence
1
2
R ) CO2Et,
A
A
A
A
A
A
A
B
B
B
B
A
A
A
A
6
6
2a
96
92
89
91
95
93
80
75
73
78
66
93
91
86
93
3
of base in DMF at room temperature in air. The desired
product 2a was isolated in a 69% yield with high regiose-
lectivity (Table 1, entry 1). K
R ) H, R ) H 1a
1
2
3
R ) CO2Et,
2b
2c
2d
2e
2f
2
3
R ) H, R ) Me 1b
CO
3
and Cs
2
CO
3
were in-
R1 ) CO Et,
6
2
2
2
3
R ) H, R ) Ph 1c
1
2
4
R ) CO2Et,R ) H,
6
3
R ) p-Tol 1d
1
5
R ) CO2Et,
6
2
3
Table 1. Optimization of the Pd-Catalyzed Cyclization of
Propargylic Carbonate 1aa
6 4
R ) H, R ) p-ClC H 1e
R1 ) CO Et,
6
2
6
2
3
R ) H, R ) p-BrC6H4 1f
1
7
R ) CO2Et,
6
2g
2h
2i
2
3
R ) H, R ) 2-furyl 1g
1
8
R ) COMe,
8
2
3
R ) Me, R ) Me 1h
1
9
R ) COMe,
10
10
12
6
2
3
R ) R ) (CH2)4 1i
b
1
Pd
time yield
10
R ) COMe,
2j
2
3
entry
catalyst
base
solvent (mol %) (h)
(%)
2 5
R ) R ) (CH ) 1j
1
11
12
13
14
15
R ) COMe,
2k
2a
2a
2a
2a
1
2
3
4
5
6
7
8
9
Pd/C
DMF
5
14
3
69
88
96
43
56
2
3
R ) Ph, R ) Ph 1k
Pd/C
K2CO3 DMF
Cs2CO3 DMF
Cs2CO3 THF
Cs2CO3 toluene
Cs2CO3 DMF
Cs2CO3 DMF
5
1
2
R ) CO2Me,
Pd/C
5
2
3
R ) R ) H 1l
Pd/C
5
8
1
R ) COMe,
6
Pd/C
5
8
2
3
R ) R ) H 1m
c
Pd(PPh3)4
Pd2(dba)3
5
2
96
1
R ) COPh,
6
c
5
2
92
2
3
R ) R ) H 1n
c
Pd2(dba)3/dppf Cs2CO3 DMF
Pd(OAc)2/PPh3 Cs2CO3 DMF
5
14
14
3
24
1
2
R ) PO(OEt)2,
4
c
5
9
3
R ) R ) H 1o
10
11
12
Pd/C
Pd/C
Pd/C
Cs2CO3 DMF
Cs2CO3 DMF
Cs2CO3 DMF
1
96
96
64
a
0.5
0.2
6
Conditions A: 1 (0.5 mmol), Cs2CO3 (2.0 equiv), and Pd/C (0.5 mol
10
%) in DMF (3 mL) at room temperature in air. Conditions B: 1 (0.5 mmol),
Cs2CO3 (2.0 equiv), and Pd2(dba)3 (5 mol %) in DMF (3 mL) at 100 °C
under argon. b Isolated yields.
a
Reactions were carried out on a 0.5 mmol scale in 3.0 mL of solvent
at room temperature in air for the specified period of time with 1.0 equiv
of 1a, 2.0 equiv of base, and [Pd]. Isolated yields. The reactions were
b
c
run under argon.
entries 2-6). Similarly, 2-furyl-substituted propargyl com-
pound 1g led to desired product 2g in 80% yield (entry 7).
2 3
vestigated as bases. Cs CO provided an excellent yield and
short reaction time (entries 2 and 3). Other solvents such as
THF and toluene were less effective (entries 4 and 5). Next,
(13) (a) Guo, L.-N.; Duan, X.-H.; Bi, H.-P.; Liu, X.-Y.; Liang, Y.-M. J.
Org. Chem. 2006, 71, 3325. (b) Duan, X.-H.; Guo, L.-N.; Bi, H.-P.; Liu,
X.-Y.; Liang, Y.-M. Org. Lett. 2006, 8, 3053. (c) Duan, X.-H.; Guo, L.-N.;
Bi, H.-P.; Liu, X.-Y.; Liang, Y.-M. Org. Lett. 2006, 8, 5777. (d) Guo, L.-
N.; Duan, X.-H.; Bi, H.-P.; Liu, X.-Y.; Liang, Y.-M. J. Org. Chem. 2007,
72, 1538-1540. (e) Bi, H.-P.; Guo, L.-N.; Duan, X.-H.; Gou, F. -R.; Huang,
S.-H.; Liu, X.-Y.; Liang, Y.-M. Org. Lett. 2007, 9, 397.
(12) For reviews on palladium-catalyzed reactions of propargylic com-
pounds, see: (a) Tsuji, J. Acc. Chem. Res. 1969, 2, 144. (b) Tsuji, J.; Mandai.
T. Angew. Chem., Int. Ed. Engl. 1995, 34, 2589.
3528
Org. Lett., Vol. 9, No. 18, 2007

The reactions of tertiary propargyl acetates 1h, 1i, and 1j
have also been studied. Good yields of the expected products
Scheme 3
have been obtained in the presence of Pd
2 3
(dba) (entries
8
-10). Fortunately, 1,1-diaryl-1,2-allene 2k was also ob-
14
tained in a moderate yield (entry 11). Pd/C showed poor
results in the reactions of tertiary propargyl compounds.
Table 2 also shows results of propargyl substrates involving
different leaving groups. The reactions of propargyl carbonate
1l, propargyl acetate 1m, propargyl benzoate 1n, and
propargyl phosphate 1o gave the desired products 2a in
excellent yields (entries 12-15).
The facility with which this carboannulation process occurs
encouraged us to attempt a double cyclization. When
compound 1p was reacted in the presence of 1.0 mol % of
(0) initially promotes decarboxylation of propargylic com-
pound 1 to generate an allenylpalladium complex 4;1 (b)
regioselective intramolecular nucleophilic attack of the
carbanion forms product 2.
5,16
2 3
Pd/C and 4.0 equiv of Cs CO in DMF at room temperature
in air for 7 h, the double-annulation product 2p was formed
Scheme 4
in 83% yield (Scheme 2).
Scheme 2
In conclusion, we have developed a novel Pd/C-catalyzed
reaction without phosphine ligands for the synthesis of indene
derivatives from propargylic compounds with high regiose-
lectivity under ambient conditions of temperature and air. It
is noteworthy that lower catalyst loadings were used in this
process. Further studies into the chirality of the carboannu-
lation reaction are underway.
Acknowledgment. We thank the NSF (NSF-20621091,
NSF-20672049) and the “Hundred Scientist Program” from
the Chinese Academy of Sciences for financial support.
An interesting feature of this process is the fact that the
indene derivatives produced by carboannulation can be
further elaborated by using various Pd-catalyzed processes.
For example, the reaction of 2a with 2-iodophenols afforded
the spirocyclic products 3 in moderate yields (Scheme 3).
The mechanism shown in Scheme 4 is proposed for this
process. It consists of the following key steps: (a) palladium-
Supporting Information Available: Typical experimen-
tal procedure and characterization data for all products. This
material is available free of charge via the Internet at
http://pubs.acs.org.
OL071385U
(15) (a) Yoshida, M.; Morishita, Y.; Fujita, M.; Ihara, M. Tetrahedron
Lett. 2004, 45, 1861. (b) Yoshida, M.; Morishita, Y.; Fujita, M.; Ihara, M.
Tetrahedron 2005, 61, 4381.
(16) Kozawa, Y.; Mori, M. J. Org. Chem. 2003, 68, 8068.
(
14) The methods for the synthesis 1,1-diaryl-1,2-allenes seem limited
probably due to the steric hindrance and instability; see ref 9.
Org. Lett., Vol. 9, No. 18, 2007
3529